Blood-Brain Barrier Alterations Provide Evidence of Subacute Diaschisis in an Ischemic Stroke Rat Model

PubMed Central

Garbuzova-Davis, Svitlana; Rodrigues, Maria C. O.; Hernandez-Ontiveros, Diana G.; Tajiri, Naoki; Frisina-Deyo, Aric; Boffeli, Sean M.; Abraham, Jerry V.; Pabon, Mibel; Wagner, Andrew; Ishikawa, Hiroto; Shinozuka, Kazutaka; Haller, Edward; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesario V.

2013-01-01

Background Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB) competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB integrity and related pathogenic processes in contralateral brain areas. Methodology/Principal Findings In ipsilateral hemisphere 7 days after transient middle cerebral artery occlusion (tMCAO), significant BBB alterations characterized by large Evans Blue (EB) parenchymal extravasation, autophagosome accumulation, increased reactive astrocytes and activated microglia, demyelinization, and neuronal damage were detected in the striatum, motor and somatosensory cortices. Vascular damage identified by ultrastuctural and immunohistochemical analyses also occurred in the contralateral hemisphere. In contralateral striatum and motor cortex, major ultrastructural BBB changes included: swollen and vacuolated endothelial cells containing numerous autophagosomes, pericyte degeneration, and perivascular edema. Additionally, prominent EB extravasation, increased endothelial autophagosome formation, rampant astrogliosis, activated microglia, widespread neuronal pyknosis and decreased myelin were observed in contralateral striatum, and motor and somatosensory cortices. Conclusions/Significance These results demonstrate focal ischemic stroke-induced pathological disturbances in ipsilateral, as well as in contralateral brain areas, which were shown to be closely associated with BBB breakdown in remote brain microvessels and endothelial autophagosome accumulation. This microvascular damage in subacute phase likely revealed ischemic diaschisis and should be considered in development of treatment strategies for stroke. PMID:23675488

[A correlation between diffusion kurtosis imaging and the proliferative activity of brain glioma].

PubMed

Tonoyan, A S; Pronin, I N; Pitshelauri, D I; Shishkina, L V; Fadeeva, L M; Pogosbekyan, E L; Zakharova, N E; Shults, E I; Khachanova, N V; Kornienko, V N; Potapov, A A

2015-01-01

The aim of the study was to assess the capabilities of diffusion kurtosis imaging (DKI) in diagnosis of the glioma proliferative activity and to evaluate a relationship between the glioma proliferative activity index and diffusion parameters of the contralateral normal appearing white matter (CNAWM). The study included 47 patients with newly diagnosed brain gliomas (23 low grade, 13 grade III, and 11 grade IV gliomas). We determined a relationship between absolute and normalized parameters of the diffusion tensor (mean (MD), axial (AD), and radial (RD) diffusivities; fractional (FA) and relative (RA) anisotropies) and diffusion kurtosis (mean (MK), axial (AK), and radial (RK) kurtosis; kurtosis anisotropy (KA)) and the proliferative activity index in the most malignant glioma parts (p<0.05). We also established a relationship between the tensor and kurtosis parameters of CNAWM and the glioma proliferative activity index (p<0.05). The correlation between all the absolute and normalized diffusion parameters and the glioma proliferative activity index, except absolute and normalized FA and RA values, was found to be statistically significant (p<0.05). Kurtosis (MK, AK, and RK) and anisotropy (KA, FA, RA) values increased, and diffusivity (MD, AD, RD) values decreased as the glioma proliferative activity index increased. A strong correlation between the proliferative activity index and absolute RK (r=0,71; p=0.000001) and normalized values of MK (r=0.8; p=0.000001), AK (r=0.71; p=0.000001), RK (r=0.81; p=0.000001), and RD (r=-0.71; p=0.000001) was found. A weak, but statistically significant correlation between the glioma proliferative activity index and diffusion values RK (r=-0.36; p=0.014), KA (r=-0.39; p=0.007), RD (r=0.35; p=0.017), FA (r=-0.42; p=0.003), and RA (r=-0.41; p=0.004) of CNAWM was found. DKI has good capabilities to detect immunohistochemical changes in gliomas. DKI demonstrated a high sensitivity in detection of microstructural changes in the contralateral normal appearing white matter in patients with brain gliomas.

Contralateral Masking in Bilateral Cochlear Implant Patients: A Model of Medial Olivocochlear Function Loss

PubMed Central

Aronoff, Justin M.; Padilla, Monica; Fu, Qian-Jie; Landsberger, David M.

2015-01-01

Contralateral masking is the phenomenon where a masker presented to one ear affects the ability to detect a signal in the opposite ear. For normal hearing listeners, contralateral masking results in masking patterns that are both sharper and dramatically smaller in magnitude than ipsilateral masking. The goal of this study was to investigate whether medial olivocochlear (MOC) efferents are needed for the sharpness and relatively small magnitude of the contralateral masking function. To do this, bilateral cochlear implant patients were tested because, by directly stimulating the auditory nerve, cochlear implants circumvent the effects of the MOC efferents. The results indicated that, as with normal hearing listeners, the contralateral masking function was sharper than the ipsilateral masking function. However, although there was a reduction in the magnitude of the contralateral masking function compared to the ipsilateral masking function, it was relatively modest. This is in sharp contrast to the results of normal hearing listeners where the magnitude of the contralateral masking function is greatly reduced. These results suggest that MOC function may not play a large role in the sharpness of the contralateral masking function but may play a considerable role in the magnitude of the contralateral masking function. PMID:25798581

Cognitive levels of performance account for hemispheric lateralisation effects in dyslexic and normally reading children.

PubMed

Heim, Stefan; Grande, Marion; Meffert, Elisabeth; Eickhoff, Simon B; Schreiber, Helen; Kukolja, Juraj; Shah, Nadim Jon; Huber, Walter; Amunts, Katrin

2010-12-01

Recent theories of developmental dyslexia explain reading deficits in terms of deficient phonological awareness, attention, visual and auditory processing, or automaticity. Since dyslexia has a neurobiological basis, the question arises how the reader's proficiency in these cognitive variables affects the brain regions involved in visual word recognition. This question was addressed in two fMRI experiments with 19 normally reading children (Experiment 1) and 19 children with dyslexia (Experiment 2). First, reading-specific brain activation was assessed by contrasting the BOLD signal for reading aloud words vs. overtly naming pictures of real objects. Next, ANCOVAs with brain activation during reading the individuals' scores for all five cognitive variables assessed outside the scanner as covariates were performed. Whereas the normal readers' brain activation during reading showed co-variation effects predominantly in the right hemisphere, the reverse pattern was observed for the dyslexics. In particular, middle frontal gyrus, inferior parietal cortex, and precuneus showed contralateral effects for controls as compared to dyslexics. In line with earlier findings in the literature, these data hint at a global change in hemispheric asymmetry during cognitive processing in dyslexic readers, which, in turn, might affect reading proficiency. Copyright © 2010 Elsevier Inc. All rights reserved.

SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, P; Park, P; Li, H

Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated withmore » PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.« less

Peripapillary Pachychoroid in Nonarteritic Anterior Ischemic Optic Neuropathy

PubMed Central

Nagia, Lina; Huisingh, Carrie; Johnstone, John; Kline, Lanning B.; Clark, Mark; Girard, Michael J. A.; Mari, Jean Martial; Girkin, Christopher A.

2016-01-01

Purpose This study examined the peripapillary choroidal thickness (PCT) in nonarteritic ischemic optic neuropathy (NAION) in comparison to contralateral eyes and normal eyes. Methods We used enhanced depth imaging spectral-domain optical coherence tomography to image the optic nerve head of 20 NAION, 10 contralateral eyes, and 102 normal eyes. Following compensation, the scans were manually delineated to identify relevant surfaces including Bruch's membrane opening (BMO), Bruch's membrane, and anterior sclera. The PCT was defined as the measurement between Bruch's membrane and the anterior sclera and was measured at increasing distance from BMO. Models adjusted for age, BMO area, and axial length were used to compare the mean PCT between NAION and normal eyes, and contralateral eyes and normal eyes. Paired t-tests were used to compare the PCT between NAION and contralateral eyes. Results The mean PCT was thicker in NAION and contralateral eyes when compared with normal eyes at all distances from BMO (P < 0.001). The PCT was not significantly thicker in contralateral eyes when compared with affected NAION eyes. Choroidal thickness was thinnest in the inferior quadrant in all eyes regardless of the group. Conclusions Increased peripapillary choroidal thickness was noted in both NAION and contralateral eyes. The thicker choroid may be an associated feature or a result of the disorder. Although further longitudinal study is required to determine causation, these findings may suggest that a thickened peripapillary choroid may be a component of the disk-at-risk clinical phenotype. PMID:27583829

Slump Test: Effect of Contralateral Knee Extension on Response Sensations in Asymptomatic Subjects and Cadaver Study.

PubMed

Shacklock, Michael; Yee, Brian; Van Hoof, Tom; Foley, Russ; Boddie, Keith; Lacey, Erin; Poley, J Bryan; Rade, Marinko; Kankaanpää, Markku; Kröger, Heikki; Airaksinen, Olavi

2016-02-01

Part 1: A randomized, single-blind study on the effect of contralateral knee extension on sensations produced by the slump test (ST) in asymptomatic subjects. Part 2: A cadaver study simulating the nerve root behavior of part 1. Part 1: Test if contralateral knee extension consistently reduces normal stretch sensations with the ST.Part 2: Ascertain in cadavers an explanation for the results. In asymptomatic subjects, contralateral knee extension reduces stretch sensations with the ST. In sciatica patients, contralateral SLR also can temporarily reduce sciatica. We studied this methodically in asymptomatic subjects before considering a clinical population. Part 1: Sixty-one asymptomatic subjects were tested in control (ST), sham, or intervention (contralateral ST) groups and their sensation response intensity compared.Part 2: Caudal tension was applied to the L5 nerve root of 3 cadavers and tension behavior of the contralateral neural tissue recorded visually. Part 1: Reduction of stretch sensations occurred in the intervention group but not in control and sham groups (P ≤ 0.001).Part 2: Tension in the contralateral lumbar nerve roots and dura reduced in a manner consistent with the responses in the intervention (contralateral ST) group. Part 1: In asymptomatic subjects, normal thigh stretch sensations with the ST reduced consistently with the contralateral ST, showing that this is normal and may now be compared with patients with sciatica.Part 2: Contralateral reduction in lumbar neural tension with unilateral application of tension-producing movements also occurred in cadavers, supporting the proposed explanatory hypothesis.

Dynamic changes in oxygenation of intracranial tumor and contralateral brain during tumor growth and carbogen breathing: A multisite EPR oximetry with implantable resonators

PubMed Central

Hou, Huagang; Dong, Ruhong; Li, Hongbin; Williams, Benjamin; Lariviere, Jean P.; Hekmatyar, S.K.; Kauppinen, Risto A.; Khan, Nadeem; Swartz, Harold

2013-01-01

Introduction Several techniques currently exist for measuring tissue oxygen; however technical difficulties have limited their usefulness and general application. We report a recently developed electron paramagnetic resonance (EPR) oximetry approach with multiple probe implantable resonators (IRs) that allow repeated measurements of oxygen in tissue at depths of greater than 10 mm. Methods The EPR signal to noise (S/N) ratio of two probe IRs was compared with that of LiPc deposits. The feasibility of intracranial tissue pO2 measurements by EPR oximetry using IRs was tested in normal rats and rats bearing intracerebral F98 tumors. The dynamic changes in the tissue pO2 were assessed during repeated hyperoxia with carbogen breathing. Results A 6–10 times increase in the S/N ratio was observed with IRs as compared to LiPc deposits. The mean brain pO2 of normal rats was stable and increased significantly during carbogen inhalation in experiments repeated for 3 months. The pO2 of F98 glioma declined gradually, while the pO2 of contralateral brain essentially remained the same. Although a significant increase in the glioma pO2 was observed during carbogen inhalation, this effect declined in experiments repeated over days. Conclusion EPR oximetry with IRs provides a significant increase in S/N ratio. The ability to repeatedly assess orthotopic glioma pO2 is likely to play a vital role in understanding the dynamics of tissue pO2 during tumor growth and therapies designed to modulate tumor hypoxia. This information could then be used to optimize chemoradiation by scheduling treatments at times of increased glioma oxygenation. PMID:22033225

MMP-2 as an early synovial biomarker for cranial cruciate ligament disease in dogs.

PubMed

Boland, L; Danger, R; Cabon, Q; Rabillard, M; Brouard, S; Bouvy, B; Gauthier, O

2014-01-01

To measure the activity of matrix metalloproteinases (MMP)-2 and -9 in synovial fluid from the stifle joints of dogs with cranial cruciate ligament (CrCL) rupture and to compare that to values from contralateral stifle joints and dogs with clinically normal stifle joints. Additionally, the C-reactive protein (CRP) levels were also measured. Fourteen large breed dogs with unilateral CrCL rupture and 11 large breed normal dogs were included in this prospective clinical study. Synovial fluid was collected from CrCL-ruptured stifle joints, contralateral clinically normal stifle joints of the same dogs, and stifle joints of normal dogs. Serum was also collected. Synovial fluid activities of MMP-2 and MMP-9 and serum CRP level were measured. The MMP-2 activity in synovial fluid was significantly higher in CrCL-ruptured joints compared to contralateral joints and to stifles from normal dogs. There was no significant difference in activity of MMP-2 in contralateral joints of CrCL-ruptured dogs compared to normal dogs. Both serum CRP level and MMP-9 activity did not differ significantly between the studied conditions. It was confirmed that MMP-2 activity is significantly related to CrCL rupture, but there was a failure to demonstrate any significant increase in the contralateral joints compared to the stifle joints of normal dogs. The MMP-2 involvement in progressing CrCL disease still has to be defined.

Computed tomography demonstrates abnormalities of contralateral ear in subjects with unilateral sensorineural hearing loss.

PubMed

Marcus, Sonya; Whitlow, Christopher T; Koonce, James; Zapadka, Michael E; Chen, Michael Y; Williams, Daniel W; Lewis, Meagan; Evans, Adele K

2014-02-01

Prior studies have associated gross inner ear abnormalities with pediatric sensorineural hearing loss (SNHL) using computed tomography (CT). No studies to date have specifically investigated morphologic inner ear abnormalities involving the contralateral unaffected ear in patients with unilateral SNHL. The purpose of this study is to evaluate contralateral inner ear structures of subjects with unilateral SNHL but no grossly abnormal findings on CT. IRB-approved retrospective analysis of pediatric temporal bone CT scans. 97 temporal bone CT scans, previously interpreted as "normal" based upon previously accepted guidelines by board certified neuroradiologists, were assessed using 12 measurements of the semicircular canals, cochlea and vestibule. The control-group consisted of 72 "normal" temporal bone CTs with underlying SNHL in the subject excluded. The study-group consisted of 25 normal-hearing contralateral temporal bones in subjects with unilateral SNHL. Multivariate analysis of covariance (MANCOVA) was then conducted to evaluate for differences between the study and control group. Cochlea basal turn lumen width was significantly greater in magnitude and central lucency of the lateral semicircular canal bony island was significantly lower in density for audiometrically normal ears of subjects with unilateral SNHL compared to controls. Abnormalities of the inner ear were present in the contralateral audiometrically normal ears of subjects with unilateral SNHL. These data suggest that patients with unilateral SNHL may have a more pervasive disease process that results in abnormalities of both ears. The findings of a cochlea basal turn lumen width disparity >5% from "normal" and/or a lateral semicircular canal bony island central lucency disparity of >5% from "normal" may indicate inherent risk to the contralateral unaffected ear in pediatric patients with unilateral sensorineural hearing loss. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Differentiation of brain abscesses from glioblastomas and metastatic brain tumors: comparisons of diagnostic performance of dynamic susceptibility contrast-enhanced perfusion MR imaging before and after mathematic contrast leakage correction.

PubMed

Toh, Cheng Hong; Wei, Kuo-Chen; Chang, Chen-Nen; Ng, Shu-Hang; Wong, Ho-Fai; Lin, Ching-Po

2014-01-01

To compare the diagnostic performance of dynamic susceptibility contrast-enhanced perfusion MRI before and after mathematic contrast leakage correction in differentiating pyogenic brain abscesses from glioblastomas and/or metastatic brain tumors. Cerebral blood volume (CBV), leakage-corrected CBV and leakage coefficient K2 were measured in enhancing rims, perifocal edema and contralateral normal appearing white matter (NAWM) of 17 abscesses, 19 glioblastomas and 20 metastases, respectively. The CBV and corrected CBV were normalized by dividing the values in the enhancing rims or edema to those of contralateral NAWM. For each study group, a paired t test was used to compare the K2 of the enhancing rims or edema with those of NAWM, as well as between CBV and corrected CBV of the enhancing rims or edema. ANOVA was used to compare CBV, corrected CBV and K2 among three lesion types. The diagnostic performance of CBV and corrected CBV was assessed with receiver operating characteristic (ROC) curve analysis. The CBV and correction CBV of enhancing rim were 1.45±1.17 and 1.97±1.01 for abscesses, 3.85±2.19 and 4.39±2.33 for glioblastomas, and 2.39±0.90 and 2.97±0.78 for metastases, respectively. The CBV and corrected CBV in the enhancing rim of abscesses were significantly lower than those of glioblastomas and metastases (P = 0.001 and P = 0.007, respectively). In differentiating abscesses from glioblastomas and metastases, the AUC values of corrected CBV (0.822) were slightly higher than those of CBV (0.792). Mathematic leakage correction slightly increases the diagnostic performance of CBV in differentiating pyogenic abscesses from necrotic glioblastomas and cystic metastases. Clinically, DSC perfusion MRI may not need mathematic leakage correction in differentiating abscesses from glioblastomas and/or metastases.

Proprioception in patients with posterior cruciate ligament tears: A meta-analysis comparison of reconstructed and contralateral normal knees

PubMed Central

Ko, Seung-Nam

2017-01-01

Posterior cruciate ligament (PCL) reconstruction for patients with PCL insufficiency has been associated with postoperative improvements in proprioceptive function due to mechanoreceptor regeneration. However, it is unclear whether reconstructed PCL or contralateral normal knees have better proprioceptive function outcomes. This meta-analysis was designed to compare the proprioceptive function of reconstructed PCL or contralateral normal knees in patients with PCL insufficiency. All studies that compared proprioceptive function, as assessed with threshold to detect passive movement (TTDPM) or joint position sense (JPS) in PCL reconstructed or contralateral normal knees were included. JPS was calculated by reproducing passive positioning (RPP). Five studies met the inclusion/exclusion criteria for the meta-analysis. The proprioceptive function, defined as TTDPM (95% CI: 0.25 to 0.51°; P<0.00001) and RPP (95% CI: 0.19 to 0.45°; P<0.00001), was significantly different between the reconstructed PCL and contralateral normal knees. The mean difference in angle of error between the reconstructed PCL and contralateral normal knees was 0.06° greater in TTDPM than by RPP. In addition, results from subgroup analyses, based on the starting angles and the moving directions of the knee, that evaluated TTDPM at 15° flexion to 45° extension, TTDPM at 45° flexion to 110° flexion, RPP in flexion, and RPP in extension demonstrated that mean angles of error were significantly greater, by 0.38° (P = 0.0001), 0.36° (P = 0.02), 0.36° (P<0.00001), and 0.23° (P = 0.04), respectively, in reconstructed PCL than in contralateral normal knees. The proprioceptive function of PCL reconstructed knees was decreased, compared with contralateral normal knees, as determined by both TTDPM and RPP. In addition, the amount of loss of proprioception was greater in TTDPM than in RPP, even with minute differences. Results from subgroup analysis, that evaluated the mean angles of error in moving directions through RPP, suggested that the moving direction of flexion has a significantly greater mean for angles of error than the moving direction of extension. Although the level of differences between various parameters were statistically significant, further studies are needed to determine whether the small differences (>1°) of the loss of proprioception are clinically relevant. PMID:28922423

Quantitative measurements of regional glucose utilization and rate of valine incorporation into proteins by double-tracer autoradiography in the rat brain tumor model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kirikae, M.; Diksic, M.; Yamamoto, Y.L.

1989-02-01

We examined the rate of glucose utilization and the rate of valine incorporation into proteins using 2-(/sup 18/F)fluoro-2-deoxyglucose and L-(1-14C)-valine in a rat brain tumor model by quantitative double-tracer autoradiography. We found that in the implanted tumor the rate of valine incorporation into proteins was about 22 times and the rate of glucose utilization was about 1.5 times that in the contralateral cortex. (In the ipsilateral cortex, the tumor had a profound effect on glucose utilization but no effect on the rate of valine incorporation into proteins.) Our findings suggest that it is more useful to measure protein synthesis thanmore » glucose utilization to assess the effectiveness of antitumor agents and their toxicity to normal brain tissue. We compared two methods to estimate the rate of valine incorporation: kinetic (quantitation done using an operational equation and the average brain rate coefficients) and washed slices (unbound labeled valine removed by washing brain slices in 10% trichloroacetic acid). The results were the same using either method. It would seem that the kinetic method can thus be used for quantitative measurement of protein synthesis in brain tumors and normal brain tissue using (/sup 11/C)-valine with positron emission tomography.« less

Multichannel fiber-based diffuse reflectance spectroscopy for the rat brain exposed to a laser-induced shock wave: comparison between ipsi- and contralateral hemispheres

NASA Astrophysics Data System (ADS)

Miyaki, Mai; Kawauchi, Satoko; Okuda, Wataru; Nawashiro, Hiroshi; Takemura, Toshiya; Sato, Shunichi; Nishidate, Izumi

2015-03-01

Due to considerable increase in the terrorism using explosive devices, blast-induced traumatic brain injury (bTBI) receives much attention worldwide. However, little is known about the pathology and mechanism of bTBI. In our previous study, we found that cortical spreading depolarization (CSD) occurred in the hemisphere exposed to a laser- induced shock wave (LISW), which was followed by long-lasting hypoxemia-oligemia. However, there is no information on the events occurred in the contralateral hemisphere. In this study, we performed multichannel fiber-based diffuse reflectance spectroscopy for the rat brain exposed to an LISW and compared the results for the ipsilateral and contralateral hemispheres. A pair of optical fibers was put on the both exposed right and left parietal bone; white light was delivered to the brain through source fibers and diffuse reflectance signals were collected with detection fibers for both hemispheres. An LISW was applied to the left (ipsilateral) hemisphere. By analyzing reflectance signals, we evaluated occurrence of CSD, blood volume and oxygen saturation for both hemispheres. In the ipsilateral hemispheres, we observed the occurrence of CSD and long-lasting hypoxemia-oligemia in all rats examined (n=8), as observed in our previous study. In the contralateral hemisphere, on the other hand, no occurrence of CSD was observed, but we observed oligemia in 7 of 8 rats and hypoxemia in 1 of 8 rats, suggesting a mechanism to cause hypoxemia or oligemia or both that is (are) not directly associated with CSD in the contralateral hemisphere.

Role of inter-hemispheric transfer in generating visual evoked potentials in V1-damaged brain hemispheres

PubMed Central

Kavcic, Voyko; Triplett, Regina L.; Das, Anasuya; Martin, Tim; Huxlin, Krystel R.

2015-01-01

Partial cortical blindness is a visual deficit caused by unilateral damage to the primary visual cortex, a condition previously considered beyond hopes of rehabilitation. However, recent data demonstrate that patients may recover both simple and global motion discrimination following intensive training in their blind field. The present experiments characterized motion-induced neural activity of cortically blind (CB) subjects prior to the onset of visual rehabilitation. This was done to provide information about visual processing capabilities available to mediate training-induced visual improvements. Visual Evoked Potentials (VEPs) were recorded from two experimental groups consisting of 9 CB subjects and 9 age-matched, visually-intact controls. VEPs were collected following lateralized stimulus presentation to each of the 4 visual field quadrants. VEP waveforms were examined for both stimulus-onset (SO) and motion-onset (MO) related components in postero-lateral electrodes. While stimulus presentation to intact regions of the visual field elicited normal SO-P1, SO-N1, SO-P2 and MO-N2 amplitudes and latencies in contralateral brain regions of CB subjects, these components were not observed contralateral to stimulus presentation in blind quadrants of the visual field. In damaged brain hemispheres, SO-VEPs were only recorded following stimulus presentation to intact visual field quadrants, via inter-hemispheric transfer. MO-VEPs were only recorded from damaged left brain hemispheres, possibly reflecting a native left/right asymmetry in inter-hemispheric connections. The present findings suggest that damaged brain hemispheres contain areas capable of responding to visual stimulation. However, in the absence of training or rehabilitation, these areas only generate detectable VEPs in response to stimulation of the intact hemifield of vision. PMID:25575450

A time-course analysis of changes in cerebral metal levels following a controlled cortical impact.

PubMed

Portbury, Stuart D; Hare, Dominic J; Sgambelloni, Charlotte; Finkelstein, David I; Adlard, Paul A

2016-02-01

Traumatic brain injury (TBI) is complicated by a sudden and dramatic change in brain metal levels, including iron (Fe), copper (Cu) and zinc (Zn). Specific 'metallo-pathological' features of TBI include increased non-heme bound Fe and the liberation of free Zn ions, both of which may contribute to the pathogenesis of TBI. To further characterise the metal dyshomeostasis that occurs following brain trauma, we performed a quantitative time-course survey of spatial Fe, Cu and Zn distribution in mice receiving a controlled cortical impact TBI. Images of brain metal levels produced using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) in the upper quadrant of the ipsilateral hemisphere were compared to the corresponding contralateral hemisphere, together with regional areas radiating toward the center of the brain from the site of lesion. Significant regional and time point specific elevations in Fe, Zn and Cu were detected immediately and up to 28 days after TBI. The magnitude and timeframe of many of these changes suggest that TBI results in a pronounced and sustained alteration in normal metal levels within the brain. Such alterations are likely to play a role in both the short- and long-term consequences of head trauma and suggest that pharmacological modulation to normalize these metal levels may be efficacious in improving functional outcome.

MR imaging of a novel NOE-mediated magnetization transfer with water in rat brain at 9.4 T.

PubMed

Zhang, Xiao-Yong; Wang, Feng; Jin, Tao; Xu, Junzhong; Xie, Jingping; Gochberg, Daniel F; Gore, John C; Zu, Zhongliang

2017-08-01

To detect, map, and quantify a novel nuclear Overhauser enhancement (NOE)-mediated magnetization transfer (MT) with water at approximately -1.6 ppm [NOE(-1.6)] in rat brain using MRI. Continuous wave MT sequences with a variety of radiofrequency irradiation powers were optimized to achieve the maximum contrast of this NOE(-1.6) effect at 9.4 T. The distribution of effect magnitudes, resonance frequency offsets, and line widths in healthy rat brains and the differences of the effect between tumors and contralateral normal brains were imaged and quantified using a multi-Lorentzian fitting method. MR measurements on reconstituted model phospholipids as well as two cell lines (HEK293 and 9L) were also performed to investigate the possible molecular origin of this NOE. Our results suggest that the NOE(-1.6) effect can be detected reliably in rat brain. Pixel-wise fittings demonstrated the regional variations of the effect. Measurements in a rodent tumor model showed that the amplitude of NOE(-1.6) in brain tumor was significantly diminished compared with that in normal brain tissue. Measurements of reconstituted phospholipids suggest that this effect may originate from choline phospholipids. NOE(-1.6) could be used as a new biomarker for the detection of brain tumor. Magn Reson Med 78:588-597, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

T1-weighted dynamic contrast-enhanced brain magnetic resonance imaging: A preliminary study with low infusion rate in pediatric patients.

PubMed

Rochetams, Bruno-Bernard; Marechal, Bénédicte; Cottier, Jean-Philippe; Gaillot, Kathleen; Sembely-Taveau, Catherine; Sirinelli, Dominique; Morel, Baptiste

2017-10-01

Background The aim of this preliminary study is to evaluate the results of T1-weighted dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in pediatric patients at 1.5T, with a low peripheral intravenous gadoteric acid injection rate of 1 ml/s. Materials and methods Children with neurological symptoms were examined prospectively with conventional MRI and T1-weighted DCE MRI. An magnetic resonance perfusion analysis method was used to obtain time-concentration curves (persistent pattern, type-I; plateau pattern, type-II; washout pattern, type-III) and to calculate pharmacokinetic parameters. A total of two radiologists manually defined regions of interest (ROIs) in the part of the lesion exhibiting the greatest contrast enhancement and in the surrounding normal or contralateral tissue. Lesion/surrounding tissue or contralateral tissue pharmacokinetic parameter ratios were calculated. Tumors were categorized by grade (I-IV) using the World Health Organization (WHO) Grade. Mann-Whitney testing and receiver-operating characteristic (ROC) curves were performed. Results A total of nine boys and nine girls (mean age 10.5 years) were included. Lesions consisted of 10 brain tumors, 3 inflammatory lesions, 3 arteriovenous malformations and 2 strokes. We obtained analyzable concentration-time curves for all patients (6 type-I, 9 type-II, 3 type-III). K trans between tumor tissue and surrounding or contralateral tissue was significantly different ( p = 0.034). K trans ratios were significantly different between grade I tumors and grade IV tumors ( p = 0.027) and a K trans ratio value superior to 0.63 appeared to be discriminant to determine a grade IV of malignancy. Conclusions Our results confirm the feasibility of pediatric T1-weighted DCE MRI at 1.5T with a low injection rate, which could be of great value in differentiating brain tumor grades.

Distinctive Structural and Effective Connectivity Changes of Semantic Cognition Network across Left and Right Mesial Temporal Lobe Epilepsy Patients.

PubMed

Fan, Xiaotong; Yan, Hao; Shan, Yi; Shang, Kun; Wang, Xiaocui; Wang, Peipei; Shan, Yongzhi; Lu, Jie; Zhao, Guoguang

2016-01-01

Occurrence of language impairment in mesial temporal lobe epilepsy (mTLE) patients is common and left mTLE patients always exhibit a primary problem with access to names. To explore different neuropsychological profiles between left and right mTLE patients, the study investigated both structural and effective functional connectivity changes within the semantic cognition network between these two groups and those from normal controls. We found that gray matter atrophy of left mTLE patients was more severe than that of right mTLE patients in the whole brain and especially within the semantic cognition network in their contralateral hemisphere. It suggested that seizure attacks were rather targeted than random for patients with hippocampal sclerosis (HS) in the dominant hemisphere. Functional connectivity analysis during resting state fMRI revealed that subregions of the anterior temporal lobe (ATL) in the left HS patients were no longer effectively connected. Further, we found that, unlike in right HS patients, increased causal linking between ipsilateral regions in the left HS epilepsy patients cannot make up for their decreased contralateral interaction. It suggested that weakened contralateral connection and disrupted effective interaction between subregions of the unitary, transmodal hub of the ATL may be the primary cause of anomia in the left HS patients.

Distinctive Structural and Effective Connectivity Changes of Semantic Cognition Network across Left and Right Mesial Temporal Lobe Epilepsy Patients

PubMed Central

Fan, Xiaotong; Shang, Kun; Wang, Xiaocui; Wang, Peipei; Shan, Yongzhi; Lu, Jie

2016-01-01

Occurrence of language impairment in mesial temporal lobe epilepsy (mTLE) patients is common and left mTLE patients always exhibit a primary problem with access to names. To explore different neuropsychological profiles between left and right mTLE patients, the study investigated both structural and effective functional connectivity changes within the semantic cognition network between these two groups and those from normal controls. We found that gray matter atrophy of left mTLE patients was more severe than that of right mTLE patients in the whole brain and especially within the semantic cognition network in their contralateral hemisphere. It suggested that seizure attacks were rather targeted than random for patients with hippocampal sclerosis (HS) in the dominant hemisphere. Functional connectivity analysis during resting state fMRI revealed that subregions of the anterior temporal lobe (ATL) in the left HS patients were no longer effectively connected. Further, we found that, unlike in right HS patients, increased causal linking between ipsilateral regions in the left HS epilepsy patients cannot make up for their decreased contralateral interaction. It suggested that weakened contralateral connection and disrupted effective interaction between subregions of the unitary, transmodal hub of the ATL may be the primary cause of anomia in the left HS patients. PMID:28018680

Astrocyte Hypertrophy and Microglia Activation in the Rat Auditory Midbrain Is Induced by Electrical Intracochlear Stimulation.

PubMed

Rosskothen-Kuhl, Nicole; Hildebrandt, Heika; Birkenhäger, Ralf; Illing, Robert-Benjamin

2018-01-01

Neuron-glia interactions contribute to tissue homeostasis and functional plasticity in the mammalian brain, but it remains unclear how this is achieved. The potential of central auditory brain tissue for stimulation-dependent cellular remodeling was studied in hearing-experienced and neonatally deafened rats. At adulthood, both groups received an intracochlear electrode into the left cochlea and were continuously stimulated for 1 or 7 days after waking up from anesthesia. Normal hearing and deafness were assessed by auditory brainstem responses (ABRs). The effectiveness of stimulation was verified by electrically evoked ABRs as well as immunocytochemistry and in situ hybridization for the immediate early gene product Fos on sections through the auditory midbrain containing the inferior colliculus (IC). Whereas hearing-experienced animals showed a tonotopically restricted Fos response in the IC contralateral to electrical intracochlear stimulation, Fos-positive neurons were found almost throughout the contralateral IC in deaf animals. In deaf rats, the Fos response was accompanied by a massive increase of GFAP indicating astrocytic hypertrophy, and a local activation of microglial cells identified by IBA1. These glia responses led to a noticeable increase of neuron-glia approximations. Moreover, staining for the GABA synthetizing enzymes GAD65 and GAD67 rose significantly in neuronal cell bodies and presynaptic boutons in the contralateral IC of deaf rats. Activation of neurons and glial cells and tissue re-composition were in no case accompanied by cell death as would have been apparent by a Tunel reaction. These findings suggest that growth and activity of glial cells is crucial for the local adjustment of neuronal inhibition to neuronal excitation.

Astrocyte Hypertrophy and Microglia Activation in the Rat Auditory Midbrain Is Induced by Electrical Intracochlear Stimulation

PubMed Central

Rosskothen-Kuhl, Nicole; Hildebrandt, Heika; Birkenhäger, Ralf; Illing, Robert-Benjamin

2018-01-01

Neuron–glia interactions contribute to tissue homeostasis and functional plasticity in the mammalian brain, but it remains unclear how this is achieved. The potential of central auditory brain tissue for stimulation-dependent cellular remodeling was studied in hearing-experienced and neonatally deafened rats. At adulthood, both groups received an intracochlear electrode into the left cochlea and were continuously stimulated for 1 or 7 days after waking up from anesthesia. Normal hearing and deafness were assessed by auditory brainstem responses (ABRs). The effectiveness of stimulation was verified by electrically evoked ABRs as well as immunocytochemistry and in situ hybridization for the immediate early gene product Fos on sections through the auditory midbrain containing the inferior colliculus (IC). Whereas hearing-experienced animals showed a tonotopically restricted Fos response in the IC contralateral to electrical intracochlear stimulation, Fos-positive neurons were found almost throughout the contralateral IC in deaf animals. In deaf rats, the Fos response was accompanied by a massive increase of GFAP indicating astrocytic hypertrophy, and a local activation of microglial cells identified by IBA1. These glia responses led to a noticeable increase of neuron–glia approximations. Moreover, staining for the GABA synthetizing enzymes GAD65 and GAD67 rose significantly in neuronal cell bodies and presynaptic boutons in the contralateral IC of deaf rats. Activation of neurons and glial cells and tissue re-composition were in no case accompanied by cell death as would have been apparent by a Tunel reaction. These findings suggest that growth and activity of glial cells is crucial for the local adjustment of neuronal inhibition to neuronal excitation. PMID:29520220

Protein Kinase CK2 Content in GL261 Mouse Glioblastoma.

PubMed

Ferrer-Font, Laura; Alcaraz, Estefania; Plana, Maria; Candiota, Ana Paula; Itarte, Emilio; Arús, Carles

2016-07-01

Glioblastoma (GBM) is the most prevalent and aggressive human glial tumour with a median survival of 14-15 months. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment. Unfortunately, chemoresistence always ensues with concomitant tumour regrowth. Protein kinase CK2 (CK2) contributes to tumour development, proliferation, and suppression of apoptosis in cancer and it is overexpressed in human GBM. Targeting CK2 in GBM treatment may benefit patients. With this translational perspective in mind, we have studied the CK2 expression level by Western blot analysis in a preclinical model of GBM: GL261 cells growing orthotopically in C57BL/6 mice. The expression level of the CK2 catalytic subunit (CK2α) was higher in tumour (about 4-fold) and in contralateral brain parenchyma (more than 2-fold) than in normal brain parenchyma (p < 0.05). In contrast, no significant changes were found in CK2 regulatory subunit (CK2β) expression, suggesting an increased unbalance of CK2α/CK2β in GL261 tumours with respect to normal brain parenchyma, in agreement with a differential role of these two subunits in tumours.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lupo, Janine M., E-mail: janine.lupo@ucsf.edu; Chuang, Cynthia F.; Chang, Susan M.

Purpose: To evaluate the intermediate- and long-term imaging manifestations of radiotherapy on normal-appearing brain tissue in patients with treated gliomas using 7T susceptibility-weighted imaging (SWI). Methods and Materials: SWI was performed on 25 patients with stable gliomas on a 7 Tesla magnet. Microbleeds were identified as discrete foci of susceptibility that did not correspond to vessels. The number of microbleeds was counted within and outside of the T2-hyperintense lesion. For 3 patients, radiation dosimetry maps were reconstructed and fused with the 7T SWI data. Results: Multiple foci of susceptibility consistent with microhemorrhages were observed in patients 2 years after chemoradiation.more » These lesions were not present in patients who were not irradiated. The prevalence of microhemorrhages increased with the time since completion of radiotherapy, and these lesions often extended outside the boundaries of the initial high-dose volume and into the contralateral hemisphere. Conclusions: High-field SWI has potential for visualizing the appearance of microbleeds associated with long-term effects of radiotherapy on brain tissue. The ability to visualize these lesions in normal-appearing brain tissue may be important in further understanding the utility of this treatment in patients with longer survival.« less

Glibenclamide Produces Region-Dependent Effects on Cerebral Edema in a Combined Injury Model of Traumatic Brain Injury and Hemorrhagic Shock in Mice.

PubMed

Jha, Ruchira M; Molyneaux, Bradley J; Jackson, Travis C; Wallisch, Jessica S; Park, Seo-Young; Poloyac, Samuel; Vagni, Vincent A; Janesko-Feldman, Keri L; Hoshitsuki, Keito; Minnigh, M Beth; Kochanek, Patrick M

2018-06-06

Cerebral edema is critical to morbidity/mortality in traumatic brain injury (TBI) and is worsened by hypotension. Glibenclamide may reduce cerebral edema by inhibiting sulfonylurea receptor-1 (Sur1); its effect on diffuse cerebral edema exacerbated by hypotension/resuscitation is unknown. We aimed to determine if glibenclamide improves pericontusional and/or diffuse edema in controlled cortical impact (CCI) (5m/sec, 1 mm depth) plus hemorrhagic shock (HS) (35 min), and compare its effects in CCI alone. C57BL/6 mice were divided into five groups (n = 10/group): naïve, CCI+vehicle, CCI+glibenclamide, CCI+HS+vehicle, and CCI+HS+glibenclamide. Intravenous glibenclamide (10 min post-injury) was followed by a subcutaneous infusion for 24 h. Brain edema in injured and contralateral hemispheres was subsequently quantified (wet-dry weight). This protocol brain water (BW) = 80.4% vehicle vs. 78.3% naïve, p < 0.01) but was not reduced by glibenclamide (I%BW = 80.4%). Ipsilateral edema also developed in CCI alone (I%BW = 80.2% vehicle vs. 78.3% naïve, p < 0.01); again unaffected by glibenclamide (I%BW = 80.5%). Contralateral (C) %BW in CCI+HS was increased in vehicle (78.6%) versus naive (78.3%, p = 0.02) but unchanged in CCI (78.3%). At 24 h, glibenclamide treatment in CCI+HS eliminated contralateral cerebral edema (C%BW = 78.3%) with no difference versus naïve. By 72 h, contralateral cerebral edema had resolved (C%BW = 78.5 ± 0.09% vehicle vs. 78.3 ± 0.05% naïve). Glibenclamide decreased 24 h contralateral cerebral edema in CCI+HS. This beneficial effect merits additional exploration in the important setting of TBI with polytrauma, shock, and resuscitation. Contralateral edema did not develop in CCI alone. Surprisingly, 24 h of glibenclamide treatment failed to decrease ipsilateral edema in either model. Interspecies dosing differences versus prior studies may play an important role in these findings. Mechanisms underlying brain edema may differ regionally, with pericontusional/osmolar swelling refractory to glibenclamide but diffuse edema (via Sur1) from combined injury and/or resuscitation responsive to this therapy. TBI phenotype may mandate precision medicine approaches to treat brain edema.

The potential application of a transcriptionally regulated oncolytic herpes simplex virus for human cancer therapy

PubMed Central

Miao, L; Fraefel, C; Sia, K C; Newman, J P; Mohamed-Bashir, S A; Ng, W H; Lam, P Y P

2014-01-01

Background: Emerging studies have shown the potential benefit of arming oncolytic viruses with therapeutic genes. However, most of these therapeutic genes are placed under the regulation of ubiquitous viral promoters. Our goal is to generate a safer yet potent oncolytic herpes simplex virus type-1 (HSV-1) for cancer therapy. Methods: Using bacterial artificial chromosome (BAC) recombineering, a cell cycle-regulatable luciferase transgene cassette was replaced with the infected cell protein 6 (ICP6) coding region (encoded for UL39 or large subunit of ribonucleotide reductase) of the HSV-1 genome. These recombinant viruses, YE-PC8, were further tested for its proliferation-dependent luciferase gene expression. Results: The ability of YE-PC8 to confer proliferation-dependent transgene expression was demonstrated by injecting similar amount of viruses into the tumour-bearing region of the brain and the contralateral normal brain parenchyma of the same mouse. The results showed enhanced levels of luciferase activities in the tumour region but not in the normal brain parenchyma. Similar findings were observed in YE-PC8-infected short-term human brain patient-derived glioma cells compared with normal human astrocytes. intratumoural injection of YE-PC8 viruses resulted in 77% and 80% of tumour regression in human glioma and human hepatocellular carcinoma xenografts, respectively. Conclusion: YE-PC8 viruses confer tumour selectivity in proliferating cells and may be developed further as a feasible approach to treat human cancers. PMID:24196790

Real-time monitoring of ischemic and contralateral brain pO2 during stroke by variable length multisite resonators

PubMed Central

Hou, Huagang; Li, Hongbin; Dong, Ruhong; Khan, Nadeem; Swartz, Harold

2014-01-01

Purpose Electron paramagnetic resonance (EPR) oximetry using variable length multi-probe implantable resonator (IR), was used to investigate the temporal changes in the ischemic and contralateral brain pO2 during stroke in rats. Material and Methods The EPR signal to noise ratio (S/N) of the IR with four sensor loops at a depth of up to11 mm were compared with direct implantation of lithium phthalocyanine (LiPc, oximetry probe) deposits in vitro. These IRs were used to follow the temporal changes in pO2 at two sites in each hemisphere during ischemia induced by left middle cerebral artery occlusion (MCAO) in rats breathing 30% O2 or 100% O2. Results The S/N ratios of the IRs were significantly greater than the LiPc deposits. A similar pO2 at two sites in each hemisphere prior to the onset of ischemia was observed in rats breathing 30% O2. However, a significant decline in the pO2 of the left cortex and striatum occurred during ischemia but no change in the pO2 of the contralateral brain was observed. A significant increase in the pO2 of only the contralateral non-ischemic brain was observed in the rats breathing 100% O2. No significant difference in the infarct volume was evident between the animals breathing 30% O2 or 100% O2 during ischemia. Conclusions EPR oximetry with IRs can repeatedly assess temporal changes in the brain pO2 at four sites simultaneously during stroke. This oximetry approach can be used to test and develop interventions to rescue ischemic tissue by modulating cerebral pO2 during stroke. PMID:24629514

Diffusion tensor tractography of the arcuate fasciculus in patients with brain tumors: Comparison between deterministic and probabilistic models

PubMed Central

Li, Zhixi; Peck, Kyung K.; Brennan, Nicole P.; Jenabi, Mehrnaz; Hsu, Meier; Zhang, Zhigang; Holodny, Andrei I.; Young, Robert J.

2014-01-01

Purpose The purpose of this study was to compare the deterministic and probabilistic tracking methods of diffusion tensor white matter fiber tractography in patients with brain tumors. Materials and Methods We identified 29 patients with left brain tumors <2 cm from the arcuate fasciculus who underwent pre-operative language fMRI and DTI. The arcuate fasciculus was reconstructed using a deterministic Fiber Assignment by Continuous Tracking (FACT) algorithm and a probabilistic method based on an extended Monte Carlo Random Walk algorithm. Tracking was controlled using two ROIs corresponding to Broca’s and Wernicke’s areas. Tracts in tumoraffected hemispheres were examined for extension between Broca’s and Wernicke’s areas, anterior-posterior length and volume, and compared with the normal contralateral tracts. Results Probabilistic tracts displayed more complete anterior extension to Broca’s area than did FACT tracts on the tumor-affected and normal sides (p < 0.0001). The median length ratio for tumor: normal sides was greater for probabilistic tracts than FACT tracts (p < 0.0001). The median tract volume ratio for tumor: normal sides was also greater for probabilistic tracts than FACT tracts (p = 0.01). Conclusion Probabilistic tractography reconstructs the arcuate fasciculus more completely and performs better through areas of tumor and/or edema. The FACT algorithm tends to underestimate the anterior-most fibers of the arcuate fasciculus, which are crossed by primary motor fibers. PMID:25328583

Same-session functional assessment of rat retina and brain with manganese-enhanced MRI

PubMed Central

Bissig, David; Berkowitz, Bruce A.

2013-01-01

Manganese-enhanced MRI (MEMRI) is a powerful non-invasive approach for objectively measuring either retina or binocular visual brain activity in vivo. In this study, we investigated the sensitivity of MEMRI to monocular stimulation using a new protocol for providing within-subject functional comparisons in the retina and brain in the same scanning session. Adult Sprague Dawley or Long–Evans rats had one eye covered with an opaque patch. After intraperitoneal Mn2+ administration on the following day, rats underwent visual stimulation for 8 h. Animals were then anesthetized, and the brain and each eye examined by MEMRI. Function was assessed through pairwise comparisons of the patched (dark-adapted) versus unpatched (light-exposed) eyes, and of differentially-stimulated brain structures – the dorsal lateral geniculate nucleus, superior colliculus, and visual cortical regions – contralateral to the patched versus unpatched eye. As expected, Mn2+ uptake was greater in the outer retina of dark-adapted, relative to light-exposed, eyes (P<0.05). Contralateral to the unpatched eye, significantly more Mn2+ uptake was found throughout the visual brain regions than in the corresponding structures contralateral to the patched eye (P<0.05). Notably, this regional pattern of activity corresponded well to previous work with monocular stimulation. No stimulation-dependent differences in Mn2+ uptake were observed in negative control brain regions (P>0.05). Post-hoc assessment of functional data by animal age and strain revealed no significant effects. These results demonstrate, for the first time, the acquisition of functional MRI data from the eye and visual brain regions in a single scanning session. PMID:21749922

Backward masked fearful faces enhance contralateral occipital cortical activity for visual targets within the spotlight of attention

PubMed Central

Reinke, Karen S.; LaMontagne, Pamela J.; Habib, Reza

2011-01-01

Spatial attention has been argued to be adaptive by enhancing the processing of visual stimuli within the ‘spotlight of attention’. We previously reported that crude threat cues (backward masked fearful faces) facilitate spatial attention through a network of brain regions consisting of the amygdala, anterior cingulate and contralateral visual cortex. However, results from previous functional magnetic resonance imaging (fMRI) dot-probe studies have been inconclusive regarding a fearful face-elicited contralateral modulation of visual targets. Here, we tested the hypothesis that the capture of spatial attention by crude threat cues would facilitate processing of subsequently presented visual stimuli within the masked fearful face-elicited ‘spotlight of attention’ in the contralateral visual cortex. Participants performed a backward masked fearful face dot-probe task while brain activity was measured with fMRI. Masked fearful face left visual field trials enhanced activity for spatially congruent targets in the right superior occipital gyrus, fusiform gyrus and lateral occipital complex, while masked fearful face right visual field trials enhanced activity in the left middle occipital gyrus. These data indicate that crude threat elicited spatial attention enhances the processing of subsequent visual stimuli in contralateral occipital cortex, which may occur by lowering neural activation thresholds in this retinotopic location. PMID:20702500

Usefulness of the apparent diffusion coefficient for the evaluation of the white matter to differentiate between glioblastoma and brain metastases.

PubMed

Miquelini, L A; Pérez Akly, M S; Funes, J A; Besada, C H

2016-01-01

To determine whether there are significant differences in the apparent diffusion coefficient (ADC) between the apparently normal peritumor white matter surrounding glioblastomas and that surrounding brain metastases. We retrospectively reviewed 42 patients with histologically confirmed glioblastomas and 42 patients with a single cerebral metastasis. We measured the signal intensity in the apparently normal peritumor white matter and in the abnormal peritumor white matter on the ADC maps. We used mean ADC values in the contralateral occipital white matter as a reference from which to design normalized ADC indices. We compared mean values between the two tumor types. We calculated the area under the receiver operator characteristic curve and estimated the sensitivity and specificity of the measurements taken. Supratentorial lesions and compromise of the corpus callosum were more common in patients with glioblastoma than in patients with brain metastases. The maximum diameter of the enhanced area after injection of a contrast agent was greater in the glioblastomas (p<0.001). The minimum ADC value measured in the apparently normal peritumor white matter was higher for the glioblastomas than for the metastases (p=0.002). Significant differences in the ADC index were found only for the minimum ADC value in apparently normal peritumor white matter. The sensitivity and specificity were less than 70% for all variables analyzed. There are differences in the ADC values of apparently normal peritumor white matter between glioblastomas and cerebral metastases, but the magnitude of these differences is slight and the application of these differences in clinical practice is still limited. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Evaluation of the apparent diffusion coefficient in patients with recurrent glioblastoma under treatment with bevacizumab with radiographic pseudoresponse.

PubMed

A Auer, Timo; Breit, Hanns-Christian; Marini, Federico; Renovanz, Mirjam; A Brockmann, Marc; Tanyildizi, Yasemin

2018-05-04

Response Assessment in Neuro-Oncology Criteria (RANO), are used to asses response to first-line treatment of glioblastoma (GBM). Differentiation between response and pseudoresponse under treatment with Bevacizumab (BVZ) remains challenging. This study evaluates ADC changes in patients with radiographic pseudoresponse under treatment with (BVZ). Patients (n=40) with recurrent GBM under-treatment with BVZ underwent MRI before, two and four months after treatment with BVZ. In patients with radiological pseudoresponse (n=11), ADC analyses were performed. Areas with decreasing T1 contrast enhancement (CE) and FLAIR signal decrease were manually selected and compared to size and position matched healthy contralateral brain parenchyma. Histogram based ADC (10 -6 ×mm 2 /s) of these patients decreased significantly (P<0.005) from baseline MRI (T1-CE, FLAIR: 1124.9±160.3, 1098.4±226.2, respectively) to 2months (781.3±110.7, 783.3±103.3) and remained stable during 4months (777.0±138.5, 784.4±155.4, all mean±1 SD), despite progressive disease. Mean ADC values of the healthy contralateral brain tissue remained stable (P>0.05) (ADC values: baseline: 786.2±110.7, 2months: 781.1±76.2, 4months: 804.1±86.2). Treatment of GBM with BVZ leads to a decrease of ADC values in areas of pre-treatment T1-CE/FLAIR signal hyperintensity to levels of comparable with normal brain tissue. ADC values remained stable, even when progressive tumor growth was reported. Copyright © 2018. Published by Elsevier Masson SAS.

Magnetoencephalographic study of hand and foot sensorimotor organization in 325 consecutive patients evaluated for tumor or epilepsy surgery

PubMed Central

Willemse, Ronald B.; Hillebrand, Arjan; Ronner, Hanneke E.; Peter Vandertop, W.; Stam, Cornelis J.

2015-01-01

Objectives The presence of intracranial lesions or epilepsy may lead to functional reorganization and hemispheric lateralization. We applied a clinical magnetoencephalography (MEG) protocol for the localization of the contralateral and ipsilateral S1 and M1 of the foot and hand in patients with non-lesional epilepsy, stroke, developmental brain injury, traumatic brain injury and brain tumors. We investigated whether differences in activation patterns could be related to underlying pathology. Methods Using dipole fitting, we localized the sources underlying sensory and motor evoked magnetic fields (SEFs and MEFs) of both hands and feet following unilateral stimulation of the median nerve (MN) and posterior tibial nerve (PTN) in 325 consecutive patients. The primary motor cortex was localized using beamforming following a self-paced repetitive motor task for each hand and foot. Results The success rate for motor and sensory localization for the feet was significantly lower than for the hands (motor_hand 94.6% versus motor_feet 81.8%, p < 0.001; sensory_hand 95.3% versus sensory_feet 76.0%, p < 0.001). MN and PTN stimulation activated 86.6% in the contralateral S1, with ipsilateral activation < 0.5%. Motor cortex activation localized contralaterally in 76.1% (5.2% ipsilateral, 7.6% bilateral and 11.1% failures) of all motor MEG recordings. The ipsilateral motor responses were found in 43 (14%) out of 308 patients with motor recordings (range: 8.3–50%, depending on the underlying pathology), and had a higher occurrence in the foot than in the hand (motor_foot 44.8% versus motor_hand 29.6%, p = 0.031). Ipsilateral motor responses tended to be more frequent in patients with a history of stroke, traumatic brain injury (TBI) or developmental brain lesions (p = 0.063). Conclusions MEG localization of sensorimotor cortex activation was more successful for the hand compared to the foot. In patients with neural lesions, there were signs of brain reorganization as measured by more frequent ipsilateral motor cortical activation of the foot in addition to the traditional sensory and motor activation patterns in the contralateral hemisphere. The presence of ipsilateral neural reorganization, especially around the foot motor area, suggests that careful mapping of the hand and foot in both contralateral and ipsilateral hemispheres prior to surgery might minimize postoperative deficits. PMID:26693401

Synchrotron X-ray microtransections: a non invasive approach for epileptic seizures arising from eloquent cortical areas

PubMed Central

Pouyatos, B.; Nemoz, C.; Chabrol, T.; Potez, M.; Bräuer, E.; Renaud, L.; Pernet-Gallay, K.; Estève, F.; David, O.; Kahane, P.; Laissue, J. A.; Depaulis, A.; Serduc, R.

2016-01-01

Synchrotron-generated X-ray (SRX) microbeams deposit high radiation doses to submillimetric targets whilst minimizing irradiation of neighboring healthy tissue. We developed a new radiosurgical method which demonstrably transects cortical brain tissue without affecting adjacent regions. We made such image-guided SRX microtransections in the left somatosensory cortex in a rat model of generalized epilepsy using high radiation doses (820 Gy) in thin (200 μm) parallel slices of tissue. This procedure, targeting the brain volume from which seizures arose, altered the abnormal neuronal activities for at least 9 weeks, as evidenced by a decrease of seizure power and coherence between tissue slices in comparison to the contralateral cortex. The brain tissue located between transections stayed histologically normal, while the irradiated micro-slices remained devoid of myelin and neurons two months after irradiation. This pre-clinical proof of concept highlights the translational potential of non-invasive SRX transections for treating epilepsies that are not eligible for resective surgery. PMID:27264273

Synchrotron X-ray microtransections: a non invasive approach for epileptic seizures arising from eloquent cortical areas

NASA Astrophysics Data System (ADS)

Pouyatos, B.; Nemoz, C.; Chabrol, T.; Potez, M.; Bräuer, E.; Renaud, L.; Pernet-Gallay, K.; Estève, F.; David, O.; Kahane, P.; Laissue, J. A.; Depaulis, A.; Serduc, R.

2016-06-01

Synchrotron-generated X-ray (SRX) microbeams deposit high radiation doses to submillimetric targets whilst minimizing irradiation of neighboring healthy tissue. We developed a new radiosurgical method which demonstrably transects cortical brain tissue without affecting adjacent regions. We made such image-guided SRX microtransections in the left somatosensory cortex in a rat model of generalized epilepsy using high radiation doses (820 Gy) in thin (200 μm) parallel slices of tissue. This procedure, targeting the brain volume from which seizures arose, altered the abnormal neuronal activities for at least 9 weeks, as evidenced by a decrease of seizure power and coherence between tissue slices in comparison to the contralateral cortex. The brain tissue located between transections stayed histologically normal, while the irradiated micro-slices remained devoid of myelin and neurons two months after irradiation. This pre-clinical proof of concept highlights the translational potential of non-invasive SRX transections for treating epilepsies that are not eligible for resective surgery.

Treatment with acetazolamide of brain-stem and spinal paroxysmal disturbances in multiple sclerosis.

PubMed Central

Voiculescu, V; Pruskauer-Apostol, B; Alecu, C

1975-01-01

Nine cases of multiple sclerosis with paroxysmal disorders were treated with acetazolamide. In most cases a brain-stem origin of the seizures was suggested by their particular pattern: crossed syndromes (facial spasm associated with contralateral weakness of the arm and leg, paroxysmal paraesthesiae in one side of the face and weakness of the contralateral leg), paroxysmal dysarthria, and ataxia. One patient with a Brown-Sequard syndrome complained of paroxysmal paraesthesiae in the lower limbs, for which a spinal origin was admitted. In all patients the paroxysmal disorders were promptly suppressed or markedly reduced by acetazolamide. PMID:1151400

Generalized seizures and transient contralateral hemiparesis following retrobulbar anesthesia: a case report.

PubMed

Dettoraki, Maria; Dimitropoulou, Chrisafoula; Nomikarios, Nikolaos; Moschos, Marilita M; Brοuzas, Dimitrios

2015-07-28

Retrobulbar block is a local anesthetic technique widely used for intraocular surgery. Although retrobulbar anesthesia is considered to be relatively safe, a number of serious adverse events have been reported. To our knowledge, immediate onset of generalized seizures with contralateral hemiparesis after retrobulbar anesthesia has not been reported. A 62-year-old Caucasian healthy male with a right eye retinal detachment was admitted for pars plana vitrectomy. During retrobulbar anesthesia with ropivacaine and before needle withdrawal, the patient developed twitching of the face which rapidly progressed to generalized tonic-clonic seizures. Arterial oxygen saturation decreased to 75 %. Chin lift was performed and 100 % oxygen was administrated via face mask, which increased saturation to 99 %. Midazolam 2 mg was administrated intravenously to control seizures. After cessation of seizures, left-sided hemiparesis was evident. Brain computed tomography and electroencephalogram were normal 3 h later. The patient underwent pars plana vitrectomy under general anesthesia 4 days later. Serious complications of local anesthesia for ophthalmic surgery are uncommon. We present a case in which generalized tonic-clonic seizures developed during retrobulbar anesthesia, followed by transient contralateral hemiparesis. The early onset of seizures indicated intra-arterial injection of the anesthetic. Our case suggested the need for close monitoring during the performance of retrobulbar anesthesia and the presence of well-trained personnel for early recognition and immediate management of the complications.

Assessment of MRI Parameters as Imaging Biomarkers for Radiation Necrosis in the Rat Brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Silun; Tryggestad, Erik; Zhou Tingting

Purpose: Radiation necrosis is a major complication of radiation therapy. We explore the features of radiation-induced brain necrosis in the rat, using multiple MRI approaches, including T{sub 1}, T{sub 2}, apparent diffusion constant (ADC), cerebral blood flow (CBF), magnetization transfer ratio (MTR), and amide proton transfer (APT) of endogenous mobile proteins and peptides. Methods and Materials: Adult rats (Fischer 344; n = 15) were irradiated with a single, well-collimated X-ray beam (40 Gy; 10 Multiplication-Sign 10 mm{sup 2}) in the left brain hemisphere. MRI was acquired on a 4.7-T animal scanner at {approx}25 weeks' postradiation. The MRI signals of necroticmore » cores and perinecrotic regions were assessed with a one-way analysis of variance. Histological evaluation was accomplished with hematoxylin and eosin staining. Results: ADC and CBF MRI could separate perinecrotic and contralateral normal brain tissue (p < 0.01 and < 0.05, respectively), whereas T{sub 1}, T{sub 2}, MTR, and APT could not. MRI signal intensities were significantly lower in the necrotic core than in normal brain for CBF (p < 0.001) and APT (p < 0.01) and insignificantly higher or lower for T{sub 1}, T{sub 2}, MTR, and ADC. Histological results demonstrated coagulative necrosis within the necrotic core and reactive astrogliosis and vascular damage within the perinecrotic region. Conclusion: ADC and CBF are promising imaging biomarkers for identifying perinecrotic regions, whereas CBF and APT are promising for identifying necrotic cores.« less

Assessment of MRI parameters as imaging biomarkers for radiation necrosis in the rat brain.

PubMed

Wang, Silun; Tryggestad, Erik; Zhou, Tingting; Armour, Michael; Wen, Zhibo; Fu, De-Xue; Ford, Eric; van Zijl, Peter C M; Zhou, Jinyuan

2012-07-01

Radiation necrosis is a major complication of radiation therapy. We explore the features of radiation-induced brain necrosis in the rat, using multiple MRI approaches, including T(1), T(2), apparent diffusion constant (ADC), cerebral blood flow (CBF), magnetization transfer ratio (MTR), and amide proton transfer (APT) of endogenous mobile proteins and peptides. Adult rats (Fischer 344; n = 15) were irradiated with a single, well-collimated X-ray beam (40 Gy; 10 × 10 mm(2)) in the left brain hemisphere. MRI was acquired on a 4.7-T animal scanner at ~25 weeks' postradiation. The MRI signals of necrotic cores and perinecrotic regions were assessed with a one-way analysis of variance. Histological evaluation was accomplished with hematoxylin and eosin staining. ADC and CBF MRI could separate perinecrotic and contralateral normal brain tissue (p < 0.01 and < 0.05, respectively), whereas T(1), T(2), MTR, and APT could not. MRI signal intensities were significantly lower in the necrotic core than in normal brain for CBF (p < 0.001) and APT (p < 0.01) and insignificantly higher or lower for T(1), T(2), MTR, and ADC. Histological results demonstrated coagulative necrosis within the necrotic core and reactive astrogliosis and vascular damage within the perinecrotic region. ADC and CBF are promising imaging biomarkers for identifying perinecrotic regions, whereas CBF and APT are promising for identifying necrotic cores. Copyright © 2012 Elsevier Inc. All rights reserved.

Optimization of scan initiation timing after 11C-methionine administration for the diagnosis of suspected recurrent brain tumors.

PubMed

Nakajima, Reiko; Abe, Koichiro; Momose, Mitsuru; Fukushima, Kenji; Matsuo, Yuka; Kimura, Ken; Kondo, Chisato; Sakai, Shuji

2017-02-01

11 C-Methionine (MET) positron emission tomography (PET) imaging is a valuable technique for the evaluation of primary and recurrent brain tumors. Many studies have used MET-PET for data acquisition starting at 20 min after the tracer injection, while others have used scan initiation times at 5-15 min postinjection. No previous studies have identified the best acquisition timing during MET-PET imaging for suspected recurrent brain tumors. Here we sought to determine the optimal scan initiating timing after MET administration for the detection of recurrent brain tumors. Twenty-three consecutive patients with suspected recurrent brain tumors underwent MET-PET examinations. Brain PET images were reconstructed from the four serial data sets (10-15, 15-20, 20-25, and 25-30 min postinjection) that were obtained using the list-mode acquisition technique. We determined the maximal standardized uptake values (SUVmax) of the target lesions and the target-to-normal-tissue ratios (TNRs), calculated as the SUVmax to the SUVmean of a region of interest placed on the normal contralateral frontal cortex. Target lesions without significant MET uptake were excluded. Thirty-one lesions from 23 patients were enrolled. There were no significant differences in MET SUVmax or TNR values among the PET images that were reconstructed with the data extracted from the four phases postinjection. The MET uptake in the suspected recurrent brain tumors was comparable among all data extraction time phases from 10 to 30 min postinjection. The scan initiation time of MET-PET at 10 min after the injection is allowable for the detection of recurrent brain tumors. The registration identification number of the original study is 1002.

Chronic In Vivo Imaging Shows No Evidence of Dendritic Plasticity or Functional Remapping in the Contralesional Cortex after Stroke

PubMed Central

Johnston, David G.; Denizet, Marie; Mostany, Ricardo

2013-01-01

Most stroke survivors exhibit a partial recovery from their deficits. This presumably occurs because of remapping of lost capabilities to functionally related brain areas. Functional brain imaging studies suggest that remapping in the contralateral uninjured cortex might represent a transient stage of compensatory plasticity. Some postmortem studies have also shown that cortical lesions, including stroke, can trigger dendritic plasticity in the contralateral hemisphere, but the data are controversial. We used longitudinal in vivo two-photon microscopy in the contralateral homotopic cortex to record changes in dendritic spines of layer 5 pyramidal neurons in green fluorescent protein mice. We could not detect de novo growth of dendrites or changes in the density or turnover of spines for up to 4 weeks after stroke. We also used intrinsic optical signal imaging to investigate whether the forepaw (FP) sensory representation is remapped to the spared homotopic cortex after stroke. Stimulation of the contralateral FP reliably produced strong intrinsic signals in the spared hemisphere, but we could never detect a signal with ipsilateral FP stimulation after stroke. This lack of contralateral plasticity at the level of apical dendrites of layer 5 pyramidal neurons and FP sensory maps suggests that the contralesional cortex may not contribute to functional recovery after stroke and that, at least in mice, the peri-infarct cortex plays the dominant role in postischemic plasticity. PMID:22499800

Chronic in vivo imaging shows no evidence of dendritic plasticity or functional remapping in the contralesional cortex after stroke.

PubMed

Johnston, David G; Denizet, Marie; Mostany, Ricardo; Portera-Cailliau, Carlos

2013-04-01

Most stroke survivors exhibit a partial recovery from their deficits. This presumably occurs because of remapping of lost capabilities to functionally related brain areas. Functional brain imaging studies suggest that remapping in the contralateral uninjured cortex might represent a transient stage of compensatory plasticity. Some postmortem studies have also shown that cortical lesions, including stroke, can trigger dendritic plasticity in the contralateral hemisphere, but the data are controversial. We used longitudinal in vivo two-photon microscopy in the contralateral homotopic cortex to record changes in dendritic spines of layer 5 pyramidal neurons in green fluorescent protein mice. We could not detect de novo growth of dendrites or changes in the density or turnover of spines for up to 4 weeks after stroke. We also used intrinsic optical signal imaging to investigate whether the forepaw (FP) sensory representation is remapped to the spared homotopic cortex after stroke. Stimulation of the contralateral FP reliably produced strong intrinsic signals in the spared hemisphere, but we could never detect a signal with ipsilateral FP stimulation after stroke. This lack of contralateral plasticity at the level of apical dendrites of layer 5 pyramidal neurons and FP sensory maps suggests that the contralesional cortex may not contribute to functional recovery after stroke and that, at least in mice, the peri-infarct cortex plays the dominant role in postischemic plasticity.

Polyamine catabolism is enhanced after traumatic brain injury.

PubMed

Zahedi, Kamyar; Huttinger, Francis; Morrison, Ryan; Murray-Stewart, Tracy; Casero, Robert A; Strauss, Kenneth I

2010-03-01

Polyamines spermine and spermidine are highly regulated, ubiquitous aliphatic cations that maintain DNA structure and function as immunomodulators and as antioxidants. Polyamine homeostasis is disrupted after brain injuries, with concomitant generation of toxic metabolites that may contribute to secondary injuries. To test the hypothesis of increased brain polyamine catabolism after traumatic brain injury (TBI), we determined changes in catabolic enzymes and polyamine levels in the rat brain after lateral controlled cortical impact TBI. Spermine oxidase (SMO) catalyzes the degradation of spermine to spermidine, generating H2O2 and aminoaldehydes. Spermidine/spermine-N(1)-acetyltransferase (SSAT) catalyzes acetylation of these polyamines, and both are further oxidized in a reaction that generates putrescine, H2O2, and aminoaldehydes. In a rat cortical impact model of TBI, SSAT mRNA increased subacutely (6-24 h) after TBI in ipsilateral cortex and hippocampus. SMO mRNA levels were elevated late, from 3 to 7 days post-injury. Polyamine catabolism increased as well. Spermine levels were normal at 6 h and decreased slightly at 24 h, but were normal again by 72 h post-injury. Spermidine levels also decreased slightly (6-24 h), then increased by approximately 50% at 72 h post-injury. By contrast, normally low putrescine levels increased up to sixfold (6-72 h) after TBI. Moreover, N-acetylspermidine (but not N-acetylspermine) was detectable (24-72 h) near the site of injury, consistent with increased SSAT activity. None of these changes were seen in the contralateral hemisphere. Immunohistochemical confirmation indicated that SSAT and SMO were expressed throughout the brain. SSAT-immunoreactivity (SSAT-ir) increased in both neuronal and nonneuronal (likely glial) populations ipsilateral to injury. Interestingly, bilateral increases in cortical SSAT-ir neurons occurred at 72 h post-injury, whereas hippocampal changes occurred only ipsilaterally. Prolonged increases in brain polyamine catabolism are the likely cause of loss of homeostasis in this pathway. The potential for simple therapeutic interventions (e.g., polyamine supplementation or inhibition of polyamine oxidation) is an exciting implication of these studies.

The evolution of contralateral control of the body by the brain: is it a protective mechanism?

PubMed

Whitehead, Lorne; Banihani, Saleh

2014-01-01

Contralateral control, the arrangement whereby most of the human motor and sensory fibres cross the midline in order to provide control for contralateral portions of the body, presents a puzzle from an evolutionary perspective. What caused such a counterintuitive and complex arrangement to become dominant? In this paper we offer a new perspective on this question by showing that in a complex interactive control system there could be a significant net survival advantage with contralateral control, associated with the effect of injuries of intermediate severity. In such cases an advantage could arise from a combination of non-linear system response combined with correlations between injuries on the same side of the head and body. We show that a simple mathematical model of these ideas emulates such an advantage. Based on this model, we conclude that effects of this kind are a plausible driving force for the evolution of contralateral control.

Dynamic glucose enhanced (DGE) MRI for combined imaging of blood-brain barrier break down and increased blood volume in brain cancer.

PubMed

Xu, Xiang; Chan, Kannie W Y; Knutsson, Linda; Artemov, Dmitri; Xu, Jiadi; Liu, Guanshu; Kato, Yoshinori; Lal, Bachchu; Laterra, John; McMahon, Michael T; van Zijl, Peter C M

2015-12-01

Recently, natural d-glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d-glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown. Mice were inoculated orthotopically with human U87-EGFRvIII glioma cells. Time-resolved glucose signal changes were detected using chemical exchange saturation transfer (glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response to an intravenous bolus of d-glucose. DGE images of mouse brains bearing human glioma showed two times higher and persistent changes in tumor compared with contralateral brain. Area-under-curve (AUC) analysis of DGE delineated blood vessels and tumor and had contrast comparable to the AUC determined using dynamic contrast enhanced (DCE) MRI with GdDTPA, both showing a significantly higher AUC in tumor than in brain (P < 0.005). Both CEST and relaxation effects contribute to the signal change. DGE MRI is a feasible technique for studying brain tumor enhancement reflecting differences in tumor blood volume and permeability with respect to normal brain. We expect DGE will provide a low-risk and less expensive alternative to DCE MRI for imaging cancer in vulnerable populations, such as children and patients with renal impairment. © 2015 Wiley Periodicals, Inc.

Dynamic Glucose Enhanced (DGE) MRI for Combined Imaging of Blood Brain Barrier Break Down and Increased Blood Volume in Brain Cancer

PubMed Central

Xu, Xiang; Chan, Kannie WY; Knutsson, Linda; Artemov, Dmitri; Xu, Jiadi; Liu, Guanshu; Kato, Yoshinori; Lal, Bachchu; Laterra, John; McMahon, Michael T.; van Zijl, Peter C.M.

2015-01-01

Purpose Recently, natural d-glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d-glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown. Methods Mice were inoculated orthotopically with human U87-EGFRvIII glioma cells. Time-resolved glucose signal changes were detected using chemical exchange saturation transfer (glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response to an intravenous bolus of d-glucose. Results DGE images of mouse brains bearing human glioma showed two times higher and persistent changes in tumor compared to contralateral brain. Area-under-curve (AUC) analysis of DGE delineated blood vessels and tumor and had contrast comparable to the AUC determined using dynamic contrast enhanced (DCE) MRI with GdDTPA, both showing a significantly higher AUC in tumor than in brain (p<0.005). Both CEST and relaxation effects contribute to the signal change. Conclusion DGE MRI is a feasible technique for studying brain tumor enhancement reflecting differences in tumor blood volume and permeability with respect to normal brain. We expect DGE will provide a low-risk and less expensive alternative to DCE MRI for imaging cancer in vulnerable populations, such as children and patients with renal impairment. PMID:26404120

Half brain irradiation in a murine model of breast cancer brain metastasis: magnetic resonance imaging and histological assessments of dose-response.

PubMed

Zarghami, Niloufar; Murrell, Donna H; Jensen, Michael D; Dick, Frederick A; Chambers, Ann F; Foster, Paula J; Wong, Eugene

2018-06-01

Brain metastasis is becoming increasingly prevalent in breast cancer due to improved extra-cranial disease control. With emerging availability of modern image-guided radiation platforms, mouse models of brain metastases and small animal magnetic resonance imaging (MRI), we examined brain metastases' responses from radiotherapy in the pre-clinical setting. In this study, we employed half brain irradiation to reduce inter-subject variability in metastases dose-response evaluations. Half brain irradiation was performed on a micro-CT/RT system in a human breast cancer (MDA-MB-231-BR) brain metastasis mouse model. Radiation induced DNA double stranded breaks in tumors and normal mouse brain tissue were quantified using γ-H2AX immunohistochemistry at 30 min (acute) and 11 days (longitudinal) after half-brain treatment for doses of 8, 16 and 24 Gy. In addition, tumor responses were assessed volumetrically with in-vivo longitudinal MRI and histologically for tumor cell density and nuclear size. In the acute setting, γ-H2AX staining in tumors saturated at higher doses while normal mouse brain tissue continued to increase linearly in the phosphorylation of H2AX. While γ-H2AX fluorescence intensities returned to the background level in the brain 11 days after treatment, the residual γ-H2AX phosphorylation in the radiated tumors remained elevated compared to un-irradiated contralateral tumors. With radiation, MRI-derived relative tumor growth was significantly reduced compared to the un-irradiated side. While there was no difference in MRI tumor volume growth between 16 and 24 Gy, there was a significant reduction in tumor cell density from histology with increasing dose. In the longitudinal study, nuclear size in the residual tumor cells increased significantly as the radiation dose was increased. Radiation damages to the DNAs in the normal brain parenchyma are resolved over time, but remain unrepaired in the treated tumors. Furthermore, there is a radiation dose response in nuclear size of surviving tumor cells. Increase in nuclear size together with unrepaired DNA damage indicated that the surviving tumor cells post radiation had continued to progress in the cell cycle with DNA replication, but failed cytokinesis. Half brain irradiation provides efficient evaluation of dose-response for cancer cell lines, a pre-requisite to perform experiments to understand radio-resistance in brain metastases.

Interaction of acupuncture treatment and manipulation laterality modulated by the default mode network

PubMed Central

Niu, Xuan; Zhang, Ming; Liu, Zhenyu; Sun, Chuanzhu; Wang, Shan; Wang, Xiaocui; Chen, Zhen; Chen, Hongyan; Tian, Jie

2016-01-01

Appropriate selection of ipsilateral or contralateral electroacupuncture (corresponding to the pain site) plays an important role in reaching its better curative effect; however, the involving brain mechanism still remains unclear. Compared with the heat pain model generally established in previous study, capsaicin pain model induces reversible cutaneous allodynia and is proved to be better simulating aspects of clinical nociceptive and neuropathic pain. In the current study, 24 subjects were randomly divided into two groups with a 2 × 2 factorial design: laterality (ipsi- or contralateral side, inter-subject) × treatment with counter-balanced at an interval of one week (verum and placebo electroacupuncture, within-subject). We observed subjective pain intensity and brain activations changes induced by capsaicin allodynia pain stimuli before and after electroacupuncture treatment at acupoint LI4 for 30 min. Analysis of variance results indicated that ipsilateral electroacupuncture treatment produced significant pain relief and wide brain signal suppressions in pain-related brain areas compared with contralateral electroacupuncture. We also found that verum electroacupuncture at either ipsi- or contralateral side to the pain site exhibited comparable significant magnitudes of analgesic effect. By contrast, placebo electroacupuncture elicited significant pain reductions only on the ipsilateral rather than contralateral side. It was inferred that placebo analgesia maybe attenuated on the region of the body (opposite to pain site) where attention was less focused, suggesting that analgesic effect of placebo electroacupuncture mainly rely on the motivation of its spatial-specific placebo responses via attention mechanism. This inference can be further supported by the evidence that the significant interaction effect of manipulation laterality and treatment was exclusively located within the default mode network, including the bilateral superior parietal lobule, inferior parietal lobule, precuneus, and left posterior cingulate cortex. It is also proved that disruptions of the default mode network may account for the cognitive and behavioral impairments in chronic pain patients. Our findings further suggested that default mode network participates in the modulation of spatial-oriented attention on placebo analgesia as a mechanism underlying the degree to which treatment side corresponding to the pain. PMID:28326925

Interaction of acupuncture treatment and manipulation laterality modulated by the default mode network.

PubMed

Niu, Xuan; Zhang, Ming; Liu, Zhenyu; Bai, Lijun; Sun, Chuanzhu; Wang, Shan; Wang, Xiaocui; Chen, Zhen; Chen, Hongyan; Tian, Jie

2017-01-01

Appropriate selection of ipsilateral or contralateral electroacupuncture (corresponding to the pain site) plays an important role in reaching its better curative effect; however, the involving brain mechanism still remains unclear. Compared with the heat pain model generally established in previous study, capsaicin pain model induces reversible cutaneous allodynia and is proved to be better simulating aspects of clinical nociceptive and neuropathic pain. In the current study, 24 subjects were randomly divided into two groups with a 2 × 2 factorial design: laterality (ipsi- or contralateral side, inter-subject) × treatment with counter-balanced at an interval of one week (verum and placebo electroacupuncture, within-subject). We observed subjective pain intensity and brain activations changes induced by capsaicin allodynia pain stimuli before and after electroacupuncture treatment at acupoint LI4 for 30 min. Analysis of variance results indicated that ipsilateral electroacupuncture treatment produced significant pain relief and wide brain signal suppressions in pain-related brain areas compared with contralateral electroacupuncture. We also found that verum electroacupuncture at either ipsi- or contralateral side to the pain site exhibited comparable significant magnitudes of analgesic effect. By contrast, placebo electroacupuncture elicited significant pain reductions only on the ipsilateral rather than contralateral side. It was inferred that placebo analgesia maybe attenuated on the region of the body (opposite to pain site) where attention was less focused, suggesting that analgesic effect of placebo electroacupuncture mainly rely on the motivation of its spatial-specific placebo responses via attention mechanism. This inference can be further supported by the evidence that the significant interaction effect of manipulation laterality and treatment was exclusively located within the default mode network, including the bilateral superior parietal lobule, inferior parietal lobule, precuneus, and left posterior cingulate cortex. It is also proved that disruptions of the default mode network may account for the cognitive and behavioral impairments in chronic pain patients. Our findings further suggested that default mode network participates in the modulation of spatial-oriented attention on placebo analgesia as a mechanism underlying the degree to which treatment side corresponding to the pain.

Cytokine Response, Tract-Specific Fractional Anisotropy, and Brain Morphometry in Post-Stroke Cognitive Impairment.

PubMed

Kulesh, Aleksey; Drobakha, Viktor; Kuklina, Elena; Nekrasova, Irina; Shestakov, Vladimir

2018-07-01

Post-stroke cognitive impairment is a clinically heterogeneous condition and its types have a different course and prognosis. The aim of the present study is to address the roles of inflammation, white matter pathology, and brain atrophy in different neuropsychological types of cognitive impairment in the acute period of ischemic stroke. In 92 patients, we performed an assessment of the cognitive status and measured concentrations of cytokines (interleukin [IL]-1β, IL-6, tumor necrosis factor-alpha, IL-10) in liquor and serum, as well as a number of magnetic resonance imaging (MRI) morphometric parameters and fractional anisotropy. The control group consisted of 14 individuals without cerebrovascular disease. All patients had a higher level of IL-10 in serum than the control group. Patients with dysexecutive cognitive impairment had a higher concentration of IL-1β and IL-10 in liquor, IL-6 level in serum, and a lower fractional anisotropy of the ipsilateral thalamus than patients with normal cognition. Patients with mixed cognitive impairment were characterized by a lower fractional anisotropy of contralateral fronto-occipital fasciculus, compared with patients with dysexecutive cognitive impairment. Patients with both dysexecutive and mixed cognitive deficit had a wide area of leukoaraiosis and a reduced fractional anisotropy of the contralateral cingulum, compared with patients without cognitive impairment. Also, we found numerous correlations between cognitive status and levels of cytokines, MRI morphometric parameters, and fractional anisotropy of certain regions of the brain. The concentrations of cytokines in serum and cerebrospinal fluid studied in combination with MRI morphometric parameters and fractional anisotropy appear to be informative biomarkers of clinical types of post-stroke cognitive impairment. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Hippocampus-sparing radiotherapy using volumetric modulated arc therapy (VMAT) to the primary brain tumor: the result of dosimetric study and neurocognitive function assessment.

PubMed

Kim, Kyung Su; Wee, Chan Woo; Seok, Jin-Yong; Hong, Joo Wan; Chung, Jin-Beom; Eom, Keun-Yong; Kim, Jae-Sung; Kim, Chae-Yong; Park, Young Ho; Kim, Yu Jung; Kim, In Ah

2018-02-20

We hypothesized that hippocampal-sparing radiotherapy via volumetric modulated arc therapy (VMAT) could preserve the neurocognitive function (NCF) of patients with primary brain tumors treated with radiotherapy. We reviewed data from patients with primary brain tumors who underwent hippocampal-sparing brain radiotherapy via VMAT between February 2014 and December 2015. The optimization criteria for the contralateral hippocampus was a maximum dose (D max ) of less than 17 Gy. For NCF evaluations, the Seoul Verbal Learning Test for total recall, delayed recall, and recognition (SVLT-TR, DR, and Recognition) was performed at baseline and at seven months after radiotherapy. A total of 26 patients underwent NCF testing seven months after radiotherapy. Their median age was 49.5 years (range 26-77 years), and 14 (53.8%) had grade III/IV tumors. The median D max to the contralateral hippocampus was 16.4 Gy (range 3.5-63.4). The median mean dose to the contralateral hippocampus, expressed as equivalent to a 2-Gy dose (EQD 2/2 ), was 7.4 Gy 2 (0.7-13.1). The mean relative changes in SVLT-TR, SVLT-DR, and SVLT-Recognition at seven months compared to the baseline were - 7.7% (95% confidence interval [CI], - 19.6% to 4.2%), - 9.2% (95% CI, - 25.4% to 7.0%), and - 3.4% (- 12.7% to 5.8%), respectively. Two patients (7.7%) showed deteriorated NCF in the SVLT-TR and SVLT-DR, and three (11.5%) in the SVLT-Recognition. The mean dose of the left hippocampus and bilateral hippocampi were significantly higher in patients showing deterioration of the SVLT-TR and SVLT-Recognition than in those without deterioration. The contralateral hippocampus could be effectively spared in patients with primary brain tumor via VMAT to preserve the verbal memory function. Further investigation is needed to identify those patients who will most benefit from hippocampal-sparing radiotherapy of the primary brain tumor.

Structure changes of human brain gray matter neurons and astrocytes in acute local ischemic injury.

PubMed

Sergeeva, S P; Shishkina, L V; Litvitskiy, P F; Breslavich, I D; Vinogradov, E V

2016-01-01

The purpose to identify key morphological features of the Astrocytes and Neurons in the acute local cerebral ischemia human cortex. Left middle cerebral artery ischemic stroke died persons (n = 9) brain tissue samples from 3 zones: 1st - contiguous to the tissue necrotic damage site zone, 2nd - 5-10 cm distant from the previous one, 3rd - the damage site symmetrical zone of the contralateral hemisphere. For GFAP, MAP-2, NSE, p53 detection indirect immunoperoxidase immunohistochemical staining method has been used. Also, the samples were Nissl and Hematoxylin-Eosin stained. The most pronounced changes in the quantity and morphological structure of astrocytes and neurons are found in directly adjacent to the necrotic core region of theleft middle cerebral artery ischemic stroke brain. This indicates the prevalence of the inflammation processes around the area of nerve tissueischemic destruction. Morphological changes of neurons and astrocytes, apoptosis, enhanced neuron-astrocyte interaction found in the area bordering on necrotic core (5-10 cm from it), as well as ischemic hearth symmetrical sites of the contralateral hemisphere. This interaction is essential for the neuroplasticityrealization in the local ischemic brain injury. The results obtained were shown the nerve tissue morphological characteristics changes occur in local cerebral cortex ischemic injury not only in the lesion, but also in the contralateral hemisphere. These changes are probably related to the implementation of neuroplasticity.

Analysis of Time-Dependent Brain Network on Active and MI Tasks for Chronic Stroke Patients

PubMed Central

Chang, Won Hyuk; Kim, Yun-Hee; Lee, Seong-Whan; Kwon, Gyu Hyun

2015-01-01

Several researchers have analyzed brain activities by investigating brain networks. However, there is a lack of the research on the temporal characteristics of the brain network during a stroke by EEG and the comparative studies between motor execution and imagery, which became known to have similar motor functions and pathways. In this study, we proposed the possibility of temporal characteristics on the brain networks of a stroke. We analyzed the temporal properties of the brain networks for nine chronic stroke patients by the active and motor imagery tasks by EEG. High beta band has a specific role in the brain network during motor tasks. In the high beta band, for the active task, there were significant characteristics of centrality and small-worldness on bilateral primary motor cortices at the initial motor execution. The degree centrality significantly increased on the contralateral primary motor cortex, and local efficiency increased on the ipsilateral primary motor cortex. These results indicate that the ipsilateral primary motor cortex constructed a powerful subnetwork by influencing the linked channels as compensatory effect, although the contralateral primary motor cortex organized an inefficient network by using the connected channels due to lesions. For the MI task, degree centrality and local efficiency significantly decreased on the somatosensory area at the initial motor imagery. Then, there were significant correlations between the properties of brain networks and motor function on the contralateral primary motor cortex and somatosensory area for each motor execution/imagery task. Our results represented that the active and MI tasks have different mechanisms of motor acts. Based on these results, we indicated the possibility of customized rehabilitation according to different motor tasks. We expect these results to help in the construction of the customized rehabilitation system depending on motor tasks by understanding temporal functional characteristics on brain network for a stroke. PMID:26656269

Trans sodium crocetinate: functional neuroimaging studies in a hypoxic brain tumor.

PubMed

Sheehan, Jason P; Popp, Britney; Monteith, Stephen; Toulmin, Sushila; Tomlinson, Jennifer; Martin, Jessica; Cifarelli, Christopher P; Lee, Dae-Hee; Park, Deric M

2011-10-01

Intratumoral hypoxia is believed to be exhibited in high-grade gliomas. Trans sodium crocetinate (TSC) has been shown to increase oxygen diffusion to hypoxic tissues. In this research, the authors use oxygen-sensitive PET studies to evaluate the extent of hypoxia in vivo in a glioblastoma model and the effect of TSC on the baseline oxygenation of the tumor. The C6 glioma cells were stereotactically implanted in the right frontal region of rat brains. Formation of intracranial tumors was confirmed on MR imaging. Animals were injected with Copper(II) diacetyl-di(N4-methylthiosemicarbazone) (Cu-ATSM) and then either TSC or saline (6 rats each). Positron emission tomography imaging was performed, and relative uptake values were computed to determine oxygenation within the tumor and normal brain parenchyma. Additionally, TSC or saline was infused into the animals, and carbonic anhydrase 9 (CA9) and hypoxia-inducing factor-1α (HIF-1α) protein expression were measured 1 day afterward. On PET imaging, all glioblastoma tumors demonstrated a statistically significant decrease in uptake of Cu-ATSM compared with the contralateral cerebral hemisphere (p = 0.000002). The mean relative uptake value of the tumor was 3900 (range 2203-6836), and that of the contralateral brain tissue was 1017 (range 488-2304). The mean relative hypoxic tumor volume for the saline group and TSC group (6 rats each) was 1.01 ± 0.063 and 0.69 ± 0.062, respectively (mean ± SEM, p = 0.002). Infusion of TSC resulted in a 31% decrease in hypoxic volume. Immunoblot analysis revealed expression of HIF-1α and CA9 in all tumor specimens. Some glioblastomas exhibit hypoxia that is demonstrable on oxygen-specific PET imaging. It appears that TSC lessens intratumoral hypoxia on functional imaging. Further studies should explore relative hypoxia in glioblastoma and the potential therapeutic gains that can be achieved by lessening hypoxia during delivery of adjuvant treatment.

Contralateral suppression of transient-evoked otoacoustic emissions in children with sickle cell disease.

PubMed

Stuart, Andrew; Preast, June L

2012-01-01

In previous studies, otoacoustic emissions (OAEs) have been found to be larger in normal-hearing children with sickle cell disease (SCD). It was hypothesized that some dysfunction or reduction in the medial olivocochlear efferent suppression of outer hair cell activity was responsible for this phenomenon. To test this hypothesis, contralateral suppression of transient-evoked otoacoustic emissions (TEOAEs) was examined in children with and without SCD. Thirteen African American school-aged normal-hearing children with homozygous SCD and 13 age- and gender-matched control children participated. TEOAEs were obtained bilaterally with 80 dB peSPL nonlinear click stimuli. To examine contralateral suppression, TEOAEs were obtained with 60 dB peSPL linear click stimuli with and without a contralateral 65 dB SPL white noise suppressor. Overall and half-octave band TEOAE levels were found to be larger in children with SCD relative to the normal control children (p < 0.05), consistent with previous reports of increased OAE levels. There was no significant difference (p > 0.05) in the absolute or proportional amount of TEOAE suppression as a function of group and ear. There were also no significant correlations or linear predictive relationships between TEOAE suppression and TEOAE level for either ear or group (p > 0.05). These findings do not support the notion that increased OAE levels in children with SCD are a consequence of abnormal medial olivocochlear system function as assessed with contralateral suppression of TEOAEs.

Reducing contralateral SI activity reveals hindlimb receptive fields in the SI forelimb-stump representation of neonatally amputated rats.

PubMed

Pluto, Charles P; Chiaia, Nicolas L; Rhoades, Robert W; Lane, Richard D

2005-09-01

In adult rats that sustained forelimb amputation on the day of birth, >30% of multiunit recording sites in the forelimb-stump representation of primary somatosensory cortex (SI) also respond to cutaneous hindlimb stimulation when cortical GABA(A+B) receptors are blocked (GRB). This study examined whether hindlimb receptive fields could also be revealed in forelimb-stump sites by reducing one known source of excitatory input to SI GABAergic neurons, the contralateral SI cortex. Corpus callosum projection neurons connect homotopic SI regions, making excitatory contacts onto pyramidal cells and interneurons. Thus in addition to providing monosynaptic excitation in SI, callosal fibers can produce disynaptic inhibition through excitatory synapses with inhibitory interneurons. Based on the latter of these connections, we hypothesized that inactivating the contralateral (intact) SI forelimb region would "unmask" normally suppressed hindlimb responses by reducing the activity of SI GABAergic neurons. The SI forelimb-stump representation was first mapped under normal conditions and then during GRB to identify stump/hindlimb responsive sites. After GRB had dissipated, the contralateral (intact) SI forelimb region was mapped and reversibly inactivated with injections of 4% lidocaine, and selected forelimb-stump sites were retested. Contralateral SI inactivation revealed hindlimb responses in approximately 60% of sites that were stump/hindlimb responsive during GRB. These findings indicate that activity in the contralateral SI contributes to the suppression of reorganized hindlimb receptive fields in neonatally amputated rats.

No improvement of neuronal metabolism in the reperfusion phase with melatonin treatment after hypoxic-ischemic brain injury in the neonatal rat.

PubMed

Berger, Hester R; Morken, Tora Sund; Vettukattil, Riyas; Brubakk, Ann-Mari; Sonnewald, Ursula; Widerøe, Marius

2016-01-01

Mitochondrial impairment is a key feature underlying neonatal hypoxic-ischemic (HI) brain injury and melatonin is potentially neuroprotective through its effects on mitochondria. In this study, we have used (1) H and (13) C NMR spectroscopy after injection of [1-(13) C]glucose and [1,2-(13) C]acetate to examine neuronal and astrocytic metabolism in the early reperfusion phase after unilateral HI brain injury in 7-day-old rat pups, exploring the effects of HI on mitochondrial function and the potential protective effects of melatonin on brain metabolism. One hour after hypoxia-ischemia, astrocytic metabolism was recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was clearly impaired. Pyruvate carboxylation was also lower in both hemispheres after HI. The transfer of glutamate from neurons to astrocytes was higher whereas the transfer of glutamine from astrocytes to neurons was lower 1 h after HI in the contralateral hemisphere. Neuronal metabolism was equally affected in pups treated with melatonin (10 mg/kg) immediately after HI as in vehicle treated pups indicating that the given dose of melatonin was not capable of protecting the neuronal mitochondria in this early phase after HI brain injury. However, any beneficial effects of melatonin might have been masked by modulatory effects of the solvent dimethyl sulfoxide on cerebral metabolism. Neuronal and astrocytic metabolism was examined by (13) C and (1) H NMR spectroscopy in the early reperfusion phase after unilateral hypoxic-ischemic brain injury and melatonin treatment in neonatal rats. One hour after hypoxia-ischemia astrocytic mitochondrial metabolism had recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was impaired. Melatonin treatment did not show a protective effect on neuronal metabolism. © 2015 International Society for Neurochemistry.

Differentiation of Glioblastoma from Brain Metastasis: Qualitative and Quantitative Analysis Using Arterial Spin Labeling MR Imaging.

PubMed

Sunwoo, Leonard; Yun, Tae Jin; You, Sung-Hye; Yoo, Roh-Eul; Kang, Koung Mi; Choi, Seung Hong; Kim, Ji-Hoon; Sohn, Chul-Ho; Park, Sun-Won; Jung, Cheolkyu; Park, Chul-Kee

2016-01-01

To evaluate the diagnostic performance of cerebral blood flow (CBF) by using arterial spin labeling (ASL) perfusion magnetic resonance (MR) imaging to differentiate glioblastoma (GBM) from brain metastasis. The institutional review board of our hospital approved this retrospective study. The study population consisted of 128 consecutive patients who underwent surgical resection and were diagnosed as either GBM (n = 89) or brain metastasis (n = 39). All participants underwent preoperative MR imaging including ASL. For qualitative analysis, the tumors were visually graded into five categories based on ASL-CBF maps by two blinded reviewers. For quantitative analysis, the reviewers drew regions of interest (ROIs) on ASL-CBF maps upon the most hyperperfused portion within the tumor and upon peritumoral T2 hyperintensity area. Signal intensities of intratumoral and peritumoral ROIs for each subject were normalized by dividing the values by those of contralateral normal gray matter (nCBFintratumoral and nCBFperitumoral, respectively). Visual grading scales and quantitative parameters between GBM and brain metastasis were compared. In addition, the area under the receiver-operating characteristic curve was used to evaluate the diagnostic performance of ASL-driven CBF to differentiate GBM from brain metastasis. For qualitative analysis, GBM group showed significantly higher grade compared to metastasis group (p = 0.001). For quantitative analysis, both nCBFintratumoral and nCBFperitumoral in GBM were significantly higher than those in metastasis (both p < 0.001). The areas under the curve were 0.677, 0.714, and 0.835 for visual grading, nCBFintratumoral, and nCBFperitumoral, respectively (all p < 0.001). ASL perfusion MR imaging can aid in the differentiation of GBM from brain metastasis.

Complement mRNA in the mammalian brain: responses to Alzheimer's disease and experimental brain lesioning.

PubMed

Johnson, S A; Lampert-Etchells, M; Pasinetti, G M; Rozovsky, I; Finch, C E

1992-01-01

This study describes evidence in the adult human and rat brain for mRNAs that encode two complement (C) proteins, C1qB and C4. C proteins are important effectors of humoral immunity and inflammation in peripheral tissues but have not been considered as normally present in brain. Previous immunocytochemical studies showed that C proteins are associated with plaques, tangles, and dystrophic neurites in Alzheimer's disease (AD), but their source is unknown. Combined immunocytochemistry and in situ hybridization techniques show C4 mRNA in pyramidal neurons and C1qB mRNA in microglia. Primary rat neuron cultures also show C1qB mRNA. In the cortex from AD brains, there were two- to threefold increases of C1qB mRNA and C4 mRNA, and increased C1qB mRNA prevalence was in part associated with microglia. As a model for AD, we examined entorhinal cortex perforant path transection in the rat brain, which caused rapid increases of C1qB mRNA in the ipsilateral, but not contralateral, hippocampus and entorhinal cortex. The role of brain-derived acute and chronic C induction during AD and experimental lesions can now be considered in relation to functions of C proteins that pertain to cell degeneration and/or cell preservation and synaptic plasticity.

Cerebral schistosomiasis: diffusion-weighted imaging helps to differentiate from brain glioma and metastasis.

PubMed

Huang, Jinbai; Luo, Jing; Peng, Jie; Yang, Tao; Zheng, Huanghua; Mao, Chunping

2017-11-01

Background Diffusion-weighted imaging (DWI) was introduced into clinical use some years ago. However, its use in the diagnosis of cerebral schistosomiasis has not been reported. Purpose To investigate the ability of the apparent diffusion coefficient (ADC) value of DWI in the diagnosis of cerebral schistosomiasis, and to differentiate it from brain high-grade gliomas and metastasis. Material and Methods Conventional brain MRI with pre-contrast, post-contrast, and DWI was performed on 50 cases of cerebral schistosomiasis, high-grade glioma, and brain metastasis. The ADC values of the three lesions, the proximal and the distal perifocal edema were measured. In order to remove the individual difference effect of ADC values, relative ADC (rADC) values were calculated through dividing the ADC value of the lesion area by that of the contralateral normal white matter. rADC values were used to evaluate the differences among cerebral schistosomiasis, brain high-grade gliomas, and metastasis. Results rADC of cerebral schistosomiasis was significantly lower than rADC of brain metastasis ( P < 0.05), without any significant differences when compared with high-grade gliomas. rADC of proximal perifocal edema in cerebral schistosomiasis was significantly higher than in high-grade gliomas ( P < 0.010), but not different compared with brain metastasis. Conclusion DWI examination with ADC values of lesions and proximal perifocal edema might be helpful in the exact diagnosis of cerebral schistosomiasis.

Facilitated beam-walking recovery during acute phase by kynurenic acid treatment in a rat model of photochemically induced thrombosis causing focal cerebral ischemia.

PubMed

Abo, Masahiro; Yamauchi, Hideki; Suzuki, Masahiko; Sakuma, Mio; Urashima, Mitsuyoshi

We previously demonstrated the presence of activated areas in the non-injured contralateral sensorimotor cortex in addition to the ipsilateral sensorimotor cortex of the area surrounding a brain infarction, using a rat model of focal photochemically induced thrombosis (PIT) and functional magnetic resonance imaging. Using this model, we next applied gene expression profiling to screen key molecules upregulated in the activated area. RNA was extracted from the ipsilateral and contralateral sensorimotor cortex to the focal brain infarction and from the sham controlled cortex, and hybridized to gene-expression profiling arrays containing 1,322 neurology-related genes. Results showed that glycine receptors were upregulated in both the ipsilateral and contralateral cortex to the focal ischemic lesion. To prove the preclinical significance of upregulated glycine receptors, kynurenic acid, an endogenous antagonist to glycine receptors on neuronal cells, was administered intrathecally. As a result, the kynurenic acid significantly improved behavioral recovery within 10 days from paralysis induced by the focal PIT (p < 0.0001), as evaluated with beam walking. These results suggest that intrathecal administration of a glycine receptor antagonist may facilitate behavioral recovery during the acute phase after brain infarction. Copyright (c) 2006 S. Karger AG, Basel.

Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Plaga, Alexis; Shields, Lisa B.E.; Sun, David A.

Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority givenmore » to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study may help to stratify patients at risk for late effects to develop strategies to reduce frequency and severity of radiation sequelae.« less

Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation.

PubMed

Plaga, Alexis; Shields, Lisa B E; Sun, David A; Vitaz, Todd W; Spalding, Aaron C

2012-01-01

Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study may help to stratify patients at risk for late effects to develop strategies to reduce frequency and severity of radiation sequelae. Copyright © 2012 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Variations in cerebral organization as a function of handedness, hand posture in writing, and sex.

PubMed

Levy, J; Reid, M

1978-06-01

During the past century, it has become increasingly apparent that there is a great deal of variation in the direction and degree of cerebral lateralization, a plurality of people having language and related functions strongly specialized to the left hemisphere and visuospatial functions strongly specialized to the right, with substantial minorities manifesting various deviations from this pattern. In particular, in 35%-50% of sinistrals and 1%-10% of dextrals, the right hemisphere is specialized for linguistic skills, and in some unknown fraction of the two handedness groups, verbal and/or spatial abilities are, to varying extents, bilateralized. Levy (1973) suggested that the hand posture adopted during writing might be an index of the lateral relationship between the dominant writing hand and the language hemisphere, a normal posture indicating contralateral language specialization, and an inverted posture indicating ipsilateral language specialization. In the present investigation, two tachistoscopic tests of cerebral lateralization, one measuring spatial functions and one measuring verbal function, were administered to 73 subjects classified by handedness, hand posture during writing, and sex. Among both dextral and sinistral subjects with a normal writing posture, language and spatial functions were specialized to the contralateral and ipsilateral hemispheres, respectively, and lateral differentiation of the brain was strong. The reverse was seen in subjects having an inverted writing posture. In all groups, females were less laterally differentiated than males. In 70 out of 73 subjects, the direction of cerebral laterization was accurately predicted by handedness and hand posture. The 3 subjects (2 females and 1 male) who failed to manifest the predicted relations were all left-handers having an inverted hand posture . In this group, lateral differentiation was so weak that the reliability of the tachistoscopic tests was reduced, and we attribute these three predictive failures to this cause. Thus, almost all of the variation in the lateral organization of the brain was accounted for by handedness, hand posture, and sex.

Granger causal time-dependent source connectivity in the somatosensory network

NASA Astrophysics Data System (ADS)

Gao, Lin; Sommerlade, Linda; Coffman, Brian; Zhang, Tongsheng; Stephen, Julia M.; Li, Dichen; Wang, Jue; Grebogi, Celso; Schelter, Bjoern

2015-05-01

Exploration of transient Granger causal interactions in neural sources of electrophysiological activities provides deeper insights into brain information processing mechanisms. However, the underlying neural patterns are confounded by time-dependent dynamics, non-stationarity and observational noise contamination. Here we investigate transient Granger causal interactions using source time-series of somatosensory evoked magnetoencephalographic (MEG) elicited by air puff stimulation of right index finger and recorded using 306-channel MEG from 21 healthy subjects. A new time-varying connectivity approach, combining renormalised partial directed coherence with state space modelling, is employed to estimate fast changing information flow among the sources. Source analysis confirmed that somatosensory evoked MEG was mainly generated from the contralateral primary somatosensory cortex (SI) and bilateral secondary somatosensory cortices (SII). Transient Granger causality shows a serial processing of somatosensory information, 1) from contralateral SI to contralateral SII, 2) from contralateral SI to ipsilateral SII, 3) from contralateral SII to contralateral SI, and 4) from contralateral SII to ipsilateral SII. These results are consistent with established anatomical connectivity between somatosensory regions and previous source modeling results, thereby providing empirical validation of the time-varying connectivity analysis. We argue that the suggested approach provides novel information regarding transient cortical dynamic connectivity, which previous approaches could not assess.

Effect of visual feedback on brain activation during motor tasks: an FMRI study.

PubMed

Noble, Jeremy W; Eng, Janice J; Boyd, Lara A

2013-07-01

This study examined the effect of visual feedback and force level on the neural mechanisms responsible for the performance of a motor task. We used a voxel-wise fMRI approach to determine the effect of visual feedback (with and without) during a grip force task at 35% and 70% of maximum voluntary contraction. Two areas (contralateral rostral premotor cortex and putamen) displayed an interaction between force and feedback conditions. When the main effect of feedback condition was analyzed, higher activation when visual feedback was available was found in 22 of the 24 active brain areas, while the two other regions (contralateral lingual gyrus and ipsilateral precuneus) showed greater levels of activity when no visual feedback was available. The results suggest that there is a potentially confounding influence of visual feedback on brain activation during a motor task, and for some regions, this is dependent on the level of force applied.

Difference of motor overflow depending on the impaired or unimpaired hand in stroke patients.

PubMed

Kim, Yushin; Kim, Woo-Sub; Shim, Jae Kun; Suh, Dong Won; Kim, TaeYeong; Yoon, BumChul

2015-02-01

The aim of this study was to investigate the patterns of contralateral motor overflow (i.e. mirror movement) between the homologous body parts on the right and left side, in stroke patients during single-finger and multi-finger maximum force production tasks. Forty subjects, including stroke (n=20) and normal subjects (n=20), participated in this study. The stroke subjects maximally pressed force sensors with their fingers in a flexed position using a single (index, middle, ring, or little) or all fingers (all 4 fingers) using the impaired (IH) or unimpaired (UIH) hand, while the non-patient subjects used their right hands for the same tasks. The maximal voluntary forces in the ipsilateral and unintended pressing forces of each contralateral finger were recorded during the tasks. The magnitude of motor overflow to the contralateral side was calculated using the index of contralateral independence (CI). During the single finger tasks, the finger CI was significantly decreased in the UIH (91%) compared with that in the IH (99%) or normal hands (99%). Likewise, the multiple finger tasks showed that the CI was significantly lower in the UIH (84%) compared with that in the IH (96%) or normal hands (99%). However, the maximal forces were significantly lower in the IH relative to those in the UIH and normal hands. These data demonstrate that stroke patients have greater motor overflow from the UIH to the IH. Copyright © 2014 Elsevier B.V. All rights reserved.

Causal functional contributions and interactions in the attention network of the brain: an objective multi-perturbation analysis.

PubMed

Zavaglia, Melissa; Hilgetag, Claus C

2016-06-01

Spatial attention is a prime example for the distributed network functions of the brain. Lesion studies in animal models have been used to investigate intact attentional mechanisms as well as perspectives for rehabilitation in the injured brain. Here, we systematically analyzed behavioral data from cooling deactivation and permanent lesion experiments in the cat, where unilateral deactivation of the posterior parietal cortex (in the vicinity of the posterior middle suprasylvian cortex, pMS) or the superior colliculus (SC) cause a severe neglect in the contralateral hemifield. Counterintuitively, additional deactivation of structures in the opposite hemisphere reverses the deficit. Using such lesion data, we employed a game-theoretical approach, multi-perturbation Shapley value analysis (MSA), for inferring functional contributions and network interactions of bilateral pMS and SC from behavioral performance in visual attention studies. The approach provides an objective theoretical strategy for lesion inferences and allows a unique quantitative characterization of regional functional contributions and interactions on the basis of multi-perturbations. The quantitative analysis demonstrated that right posterior parietal cortex and superior colliculus made the strongest positive contributions to left-field orienting, while left brain regions had negative contributions, implying that their perturbation may reverse the effects of contralateral lesions or improve normal function. An analysis of functional modulations and interactions among the regions revealed redundant interactions (implying functional overlap) between regions within each hemisphere, and synergistic interactions between bilateral regions. To assess the reliability of the MSA method in the face of variable and incomplete input data, we performed a sensitivity analysis, investigating how much the contribution values of the four regions depended on the performance of specific configurations and on the prediction of unknown performances. The results suggest that the MSA approach is sensitive to categorical, but insensitive to gradual changes in the input data. Finally, we created a basic network model that was based on the known anatomical interactions among cortical-tectal regions and reproduced the experimentally observed behavior in visual orienting. We discuss the structural organization of the network model relative to the causal modulations identified by MSA, to aid a mechanistic understanding of the attention network of the brain.

Contralateral Noise Stimulation Delays P300 Latency in School-Aged Children.

PubMed

Ubiali, Thalita; Sanfins, Milaine Dominici; Borges, Leticia Reis; Colella-Santos, Maria Francisca

2016-01-01

The auditory cortex modulates auditory afferents through the olivocochlear system, which innervates the outer hair cells and the afferent neurons under the inner hair cells in the cochlea. Most of the studies that investigated the efferent activity in humans focused on evaluating the suppression of the otoacoustic emissions by stimulating the contralateral ear with noise, which assesses the activation of the medial olivocochlear bundle. The neurophysiology and the mechanisms involving efferent activity on higher regions of the auditory pathway, however, are still unknown. Also, the lack of studies investigating the effects of noise on human auditory cortex, especially in peadiatric population, points to the need for recording the late auditory potentials in noise conditions. Assessing the auditory efferents in schoolaged children is highly important due to some of its attributed functions such as selective attention and signal detection in noise, which are important abilities related to the development of language and academic skills. For this reason, the aim of the present study was to evaluate the effects of noise on P300 responses of children with normal hearing. P300 was recorded in 27 children aged from 8 to 14 years with normal hearing in two conditions: with and whitout contralateral white noise stimulation. P300 latencies were significantly longer at the presence of contralateral noise. No significant changes were observed for the amplitude values. Contralateral white noise stimulation delayed P300 latency in a group of school-aged children with normal hearing. These results suggest a possible influence of the medial olivocochlear activation on P300 responses under noise condition.

Beta activity in the premotor cortex is increased during stabilized as compared to normal walking

PubMed Central

Bruijn, Sjoerd M.; Van Dieën, Jaap H.; Daffertshofer, Andreas

2015-01-01

Walking on two legs is inherently unstable. Still, we humans perform remarkable well at it, mostly without falling. To gain more understanding of the role of the brain in controlling gait stability we measured brain activity using electro-encephalography (EEG) during stabilized and normal walking. Subjects walked on a treadmill in two conditions, each lasting 10 min; normal, and while being laterally stabilized by elastic cords. Kinematics of trunk and feet, electro-myography (EMG) of neck muscles, as well as 64-channel EEG were recorded. To assess gait stability the local divergence exponent, step width, and trunk range of motion were calculated from the kinematic data. We used independent component (IC) analysis to remove movement, EMG, and eyeblink artifacts from the EEG, after which dynamic imaging of coherent sources beamformers were determined to identify cortical sources that showed a significant difference between conditions. Stabilized walking led to a significant increase in gait stability, i.e., lower local divergence exponents. Beamforming analysis of the beta band activity revealed significant sources in bilateral pre-motor cortices. Projection of sensor data on these sources showed a significant difference only in the left premotor area, with higher beta power during stabilized walking, specifically around push-off, although only significant around contralateral push-off. It appears that even during steady gait the cortex is involved in the control of stability. PMID:26578937

Effects of smoking marijuana on focal attention and brain blood flow.

PubMed

O'Leary, Daniel S; Block, Robert I; Koeppel, Julie A; Schultz, Susan K; Magnotta, Vincent A; Ponto, Laura Boles; Watkins, G Leonard; Hichwa, Richard D

2007-04-01

Using an attention task to control cognitive state, we previously found that smoking marijuana changes regional cerebral blood flow (rCBF). The present study measured rCBF during tasks requiring attention to left and right ears in different conditions. Twelve occasional marijuana users (mean age 23.5 years) were imaged with PET using [15O]water after smoking marijuana or placebo cigarettes as they performed a reaction time (RT) baseline task, and a dichotic listening task with attend-right- and attend-left-ear instructions. Smoking marijuana, but not placebo, resulted in increased normalized rCBF in orbital frontal cortex, anterior cingulate, temporal pole, insula, and cerebellum. RCBF was reduced in visual and auditory cortices. These changes occurred in all three tasks and replicated our earlier studies. They appear to reflect the direct effects of marijuana on the brain. Smoking marijuana lowered rCBF in auditory cortices compared to placebo but did not alter the normal pattern of attention-related rCBF asymmetry (i.e., greater rCBF in the temporal lobe contralateral to the direction of attention) that was also observed after placebo. These data indicate that marijuana has dramatic direct effects on rCBF, but causes relatively little change in the normal pattern of task-related rCBF on this auditory focused attention task. Copyright 2007 John Wiley & Sons, Ltd.

Study of the influence of the laterality of mobile phone use on the SAR induced in two head models

NASA Astrophysics Data System (ADS)

Ghanmi, Amal; Varsier, Nadège; Hadjem, Abdelhamid; Conil, Emmanuelle; Picon, Odile; Wiart, Joe

2013-05-01

The objective of this paper is to investigate and to analyse the influence of the laterality of mobile phone use on the exposure of the brain to radio-frequencies (RF) and electromagnetic fields (EMF) from different mobile phone models using the finite-difference time-domain (FDTD) method. The study focuses on the comparison of the specific absorption rate (SAR) induced on the right and left sides of two numerical adult and child head models. The heads are exposed by both phone models operating in GSM frequency bands for both ipsilateral and contralateral configurations. A slight SAR difference between the two sides of the heads is noted. The results show that the variation between the left and the right sides is more important at 1800 MHz for an ipsilateral use. Indeed, at this frequency, the variation can even reach 20% for the SAR10g and the SAR1g induced in the head and in the brain, respectively. Moreover, the average SAR induced by the mobile phone in the half hemisphere of the brain in ipsilateral exposure is higher than in contralateral exposure. Owing to the superficial character of energy deposition at 1800 MHz, this difference in the SAR induced for the ipsilateral and contralateral usages is more significant at 1800 MHz than at 900 MHz. The results have shown that depending on the phantom head models, the SAR distribution in the brain can vary because of differences in anatomical proportions and in the geometry of the head models. The induced SAR in child head and in sub-regions of the brain is significantly higher (up to 30%) compared to the adult head. This paper confirms also that the shape/design of the mobile and the location of the antenna can have a large influence at high frequency on the exposure of the brain, particularly on the SAR distribution and on the distinguished brain regions.

Futurism - Neither Nurturing Nor Training for Education.

ERIC Educational Resources Information Center

Kise, Leonard K.; Swanson, Jennie E.

The paper considers the future of education, particularly special education, in terms of theory. Reviewed is research in neurology relating to contra-lateral development in brain hemispheres, cephalo-caudal and caudal-cephalo myelination patterns or neural systems, and integration of neural patterns and neo-cortical control of the brain. Also…

Affect of deep brain stimulation on limb paresis after stroke.

PubMed

Phillips, N I; Bhakta, B B

2000-07-15

A deep brain stimulator was implanted in the periventricular grey matter of the third ventricle for pain after stroke in a man aged 48 years. As well as a beneficial analgesic effect, the patient reported improved function in the contralateral paretic arm, which was confirmed on formal testing.

Polyamine Catabolism Is Enhanced after Traumatic Brain Injury

PubMed Central

Zahedi, Kamyar; Huttinger, Francis; Morrison, Ryan; Murray-Stewart, Tracy; Casero, Robert A.

2010-01-01

Abstract Polyamines spermine and spermidine are highly regulated, ubiquitous aliphatic cations that maintain DNA structure and function as immunomodulators and as antioxidants. Polyamine homeostasis is disrupted after brain injuries, with concomitant generation of toxic metabolites that may contribute to secondary injuries. To test the hypothesis of increased brain polyamine catabolism after traumatic brain injury (TBI), we determined changes in catabolic enzymes and polyamine levels in the rat brain after lateral controlled cortical impact TBI. Spermine oxidase (SMO) catalyzes the degradation of spermine to spermidine, generating H2O2 and aminoaldehydes. Spermidine/spermine-N1-acetyltransferase (SSAT) catalyzes acetylation of these polyamines, and both are further oxidized in a reaction that generates putrescine, H2O2, and aminoaldehydes. In a rat cortical impact model of TBI, SSAT mRNA increased subacutely (6–24 h) after TBI in ipsilateral cortex and hippocampus. SMO mRNA levels were elevated late, from 3 to 7 days post-injury. Polyamine catabolism increased as well. Spermine levels were normal at 6 h and decreased slightly at 24 h, but were normal again by 72 h post-injury. Spermidine levels also decreased slightly (6–24 h), then increased by ∼50% at 72 h post-injury. By contrast, normally low putrescine levels increased up to sixfold (6–72 h) after TBI. Moreover, N-acetylspermidine (but not N-acetylspermine) was detectable (24–72 h) near the site of injury, consistent with increased SSAT activity. None of these changes were seen in the contralateral hemisphere. Immunohistochemical confirmation indicated that SSAT and SMO were expressed throughout the brain. SSAT-immunoreactivity (SSAT-ir) increased in both neuronal and nonneuronal (likely glial) populations ipsilateral to injury. Interestingly, bilateral increases in cortical SSAT-ir neurons occurred at 72 h post-injury, whereas hippocampal changes occurred only ipsilaterally. Prolonged increases in brain polyamine catabolism are the likely cause of loss of homeostasis in this pathway. The potential for simple therapeutic interventions (e.g., polyamine supplementation or inhibition of polyamine oxidation) is an exciting implication of these studies. PMID:19968558

Malalignment and subchondral bone turnover in contralateral knees of overweight/obese women with unilateral osteoarthritis: implications for bilateral disease.

PubMed

Mazzuca, Steven A; Brandt, Kenneth D; Lane, Kathleen A; Chakr, Rafael

2011-11-01

To explore whether the risk of incident tibiofemoral (TF) osteoarthritis (OA) in the radiographically normal contralateral knee of overweight/obese women with unilateral knee OA is mediated by malalignment and/or preceded by increased turnover of subchondral bone. We used data of post hoc analyses from a randomized controlled trial. Cross-sectional analyses evaluated the baseline association between frontal plane alignment and bone turnover in the medial TF compartment in 78 radiographically normal contralateral knees. Longitudinal analyses ascertained whether incident radiographic OA (TF osteophyte formation within 30 months) was associated with malalignment and/or increased bone turnover at baseline. Alignment subcategories (varus/neutral/valgus) were based on the anatomic axis angle. (99m)Tc-methylene diphosphonate uptake in a late-phase bone scan was quantified in regions of interest in the medial tibia (MT) and medial femur (MF) and adjusted for uptake in a reference segment of the ipsilateral tibial shaft (TS). MF and MT uptake in varus contralateral knees was 50-55% greater than in the TS. Adjusted MT uptake in varus contralateral knees was significantly greater than that in neutral and valgus contralateral knees (mean 1.55 versus 1.38 and 1.43, respectively; P < 0.05). Among 69 contralateral knees followed longitudinally, 22 (32%) developed TF OA. Varus angulation was associated with a marginally significant increase in the odds of incident OA (adjusted odds ratio 3.98, P = 0.067). While the small sample size limited our ability to detect statistically significant risk factors, these data suggest that the risk of developing bilateral TF OA in overweight/obese women may be mediated by varus malalignment. Copyright © 2011 by the American College of Rheumatology.

Diagnostic Value of 68Ga PSMA-11 PET/CT Imaging of Brain Tumors-Preliminary Analysis.

PubMed

Sasikumar, Arun; Joy, Ajith; Pillai, M R A; Nanabala, Raviteja; Anees K, Muhammed; Jayaprakash, P G; Madhavan, Jayaprakash; Nair, Suresh

2017-01-01

To evaluate the feasibility of using Ga PSMA-11 PET/CT for imaging brain lesions and its comparison with F-FDG. Ten patients with brain lesions were included in the study. Five patients were treated cases of glioblastoma with suspected recurrence. F-FDG and Ga PSMA-11 brain scans were done for these patients. Five patients were sent for assessing the nature (primary lesion/metastasis) of space occupying lesion in brain. They underwent whole body F-FDG PET/CT scan and a primary site elsewhere in the body was ruled out. Subsequently they underwent Ga PSMA-11 brain PET/CT imaging. Target to background ratios (TBR) for the brain lesions were calculated using contralateral cerebellar uptake as background. In five treated cases of glioblastoma with suspected recurrence the findings of Ga PSMA-11 PET/CT showed good correlation with that of F-FDG PET/CT scan. Compared to the F-FDG, Ga PSMA-11 PET/CT showed better visualization of the recurrent lesion (presence/absence) owing to its significantly high TBR. Among the five cases evaluated for lesion characterization glioma and atypical meningioma patients showed higher SUVmax in the lesion with Ga PSMA-11 than with F-FDG and converse in cases of lymphoma. TBR was better with Ga PSMA PET/CT in all cases. Ga PSMA-11 PET/CT brain imaging is a potentially useful imaging tool in the evaluation of brain lesions. Absence of physiological uptake of Ga PSMA-11 in the normal brain parenchyma results in high TBR values and consequently better visualization of metabolically active disease in brain.

In vivo imaging of reactive oxygen species in mouse brain by using [3H]Hydromethidine as a potential radical trapping radiotracer

PubMed Central

Abe, Kohji; Takai, Nozomi; Fukumoto, Kazumi; Imamoto, Natsumi; Tonomura, Misato; Ito, Miwa; Kanegawa, Naoki; Sakai, Katsunori; Morimoto, Kenji; Todoroki, Kenichiro; Inoue, Osamu

2014-01-01

To assess reactive oxygen species (ROS) production by detecting the fluorescent oxidation product, hydroethidine has been used extensively. The present study was undertaken to evaluate the potential of the hydroethidine derivative as a radiotracer to measure in vivo brain ROS production. [3H]-labeled N-methyl-2,3-diamino-6-phenyl-dihydrophenanthridine ([3H]Hydromethidine) was synthesized, and evaluated using in vitro radical-induced oxidization and in vivo brain ROS production model. In vitro studies have indicated that [3H]Hydromethidine is converted to oxidized products by a superoxide radical (O2•−) and a hydroxyl radical (OH•−) but not hydrogen peroxide (H2O2). In vivo whole-body distribution study showed that [3H]Hydromethidine rapidly penetrated the brain and then was washed out in normal mice. Microinjection of sodium nitroprusside (SNP) into the brain was performed to produce ROS such as OH•− via Fenton reaction. A significant accumulation of radioactivity immediately after [3H]Hydromethidine injection was seen in the side of the brain treated with SNP (5 and 20 nmol) compared with that in the contralateral side. These results indicated that [3H]Hydromethidine freely penetrated into the brain where it was rapidly converted to oxidized forms, which were trapped there in response to the production of ROS. Thus, [3H]Hydromethidine should be useful as a radical trapping radiotracer in the brain. PMID:25227606

Blindsight and Unconscious Vision: What They Teach Us about the Human Visual System

PubMed Central

Ajina, Sara; Bridge, Holly

2017-01-01

Damage to the primary visual cortex removes the major input from the eyes to the brain, causing significant visual loss as patients are unable to perceive the side of the world contralateral to the damage. Some patients, however, retain the ability to detect visual information within this blind region; this is known as blindsight. By studying the visual pathways that underlie this residual vision in patients, we can uncover additional aspects of the human visual system that likely contribute to normal visual function but cannot be revealed under physiological conditions. In this review, we discuss the residual abilities and neural activity that have been described in blindsight and the implications of these findings for understanding the intact system. PMID:27777337

Quantification of Contralateral Breast Dose and Risk Estimate of Radiation-Induced Contralateral Breast Cancer Among Young Women Using Tangential Fields and Different Modes of Breathing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zurl, Brigitte, E-mail: brigitte.zurl@klinikum-graz.at; Stranzl, Heidi; Winkler, Peter

2013-02-01

Purpose: Whole breast irradiation with deep-inspiration breath-hold (DIBH) technique among left-sided breast cancer patients significantly reduces cardiac irradiation; however, a potential disadvantage is increased incidental irradiation of the contralateral breast. Methods and Materials: Contralateral breast dose (CBD) was calculated by comparing 400 treatment plans of 200 left-sided breast cancer patients whose tangential fields had been planned on gated and nongated CT data sets. Various anatomic and field parameters were analyzed for their impact on CBD. For a subgroup of patients (aged {<=}45 years) second cancer risk in the contralateral breast (CB) was modeled by applying the linear quadratic model, compoundmore » models, and compound models considering dose-volume information (DVH). Results: The mean CBD was significantly higher in DIBH with 0.69 Gy compared with 0.65 Gy in normal breathing (P=.01). The greatest impact on CBD was due to a shift of the inner field margin toward the CB in DIBH (mean 0.4 cm; range, 0-2), followed by field size in magnitude. Calculation with different risk models for CBC revealed values of excess relative risk/Gy ranging from 0.48-0.65 vs 0.46-0.61 for DIBH vs normal breathing, respectively. Conclusion: Contralateral breast dose, although within a low dose range, was mildly but significantly increased in 200 treatment plans generated under gated conditions, predominately due to a shift in the medial field margin. Risk modeling for CBC among women aged {<=}45 years also pointed to a higher risk when comparing DIBH with normal breathing. This risk, however, was substantially lower in the model considering DVH information. We think that clinical decisions should not be affected by this small increase in CBD with DIBH because DIBH is effective in reducing the dose to the heart in all patients.« less

Regulation of myeloid leukemia factor-1 interacting protein (MLF1IP) expression in glioblastoma.

PubMed

Hanissian, Silva H; Teng, Bin; Akbar, Umar; Janjetovic, Zorica; Zhou, Qihong; Duntsch, Christopher; Robertson, Jon H

2005-06-14

The myelodysplasia/myeloid leukemia factor 1-interacting protein MLF1IP is a novel gene which encodes for a putative transcriptional repressor. It is localized to human chromosome 4q35.1 and is expressed in both the nuclei and cytoplasm of cells. Northern and Western blot analyses have revealed MLF1IP to be present at very low amounts in normal brain tissues, whereas a number of human and rat glioblastoma (GBM) cell lines demonstrated a high level expression of the MLF1IP protein. Immunohistochemical analysis of rat F98 and C6 GBM tumor models showed that MLF1IP was highly expressed in the tumor core where it was co-localized with MLF1 and nestin. Moreover, MLF1IP expression was elevated in the contralateral brain where no tumor cells were detected. These observations, together with previous data demonstrating a role for MLF1IP in erythroleukemias, suggest a possible function for this protein in glioma pathogenesis and potentially in other types of malignancies.

Magnetic Resonance Imaging at 1.5 Tesla With a Cochlear Implant Magnet in Place: Image Quality and Usability.

PubMed

Sharon, Jeffrey D; Northcutt, Benjamin G; Aygun, Nafi; Francis, Howard W

2016-10-01

To study the quality and usability of magnetic resonance imaging (MRI) obtained with a cochlear implant magnet in situ. Retrospective chart review. Tertiary care center. All patients who underwent brain MRI with a cochlear implant magnet in situ from 2007 to 2016. None. Grade of view of the ipsilateral internal auditory canal (IAC) and cerebellopontine angle (CPA). Inclusion criteria were met by 765 image sequences in 57 MRI brain scans. For the ipsilateral IAC, significant predictors of a grade 1 (normal) view included: absence of fat saturation algorithm (p = 0.001), nonaxial plane of imaging (p = 0.01), and contrast administration (p = 0.001). For the ipsilateral CPA, significant predictors of a grade 1 view included: absence of fat saturation algorithm (p = 0.001), high-resolution images (p = 0.001), and nonaxial plane of imaging (p = 0.001). Overall, coronal T1 high-resolution images produced the highest percentage of grade 1 views (89%). Fat saturation also caused a secondary ring-shaped distortion artifact, which impaired the view of the contralateral CPA 52.7% of the time, and the contralateral IAC 42.8% of the time. MRI scans without any usable (grade 1) sequences had fewer overall sequences (N = 4.3) than scans with at least one usable sequence (N = 7.1, p = 0.001). MRI image quality with a cochlear implant magnet in situ depends on several factors, which can be modified to maximize image quality in this unique patient population.

Four-Dimensional CT of the Diaphragm in Children: Initial Experience

PubMed Central

2018-01-01

Objective To evaluate the technical feasibility of four-dimensional (4D) CT for the functional evaluation of the pediatric diaphragm. Materials and Methods In 22 consecutive children (median age 3.5 months, age range 3 days–3 years), 4D CT was performed to assess diaphragm motion. Diaphragm abnormalities were qualitatively evaluated and diaphragm motion was quantitatively measured on 4D CT. Lung density changes between peak inspiration and expiration were measured in the basal lung parenchyma. The diaphragm motions and lung density changes measured on 4D CT were compared between various diaphragm conditions. In 11 of the 22 children, chest sonography was available for comparison. Results Four-dimensional CT demonstrated normal diaphragm (n = 8), paralysis (n = 10), eventration (n = 3), and diffusely decreased motion (n = 1). Chest sonography demonstrated normal diaphragm (n = 2), paralysis (n = 6), eventration (n = 2), and right pleural effusion (n = 1). The sonographic findings were concordant with the 4D CT findings in 90.9% (10/11) of the patients. In diaphragm paralysis, the affected diaphragm motion was significantly decreased compared with the contralateral normal diaphragm motion (−1.1 ± 2.2 mm vs. 7.6 ± 3.8 mm, p = 0.005). The normal diaphragms showed significantly greater motion than the paralyzed diaphragms (4.5 ± 2.1 mm vs. −1.1 ± 2.2 mm, p < 0.0001), while the normal diaphragm motion was significantly smaller than the motion of the contralateral normal diaphragm in paralysis (4.5 ± 2.1 mm vs. 7.6 ± 3.8 mm, p = 0.01). Basal lung density change of the affected side was significantly smaller than that of the contralateral side in diaphragm paralysis (89 ± 73 Hounsfield units [HU] vs. 180 ± 71 HU, p = 0.03), while no significant differences were found between the normal diaphragms and the paralyzed diaphragms (136 ± 66 HU vs. 89 ± 73 HU, p = 0.1) or between the normal diaphragms and the contralateral normal diaphragms in paralysis (136 ± 66 HU vs. 180 ± 71 HU, p = 0.1). Conclusion The functional evaluation of the pediatric diaphragm is feasible with 4D CT in select children. PMID:29354007

Unilateral hearing during development: hemispheric specificity in plastic reorganizations

PubMed Central

Kral, Andrej; Heid, Silvia; Hubka, Peter; Tillein, Jochen

2013-01-01

The present study investigates the hemispheric contributions of neuronal reorganization following early single-sided hearing (unilateral deafness). The experiments were performed on ten cats from our colony of deaf white cats. Two were identified in early hearing screening as unilaterally congenitally deaf. The remaining eight were bilaterally congenitally deaf, unilaterally implanted at different ages with a cochlear implant. Implanted animals were chronically stimulated using a single-channel portable signal processor for two to five months. Microelectrode recordings were performed at the primary auditory cortex under stimulation at the hearing and deaf ear with bilateral cochlear implants. Local field potentials (LFPs) were compared at the cortex ipsilateral and contralateral to the hearing ear. The focus of the study was on the morphology and the onset latency of the LFPs. With respect to morphology of LFPs, pronounced hemisphere-specific effects were observed. Morphology of amplitude-normalized LFPs for stimulation of the deaf and the hearing ear was similar for responses recorded at the same hemisphere. However, when comparisons were performed between the hemispheres, the morphology was more dissimilar even though the same ear was stimulated. This demonstrates hemispheric specificity of some cortical adaptations irrespective of the ear stimulated. The results suggest a specific adaptation process at the hemisphere ipsilateral to the hearing ear, involving specific (down-regulated inhibitory) mechanisms not found in the contralateral hemisphere. Finally, onset latencies revealed that the sensitive period for the cortex ipsilateral to the hearing ear is shorter than that for the contralateral cortex. Unilateral hearing experience leads to a functionally-asymmetric brain with different neuronal reorganizations and different sensitive periods involved. PMID:24348345

Unilateral hearing during development: hemispheric specificity in plastic reorganizations.

PubMed

Kral, Andrej; Heid, Silvia; Hubka, Peter; Tillein, Jochen

2013-01-01

The present study investigates the hemispheric contributions of neuronal reorganization following early single-sided hearing (unilateral deafness). The experiments were performed on ten cats from our colony of deaf white cats. Two were identified in early hearing screening as unilaterally congenitally deaf. The remaining eight were bilaterally congenitally deaf, unilaterally implanted at different ages with a cochlear implant. Implanted animals were chronically stimulated using a single-channel portable signal processor for two to five months. Microelectrode recordings were performed at the primary auditory cortex under stimulation at the hearing and deaf ear with bilateral cochlear implants. Local field potentials (LFPs) were compared at the cortex ipsilateral and contralateral to the hearing ear. The focus of the study was on the morphology and the onset latency of the LFPs. With respect to morphology of LFPs, pronounced hemisphere-specific effects were observed. Morphology of amplitude-normalized LFPs for stimulation of the deaf and the hearing ear was similar for responses recorded at the same hemisphere. However, when comparisons were performed between the hemispheres, the morphology was more dissimilar even though the same ear was stimulated. This demonstrates hemispheric specificity of some cortical adaptations irrespective of the ear stimulated. The results suggest a specific adaptation process at the hemisphere ipsilateral to the hearing ear, involving specific (down-regulated inhibitory) mechanisms not found in the contralateral hemisphere. Finally, onset latencies revealed that the sensitive period for the cortex ipsilateral to the hearing ear is shorter than that for the contralateral cortex. Unilateral hearing experience leads to a functionally-asymmetric brain with different neuronal reorganizations and different sensitive periods involved.

Correlation of Fos expression and circling asymmetry during gerbil vestibular compensation

NASA Technical Reports Server (NTRS)

Kaufman, G. D.; Shinder, M. E.; Perachio, A. A.

1999-01-01

Vestibular compensation is a central nervous system process resulting in recovery of functional movement and control following a unilateral vestibular lesion. Small pressure injections of phosphorothioate 20mer oligonucleotides were used to probe the role of the Fos transcription protein during vestibular compensation in the gerbil brainstem. During isoflurane gas anesthesia, antisense probes against the c-fos mRNA sequence were injected into the medial vestibular and prepositus nuclei unilaterally prior to a unilateral surgical labyrinthectomy. Anionic dyes, which did not interact with the oligonucleotides, were used to mark the injection site and help determine the extent of diffusion. The antiFos oligonucleotide injections reduced Fos expression at the injection site in neurons which normally express Fos after the lesion, and also affected circling behavior induced by hemilabyrinthectomy. With both ipsilateral and contralateral medial vestibular and prepositus nuclei injections, less ipsilateral and more contralateral circling was noted in animals injected with antiFos injections as compared to non-injected controls. The degree of change in these behaviors was dependent upon the side of the injection. Histologically, antiFos injections reduced the number of Fos immunolabeled neurons around the injection site, and increased Fos expression contralaterally. The correlation of the number of neurons with Fos expression to turning behavior was stronger for contralateral versus ipsilateral turns, and for neurons in the caudal and ipsilateral sub-regions of the medial vestibular and prepositus nuclei. The results are discussed in terms of neuronal firing activity versus translational activity based on the asymmetrical expression of the Fos inducible transcription factor in the medial vestibular and prepositus nuclei. Although ubiquitous in the brain, transcription factors like Fos can serve localized and specific roles in sensory-specific adaptive stimuli. Antisense injections can be an effective procedure for localized intervention into complex physiological functions, e.g. vestibular compensation. Copyright 1999 Elsevier Science B.V.

Arterial spin-labeling assessment of normalized vascular intratumoral signal intensity as a predictor of histologic grade of astrocytic neoplasms.

PubMed

Furtner, J; Schöpf, V; Schewzow, K; Kasprian, G; Weber, M; Woitek, R; Asenbaum, U; Preusser, M; Marosi, C; Hainfellner, J A; Widhalm, G; Wolfsberger, S; Prayer, D

2014-03-01

Pulsed arterial spin-labeling is a noninvasive MR imaging perfusion method performed with the use of water in the arterial blood as an endogenous contrast agent. The purpose of this study was to determine the inversion time with the largest difference in normalized intratumoral signal intensity between high-grade and low-grade astrocytomas. Thirty-three patients with gliomas, histologically classified as low-grade (n = 7) or high-grade astrocytomas (n = 26) according to the World Health Organization brain tumor classification, were included. A 3T MR scanner was used to perform pulsed arterial spin-labeling measurements at 8 different inversion times (370 ms, 614 ms, 864 ms, 1114 ms, 1364 ms, 1614 ms, 1864 ms, and 2114 ms). Normalized intratumoral signal intensity was calculated, which was defined by the signal intensity ratio of the tumor and the contralateral normal brain tissue for all fixed inversion times. A 3-way mixed ANOVA was used to reveal potential differences in the normalized vascular intratumoral signal intensity between high-grade and low-grade astrocytomas. The difference in normalized vascular intratumoral signal intensity between high-grade and low-grade astrocytomas obtained the most statistically significant results at 370 ms (P = .003, other P values ranged from .012-.955). The inversion time by which to differentiate high-grade and low-grade astrocytomas by use of normalized vascular intratumoral signal intensity was 370 ms in our study. The normalized vascular intratumoral signal intensity values at this inversion time mainly reflect the labeled intra-arterial blood bolus and therefore could be referred to as normalized vascular intratumoral signal intensity. Our data indicate that the use of normalized vascular intratumoral signal intensity values allows differentiation between low-grade and high-grade astrocytomas and thus may serve as a new, noninvasive marker for astrocytoma grading.

Cytokine mRNA expression in synovial fluid of affected and contralateral stifle joints and the left shoulder joint in dogs with unilateral disease of the stifle joint.

PubMed

de Bruin, Tanya; de Rooster, Hilde; van Bree, Henri; Duchateau, Luc; Cox, Eric

2007-09-01

To examine mRNA expression of cytokines in synovial fluid (SF) cells from dogs with cranial cruciate ligament (CrCL) rupture and medial patellar luxation (MPL) and determine mRNA expression for 3 joints (affected stifle, unaffected contralateral stifle, and left shoulder joints) in dogs with unilateral CrCL rupture. 29 stifle joints with CrCL rupture (29 dogs), 8 stifle joints with MPL (7 dogs), and 24 normal stifle joints (16 clinically normal dogs). Immediately before reconstructive surgery, SF was aspirated from the cruciate-deficient stifle joint or stifle joint with MPL. Fourteen of 29 dogs had unilateral CrCL rupture; SF was also aspirated from the unaffected contralateral stifle joint and left shoulder joint. Those 14 dogs were examined 6 and 12 months after reconstructive surgery. Total RNA was extracted from SF cells and reverse transcription-PCR assay was performed to obtain cDNA. Canine-specific cytokine mRNA expression was determined by use of a real-time PCR assay. Interleukin (IL)-8 and -10 and interferon-gamma expression differed significantly between dogs with arthropathies and dogs with normal stifle joints. For the 14 dogs with unilateral CrCL rupture, a significant difference was found for IL-8 expression. Before reconstructive surgery, IL-8 expression differed significantly between the affected stifle joint and left shoulder joint or contralateral stifle joint. Six months after surgery, IL-8 expression was significantly increased in the unaffected contralateral stifle joint, compared with the shoulder joint. No conclusions can be made regarding the role of the examined cytokines in initiation of CrCL disease.

Quantitative Analysis of Geometry and Lateral Symmetry of Proximal Middle Cerebral Artery.

PubMed

Peter, Roman; Emmer, Bart J; van Es, Adriaan C G M; van Walsum, Theo

2017-10-01

The purpose of our work is to quantitatively assess clinically relevant geometric properties of proximal middle cerebral arteries (pMCA), to investigate the degree of their lateral symmetry, and to evaluate whether the pMCA can be modeled by using state-of-the-art deformable image registration of the ipsi- and contralateral hemispheres. Individual pMCA segments were identified, quantified, and statistically evaluated on a set of 55 publicly available magnetic resonance angiography time-of-flight images. Rigid and deformable image registrations were used for geometric alignment of the ipsi- and contralateral hemispheres. Lateral symmetry of relevant geometric properties was evaluated before and after the image registration. No significant lateral differences regarding tortuosity and diameters of contralateral M1 segments of pMCA were identified. Regarding the length of M1 segment, 44% of all subjects could be considered laterally symmetrical. Dominant M2 segment was identified in 30% of men and 9% of women in both brain hemispheres. Deformable image registration performed significantly better (P < .01) than rigid registration with regard to distances between the ipsi- and the contralateral centerlines of M1 segments (1.5 ± 1.1 mm versus 2.8 ± 1.2 mm respectively) and between the M1 and the anterior cerebral artery (ACA) branching points (1.6 ± 1.4 mm after deformable registration). Although natural lateral variation of the length of M1 may not allow for sufficient modeling of the complete pMCA, deformable image registration of the contralateral brain hemisphere to the ipsilateral hemisphere is feasible for localization of ACA-M1 branching point and for modeling 71 ± 23% of M1 segment. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Changes in Abundance of Oral Microbiota Associated with Oral Cancer

PubMed Central

Schmidt, Brian L.; Kuczynski, Justin; Bhattacharya, Aditi; Huey, Bing; Corby, Patricia M.; Queiroz, Erica L. S.; Nightingale, Kira; Kerr, A. Ross; DeLacure, Mark D.; Veeramachaneni, Ratna; Olshen, Adam B.; Albertson, Donna G.

2014-01-01

Individual bacteria and shifts in the composition of the microbiome have been associated with human diseases including cancer. To investigate changes in the microbiome associated with oral cancers, we profiled cancers and anatomically matched contralateral normal tissue from the same patient by sequencing 16S rDNA hypervariable region amplicons. In cancer samples from both a discovery and a subsequent confirmation cohort, abundance of Firmicutes (especially Streptococcus) and Actinobacteria (especially Rothia) was significantly decreased relative to contralateral normal samples from the same patient. Significant decreases in abundance of these phyla were observed for pre-cancers, but not when comparing samples from contralateral sites (tongue and floor of mouth) from healthy individuals. Weighted UniFrac principal coordinates analysis based on 12 taxa separated most cancers from other samples with greatest separation of node positive cases. These studies begin to develop a framework for exploiting the oral microbiome for monitoring oral cancer development, progression and recurrence. PMID:24887397

Combination of blood flow asymmetry in the cerebral and cerebellar hemispheres on brain perfusion SPECT predicts 5-year outcome in patients with symptomatic unilateral major cerebral artery occlusion.

PubMed

Nomura, Jun-ichi; Ogasawara, Kuniaki; Saito, Hideo; Terasaki, Kazunori; Matsumoto, Yoshiyasu; Takahashi, Yoshihiro; Ogasawara, Yasushi; Saura, Hiroaki; Yoshida, Koji; Sato, Yuiko; Kubo, Yoshitaka; Ogawa, Akira

2014-03-01

Misery perfusion increases the risk of stroke recurrence in patients with symptomatic major cerebral artery occlusion. The ratio of brain perfusion contralateral-to-affected asymmetry in the cerebellar hemisphere to brain perfusion affected-to-contralateral asymmetry in the cerebral hemisphere (CblPR/CbrPR) indicates affected-to-contralateral asymmetry of oxygen extraction fraction (OEF) in the cerebral hemisphere. The purpose of the present study was to determine whether the CblPR/CbrPR on brain perfusion single-photon emission computed tomography (SPECT) predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the middle cerebral artery (MCA) or internal carotid artery (ICA). Brain perfusion was assessed using N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) SPECT in 70 patients. A region of interest (ROI) was manually placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres, and the CblPR/CbrPR was calculated. All patients were prospectively followed for 5 years. The primary end points were stroke recurrence or death. A total of 17 patients exhibited the primary end points, 11 of whom experienced subsequent ipsilateral strokes. Multivariate analysis revealed that only high CblPR/CbrPR was significantly associated with the development of the primary end point or subsequent ipsilateral strokes (95% confidential limits [CIs], 1.130-3.145; P  =  0.0114 or 95% CIs, 2.558-5.140; P  =  0.0045, respectively). The CblPR/CbrPR provided 65% (11/17) or 91% (10/11) sensitivity and 88% (47/53) or 88% (52/59) specificity in predicting the primary end point or subsequent ipsilateral strokes, respectively. The CblPR/CbrPR on brain perfusion SPECT predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the MCA or ICA.

Esophagus and Contralateral Lung-Sparing IMRT for Locally Advanced Lung Cancer in the Community Hospital Setting.

PubMed

Kao, Johnny; Pettit, Jeffrey; Zahid, Soombal; Gold, Kenneth D; Palatt, Terry

2015-01-01

The optimal technique for performing lung IMRT remains poorly defined. We hypothesize that improved dose distributions associated with normal tissue-sparing IMRT can allow safe dose escalation resulting in decreased acute and late toxicity. We performed a retrospective analysis of 82 consecutive lung cancer patients treated with curative intent from 1/10 to 9/14. From 1/10 to 4/12, 44 patients were treated with the community standard of three-dimensional conformal radiotherapy or IMRT without specific esophagus or contralateral lung constraints (standard RT). From 5/12 to 9/14, 38 patients were treated with normal tissue-sparing IMRT with selective sparing of contralateral lung and esophagus. The study endpoints were dosimetry, toxicity, and overall survival. Despite higher mean prescribed radiation doses in the normal tissue-sparing IMRT cohort (64.5 vs. 60.8 Gy, p = 0.04), patients treated with normal tissue-sparing IMRT had significantly lower lung V20, V10, V5, mean lung, esophageal V60, and mean esophagus doses compared to patients treated with standard RT (p ≤ 0.001). Patients in the normal tissue-sparing IMRT group had reduced acute grade ≥3 esophagitis (0 vs. 11%, p < 0.001), acute grade ≥2 weight loss (2 vs. 16%, p = 0.04), and late grade ≥2 pneumonitis (7 vs. 21%, p = 0.02). The 2-year overall survival was 52% with normal tissue-sparing IMRT arm compared to 28% for standard RT (p = 0.015). These data provide proof of principle that suboptimal radiation dose distributions are associated with significant acute and late lung and esophageal toxicity that may result in hospitalization or even premature mortality. Strict attention to contralateral lung and esophageal dose-volume constraints are feasible in the community hospital setting without sacrificing disease control.

Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse.

PubMed

Shelton, Laura M; Huysentruyt, Leanne C; Mukherjee, Purna; Seyfried, Thomas N

2010-07-23

GBM (glioblastoma multiforme) is the most aggressive and invasive form of primary human brain cancer. We recently developed a novel brain cancer model in the inbred VM mouse strain that shares several characteristics with human GBM. Using bioluminescence imaging, we tested the efficacy of CR (calorie restriction) for its ability to reduce tumour size and invasion. CR targets glycolysis and rapid tumour cell growth in part by lowering circulating glucose levels. The VM-M3 tumour cells were implanted intracerebrally in the syngeneic VM mouse host. Approx. 12-15 days post-implantation, brains were removed and both ipsilateral and contralateral hemispheres were imaged to measure bioluminescence of invading tumour cells. CR significantly reduced the invasion of tumour cells from the implanted ipsilateral hemisphere into the contralateral hemisphere. The total percentage of Ki-67-stained cells within the primary tumour and the total number of blood vessels was also significantly lower in the CR-treated mice than in the mice fed ad libitum, suggesting that CR is anti-proliferative and anti-angiogenic. Our findings indicate that the VM-M3 GBM model is a valuable tool for studying brain tumour cell invasion and for evaluating potential therapeutic approaches for managing invasive brain cancer. In addition, we show that CR can be effective in reducing malignant brain tumour growth and invasion.

Sensitivity to Pigment-Dispersing Factor (PDF) Is Cell-Type Specific among PDF-Expressing Circadian Clock Neurons in the Madeira Cockroach.

PubMed

Gestrich, Julia; Giese, Maria; Shen, Wen; Zhang, Yi; Voss, Alexandra; Popov, Cyril; Stengl, Monika; Wei, HongYing

2018-02-01

Transplantation studies have pinpointed the circadian clock of the Madeira cockroach to the accessory medulla (AME) of the brain's optic lobes. The AME is innervated by approximately 240 adjacent neuropeptidergic neurons, including 12 pigment-dispersing factor (PDF)-expressing neurons anterior to the AME (aPDFMEs). Four of the aPDFMEs project contralaterally, controlling locomotor activity rhythms of the night-active cockroach. The present in vitro Ca 2+ imaging analysis focuses on contralaterally projecting AME neurons and their responses to PDF, GABA, and acetylcholine (ACh). First, rhodamine-dextran backfills from the contralateral optic stalk identified contralaterally projecting AME neurons, which were then dispersed in primary cell cultures. After characterization of PDF, GABA, and ACh responses, PDF immunocytochemistry identified ipsilaterally and contralaterally projecting PDFMEs. All PDF-sensitive clock neurons, PDF-immunoreactive clock neurons, and the majority of ipsilaterally and contralaterally projecting cells were excited by ACh. GABA inhibited all PDF-expressing clock neurons, and about half of other ipsilaterally projecting and most contralaterally projecting clock neurons. For the first time, we identified PDF autoreceptors in PDF-secreting cockroach circadian pacemakers. The medium-sized aPDFMEs and all other contralaterally projecting PDF-sensitive clock cells were inhibited by PDF. The ipsilaterally remaining small PDF-sensitive clock cells were activated by PDF. Only the largest aPDFME did not express PDF autoreceptors. We hypothesize that opposing PDF signaling generates 2 different ensembles of clock cells with antiphasic activity, regulating and maintaining a constant phase relationship between rest and activity cycles of the night-active cockroach.

Tinnitus Intensity Dependent Gamma Oscillations of the Contralateral Auditory Cortex

PubMed Central

van der Loo, Elsa; Gais, Steffen; Congedo, Marco; Vanneste, Sven; Plazier, Mark; Menovsky, Tomas; Van de Heyning, Paul; De Ridder, Dirk

2009-01-01

Background Non-pulsatile tinnitus is considered a subjective auditory phantom phenomenon present in 10 to 15% of the population. Tinnitus as a phantom phenomenon is related to hyperactivity and reorganization of the auditory cortex. Magnetoencephalography studies demonstrate a correlation between gamma band activity in the contralateral auditory cortex and the presence of tinnitus. The present study aims to investigate the relation between objective gamma-band activity in the contralateral auditory cortex and subjective tinnitus loudness scores. Methods and Findings In unilateral tinnitus patients (N = 15; 10 right, 5 left) source analysis of resting state electroencephalographic gamma band oscillations shows a strong positive correlation with Visual Analogue Scale loudness scores in the contralateral auditory cortex (max r = 0.73, p<0.05). Conclusion Auditory phantom percepts thus show similar sound level dependent activation of the contralateral auditory cortex as observed in normal audition. In view of recent consciousness models and tinnitus network models these results suggest tinnitus loudness is coded by gamma band activity in the contralateral auditory cortex but might not, by itself, be responsible for tinnitus perception. PMID:19816597

The role of nervus intermedius in side specific nasal responses.

PubMed

Nichani, J R; Malik, V; Woolford, T J; Ramsden, R T; Homer, J J

2010-03-02

Nervus intermedius (NI) dysfunction is common in patients who have had vestibular schwannoma (VS) surgery. Such patients have a unilateral parasympathetic-denervated nasal cavity. A number of side-specific nasal reflexes have been demonstrated in normal individuals, including hand cold-water immersion. It is not understood whether these reflexes have parasympathetic or sympathic efferent pathways. We aimed to evaluate the side specific nasal reflex to cold-water immersion in post-operative VS patients with NI dysfunction, in order to determine the nature of the efferent pathway of these reflexes. Side specific responses to cold-water immersion were tested by acoustic rhinometry in 10 normal individuals and 18 patients with NI dysfunction (proven by Schirmer s test) after VS surgery. A consistent pattern of ipsilateral congestion and contralateral decongestion after the cold-water immersion was seen in normal individuals (p smaller than 0.001). We found no consistent response in VS patients both ipsilateral and contralateral to the side of NI dysfunction. We confirm the consistent side-specific nasal reflexes to cold-water hand immersion in normal individuals. This is disturbed in patients with NI dysfunction. We have also shown unexpectantly that the contralateral side-specific reflex is disturbed in these patients. These data suggest that the reflex is parasympathetic and crosses the midline.

Practice on an augmented reality/haptic simulator and library of virtual brains improves residents' ability to perform a ventriculostomy.

PubMed

Yudkowsky, Rachel; Luciano, Cristian; Banerjee, Pat; Schwartz, Alan; Alaraj, Ali; Lemole, G Michael; Charbel, Fady; Smith, Kelly; Rizzi, Silvio; Byrne, Richard; Bendok, Bernard; Frim, David

2013-02-01

Ventriculostomy is a neurosurgical procedure for providing therapeutic cerebrospinal fluid drainage. Complications may arise during repeated attempts at placing the catheter in the ventricle. We studied the impact of simulation-based practice with a library of virtual brains on neurosurgery residents' performance in simulated and live surgical ventriculostomies. Using computed tomographic scans of actual patients, we developed a library of 15 virtual brains for the ImmersiveTouch system, a head- and hand-tracked augmented reality and haptic simulator. The virtual brains represent a range of anatomies including normal, shifted, and compressed ventricles. Neurosurgery residents participated in individual simulator practice on the library of brains including visualizing the 3-dimensional location of the catheter within the brain immediately after each insertion. Performance of participants on novel brains in the simulator and during actual surgery before and after intervention was analyzed using generalized linear mixed models. Simulator cannulation success rates increased after intervention, and live procedure outcomes showed improvement in the rate of successful cannulation on the first pass. However, the incidence of deeper, contralateral (simulator) and third-ventricle (live) placements increased after intervention. Residents reported that simulations were realistic and helpful in improving procedural skills such as aiming the probe, sensing the pressure change when entering the ventricle, and estimating how far the catheter should be advanced within the ventricle. Simulator practice with a library of virtual brains representing a range of anatomies and difficulty levels may improve performance, potentially decreasing complications due to inexpert technique.

Sensory Feedback in Interlimb Coordination: Contralateral Afferent Contribution to the Short-Latency Crossed Response during Human Walking.

PubMed

Gervasio, Sabata; Voigt, Michael; Kersting, Uwe G; Farina, Dario; Sinkjær, Thomas; Mrachacz-Kersting, Natalie

2017-01-01

A constant coordination between the left and right leg is required to maintain stability during human locomotion, especially in a variable environment. The neural mechanisms underlying this interlimb coordination are not yet known. In animals, interneurons located within the spinal cord allow direct communication between the two sides without the need for the involvement of higher centers. These may also exist in humans since sensory feedback elicited by tibial nerve stimulation on one side (ipsilateral) can affect the muscles activation in the opposite side (contralateral), provoking short-latency crossed responses (SLCRs). The current study investigated whether contralateral afferent feedback contributes to the mechanism controlling the SLCR in human gastrocnemius muscle. Surface electromyogram, kinematic and kinetic data were recorded from subjects during normal walking and hybrid walking (with the legs moving in opposite directions). An inverse dynamics model was applied to estimate the gastrocnemius muscle proprioceptors' firing rate. During normal walking, a significant correlation was observed between the magnitude of SLCRs and the estimated muscle spindle secondary afferent activity (P = 0.04). Moreover, estimated spindle secondary afferent and Golgi tendon organ activity were significantly different (P ≤ 0.01) when opposite responses have been observed, that is during normal (facilitation) and hybrid walking (inhibition) conditions. Contralateral sensory feedback, specifically spindle secondary afferents, likely plays a significant role in generating the SLCR. This observation has important implications for our understanding of what future research should be focusing on to optimize locomotor recovery in patient populations.

A Dosimetric Comparison of Proton and Intensity-Modulated Photon Radiotherapy for Pediatric Parameningeal Rhabdomyosarcomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kozak, Kevin R.; Adams, Judith; Krejcarek, Stephanie J.

Purpose: We compared tumor and normal tissue dosimetry of proton radiation therapy with intensity-modulated radiation therapy (IMRT) for pediatric parameningeal rhabdomyosarcomas (PRMS). Methods and Materials: To quantify dosimetric differences between contemporary proton and photon treatment for pediatric PRMS, proton beam plans were compared with IMRT plans. Ten patients treated with proton radiation therapy at Massachusetts General Hospital had IMRT plans generated. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Results: Proton and IMRT plans provided acceptable and comparable target volume coverage, with atmore » least 99% of the CTV receiving 95% of the prescribed dose in all cases. Improved dose conformality provided by proton therapy resulted in significant sparing of all examined normal tissues except for ipsilateral cochlea and mastoid; ipsilateral parotid gland sparing was of borderline statistical significance (p = 0.05). More profound sparing of contralateral structures by protons resulted in greater dose asymmetry between ipsilateral and contralateral retina, optic nerves, cochlea, and mastoids; dose asymmetry between ipsilateral and contralateral parotids was of borderline statistical significance (p = 0.05). Conclusions: For pediatric PRMS, superior normal tissue sparing is achieved with proton radiation therapy compared with IMRT. Because of enhanced conformality, proton plans also demonstrate greater normal tissue dose distribution asymmetry. Longitudinal studies assessing the impact of proton radiotherapy and IMRT on normal tissue function and growth symmetry are necessary to define the clinical consequences of these differences.« less

Single-voxel and multi-voxel spectroscopy yield comparable results in the normal juvenile canine brain when using 3 Tesla magnetic resonance imaging.

PubMed

Lee, Alison M; Beasley, Michaela J; Barrett, Emerald D; James, Judy R; Gambino, Jennifer M

2018-06-10

Conventional magnetic resonance imaging (MRI) characteristics of canine brain diseases are often nonspecific. Single- and multi-voxel spectroscopy techniques allow quantification of chemical biomarkers for tissues of interest and may help to improve diagnostic specificity. However, published information is currently lacking for the in vivo performance of these two techniques in dogs. The aim of this prospective, methods comparison study was to compare the performance of single- and multi-voxel spectroscopy in the brains of eight healthy, juvenile dogs using 3 Tesla MRI. Ipsilateral regions of single- and multi-voxel spectroscopy were performed in symmetric regions of interest of each brain in the parietal (n = 3), thalamic (n = 2), and piriform lobes (n = 3). In vivo single-voxel spectroscopy and multi-voxel spectroscopy metabolite ratios from the same size and multi-voxel spectroscopy ratios from different sized regions of interest were compared. No significant difference was seen between single-voxel spectroscopy and multi-voxel spectroscopy metabolite ratios for any lobe when regions of interest were similar in size and shape. Significant lobar single-voxel spectroscopy and multi-voxel spectroscopy differences were seen between the parietal lobe and thalamus (P = 0.047) for the choline to N-acetyl aspartase ratios when large multi-voxel spectroscopy regions of interest were compared to very small multi-voxel spectroscopy regions of interest within the same lobe; and for the N-acetyl aspartase to creatine ratios in all lobes when single-voxel spectroscopy was compared to combined (pooled) multi-voxel spectroscopy datasets. Findings from this preliminary study indicated that single- and multi-voxel spectroscopy techniques using 3T MRI yield comparable results for similar sized regions of interest in the normal canine brain. Findings also supported using the contralateral side as an internal control for dogs with brain lesions. © 2018 American College of Veterinary Radiology.

Perilesional and contralateral white matter evolution and integrity in patients with periventricular nodular heterotopia and epilepsy: a longitudinal diffusion tensor imaging study.

PubMed

Liu, W; Yan, B; An, D; Niu, R; Tang, Y; Tong, X; Gong, Q; Zhou, D

2017-12-01

This study aimed to assess the evolution of perinodular and contralateral white matter abnormalities in patients with periventricular nodular heterotopia (PNH) and epilepsy. Diffusion tensor imaging (DTI) (64 directions) and 3 T structural magnetic resonance imaging were performed in 29 PNH patients (mean age 27.3 years), and 16 patients underwent a second scan (average time between the two scans 1.1 years). Fractional anisotropy and mean diffusivity were measured within the perilesional and contralateral white matter. Longitudinal analysis showed that white matter located 10 mm from the focal nodule displayed characteristics intermediate to tissue 5 mm away, and normal-appearing white matter (NAWM) also established evolution profiles of perinodular white matter in different cortical lobes. Compared to 29 age- and sex-matched healthy controls, significant decreased fractional anisotropy and elevated mean diffusivity values were observed in regions 5 and 10 mm from nodules (P < 0.01), whilst DTI metrics of the remaining NAWM did not differ significantly from controls. Additionally, normal DTI metrics were shown in the contralateral region in patients with unilateral PNH. Periventricular nodular heterotopia is associated with microstructural abnormalities within the perilesional white matter and the extent decreases with increasing distance from the nodule. In the homologous contralateral region, white matter diffusion metrics were unchanged in unilateral PNH. These findings have clinical implications with respect to the medical and surgical interventions of PNH-related epilepsy. © 2017 EAN.

Microstructure of transcallosal motor fibers reflects type of cortical (re-)organization in congenital hemiparesis.

PubMed

Juenger, Hendrik; Koerte, Inga K; Muehlmann, Marc; Mayinger, Michael; Mall, Volker; Krägeloh-Mann, Ingeborg; Shenton, Martha E; Berweck, Steffen; Staudt, Martin; Heinen, Florian

2014-11-01

Early unilateral brain lesions can lead to different types of corticospinal (re-)organization of motor networks. In one group of patients, the contralesional hemisphere exerts motor control not only over the contralateral non-paretic hand but also over the (ipsilateral) paretic hand, as the primary motor cortex is (re-)organized in the contralesional hemisphere. Another group of patients with early unilateral lesions shows "normal" contralateral motor projections starting in the lesioned hemisphere. We investigated how these different patterns of cortical (re-)organization affect interhemispheric transcallosal connectivity in patients with congenital hemiparesis. Eight patients with ipsilateral motor projections (group IPSI) versus 7 patients with contralateral motor projections (group CONTRA) underwent magnetic resonance diffusion tensor imaging (DTI). The corpus callosum (CC) was subdivided in 5 areas (I-V) in the mid-sagittal slice and volumetric information. The following diffusion parameters were calculated: fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD). DTI revealed significantly lower FA, increased trace and RD for group IPSI compared to group CONTRA in area III of the corpus callosum, where transcallosal motor fibers cross the CC. In the directly neighboring area IV, where transcallosal somatosensory fibers cross the CC, no differences were found for these DTI parameters between IPSI and CONTRA. Volume of callosal subsections showed significant differences for area II (connecting premotor cortices) and III, where group IPSI had lower volume. The results of this study demonstrate that the callosal microstructure in patients with congenital hemiparesis reflects the type of cortical (re-)organization. Early lesions disrupting corticospinal motor projections to the paretic hand consecutively affect the development or maintenance of transcallosal motor fibers. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Improvement in Cerebral and Ocular Hemodynamics Early after Carotid Endarterectomy in Patients of Severe Carotid Artery Stenosis with or without Contralateral Carotid Occlusion.

PubMed

Wang, Jian; Wang, Weici; Jin, Bi; Zhang, Yanrong; Xu, Ping; Xiang, Feixiang; Zheng, Yi; Chen, Juan; Sheng, Shi; Ouyang, Chenxi; Li, Yiqing

2016-01-01

Purpose. To investigate the alternation in cerebral and ocular blood flow velocity (BFV) in patients of carotid stenosis (CS) with or without contralateral carotid occlusion (CO) early after carotid endarterectomy (CEA). Patients and Methods. Nineteen patients underwent CEA for ≥50% CS. Fourteen patients had the unilateral CS, and five patients had the ipsilateral CS and the contralateral CO. Transcranial Doppler (TCD) and Color Doppler Imaging (CDI) were performed before and early after CEA. Results. In patients with unilateral CS, significant improvements in BFV were observed in anterior cerebral artery (ACA) and middle cerebral artery (MCA) on the ipsilateral side after CEA. In patients of ipsilateral CS and contralateral CO, significant improvements in BFV were observed in the ACA and MCA not only on the ipsilateral side but also on the contralateral side postoperatively. The ipsilateral ophthalmic artery (OA) retrograde flows in two patients were recovered to anterograde direction following CEA. The BFV in short posterior ciliary artery (SPCA) of the ipsilateral side significantly increased postoperatively irrespective of the presence of contralateral CO. Conclusions. CEA improved cerebral anterior circulation hemodynamics especially in patients of unilateral CS and contralateral CO, normalized the OA reverse flow, and increased the blood perfusion of SPCA.

Long-Lasting Cortical Reorganization as the Result of Motor Imagery of Throwing a Ball in a Virtual Tennis Court

PubMed Central

Cebolla, Ana M.; Petieau, Mathieu; Cevallos, Carlos; Leroy, Axelle; Dan, Bernard; Cheron, Guy

2015-01-01

In order to characterize the neural signature of a motor imagery (MI) task, the present study investigates for the first time the oscillation characteristics including both of the time-frequency measurements, event related spectral perturbation and intertrial coherence (ITC) underlying the variations in the temporal measurements (event related potentials, ERP) directly related to a MI task. We hypothesize that significant variations in both of the time-frequency measurements underlie the specific changes in the ERP directly related to MI. For the MI task, we chose a simple everyday task (throwing a tennis ball), that does not require any particular motor expertise, set within the controlled virtual reality scenario of a tennis court. When compared to the rest condition a consistent, long-lasting negative fronto-central ERP wave was accompanied by significant changes in both time frequency measurements suggesting long-lasting cortical activity reorganization. The ERP wave was characterized by two peaks at about 300 ms (N300) and 1000 ms (N1000). The N300 component was centrally localized on the scalp and was accompanied by significant phase consistency in the delta brain rhythms in the contralateral central scalp areas. The N1000 component spread wider centrally and was accompanied by a significant power decrease (or event related desynchronization) in low beta brain rhythms localized in fronto-precentral and parieto-occipital scalp areas and also by a significant power increase (or event related synchronization) in theta brain rhythms spreading fronto-centrally. During the transition from N300 to N1000, a contralateral alpha (mu) as well as post-central and parieto-theta rhythms occurred. The visual representation of movement formed in the minds of participants might underlie a top-down process from the fronto-central areas which is reflected by the amplitude changes observed in the fronto-central ERPs and by the significant phase synchrony in contralateral fronto-central delta and contralateral central mu to parietal theta presented here. PMID:26648903

Central masking with bilateral cochlear implants

PubMed Central

Lin, Payton; Lu, Thomas; Zeng, Fan-Gang

2013-01-01

Across bilateral cochlear implants, contralateral threshold shift has been investigated as a function of electrode difference between the masking and probe electrodes. For contralateral electric masking, maximum threshold elevations occurred when the position of the masker and probe electrode was approximately place-matched across ears. The amount of masking diminished with increasing masker-probe electrode separation. Place-dependent masking occurred in both sequentially implanted ears, and was not affected by the masker intensity or the time delay from the masker onset. When compared to previous contralateral masking results in normal hearing, the similarities between place-dependent central masking patterns suggest comparable mechanisms of overlapping excitation in the central auditory nervous system. PMID:23363113

Does the corticoadrenal adenoma with ''pre-Cushing's syndrome'' exist

DOE Office of Scientific and Technical Information (OSTI.GOV)

Charbonnel, B.; Chatal, J.F.; Ozanne, P.

1981-12-01

An adrenal tumor was discovered fortuitously in a patient with no clinical features of Cushing's syndrome. On adrenal imaging, there was good uptake in the nodule but no visualization of the contralateral adrenal. The latter was seen, however, in a second scan performed under ACTH treatment. In the hormone assessment, basal cortisol and 17-hydroxycorticoids were normal and cortisol diurnal variation was near normal, but a dexamethasone suppression test and ACTH responses to metyrapone and insulin hypoglycemia were abnormal. Eight months after excision of a spongiocytic-type adenoma, the remaining adrenal was visible on scintigram and the hormonal tests were normal. Thismore » pattern suggests that the clinical Cushing's syndrome was enough to partially suppress ACTH and, consequently, visualization of the contralateral gland.« less

Effects of contralateral white noise stimulation on distortion product otoacoustic emissions in myasthenic patients.

PubMed

Di Girolamo, S; d'Ecclesia, A; Quaranta, N; Garozzo, A; Evoli, A; Paludetti, G

2001-12-01

Myasthenia gravis (MG) induces a reduction of transient evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs) that reverses partially after administration of an acetylcholinesterase (AChE) inhibitor. In normal subjects a contralateral acoustic stimulation (CAS) produces an amplitude reduction of TEOAEs and DPOAEs. This effect, called contralateral suppression (CS), is mediated by the efferent auditory system. Twenty subjects affected by MG underwent DPOAE recording with and without contralateral white noise in a drug-free baseline period ('basal') and 1 h ('post') after administration of a reversible AChE inhibitor. In 'basal' condition CAS did not induce significant DPOAE amplitude changes but a paradoxical slight increase was observed. After drug administration, CAS produced a significant decrease of DPOAE amplitudes for middle frequencies (f(2) between 1306 and 2600 Hz). In normal controls CAS caused a significant decrease (P<0.001) for all frequencies. The amount of CS in controls and in the MG 'post' condition was not significantly different. The increased acetylcholine (ACh) availability following drug consumption seems to partially restore outer hair cell function and enhances their electromotility; a further influx of ACh due to CAS yields to restoration of the CS. These findings also suggest that DPOAEs may be useful in the diagnosis of MG and for monitoring the effectiveness of treatment.

An fMRI study of musicians with focal dystonia during tapping tasks.

PubMed

Kadota, Hiroshi; Nakajima, Yasoichi; Miyazaki, Makoto; Sekiguchi, Hirofumi; Kohno, Yutaka; Amako, Masatoshi; Arino, Hiroshi; Nemoto, Koichi; Sakai, Naotaka

2010-07-01

Musician's dystonia is a type of task specific dystonia for which the pathophysiology is not clear. In this study, we performed functional magnetic resonance imaging to investigate the motor-related brain activity associated with musician's dystonia. We compared brain activities measured from subjects with focal hand dystonia and normal (control) musicians during right-hand, left-hand, and both-hands tapping tasks. We found activations in the thalamus and the basal ganglia during the tapping tasks in the control group but not in the dystonia group. For both groups, we detected significant activations in the contralateral sensorimotor areas, including the premotor area and cerebellum, during each tapping task. Moreover, direct comparison between the dystonia and control groups showed that the dystonia group had greater activity in the ipsilateral premotor area during the right-hand tapping task and less activity in the left cerebellum during the both-hands tapping task. Thus, the dystonic musicians showed irregular activation patterns in the motor-association system. We suggest that irregular neural activity patterns in dystonic subjects reflect dystonic neural malfunction and consequent compensatory activity to maintain appropriate voluntary movements.

Diagnostic accuracy of automatic normalization of CBV in glioma grading using T1- weighted DCE-MRI.

PubMed

Sahoo, Prativa; Gupta, Rakesh K; Gupta, Pradeep K; Awasthi, Ashish; Pandey, Chandra M; Gupta, Mudit; Patir, Rana; Vaishya, Sandeep; Ahlawat, Sunita; Saha, Indrajit

2017-12-01

Aim of this retrospective study was to compare diagnostic accuracy of proposed automatic normalization method to quantify the relative cerebral blood volume (rCBV) with existing contra-lateral region of interest (ROI) based CBV normalization method for glioma grading using T1-weighted dynamic contrast enhanced MRI (DCE-MRI). Sixty patients with histologically confirmed gliomas were included in this study retrospectively. CBV maps were generated using T1-weighted DCE-MRI and are normalized by contralateral ROI based method (rCBV_contra), unaffected white matter (rCBV_WM) and unaffected gray matter (rCBV_GM), the latter two of these were generated automatically. An expert radiologist with >10years of experience in DCE-MRI and a non-expert with one year experience were used independently to measure rCBVs. Cutoff values for glioma grading were decided from ROC analysis. Agreement of histology with rCBV_WM, rCBV_GM and rCBV_contra respectively was studied using Kappa statistics and intra-class correlation coefficient (ICC). The diagnostic accuracy of glioma grading using the measured rCBV_contra by expert radiologist was found to be high (sensitivity=1.00, specificity=0.96, p<0.001) compared to the non-expert user (sensitivity=0.65, specificity=0.78, p<0.001). On the other hand, both the expert and non-expert user showed similar diagnostic accuracy for automatic rCBV_WM (sensitivity=0.89, specificity=0.87, p=0.001) and rCBV_GM (sensitivity=0.81, specificity=0.78, p=0.001) measures. Further, it was also observed that, contralateral based method by expert user showed highest agreement with histological grading of tumor (kappa=0.96, agreement 98.33%, p<0.001), however; automatic normalization method showed same percentage of agreement for both expert and non-expert user. rCBV_WM showed an agreement of 88.33% (kappa=0.76,p<0.001) with histopathological grading. It was inferred from this study that, in the absence of expert user, automated normalization of CBV using the proposed method could provide better diagnostic accuracy compared to the manual contralateral based approach. Copyright © 2017 Elsevier Inc. All rights reserved.

Estimating associations of mobile phone use and brain tumours taking into account laterality: a comparison and theoretical evaluation of applied methods.

PubMed

Frederiksen, Kirsten; Deltour, Isabelle; Schüz, Joachim

2012-12-10

Estimating exposure-outcome associations using laterality information on exposure and on outcome is an issue, when estimating associations of mobile phone use and brain tumour risk. The exposure is localized; therefore, a potential risk is expected to exist primarily on the side of the head, where the phone is usually held (ipsilateral exposure), and to a lesser extent at the opposite side of the head (contralateral exposure). Several measures of the associations with ipsilateral and contralateral exposure, dealing with different sampling designs, have been presented in the literature. This paper presents a general framework for the analysis of such studies using a likelihood-based approach in a competing risks model setting. The approach clarifies the implicit assumptions required for the validity of the presented estimators, particularly that in some approaches the risk with contralateral exposure is assumed to be zero. The performance of the estimators is illustrated in a simulation study showing for instance that while in some scenarios there is a loss of statistical power, others - in case of a positive ipsilateral exposure-outcome association - would result in a negatively biased estimate of the contralateral exposure parameter, irrespective of any additional recall bias. In conclusion, our theoretical evaluations and results from the simulation study emphasize the importance of setting up a formal model, which furthermore allows for estimation in more complicated and perhaps more realistic exposure settings, such as taking into account exposure to both sides of the head. Copyright © 2012 John Wiley & Sons, Ltd.

A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury

DTIC Science & Technology

2011-09-01

parietal bones, and a threaded rod was implanted into the interparietal bone. These were affixed to the skull with dental acrylic. A hybrid, 16...then sealed with a silicone polymer (Kwik-Cast, WPI). The base of the probe connector was lowered onto the dental acrylic and fixed into place. An...the skull using a dental drill with a trephine bit over the cortex contralateral to the dominant forelimb. A total of 14 animals received CCI in the

Metabolic brain imaging correlated with clinical features of brain tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alavi, J.; Alavi, A.; Dann, R.

1985-05-01

Nineteen adults with brain tumors have been studied with positron emission tomography utilizing FDG. Fourteen had biopsy proven cerebral malignant glioma, one each had meningioma, hemangiopericytoma, primitive neuroectodermal tumor (PNET), two had unbiopsied lesions, and one patient had an area of biopsy proven radiation necrosis. Three different patterns of glucose metabolism are observed: marked increase in metabolism at the site of the known tumor in (10 high grade gliomas and the PNET), lower than normal metabolism at the tumor (in 1 grade II glioma, 3 grade III gliomas, 2 unbiopsied low density nonenhancing lesions, and the meningioma), no abnormality (1more » enhancing glioma, the hemangiopericytoma and the radiation necrosis.) The metabolic rate of the tumor or the surrounding brain did not appear to be correlated with the history of previous irradiation or chemotherapy. Decreased metabolism was frequently observed in the rest of the affected hemisphere and in the contralateral cerebellum. Tumors of high grade or with enhancing CT characteristics were more likely to show increased metabolism. Among the patients with proven gliomas, survival after PETT scan tended to be longer for those with low metabolic activity tumors than for those with highly active tumors. The authors conclude that PETT may help to predict the malignant potential of tumors, and may add useful clinical information to the CT scan.« less

Hindlimb spasticity after unilateral motor cortex lesion in rats is reduced by contralateral nerve root transfer.

PubMed

Zong, Haiyang; Ma, Fenfen; Zhang, Laiyin; Lu, Huiping; Gong, Jingru; Cai, Min; Lin, Haodong; Zhu, Yizhun; Hou, Chunlin

2016-12-01

Lower extremity spasticity is a common sequela among patients with acquired brain injury. The optimum treatment remains controversial. The aim of our study was to test the feasibility and effectiveness of contralateral nerve root transfer in reducing post stroke spasticity of the affected hindlimb muscles in rats. In our study, we for the first time created a novel animal hindlimb spastic hemiplegia model in rats with photothrombotic lesion of unilateral motor cortex and we established a novel surgical procedure in reducing motor cortex lesion-induced hindlimb spastic hemiplegia in rats. Thirty six rats were randomized into three groups. In group A, rats received sham operation. In group B, rats underwent unilateral hindlimb motor cortex lesion. In group C, rats underwent unilateral hindlimb cortex lesion followed by contralateral L4 ventral root transfer to L5 ventral root of the affected side. Footprint analysis, Hoffmann reflex (H-reflex), cholera toxin subunit B (CTB) retrograde tracing of gastrocnemius muscle (GM) motoneurons and immunofluorescent staining of vesicle glutamate transporter 1 (VGLUT1) on CTB-labelled motoneurons were used to assess spasticity of the affected hindlimb. Sixteen weeks postoperatively, toe spread and stride length recovered significantly in group C compared with group B (P<0.001). H max (H-wave maximum amplitude)/M max (M-wave maximum amplitude) ratio of gastrocnemius and plantaris muscles (PMs) significantly reduced in group C (P<0.01). Average VGLUT1 positive boutons per CTB-labelled motoneurons significantly reduced in group C (P<0.001). We demonstrated for the first time that contralateral L4 ventral root transfer to L5 ventral root of the affected side was effective in relieving unilateral motor cortex lesion-induced hindlimb spasticity in rats. Our data indicated that this could be an alternative treatment for unilateral lower extremity spasticity after brain injury. Therefore, contralateral neurotization may exert a potential therapeutic candidate to improve the function of lower extremity in patients with spastic hemiplegia. © 2016 The Author(s).

Forebrain Mechanisms of Nociception and Pain: Analysis through Imaging

NASA Astrophysics Data System (ADS)

Casey, Kenneth L.

1999-07-01

Pain is a unified experience composed of interacting discriminative, affective-motivational, and cognitive components, each of which is mediated and modulated through forebrain mechanisms acting at spinal, brainstem, and cerebral levels. The size of the human forebrain in relation to the spinal cord gives anatomical emphasis to forebrain control over nociceptive processing. Human forebrain pathology can cause pain without the activation of nociceptors. Functional imaging of the normal human brain with positron emission tomography (PET) shows synaptically induced increases in regional cerebral blood flow (rCBF) in several regions specifically during pain. We have examined the variables of gender, type of noxious stimulus, and the origin of nociceptive input as potential determinants of the pattern and intensity of rCBF responses. The structures most consistently activated across genders and during contact heat pain, cold pain, cutaneous laser pain or intramuscular pain were the contralateral insula and anterior cingulate cortex, the bilateral thalamus and premotor cortex, and the cerebellar vermis. These regions are commonly activated in PET studies of pain conducted by other investigators, and the intensity of the brain rCBF response correlates parametrically with perceived pain intensity. To complement the human studies, we developed an animal model for investigating stimulus-induced rCBF responses in the rat. In accord with behavioral measures and the results of human PET, there is a progressive and selective activation of somatosensory and limbic system structures in the brain and brainstem following the subcutaneous injection of formalin. The animal model and human PET studies should be mutually reinforcing and thus facilitate progress in understanding forebrain mechanisms of normal and pathological pain.

Contralateral Cortical Organisation of Information in Visual Short-Term Memory: Evidence from Lateralized Brain Activity during Retrieval

ERIC Educational Resources Information Center

Fortier-Gauthier, Ulysse; Moffat, Nicolas; Dell'Acqua, Robert; McDonald, John J.; Jolicoeur, Pierre

2012-01-01

We studied brain activity during retention and retrieval phases of two visual short-term memory (VSTM) experiments. Experiment 1 used a balanced memory array, with one color stimulus in each hemifield, followed by a retention interval and a central probe, at the fixation point that designated the target stimulus in memory about which to make a…

Brain activity during bilateral rapid alternate finger tapping measured with magnetoencephalography

NASA Astrophysics Data System (ADS)

Fukuda, Hiroshi; Odagaki, Masato; Hiwaki, Osamu; Kodabashi, Atsushi; Fujimoto, Toshiro

2009-04-01

Using magnetoencephalography (MEG), brain regions involved in an alternate bimanual tapping task by index fingers triggered with spontaneous timing were investigated. The tapping mode in which both index fingers moved simultaneously was interlaced during the task. The groups of the alternate tapping (AL mode) and the simultaneous tapping (SI mode) were extracted from the successive alternating taps with a histogram of intervals between the right and left index fingers. MEG signals in each mode were averaged separately before and after the tapping initiation of the dominant index finger. The activities of the contralateral sensorimotor cortex before and after the tapping initiation in the AL mode were larger than that in the SI mode. The result indicates that the activity of the contralateral sensorimotor cortex depends on the degree of achievement in the difficult motor task such as the voluntary alternate tapping movements.

Age-related changes in brain structural covariance networks.

PubMed

Li, Xinwei; Pu, Fang; Fan, Yubo; Niu, Haijun; Li, Shuyu; Li, Deyu

2013-01-01

Previous neuroimaging studies have suggested that cerebral changes over normal aging are not simply characterized by regional alterations, but rather by the reorganization of cortical connectivity patterns. The investigation of structural covariance networks (SCNs) using voxel-based morphometry is an advanced approach to examining the pattern of covariance in gray matter (GM) volumes among different regions of the human cortex. To date, how the organization of critical SCNs change during normal aging remains largely unknown. In this study, we used an SCN mapping approach to investigate eight large-scale networks in 240 healthy participants aged 18-89 years. These participants were subdivided into young (18-23 years), middle aged (30-58 years), and older (61-89 years) subjects. Eight seed regions were chosen from widely reported functional intrinsic connectivity networks. The voxels showing significant positive associations with these seed regions were used to describe the topological organization of an SCN. All of these networks exhibited non-linear patterns in their spatial extent that were associated with normal aging. These networks, except the primary motor network, had a distributed topology in young participants, a sharply localized topology in middle aged participants, and were relatively stable in older participants. The structural covariance derived using the primary motor cortex was limited to the ipsilateral motor regions in the young and older participants, but included contralateral homologous regions in the middle aged participants. In addition, there were significant between-group differences in the structural networks associated with language-related speech and semantics processing, executive control, and the default-mode network (DMN). Taken together, the results of this study demonstrate age-related changes in the topological organization of SCNs, and provide insights into normal aging of the human brain.

Contralateral Hyperalgesia from Injection of Endothelin-1 into the Ipsilateral Paw Requires Efferent Conduction into the Contralateral Paw.

PubMed

Strichartz, Gary R; Khodorova, Alla; Wang, Jeffrey Chi-Fei; Chen, Yu-Wen; Huang, Chuan-Chin

2015-10-01

Contralateral hyperalgesia, occurring after unilateral injury, is usually explained by central sensitization in spinal cord and brain. We previously reported that injection of endothelin-1 (ET-1) into one rat hindpaw induces prolonged mechanical and chemical sensitization of the contralateral hindpaw. Here, we examined the role of contralateral efferent activity in this process. ET-1 (2 nmol, 10 μL) was injected subcutaneously into the plantar surface of right (ipsilateral) hindpaw (ILP), and the thermal response latency and mechanical threshold for nocifensive withdrawal were determined by the use of, respectively, plantar radiant heating and von Frey filaments, for both ILP and contralateral hindpaws (CLP). Either paw was anesthetized for 60 minutes by direct injection of bupivacaine (0.25%, 40 μL), 30 minutes before ET-1. Alternatively, the contralateral sciatic nerve was blocked for 6 to 12 hours by percutaneous injection of bupivacaine-releasing microspheres 30 minutes before injection of ET-1. Systemic actions of these bupivacaine formulations were simulated by subcutaneous injection at the nuchal midline. After the injection of ET-1, the mechanical threshold of both ILP and CLP decreased by 2 hours, appeared to be lowest around 24 hours, and recovered through 48 hours to preinjection baseline at 72 hours. These hypersensitive responses were suppressed by bupivacaine injected into the ipsilateral paw before ET-1. Injection of the CLP by bupivacaine also suppressed the hypersensitivity of the CLP at all test times, and that of the ILP, except at 2 hours when it increased the sensitivity. This same pattern of change occurred when the contralateral sciatic nerve was blocked by bupivacaine-releasing microspheres. The systemic actions of these bupivacaine formulations were much smaller and only reached significance at 24 hours post-ET-1. Thermal hypersensitivity after ET-1 injection also occurred in both ILP and CLP and showed the same pattern in response to the 2 contralateral anesthetic procedures. These results show that efferent transmission through the contralateral innervation into the paw is necessary for contralateral sensitization by ET-1, suggesting that the release of substances by distal nerve endings is involved. The release of substances in the periphery is essential for contralateral sensitization by ET-1 and may also contribute to secondary hyperalgesia, occurring at loci distant from the primary injury, that occurs after surgery or nerve damage.

Magnetic resonance imaging demonstrates compartmental muscle mechanisms of human vertical fusional vergence

PubMed Central

Clark, Robert A.

2015-01-01

Vertical fusional vergence (VFV) normally compensates for slight vertical heterophorias. We employed magnetic resonance imaging to clarify extraocular muscle contributions to VFV induced by monocular two-prism diopter (1.15°) base-up prism in 14 normal adults. Fusion during prism viewing requires monocular infraduction. Scans were repeated without prism, and with prism shifted contralaterally. Contractility indicated by morphometric indexes was separately analyzed in medial and lateral vertical rectus and superior oblique (SO) putative compartments, and superior and inferior horizontal rectus extraocular muscle putative compartments, but in the whole inferior oblique (IO). Images confirmed appropriate VFV that was implemented by the inferior rectus (IR) medial compartment contracting ipsilateral and relaxing contralateral to prism. There was no significant contractility in the IR lateral compartment. The superior but not inferior lateral rectus (LR) compartment contracted significantly in the prism viewing eye, but not contralateral to prism. The IO contracted ipsilateral but not contralateral to the prism. In the infraducting eye, the SO medial compartment relaxed significantly, while the lateral compartment was unchanged; contralateral to prism, the SO lateral compartment contracted, while the medial compartment was unchanged. There was no contractility in the superior or medial rectus muscles in either eye. There was no globe retraction. We conclude that the vertical component of VFV is primarily implemented by IR medial compartment contraction. Since appropriate vertical rotation is not directly implemented, or is opposed, by associated differential LR and SO compartmental activity, and IO contraction, these actions probably implement a torsional component of VFV. PMID:25589593

Bilateral Activity-Dependent Interactions in the Developing Corticospinal System

PubMed Central

Friel, Kathleen M.; Martin, John H.

2009-01-01

Activity-dependent competition between the corticospinal (CS) systems in each hemisphere drives postnatal development of motor skills and stable CS tract connections with contralateral spinal motor circuits. Unilateral restriction of motor cortex (M1) activity during an early postnatal critical period impairs contralateral visually guided movements later in development and in maturity. Silenced M1 develops aberrant connections with the contralateral spinal cord whereas the initially active M1, in the other hemisphere, develops bilateral connections. In this study, we determined whether the aberrant pattern of CS tract terminations and motor impairments produced by early postnatal M1 activity restriction could be abrogated by reducing activity-dependent synaptic competition from the initially active M1 later in development. We first inactivated M1 unilaterally between postnatal weeks 5–7. We next inactivated M1 on the other side from weeks 7–11 (alternate inactivation), to reduce the competitive advantage that this side may have over the initially inactivated side. Alternate inactivation redirected aberrant contralateral CS tract terminations from the initially silenced M1 to their normal spinal territories and reduced the density of aberrant ipsilateral terminations from the initially active side. Normal movement endpoint control during visually guided locomotion was fully restored. This reorganization of CS terminals reveals an unsuspected late plasticity after the critical period for establishing the pattern of CS terminations in the spinal cord. Our findings show that robust bilateral interactions between the developing CS systems on each side are important for achieving balance between contralateral and ipsilateral CS tract connections and visuomotor control. PMID:17928450

Correlation between blink reflex abnormalities and magnetic resonance imaging findings in patients with multiple sclerosis.

PubMed

Degirmenci, Eylem; Erdogan, Cagdas; Bir, Levent Sinan

2013-09-01

This study investigates the correlation between brain magnetic resonance imaging findings and blink reflex abnormalities in patients with relapsing remitting multiple sclerosis. Twenty-six patients and 17 healthy subjects were included in this study. Blink reflex test (BRT) results were obtained using right and left stimulations; thus, 52 BRT results were recorded for the patient group, and 34 BRT results were recorded for the control group. The magnetic resonance imaging (MRI) findings were classified based on the existence of brainstem lesions (hyperintense lesion on T2 weighted (W) and fast fluid-attenuated inversion recovery MRI or contrast-enhancing lesion on T1W MRI). Correlation analysis was performed for the BRT and MRI findings. The percentage of individuals with abnormal BRT results (including R1 latency, ipsilateral R2 latency, and contralateral R2 latency) was significantly higher in the patient group as compared to the control group (p values: 0.015, 0.001, and 0.002, respectively). Correlation analysis revealed significant correlations between contralateral R2 latency abnormalities and brainstem lesions (p value: 0.011). Our results showed significant correlation correlations between contralateral R2 latency abnormalities and brainstem lesions and these results may be explained the effects of multiple demyelinating lesions of the brain stem of patients with relapsing remitting multiple sclerosis.

Cooperative dynamics in auditory brain response

NASA Astrophysics Data System (ADS)

Kwapień, J.; DrożdŻ, S.; Liu, L. C.; Ioannides, A. A.

1998-11-01

Simultaneous estimates of activity in the left and right auditory cortex of five normal human subjects were extracted from multichannel magnetoencephalography recordings. Left, right, and binaural stimulations were used, in separate runs, for each subject. The resulting time series of left and right auditory cortex activity were analyzed using the concept of mutual information. The analysis constitutes an objective method to address the nature of interhemispheric correlations in response to auditory stimulations. The results provide clear evidence of the occurrence of such correlations mediated by a direct information transport, with clear laterality effects: as a rule, the contralateral hemisphere leads by 10-20 ms, as can be seen in the average signal. The strength of the interhemispheric coupling, which cannot be extracted from the average data, is found to be highly variable from subject to subject, but remarkably stable for each subject.

Effects of brain-derived neurotrophic factor (BDNF) on the cochlear nucleus in cats deafened as neonates.

PubMed

Kandathil, Cherian K; Stakhovskaya, Olga; Leake, Patricia A

2016-12-01

Many previous studies have shown significant neurotrophic effects of intracochlear delivery of BDNF in preventing degeneration of cochlear spiral ganglion (SG) neurons after deafness in rodents and our laboratory has shown similar results in developing cats deafened prior to hearing onset. This study examined the morphology of the cochlear nucleus (CN) in a group of neonatally deafened cats from a previous study in which infusion of BDNF elicited a significant improvement in survival of the SG neurons. Five cats were deafened by systemic injections of neomycin sulfate (60 mg/kg, SQ, SID) starting one day after birth, and continuing for 16-18 days until auditory brainstem response (ABR) testing demonstrated profound bilateral hearing loss. The animals were implanted unilaterally at about 1 month of age using custom-designed electrodes with a drug-delivery cannula connected to an osmotic pump. BDNF (94 μg/ml; 0.25 μl/hr) was delivered for 10 weeks. The animals were euthanized and studied at 14-23 weeks of age. Consistent with the neurotrophic effects of BDNF on SG survival, the total CN volume in these animals was significantly larger on the BDNF-treated side than on the contralateral side. However, total CN volume, both ipsi- and contralateral to the implants in these deafened juvenile animals, was markedly smaller than the CN in normal adult animals, reflecting the severe effects of deafness on the central auditory system during development. Data from the individual major CN subdivisions (DCN, Dorsal Cochlear Nucleus; PVCN, Posteroventral Cochlear Nucleus; AVCN, Anteroventral Cochlear Nucleus) also were analyzed. A significant difference was observed between the BDNF-treated and control sides only in the AVCN. Measurements of the cross-sectional areas of spherical cells showed that cells were significantly larger in the AVCN ipsilateral to the implant than on the contralateral side. Further, the numerical density of spherical cells was significantly lower in the AVCN ipsilateral to the implant than on the contralateral side, consistent with the larger AVCN volume observed with BDNF treatment. Together, findings indicate significant neurotrophic effects of intracochlear BDNF infusion on the developing CN. Copyright © 2016 Elsevier B.V. All rights reserved.

Analysis of boron distribution in vivo for boron neutron capture therapy using two different boron compounds by secondary ion mass spectrometry.

PubMed

Yokoyama, Kunio; Miyatake, Shin-Ichi; Kajimoto, Yoshinaga; Kawabata, Shinji; Doi, Atsushi; Yoshida, Toshiko; Okabe, Motonori; Kirihata, Mitsunori; Ono, Koji; Kuroiwa, Toshihiko

2007-01-01

The efficiency of boron neutron capture therapy (BNCT) for malignant gliomas depends on the selective and absolute accumulation of (10)B atoms in tumor tissues. Only two boron compounds, BPA and BSH, currently can be used clinically. However, the detailed distributions of these compounds have not been determined. Here we used secondary ion mass spectrometry (SIMS) to determine the histological distribution of (10)B atoms derived from the boron compounds BSH and BPA. C6 tumor-bearing rats were given 500 mg/kg of BPA or 100 mg/kg of BSH intraperitoneally; 2.5 h later, their brains were sectioned and subjected to SIMS. In the main tumor mass, BPA accumulated heterogeneously, while BSH accumulated homogeneously. In the peritumoral area, both BPA and BSH accumulated measurably. Interestingly, in this area, BSH accumulated distinctively in a diffuse manner even 800 microm distant from the interface between the main tumor and normal brain. In the contralateral brain, BPA accumulated measurably, while BSH did not. In conclusion, both BPA and BSH each have advantages and disadvantages. These compounds are considered to be essential as boron delivery agents independently for clinical BNCT. There is some rationale for the simultaneous use of both compounds in clinical BNCT for malignant gliomas.

Mind-Matter Interactions and the Frontal Lobes of the Brain: A Novel Neurobiological Model of Psi Inhibition.

PubMed

Freedman, Morris; Binns, Malcolm; Gao, Fuqiang; Holmes, Melissa; Roseborough, Austyn; Strother, Stephen; Vallesi, Antonino; Jeffers, Stanley; Alain, Claude; Whitehouse, Peter; Ryan, Jennifer D; Chen, Robert; Cusimano, Michael D; Black, Sandra E

Despite a large literature on psi, which encompasses a range of experiences including putative telepathy (mind-mind connections), clairvoyance (perceiving distant objects or events), precognition (perceiving future events), and mind-matter interactions, there has been insufficient focus on the brain in relation to this controversial phenomenon. In contrast, our research is based on a novel neurobiological model suggesting that frontal brain systems act as a filter to inhibit psi and that the inhibitory mechanisms may relate to self-awareness. To identify frontal brain regions that may inhibit psi. We used mind-matter interactions to study psi in two participants with frontal lobe damage. The experimental task was to influence numerical output of a Random Event Generator translated into movement of an arrow on a computer screen to the right or left. Brain MRI was analyzed to determine frontal volume loss. The primary area of lesion overlap between the participants was in the left medial middle frontal region, an area related to self-awareness, and involved Brodmann areas 9, 10, and 32. Both participants showed a significant effect in moving the arrow to the right, i.e., contralateral to the side of primary lesion overlap. Effect sizes were much larger compared to normal participants. The medial frontal lobes may act as a biological filter to inhibit psi through mechanisms related to self-awareness. Neurobiological studies with a focus on the brain may open new avenues of research on psi and may significantly advance the state of this poorly understood field. Copyright © 2018 Elsevier Inc. All rights reserved.

Utility of 68Ga-PSMA-11 PET/CT in Imaging of Glioma-A Pilot Study.

PubMed

Sasikumar, Arun; Kashyap, Raghava; Joy, Ajith; Charan Patro, Kanhu; Bhattacharya, Parthasarathy; Reddy Pilaka, Venkata Krishna; Oommen, Karuna Elza; Pillai, Maroor Raghavan Ambikalmajan

2018-06-22

Imaging of gliomas remains challenging. The aim of the study was to assess the feasibility of using Ga-PSMA-11 PET/CT for imaging gliomas. Fifteen patients with glioma from 2 centers were included in the study. Ten patients were treated cases of glioblastoma with suspected recurrence. Two patients were sent for assessing the nature (primary lesion/metastasis) of space-occupying lesion in the brain; 3 patients were imaged immediately after surgery and before radiotherapy. Target-to-background ratios (TBR) for the brain lesions were calculated using contralateral cerebellar uptake as background. Among the 10 cases with suspected recurrence, scan was positive in 9, subsequent surgery was done, and histopathology proved it to be true recurrence. In the scan-negative case on follow-up, no evidence of disease could be made clinically or radiologically. Among the other cases the presence or absence of disease could be unequivocally identified on the Ga-PSMA-11 brain scan and correlated with the histopathology or other imaging. Apart from the visual assessment quantitative assessment of the lesions with TBR also showed a significantly high TBR value for those with true disease compared with those with no disease. In the evaluation of gliomas, Ga-PSMA-11 PET/CT brain imaging is a potentially useful imaging tool. The use of Ga-PSMA-11 brain PET/CT in evaluation of recurrent glioma seems promising. Absence of physiological uptake of Ga-PSMA-11 in the normal brain parenchyma results in high TBR values and consequently better visualization of glioma lesions.

Contralateral migration of oculomotor neurons is regulated by Slit/Robo signaling.

PubMed

Bjorke, Brielle; Shoja-Taheri, Farnaz; Kim, Minkyung; Robinson, G Eric; Fontelonga, Tatiana; Kim, Kyung-Tai; Song, Mi-Ryoung; Mastick, Grant S

2016-10-22

Oculomotor neurons develop initially like typical motor neurons, projecting axons out of the ventral midbrain to their ipsilateral targets, the extraocular muscles. However, in all vertebrates, after the oculomotor nerve (nIII) has reached the extraocular muscle primordia, the cell bodies that innervate the superior rectus migrate to join the contralateral nucleus. This motor neuron migration represents a unique strategy to form a contralateral motor projection. Whether migration is guided by diffusible cues remains unknown. We examined the role of Slit chemorepellent signals in contralateral oculomotor migration by analyzing mutant mouse embryos. We found that the ventral midbrain expresses high levels of both Slit1 and 2, and that oculomotor neurons express the repellent Slit receptors Robo1 and Robo2. Therefore, Slit signals are in a position to influence the migration of oculomotor neurons. In Slit 1/2 or Robo1/2 double mutant embryos, motor neuron cell bodies migrated into the ventral midbrain on E10.5, three days prior to normal migration. These early migrating neurons had leading projections into and across the floor plate. In contrast to the double mutants, embryos which were mutant for single Slit or Robo genes did not have premature migration or outgrowth on E10.5, demonstrating a cooperative requirement of Slit1 and 2, as well as Robo1 and 2. To test how Slit/Robo midline repulsion is modulated, we found that the normal migration did not require the receptors Robo3 and CXCR4, or the chemoattractant, Netrin 1. The signal to initiate contralateral migration is likely autonomous to the midbrain because oculomotor neurons migrate in embryos that lack either nerve outgrowth or extraocular muscles, or in cultured midbrains that lacked peripheral tissue. Overall, our results demonstrate that a migratory subset of motor neurons respond to floor plate-derived Slit repulsion to properly control the timing of contralateral migration.

Distinct patterns of brain activity evoked by histamine-induced itch reveal an association with itch intensity and disease severity in atopic dermatitis

PubMed Central

Ishiuji, Y.; Coghill, R.C.; Patel, T.S.; Oshiro, Y.; Kraft, R.A.; Yosipovitch, G.

2009-01-01

Summary Background Little is known about brain mechanisms supporting the experience of chronic puritus in disease states. Objectives To examine the difference in brain processing of histamine-induced itch in patients with active atopic dermatitis (AD) vs. healthy controls with the emerging technique of functional magnetic resonance imaging (fMRI) using arterial spin labelling (ASL). Methods Itch was induced with histamine iontophoresis in eight patients with AD and seven healthy subjects. Results We found significant differences in brain processing of histamine-induced itch between patients with AD and healthy subjects. Patients with AD exhibited bilateral activation of the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), retrosplenial cingulate cortex and dorsolateral prefrontal cortex (DLPFC) as well as contralateral activation of the caudate nucleus and putamen. In contrast, healthy subjects activated the primary motor cortex, primary somatosensory cortex and superior parietal lobe. The PCC and precuneus exhibited significantly greater activity in patients vs. healthy subjects. A significant correlation between percentage changes of brain activation was noted in the activation of the ACC and contralateral insula and histamine-induced itch intensity as well as disease severity in patients with AD. In addition, an association was noted between DLPFC activity and disease severity. Conclusions Our results demonstrate that ASL fMRI is a promising technique to assess brain activity in chronic itch. Brain activity of acute itch in AD seems to differ from that in healthy subjects. Moreover, the activity in cortical areas involved in affect and emotion correlated to measures of disease severity. PMID:19663870

Abnormal functional motor lateralization in healthy siblings of patients with schizophrenia.

PubMed

Altamura, Mario; Fazio, Leonardo; De Salvia, Michela; Petito, Annamaria; Blasi, Giuseppe; Taurisano, Paolo; Romano, Raffaella; Gelao, Barbara; Bellomo, Antonello; Bertolino, Alessandro

2012-07-30

Earlier neuroimaging studies of motor function in schizophrenia have demonstrated reduced functional lateralization in the motor network during motor tasks. Here, we used event-related functional magnetic resonance imaging during a visually guided motor task in 18 clinically unaffected siblings of patients with schizophrenia and 24 matched controls to investigate if abnormal functional lateralization is related to genetic risk for this brain disorder. Whereas activity associated with motor task performance was mainly contralateral with only a marginal ipsilateral component in healthy participants, unaffected siblings had strong bilateral activity with significantly greater response in ipsilateral and contralateral premotor areas as well as in contralateral subcortical motor regions relative to controls. Reduced lateralization in siblings was also identified with a measure of laterality quotient. These findings suggest that abnormal functional lateralization of motor circuitry is related to genetic risk of schizophrenia. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Combined SCI and TBI: Recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement

PubMed Central

Inoue, Tomoo; Lin, Amity; Ma, Xiaokui; McKenna, Stephen L.; Creasey, Graham H.; Manley, Geoffrey T.; Ferguson, Adam R.; Bresnahan, Jacqueline C.; Beattie, Michael S.

2015-01-01

A significant proportion (estimates range from 16–74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0 mm depth, 4.0 m/s velocity impact on the forelimb sensori-motor cortex), or both SCI + TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6 weeks, in the paw placement test, SCI + contralateral TBI produced a profound deficit that failed to recover, but SCI + ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI + contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI + contralateral TBI revealed a severe deficit that recovered in 3 weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2 weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the contralateral hemisphere in all tests, but forepaw placements were relatively increased by an ipsilateral TBI relative to SCI alone, perhaps due to the dual competing injuries influencing the use of both forelimbs. These findings emphasize the complexity of recovery from combined CNS injuries, and the possible role of plasticity and laterality in rehabilitation, and provide a start towards a useful preclinical model for evaluating effective therapies for combine SCI and TBI. PMID:23770071

Combined SCI and TBI: recovery of forelimb function after unilateral cervical spinal cord injury (SCI) is retarded by contralateral traumatic brain injury (TBI), and ipsilateral TBI balances the effects of SCI on paw placement.

PubMed

Inoue, Tomoo; Lin, Amity; Ma, Xiaokui; McKenna, Stephen L; Creasey, Graham H; Manley, Geoffrey T; Ferguson, Adam R; Bresnahan, Jacqueline C; Beattie, Michael S

2013-10-01

A significant proportion (estimates range from 16 to 74%) of patients with spinal cord injury (SCI) have concomitant traumatic brain injury (TBI), and the combination often produces difficulties in planning and implementing rehabilitation strategies and drug therapies. For example, many of the drugs used to treat SCI may interfere with cognitive rehabilitation, and conversely drugs that are used to control seizures in TBI patients may undermine locomotor recovery after SCI. The current paper presents an experimental animal model for combined SCI and TBI to help drive mechanistic studies of dual diagnosis. Rats received a unilateral SCI (75 kdyn) at C5 vertebral level, a unilateral TBI (2.0 mm depth, 4.0 m/s velocity impact on the forelimb sensori-motor cortex), or both SCI+TBI. TBI was placed either contralateral or ipsilateral to the SCI. Behavioral recovery was examined using paw placement in a cylinder, grooming, open field locomotion, and the IBB cereal eating test. Over 6weeks, in the paw placement test, SCI+contralateral TBI produced a profound deficit that failed to recover, but SCI+ipsilateral TBI increased the relative use of the paw on the SCI side. In the grooming test, SCI+contralateral TBI produced worse recovery than either lesion alone even though contralateral TBI alone produced no observable deficit. In the IBB forelimb test, SCI+contralateral TBI revealed a severe deficit that recovered in 3 weeks. For open field locomotion, SCI alone or in combination with TBI resulted in an initial deficit that recovered in 2 weeks. Thus, TBI and SCI affected forelimb function differently depending upon the test, reflecting different neural substrates underlying, for example, exploratory paw placement and stereotyped grooming. Concurrent SCI and TBI had significantly different effects on outcomes and recovery, depending upon laterality of the two lesions. Recovery of function after cervical SCI was retarded by the addition of a moderate TBI in the contralateral hemisphere in all tests, but forepaw placements were relatively increased by an ipsilateral TBI relative to SCI alone, perhaps due to the dual competing injuries influencing the use of both forelimbs. These findings emphasize the complexity of recovery from combined CNS injuries, and the possible role of plasticity and laterality in rehabilitation, and provide a start towards a useful preclinical model for evaluating effective therapies for combine SCI and TBI. Copyright © 2013 Elsevier Inc. All rights reserved.

Antidepressant Effects of Electroconvulsive Therapy Correlate With Subgenual Anterior Cingulate Activity and Connectivity in Depression

PubMed Central

Liu, Yi; Du, Lian; Li, Yongmei; Liu, Haixia; Zhao, Wenjing; Liu, Dan; Zeng, Jinkun; Li, Xingbao; Fu, Yixiao; Qiu, Haitang; Li, Xirong; Qiu, Tian; Hu, Hua; Meng, Huaqing; Luo, Qinghua

2015-01-01

Abstract The mechanisms underlying the effects of electroconvulsive therapy (ECT) in major depressive disorder (MDD) are not fully understood. Resting-state functional magnetic resonance imaging (rs-fMRI) is a new tool to study the effects of brain stimulation interventions, particularly ECT. The authors aim to investigate the mechanisms of ECT in MDD by rs-fMRI. They used rs-fMRI to measure functional changes in the brain of first-episode, treatment-naive MDD patients (n = 23) immediately before and then following 8 ECT sessions (brief-pulse square-wave apparatus, bitemporal). They also computed voxel-wise amplitude of low-frequency fluctuation (ALFF) as a measure of regional brain activity and selected the left subgenual anterior cingulate cortex (sgACC) to evaluate functional connectivity between the sgACC and other brain regions. Increased regional brain activity measured by ALFF mainly in the left sgACC following ECT. Functional connectivity of the left sgACC increased in the ipsilateral parahippocampal gyrus, pregenual ACC, contralateral middle temporal pole, and orbitofrontal cortex. Importantly, reduction in depressive symptoms were negatively correlated with increased ALFF in the left sgACC and left hippocampus, and with distant functional connectivity between the left sgACC and contralateral middle temporal pole. That is, across subjects, as depression improved, regional brain activity in sgACC and its functional connectivity increased in the brain. Eight ECT sessions in MDD patients modulated activity in the sgACC and its networks. The antidepressant effects of ECT were negatively correlated with sgACC brain activity and connectivity. These findings suggest that sgACC-associated prefrontal-limbic structures are associated with the therapeutic effects of ECT in MDD. PMID:26559309

Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity.

PubMed

Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N

2015-01-01

To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen-Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure-function relationships but requires further validation in other populations of CP.

Robotic simulation of identical athletic-task kinematics on cadaveric limbs exhibits a lack of differences in knee mechanics between contralateral pairs

PubMed Central

Bates, Nathaniel A.; McPherson, April L.; Nesbitt, Rebecca J.; Shearn, Jason T.; Myer, Gregory D.; Hewett, Timothy E.

2017-01-01

Limb asymmetry is a known factor for increased ACL injury risk. These asymmetries are normally observed during in vivo testing. Prior studies have developed in vitro testing methodologies driven by in vivo kinematics to investigate knee mechanics relative to ACL injury. The objective of this study was to determine if mechanical side-to-side asymmetries persist in contralateral pairs during in vitro simulation testing. In vivo kinematics were recorded for male and female drop vertical jump and sidestep cutting tasks. The recorded kinematics were used to robotically simulate the motions on 7 contralateral pairs of cadaveric lower extremities specimens. ACL and MCL force, torque, and strains were recorded and analyzed for differences between contralateral pairs. There was a general lack of mechanical differences between limb sides. Adduction peak torque for the male sidestep cut movement was significantly different between limb sides (p = 0.04). However, this is consistent with ACL injury mechanics in that movement in the frontal plane (abduction/adduction) increases injury risk and it is possible loading differences in this plane may have resulted from tolerances within the setup process. The findings of this study indicate that contralateral knee joints were representative of each other during biomechanical in vitro tests. In future cadaveric robotic simulations, contralateral limbs can be used interchangeably. In addition, direct comparisons of the structural behaviors of isolated conditions for contralateral knee joints can be performed. PMID:28062120

Early growth hormone (GH) treatment promotes relevant motor functional improvement after severe frontal cortex lesion in adult rats.

PubMed

Heredia, Margarita; Fuente, A; Criado, J; Yajeya, J; Devesa, J; Riolobos, A S

2013-06-15

A number of studies, in animals and humans, describe the positive effects of the growth hormone (GH) treatment combined with rehabilitation on brain reparation after brain injury. We examined the effect of GH treatment and rehabilitation in adult rats with severe frontal motor cortex ablation. Thirty-five male rats were trained in the paw-reaching-for-food task and the preferred forelimb was recorded. Under anesthesia, the motor cortex contralateral to the preferred forelimb was aspirated or sham-operated. Animals were then treated with GH (0.15 mg/kg/day, s.c) or vehicle during 5 days, commencing immediately or 6 days post-lesion. Rehabilitation was applied at short- and long-term after GH treatment. Behavioral data were analized by ANOVA following Bonferroni post hoc test. After sacrifice, immunohistochemical detection of glial fibrillary acid protein (GFAP) and nestin were undertaken in the brain of all groups. Animal group treated with GH immediately after the lesion, but not any other group, showed a significant improvement of the motor impairment induced by the motor lesion, and their performances in the motor test were no different from sham-operated controls. GFAP immunolabeling and nestin immunoreactivity were observed in the perilesional area in all injured animals; nestin immunoreactivity was higher in GH-treated injured rats (mainly in animals GH-treated 6 days post-lesion). GFAP immunoreactivity was similar among injured rats. Interestingly, nestin re-expression was detected in the contralateral undamaged motor cortex only in GH-treated injured rats, being higher in animals GH-treated immediately after the lesion than in animals GH-treated 6 days post-lesion. Early GH treatment induces significant recovery of the motor impairment produced by frontal cortical ablation. GH effects include increased neurogenesis for reparation (perilesional area) and for increased brain plasticity (contralateral motor area). Copyright © 2013 Elsevier B.V. All rights reserved.

Value of 18F-3,4-dihydroxyphenylalanine PET/MR image fusion in pediatric supratentorial infiltrative astrocytomas: a prospective pilot study.

PubMed

Morana, Giovanni; Piccardo, Arnoldo; Milanaccio, Claudia; Puntoni, Matteo; Nozza, Paolo; Cama, Armando; Zefiro, Daniele; Cabria, Massimo; Rossi, Andrea; Garrè, Maria Luisa

2014-05-01

Infiltrative astrocytomas (IAs) represent a group of astrocytic gliomas ranging from low-grade to highly malignant, characterized by diffuse invasion of the brain parenchyma. When compared with their adult counterpart, pediatric IAs may be considered biologically distinct entities; nevertheless, similarly to those in adults they represent a complex oncologic challenge. The aim of this study was to investigate the diagnostic role, clinical contribution, and prognostic value of fused (18)F-3,4-dihydroxyphenylalanine ((18)F-DOPA) PET/MR images in pediatric supratentorial IAs. Pediatric patients with supratentorial IAs involving at least 2 cerebral lobes, either newly diagnosed or with suspected disease progression, prospectively underwent (18)F-DOPA PET and conventional MR imaging, performed within 10 d of each other. (18)F-DOPA PET data were interpreted qualitatively and semiquantitatively, fusing images with MR images. PET scans were classified as positive if tumors identified on MR imaging exhibited tracer uptake above the level of the corresponding contralateral normal brain. Maximum standardized uptake values, tumor-to-normal contralateral tissue ratios, and tumor-to-normal striatum ratios were calculated for all tumors. Correlations between the degree and extent of (18)F-DOPA uptake, MR imaging tumor characteristics, and histologic results were investigated. The contribution of (18)F-DOPA PET/MR image fusion was considered relevant if it enabled one to select the most appropriate biopsy site, discriminate between disease progression and treatment-related changes, or influence treatment strategy. The patient's outcome was finally correlated with (18)F-DOPA uptake. Thirteen patients (8 boys and 5 girls) were included (5 diffuse astrocytomas, 2 anaplastic astrocytomas, 5 gliomatosis cerebri, and 1 glioblastoma multiforme). The (18)F-DOPA uptake pattern was heterogeneous in all positive scans (9/13), revealing metabolic heterogeneities within each tumor. Significant differences in terms of (18)F-DOPA uptake were found between low- and high-grade lesions (P < 0.05). The diagnostic and therapeutic contribution of (18)F-DOPA PET/MR image fusion was relevant in 9 of 13 patients (69%). (18)F-DOPA uptake correlated significantly with progression-free survival (P = 0.004). Our results indicate that (18)F-DOPA PET/MR image fusion may be a reliable imaging biomarker of pediatric IAs. Information gathered by this combined imaging approach can be readily transferred to the everyday practice and may help clinicians to better stratify patients with IAs, especially diffuse astrocytomas and gliomatosis cerebri, for diagnostic, therapeutic, and prognostic purposes.

Magnetic-Stimulation-Related Physiological Artifacts in Hemodynamic Near-Infrared Spectroscopy Signals

PubMed Central

Näsi, Tiina; Mäki, Hanna; Kotilahti, Kalle; Nissilä, Ilkka; Haapalahti, Petri; Ilmoniemi, Risto J.

2011-01-01

Hemodynamic responses evoked by transcranial magnetic stimulation (TMS) can be measured with near-infrared spectroscopy (NIRS). This study demonstrates that cerebral neuronal activity is not their sole contributor. We compared bilateral NIRS responses following brain stimulation to those from the shoulders evoked by shoulder stimulation and contrasted them with changes in circulatory parameters. The left primary motor cortex of ten subjects was stimulated with 8-s repetitive TMS trains at 0.5, 1, and 2 Hz at an intensity of 75% of the resting motor threshold. Hemoglobin concentration changes were measured with NIRS on the stimulated and contralateral hemispheres. The photoplethysmograph (PPG) amplitude and heart rate were recorded as well. The left shoulder of ten other subjects was stimulated with the same protocol while the hemoglobin concentration changes in both shoulders were measured. In addition to PPG amplitude and heart rate, the pulse transit time was recorded. The brain stimulation reduced the total hemoglobin concentration (HbT) on the stimulated and contralateral hemispheres. The shoulder stimulation reduced HbT on the stimulated shoulder but increased it contralaterally. The waveforms of the HbT responses on the stimulated hemisphere and shoulder correlated strongly with each other (r = 0.65–0.87). All circulatory parameters were also affected. The results suggest that the TMS-evoked NIRS signal includes components that do not result directly from cerebral neuronal activity. These components arise from local effects of TMS on the vasculature. Also global circulatory effects due to arousal may affect the responses. Thus, studies involving TMS-evoked NIRS responses should be carefully controlled for physiological artifacts and effective artifact removal methods are needed to draw inferences about TMS-evoked brain activity. PMID:21887362

Magnetic-stimulation-related physiological artifacts in hemodynamic near-infrared spectroscopy signals.

PubMed

Näsi, Tiina; Mäki, Hanna; Kotilahti, Kalle; Nissilä, Ilkka; Haapalahti, Petri; Ilmoniemi, Risto J

2011-01-01

Hemodynamic responses evoked by transcranial magnetic stimulation (TMS) can be measured with near-infrared spectroscopy (NIRS). This study demonstrates that cerebral neuronal activity is not their sole contributor. We compared bilateral NIRS responses following brain stimulation to those from the shoulders evoked by shoulder stimulation and contrasted them with changes in circulatory parameters. The left primary motor cortex of ten subjects was stimulated with 8-s repetitive TMS trains at 0.5, 1, and 2 Hz at an intensity of 75% of the resting motor threshold. Hemoglobin concentration changes were measured with NIRS on the stimulated and contralateral hemispheres. The photoplethysmograph (PPG) amplitude and heart rate were recorded as well. The left shoulder of ten other subjects was stimulated with the same protocol while the hemoglobin concentration changes in both shoulders were measured. In addition to PPG amplitude and heart rate, the pulse transit time was recorded. The brain stimulation reduced the total hemoglobin concentration (HbT) on the stimulated and contralateral hemispheres. The shoulder stimulation reduced HbT on the stimulated shoulder but increased it contralaterally. The waveforms of the HbT responses on the stimulated hemisphere and shoulder correlated strongly with each other (r = 0.65-0.87). All circulatory parameters were also affected. The results suggest that the TMS-evoked NIRS signal includes components that do not result directly from cerebral neuronal activity. These components arise from local effects of TMS on the vasculature. Also global circulatory effects due to arousal may affect the responses. Thus, studies involving TMS-evoked NIRS responses should be carefully controlled for physiological artifacts and effective artifact removal methods are needed to draw inferences about TMS-evoked brain activity.

Polyethylene glycol restores axonal conduction after corpus callosum transection.

PubMed

Bamba, Ravinder; Riley, D Colton; Boyer, Richard B; Pollins, Alonda C; Shack, R Bruce; Thayer, Wesley P

2017-05-01

Polyethylene glycol (PEG) has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In this current experiment, coronal sectioning of the brains of Sprague-Dawley rats was performed after animal sacrifice. 3Brain high-resolution microelectrode arrays (MEA) were used to measure mean firing rate (MFR) and peak amplitude across the corpus callosum of the ex-vivo brain slices. The corpus callosum was subsequently transected and repeated measurements were performed. The cut ends of the corpus callosum were still apposite at this time. A PEG solution was applied to the injury site and repeated measurements were performed. MEA measurements showed that PEG was capable of restoring electrophysiology signaling after transection of central nerves. Before injury, the average MFRs at the ipsilateral, midline, and contralateral corpus callosum were 0.76, 0.66, and 0.65 spikes/second, respectively, and the average peak amplitudes were 69.79, 58.68, and 49.60 μV, respectively. After injury, the average MFRs were 0.71, 0.14, and 0.25 spikes/second, respectively and peak amplitudes were 52.11, 8.98, and 16.09 μV, respectively. After application of PEG, there were spikes in MFR and peak amplitude at the injury site and contralaterally. The average MFRs were 0.75, 0.55, and 0.47 spikes/second at the ipsilateral, midline, and contralateral corpus callosum, respectively and peak amplitudes were 59.44, 45.33, 40.02 μV, respectively. There were statistically differences in the average MFRs and peak amplitudes between the midline and non-midline corpus callosum groups ( P < 0.01, P < 0.05). These findings suggest that PEG restores axonal conduction between severed central nerves, potentially representing axonal fusion.

Polyethylene glycol restores axonal conduction after corpus callosum transection

PubMed Central

Bamba, Ravinder; Riley, D. Colton; Boyer, Richard B.; Pollins, Alonda C.; Shack, R. Bruce; Thayer, Wesley P.

2017-01-01

Polyethylene glycol (PEG) has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In this current experiment, coronal sectioning of the brains of Sprague-Dawley rats was performed after animal sacrifice. 3Brain high-resolution microelectrode arrays (MEA) were used to measure mean firing rate (MFR) and peak amplitude across the corpus callosum of the ex-vivo brain slices. The corpus callosum was subsequently transected and repeated measurements were performed. The cut ends of the corpus callosum were still apposite at this time. A PEG solution was applied to the injury site and repeated measurements were performed. MEA measurements showed that PEG was capable of restoring electrophysiology signaling after transection of central nerves. Before injury, the average MFRs at the ipsilateral, midline, and contralateral corpus callosum were 0.76, 0.66, and 0.65 spikes/second, respectively, and the average peak amplitudes were 69.79, 58.68, and 49.60 μV, respectively. After injury, the average MFRs were 0.71, 0.14, and 0.25 spikes/second, respectively and peak amplitudes were 52.11, 8.98, and 16.09 μV, respectively. After application of PEG, there were spikes in MFR and peak amplitude at the injury site and contralaterally. The average MFRs were 0.75, 0.55, and 0.47 spikes/second at the ipsilateral, midline, and contralateral corpus callosum, respectively and peak amplitudes were 59.44, 45.33, 40.02 μV, respectively. There were statistically differences in the average MFRs and peak amplitudes between the midline and non-midline corpus callosum groups (P < 0.01, P < 0.05). These findings suggest that PEG restores axonal conduction between severed central nerves, potentially representing axonal fusion. PMID:28616031

Neuroimaging and cognitive changes during déjà vu.

PubMed

Kovacs, Norbert; Auer, Tibor; Balas, Istvan; Karadi, Kazmer; Zambo, Katalin; Schwarcz, Attila; Klivenyi, Peter; Jokeit, Hennric; Horvath, Krisztina; Nagy, Ferenc; Janszky, Jozsef

2009-01-01

The cause or the physiological role of déjà vu (DV) in healthy people is unknown. The pathophysiology of DV-type epileptic aura is also unresolved. Here we describe a 22-year-old woman treated with deep brain stimulation (DBS) of the left internal globus pallidus for hemidystonia. At certain stimulation settings, DBS elicited reproducible episodes of DV. Neuropsychological tests and single-photon-emission computed tomography (SPECT) were performed during DBS-evoked DV and during normal DBS stimulation without DV. SPECT during DBS-evoked DV revealed hyperperfusion of the right (contralateral to the electrode) hippocampus and other limbic structures. Neuropsychological examinations performed during several evoked DV episodes revealed disturbances in nonverbal memory. Our results confirm the role of mesiotemporal structures in the pathogenesis of DV. We hypothesize that individual neuroanatomy and disturbances in gamma oscillations or in the dopaminergic system played a role in DBS-elicited DV in our patient.

The effects of brain lesions on the "hopping reaction" in newborn and adult rabbits: a model for studying age dependent recovery.

PubMed

van Hof, M W; Hobbelen, J F; Gramsbergen, A

1990-01-01

In 5 groups of rabbits (0-1, 2-3, 4-5, 6-7 and 12-13 weeks old) the left frontal, parieto-temporal and occipital cortex were removed. Beginning two weeks after the operations the hopping reaction was tested during 15 weeks. It was found in the groups operated 0-1, 2-3 and 4-5 weeks after birth, that the hopping reaction developed normally. This was not the case in the animals operated 6-7 and 12-13 weeks after birth. Brightness descrimination with the left and right eye was tested in the same animals, beginning 12 weeks after the operation. Contrary to the motor system, no age-development recovery was found in the visual system. In all age groups, brightness discrimination with the eye contralateral to the lesion was impaired.

Lateralization of brain activation to imagination and smell of odors using functional magnetic resonance imaging (fMRI): left hemispheric localization of pleasant and right hemispheric localization of unpleasant odors.

PubMed

Henkin, R I; Levy, L M

2001-01-01

Our goal was to use functional MRI (fMRI) of brain to reveal activation in each cerebral hemisphere in response to imagination and smell of odors. FMRI brain scans were obtained in 24 normal subjects using multislice fast low angle shot (FLASH) MRI in response to imagination of banana and peppermint odors and in response to smell of corresponding odors of amyl acetate and menthone, respectively, and of pyridine. Three coronal sections selected from anterior to posterior brain regions were used. Similar studies were obtained in two patients with hyposmia using FLASH MRI and in one patient with hyposmia using echo planar imaging (EPI) both before and after theophylline treatment that returned smell function to or toward normal in each patient and in two patients with birhinal phantosmia (persistent foul odor) and global phantogeusia (persistent foul taste) with FLASH and EPI fMRI before and after treatment with neuroleptic drugs that inhibited their phantosmia and phantogeusia. Activation images were derived using correlation analysis. Ratios of hemispheric areas of brain activation to total hemispheric brain areas were calculated for FLASH fMRI, and numerical counts of pixel clusters in each hemisphere were made for EPI studies. Total pixel cluster counts in localized regions of each hemispheric section were also obtained. In normal subjects, activation generally occurred in left (L) > right (R) brain hemisphere in response to banana and peppermint odor imagination and to smell of corresponding odors of amyl acetate and menthone. Whereas there were no overall hemispheric differences for pyridine odor, activation in men was R > L hemisphere. Although absolute activation in both L and R hemispheres in response to banana odor imagination and amyl acetate smell was men > women, the ratio of L to R activation was women > men. In hyposmic patients studied by FLASH fMRI, activation to banana odor imagination and amyl acetate smell was L > R hemisphere both before and after theophylline treatment. In the hyposmic patient studied with EPI before theophylline treatment, activation to banana and peppermint odor imagination and to amyl acetate, menthone, and pyridine smell was R > L hemisphere; after theophylline treatment restored normal smell function, activation shifted completely with banana and peppermint odor imagination and amyl acetate and menthone smell to L > R hemisphere, consistent with responses in normal subjects. However, this shift also occurred for pyridine smell, which is opposite to responses in normal control subjects. In patients with phantosmia and phantogeusia, activation to phantosmia and phantogeusia before treatment was R > L hemisphere; after treatment inhibited phantosmia and phantogeusia, activation shifted with a slight L > R hemispheric lateralization. Localization of all lateralized responses indicated that anterior frontal and temporal cortices were brain regions most involved with imagination and smell of odors and with phantosmia and phantogeusia presence. Imagination and smell of odors perceived as pleasant generally activated the dominant or L > R brain hemisphere. Smell of odors perceived as unpleasant and unpleasant phantosmia and phantogeusia generally activated the contralateral or R > L brain hemisphere. With remission of phantosmia and phantogeusia, hemispheric activation was not only inhibited, but also there was a slight shift to L > R hemispheric predominance. Predominant L > R hemispheric differences in brain activation in normal subjects occurred in the order amyl acetate > menthone > pyridine, consistent with the hypothesis that pleasant odors are more appreciated in L hemisphere and unpleasant odors more in R hemisphere. Anterior frontal and temporal cortex regions previously found activated by imagination and smell of odors and phantosmia and phantogeusia perception accounted for most hemispheric differences.

Non-invasive assessment of intratumoral vascularity using arterial spin labeling: A comparison to susceptibility-weighted imaging for the differentiation of primary cerebral lymphoma and glioblastoma.

PubMed

Furtner, J; Schöpf, V; Preusser, M; Asenbaum, U; Woitek, R; Wöhrer, A; Hainfellner, J A; Wolfsberger, S; Prayer, D

2014-05-01

Using conventional MRI methods, the differentiation of primary cerebral lymphomas (PCNSL) and other primary brain tumors, such as glioblastomas, is difficult due to overlapping imaging characteristics. This study was designed to discriminate tumor entities using normalized vascular intratumoral signal intensity values (nVITS) obtained from pulsed arterial spin labeling (PASL), combined with intratumoral susceptibility signals (ITSS) from susceptibility-weighted imaging (SWI). Thirty consecutive patients with glioblastoma (n=22) and PCNSL (n=8), histologically classified according to the WHO brain tumor classification, were included. MRIs were acquired on a 3T scanner, and included PASL and SWI sequences. nVITS was defined by the signal intensity ratio between the tumor and the contralateral normal brain tissue, as obtained by PASL images. ITSS was determined as intratumoral low signal intensity structures detected on SWI sequences and were divided into four different grades. Potential differences in the nVITS and ITSS between glioblastomas and PCNSLs were revealed using statistical testing. To determine sensitivity, specificity, and diagnostic accuracy, as well as an optimum cut-off value for the differentiation of PCNSL and glioblastoma, a receiver operating characteristic analysis was used. We found that nVITS (p=0.011) and ITSS (p=0.001) values were significantly higher in glioblastoma than in PCNSL. The optimal cut-off value for nVITS was 1.41 and 1.5 for ITSS, with a sensitivity, specificity, and accuracy of more than 95%. These findings indicate that nVITS values have a comparable diagnostic accuracy to ITSS values in differentiating glioblastoma and PCNSL, offering a completely non-invasive and fast assessment of tumoral vascularity in a clinical setting. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Hemispheric differences of motor execution: a near-infrared spectroscopy study.

PubMed

Helmich, Ingo; Rein, Robert; Niermann, Nico; Lausberg, Hedda

2013-01-01

Distal movements of the limbs are predominantly controlled by the contralateral hemisphere. However, functional neuroimaging studies do not unequivocally demonstrate a lateralization of the cerebral activation during hand movements. While some studies show a predominant activation of the contralateral hemisphere, other studies provide evidence for a symmetrically distributed bihemispheric activation. However, the divergent results may also be due to methodological shortcomings. Therefore, the present study using functional near-infrared spectroscopy examines cerebral activation in both hemispheres during motor actions of the right and left hands. Twenty participants performed a flexion/extension task with the right- or left-hand thumb. Cerebral oxygenation changes were recorded from 48 channels over the primary motor, pre-motor, supplementary motor, primary somatosensory cortex, subcentral area, and the supramarginal gyrus of each hemisphere. A consistent increase of cerebral oxygenation was found for oxygenated and for total hemoglobin in the hemisphere contralateral to the moving hand, regardless of the laterality. These findings are in line with previous data from localization [1-3] and brain imaging studies [4-6]. The present data support the proposition that there is no hemispheric specialization for simple distal motor tasks. Both hemispheres are equally activated during movement of the contralateral upper limb.

Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor

PubMed Central

Gibson, William S.; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P.; Welker, Kirk M.; Klassen, Bryan T.; Min, Hoon-Ki

2016-01-01

Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson’s disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal modelling revealed a correlation between therapeutic effectiveness and attenuated within-region inhibitory connectivity in cerebellum. Finally, specific subregions of sensorimotor cortex were identified in which deep brain stimulation-evoked activation correlated with the presence of unwanted paraesthesias. These results suggest that thalamic deep brain stimulation in tremor likely exerts its effects through modulation of both olivocerebellar and thalamocortical circuits. In addition, our findings indicate that deep brain stimulation-evoked functional activation maps obtained intraoperatively may contain predictive information pertaining to the therapeutic and adverse effects induced by deep brain stimulation. PMID:27329768

Mild traumatic brain injury results in depressed cerebral glucose uptake: An (18)FDG PET study.

PubMed

Selwyn, Reed; Hockenbury, Nicole; Jaiswal, Shalini; Mathur, Sanjeev; Armstrong, Regina C; Byrnes, Kimberly R

2013-12-01

Moderate to severe traumatic brain injury (TBI) in humans and rats induces measurable metabolic changes, including a sustained depression in cerebral glucose uptake. However, the effect of a mild TBI on brain glucose uptake is unclear, particularly in rodent models. This study aimed to determine the glucose uptake pattern in the brain after a mild lateral fluid percussion (LFP) TBI. Briefly, adult male rats were subjected to a mild LFP and positron emission tomography (PET) imaging with (18)F-fluorodeoxyglucose ((18)FDG), which was performed prior to injury and at 3 and 24 h and 5, 9, and 16 days post-injury. Locomotor function was assessed prior to injury and at 1, 3, 7, 14, and 21 days after injury using modified beam walk tasks to confirm injury severity. Histology was performed at either 10 or 21 days post-injury. Analysis of function revealed a transient impairment in locomotor ability, which corresponds to a mild TBI. Using reference region normalization, PET imaging revealed that mild LFP-induced TBI depresses glucose uptake in both the ipsilateral and contralateral hemispheres in comparison with sham-injured and naïve controls from 3 h to 5 days post-injury. Further, areas of depressed glucose uptake were associated with regions of glial activation and axonal damage, but no measurable change in neuronal loss or gross tissue damage was observed. In conclusion, we show that mild TBI, which is characterized by transient impairments in function, axonal damage, and glial activation, results in an observable depression in overall brain glucose uptake using (18)FDG-PET.

Neural connectivity of the lateral geniculate body in the human brain: diffusion tensor imaging study.

PubMed

Kwon, Hyeok Gyu; Jang, Sung Ho

2014-08-22

A few studies have reported on the neural connectivity of some neural structures of the visual system in the human brain. However, little is known about the neural connectivity of the lateral geniculate body (LGB). In the current study, using diffusion tensor tractography (DTT), we attempted to investigate the neural connectivity of the LGB in normal subjects. A total of 52 healthy subjects were recruited for this study. A seed region of interest was placed on the LGB using the FMRIB Software Library which is a probabilistic tractography method based on a multi-fiber model. Connectivity was defined as the incidence of connection between the LGB and target brain areas at the threshold of 5, 25, and 50 streamlines. In addition, connectivity represented the percentage of connection in all hemispheres of 52 subjects. We found the following characteristics of connectivity of the LGB at the threshold of 5 streamline: (1) high connectivity to the corpus callosum (91.3%) and the contralateral temporal cortex (56.7%) via the corpus callosum, (2) high connectivity to the ipsilateral cerebral cortex: the temporal lobe (100%), primary visual cortex (95.2%), and visual association cortex (77.9%). The LGB appeared to have high connectivity to the corpus callosum and both temporal cortexes as well as the ipsilateral occipital cortex. We believe that the results of this study would be helpful in investigation of the neural network associated with the visual system and brain plasticity of the visual system after brain injury. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Typical cerebral metabolic patterns in neurodegenerative brain diseases.

PubMed

Teune, Laura K; Bartels, Anna L; de Jong, Bauke M; Willemsen, Antoon T M; Eshuis, Silvia A; de Vries, Jeroen J; van Oostrom, Joost C H; Leenders, Klaus L

2010-10-30

The differential diagnosis of neurodegenerative brain diseases on clinical grounds is difficult, especially at an early disease stage. Several studies have found specific regional differences of brain metabolism applying [(18)F]-fluoro-deoxyglucose positron emission tomography (FDG-PET), suggesting that this method can assist in early differential diagnosis of neurodegenerative brain diseases.We have studied patients who had an FDG-PET scan on clinical grounds at an early disease stage and included those with a retrospectively confirmed diagnosis according to strictly defined clinical research criteria. Ninety-six patients could be included of which 20 patients with Parkinson's disease (PD), 21 multiple system atrophy (MSA), 17 progressive supranuclear palsy (PSP), 10 corticobasal degeneration (CBD), 6 dementia with Lewy bodies (DLB), 15 Alzheimer's disease (AD), and 7 frontotemporal dementia (FTD). FDG PET images of each patient group were analyzed and compared to18 healthy controls using Statistical Parametric Mapping (SPM5).Disease-specific patterns of relatively decreased metabolic activity were found in PD (contralateral parietooccipital and frontal regions), MSA (bilateral putamen and cerebellar hemispheres), PSP (prefrontal cortex and caudate nucleus, thalamus, and mesencephalon), CBD (contralateral cortical regions), DLB (occipital and parietotemporal regions), AD (parietotemporal regions), and FTD (frontotemporal regions).The integrated method addressing a spectrum of various neurodegenerative brain diseases provided means to discriminate patient groups also at early disease stages. Clinical follow-up enabled appropriate patient inclusion. This implies that an early diagnosis in individual patients can be made by comparing each subject's metabolic findings with a complete database of specific disease related patterns.

Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects

PubMed Central

Bi, Chenchen; Duan, Dongyu; Chu, Liuxiang; Yu, Xin; Wu, Zimei; Wang, Aiping; Sun, Kaoxiang

2018-01-01

Introduction Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson’s disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD. Materials and methods The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs. Results Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference (P<0.05) in contralateral rotations between rats treated with Lf-R-NPs and those treated with R-NPs. Furthermore, Lf-R-NPs significantly alleviated nigrostriatal dopaminergic neurodegeneration in the rat model of 6-hydroxydopamine-induced PD. Conclusion Our findings show that Lf-R-NPs deliver rotigotine more efficiently to the brain, thereby enhancing efficacy. Therefore, Lf-R-NPs might have therapeutic potential for the treatment of PD. PMID:29391788

Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects.

PubMed

Yan, Xiuju; Xu, Lixiao; Bi, Chenchen; Duan, Dongyu; Chu, Liuxiang; Yu, Xin; Wu, Zimei; Wang, Aiping; Sun, Kaoxiang

2018-01-01

Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson's disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD. The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs. Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference ( P <0.05) in contralateral rotations between rats treated with Lf-R-NPs and those treated with R-NPs. Furthermore, Lf-R-NPs significantly alleviated nigrostriatal dopaminergic neurodegeneration in the rat model of 6-hydroxydopamine-induced PD. Our findings show that Lf-R-NPs deliver rotigotine more efficiently to the brain, thereby enhancing efficacy. Therefore, Lf-R-NPs might have therapeutic potential for the treatment of PD.

Qualitative and quantitative radiological analysis of non-contrast CT is a strong indicator in patients with acute pyelonephritis.

PubMed

El-Merhi, Fadi; Mohamad, May; Haydar, Ali; Naffaa, Lena; Nasr, Rami; Deeb, Ibrahim Al-Sheikh; Hamieh, Nadine; Tayara, Ziad; Saade, Charbel

2018-04-01

To evaluate the performance of non-contrast computed tomography (CT) by reporting the difference in attenuation between normal and inflamed renal parenchyma in patients clinically diagnosed with acute pyelonephritis (APN). This is a retrospective study concerned with non-contrast CT evaluation of 74 patients, admitted with a clinical diagnosis of APN and failed to respond to 48h antibiotics treatment. Mean attenuation values in Hounsfield units (HU) were measured in the upper, middle and lower segments of the inflamed and the normal kidney of the same patient. Independent t-test was performed for statistical analysis. Image evaluation included receiver operating characteristic (ROC), visual grading characteristic (VGC) and kappa analyses. The mean attenuation in the upper, middle and lower segments of the inflamed renal cortex was 32%, 25%, and 29% lower than the mean attenuation of the corresponding cortical segments of the contralateral normal kidney, respectively (p<0.01). The mean attenuation in the upper, middle, and lower segments of the inflamed renal medulla was 48%, 21%, and 30%, lower than the mean attenuation of the corresponding medullary segments of the contralateral normal kidney (p<0.02). The mean attenuation between the inflamed and non-inflamed renal cortex and medulla was 29% and 30% lower respectively (p<0.001). The AUCROC (p<0.001) analysis demonstrated significantly higher scores for pathology detection, irrespective of image quality, compared to clinical and laboratory results with an increased inter-reader agreement from poor to substantial. Non-contrast CT showed a significant decrease in the parenchymal density of the kidney affected with APN in comparison to the contralateral normal kidney of the same patient. This can be incorporated in the diagnostic criteria of APN in NCCT in the emergency setting. Copyright © 2017 Elsevier Inc. All rights reserved.

Neural correlates of visuospatial consciousness in 3D default space: insights from contralateral neglect syndrome.

PubMed

Jerath, Ravinder; Crawford, Molly W

2014-08-01

One of the most compelling questions still unanswered in neuroscience is how consciousness arises. In this article, we examine visual processing, the parietal lobe, and contralateral neglect syndrome as a window into consciousness and how the brain functions as the mind and we introduce a mechanism for the processing of visual information and its role in consciousness. We propose that consciousness arises from integration of information from throughout the body and brain by the thalamus and that the thalamus reimages visual and other sensory information from throughout the cortex in a default three-dimensional space in the mind. We further suggest that the thalamus generates a dynamic default three-dimensional space by integrating processed information from corticothalamic feedback loops, creating an infrastructure that may form the basis of our consciousness. Further experimental evidence is needed to examine and support this hypothesis, the role of the thalamus, and to further elucidate the mechanism of consciousness. Copyright © 2014 Elsevier Inc. All rights reserved.

F-18 choline PET does not detect increased metabolism in F-18 fluoroethyltyrosine-negative low-grade gliomas.

PubMed

Roelcke, Ulrich; Bruehlmeier, Matthias; Hefti, Martin; Hundsberger, Thomas; Nitzsche, Egbert U

2012-01-01

Positron emission tomography (PET) with radiolabeled amino acids provides information on biopsy target and chemotherapy response in patients with low-grade gliomas (LGG). In this article, we addressed whether PET with F-18 choline (CHO) detects increased metabolism in F-18 fluoroethyltyrosine (FET)-negative LGG patients. Six LGG patients with nongadolinium-enhancing (magnetic resonance) FET-negative LGG were imaged with CHO PET. Regions of interest were positioned over tumor and contralateral brain. Uptake of FET and CHO was quantified as count ratio of tumor to contralateral brain. The mean FET uptake ratio for FET-negative LGG was 0.95 ± 0.03 (mean ± standard deviation). Five tumors did not show increased uptake ratios for CHO (0.96 ± 0.12). Slightly increased CHO uptake was found in 1 patient (1.24), which, however, was not associated with tumor visualization. Amino acid and choline uptake appear to behave similar in nongadolinium-enhancing LGG. For clinical purposes, CHO PET is not superior to FET PET.

Feasibility and Safety of Intra-arterial Pericyte Progenitor Cell Delivery Following Mannitol-Induced Transient Blood-Brain Barrier Opening in a Canine Model.

PubMed

Youn, Sung Won; Jung, Keun-Hwa; Chu, Kon; Lee, Jong-Young; Lee, Soon-Tae; Bahn, Jae-jun; Park, Dong-Kyu; Yu, Jung-Suk; Kim, So-Yun; Kim, Manho; Lee, Sang Kun; Han, Moon-Hee; Roh, Jae-Kyu

2015-01-01

Stem cell therapy is currently being studied with a view to rescuing various neurological diseases. Such studies require not only the discovery of potent candidate cells but also the development of methods that allow optimal delivery of those candidates to the brain tissues. Given that the blood-brain barrier (BBB) precludes cells from entering the brain, the present study was designed to test whether hyperosmolar mannitol securely opens the BBB and enhances intra-arterial cell delivery. A noninjured normal canine model in which the BBB was presumed to be closed was used to evaluate the feasibility and safety of the tested protocol. Autologous adipose tissue-derived pericytes with platelet-derived growth factor receptor β positivity were utilized. Cells were administered 5 min after mannitol pretreatment using one of following techniques: (1) bolus injection of a concentrated suspension, (2) continuous infusion of a diluted suspension, or (3) bolus injection of a concentrated suspension that had been shaken by repeated syringe pumping. Animals administered a concentrated cell suspension without mannitol pretreatment served as a control group. Vital signs, blood parameters, neurologic status, and major artery patency were kept stable throughout the experiment and the 1-month posttreatment period. Although ischemic lesions were noted on magnetic resonance imaging in several mongrel dogs with concentrated cell suspension, the injection technique using repeated syringe shaking could avert this complication. The cells were detected in both ipsilateral and contralateral cortices and were more frequent at the ipsilateral and frontal locations, whereas very few cells were observed anywhere in the brain when mannitol was not preinjected. These data suggest that intra-arterial cell infusion with mannitol pretreatment is a feasible and safe therapeutic approach in stable brain diseases such as chronic stroke.

The cortical activation pattern by a rehabilitation robotic hand: a functional NIRS study

PubMed Central

Chang, Pyung-Hun; Lee, Seung-Hee; Gu, Gwang Min; Lee, Seung-Hyun; Jin, Sang-Hyun; Yeo, Sang Seok; Seo, Jeong Pyo; Jang, Sung Ho

2014-01-01

Introduction: Clarification of the relationship between external stimuli and brain response has been an important topic in neuroscience and brain rehabilitation. In the current study, using functional near infrared spectroscopy (fNIRS), we attempted to investigate cortical activation patterns generated during execution of a rehabilitation robotic hand. Methods: Ten normal subjects were recruited for this study. Passive movements of the right fingers were performed using a rehabilitation robotic hand at a frequency of 0.5 Hz. We measured values of oxy-hemoglobin (HbO), deoxy-hemoglobin (HbR) and total-hemoglobin (HbT) in five regions of interest: the primary sensory-motor cortex (SM1), hand somatotopy of the contralateral SM1, supplementary motor area (SMA), premotor cortex (PMC), and prefrontal cortex (PFC). Results: HbO and HbT values indicated significant activation in the left SM1, left SMA, left PMC, and left PFC during execution of the rehabilitation robotic hand (uncorrected, p < 0.01). By contrast, HbR value indicated significant activation only in the hand somatotopic area of the left SM1 (uncorrected, p < 0.01). Conclusions: Our results appear to indicate that execution of the rehabilitation robotic hand could induce cortical activation. PMID:24570660

The effect of prazosin on skin microcirculation as assessed by laser Doppler flowmetry.

PubMed Central

Khan, F; Struthers, A D; Spence, V A

1988-01-01

1. Laser Doppler flowmetry was used in six normal volunteers to record changes in fingertip skin blood flow after the administration of prazosin to block postsynaptic alpha 1-adrenoceptors. 2. Prazosin (0.5 mg orally) did not alter systolic or diastolic blood pressure or heart rate. 3. Prazosin did significantly increase basal skin blood flow 2 h after its administration but this effect was no longer evident after contralateral hand warming. Prazosin markedly reduced the skin vasoconstrictor response to deep inspiration and to contralateral hand cooling. 4. This study suggests that postsynaptic alpha 1-adrenoceptors are involved in maintaining skin vasoconstrictor tone at rest and are also involved in the rapid skin vasoconstriction seen in response to a deep inspiration and to contralateral hand cooling. PMID:2846022

Ruptured ectopic pregnancy with contralateral adnexal torsion after spontaneous conception.

PubMed

DiLuigi, Andrea J; Maier, Donald B; Benadiva, Claudio A

2008-11-01

To describe a case of ruptured ectopic pregnancy and contralateral adnexal torsion after spontaneous conception. Case report. Tertiary university medical center. A 23-year-old multiparous female with severe bilateral pelvic pain and a positive pregnancy test. Operative laparoscopy with detorsion of left adnexa, drainage of left ovarian hemorrhagic corpus luteum cyst, right salpingectomy, and dilation and curettage. Laparoscopy revealed a 5 cm hemorrhagic corpus luteum cyst of the left ovary, torsion of the left ovary and fallopian tube, and a ruptured right ampullary ectopic pregnancy. Normal perfusion of left ovary and fallopian tube after detorsion, resolution of left ovarian hemorrhagic corpus luteum cyst, patent left fallopian tube with chromopertubation, and successful removal of ectopic pregnancy. This is a unique case of adnexal torsion and contralateral ectopic pregnancy occurring after spontaneous conception.

Leg kinematics and kinetics in landing from a single-leg hop for distance. A comparison between dominant and non-dominant leg.

PubMed

van der Harst, J J; Gokeler, A; Hof, A L

2007-07-01

Anterior cruciate ligament (ACL) deficiency can be a major problem for athletes and subsequent reconstruction of the ACL may be indicated if a conservative regimen has failed. After ACL reconstruction signs of abnormality in the use of the leg remain for a long time. It is expected that the landing after a single-leg hop for distance (horizontal hop) might give insight in the differences in kinematics and kinetics between uninjured legs and ACL-reconstructed legs. Before the ACL-reconstructed leg can be compared with the contralateral leg, knowledge of differences between legs of uninjured subjects is needed. Kinematic and kinetic variables of both legs were measured with an optoelectronic system and a force plate and calculated by inverse dynamics. The dominant leg (the leg with biggest horizontal hop distance) and the contralateral leg of nine uninjured subjects were compared. No significant differences were found in most of the kinematic and kinetic variables between dominant leg and contralateral leg of uninjured subjects. Only hop distance and hip extension angles differed significantly. This study suggests that there are no important differences between dominant leg and contralateral leg in healthy subjects. As a consequence, the uninvolved leg of ACL-reconstructed patients can be used as a reference. The observed variables of this study can be used as a reference of normal values and normal differences between legs in healthy subjects.

Emergency Interventions After Severe Traumatic Brain Injury in Rats: Effect on Neuropathology and Functional Outcome

DTIC Science & Technology

2000-01-01

placed in a stereotaxic frame and a left parietal craniotomy was performed. The dura and bone flap were left in place until immediately before CCI. A...microtransducer) was inserted through a burr hole in the frontal bone into the contralateral (right) frontal cortex at the time of craniotomy ...immediately after injury) or vehicle. A separate sham group (all surgery including craniotomy , but no TBI was also studied. Brain temperature maintained at

T1ρ-weighted Dynamic Glucose-enhanced MR Imaging in the Human Brain.

PubMed

Paech, Daniel; Schuenke, Patrick; Koehler, Christina; Windschuh, Johannes; Mundiyanapurath, Sibu; Bickelhaupt, Sebastian; Bonekamp, David; Bäumer, Philipp; Bachert, Peter; Ladd, Mark E; Bendszus, Martin; Wick, Wolfgang; Unterberg, Andreas; Schlemmer, Heinz-Peter; Zaiss, Moritz; Radbruch, Alexander

2017-12-01

Purpose To evaluate the ability to detect intracerebral regions of increased glucose concentration at T1ρ-weighted dynamic glucose-enhanced (DGE) magnetic resonance (MR) imaging at 7.0 T. Materials and Methods This prospective study was approved by the institutional review board. Nine patients with newly diagnosed glioblastoma and four healthy volunteers were included in this study from October 2015 to July 2016. Adiabatically prepared chemical exchange-sensitive spin-lock imaging was performed with a 7.0-T whole-body unit with a temporal resolution of approximately 7 seconds, yielding the time-resolved DGE contrast. T1ρ-weighted DGE MR imaging was performed with injection of 100 mL of 20% d-glucose via the cubital vein. Glucose enhancement, given by the relative signal intensity change at T1ρ-weighted MR imaging (DGEρ), was quantitatively investigated in brain gray matter versus white matter of healthy volunteers and in tumor tissue versus normal-appearing white matter of patients with glioblastoma. The median signal intensities of the assessed brain regions were compared by using the Wilcoxon rank-sum test. Results In healthy volunteers, the median signal intensity in basal ganglia gray matter (DGEρ = 4.59%) was significantly increased compared with that in white matter tissue (DGEρ = 0.65%) (P = .028). In patients, the median signal intensity in the glucose-enhanced tumor region as displayed on T1ρ-weighted DGE images (DGEρ = 2.02%) was significantly higher than that in contralateral normal-appearing white matter (DGEρ = 0.08%) (P < .0001). Conclusion T1ρ-weighted DGE MR imaging in healthy volunteers and patients with newly diagnosed, untreated glioblastoma enabled visualization of brain glucose physiology and pathophysiologically increased glucose uptake and may have the potential to provide information about glucose metabolism in tumor tissue. © RSNA, 2017 Online supplemental material is available for this article.

Linear-array based full-view high-resolution photoacoustic computed tomography of whole mouse brain functions in vivo

NASA Astrophysics Data System (ADS)

Li, Lei; Zhang, Pengfei; Wang, Lihong V.

2018-02-01

Photoacoustic computed tomography (PACT) is a non-invasive imaging technique offering high contrast, high resolution, and deep penetration in biological tissues. We report a photoacoustic computed tomography (PACT) system equipped with a high frequency linear array for anatomical and functional imaging of the mouse whole brain. The linear array was rotationally scanned in the coronal plane to achieve the full-view coverage. We investigated spontaneous neural activities in the deep brain by monitoring the hemodynamics and observed strong interhemispherical correlations between contralateral regions, both in the cortical layer and in the deep regions.

Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from recrossing, allowing for unilateral motor control.

PubMed

Kullander, K; Croll, S D; Zimmer, M; Pan, L; McClain, J; Hughes, V; Zabski, S; DeChiara, T M; Klein, R; Yancopoulos, G D; Gale, N W

2001-04-01

Growing axons follow highly stereotypical pathways, guided by a variety of attractive and repulsive cues, before establishing specific connections with distant targets. A particularly well-known example that illustrates the complexity of axonal migration pathways involves the axonal projections of motor neurons located in the motor cortex. These projections take a complex route during which they first cross the midline, then form the corticospinal tract, and ultimately connect with motor neurons in the contralateral side of the spinal cord. These obligatory contralateral connections account for why one side of the brain controls movement on the opposing side of the body. The netrins and slits provide well-known midline signals that regulate axonal crossings at the midline. Herein we report that a member of the ephrin family, ephrin-B3, also plays a key role at the midline to regulate axonal crossing. In particular, we show that ephrin-B3 acts as the midline barrier that prevents corticospinal tract projections from recrossing when they enter the spinal gray matter. We report that in ephrin-B3(-/-) mice, corticospinal tract projections freely recross in the spinal gray matter, such that the motor cortex on one side of the brain now provides bilateral input to the spinal cord. This neuroanatomical abnormality in ephrin-B3(-/-) mice correlates with loss of unilateral motor control, yielding mice that simultaneously move their right and left limbs and thus have a peculiar hopping gait quite unlike the alternate step gait displayed by normal mice. The corticospinal and walking defects in ephrin-B3(-/-) mice resemble those recently reported for mice lacking the EphA4 receptor, which binds ephrin-B3 as well as other ephrins, suggesting that the binding of EphA4-bearing axonal processes to ephrin-B3 at the midline provides the repulsive signal that prevents corticospinal tract projections from recrossing the midline in the developing spinal cord.

Contralateral suppression of transient otoacoustic emissions and sentence recognition in noise in young adults.

PubMed

Stuart, Andrew; Butler, Alyson K

2012-10-01

One purported role of the medial olivocochlear (MOC) efferent system is to reduce the effects of masking noise. MOC system functioning can be evaluated noninvasively in humans through contralateral suppression of otoacoustic emissions. It has been suggested that the strength of the MOC efferent activity should be positively associated with listening performance in noise. The objective of the study was to further explore this notion by examining contralateral suppression of transient evoked otoacoustic emissions (TEOAEs) and sentence recognition in two noises with normal hearing young adults. A repeated measures multivariate quasi-experimental design was employed. Thirty-two normal hearing young adult females participated. Reception thresholds for sentences (RTSs) were determined monaurally and binaurally in quiet and in competing continuous and interrupted noises. Both noises had an identical power spectrum and differed only in their temporal continuity. "Release from masking" was computed by subtracting RTS signal-to-noise ratios in interrupted from continuous noise. TEOAEs were evoked with 80 dB peSPL click stimuli. To examine contralateral suppression, TEOAEs were evaluated with 60 dB peSPL click stimuli with and without a contralateral 65 dB SPL white noise suppressor. A binaural advantage was observed for RTSs in quiet and noise (p < .0001) while there was no difference between ears (p >.05). In noise, performance was superior in the interrupted noise (i.e., RTSs were lower vs. continuous noise; p < .0001). There were no statistically significant differences in TEOAE levels between ears (p >.05). There was also no significant difference in the amount of suppression between ears (p = .41). There were no significant correlations or predictive linear relations between the amount of TEOAE suppression and any indices of sentence recognition in noise (i.e., RTS signal-to-noise ratios and release from masking; p > .05). The findings are not consistent with the notion that increased medial olivocochlear efferent feedback, as assessed via contralateral suppression of TEOAEs, is associated with improved speech perception in continuous and interrupted noise. American Academy of Audiology.

Three-dimensional in vivo patellofemoral kinematics and contact area of anterior cruciate ligament-deficient and -reconstructed subjects using magnetic resonance imaging.

PubMed

Shin, Choongsoo S; Carpenter, R Dana; Majumdar, Sharmila; Ma, C Benjamin

2009-11-01

The purpose of this study was to test whether (1) the 3-dimensional in vivo patellofemoral kinematics and patellofemoral contact area of anterior cruciate ligament (ACL)-deficient knees are different from those of normal, contralateral knees and (2) ACL reconstruction restores in vivo patellofemoral kinematics and contact area. Ten ACL-deficient knees and twelve ACL-reconstructed knees, as well as the contralateral uninjured knees, were tested. Magnetic resonance imaging was performed at full extension and 40 degrees of flexion under simulated partial weight-bearing conditions. Six-degrees of freedom patellofemoral kinematics, patellofemoral contact area, and contact location were analyzed by use of magnetic resonance image-based 3-dimensional patellofemoral knee models. The patella in the ACL-deficient knees underwent significantly more lateral tilt during flexion (P < .05) and tended to translate more laterally (P = .083) than the patella in contralateral knees. After ACL reconstruction, no kinematic parameters were significantly different from those in contralateral knees. The patellofemoral contact areas of ACL-deficient knees at both the extended and flexed positions (37 +/- 22 mm(2) and 357 +/- 53 mm(2), respectively) were significantly smaller than those of contralateral knees (78 +/- 45 mm(2) and 437 +/- 119 mm(2), respectively) (P < .05). After reconstruction, the patellofemoral contact area of ACL-reconstructed knees in the extended position (86 +/- 41 mm(2)) was significantly larger (P < .05) than that of contralateral knees (50 +/- 34 mm(2)), but no difference was detected in the flexed position. Reproducibility of all patellofemoral kinematic parameters, contact centroid translation, and contact area showed coefficients of variation of less than 6.8%. ACL injuries alter patellofemoral kinematics including patellar tilt and patellar lateral translation, but ACL reconstruction with hamstring or allograft restores altered patellar tilt. ACL injuries reduce the patellofemoral contact area at both the extended and flexed positions, but ACL reconstruction enlarges the patellofemoral contact area at extension and restores the normal contact area at low angles of flexion. Level III, case-control study.

Monaural and binaural contributions to interaural-level-difference sensitivity in human auditory cortex.

PubMed

Stecker, G Christopher; McLaughlin, Susan A; Higgins, Nathan C

2015-10-15

Whole-brain functional magnetic resonance imaging was used to measure blood-oxygenation-level-dependent (BOLD) responses in human auditory cortex (AC) to sounds with intensity varying independently in the left and right ears. Echoplanar images were acquired at 3 Tesla with sparse image acquisition once per 12-second block of sound stimulation. Combinations of binaural intensity and stimulus presentation rate were varied between blocks, and selected to allow measurement of response-intensity functions in three configurations: monaural 55-85 dB SPL, binaural 55-85 dB SPL with intensity equal in both ears, and binaural with average binaural level of 70 dB SPL and interaural level differences (ILD) ranging ±30 dB (i.e., favoring the left or right ear). Comparison of response functions equated for contralateral intensity revealed that BOLD-response magnitudes (1) generally increased with contralateral intensity, consistent with positive drive of the BOLD response by the contralateral ear, (2) were larger for contralateral monaural stimulation than for binaural stimulation, consistent with negative effects (e.g., inhibition) of ipsilateral input, which were strongest in the left hemisphere, and (3) also increased with ipsilateral intensity when contralateral input was weak, consistent with additional, positive, effects of ipsilateral stimulation. Hemispheric asymmetries in the spatial extent and overall magnitude of BOLD responses were generally consistent with previous studies demonstrating greater bilaterality of responses in the right hemisphere and stricter contralaterality in the left hemisphere. Finally, comparison of responses to fast (40/s) and slow (5/s) stimulus presentation rates revealed significant rate-dependent adaptation of the BOLD response that varied across ILD values. Copyright © 2015. Published by Elsevier Inc.

Functional Connectivity and Genetic Profile of a “Double-Cortex”-Like Malformation

PubMed Central

Sprugnoli, Giulia; Vatti, Giampaolo; Rossi, Simone; Cerase, Alfonso; Renieri, Alessandra; Mencarelli, Maria A.; Zara, Federico; Rossi, Alessandro; Santarnecchi, Emiliano

2018-01-01

Laminar heterotopia is a rare condition consisting in an extra layer of gray matter under properly migrated cortex; it configures an atypical presentation of periventricular nodular heterotopia (PNH) or a double cortex (DC) syndrome. We conducted an original functional MRI (fMRI) analysis in a drug-resistant epilepsy patient with “double-cortex”-like malformation to reveal her functional connectivity (FC) as well as a wide genetic analysis to identify possible genetic substrates. Heterotopias were segmented into region of interests (ROIs), whose voxel-wise FC was compared to that of (i) its normally migrated counterpart, (ii) its contralateral homologous, and (iii) those of 30 age-matched healthy controls. Extensive genetic analysis was conducted to screen cortical malformations-associated genes. Compared to healthy controls, both laminar heterotopias and the overlying cortex showed significant reduction of FC with the contralateral hemisphere. Two heterozygous variants of uncertain clinical significance were found, involving autosomal recessive disease-causing genes, FAT4 and COL18A1. This first FC analysis of a unique case of “double-cortex”-like malformation revealed a hemispheric connectivity segregation both in the laminar cortex as in the correctly migrated one, with a new pattern of genes’ mutations. Our study suggests the altered FC could have an electrophysiological and functional impact on large-scale brain networks, and the involvement of not yet identified genes in “double-cortex”-like malformation with a possible role of rare variants in recessive genes as pathogenic cofactors. PMID:29946244

The neuronal correlates of mirror illusion in children with spastic hemiparesis: a study with functional magnetic resonance imaging.

PubMed

Weisstanner, Christian; Saxer, Stefanie; Wiest, Roland; Kaelin-Lang, Alain; Newman, Christopher J; Steinlin, Maja; Grunt, Sebastian

2017-03-21

To investigate the neuronal activation pattern underlying the effects of mirror illusion in children/adolescents with normal motor development and in children/adolescents with hemiparesis and preserved contralateral corticospinal organisation. The type of cortical reorganisation was classified according to results of transcranial magnetic stimulation. Only subjects with congenital lesions and physiological contralateral cortical reorganisation were included. Functional magnetic resonance imaging was performed to investigate neuronal activation patterns with and without a mirror box. Each test consisted of a unimanual and a bimanual motor task. Seven children/adolescents with congenital hemiparesis (10-20 years old, three boys and four girls) and seven healthy subjects (8-17 years old, four boys and three girls) participated in this study. In the bimanual experiment, children with hemiparesis showed a significant effect of the mirror illusion (p<0.001 at voxel level, family-wise error corrected at cluster level) in the dorsolateral prefrontal cortex and anterior cingulate cortex of the affected and unaffected hemispheres, respectively. No significant effects of the mirror illusion were observed in unimanual experiments and in healthy participants. Mirror illusion in children/adolescents with hemiparesis leads to activation of brain areas involved in visual conflict detection and cognitive control to resolve this conflict. This effect is observed only in bimanual training. We consider that for mirror therapy in children and adolescents with hemiparesis a bimanual approach is more suitable than a unimanual approach.

Glioblastoma (GBM) effects on quantitative MRI of contralateral normal appearing white matter.

PubMed

Mehrabian, Hatef; Lam, Wilfred W; Myrehaug, Sten; Sahgal, Arjun; Stanisz, Greg J

2018-03-28

The objective was to investigate (with quantitative MRI) whether the normal appearing white matter (NAWM) of glioblastoma (GBM) patients on the contralateral side (cNAWM) was different from NAWM of healthy controls. Thirteen patients with newly diagnosed GBM and nine healthy age-matched controls were MRI-scanned with quantitative magnetization transfer (qMT), chemical exchange saturation transfer (CEST), and transverse relaxation time (T 2 )-mapping. MRI scans were performed after surgery and before chemo-radiation treatment. Comprehensive qMT, CEST, T 2 data were acquired. A two-pool MT model was fit to qMT data in transient state, to calculate MT model parameters [Formula: see text]. CEST signal was isolated by removing the contributions from the MT and direct water saturation, and CEST signal was calculated for Amide (CEST Amide ), Amine (CEST Amine ) and nuclear overhauser effect, NOE (CEST NOE ). There was no difference between GBM patients and normal controls in the qMT properties of the macromolecular pool [Formula: see text]. However, their free water pool spectrum was different (1/R a T 2a , patient  = 28.1 ± 3.9, 1/R a T 2a , control  = 25.0 ± 1.1, p = 0.03). This difference could be attributed to the difference in their T 2 time ([Formula: see text] = 83 ± 4, [Formula: see text] = 88 ± 1, p = 0.004). CEST signals were statistically significantly different with the CEST Amide having the largest difference between the two cohorts (CEST Amide,patient  = 2.8 ± 0.4, CEST Amide,control  = 3.4 ± 0.5, p = 0.009). CEST in cNAWM of GBM patients was lower than healthy controls which could be caused by modified brain metabolism due to tumor cell infiltration. There was no difference in MT properties of the patients and controls, however, the differences in free water pool properties were mainly due to reduced T 2 in cNAWM of the patients (resulting from structural changes and increased cellularity).

Complex Regional Pain Syndrome Type I Affects Brain Structure in Prefrontal and Motor Cortex

PubMed Central

Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin

2014-01-01

The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the “non-flipped” data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the “flipped” data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control. PMID:24416397

Aberrant topological patterns of brain structural network in temporal lobe epilepsy.

PubMed

Yasuda, Clarissa Lin; Chen, Zhang; Beltramini, Guilherme Coco; Coan, Ana Carolina; Morita, Marcia Elisabete; Kubota, Bruno; Bergo, Felipe; Beaulieu, Christian; Cendes, Fernando; Gross, Donald William

2015-12-01

Although altered large-scale brain network organization in patients with temporal lobe epilepsy (TLE) has been shown using morphologic measurements such as cortical thickness, these studies, have not included critical subcortical structures (such as hippocampus and amygdala) and have had relatively small sample sizes. Here, we investigated differences in topological organization of the brain volumetric networks between patients with right TLE (RTLE) and left TLE (LTLE) with unilateral hippocampal atrophy. We performed a cross-sectional analysis of 86 LTLE patients, 70 RTLE patients, and 116 controls. RTLE and LTLE groups were balanced for gender (p = 0.64), seizure frequency (Mann-Whitney U test, p = 0.94), age (p = 0.39), age of seizure onset (p = 0.21), and duration of disease (p = 0.69). Brain networks were constructed by thresholding correlation matrices of volumes from 80 cortical/subcortical regions (parcellated with Freesurfer v5.3 https://surfer.nmr.mgh.harvard.edu/) that were then analyzed using graph theoretical approaches. We identified reduced cortical/subcortical connectivity including bilateral hippocampus in both TLE groups, with the most significant interregional correlation increases occurring within the limbic system in LTLE and contralateral hemisphere in RTLE. Both TLE groups demonstrated less optimal topological organization, with decreased global efficiency and increased local efficiency and clustering coefficient. LTLE also displayed a more pronounced network disruption. Contrary to controls, hub nodes in both TLE groups were not distributed across whole brain, but rather found primarily in the paralimbic/limbic and temporal association cortices. Regions with increased centrality were concentrated in occipital lobes for LTLE and contralateral limbic/temporal areas for RTLE. These findings provide first evidence of altered topological organization of the whole brain volumetric network in TLE, with disruption of the coordinated patterns of cortical/subcortical morphology. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Decoding the individual finger movements from single-trial functional magnetic resonance imaging recordings of human brain activity.

PubMed

Shen, Guohua; Zhang, Jing; Wang, Mengxing; Lei, Du; Yang, Guang; Zhang, Shanmin; Du, Xiaoxia

2014-06-01

Multivariate pattern classification analysis (MVPA) has been applied to functional magnetic resonance imaging (fMRI) data to decode brain states from spatially distributed activation patterns. Decoding upper limb movements from non-invasively recorded human brain activation is crucial for implementing a brain-machine interface that directly harnesses an individual's thoughts to control external devices or computers. The aim of this study was to decode the individual finger movements from fMRI single-trial data. Thirteen healthy human subjects participated in a visually cued delayed finger movement task, and only one slight button press was performed in each trial. Using MVPA, the decoding accuracy (DA) was computed separately for the different motor-related regions of interest. For the construction of feature vectors, the feature vectors from two successive volumes in the image series for a trial were concatenated. With these spatial-temporal feature vectors, we obtained a 63.1% average DA (84.7% for the best subject) for the contralateral primary somatosensory cortex and a 46.0% average DA (71.0% for the best subject) for the contralateral primary motor cortex; both of these values were significantly above the chance level (20%). In addition, we implemented searchlight MVPA to search for informative regions in an unbiased manner across the whole brain. Furthermore, by applying searchlight MVPA to each volume of a trial, we visually demonstrated the information for decoding, both spatially and temporally. The results suggest that the non-invasive fMRI technique may provide informative features for decoding individual finger movements and the potential of developing an fMRI-based brain-machine interface for finger movement. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Foxg1 regulates retinal axon pathfinding by repressing an ipsilateral program in nasal retina and by causing optic chiasm cells to exert a net axonal growth-promoting activity.

PubMed

Tian, Natasha M; Pratt, Thomas; Price, David J

2008-12-01

Mammalian binocular vision relies on the divergence of retinal ganglion cell axons at the optic chiasm, with strictly controlled numbers projecting contralaterally and ipsilaterally. In mouse, contralateral projections arise from the entire retina, whereas ipsilateral projections arise from ventrotemporal retina. We investigate how development of these patterns of projection is regulated by the contralateral determinant Foxg1, a forkhead box transcription factor expressed in nasal retina and at the chiasm. In nasal retina, loss of Foxg1 causes increased numbers of ipsilateral projections and ectopic expression of the ipsilateral determinants Zic2, Ephb1 and Foxd1, indicating that nasal retina is competent to express an ipsilateral program that is normally suppressed by Foxg1. Using co-cultures that combine Foxg1-expressing with Foxg1-null retinal explants and chiasm cells, we provide functional evidence that Foxg1 promotes contralateral projections through actions in nasal retina, and that in chiasm cells, Foxg1 is required for the generation of a hitherto unrecognized activity supporting RGC axon growth.

Magnetic Resonance Imaging Profile of Blood–Brain Barrier Injury in Patients With Acute Intracerebral Hemorrhage

PubMed Central

Aksoy, Didem; Bammer, Roland; Mlynash, Michael; Venkatasubramanian, Chitra; Eyngorn, Irina; Snider, Ryan W.; Gupta, Sandeep N.; Narayana, Rashmi; Fischbein, Nancy; Wijman, Christine A. C.

2013-01-01

Background Spontaneous intracerebral hemorrhage (ICH) is associated with blood–brain barrier (BBB) injury, which is a poorly understood factor in ICH pathogenesis, potentially contributing to edema formation and perihematomal tissue injury. We aimed to assess and quantify BBB permeability following human spontaneous ICH using dynamic contrast‐enhanced magnetic resonance imaging (DCE MRI). We also investigated whether hematoma size or location affected the amount of BBB leakage. Methods and Results Twenty‐five prospectively enrolled patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were examined using DCE MRI at 1 week after symptom onset. Contrast agent dynamics in the brain tissue and general tracer kinetic modeling were used to estimate the forward leakage rate (Ktrans) in regions of interest (ROI) in and surrounding the hematoma and in contralateral mirror–image locations (control ROI). In all patients BBB permeability was significantly increased in the brain tissue immediately adjacent to the hematoma, that is, the hematoma rim, compared to the contralateral mirror ROI (P<0.0001). Large hematomas (>30 mL) had higher Ktrans values than small hematomas (P<0.005). Ktrans values of lobar hemorrhages were significantly higher than the Ktrans values of deep hemorrhages (P<0.005), independent of hematoma volume. Higher Ktrans values were associated with larger edema volumes. Conclusions BBB leakage in the brain tissue immediately bordering the hematoma can be measured and quantified by DCE MRI in human ICH. BBB leakage at 1 week is greater in larger hematomas as well as in hematomas in lobar locations and is associated with larger edema volumes. PMID:23709564

Upregulation of neuronal kynurenine 3-monooxygenase mediates depression-like behavior in a mouse model of neuropathic pain.

PubMed

Laumet, Geoffroy; Zhou, Wenjun; Dantzer, Robert; Edralin, Jules D; Huo, XiaoJiao; Budac, David P; O'Connor, Jason C; Lee, Anna W; Heijnen, Cobi J; Kavelaars, Annemieke

2017-11-01

Pain and depression often co-occur, but the underlying mechanisms have not been elucidated. Here, we used the spared nerve injury (SNI) model in mice to induce both neuropathic pain and depression-like behavior. We investigated whether brain interleukin (IL)-1 signaling and activity of kynurenine 3-monoxygenase (KMO), a key enzyme for metabolism of kynurenine into the neurotoxic NMDA receptor agonist quinolinic acid, are necessary for comorbid neuropathic pain and depression-like behavior. SNI mice showed increased expression levels of Il1b and Kmo mRNA in the contralateral side of the brain. The SNI-induced increase of Kmo mRNA was associated with increased KMO protein and elevated quinolinic acid and reduced kynurenic acid in the contralateral hippocampus. The increase in KMO-protein in response to SNI mostly took place in hippocampal NeuN-positive neurons rather than microglia. Inhibition of brain IL-1 signaling by intracerebroventricular administration of IL-1 receptor antagonist after SNI prevented the increase in Kmo mRNA and depression-like behavior measured by forced swim test. However, inhibition of brain IL-1 signaling has no effect on mechanical allodynia. In addition, intracerebroventricular administration of the KMO inhibitor Ro 61-8048 abrogated depression-like behavior without affecting mechanical allodynia after SNI. We show for the first time that the development of depression-like behavior in the SNI model requires brain IL-1 signaling and activation of neuronal KMO, while pain is independent of this pathway. Inhibition of KMO may represent a promising target for treating depression. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes in Serial Optical Topography and TMS during Task Performance after Constraint-Induced Movement Therapy in Stroke: A Case Study

PubMed Central

Park, Si-Woon; Butler, Andrew J.; Cavalheiro, Vanessa; Alberts, Jay L.; Wolf, Steven L.

2013-01-01

The authors examined serial changes in optical topography in a stroke patient performing a functional task, as well as clinical and physiologic measures while undergoing constraint-induced therapy (CIT). A 73-year-old right hemiparetic patient, who had a subcortical stroke 4 months previously, received 2 weeks of CIT. During the therapy, daily optical topography imaging using near-infrared light was measured serially while the participant performed a functional key-turning task. Clinical outcome measures included the Wolf Motor Function Test (WMFT), Motor Activity Log (MAL), and functional key grip test. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) were also used to map cortical areas and hemodynamic brain responses, respectively. Optical topography measurement showed an overall decrease in oxy-hemoglobin concentration in both hemispheres as therapy progressed and the laterality index increased toward the contralateral hemisphere. An increased TMS motor map area was observed in the contralateral cortex following treatment. Posttreatment fMRI showed bilateral primary motor cortex activation, although slightly greater in the contralateral hemisphere, during affected hand movement. Clinical scores revealed marked improvement in functional activities. In one patient who suffered a stroke, 2 weeks of CIT led to improved function and cortical reorganization in the hemisphere contralateral to the affected hand. PMID:15228805

Computer-Aided Diagnostic (CAD) Scheme by Use of Contralateral Subtraction Technique

NASA Astrophysics Data System (ADS)

Nagashima, Hiroyuki; Harakawa, Tetsumi

We developed a computer-aided diagnostic (CAD) scheme for detection of subtle image findings of acute cerebral infarction in brain computed tomography (CT) by using a contralateral subtraction technique. In our computerized scheme, the lateral inclination of image was first corrected automatically by rotating and shifting. The contralateral subtraction image was then derived by subtraction of reversed image from original image. Initial candidates for acute cerebral infarctions were identified using the multiple-thresholding and image filtering techniques. As the 1st step for removing false positive candidates, fourteen image features were extracted in each of the initial candidates. Halfway candidates were detected by applying the rule-based test with these image features. At the 2nd step, five image features were extracted using the overlapping scale with halfway candidates in interest slice and upper/lower slice image. Finally, acute cerebral infarction candidates were detected by applying the rule-based test with five image features. The sensitivity in the detection for 74 training cases was 97.4% with 3.7 false positives per image. The performance of CAD scheme for 44 testing cases had an approximate result to training cases. Our CAD scheme using the contralateral subtraction technique can reveal suspected image findings of acute cerebral infarctions in CT images.

Multiple foci of spatial attention in multimodal working memory.

PubMed

Katus, Tobias; Eimer, Martin

2016-11-15

The maintenance of sensory information in working memory (WM) is mediated by the attentional activation of stimulus representations that are stored in perceptual brain regions. Using event-related potentials (ERPs), we measured tactile and visual contralateral delay activity (tCDA/CDA components) in a bimodal WM task to concurrently track the attention-based maintenance of information stored in anatomically segregated (somatosensory and visual) brain areas. Participants received tactile and visual sample stimuli on both sides, and in different blocks, memorized these samples on the same side or on opposite sides. After a retention delay, memory was unpredictably tested for touch or vision. In the same side blocks, tCDA and CDA components simultaneously emerged over the same hemisphere, contralateral to the memorized tactile/visual sample set. In opposite side blocks, these two components emerged over different hemispheres, but had the same sizes and onset latencies as in the same side condition. Our results reveal distinct foci of tactile and visual spatial attention that were concurrently maintained on task-relevant stimulus representations in WM. The independence of spatially-specific biasing mechanisms for tactile and visual WM content suggests that multimodal information is stored in distributed perceptual brain areas that are activated through modality-specific processes that can operate simultaneously and largely independently of each other. Copyright © 2016 Elsevier Inc. All rights reserved.

Triple stimulation technique in patients with spinocerebellar ataxia type 6.

PubMed

Sakuma, Kenji; Adachi, Yoshiki; Fukuda, Hiroki; Kai, Tohru; Nakashima, Kenji

2005-11-01

To establish further evidence that SCA6 may not be a pure cerebellar syndrome. Seven patients with genetically confirmed SCA6 and 9 age-matched normal controls were studied. Recordings of the CMAP were obtained from the right first dorsal interosseus muscle. Transcranial magnetic stimulation of the left motor cortex was applied to the contralateral scalp with a plane figure-of-8 coil. Conventional transcranial magnetic stimulation (TMS), central motor conduction time (CMCT) by F-wave method and the triple stimulation technique (TST) amplitude ratio (TST test/TST control) were investigated. The mean resting motor threshold and mean CMCT did not show significant differences between normal controls and patients, but the mean TST amplitude ratio was significantly smaller in patients than in controls. An abnormal TST represents upper motor neuron loss, central axon lesions or conduction blocks, or inexcitability in response to TMS. The lack of pathological changes in the corticospinal tract of patients with SCA6 indicates that this abnormality may be caused by crossed cerebellar diaschisis, or a functional disorder in the brain resulting from CACNA1A mutations. TST is a useful method for quantifying corticospinal tract dysfunction.

Avascular Necrosis in the Contralateral Hip in Patients With Congenital Femoral Deficiency: A Report of 3 Cases.

PubMed

Brown, Timothy S; Wimberly, Robert L; Birch, John G

2017-01-01

Congenital femoral deficiency is an uncommon clinical entity. We report 3 patients who developed avascular necrosis of the hip in the long (normal) leg during longitudinal observation and/or treatment of congenital femoral deficiency. Patients were identified in limb length discrepancy clinic and their charts were retrospectively reviewed for clinical and radiographic data collection. We describe the occurrence of idiopathic avascular necrosis in the normal limb in patients being followed for limb length discrepancy. Although no conclusion could be drawn about the etiology of the avascular necrosis, we describe a previously undocumented relationship between congenital femoral deficiency and avascular necrosis in the contralateral hip. This occurred in our congenital femoral deficiency population at a rate higher than expected compared with published incidences of avascular necrosis of the hip in children. Level IV-case series.

Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity

PubMed Central

Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S.; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N.

2015-01-01

Aim To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Methods Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen–Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Results Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. Conclusion The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure–function relationships but requires further validation in other populations of CP. PMID:26106533

Impact of Methamphetamine on Regional Metabolism and Cerebral Blood Flow after Traumatic Brain Injury

PubMed Central

O'Phelan, Kristine; Ernst, Thomas; Park, Dalnam; Stenger, Andrew; Denny, Katherine; Green, Deborah; Chang, Cherylee; Chang, Linda

2014-01-01

Substance abuse is a frequent comorbid condition among patients with Traumatic Brain Injury (TBI), but little is known about its potential additive or interactive effects on tissue injury or recovery from TBI. This study aims to evaluate changes in regional metabolism and cerebral perfusion in subjects who used methamphetamine(METH) prior to sustaining a TBI. We hypothesized that METH use would decrease pericontusional cerebral perfusion and markers of neuronal metabolism, in TBI patients compared to those without METH use. Methods This is a single center prospective observational study. Adults with moderate and severe TBI were included. MRI scanning was performed on a 3 Tesla scanner. MP-RAGE and FLAIR sequences as well as Metabolite spectra of NAA and lactate in pericontusional and contralateral voxels identified on the MP-RAGE scans. A spiral-based FAIR sequence was used for the acquisition of cerebral blood flow (CBF) maps. Regional CBF images were analyzed using Image J open source software. Pericontusional and contralateral CBF, NAA and lactate were assessed in the entire cohort and in the METH and non-METH groups. Results 17 subjects completed the MR studies. Analysis of entire cohort: Pericontusional NAA concentrations (5.81 ± 2.0 mM/kg) were 12% lower compared to the contralateral NAA (6.98 ± 1.2 mM/kg; p=0.03). Lactate concentrations and CBF were not significantly different between the two regions, however, regional cerebral blood flow was equally reduced in the two regions. Subgroup analysis: 41% of subjects tested positive for METH. The mean age, Glasgow Coma Scale and time to scan did not differ between groups. The two subject groups also had similar regional NAA and lactate. Pericontusional CBF was 60% lower in the METH users than the non-users, p=0.04; contralateral CBF did not differ between the groups. Conclusion This small study demonstrates that tissue metabolism is regionally heterogeneous after TBI and pericontusional perfusion was significantly reduced in the METH subgroup. PMID:23836426

Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery.

PubMed

Kubis, Nathalie

2016-01-01

Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first day, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excitability at the acute phase and a suspension of the topographic representation of affected muscles, whereas the contralateral motor cortex has an increased excitability and an enlarged somatomotor representation; furthermore, contralateral cortex exerts a transcallosal interhemispheric inhibition on the ischemic cortex. This results from the imbalance of the physiological reciprocal interhemispheric inhibition of each hemisphere on the other, contributing to worsening of neurological deficit. Cortical excitability is measurable through transcranial magnetic stimulation (TMS) and prognosis has been established according to the presence of motor evoked potentials (MEP) at the acute phase of stroke, which is predictive of better recovery. Conversely, the lack of response to early stimulation is associated with a poor functional outcome. Non-invasive stimulation techniques such as repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS) have the potential to modulate brain cortical excitability with long lasting effects. In the setting of cerebrovascular disease, around 1000 stroke subjects have been included in placebo-controlled trials so far, most often with an objective of promoting motor recovery of the upper limb. High frequency repetitive stimulation (>3 Hz) rTMS, aiming to increase excitability of the ischemic cortex, or low frequency repetitive stimulation (≤1 Hz), aiming to reduce excitability of the contralateral homonymous cortex, or combined therapies, have shown various effects on the functional disability score and neurological scales of treated patients and on the duration of the treatment. We review here the patients' characteristics and parameters of stimulation that could predict a good response, as well as safety issues. At last, we review what we have learnt from experimental studies and discuss potential directions to conduct future studies.

Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery

PubMed Central

Kubis, Nathalie

2016-01-01

Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first day, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excitability at the acute phase and a suspension of the topographic representation of affected muscles, whereas the contralateral motor cortex has an increased excitability and an enlarged somatomotor representation; furthermore, contralateral cortex exerts a transcallosal interhemispheric inhibition on the ischemic cortex. This results from the imbalance of the physiological reciprocal interhemispheric inhibition of each hemisphere on the other, contributing to worsening of neurological deficit. Cortical excitability is measurable through transcranial magnetic stimulation (TMS) and prognosis has been established according to the presence of motor evoked potentials (MEP) at the acute phase of stroke, which is predictive of better recovery. Conversely, the lack of response to early stimulation is associated with a poor functional outcome. Non-invasive stimulation techniques such as repetitive TMS (rTMS) or transcranial direct current stimulation (tDCS) have the potential to modulate brain cortical excitability with long lasting effects. In the setting of cerebrovascular disease, around 1000 stroke subjects have been included in placebo-controlled trials so far, most often with an objective of promoting motor recovery of the upper limb. High frequency repetitive stimulation (>3 Hz) rTMS, aiming to increase excitability of the ischemic cortex, or low frequency repetitive stimulation (≤1 Hz), aiming to reduce excitability of the contralateral homonymous cortex, or combined therapies, have shown various effects on the functional disability score and neurological scales of treated patients and on the duration of the treatment. We review here the patients’ characteristics and parameters of stimulation that could predict a good response, as well as safety issues. At last, we review what we have learnt from experimental studies and discuss potential directions to conduct future studies. PMID:27512367

Movement-related neuromagnetic fields in preschool age children.

PubMed

Cheyne, Douglas; Jobst, Cecilia; Tesan, Graciela; Crain, Stephen; Johnson, Blake

2014-09-01

We examined sensorimotor brain activity associated with voluntary movements in preschool children using a customized pediatric magnetoencephalographic system. A videogame-like task was used to generate self-initiated right or left index finger movements in 17 healthy right-handed subjects (8 females, ages 3.2-4.8 years). We successfully identified spatiotemporal patterns of movement-related brain activity in 15/17 children using beamformer source analysis and surrogate MRI spatial normalization. Readiness fields in the contralateral sensorimotor cortex began ∼0.5 s prior to movement onset (motor field, MF), followed by transient movement-evoked fields (MEFs), similar to that observed during self-paced movements in adults, but slightly delayed and with inverted source polarities. We also observed modulation of mu (8-12 Hz) and beta (15-30 Hz) oscillations in sensorimotor cortex with movement, but with different timing and a stronger frequency band coupling compared to that observed in adults. Adult-like high-frequency (70-80 Hz) gamma bursts were detected at movement onset. All children showed activation of the right superior temporal gyrus that was independent of the side of movement, a response that has not been reported in adults. These results provide new insights into the development of movement-related brain function, for an age group in which no previous data exist. The results show that children under 5 years of age have markedly different patterns of movement-related brain activity in comparison to older children and adults, and indicate that significant maturational changes occur in the sensorimotor system between the preschool years and later childhood. Copyright © 2014 Wiley Periodicals, Inc.

Three-dimensional functional magnetic resonance imaging of human brain on a clinical 1.5-T scanner.

PubMed Central

van Gelderen, P; Ramsey, N F; Liu, G; Duyn, J H; Frank, J A; Weinberger, D R; Moonen, C T

1995-01-01

Functional magnetic resonance imaging (fMRI) is a tool for mapping brain function that utilizes neuronal activity-induced changes in blood oxygenation. An efficient three-dimensional fMRI method is presented for imaging brain activity on conventional, widely available, 1.5-T scanners, without additional hardware. This approach uses large magnetic susceptibility weighting based on the echo-shifting principle combined with multiple gradient echoes per excitation. Motor stimulation, induced by self-paced finger tapping, reliably produced significant signal increase in the hand region of the contralateral primary motor cortex in every subject tested. Images Fig. 2 Fig. 3 PMID:7624341

Neural Mechanisms Underlying Action Observation in Adults with Down Syndrome

ERIC Educational Resources Information Center

Virji-Babul, Naznin; Moiseev, Alexander; Cheung, Teresa; Weeks, Daniel J.; Cheyne, Douglas; Ribary, Urs

2010-01-01

Results of a magnetoencephalography (MEG) brain imaging study conducted to examine the cortical responses during action execution and action observation in 10 healthy adults and 8 age-matched adults with Down syndrome are reported. During execution, the motor responses were strongly lateralized on the ipsilateral rather than the contralateral side…

The functional anatomy of suggested limb paralysis.

PubMed

Deeley, Quinton; Oakley, David A; Toone, Brian; Bell, Vaughan; Walsh, Eamonn; Marquand, Andre F; Giampietro, Vincent; Brammer, Michael J; Williams, Steven C R; Mehta, Mitul A; Halligan, Peter W

2013-02-01

Suggestions of limb paralysis in highly hypnotically suggestible subjects have been employed to successfully model conversion disorders, revealing similar patterns of brain activation associated with attempted movement of the affected limb. However, previous studies differ with regard to the executive regions involved during involuntary inhibition of the affected limb. This difference may have arisen as previous studies did not control for differences in hypnosis depth between conditions and/or include subjective measures to explore the experience of suggested paralysis. In the current study we employed functional magnetic resonance imaging (fMRI) to examine the functional anatomy of left and right upper limb movements in eight healthy subjects selected for high hypnotic suggestibility during (i) hypnosis (NORMAL) and (ii) attempted movement following additional left upper limb paralysis suggestions (PARALYSIS). Contrast of left upper limb motor function during NORMAL relative to PARALYSIS conditions revealed greater activation of contralateral M1/S1 and ipsilateral cerebellum, consistent with the engagement of these regions in the completion of movements. By contrast, two significant observations were noted in PARALYSIS relative to NORMAL conditions. In conjunction with reports of attempts to move the paralysed limb, greater supplementary motor area (SMA) activation was observed, a finding consistent with the role of SMA in motor intention and planning. The anterior cingulate cortex (ACC, BA 24) was also significantly more active in PARALYSIS relative to NORMAL conditions - suggesting that ACC (BA 24) may be implicated in involuntary, as well as voluntary inhibition of prepotent motor responses. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lassa-Vesicular Stomatitis Chimeric Virus Safely Destroys Brain Tumors

PubMed Central

Wollmann, Guido; Drokhlyansky, Eugene; Davis, John N.; Cepko, Connie

2015-01-01

ABSTRACT High-grade tumors in the brain are among the deadliest of cancers. Here, we took a promising oncolytic virus, vesicular stomatitis virus (VSV), and tested the hypothesis that the neurotoxicity associated with the virus could be eliminated without blocking its oncolytic potential in the brain by replacing the neurotropic VSV glycoprotein with the glycoprotein from one of five different viruses, including Ebola virus, Marburg virus, lymphocytic choriomeningitis virus (LCMV), rabies virus, and Lassa virus. Based on in vitro infections of normal and tumor cells, we selected two viruses to test in vivo. Wild-type VSV was lethal when injected directly into the brain. In contrast, a novel chimeric virus (VSV-LASV-GPC) containing genes from both the Lassa virus glycoprotein precursor (GPC) and VSV showed no adverse actions within or outside the brain and targeted and completely destroyed brain cancer, including high-grade glioblastoma and melanoma, even in metastatic cancer models. When mice had two brain tumors, intratumoral VSV-LASV-GPC injection in one tumor (glioma or melanoma) led to complete tumor destruction; importantly, the virus moved contralaterally within the brain to selectively infect the second noninjected tumor. A chimeric virus combining VSV genes with the gene coding for the Ebola virus glycoprotein was safe in the brain and also selectively targeted brain tumors but was substantially less effective in destroying brain tumors and prolonging survival of tumor-bearing mice. A tropism for multiple cancer types combined with an exquisite tumor specificity opens a new door to widespread application of VSV-LASV-GPC as a safe and efficacious oncolytic chimeric virus within the brain. IMPORTANCE Many viruses have been tested for their ability to target and kill cancer cells. Vesicular stomatitis virus (VSV) has shown substantial promise, but a key problem is that if it enters the brain, it can generate adverse neurologic consequences, including death. We tested a series of chimeric viruses containing genes coding for VSV, together with a gene coding for the glycoprotein from other viruses, including Ebola virus, Lassa virus, LCMV, rabies virus, and Marburg virus, which was substituted for the VSV glycoprotein gene. Ebola and Lassa chimeric viruses were safe in the brain and targeted brain tumors. Lassa-VSV was particularly effective, showed no adverse side effects even when injected directly into the brain, and targeted and destroyed two different types of deadly brain cancer, including glioblastoma and melanoma. PMID:25878115

Vestibular evoked myogenic potentials in response to lateral skull taps are dependent on two different mechanisms.

PubMed

Brantberg, Krister; Westin, Magnus; Löfqvist, Lennart; Verrecchia, Luca; Tribukait, Arne

2009-05-01

To explore the mechanisms for skull tap induced vestibular evoked myogenic potentials (VEMP). The muscular responses were recorded over both sternocleidomastoid (SCM) muscles using skin electrodes. A skull tapper which provided a constant stimulus intensity was used to test cervical vestibular evoked myogenic potentials (VEMP) in response to lateral skull taps in healthy subjects (n=10) and in patients with severe unilateral loss of vestibular function (n=10). Skull taps applied approximately 2 cm above the outer ear canal caused highly reproducible VEMP. There were differences in VEMP in both normals and patients depending on side of tapping. In normals, there was a positive-negative ("normal") VEMP on the side contra-lateral to the skull tapping, but no significant VEMP ipsi-laterally. In patients, skull taps above the lesioned ear caused a contra-lateral positive-negative VEMP (as it did in the normals), in addition there was an ipsi-lateral negative-positive ("inverted") VEMP. When skull taps were presented above the healthy ear there was only a small contra-lateral positive-negative VEMP but, similar to the normals, no VEMP ipsi-laterally. The present data, in conjunction with earlier findings, support a theory that skull-tap VEMP responses are mediated by two different mechanisms. It is suggested that skull tapping causes both a purely ipsi-lateral stimulus side independent SCM response and a bilateral and of opposite polarity SCM response that is stimulus side dependent. Possibly, the skull tap induced VEMP responses are the sum of a stimulation of two species of vestibular receptors, one excited by vibration (which is rather stimulus site independent) and one excited by translation (which is more stimulus site dependent). Skull-tap VEMP probably have two different mechanisms. Separation of the two components might reveal the status of different labyrinthine functions.

Topographic measurements of eyelids and orbit in enucleated eyes with hydroxyapatite integrated implant versus PMMA implant.

PubMed

Gradinaru, S; Totir, M; Iancu, R; Leasu, C; Pricopie, S; Yasin, S; Ciuluvica, R; Ungureanu, E

2014-01-01

This study reports our results relating to palpebral eyelid fissure and orbital measurements following evisceration with orbital implantation of hydroxyapatite integrated implant and PMMA implant. This study is a prospective study of 43 patients that underwent evisceration for different ocular affections at University Emergency Hospital Bucharest, Ophthalmology department between January 2009 and September 2010 (Group A comprising of twenty patients had the coralline hydroxyapatite implant -Integrated Ocular Implants, USA and Group B comprising of twenty-three received non-integrated PMMA ocular implants) .The outcomes measured were the degree of exo /enophthalmos, horizontal eyelid fissure and palpebral fissure height at 4 years after surgical intervention related to measurement to the contralateral eye. Horizontal eyelid fissure (HEF) was suffering a shortening of 7.4% in the group B versus the contralateral eye, and only 1.9% in the group A related to the contralateral eye. Eyelid fissure height was greater in the group B with 5.2% regarding the contralateral eye, and 1.2% in group A. The degree of enophthalmia was higher in the group B of 4 mm versus the contralateral eye and lower in group A 1.5 mm regarding the contralateral eye. . Although a hydroxyapatite implant may be not as economic as a PMMA implant, a patient must be warned about the effect on its ocular structures in time and that cosmetic appearance over years will change more dramatically than in the fellow normal eye. Therefore preoperative counseling of the patient is crucial in long term patient satisfaction.

Afferent projections to the deep mesencephalic nucleus in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veazey, R.B.; Severin, C.M.

1982-01-10

Afferent projections to the deep mesencephalic nucleus (DMN) of the rat were demonstrated with axonal transport techniques. Potential sources for projections to the DMN were first identified by injecting the nucleus with HRP and examining the cervical spinal cord, brain stem, and cortex for retrogradely labeled neurons. Areas consistently labeled were then injected with a tritiated radioisotope, the tissue processed for autoradiography, and the DMN examined for anterograde labeling. Afferent projections to the medial and/or lateral parts of the DMN were found to originate from a number of spinal, bulbar, and cortical centers. Rostral brain centers projecting to both medialmore » and lateral parts of the DMN include the ipsilateral motor and somatosensory cortex, the entopeduncular nucleus, and zona incerta. at the level of the midbrain, the ipsilateral substantia nigra and contralateral DMN likewise project to the DMN. Furthermore, the ipsilateral superior colliculus projects to the DMN, involving mainly the lateral part of the nucleus. Afferents from caudal centers include bilateral projections from the sensory nucleus of the trigeminal complex and the nucleus medulla oblongata centralis, as well as from the contralateral dentate nucleus. The projections from the trigeminal complex and nucleus medullae oblongatae centralis terminate in the intermediate and medial parts of the DMN, whereas projections from the contralateral dentate nucleus terminate mainly in its lateral part. In general, the afferent connections of the DMN arise from diverse areas of the brain. Although most of these projections distribute throughout the entire extent of the DMN, some of them project mainly to either medial or lateral parts of the nucleus, thus suggesting that the organization of the DMN is comparable, at least in part, to that of the reticular formation of the pons and medulla, a region in which hodological differences between medial and lateral subdivisions are known to exist.« less

Segmental Blood Flow and Hemodynamic State of Lymphedematous and Nonlymphedematous Arms

PubMed Central

Montgomery, Leslie D.; Dietrich, Mary S.; Armer, Jane M.; Stewart, B. R.

2011-01-01

Abstract Background Findings regarding the influence hemodynamic factors, such as increased arterial blood flow or venous abnormalities, on breast cancer treatment-related lymphedema are mixed. The purpose of this study was to compare segmental arterial blood flow, venous blood return, and blood volumes between breast cancer survivors with treatment-related lymphedema and healthy normal individuals without lymphedema. Methods and Results A Tetrapolar High Resolution Impedance Monitor and Cardiotachometer were used to compare segmental arterial blood flow, venous blood return, and blood volumes between breast cancer survivors with treatment-related lymphedema and healthy normal volunteers. Average arterial blood flow in lymphedema-affected arms was higher than that in arms of healthy normal volunteers or in contralateral nonlymphedema affected arms. Time of venous outflow period of blood flow pulse was lower in lymphedema-affected arms than in healthy normal or lymphedema nonaffected arms. Amplitude of the venous component of blood flow pulse signal was lower in lymphedema-affected arms than in healthy or lymphedema nonaffected arms. Index of venular tone was also lower in lymphedema-affected arms than healthy or lymphedema nonaffected arms. Conclusions Both arterial and venous components may be altered in the lymphedema-affected arms when compared to healthy normal arms and contralateral arms in the breast cancer survivors. PMID:21417765

Bumetanide augments the neuroprotective efficacy of phenobarbital plus hypothermia in a neonatal hypoxia-ischemia model

PubMed Central

Liu, YiQing; Shangguan, Yu; Barks, John D.E.; Silverstein, Faye S.

2014-01-01

The NaKCl cotransporter NKCC1 facilitates intraneuronal chloride accumulation in the developing brain. Bumetanide, a clinically available diuretic, inhibits this chloride transporter, and augments the antiepileptic effects of phenobarbital in neonatal rodents. In a neonatal cerebral hypoxia-ischemia (HI) model, elicited by right carotid ligation, followed by 90 min 8% O2 exposure in 7-day-old(P7) rats, phenobarbital(PB) increases the neuroprotective efficacy of hypothermia. We evaluated whether bumetanide influenced the neuroprotective efficacy of combination treatment with PB and hypothermia(HT). P7 rats underwent HI lesioning; 15 min later, all received PB (30 mg/kg). 10 min later, half received bumetanide (10 mg/kg, PB-HT+BUM) and half received saline (PB-HT+SAL). One hour after HI, all were cooled (30°C, 3h). Contralateral forepaw sensorimotor function and brain damage were evaluated 1 to 4 weeks later. Forepaw functional measures were close to normal in the PB-HT+BUM group, while deficits persisted in PB-HT+SAL controls; there were corresponding reductions in right cerebral hemisphere damage (at P35, % damage: PB-HT+BUM, 21±16 versus 38±20 in controls). These results provide evidence that NKCC1 inhibition amplifies phenobarbital bioactivity in the immature brain, and suggest that co-administration of phenobarbital and bumetanide may represent a clinically feasible therapy to augment the neuroprotective efficacy of therapeutic hypothermia in asphyxiated neonates. PMID:22398701

Effect of low-frequency rTMS on electromagnetic tomography (LORETA) and regional brain metabolism (PET) in schizophrenia patients with auditory hallucinations.

PubMed

Horacek, Jiri; Brunovsky, Martin; Novak, Tomas; Skrdlantova, Lucie; Klirova, Monika; Bubenikova-Valesova, Vera; Krajca, Vladimir; Tislerova, Barbora; Kopecek, Milan; Spaniel, Filip; Mohr, Pavel; Höschl, Cyril

2007-01-01

Auditory hallucinations are characteristic symptoms of schizophrenia with high clinical importance. It was repeatedly reported that low frequency (

The compensatory dynamic of inter-hemispheric interactions in visuospatial attention revealed using rTMS and fMRI.

PubMed

Plow, Ela B; Cattaneo, Zaira; Carlson, Thomas A; Alvarez, George A; Pascual-Leone, Alvaro; Battelli, Lorella

2014-01-01

A balance of mutual tonic inhibition between bi-hemispheric posterior parietal cortices is believed to play an important role in bilateral visual attention. However, experimental support for this notion has been mainly drawn from clinical models of unilateral damage. We have previously shown that low-frequency repetitive TMS (rTMS) over the intraparietal sulcus (IPS) generates a contralateral attentional deficit in bilateral visual tracking. Here, we used functional magnetic resonance imaging (fMRI) to study whether rTMS temporarily disrupts the inter-hemispheric balance between bilateral IPS in visual attention. Following application of 1 Hz rTMS over the left IPS, subjects performed a bilateral visual tracking task while their brain activity was recorded using fMRI. Behaviorally, tracking accuracy was reduced immediately following rTMS. Areas ventro-lateral to left IPS, including inferior parietal lobule (IPL), lateral IPS (LIPS), and middle occipital gyrus (MoG), showed decreased activity following rTMS, while dorsomedial areas, such as Superior Parietal Lobule (SPL), Superior occipital gyrus (SoG), and lingual gyrus, as well as middle temporal areas (MT+), showed higher activity. The brain activity of the homologues of these regions in the un-stimulated, right hemisphere was reversed. Interestingly, the evolution of network-wide activation related to attentional behavior following rTMS showed that activation of most occipital synergists adaptively compensated for contralateral and ipsilateral decrement after rTMS, while activation of parietal synergists, and SoG remained competing. This pattern of ipsilateral and contralateral activations empirically supports the hypothesized loss of inter-hemispheric balance that underlies clinical manifestation of visual attentional extinction.

Meta-analysis of long-term mobile phone use and the association with brain tumours.

PubMed

Hardell, Lennart; Carlberg, Michael; Söderqvist, Fredrik; Hansson Mild, Kjell

2008-05-01

We evaluated long-term use of mobile phones and the risk for brain tumours in case-control studies published so far on this issue. We identified ten studies on glioma and meta-analysis yielded OR = 0.9, 95% CI = 0.8-1.1. Latency period of > or =10-years gave OR = 1.2, 95% CI = 0.8-1.9 based on six studies, for ipsilateral use (same side as tumour) OR = 2.0, 95% CI = 1.2-3.4 (four studies), but contralateral use did not increase the risk significantly, OR = 1.1, 95% CI = 0.6-2.0. Meta-analysis of nine studies on acoustic neuroma gave OR = 0.9, 95% CI = 0.7-1.1 increasing to OR = 1.3, 95% CI = 0.6-2.8 using > or =10-years latency period (four studies). Ipsilateral use gave OR = 2.4, 95% CI = 1.1-5.3 and contra-lateral OR = 1.2, 95% CI = 0.7-2.2 in the > or =10-years latency period group (three studies). Seven studies gave results for meningioma yielding overall OR = 0.8, 95% CI = 0.7-0.99. Using > or =10-years latency period OR = 1.3, 95% CI = 0.9-1.8 was calculated (four studies) increasing to OR = 1.7, 95% CI = 0.99-3.1 for ipsilateral use and OR = 1.0, 95% CI = 0.3-3.1 for contralateral use (two studies). We conclude that this meta-analysis gave a consistent pattern of an association between mobile phone use and ipsilateral glioma and acoustic neuroma using > or =10-years latency period.

The lateralized smell test for detecting Alzheimer's disease: failure to replicate.

PubMed

Doty, Richard L; Bayona, Edgardo A; Leon-Ariza, Daniel S; Cuadros, Juan; Chung, Inna; Vazquez, Britney; Leon-Sarmiento, Fidias E

2014-05-15

A widely publicized study by Stamps, Bartoshuk and Heilman (2013) reported that a simple measure of left:right naris differences in the ability to detect the odor of peanut butter is a sensitive marker of Alzheimer's disease (AD). AD patients were said to have abnormal smell function on the left side of the nose and normal function on right side of the nose. In light of its implications for medical practice and the world-wide publicity that it engendered, we sought to replicate and expand this work. Two studies were performed. In the first, 15 AD patients were tested according to the procedures described by Stamps et al. in which the nostril contralateral to the tested side was occluded by the patient using lateral pressure from the index finger. Since this can potentially distort the contralateral naris, we repeated the testing using tape for naris occlusion. In the second, 20 AD patients were administered 20 odors of the University of Pennsylvania Smell Identification Test (UPSIT) to each side of the nose, with the contralateral naris being closed with tape. In both studies, the order of the side of testing was systematically counterbalanced. No evidence of a left:right asymmetry on any test measure was observed. Although hyposmia is well-established in AD, no meaningful asymmetry in smell perception is apparent. If olfactory function on the right side of the nose was normal as claimed, then AD patients should exhibit normal function when tested bilaterally, a phenomenon not seen in dozens of AD-related olfactory studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Patient-reported speech in noise difficulties and hyperacusis symptoms and correlation with test results.

PubMed

Spyridakou, Chrysa; Luxon, Linda M; Bamiou, Doris E

2012-07-01

To compare self-reported symptoms of difficulty hearing speech in noise and hyperacusis in adults with auditory processing disorders (APDs) and normal controls; and to compare self-reported symptoms to objective test results (speech in babble test, transient evoked otoacoustic emission [TEOAE] suppression test using contralateral noise). A prospective case-control pilot study. Twenty-two participants were recruited in the study: 10 patients with reported hearing difficulty, normal audiometry, and a clinical diagnosis of APD; and 12 normal age-matched controls with no reported hearing difficulty. All participants completed the validated Amsterdam Inventory for Auditory Disability questionnaire, a hyperacusis questionnaire, a speech in babble test, and a TEOAE suppression test using contralateral noise. Patients had significantly worse scores than controls in all domains of the Amsterdam Inventory questionnaire (with the exception of sound detection) and the hyperacusis questionnaire (P < .005). Patients also had worse TEOAE suppression test results in both ears than controls; however, this result was not significant after Bonferroni correction. Strong correlations were observed between self-reported symptoms of difficulty hearing speech in noise and speech in babble test results in the right ear (ρ = 0.624, P = .002), and between self-reported symptoms of hyperacusis and TEOAE suppression test results in the right ear (ρ = -0.597 P = .003). There was no significant correlation between the two tests. A strong correlation was observed between right ear speech in babble and patient-reported intelligibility of speech in noise, and right ear TEOAE suppression by contralateral noise and hyperacusis questionnaire. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Biomechanical Changes in the Sclera of Monkey Eyes Exposed to Chronic IOP Elevations

PubMed Central

Girard, Michaël J. A.; Suh, J.-K. Francis; Bottlang, Michael; Burgoyne, Claude F.

2011-01-01

Purpose. To characterize scleral biomechanics in both eyes of eight monkeys in which chronic intraocular pressure (IOP) elevation was induced in one eye. Methods. Each posterior sclera was mounted on a pressurization apparatus, IOP was elevated from 5 to 45 mm Hg while the 3D displacements of the scleral surface were measured by speckle interferometry. Finite element (FE) models of each scleral shell were constructed that incorporated stretch-induced stiffening and multidirectionality of the collagen fibers. FE model predictions were then iteratively matched to experimental displacements to extract unique sets of scleral biomechanical properties. Results. For all eyes, the posterior sclera exhibited inhomogeneous, anisotropic, nonlinear biomechanical behavior. Biomechanical changes caused by chronic IOP elevation were complex and specific to each subject. Specifically: (1) Glaucomatous eyes in which the contralateral normal eyes displayed large modulus or thickness were less prone to biomechanical changes; (2) glaucomatous scleral modulus associated with an IOP of 10 mm Hg decreased (when compared with that of the contralateral normal) after minimal chronic IOP elevation; (3) glaucomatous scleral modulus associated with IOPs of 30 and 45 mm Hg increased (when compared with that of the contralateral normal) after moderate IOP elevation; and (4) FE-based estimates of collagen fiber orientation demonstrated no change in the glaucomatous eyes. Conclusions. Significant stiffening of the sclera follows exposure to moderate IOP elevations in most eyes. Scleral hypercompliance may precede stiffening or be a unique response to minimal chronic IOP elevation in some eyes. These biomechanical changes are likely to be the result of scleral extracellular matrix remodeling. PMID:21519033

Klotho and activin A in kidney injury: plasma Klotho is maintained in unilateral obstruction despite no upregulation of Klotho biosynthesis in the contralateral kidney.

PubMed

Nordholm, Anders; Mace, Maria L; Gravesen, Eva; Hofman-Bang, Jacob; Morevati, Marya; Olgaard, Klaus; Lewin, Ewa

2018-05-01

In a new paradigm of etiology related to chronic kidney disease-mineral and bone disorder (CKD-MBD), kidney injury may cause induction of factors in the injured kidney that are released into the circulation and thereby initiate and maintain renal fibrosis and CKD-MBD. Klotho is believed to ameliorate renal fibrosis and CKD-MBD, while activin A might have detrimental effects. The unilateral ureter obstruction (UUO) model is used here to examine this concept by investigating early changes related to renal fibrosis in the obstructed kidney, untouched contralateral kidney, and vasculature which might be affected by secreted factors from the obstructed kidney, and comparing with unilateral nephrectomized controls (UNX). Obstructed kidneys showed early Klotho gene and protein depletion, whereas plasma Klotho increased in both UUO and UNX rats, indicating an altered metabolism of Klotho. Contralateral kidneys had no compensatory upregulation of Klotho and maintained normal expression of the examined fibrosis-related genes, as did remnant UNX kidneys. UUO caused upregulation of transforming growth factor-β and induction of periostin and activin A in obstructed kidneys without changes in the contralateral kidneys. Plasma activin A doubled in UUO rats after 10 days while no changes were seen in UNX rats, suggesting secretion of activin A from the obstructed kidney with potentially systemic effects on CKD-MBD. As such, increased aortic sclerostin was observed in UUO rats compared with UNX and normal controls. The present results are in line with the new paradigm and show very early vascular effects of unilateral kidney fibrosis, supporting the existence of a new kidney-vasculature axis.

Unique cortical physiology associated with ipsilateral hand movements and neuroprosthetic implications.

PubMed

Wisneski, Kimberly J; Anderson, Nicholas; Schalk, Gerwin; Smyth, Matt; Moran, Daniel; Leuthardt, Eric C

2008-12-01

Brain computer interfaces (BCIs) offer little direct benefit to patients with hemispheric stroke because current platforms rely on signals derived from the contralateral motor cortex (the same region injured by the stroke). For BCIs to assist hemiparetic patients, the implant must use unaffected cortex ipsilateral to the affected limb. This requires the identification of distinct electrophysiological features from the motor cortex associated with ipsilateral hand movements. In this study we studied 6 patients undergoing temporary placement of intracranial electrode arrays. Electrocorticographic (ECoG) signals were recorded while the subjects engaged in specific ipsilateral or contralateral hand motor tasks. Spectral changes were identified with regards to frequency, location, and timing. Ipsilateral hand movements were associated with electrophysiological changes that occur in lower frequency spectra, at distinct anatomic locations, and earlier than changes associated with contralateral hand movements. In a subset of 3 patients, features specific to ipsilateral and contralateral hand movements were used to control a cursor on a screen in real time. In ipsilateral derived control this was optimal with lower frequency spectra. There are distinctive cortical electrophysiological features associated with ipsilateral movements which can be used for device control. These findings have implications for patients with hemispheric stroke because they offer a potential methodology for which a single hemisphere can be used to enhance the function of a stroke induced hemiparesis.

Contralateral Disconnection of the Rat Prelimbic Cortex and Dorsomedial Striatum Impairs Cue-Guided Behavioral Switching

ERIC Educational Resources Information Center

Baker, Phillip M.; Ragozzino, Michael E.

2014-01-01

Switches in reward outcomes or reward-predictive cues are two fundamental ways in which information is used to flexibly shift response patterns. The rat prelimbic cortex and dorsomedial striatum support behavioral flexibility based on a change in outcomes. The present experiments investigated whether these two brain regions are necessary for…

Unilateral brain hypothermia as a method to examine efficacy and mechanisms of neuroprotection against global ischemia.

PubMed

Silasi, Gergely; Colbourne, Frederick

2011-01-01

Hypothermia, especially applied during ischemia, is the gold-standard neuroprotectant. When delayed, cooling must often be maintained for a day or more to achieve robust, permanent protection. Most animal and clinical studies use whole-body cooling-an arduous technique that can cause systemic complications. Brain-selective cooling may avoid such problems. Thus, in this rat study, we used a method that cools one hemisphere without affecting the contralateral side or the body. Localized brain hypothermia was achieved by flushing cold water through a metal tube attached to the rats' skull. First, in anesthetized rats we measured temperature in the cooled and contralateral hemisphere to demonstrate selective unilateral cooling. Subsequent telemetry recordings in awake rats confirmed that brain cooling did not cause systemic hypothermia during prolonged treatment. Additionally, we subjected rats to transient global ischemia and after recovering from anesthesia they remained at normothermia or had their right hemisphere cooled for 2 days (∼32°C-33°C). Hypothermia significantly lessened CA1 injury and microglia activation on the right side at 1 and 4 week survival times. Near-complete injury and a strong microglia response occurred in the left (normothermic) hippocampus as occurred in both hippocampi of the untreated group. Thus, this focal cooling method is suitable for evaluating the efficacy and mechanisms of hypothermic neuroprotection in global ischemia models. This method also has advantages over many current systemic cooling protocols in rodents, namely: (1) lower cost, (2) simplicity, (3) safety and suitability for long-term cooling, and (4) an internal control-the normothermic hemisphere.

The differential effects of acute right- vs. left-sided vestibular failure on brain metabolism.

PubMed

Becker-Bense, Sandra; Dieterich, Marianne; Buchholz, Hans-Georg; Bartenstein, Peter; Schreckenberger, Mathias; Brandt, Thomas

2014-07-01

The human vestibular system is represented in the brain bilaterally, but it has functional asymmetries, i.e., a dominance of ipsilateral pathways and of the right hemisphere in right-handers. To determine if acute right- or left-sided unilateral vestibular neuritis (VN) is associated with differential patterns of brain metabolism in areas representing the vestibular network and the visual-vestibular interaction, patients with acute VN (right n = 9; left n = 13) underwent resting state (18)F-FDG PET once in the acute phase and once 3 months later after central vestibular compensation. The contrast acute vs. chronic phase showed signal differences in contralateral vestibular areas and the inverse contrast in visual cortex areas, both more pronounced in VN right. In VN left additional regions were found in the cerebellar hemispheres and vermis bilaterally, accentuated in severe cases. In general, signal changes appeared more pronounced in patients with more severe vestibular deficits. Acute phase PET data of patients compared to that of age-matched healthy controls disclosed similarities to these patterns, thus permitting the interpretation that the signal changes in vestibular temporo-parietal areas reflect signal increases, and in visual areas, signal decreases. These data imply that brain activity in the acute phase of right- and left-sided VN exhibits different compensatory patterns, i.e., the dominant ascending input is shifted from the ipsilateral to the contralateral pathways, presumably due to the missing ipsilateral vestibular input. The visual-vestibular interaction patterns were preserved, but were of different prominence in each hemisphere and more pronounced in patients with right-sided failure and more severe vestibular deficits.

Single severe traumatic brain injury produces progressive pathology with ongoing contralateral white matter damage one year after injury.

PubMed

Pischiutta, Francesca; Micotti, Edoardo; Hay, Jennifer R; Marongiu, Ines; Sammali, Eliana; Tolomeo, Daniele; Vegliante, Gloria; Stocchetti, Nino; Forloni, Gianluigi; De Simoni, Maria-Grazia; Stewart, William; Zanier, Elisa R

2018-02-01

There is increasing recognition that traumatic brain injury (TBI) may initiate long-term neurodegenerative processes, particularly chronic traumatic encephalopathy. However, insight into the mechanisms transforming an initial biomechanical injury into a neurodegenerative process remain elusive, partly as a consequence of the paucity of informative pre-clinical models. This study shows the functional, whole brain imaging and neuropathological consequences at up to one year survival from single severe TBI by controlled cortical impact in mice. TBI mice displayed persistent sensorimotor and cognitive deficits. Longitudinal T2 weighted magnetic resonance imaging (MRI) showed progressive ipsilateral (il) cortical, hippocampal and striatal volume loss, with diffusion tensor imaging demonstrating decreased fractional anisotropy (FA) at up to one year in the il-corpus callosum (CC: -30%) and external capsule (EC: -21%). Parallel neuropathological studies indicated reduction in neuronal density, with evidence of microgliosis and astrogliosis in the il-cortex, with further evidence of microgliosis and astrogliosis in the il-thalamus. One year after TBI there was also a decrease in FA in the contralateral (cl) CC (-17%) and EC (-13%), corresponding to histopathological evidence of white matter loss (cl-CC: -68%; cl-EC: -30%) associated with ongoing microgliosis and astrogliosis. These findings indicate that a single severe TBI induces bilateral, long-term and progressive neuropathology at up to one year after injury. These observations support this model as a suitable platform for exploring the mechanistic link between acute brain injury and late and persistent neurodegeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

The extrastriate body area is involved in illusory limb ownership.

PubMed

Limanowski, Jakub; Lutti, Antoine; Blankenburg, Felix

2014-02-01

The Rubber Hand Illusion (RHI) is an established paradigm for studying body ownership, and several studies have implicated premotor and temporo-parietal brain regions in its neuronal foundation. Here we used an automated setup to induce a novel multi-site version of the RHI in healthy human participants inside an MR-scanner, with a RHI and control condition that were matched in terms of synchrony of visual and tactile stimulation. Importantly, as previous research has shown that most of the ownership-related brain areas also respond to observed human actions and touch, or body parts of others, here such potential effects of the experimenter were eliminated by the automated procedure. The RHI condition induced a strong ownership illusion; we found correspondingly stronger brain activity during the RHI versus control condition in contralateral middle occipital gyrus (mOCG) and bilateral anterior insula, which have previously been related to illusory body ownership. Using independent functional localizers, we confirmed that the activity in mOCG was located within the body-part selective extrastriate body area (EBA). Crucially, activity differences in participants' peak voxels within the left EBA correlated strongly positively with their behavioral illusion scores. Thus EBA activity also reflected interindividual differences in the experienced intensity of illusory limb ownership. Moreover, psychophysiological interaction analyses (PPI) revealed that contralateral primary somatosensory cortex had stronger brain connectivity with EBA during the RHI versus control condition, while EBA was more strongly interacting with temporo-parietal multisensory regions. In sum, our findings demonstrate a direct involvement of EBA in limb ownership. © 2013 Elsevier Inc. All rights reserved.

Contralateral peripheral neurotization for a hemiplegic hindlimb after central neurological injury.

PubMed

Zheng, Mou-Xiong; Hua, Xu-Yun; Jiang, Su; Qiu, Yan-Qun; Shen, Yun-Dong; Xu, Wen-Dong

2018-01-01

OBJECTIVE Contralateral peripheral neurotization surgery has been successfully applied to rescue motor function of the hemiplegic upper extremity in patients with central neurological injury (CNI). It may contribute to strengthened neural pathways between the contralesional cortex and paretic limbs. However, the effect of this surgery in the lower extremities remains unknown. In the present study the authors explored the effectiveness and safety of contralateral peripheral neurotization in treating a hemiplegic lower extremity following CNI in adult rats. METHODS Controlled cortical impact (CCI) was performed on the hindlimb motor cortex of 36 adult Sprague-Dawley rats to create severe unilateral traumatic brain injury models. These CCI rats were randomly divided into 3 groups. At 1 month post-CCI, the experimental group (Group 1, 12 rats) underwent contralateral L-6 to L-6 transfer, 1 control group (Group 2, 12 rats) underwent bilateral L-6 nerve transection, and another control group (Group 3, 12 rats) underwent an L-6 laminectomy without injuring the L-6 nerves. Bilateral L-6 nerve transection rats without CCI (Group 4, 12 rats) and naïve rats (Group 5, 12 rats) were used as 2 additional control groups. Beam and ladder rung walking tests and CatWalk gait analysis were performed in each rat at baseline and at 0.5, 1, 2, 4, 6, 8, and 10 months to detect the skilled walking functions and gait parameters of both hindlimbs. Histological and electromyography studies were used at the final followup to verify establishment of the traumatic brain injury model and regeneration of the L6-L6 neural pathway. RESULTS In behavioral tests, comparable motor injury in the paretic hindlimbs was observed after CCI in Groups 1-3. Group 1 started to show significantly lower slip and error rates in the beam and ladder rung walking tests than Groups 2 and 3 at 6 months post-CCI (p < 0.05). In the CatWalk analysis, Group 1 also showed a higher mean intensity and swing speed after 8 months post-CCI and a longer stride length after 6 months post-CCI than Groups 2 and 3 (p < 0.05). Transection of L-6 resulted in transient skilled walking impairment in the intact hindlimbs in Groups 1 and 2 (compared with Group 3) and in the bilateral hindlimbs in Group 4 (compared with Group 5). All recovered to baseline level within 2 months. Histological study of the rat brains verified comparable injured volumes among Groups 1-3 at final examinations, and electromyography and toluidine blue staining indicated successful regeneration of the L6-L6 neural pathways in Group 1. CONCLUSIONS Contralateral L-6 neurotization could be a promising and safe surgical approach for improving motor recovery of the hemiplegic hindlimb after unilateral CNI in adult rats. Further investigations are needed before extrapolating the present conclusions to humans.

Use-Dependent Dendritic Regrowth Is Limited after Unilateral Controlled Cortical Impact to the Forelimb Sensorimotor Cortex

PubMed Central

Jones, Theresa A.; Liput, Daniel J.; Maresh, Erin L.; Donlan, Nicole; Parikh, Toral J.; Marlowe, Dana

2012-01-01

Abstract Compensatory neural plasticity occurs in both hemispheres following unilateral cortical damage incurred by seizures, stroke, and focal lesions. Plasticity is thought to play a role in recovery of function, and is important for the utility of rehabilitation strategies. Such effects have not been well described in models of traumatic brain injury (TBI). We examined changes in immunoreactivity for neural structural and plasticity-relevant proteins in the area surrounding a controlled cortical impact (CCI) to the forelimb sensorimotor cortex (FL-SMC), and in the contralateral homotopic cortex over time (3–28 days). CCI resulted in considerable motor deficits in the forelimb contralateral to injury, and increased reliance on the ipsilateral forelimb. The density of dendritic processes, visualized with immunostaining for microtubule-associated protein-2 (MAP-2), were bilaterally decreased at all time points. Synaptophysin (SYN) immunoreactivity increased transiently in the injured hemisphere, but this reflected an atypical labeling pattern, and it was unchanged in the contralateral hemisphere compared to uninjured controls. The lack of compensatory neuronal structural plasticity in the contralateral homotopic cortex, despite behavioral asymmetries, is in contrast to previous findings in stroke models. In the cortex surrounding the injury (but not the contralateral cortex), decreases in dendrites were accompanied by neurodegeneration, as indicated by Fluoro-Jade B (FJB) staining, and increased expression of the growth-inhibitory protein Nogo-A. These studies indicate that, following unilateral CCI, the cortex undergoes neuronal structural degradation in both hemispheres out to 28 days post-injury, which may be indicative of compromised compensatory plasticity. This is likely to be an important consideration in designing therapeutic strategies aimed at enhancing plasticity following TBI. PMID:22352953

The central pattern generator underlying swimming in Dendronotus iris: a simple half-center network oscillator with a twist.

PubMed

Sakurai, Akira; Katz, Paul S

2016-10-01

The nudibranch mollusc, Dendronotus iris, swims by rhythmically flexing its body from left to right. We identified a bilaterally represented interneuron, Si3, that provides strong excitatory drive to the previously identified Si2, forming a half-center oscillator, which functions as the central pattern generator (CPG) underlying swimming. As with Si2, Si3 inhibited its contralateral counterpart and exhibited rhythmic bursts in left-right alternation during the swim motor pattern. Si3 burst almost synchronously with the contralateral Si2 and was coactive with the efferent impulse activity in the contralateral body wall nerve. Perturbation of bursting in either Si3 or Si2 by current injection halted or phase-shifted the swim motor pattern, suggesting that they are both critical CPG members. Neither Si2 nor Si3 exhibited endogenous bursting properties when activated alone; activation of all four neurons was necessary to initiate and maintain the swim motor pattern. Si3 made a strong excitatory synapse onto the contralateral Si2 to which it is also electrically coupled. When Si3 was firing tonically but not exhibiting bursting, artificial enhancement of the Si3-to-Si2 synapse using dynamic clamp caused all four neurons to burst. In contrast, negation of the Si3-to-Si2 synapse by dynamic clamp blocked ongoing swim motor patterns. Together, these results suggest that the Dendronotus swim CPG is organized as a "twisted" half-center oscillator in which each "half" is composed of two excitatory-coupled neurons from both sides of the brain, each of which inhibits its contralateral counterpart. Consisting of only four neurons, this is perhaps the simplest known network oscillator for locomotion. Copyright © 2016 the American Physiological Society.

Area- and band-specific representations of hand movements by local field potentials in caudal cingulate motor area and supplementary motor area of monkeys

PubMed Central

Yokoyama, Osamu; Nakayama, Yoshihisa

2016-01-01

The caudal cingulate motor area (CMAc) and the supplementary motor area (SMA) play important roles in movement execution. The present study examined the neural mechanisms underlying these roles by investigating local field potentials (LFPs) from these areas while monkeys pressed buttons with either their left or right hand. During hand movement, power increases in the high-gamma (80–120 Hz) and theta (3–8 Hz) bands and a power decrease in the beta (12–30 Hz) band were observed in both the CMAc and SMA. High-gamma and beta activity in the SMA predominantly represented contralateral hand movements, whereas activity in the CMAc preferentially represented movement of either hand. Theta activity in both brain regions most frequently reflected movement of either hand, but a contralateral hand bias was more evident in the SMA than in the CMAc. An analysis of the relationships of the laterality representations between the high-gamma and theta bands at each recording site revealed that, irrespective of the hand preference for the theta band, the high-gamma band in the SMA preferentially represented contralateral hand movement, whereas the high-gamma band in the CMAc represented movement of either hand. These findings suggest that the input-output relationships for ipsilateral and contralateral hand movements in the CMAc and SMA differ in terms of their functionality. The CMAc may transform the input signals representing general aspects of movement into commands to perform movements with either hand, whereas the SMA may transform the input signals into commands to perform movement with the contralateral hand. PMID:26792884

Use-dependent dendritic regrowth is limited after unilateral controlled cortical impact to the forelimb sensorimotor cortex.

PubMed

Jones, Theresa A; Liput, Daniel J; Maresh, Erin L; Donlan, Nicole; Parikh, Toral J; Marlowe, Dana; Kozlowski, Dorothy A

2012-05-01

Compensatory neural plasticity occurs in both hemispheres following unilateral cortical damage incurred by seizures, stroke, and focal lesions. Plasticity is thought to play a role in recovery of function, and is important for the utility of rehabilitation strategies. Such effects have not been well described in models of traumatic brain injury (TBI). We examined changes in immunoreactivity for neural structural and plasticity-relevant proteins in the area surrounding a controlled cortical impact (CCI) to the forelimb sensorimotor cortex (FL-SMC), and in the contralateral homotopic cortex over time (3-28 days). CCI resulted in considerable motor deficits in the forelimb contralateral to injury, and increased reliance on the ipsilateral forelimb. The density of dendritic processes, visualized with immunostaining for microtubule-associated protein-2 (MAP-2), were bilaterally decreased at all time points. Synaptophysin (SYN) immunoreactivity increased transiently in the injured hemisphere, but this reflected an atypical labeling pattern, and it was unchanged in the contralateral hemisphere compared to uninjured controls. The lack of compensatory neuronal structural plasticity in the contralateral homotopic cortex, despite behavioral asymmetries, is in contrast to previous findings in stroke models. In the cortex surrounding the injury (but not the contralateral cortex), decreases in dendrites were accompanied by neurodegeneration, as indicated by Fluoro-Jade B (FJB) staining, and increased expression of the growth-inhibitory protein Nogo-A. These studies indicate that, following unilateral CCI, the cortex undergoes neuronal structural degradation in both hemispheres out to 28 days post-injury, which may be indicative of compromised compensatory plasticity. This is likely to be an important consideration in designing therapeutic strategies aimed at enhancing plasticity following TBI.

Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation.

PubMed

Unkelbach, Jan; Menze, Bjoern H; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A

2014-02-07

Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most crucial model input. We conclude that the tumor growth model provides a method to account for anisotropic growth patterns of glioma, and may therefore provide a tool to make target delineation more objective and automated.

Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation

NASA Astrophysics Data System (ADS)

Unkelbach, Jan; Menze, Bjoern H.; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A.

2014-02-01

Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most crucial model input. We conclude that the tumor growth model provides a method to account for anisotropic growth patterns of glioma, and may therefore provide a tool to make target delineation more objective and automated.

The Hyperactivity of Efferent Auditory System in Patients with Schizophrenia: A Transient Evoked Otoacoustic Emissions Study

PubMed Central

Wahab, Suzaily; Abdul Rahman, Abdul Hamid; Sidek, Dinsuhaimi; Zakaria, Mohd. Normani

2016-01-01

Objective Electrophysiological studies, which are mostly focused on afferent pathway, have proven that auditory processing deficits exist in patients with schizophrenia. Nevertheless, reports on the suppressive effect of efferent auditory pathway on cochlear outer hair cells among schizophrenia patients are limited. The present, case-control, study examined the contralateral suppression of transient evoked otoacoustic emissions (TEOAEs) in patients with schizophrenia. Methods Participants were twenty-three healthy controls and sixteen schizophrenia patients with normal hearing, middle ear and cochlear outer hair cells function. Absolute non-linear and linear TEOAEs were measured in both ears by delivering clicks stimuli at 80 dB SPL and 60 dB SPL respectively. Subsequently, contralateral suppression was determined by subtracting the absolute TEOAEs response obtained at 60 dBpe SPL during the absence and presence of contralateral white noise delivered at 65 dB HL. No attention tasks were conducted during measurements. Results We found no significant difference in absolute TEOAEs responses at 80 dB SPL, in either diagnosis or ear groups (p>0.05). However, the overall contralateral suppression was significantly larger in schizophrenia patients (p<0.05). Specifically, patients with schizophrenia demonstrated significantly increased right ear contralateral suppression compared to healthy control (p<0.05). Conclusion The present findings suggest increased inhibitory effect of efferent auditory pathway especially on the right cochlear outer hair cells. Further studies to investigate increased suppressive effects are crucial to expand the current understanding of auditory hallucination mechanisms in schizophrenia patients. PMID:26766950

The MOC reflex during active listening to speech.

PubMed

Garinis, Angela C; Glattke, Theodore; Cone, Barbara K

2011-10-01

The purpose of this study was to test the hypothesis that active listening to speech would increase medial olivocochlear (MOC) efferent activity for the right vs. the left ear. Click-evoked otoacoustic emissions (CEOAEs) were evoked by 60-dB p.e. SPL clicks in 13 normally hearing adults in 4 test conditions for each ear: (a) in quiet; (b) with 60-dB SPL contralateral broadband noise; (c) with words embedded (at -3-dB signal-to-noise ratio [SNR]) in 60-dB SPL contralateral noise during which listeners directed attention to the words; and (d) for the same SNR as in the 3rd condition, with words played backwards. There was greater suppression during active listening compared with passive listening that was apparent in the latency range of 6- to 18-ms poststimulus onset. Ear differences in CEOAE amplitude were observed in all conditions, with right-ear amplitudes larger than those for the left. The absolute difference between CEOAE amplitude in quiet and with contralateral noise, a metric of suppression, was equivalent for right and left ears. When the amplitude differences were normalized, suppression was greater for noise presented to the right and the effect measured for a probe in the left ear. The findings support the theory that cortical mechanisms involved in listening to speech affect cochlear function through the MOC efferent system.

Differential coding of hyperalgesia in the human brain: a functional MRI study.

PubMed

Maihöfner, Christian; Handwerker, Hermann O

2005-12-01

Neuropathic pain can be both ongoing or stimulus-induced. Stimulus-induced pain, also known as hyperalgesia, can be differentiated into primary and secondary hyperalgesia. The former results from sensitization of peripheral nociceptive structures, the latter involves sensitization processes within the central nervous system (CNS). Hypersensitivity towards heat stimuli, i.e. thermal hyperalgesia, is a key feature of primary hyperalgesia, whereas secondary hyperalgesia is characterized by hypersensitivity towards mechanical (e.g. pin-prick) stimulation. Using functional magnetic resonance imaging (fMRI), we investigated if brain activation patterns associated with primary and secondary hyperalgesia might differ. Thermal and pin-prick hyperalgesia were induced on the left forearm in 12 healthy subjects by topical capsaicin (2.5%, 30 min) application. Equal pain intensities of both hyperalgesia types were applied during fMRI experiments, based on previous quantitative sensory testing. Simultaneously, subjects had to rate the unpleasantness of stimulus-related pain. Pin-prick hyperalgesia (i.e. subtraction of brain activations during pin-prick stimulation before and after capsaicin exposure) led to activations of primary and secondary somatosensory cortices (S1 and S2), associative-somatosensory cortices, insula and superior and inferior frontal cortices (SFC, IFC). Brain areas activated during thermal hyperalgesia (i.e. subtraction of brain activations during thermal stimulation before and after capsaicin exposure) were S1 and S2, insula, associative-somatosensory cortices, cingulate cortex (GC), SFC, middle frontal cortex (MFC) and IFC. When compared to pin-prick hyperalgesia, thermal hyperalgesia led to an increased activation of bilateral anterior insular cortices, MFC, GC (Brodmann area 24' and 32') and contralateral SFC and IFC, despite equal pain intensities. Interestingly, stronger activations of GC, contralateral MFC and anterior insula significantly correlated to higher ratings of the stimulus-related unpleasantness. We conclude that thermal and mechanical hyperalgesia produce substantially different brain activation patterns. This is linked to different psychophysical properties.

Stability of the Medial Olivocochlear Reflex as Measured by Distortion Product Otoacoustic Emissions

PubMed Central

Abdala, Carolina

2015-01-01

Purpose The purpose of this study was to assess the repeatability of a fine-resolution, distortion product otoacoustic emission (DPOAE)–based assay of the medial olivocochlear (MOC) reflex in normal-hearing adults. Method Data were collected during 36 test sessions from 4 normal-hearing adults to assess short-term stability and 5 normal-hearing adults to assess long-term stability. DPOAE level and phase measurements were recorded with and without contralateral acoustic stimulation. MOC reflex indices were computed by (a) noting contralateral acoustic stimulation-induced changes in DPOAE level (both absolute and normalized) at fine-structure peaks, (b) recording the effect as a vector difference, and (c) separating DPOAE components and considering a component-specific metric. Results Analyses indicated good repeatability of all indices of the MOC reflex in most frequency ranges. Short- and long-term repeatability were generally comparable. Indices normalized to a subject's own baseline fared best, showing strong short- and long-term stability across all frequency intervals. Conclusions These results suggest that fine-resolution DPOAE-based measures of the MOC reflex measured at strategic frequencies are stable, and natural variance from day-to-day or week-to-week durations is small enough to detect between-group differences and possibly to monitor intervention-related success. However, this is an empirical question that must be directly tested to confirm its utility. PMID:25320951

Long-term Brain Tissue Monitoring after Semi-brain Irradiation in Rats Using Proton Magnetic Resonance Spectroscopy: A Preliminary Study In vivo

PubMed Central

Chen, Hong; Cheng, Yu-Shu; Zhou, Zheng-Rong

2017-01-01

Background: In head and neck neoplasm survivors treated with brain irradiation, metabolic alterations would occur in the radiation-induced injury area. The mechanism of these metabolic alterations has not been fully understood, while the alternations could be sensitively detected by proton (1H) nuclear magnetic resonance spectroscopy (MRS). In this study, we investigated the metabolic characteristics of radiation-induced brain injury through a long-term follow-up after radiation treatment using MRS in vivo. Methods: A total of 12 adult Sprague-Dawley rats received a single dose of 30 Gy radiation treatment to semi-brain (field size: 1.0 cm × 2.0 cm; anterior limit: binocular posterior inner canthus connection; posterior limit: external acoustic meatus connection; internal limit: sagittal suture). Conventional magnetic resonance imaging and single-voxel 1H-MRS were performed at different time points (in month 0 before irradiation as well as in the 1st, 3rd, 5th, 7th, and 9th months after irradiation) to investigate the alternations in irradiation field. N-acetylaspartate/choline (NAA/Cho), NAA/creatinine (Cr), and Cho/Cr ratios were measured in the bilateral hippocampus and quantitatively analyzed with a repeated-measures mixed-effects model and multiple comparison test. Results: Significant changes in the ratios of NAA/Cho (F = 57.37, Pg < 0.001), NAA/Cr (F = 54.49, Pg < 0.001), and Cho/Cr (F = 9.78, Pg = 0.005) between the hippocampus region of the irradiated semi-brain and the contralateral semi-brain were observed. There were significant differences in NAA/Cho (F = 9.17, Pt < 0.001) and NAA/Cr (F = 13.04, Pt < 0.001) ratios over time. The tendency of NAA/Cr to change with time showed no significant difference between the irradiated and contralateral sides. Nevertheless, there were significant differences in the Cho/Cr ratio between these two sides. Conclusions: MRS can sensitively detect metabolic alternations. Significant changes of metabolites ratio in the first few months after radiation treatment reflect the metabolic disturbance in the acute and early-delayed stages of radiation-induced brain injuries. PMID:28397726

Contingent Attentional Capture by Top-Down Control Settings: Converging Evidence from Event-Related Potentials

ERIC Educational Resources Information Center

Lien, Mei-Ching; Ruthruff, Eric; Goodin, Zachary; Remington, Roger W.

2008-01-01

Theories of attentional control are divided over whether the capture of spatial attention depends primarily on stimulus salience or is contingent on attentional control settings induced by task demands. The authors addressed this issue using the N2-posterior-contralateral (N2pc) effect, a component of the event-related brain potential thought to…

Neuromagnetic brain activity associated with anticipatory postural adjustments for bimanual load lifting.

PubMed

Ng, Tommy H B; Sowman, Paul F; Brock, Jon; Johnson, Blake W

2013-02-01

During bimanual load lifting, the brain must anticipate the effects of unloading upon the load-bearing arm. Little is currently known about the neural networks that coordinate these anticipatory postural adjustments. We measured neuromagnetic brain activity with whole-head magnetoencephalography while participants performed a bimanual load-lifting task. Anticipatory adjustments were associated with reduction in biceps brachii muscle activity of the load-bearing arm and pre-movement desynchronization of the cortical beta rhythm. Beamforming analyses localized anticipatory brain activity to the precentral gyrus, basal ganglia, supplementary motor area, and thalamus, contralateral to the load-bearing arm. To our knowledge this is the first human neuroimaging study to directly investigate anticipatory postural adjustments and to explicitly partition the anticipatory and volitional aspects of brain activity in bimanual load lifting. These data contribute to our understanding of the neural systems supporting anticipatory postural adjustments in healthy adults. Copyright © 2012 Elsevier Inc. All rights reserved.

Differences in hemispherical thalamo-cortical causality analysis during resting-state fMRI.

PubMed

Anwar, Abdul Rauf; Muthalib, Makii; Perrey, Stephane; Wolff, Stephan; Deuschl, Guunther; Heute, Ulrich; Muthuraman, Muthuraman

2014-01-01

Thalamus is a very important part of the human brain. It has been reported to act as a relay for the messaging taking place between the cortical and sub-cortical regions of the brain. In the present study, we analyze the functional network between both hemispheres of the brain with the focus on thalamus. We used conditional Granger causality (CGC) and time-resolved partial directed coherence (tPDC) to investigate the functional connectivity. Results of CGC analysis revealed the asymmetry between connection strengths of the bilateral thalamus. Upon testing the functional connectivity of the default-mode network (DMN) at low-frequency fluctuations (LFF) and comparing coherence vectors using Spearman's rank correlation, we found that thalamus is a better source for the signals directed towards the contralateral regions of the brain, however, when thalamus acts as sink, it is a better sink for signals generated from ipsilateral regions of the brain.

A MEG investigation of somatosensory processing in the rhesus monkey

PubMed Central

Wilson, Tony W.; Godwin, Dwayne W.; Czoty, Paul W.; Nader, Michael A.; Kraft, Robert A.; Buchheimer, Nancy C.; Daunais, James B.

2009-01-01

The use of minimally and non-invasive neuroimaging methods in animal models has sharply increased over the past decade. Such studies have enhanced understanding of the neural basis of the physical signals quantified by these tools, and have addressed an assortment of fundamental and otherwise intractable questions in neurobiology. To date, these studies have almost exclusively utilized positron-emission tomography or variants of magnetic resonance based imaging. These methods provide largely indirect measures of brain activity and are strongly reliant on intact vasculature and normal blood flow, which is known to be compromised in many clinical conditions. The current study provides the first demonstration of whole-head magnetoencephalography (MEG), a non-invasive and direct measure of neuronal activity, in a rhesus monkey, and in the process supplies the initial data on systems-level dynamics in somatosensory cortices. An adult rhesus monkey underwent three separate studies of tactile stimulation on the pad of the right second or fifth digit as whole-head MEG data were acquired. The neural generators of the primary neuromagnetic components were localized using an equivalent-current-dipole model. Second digit stimulation produced an initial cortical response peaking ∼16 ms after stimulus onset in the contralateral somatosensory cortices, with a later response at ∼96 ms in an overlapping or nearby neural area with a roughly orthogonal orientation. Stimulation of the fifth digit produced similar results, the main exception being a substantially weaker later response. We believe the 16ms response is likely the monkey homologue of the human M50 response, as both are the earliest cortical response and localize to the contralateral primary somatosensory area. Thus, these data suggest that mechanoreception in nonhuman primates operates substantially faster than that in adult humans. More broadly, these results demonstrate that it is feasible to use current human whole-head MEG instrumentation to record neuromagnetic responses in adult rhesus monkeys. Nonhuman primate models of human disease provide the closest phylogenetic link to humans. The present, non-invasive imaging study could promote exciting links between invasive animal studies and non-invasive human studies, allowing experimentally induced deficits and pharmacological treatments to be interpreted in light of resulting brain network interactions. PMID:19306931

The medial olivocochlear reflex in children during active listening.

PubMed

Smith, Spencer B; Cone, Barbara

2015-08-01

To determine if active listening modulates the strength of the medial olivocochlear (MOC) reflex in children. Click-evoked otoacoustic emissions (CEOAEs) were recorded from the right ear in quiet and in four test conditions: one with contralateral broadband noise (BBN) only, and three with active listening tasks wherein attention was directed to speech embedded in contralateral BBN. Fifteen typically-developing children (ranging in age from 8 to14 years) with normal hearing. CEOAE levels were reduced in every condition with contralateral acoustic stimulus (CAS) when compared to preceding quiet conditions. There was an additional systematic decrease in CEOAE level with increased listening task difficulty, although this effect was very small. These CEOAE level differences were most apparent in the 8-18 ms region after click onset. Active listening may change the strength of the MOC reflex in children, although the effects reported here are very subtle. Further studies are needed to verify that task difficulty modulates the activity of the MOC reflex in children.

The medial olivocochlear reflex in children during active listening

PubMed Central

Smith, Spencer B.; Cone, Barbara

2015-01-01

Objective To determine if active listening modulates the strength of the medial olivocochlear (MOC) reflex in children. Design Click-evoked otoacoustic emissions (CEOAEs) were recorded from the right ear in quiet and in four test conditions: one with contralateral broadband noise (BBN) only, and three with active listening tasks wherein attention was directed to speech embedded in contralateral BBN. Study sample Fifteen typically-developing children (ranging in age from 8 to 14 years) with normal hearing. Results CEOAE levels were reduced in every condition with contralateral acoustic stimulus (CAS) when compared to preceding quiet conditions. There was an additional systematic decrease in CEOAE level with increased listening task difficulty, although this effect was very small. These CEOAE level differences were most apparent in the 8–18 ms region after click onset. Conclusions Active listening may change the strength of the MOC reflex in children, although the effects reported here are very subtle. Further studies are needed to verify that task difficulty modulates the activity of the MOC reflex in children. PMID:25735203

Intracarotid Infusion of Mesenchymal Stem Cells in an Animal Model of Parkinson's Disease, Focusing on Cell Distribution and Neuroprotective and Behavioral Effects.

PubMed

Cerri, Silvia; Greco, Rosaria; Levandis, Giovanna; Ghezzi, Cristina; Mangione, Antonina Stefania; Fuzzati-Armentero, Marie-Therese; Bonizzi, Arianna; Avanzini, Maria Antonietta; Maccario, Rita; Blandini, Fabio

2015-09-01

Mesenchymal stem cells (MSCs) have been proposed as a potential therapeutic tool for Parkinson's disease (PD) and systemic administration of these cells has been tested in preclinical and clinical studies. However, no information on survival and actual capacity of MSCs to reach the brain has been provided. In this study, we evaluated homing of intraarterially infused rat MSCs (rMSCs) in the brain of rats bearing a 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal tract, to establish whether the toxin-induced damage is sufficient to grant MSC passage across the blood-brain barrier (BBB) or if a transient BBB disruption is necessary. The rMSC distribution in peripheral organs and the effects of cell infusion on neurodegenerative process and motor deficits were also investigated. rMSCs were infused 14 days after 6-OHDA injection. A hyperosmolar solution of mannitol was used to transiently permeabilize the BBB. Behavioral impairment was assessed by adjusting step test and response to apomorphine. Animals were sacrificed 7 and 28 days after cell infusion. Our work shows that appreciable delivery of rMSCs to the brain of 6-OHDA-lesioned animals can be obtained only after mannitol pretreatment. A notable percentage of infused cells accumulated in peripheral organs. Infusion of rMSCs did not modify the progression of 6-OHDA-induced damage or the motor impairment at the stepping test, but induced progressive normalization of the pathological response (contralateral turning) to apomorphine administration. These findings suggest that many aspects should be further investigated before considering any translation of MSC systemic administration into the clinical setting for PD treatment. This study demonstrates that mesenchymal stem cells infused through the carotid artery do not efficiently cross the blood-brain barrier in rats with a Parkinson's disease-like degeneration of nigrostriatal neurons, unless a permeabilizing agent (e.g., mannitol) is used. The infusion did not reduce the neuronal damage and associated motor impairment, but abolished the motor abnormalities these animals typically show when challenged with a dopaminergic agonist. Therefore, although arterially infused mesenchymal stem cells did not show neurorestorative effects in this study's Parkinson's disease model, they appeared to normalize the pathological responsiveness of striatal neurons to dopaminergic stimulation. This capability should be further explored in future studies. ©AlphaMed Press.

Repeated assessment of orthotopic glioma pO2 by multi-site EPR oximetry: A technique with the potential to guide therapeutic optimization by repeated measurements of oxygen

PubMed Central

Khan, Nadeem; Mupparaju, Sriram; Hou, Huagang; Williams, Benjamin B.; Swartz, Harold

2011-01-01

Tumor hypoxia plays a vital role in therapeutic resistance. Consequently, measurements of tumor pO2 could be used to optimize the outcome of oxygen-dependent therapies, such as, chemoradiation. However, the potential optimizations are restricted by the lack of methods to repeatedly and quantitatively assess tumor pO2 during therapies, particularly in gliomas. We describe the procedures for repeated measurements of orthotopic glioma pO2 by multi-site electron paramagnetic resonance (EPR) oximetry. This oximetry approach provides simultaneous measurements of pO2 at more than one site in the glioma and contralateral cerebral tissue. The pO2 of intracerebral 9L, C6, F98 and U251 tumors, as well as contralateral brain, were measured repeatedly for five consecutive days. The 9L glioma was well oxygenated with pO2 of 27 - 36 mm Hg, while C6, F98 and U251 glioma were hypoxic with pO2 of 7 - 12 mm Hg. The potential of multi-site EPR oximetry to assess temporal changes in tissue pO2 was investigated in rats breathing 100% O2. A significant increase in F98 tumor and contralateral brain pO2 was observed on day 1 and day 2, however, glioma oxygenation declined on subsequent days. In conclusion, EPR oximetry provides the capability to repeatedly assess temporal changes in orthotopic glioma pO2. This information could be used to test and optimize the methods being developed to modulate tumor hypoxia. Furthermore, EPR oximetry could be potentially used to enhance the outcome of chemoradiation by scheduling treatments at times of increase in glioma pO2. PMID:22079559

Repeated assessment of orthotopic glioma pO(2) by multi-site EPR oximetry: a technique with the potential to guide therapeutic optimization by repeated measurements of oxygen.

PubMed

Khan, Nadeem; Mupparaju, Sriram; Hou, Huagang; Williams, Benjamin B; Swartz, Harold

2012-02-15

Tumor hypoxia plays a vital role in therapeutic resistance. Consequently, measurements of tumor pO(2) could be used to optimize the outcome of oxygen-dependent therapies, such as, chemoradiation. However, the potential optimizations are restricted by the lack of methods to repeatedly and quantitatively assess tumor pO(2) during therapies, particularly in gliomas. We describe the procedures for repeated measurements of orthotopic glioma pO(2) by multi-site electron paramagnetic resonance (EPR) oximetry. This oximetry approach provides simultaneous measurements of pO(2) at more than one site in the glioma and contralateral cerebral tissue. The pO(2) of intracerebral 9L, C6, F98 and U251 tumors, as well as contralateral brain, were measured repeatedly for five consecutive days. The 9L glioma was well oxygenated with pO(2) of 27-36 mm Hg, while C6, F98 and U251 glioma were hypoxic with pO(2) of 7-12mm Hg. The potential of multi-site EPR oximetry to assess temporal changes in tissue pO(2) was investigated in rats breathing 100% O(2). A significant increase in F98 tumor and contralateral brain pO(2) was observed on day 1 and day 2, however, glioma oxygenation declined on subsequent days. In conclusion, EPR oximetry provides the capability to repeatedly assess temporal changes in orthotopic glioma pO(2). This information could be used to test and optimize the methods being developed to modulate tumor hypoxia. Furthermore, EPR oximetry could be potentially used to enhance the outcome of chemoradiation by scheduling treatments at times of increase in glioma pO(2). Copyright © 2011 Elsevier B.V. All rights reserved.

The compensatory dynamic of inter-hemispheric interactions in visuospatial attention revealed using rTMS and fMRI

PubMed Central

Plow, Ela B.; Cattaneo, Zaira; Carlson, Thomas A.; Alvarez, George A.; Pascual-Leone, Alvaro; Battelli, Lorella

2014-01-01

A balance of mutual tonic inhibition between bi-hemispheric posterior parietal cortices is believed to play an important role in bilateral visual attention. However, experimental support for this notion has been mainly drawn from clinical models of unilateral damage. We have previously shown that low-frequency repetitive TMS (rTMS) over the intraparietal sulcus (IPS) generates a contralateral attentional deficit in bilateral visual tracking. Here, we used functional magnetic resonance imaging (fMRI) to study whether rTMS temporarily disrupts the inter-hemispheric balance between bilateral IPS in visual attention. Following application of 1 Hz rTMS over the left IPS, subjects performed a bilateral visual tracking task while their brain activity was recorded using fMRI. Behaviorally, tracking accuracy was reduced immediately following rTMS. Areas ventro-lateral to left IPS, including inferior parietal lobule (IPL), lateral IPS (LIPS), and middle occipital gyrus (MoG), showed decreased activity following rTMS, while dorsomedial areas, such as Superior Parietal Lobule (SPL), Superior occipital gyrus (SoG), and lingual gyrus, as well as middle temporal areas (MT+), showed higher activity. The brain activity of the homologues of these regions in the un-stimulated, right hemisphere was reversed. Interestingly, the evolution of network-wide activation related to attentional behavior following rTMS showed that activation of most occipital synergists adaptively compensated for contralateral and ipsilateral decrement after rTMS, while activation of parietal synergists, and SoG remained competing. This pattern of ipsilateral and contralateral activations empirically supports the hypothesized loss of inter-hemispheric balance that underlies clinical manifestation of visual attentional extinction. PMID:24860462

Serial analysis of 3D H-1 MRSI for patients with newly diagnosed GBM treated with combination therapy that includes bevacizumab.

PubMed

Nelson, Sarah J; Li, Yan; Lupo, Janine M; Olson, Marram; Crane, Jason C; Molinaro, Annette; Roy, Ritu; Clarke, Jennifer; Butowski, Nicholas; Prados, Michael; Cha, Soonmee; Chang, Susan M

2016-10-01

Interpretation of changes in the T1- and T2-weighted MR images from patients with newly diagnosed glioblastoma (GBM) treated with standard of care in conjunction with anti-angiogenic agents is complicated by pseudoprogression and pseudoresponse. The hypothesis being tested in this study was that 3D H-1 magnetic resonance spectroscopic imaging (MRSI) provides estimates of levels of choline, creatine, N-acetylaspartate (NAA), lactate and lipid that change in response to treatment and that metrics describing these characteristics are associated with survival. Thirty-one patients with newly diagnosed GBM and being treated with radiation therapy (RT), temozolomide, erlotinib and bevacizumab were recruited to receive serial MR scans that included 3-D lactate edited MRSI at baseline, mid-RT, post-RT and at specific follow-up time points. The data were processed to provide estimates of metrics representing changes in metabolite levels relative to normal appearing brain. Cox proportional hazards analysis was applied to examine the relationship of these parameters with progression free survival (PFS) and overall survival (OS). There were significant reductions in parameters that describe relative levels of choline to NAA and creatine, indicating that the treatment caused a decrease in tumor cellularity. Changes in the levels of lactate and lipid relative to the NAA from contralateral brain were consistent with vascular normalization. Metabolic parameters from the first serial follow-up scan were associated with PFS and OS, when accounting for age and extent of resection. Integrating metabolic parameters into the assessment of patients with newly diagnosed GBM receiving therapies that include anti-angiogenic agents may be helpful for tracking changes in tumor burden, resolving ambiguities in anatomic images caused by non-specific treatment effects and for predicting outcome.

Prospective flutemetamol positron emission tomography and histopathology in normal pressure hydrocephalus.

PubMed

Rinne, Juha O; Frantzen, Janek; Leinonen, Ville; Lonnrot, Kimmo; Laakso, Aki; Virtanen, Kirsi A; Solin, Olof; Kotkansalo, Anna; Koivisto, Anne; Sajanti, Juha; Karppinen, Atte; Lehto, Hanna; Rummukainen, Jaana; Buckley, Chris; Smith, Adrian; Jones, Paul A; Sherwin, Paul; Farrar, Gill; McLain, Richard; Kailajarvi, Marita; Grachev, Igor D

2014-01-01

BACKGOUND/OBJECTIVE: To determine the level of association between uptake of the amyloid positron emission tomography (PET) imaging agent [(18)F]flutemetamol and the level of amyloid-β measured by immunohistochemical and histochemical staining in a frontal cortical region biopsy site. Seventeen patients with probable normal pressure hydrocephalus (NPH) underwent prospective [(18)F]flutemetamol PET and subsequent frontal cortical brain biopsy during ventriculoperitoneal shunting. Tissue amyloid-β was evaluated using the monoclonal antibody 4G8, thioflavin S and Bielschowsky silver stain. Four of the 17 patients (23.5%) had amyloid-β pathology based on the overall pathology read and also showed increased [(18)F]flutemetamol uptake. [(18)F]Flutemetamol standardized uptake values from the biopsy site were significantly associated with biopsy specimen amyloid-β levels (Pearson's r = 0.67; p = 0.006). There was also good correlation between the biopsy specimen amyloid-β level and uptake of [(18)F]flutemetamol in the region contralateral to the biopsy site (r = 0.67; p = 0.006), as well as with composite cortical [(18)F]flutemetamol uptake (r = 0.65; p = 0.008). The blinded visual read showed a high level of agreement between all readers (κ = 0.88). Two of 3 readers were in full agreement on all images; 1 reader disagreed on 1 of the 17 NPH cases. Blinded visual assessments of PET images by 1 reader were associated with 100% sensitivity to the overall pathology read, and assessments by the 2 others were associated with 75% sensitivity (overall sensitivity by majority read was 75%); specificity of all readers was 100%. [(18)F]Flutemetamol detects brain amyloid-β in vivo and shows promise as a valuable tool to study and possibly facilitate diagnosis of Alzheimer's disease both in patients with suspected NPH and among the wider population.

Hemispheric asymmetry of ERPs and MMNs evoked by slow, fast and abrupt auditory motion.

PubMed

Shestopalova, L B; Petropavlovskaia, E A; Vaitulevich, S Ph; Nikitin, N I

2016-10-01

The current MMN study investigates whether brain lateralization during automatic discrimination of sound stimuli moving at different velocities is consistent with one of the three models of asymmetry: the right-hemispheric dominance model, the contralateral dominance model, or the neglect model. Auditory event-related potentials (ERPs) were recorded for three patterns of sound motion produced by linear or abrupt changes of interaural time differences. The slow motion (450deg/s) was used as standard, and the fast motion (620deg/s) and the abrupt sound shift served as deviants in the oddball blocks. All stimuli had the same onset/offset spatial positions. We compared the effects of the recording side (left, right) and of the direction of sound displacement (ipsi- or contralateral with reference to the side of recording) on the ERPs and mismatch negativity (MMN). Our results indicated different patterns of asymmetry for the ERPs and MMN responses. The ERPs showed a velocity-independent right-hemispheric dominance that emerged at the descending limb of N1 wave (at around 120-160ms) and could be related to overall context of the preattentive spatial perception. The MMNs elicited in the left hemisphere (at around 230-270ms) exhibited a contralateral dominance, whereas the right-hemispheric MMNs were insensitive to the direction of sound displacement. These differences in contralaterality between MMN responses produced by the left and the right hemisphere favour the neglect model of the preattentive motion processing indexed by MMN. Copyright © 2016 Elsevier Ltd. All rights reserved.

Unilateral vs bilateral hip bone mineral density measurement for the diagnosis of osteoporosis.

PubMed

Ikegami, Shota; Kamimura, Mikio; Uchiyama, Shigeharu; Mukaiyama, Keijiro; Kato, Hiroyuki

2014-01-01

It has not been established whether unilateral or bilateral hip dual-energy X-ray absorptiometry (DXA) is preferable for the diagnosis of osteoporosis. We investigated the discordance in DXA measurements in bilateral hips to determine whether unilateral DXA is valid for osteoporosis diagnosis. The subjects were 2964 Japanese patients without a previous diagnosis of primary osteoporosis. We measured bilateral femoral bone mineral density (BMD) and calculated indices, related to the unilateral results, for predicting contralateral hip osteoporosis. A likelihood ratio (LR) of a negative test (LR [-]) of less than 0.2 was considered to exclude the diagnosis. In the normal spinal BMD group, the sensitivity of unilateral DXA for women was 27-73% and LR (-) was 0.28-0.73; the sensitivity for men was 0-50% and LR (-) was 0.51-1.00; the diagnosis of contralateral osteoporosis was not excluded. Sensitivity increased and LR (-) increased with worsening spinal BMD status; however, LR (-) did not meet the cutoff for exclusion. We could exclude unilateral hip osteoporosis, in women only, by performing contralateral femoral DXA; this necessitated lowering the T-score cutoff from -2.5 to -2.0. Unilateral femoral DXA is not useful for excluding the diagnosis of contralateral hip osteoporosis. Copyright © 2014 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Contralateral disconnection of the rat prelimbic cortex and dorsomedial striatum impairs cue-guided behavioral switching

PubMed Central

Baker, Phillip M.

2014-01-01

Switches in reward outcomes or reward-predictive cues are two fundamental ways in which information is used to flexibly shift response patterns. The rat prelimbic cortex and dorsomedial striatum support behavioral flexibility based on a change in outcomes. The present experiments investigated whether these two brain regions are necessary for conditional discrimination performance in which a switch in reward-predictive cues occurs every three to six trials. The GABA agonists baclofen and muscimol infused into the prelimbic cortex significantly impaired performance leading rats to adopt an inappropriate turn strategy. The NMDA receptor antagonist D-AP5 infused into the dorsomedial striatum or prelimbic cortex and dorsomedial striatum contralateral disconnection impaired performance due to a rat failing to switch a response choice for an entire trial block in about two out of 13 test blocks. In an additional study, contralateral disconnection did not affect nonswitch discrimination performance. The results suggest that the prelimbic cortex and dorsomedial striatum are necessary to support cue-guided behavioral switching. The prelimbic cortex may be critical for generating alternative response patterns while the dorsomedial striatum supports the selection of an appropriate response when cue information must be used to flexibly switch response patterns. PMID:25028395

Altered contralateral sensorimotor system organization after experimental hemispherectomy: a structural and functional connectivity study.

PubMed

Otte, Willem M; van der Marel, Kajo; van Meer, Maurits P A; van Rijen, Peter C; Gosselaar, Peter H; Braun, Kees P J; Dijkhuizen, Rick M

2015-08-01

Hemispherectomy is often followed by remarkable recovery of cognitive and motor functions. This reflects plastic capacities of the remaining hemisphere, involving large-scale structural and functional adaptations. Better understanding of these adaptations may (1) provide new insights in the neuronal configuration and rewiring that underlies sensorimotor outcome restoration, and (2) guide development of rehabilitation strategies to enhance recovery after hemispheric lesioning. We assessed brain structure and function in a hemispherectomy model. With MRI we mapped changes in white matter structural integrity and gray matter functional connectivity in eight hemispherectomized rats, compared with 12 controls. Behavioral testing involved sensorimotor performance scoring. Diffusion tensor imaging and resting-state functional magnetic resonance imaging were acquired 7 and 49 days post surgery. Hemispherectomy caused significant sensorimotor deficits that largely recovered within 2 weeks. During the recovery period, fractional anisotropy was maintained and white matter volume and axial diffusivity increased in the contralateral cerebral peduncle, suggestive of preserved or improved white matter integrity despite overall reduced white matter volume. This was accompanied by functional adaptations in the contralateral sensorimotor network. The observed white matter modifications and reorganization of functional network regions may provide handles for rehabilitation strategies improving functional recovery following large lesions.

Determination of the toxicity of intravitreal minocycline in rabbit eyes.

PubMed

Falavarjani, Khalil Ghasemi; Pourhabibi, Arash; Aghdam, Kaveh Abri; Hosseini, Seyed Bagher; Modarres, Mehdi; Pazouki, Abdolreza; Khanamiri, Hossein Nazari

2016-09-01

To evaluate the retinal toxicity of intravitreal minocycline in rabbit eyes. Intravitreal injection of minocycline with concentrations of 1000, 500, 250, 125 and 62.5 μg in 0.1 ml was performed in 10 New Zealand albino rabbits. Each concentration was injected into two rabbit eyes. For each dose, normal saline was injected in one contralateral eye and the other fellow eye remained non-injected. Electrophysiologic testing was performed before and 4 weeks after injections. The eyes were enucleated 4 weeks after injections and examined using light microscopy. The clinical examination was unremarkable after injections. Electroretinography recordings were significantly affected at all doses in at least one of the a- or b-waves of photopic or scotopic responses. Histopathologic examination revealed marked atrophy and loss of integrity in all retinal layers in all minocycline injected eyes. Contralateral eyes were normal. In our study, intravitreal minocycline was toxic to the retina in albino rabbits even at a concentration of 62.5 µg/0.1 ml.

Altered regional and circuit resting-state activity in patients with occult spastic diplegic cerebral palsy.

PubMed

Mu, Xuetao; Wang, Zhiqun; Nie, Binbin; Duan, Shaofeng; Ma, Qiaozhi; Dai, Guanghui; Wu, Chunnan; Dong, Yuru; Shan, Baoci; Ma, Lin

2017-10-07

Very few studies have been made to investigate functional activity changes in occult spastic diplegic cerebral palsy (SDCP). The purpose of this study was to analyze whole-brain resting state regional brain activity and functional connectivity (FC) changes in patients with SDCP. We examined 12 occult SDCP and 14 healthy control subjects using resting-state functional magnetic resonance imaging. The data were analyzed using Resting-State fMRI Data Analysis Toolkit (REST) software. The regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and whole brain FC of the motor cortex and thalamus were analyzed and compared between the occult SDCP and control groups. Compared with the control group, the occult SDCP group showed decreased ReHo regions, including the bilateral frontal, parietal, and temporal lobes, the cerebellum, right cingulate gyrus, and right lenticular nucleus, whereas an increased ReHo value was observed in the left precuneus, calcarine, fusiform gyrus, and right precuneus. Compared with the control group, no significant differences in ALFF were noted in the occult SDCP group. With the motor cortex as the region of interest, the occult SDCP group showed decreased connectivity regions in the bilateral fusiform and lingual gyrus, but increased connectivity regions in the contralateral precentral and postcentral gyrus, supplementary motor area, and the ipsilateral postcentral gyrus. With the thalamus being regarded as the region of interest, the occult SDCP group showed decreased connectivity regions in the bilateral basal ganglia, cingulate, and prefrontal cortex, but increased connectivity regions in the bilateral precentral gyrus, the contralateral cerebellum, and inferior temporal gyrus. Resting-state regional brain activities and FC changes in the patients with occult SDCP exhibited a special distribution pattern, which is consistent with the pathology of the disease. Copyright © 2017. Published by Elsevier B.V.

Perifocal and remote blood-brain barrier disruption in cortical photothrombotic ischemic lesion and its modulation by the choice of anesthesia.

PubMed

Krysl, D; Deykun, K; Lambert, L; Pokorny, J; Mares, J

2012-04-01

We assessed blood-brain barrier (BBB) disruption in early stage of photothrombotic focal cerebral ischemia in the rat. We specifically looked for contralateral changes in BBB permeability and tested the influence of two anesthetics on the results. Adult Wistar rats were randomly anesthetized with pentobarbital (PB) or ketamine-xylazine (KX). Rats received intravenously (i.v.) Rose Bengal followed by Evans Blue (EB). Stereotactically defined spots on denuded skull were irradiated by laser (532 nm) for 18 min. Twenty four hours later, rats were killed, brains perfused, fixated, sectioned and slices analyzed by fluorescence microscopy. Volume of necrosis and volume of EB-albumin extravasation were calculated. Evidence of BBB breakdown in remote brain areas was sought and compared to sham handled controls. BBB disruption was consistently present, frequently with EB-albumin accumulating cells. Total lesion volume did not significantly differ among groups (TLVPB=9.4±1.3 mm³ vs. TLVKX=8.3±2.1 mm³); same was true for the volume of necrosis (NVPB=5.1±0.7 mm³ vs. NVKX=6.3±1.9 mm³). However, volume of EB-albumin extravasation area was significantly smaller in KX group (EBEVPB=4.3±0.8 mm³ vs. EBEVKX=2.0±0.5 mm³; p=0.0293). Median background EB-fluorescence signal density was higher in PB group (p<0.0001). Furthermore, regional increase in EB-fluorescence was found in two animals in PB group. Our study shows that anesthesia with NMDA-antagonist ketamine and α2-adrenergic agonist xylazine may reduce BBB breakdown in photothrombosis. Pentobarbital anesthesia lead to increased BBB permeability in the contralateral hemisphere.

In vivo detection of acute intracellular acidification in glioblastoma multiforme following a single dose of cariporide.

PubMed

Albatany, Mohammed; Li, Alex; Meakin, Susan; Bartha, Robert

2018-05-10

Glioblastoma is an aggressive brain cancer that is very difficult to treat. Clinically, it is important to be able to distinguish aggressive from non-aggressive brain tumors. Previous studies have shown that some drugs can induce a rapid change in intracellular pH that could help to identify aggressive cancer. The sodium proton exchanger (NHE1) plays a significant role in maintaining pH balance in the tumor microenvironment. Cariporide is a sodium proton exchange inhibitor that is well tolerated by humans in cardiac applications. We hypothesized that cariporide could selectively acidify brain tumors. The purpose of this study was to determine whether amine/amide concentration-independent detection (AACID) chemical exchange saturation transfer (CEST) MRI measurement of tumor pH i could detect acidification after cariporide injection. Using a 9.4T MRI scanner, CEST spectra were acquired in six mice approximately 14 days after implanting 10 5 U87 human glioblastoma multiforme cells in the brain, before and after administration of cariporide (dose: 6 mg/kg) by intraperitoneal injection. Three additional mice were studied as controls and received only vehicle injection (DMSO + PBS). Repeated measures t test was used to examine changes in tumor and contralateral tissue regions of interest. Two hours after cariporide injection, there was a significant 0.12 ± 0.03 increase in tumor AACID value corresponding to a 0.48 decrease in pH i and no change in AACID value in contralateral tissue. A small but significant increase of 0.04 ± 0.017 in tumor AACID value was also observed following vehicle injection. This study demonstrates that acute CEST MRI contrast changes, indicative of intracellular acidification, after administration of cariporide could help localize glioblastoma.

Effective Connectivity of Cortical Sensorimotor Networks During Finger Movement Tasks: A Simultaneous fNIRS, fMRI, EEG Study.

PubMed

Anwar, A R; Muthalib, M; Perrey, S; Galka, A; Granert, O; Wolff, S; Heute, U; Deuschl, G; Raethjen, J; Muthuraman, Muthuraman

2016-09-01

Recently, interest has been growing to understand the underlying dynamic directional relationship between simultaneously activated regions of the brain during motor task performance. Such directionality analysis (or effective connectivity analysis), based on non-invasive electrophysiological (electroencephalography-EEG) and hemodynamic (functional near infrared spectroscopy-fNIRS; and functional magnetic resonance imaging-fMRI) neuroimaging modalities can provide an estimate of the motor task-related information flow from one brain region to another. Since EEG, fNIRS and fMRI modalities achieve different spatial and temporal resolutions of motor-task related activation in the brain, the aim of this study was to determine the effective connectivity of cortico-cortical sensorimotor networks during finger movement tasks measured by each neuroimaging modality. Nine healthy subjects performed right hand finger movement tasks of different complexity (simple finger tapping-FT, simple finger sequence-SFS, and complex finger sequence-CFS). We focused our observations on three cortical regions of interest (ROIs), namely the contralateral sensorimotor cortex (SMC), the contralateral premotor cortex (PMC) and the contralateral dorsolateral prefrontal cortex (DLPFC). We estimated the effective connectivity between these ROIs using conditional Granger causality (GC) analysis determined from the time series signals measured by fMRI (blood oxygenation level-dependent-BOLD), fNIRS (oxygenated-O2Hb and deoxygenated-HHb hemoglobin), and EEG (scalp and source level analysis) neuroimaging modalities. The effective connectivity analysis showed significant bi-directional information flow between the SMC, PMC, and DLPFC as determined by the EEG (scalp and source), fMRI (BOLD) and fNIRS (O2Hb and HHb) modalities for all three motor tasks. However the source level EEG GC values were significantly greater than the other modalities. In addition, only the source level EEG showed a significantly greater forward than backward information flow between the ROIs. This simultaneous fMRI, fNIRS and EEG study has shown through independent GC analysis of the respective time series that a bi-directional effective connectivity occurs within a cortico-cortical sensorimotor network (SMC, PMC and DLPFC) during finger movement tasks.

Proton magnetic resonance spectroscopic findings of cerebral fat embolism induced by triolein emulsion in cats.

PubMed

Baik, S K; Kim, Y-W; Kim, H J; Lee, J W; Cho, B M; Kim, D-H; Choi, S H; Lee, S H; Chang, K H

2008-12-01

In experimental studies, embolization of the cerebral hemisphere with triolein emulsion has revealed reversible magnetic resonance imaging (MRI) findings in the subacute stage. To investigate the changes in the major metabolites, by proton magnetic resonance spectroscopy (MRS), in a cerebral fat embolism induced by a triolein emulsion. The internal carotid arteries of 19 cats were injected with a triolein emulsion, and multivoxel MRS was performed 30 min, 1 day, and 7 days later. In the control group, six cats were injected with normal saline. The MR spectra were evaluated for N-acetyl aspartate (NAA), creatine (Cr), and choline (Cho), along with the presence of lipid and lactate. Semiquantitative analyses of NAA/Cr, Cho/Cr, NAA/Cho, and lipid/Cr ratios compared the median values of the ipsilateral metabolite ratios with those of the contralateral side and in the control group for each point in time. The NAA/Cr, Cho/Cr, and NAA/Cho ratios in the ipsilateral cerebral hemisphere of the embolized group after 30 min, 1 day, and 7days were not significantly different from the contralateral hemisphere of the embolized and control groups (P>0.05). The lipid/Cr ratio in the ipsilateral cerebral hemisphere of the embolized group was significantly higher when compared with the control group (P=0.012 at 30 min, P=0.001 on day 1, and P=0.018 on day 7). Cerebral fat embolism induced by a triolein emulsion resulted in no significant change in the major metabolites of the brain in the acute stage, except for an elevated lipid/Cr ratio, which suggests the absence of any significant hypoxic-ischemic changes in the lesions embolized using a fat emulsion.

Neuropilin 2 deficiency does not affect cortical neuronal viability in response to oxygen-glucose-deprivation and transient middle cerebral artery occlusion.

PubMed

Hou, Sheng T; Jiang, Susan X; Slinn, Jacqueline; O'Hare, Michael; Karchewski, Laurie

2010-04-01

Neuropilin 2 (NRP2) is a type I transmembrane protein that binds to distinct members of the class III secreted Semaphorin subfamily. NRP2 plays important roles in repulsive axon guidance, angiogenesis and vasculogenesis through partnering with co-receptors such as vascular endothelial growth factor receptors (VEGFRs) during development. Emerging evidence also suggests that NRP2 contributes to injury response and environment changes in adult brains. In this study, we examined the contribution of NRP2 gene to cerebral ischemia-induced brain injury using NRP2 deficient mouse. To our surprise, the lack of NRP2 expression does not affect the outcome of brain injury induced by transient occlusion of the middle cerebral artery (MCAO) in mouse. The cerebral vasculature in terms of the middle cerebral artery anatomy and microvessel density in the cerebral cortex of NRP2 deficient homozygous (NRP2(-/-)) mice are normal and almost identical to those of the heterozygous (NRP2(+/-)) and wild type (NRP2(+/+)) littermates. MCAO (1h) and 24h reperfusion caused a brain infarction of 23% (compared to the contralateral side) in NRP2(-/-) mice, which is not different from those in NRP2(+/- and +/+) mice at 22 and 21%, respectively (n=19, p>0.05). Correspondingly, NRP2(-/-) mouse also showed a similar level of deterioration of neurological functions after stroke compared with their NRP2(+/- and +/+) littermates. Oxygen-glucose-deprivation (OGD) caused a significant neuronal death in NRP2(-/-) cortical neurons, at the level similar to that in NRP(+/+) cortical neurons (72% death in NRP(-/-) neurons vs. 75% death in NRP2(+/+) neurons; n=4; p>0.05). Together, these loss-of-function studies demonstrated that despite of its critical role in neuronal guidance and vascular formation during development, NRP2 expression dose not affect adult brain response to cerebral ischemia. Crown Copyright 2009. Published by Elsevier Ireland Ltd. All rights reserved.

Contralateral Dpoae Suppression in Humans at Very Low Sound Intensities

NASA Astrophysics Data System (ADS)

Janssen, T.; Gehr, D. D.; Kevanishvili, Z.

2003-02-01

Different functions are attributed to the olivo-cochlear bundle system (OCBS) such as protecting the ear from acoustic injury, improving signal detection in noise, and mediating selective attention. OCBS reflex strength can be evaluated, in animals as well as in humans, by measuring the degree of suppression of an ipsilateral DPOAE by a contralateral sound. The purpose of the study was to evaluate OCBS reflex strength depending on ipsilateral stimulus level, especially at threshold, by means of extrapolated DPOAE I/O-functions. Additionally, DPOAE was measured at near-to-threshold contralateral stimulus levels when using low-level ipsilateral stimulation for investigating possible enhancement of outer hair cell motion in the presence of low-level contralateral sound. The recording of the 2f1-f2 DPOAE in the presence or absence of contralateral sound was performed in normally hearing human subjects at f2 = 2 kHz. DPOAE I/O-functions were measured in a primary tone level range from L2 = 20 to L2 = 65 dB SPL (L1 = 0.4L2 + 39, f2/f1=1.2). Broad-band noise (BBN), narrow-band noise from 1720 to 2320 Hz (NBN), and pure tones (PT) at f2, 2f1-f2, geometric mean of f1 and f2, and 0.1oct + f2 were used for contralateral stimulation. The contralateral stimulus level (Ls) was decreased from 70 down to 10 dB SPL in 10 dB steps. DPOAE suppression was highest at the lowest primary tone level and was more pronounced for BBN and NBN than for pure tones, suggesting a more diffuse than a strong tonotopic organisation of the OCBS. The contralateral stimulus level at which significant DPOAE suppression occurred (p < 0.05) was different for the different stimuli being 20, 40, and 70 dB SPL for BBN, NBN, and pure-tone (f2), respectively. Significant DPOAE suppression to BBN and NBN occurred at Ls well below audiological middle-ear reflex threshold. DPOAE time course was different for Ls below and above middle-ear reflex threshold. Thus, middle-ear muscle contraction is suggested not to be involved in DPOAE suppression at low Ls. No enhancement of DPOAE could be found. The findings suggest the OCBS to be functioning in a more protective way than for improving signal detection in noise.

Progressive contralateral hippocampal atrophy following surgery for medically refractory temporal lobe epilepsy.

PubMed

Elliott, Cameron A; Gross, Donald W; Wheatley, B Matt; Beaulieu, Christian; Sankar, Tejas

2016-09-01

Determine the extent and time course of volumetric changes in the contralateral hippocampus following surgery for medically refractory temporal lobe epilepsy (TLE). Serial T1-weighted MRI brain scans were obtained in 26 TLE patients pre- and post-temporal lobe epilepsy surgery as well as in 12 control subjects of similar age. Patients underwent either anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH). Blinded, manual hippocampal volumetry (head, body, and tail) was performed in two groups: 1) two scan group [ATL (n=6); SAH (n=10)], imaged pre-surgery and on average at 5.4 years post-surgery; and 2) longitudinal group [ATL (n=8); SAH (n=2)] imaged pre-surgery and on post-operative day 1, 2, 3, 6, 60, 120 and a delayed time point (average 2.4 years). In the two scan group, there was atrophy by 12% of the unresected contralateral hippocampus (p<0.001), with atrophy being most pronounced (27%) in the hippocampal body (p<0.001) with no significant differences seen for the hippocampal head or tail. In the longitudinal group, significant atrophy was also observed for the whole hippocampus and the body with atrophy seen as early as post-operative day #1 which progressed significantly over the first post-operative week (1.3%/day and 3.0%./day, respectively) before stabilizing over the long-term to a 13% reduction in total volume. There was no significant difference in atrophy compared by surgical approach (ATL vs. SAH; p=0.94) or side (p=0.31); however, atrophy was significantly more pronounced in patients with ongoing post-operative seizures (hippocampal body, p=0.019; whole hippocampus, p=0.048). There were no detectable post-operative neuropsychological deficits attributable to contralateral hippocampal atrophy. Significant contralateral hippocampal atrophy occurs following TLE surgery, which begins immediately and progresses over the first post-operative week. The observation that seizure free patients had significantly less atrophy of the contralateral hippocampus after surgery suggests the possibility of an early post-operative imaging marker to predict surgical outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

On the Relationship Between Musicianship and Contralateral Suppression of Transient-Evoked Otoacoustic Emissions.

PubMed

Stuart, Andrew; Daughtrey, Emma R

2016-04-01

The medial olivocochlear (MOC) efferent reflex that modulates outer hair cell function has been shown to be more robust in musicians versus nonmusicians as evidenced in greater contralateral suppression of transient-evoked otoacoustic emissions (TEOAEs). All previous research comparing musical ability and MOC efferent strength has defined musicianship dichotomously (i.e., high-level music students or professional classical musicians versus nonmusicians). The objective of the study was to further explore contralateral suppression of TEOAEs among adults with a full spectrum of musicianship ranging from no history of musicianship to professional musicians. Musicianship was defined by both self-report and with an objective test to quantify individual differences in perceptual music skills. A single-factor between-subjects and correlational research designs were employed. Forty-five normal-hearing young adults participated. Participants completed a questionnaire concerning their music experience and completed the Brief Profile of Music Perception Skills (PROMS) to quantify perceptual musical skills across multiple musical domains (i.e., accent, melody, tempo, and tuning). TEOAEs were evaluated with 60 dB peak equivalent sound pressure level click stimuli with and without a contralateral 65 dB sound pressure level white noise suppressor. TEOAE suppression was expressed in two ways, absolute TEOAE suppression in dB and a normalized index of TEOAE suppression (i.e., percentage of suppression). Participants who considered themselves musicians scored significantly higher on all subscales and total Brief PROMS score (p < 0.05). There was no statistically significant difference between musicians and nonmusicians in absolute TEOAE suppression or percentage of TEOAE suppression (p > 0.05). There were no statistically significant correlations or linear predictive relationships between subscale or total Brief PROMS scores with absolute and percentage of TEOAE suppression (p > 0.05). The findings do not support the notion of a graded enhancement of MOC efferent suppression among adults with varied degrees of musicianship from nonmusicians to professional musicians. American Academy of Audiology.

A Linear Temporal Increase in Thrombin Activity and Loss of Its Receptor in Mouse Brain following Ischemic Stroke.

PubMed

Bushi, Doron; Stein, Efrat Shavit; Golderman, Valery; Feingold, Ekaterina; Gera, Orna; Chapman, Joab; Tanne, David

2017-01-01

Brain thrombin activity is increased following acute ischemic stroke and may play a pathogenic role through the protease-activated receptor 1 (PAR1). In order to better assess these factors, we obtained a novel detailed temporal and spatial profile of thrombin activity in a mouse model of permanent middle cerebral artery occlusion (pMCAo). Thrombin activity was measured by fluorescence spectroscopy on coronal slices taken from the ipsilateral and contralateral hemispheres 2, 5, and 24 h following pMCAo ( n  = 5, 6, 5 mice, respectively). Its spatial distribution was determined by punch samples taken from the ischemic core and penumbra and further confirmed using an enzyme histochemistry technique ( n  = 4). Levels of PAR1 were determined using western blot. Two hours following pMCAo, thrombin activity in the stroke core was already significantly higher than the contralateral area (11 ± 5 vs. 2 ± 1 mU/ml). At 5 and 24 h, thrombin activity continued to rise linearly ( r  = 0.998, p  = 0.001) and to expand in the ischemic hemisphere beyond the ischemic core reaching deleterious levels of 271 ± 117 and 123 ± 14 mU/ml (mean ± SEM) in the basal ganglia and ischemic cortex, respectively. The peak elevation of thrombin activity in the ischemic core that was confirmed by fluorescence histochemistry was in good correlation with the infarcts areas. PAR1 levels in the ischemic core decreased as stroke progressed and thrombin activity increased. In conclusion, there is a time- and space-related increase in brain thrombin activity in acute ischemic stroke that is closely related to the progression of brain damage. These results may be useful in the development of therapeutic strategies for ischemic stroke that involve the thrombin-PAR1 pathway in order to prevent secondary thrombin related brain damage.

Role of the plasma cascade systems in ischemia/reperfusion injury of bone.

PubMed

Zhang, Shengye; Wotzkow, Carlos; Bongoni, Anjan K; Shaw-Boden, Jane; Siegrist, Mark; Taddeo, Adriano; Blank, Fabian; Hofstetter, Willy; Rieben, Robert

2017-04-01

Ischemia/reperfusion (I/R) injury has been extensively studied in organs such as heart, brain, liver, kidney, and lung. As a vascularized organ, bone is known to be susceptible to I/R injury too, but the respective mechanisms are not well understood to date. We therefore hypothesized that, similar to other organs, plasma cascade-induced inflammation also plays a role in bone I/R injury. Reperfusion injury in rat tibia was induced by unilateral clamping of the femoral artery and additional use of a tourniquet, while keeping the femoral vein patent to prevent venous congestion. Rats were subjected to 4h ischemia and 24h reperfusion. Deposition of complement fragment C3b/c and fibrin as well as expression of tissue factor (TF), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), and E-selectin was detected by immunohistochemistry. In plasma, the levels of high mobility group box1 (HMGB1) were measured by ELISA. The total level of complement in serum was assessed by the CH50 test. Our results show that deposition of C3b/c was significantly increased with respect to healthy controls in cortical bone as well as in marrow of reperfused limbs. C3b/c deposition was also increased in cortical bone, but not in bone marrow, of contralateral limbs. Deposition of fibrin, as well as expression of PAI-1, was significantly increased in bone after ischemia and reperfusion, whereas expression of tPA was reduced. These differences were most prominent in vessels of bone, both in marrow and cortical bone, and both in reperfused and contralateral limbs. However, PAI-1, was only increased in vessels of reperfused cortical bone and there were no significant changes in expression of E-selectin. With respect to solid bone tissue, a significant increase of C3b/c and fibrin deposition was shown in osteocytes, and for fibrin also in the bone matrix, in both contralateral and reperfused cortical bone compared with normal healthy controls. A slight expression of TF was visible in osteocytes of the normal healthy control group, while TF was not present in the experimental groups. Moreover, CH50 values in serum decreased over time and HMGB1 was significantly increased in plasma of animals at the end of reperfusion. We conclude that ischemia and reperfusion of bone leads to activation of the complement and coagulation systems and a downregulation of the fibrinolytic cascade. In the acute phase, a vascular inflammation induced by activation of the plasma cascade systems also occurs in the bone. This is similar to I/R injury of other vascularized organs and tissues. Copyright © 2017 Elsevier Inc. All rights reserved.

Serial computed tomography and magnetic resonance imaging findings of biphasic acute hemorrhagic leukoencephalitis localized to the brain stem and cerebellum.

PubMed

Lee, Nyoung Keun; Lee, Byung Hoon; Hwang, Yoon Joon; Kim, Su Young; Lee, Ji Young; Joo, Mee

2011-04-01

Acute hemorrhagic leukoencephalitis (AHL) is a rare and usually fatal disease characterized by an acute onset of neurological abnormalities. We describe the case of a 37-year-old man with biphasic AHL with a focus on the rare involvement of the brain stem and cerebellum. Initial computed tomography (CT) and magnetic resonance imaging revealed two hemorrhagic foci in the left middle cerebellar peduncle. After 15 days multifocal hematomas in the contralateral cerebellar hemisphere were imaged using CT. The pathological diagnosis was AHL. Following high-dose steroid treatment, the patient recovered with minor neurological sequelae.

Functional Specialization in the Human Brain Estimated By Intrinsic Hemispheric Interaction

PubMed Central

Wang, Danhong; Buckner, Randy L.

2014-01-01

The human brain demonstrates functional specialization, including strong hemispheric asymmetries. Here specialization was explored using fMRI by examining the degree to which brain networks preferentially interact with ipsilateral as opposed to contralateral networks. Preferential within-hemisphere interaction was prominent in the heteromodal association cortices and minimal in the sensorimotor cortices. The frontoparietal control network exhibited strong within-hemisphere interactions but with distinct patterns in each hemisphere. The frontoparietal control network preferentially coupled to the default network and language-related regions in the left hemisphere but to attention networks in the right hemisphere. This arrangement may facilitate control of processing functions that are lateralized. Moreover, the regions most linked to asymmetric specialization also display the highest degree of evolutionary cortical expansion. Functional specialization that emphasizes processing within a hemisphere may allow the expanded hominin brain to minimize between-hemisphere connectivity and distribute domain-specific processing functions. PMID:25209275

Control of abdominal muscles by brain stem respiratory neurons in the cat

NASA Technical Reports Server (NTRS)

Miller, Alan D.; Ezure, Kazuhisa; Suzuki, Ichiro

1985-01-01

The nature of the control of abdominal muscles by the brain stem respiratory neurons was investigated in decerebrate unanesthetized cats. First, it was determined which of the brain stem respiratory neurons project to the lumbar cord (from which the abdominal muscles receive part of their innervation), by stimulating the neurons monopolarly. In a second part of the study, it was determined if lumbar-projecting respiratory neurons make monosynaptic connections with abdominal motoneurons; in these experiments, discriminate spontaneous spikes of antidromically acivated expiratory (E) neurons were used to trigger activity from both L1 and L2 nerves. A large projection was observed from E neurons in the caudal ventral respiratory group to the contralateral upper lumber cord. However, cross-correlation experiments found only two (out of 47 neuron pairs tested) strong monosynaptic connections between brain stem neurons and abdominal motoneurons.

Separating the contributions of olivocochlear and middle ear muscle reflexes in modulation of distortion product otoacoustic emission levels.

PubMed

Wolter, Nikolaus E; Harrison, Robert V; James, Adrian L

2014-01-01

Mediated by the medial olivocochlear system (MOCS), distortion product otoacoustic emission (DPOAE) levels are reduced by presentation of contralateral acoustic stimuli. Such acoustic signals can also evoke a middle ear muscle reflex (MEMR) that also attenuates recorded DPOAE levels. Our aim is to clearly differentiate these two inhibitory mechanisms and to analyze each separately, perhaps allowing the development of novel tests of hearing function. DPOAE were recorded in real time from chinchillas with normal auditory brainstem response thresholds and middle ear function. Amplitude reduction and its onset latency caused by contralateral presentation of intermittent narrow-band noise (NBN) were measured. Stapedius and tensor tympani muscle tendons were divided without disturbing the ossicular chain, and DPOAE testing was repeated. Peak reduction of (2f1 - f2) DPOAE levels occurred when the center frequency of contralateral NBN approximated the primary tone f2, indicating an f2-frequency-specific response. For a 4.5-kHz centered NBN, DPOAE (f2 = 4.4 kHz) inhibition was 0.1 dB (p < 0.001). This response remained present after tendon division, consistent with an MOCS origin. Low-frequency NBN (center frequency: 0.5 kHz) reduced otoacoustic emission levels (0.1 dB, p < 0.001) across a wide range of DPOAE frequencies. This low-frequency response was abolished by division of the middle ear muscle tendons, clearly indicating MEMR involvement. Following middle ear muscle tendon division, DPOAE inhibition by contralateral stimuli approximating the primary tone f2 persists, whereas responses evoked by lower contralateral frequencies are abolished. This distinguishes the different roles of the MOCS (f2 frequency specific) and MEMR (low frequency only) in contralateral modulation of DPOAE. This analysis helps clarify the pathways involved in an objective test that might have clinical benefit in the testing of neonates.

Contralateral suppression of aldosterone at adrenal venous sampling predicts hyperkalemia following adrenalectomy for primary aldosteronism.

PubMed

Shariq, Omair A; Bancos, Irina; Cronin, Patricia A; Farley, David R; Richards, Melanie L; Thompson, Geoffrey B; Young, William F; McKenzie, Travis J

2018-01-01

We aimed to determine whether a greater degree of contralateral suppression of aldosterone secretion at adrenal venous sampling predicted the development of postoperative hyperkalemia after unilateral adrenalectomy for primary aldosteronism. A retrospective analysis of patients undergoing unilateral adrenalectomy for primary aldosteronism between 2004-2015 was performed. Clinical and biochemical parameters of patients who developed hyperkalemia (≥5.2 mmol/L) after unilateral adreanlectomy were compared with those who remained normokalemic. The contralateral suppression index was defined as the aldosterone-to-cortisol ratio from the nondominant adrenal vein divided by the aldosterone-to-cortisol ratio from the external iliac vein. Of 192 patients who met criteria for inclusion, 12 (6.3%) developed hyperkalemia (median serum potassium 5.5 mmol/L, range 5.2-6.2 mmol/L), with a median time to onset of 13.5 days (range 7-55 days). Five patients had transiently increased serum potassium concentrations that normalized spontaneously. Four patients received mineralocorticoid replacement therapy with fludrocortisone. On univariate analysis, hyperkalemic patients had slightly greater preoperative serum creatinine levels (1.2 vs 1.0 mg/dL, P = .01), higher postoperative creatinine (1.3 vs 1.0 mg/dL, P = .02), lesser median contralateral suppression index (0.14 vs 0.27, P = .03), and larger adenomas (1.9 vs 1.4 cm, P = .02). On multivariable logistic regression, the contralateral suppression index remained the only significant predictor of postoperative hyperkalemia (P = .04) with an optimal cut-off of <0.47. Hyperkalemia after unilateral adrenalectomy for primary aldosteronism is uncommon and usually transient, but may require mineralocorticoid supplementation. Patients with a contralateral suppression index of <0.47 require meticulous follow-up and monitoring of serum potassium concentrations after unilateral adrenalectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, H; Cape Breton Cancer Centre, Sydney, NS

Purpose: To perform the comparison of dose distributions and dosevolume- histograms generated by VMAT and conventional field-in-field technique for left-sided breast and chestwall cancers; to determine whether VMAT offers more dosimetric benefits than does the field-in-field technique. Methods: All VMAT and field-in-filed plans were produced in Eclipse(version 10). Five plans were generated for left-sided breast and leftsided chestwall with supraclavicular nodes, respectively. A clockwise arc (CW) and a counter-clockwise arc (CCW) were used with start and stop angles being 310o±10o and 140o±10o. Collimator angles were 30o for CW and 330o for CCW. The conformity index (CI) is the ratio ofmore » V95% over PTV. The homogeneity index (HI) is the ratio of the difference between D2% and D98% over the prescribed dose. The V5, as an indicator of low dose bath to organs-at-risk, was used for ipsilateral lung, heart, contralateral lung, and contralateral breast. The V20, as an indicator of radiation pneumonitis, was used for ipsilateral lung. Results: Breast/chestwall VMAT delivers much higher low dose bath to ipsilateral lung, contralateral lung and contralateral breast/chestwall for both intact breast and chestwall with nodes. V5 for heart is increased in VMAT plans. V20 for ipsilateral lung is lower in VMAT plans. PTV coverage is similar for both techniques. For one particular chestwall patient with supraclavicular and internal mammary nodes, VMAT offers superior dose coverage of PTVs with slightly more low-dose-wash to heart, contralateral lung and contralateral breast. Conclusion: This study indicates that there is generally no benefit using VMAT for left-sided intact breast, due to large low-dose-bath (5Gy) to normal tissues with insignificant improvement in PTV coverage. Dosimetric benefits will be seen in VMAT plans for some chestwall patients with large size, and/or internal mammary nodes, etc. Whether a chestwall patient is treated with VMAT should be carefully analyzed on an individual basis.« less

Effect of the chest wall on the measurement of hemoglobin concentrations by near-infrared time-resolved spectroscopy in normal breast and cancer.

PubMed

Yoshizawa, Nobuko; Ueda, Yukio; Nasu, Hatsuko; Ogura, Hiroyuki; Ohmae, Etsuko; Yoshimoto, Kenji; Takehara, Yasuo; Yamashita, Yutaka; Sakahara, Harumi

2016-11-01

Optical imaging and spectroscopy using near-infrared light have great potential in the assessment of tumor vasculature. We previously measured hemoglobin concentrations in breast cancer using a near-infrared time-resolved spectroscopy system. The purpose of the present study was to evaluate the effect of the chest wall on the measurement of hemoglobin concentrations in normal breast tissue and cancer. We measured total hemoglobin (tHb) concentration in both cancer and contralateral normal breast using a near-infrared time-resolved spectroscopy system in 24 female patients with breast cancer. Patients were divided into two groups based on menopausal state. The skin-to-chest wall distance was determined using ultrasound images obtained with an ultrasound probe attached to the spectroscopy probe. The apparent tHb concentration of normal breast increased when the skin-to-chest wall distance was less than 20 mm. The tHb concentration in pre-menopausal patients was higher than that in post-menopausal patients. Although the concentration of tHb in cancer tissue was statistically higher than that in normal breast, the contralateral normal breast showed higher tHb concentration than cancer in 9 of 46 datasets. When the curves of tHb concentrations as a function of the skin-to-chest wall distance in normal breast were applied for pre- and post-menopausal patients separately, all the cancer lesions plotted above the curves. The skin-to-chest wall distance affected the measurement of tHb concentration of breast tissue by near-infrared time-resolved spectroscopy. The tHb concentration of breast cancer tissue was more precisely evaluated by considering the skin-to-chest wall distance.

Striatal infarction in the rat causes a transient reduction of tyrosine hydroxylase immunoreactivity in the ipsilateral substantia nigra.

PubMed

Soriano, M A; Justicia, C; Ferrer, I; Rodríguez-Farré, E; Planas, A M

1997-01-01

Dopaminergic neurons of the substantia nigra pars compacta were examined in the rat brain following striatal infarction subsequent to transient focal cerebral ischemia. Rats had the middle cerebral artery occluded for 2 h or were sham-operated, and tyrosine hydroxylase immunoreactivity was evaluated by Western blot and immunohistochemistry at different times ranging from 1 to 60 days after ischemia. The number of tyrosine hydroxylase-immunoreactive cells in the substantia nigra pars compacta was counted under the light microscope and compared to that in the contralateral side and controls. No changes of tyrosine hydroxylase immunoreactivity were detected in the ipsilateral versus the contralateral substantia nigra of sham-operated rats or 1 day after ischemia. However, a statistically significant reduction of tyrosine hydroxylase-immunoreactive cells became apparent in the ipsilateral compared with the contralateral substantia nigra at 7 and 14 days after ischemia. This reduction showed a clear recovery at 30 days after ischemia, and no signs of difference between the ipsilateral and the contralateral side were apparent by 60 days. Therefore, the reduction of tyrosine hydroxylase immunoreactivity in the ipsilateral substantia nigra was only transiently seen from 1 to 2 weeks following ischemia. The observed loss of tyrosine hydroxylase was not accompanied by signs of cell death or gliosis in the ipsilateral pars compacta. The present results show a transitory reduction of tyrosine hydroxylase immunoreactivity in the ipsilateral substantia nigra pars compacta after focal ischemia and suggest that striatal infarction causes a transient deficit of dopaminergic function.

Single-unit labeling of medial olivocochlear neurons: the cochlear frequency map for efferent axons.

PubMed

Brown, M Christian

2014-06-01

Medial olivocochlear (MOC) neurons are efferent neurons that project axons from the brain to the cochlea. Their action on outer hair cells reduces the gain of the "cochlear amplifier," which shifts the dynamic range of hearing and reduces the effects of noise masking. The MOC effects in one ear can be elicited by sound in that ipsilateral ear or by sound in the contralateral ear. To study how MOC neurons project onto the cochlea to mediate these effects, single-unit labeling in guinea pigs was used to study the mapping of MOC neurons for neurons responsive to ipsilateral sound vs. those responsive to contralateral sound. MOC neurons were sharply tuned to sound frequency with a well-defined characteristic frequency (CF). However, their labeled termination spans in the organ of Corti ranged from narrow to broad, innervating between 14 and 69 outer hair cells per axon in a "patchy" pattern. For units responsive to ipsilateral sound, the midpoint of innervation was mapped according to CF in a relationship generally similar to, but with more variability than, that of auditory-nerve fibers. Thus, based on CF mappings, most of the MOC terminations miss outer hair cells involved in the cochlear amplifier for their CF, which are located more basally. Compared with ipsilaterally responsive neurons, contralaterally responsive neurons had an apical offset in termination and a larger span of innervation (an average of 10.41% cochlear distance), suggesting that when contralateral sound activates the MOC reflex, the actions are different than those for ipsilateral sound. Copyright © 2014 the American Physiological Society.

Single-unit labeling of medial olivocochlear neurons: the cochlear frequency map for efferent axons

PubMed Central

2014-01-01

Medial olivocochlear (MOC) neurons are efferent neurons that project axons from the brain to the cochlea. Their action on outer hair cells reduces the gain of the “cochlear amplifier,” which shifts the dynamic range of hearing and reduces the effects of noise masking. The MOC effects in one ear can be elicited by sound in that ipsilateral ear or by sound in the contralateral ear. To study how MOC neurons project onto the cochlea to mediate these effects, single-unit labeling in guinea pigs was used to study the mapping of MOC neurons for neurons responsive to ipsilateral sound vs. those responsive to contralateral sound. MOC neurons were sharply tuned to sound frequency with a well-defined characteristic frequency (CF). However, their labeled termination spans in the organ of Corti ranged from narrow to broad, innervating between 14 and 69 outer hair cells per axon in a “patchy” pattern. For units responsive to ipsilateral sound, the midpoint of innervation was mapped according to CF in a relationship generally similar to, but with more variability than, that of auditory-nerve fibers. Thus, based on CF mappings, most of the MOC terminations miss outer hair cells involved in the cochlear amplifier for their CF, which are located more basally. Compared with ipsilaterally responsive neurons, contralaterally responsive neurons had an apical offset in termination and a larger span of innervation (an average of 10.41% cochlear distance), suggesting that when contralateral sound activates the MOC reflex, the actions are different than those for ipsilateral sound. PMID:24598524

Proteomic analysis of trans-hemispheric motor cortex reorganization following contralateral C7 nerve transfer

PubMed Central

Yuan, Yin; Xu, Xiu-yue; Lao, Jie; Zhao, Xin

2018-01-01

Nerve transfer is the most common treatment for total brachial plexus avulsion injury. After nerve transfer, the movement of the injured limb may be activated by certain movements of the healthy limb at the early stage of recovery, i.e., trans-hemispheric reorganization. Previous studies have focused on functional magnetic resonance imaging and changes in brain-derived neurotrophic factor and growth associated protein 43, but there have been no proteomics studies. In this study, we designed a rat model of total brachial plexus avulsion injury involving contralateral C7 nerve transfer. Isobaric tags for relative and absolute quantitation and western blot assay were then used to screen differentially expressed proteins in bilateral motor cortices. We found that most differentially expressed proteins in both cortices of upper limb were associated with nervous system development and function (including neuron differentiation and development, axonogenesis, and guidance), microtubule and cytoskeleton organization, synapse plasticity, and transmission of nerve impulses. Two key differentially expressed proteins, neurofilament light (NFL) and Thy-1, were identified. In contralateral cortex, the NFL level was upregulated 2 weeks after transfer and downregulated at 1 and 5 months. The Thy-1 level was upregulated from 1 to 5 months. In the affected cortex, the NFL level increased gradually from 1 to 5 months. Western blot results of key differentially expressed proteins were consistent with the proteomic findings. These results indicate that NFL and Thy-1 play an important role in trans-hemispheric organization following total brachial plexus root avulsion and contralateral C7 nerve transfer. PMID:29557385

Chronic hyperperfusion and angiogenesis follow subacute hypoperfusion in the thalamus of rats with focal cerebral ischemia

PubMed Central

Hayward, Nick MEA; Yanev, Pavel; Haapasalo, Annakaisa; Miettinen, Riitta; Hiltunen, Mikko; Gröhn, Olli; Jolkkonen, Jukka

2011-01-01

Cerebral blood flow (CBF) is disrupted after focal ischemia in rats. We examined long-term hemodynamic and cerebrovascular changes in the rat thalamus after focal cerebral ischemia. Cerebral blood flow quantified by arterial spin labeling magnetic resonance imaging was decreased in the ipsilateral and contralateral thalamus 2 days after cerebral ischemia. Partial thalamic CBF recovery occurred by day 7, then the ipsilateral thalamus was chronically hyperperfused at 30 days and 3 months compared with its contralateral side. This contrasted with permanent hypoperfusion in the ipsilateral cortex. Angiogenesis was indicated by endothelial cell (RECA-1) immunohistochemistry that showed increased blood vessel branching in the ipsilateral thalamus at the end of the 3-month follow-up. Only transient thalamic IgG extravasation was observed, indicating that the blood–brain barrier was intact after day 2. Angiogenesis was preceded by transiently altered expression levels of cadherin family adhesion molecules, cadherin-7, protocadherin-1, and protocadherin-17. In conclusion, thalamic pathology after focal cerebral ischemia involved long-term hemodynamic changes and angiogenesis preceded by altered expression of vascular adhesion factors. Postischemic angiogenesis in the thalamus represents a novel type of remote plasticity, which may support removal of necrotic brain tissue and aid functional recovery. PMID:21081957

High femoral artery bifurcation predicts contralateral high bifurcation: implications for complex percutaneous cardiovascular procedures requiring large caliber and/or dual access.

PubMed

Gupta, Vipul; Feng, Kent; Cheruvu, Pavan; Boyer, Nathan; Yeghiazarians, Yerem; Ports, Thomas A; Zimmet, Jeffrey; Shunk, Kendrick; Boyle, Andrew J

2014-09-01

Recent advances in technology have led to an increase in the use of bilateral femoral artery access and the requirement for large-bore access. Optimal access is in the common femoral artery (CFA), rather than higher (in the external iliac artery) or lower (in one of the branches of the CFA). However, there is a paucity of data in the literature about the relationship between bifurcation level of one CFA and the contralateral CFA. To define the prevalence of high bifurcation of the CFA and the relationship between bifurcation level on both sides, we performed a retrospective analysis of all patients with bilateral femoral angiography. From 4880 femoral angiograms performed at UCSF cardiac catheterization laboratory between 2005-2013, a total of 273 patients had bilateral femoral angiograms. The prevalence of low/normal, high, and very-high femoral bifurcations was 70%, 26%, and 4%, respectively, with no difference between sides. A high or very-high bifurcation significantly increased the likelihood of a high bifurcation on the contralateral side (odds ratio >3.0). Multivariable logistic regression analysis revealed age, gender, self-reported race, height, weight, and body mass index were not predictive of high or very-high bifurcations on either side. In conclusion, high femoral artery bifurcations are common and increase the likelihood of a high bifurcation of the contralateral femoral artery.

Features of the Retinotopic Representation in the Visual Wulst of a Laterally Eyed Bird, the Zebra Finch (Taeniopygia guttata)

PubMed Central

Michael, Neethu; Löwel, Siegrid; Bischof, Hans-Joachim

2015-01-01

The visual wulst of the zebra finch comprises at least two retinotopic maps of the contralateral eye. As yet, it is not known how much of the visual field is represented in the wulst neuronal maps, how the organization of the maps is related to the retinal architecture, and how information from the ipsilateral eye is involved in the activation of the wulst. Here, we have used autofluorescent flavoprotein imaging and classical anatomical methods to investigate such characteristics of the most posterior map of the multiple retinotopic representations. We found that the visual wulst can be activated by visual stimuli from a large part of the visual field of the contralateral eye. Horizontally, the visual field representation extended from -5° beyond the beak tip up to +125° laterally. Vertically, a small strip from -10° below to about +25° above the horizon activated the visual wulst. Although retinal ganglion cells had a much higher density around the fovea and along a strip extending from the fovea towards the beak tip, these areas were not overrepresented in the wulst map. The wulst area activated from the foveal region of the ipsilateral eye, overlapped substantially with the middle of the three contralaterally activated regions in the visual wulst, and partially with the other two. Visual wulst activity evoked by stimulation of the frontal visual field was stronger with contralateral than with binocular stimulation. This confirms earlier electrophysiological studies indicating an inhibitory influence of the activation of the ipsilateral eye on wulst activity elicited by stimulating the contralateral eye. The lack of a foveal overrepresentation suggests that identification of objects may not be the primary task of the zebra finch visual wulst. Instead, this brain area may be involved in the processing of visual information necessary for spatial orientation. PMID:25853253

[Human umbilical cord blood mononuclear cell transplantation promotes long-term neurobehavioral functional development of newborn SD rats with hypoxic ischemic brain injury].

PubMed

Huang, Hui-zhi; Wen, Xiao-hong; Liu, Hui; Huang, Jin-hua; Liu, Shang-quan; Ren, Wei-hua; Fang, Wen-xiang; Qian, Yin-feng; Hou, Wei-zhu; Yan, Ming-jie; Yao, You-heng; Li, Wei-Zu; Li, Qian-Jin

2013-06-01

To explore the effect of human umbilical cord blood mononuclear cells (UCBMC) promoting nerve behavior function and brain tissue recovery of neonatal SD rat with hypoxic ischemic brain injury (HIBI). A modified newborn rat model that had a combined hypoxic and ischemic brain injury as described by Rice-Vannucci was used, early nervous reflex, the Morris water maze and walking track analysis were used to evaluate nervous behavioral function, and brain MRI, HE staining to evaluate brain damage recovery. Newborn rat Rice-Vannucci model showed significant brain atrophy, obvious hemiplegia of contralateral limbs,e.g right step length [(7.67 ± 0.46) cm vs. (8.22 ± 0.50) cm, F = 1.494] and toe distance [(0.93 ± 0.06) cm vs. (1.12 ± 0.55) cm, F = 0.186] were significantly reduced compared with left side, learning and memory ability was significantly impaired compared with normal control group (P < 0.01); Cliff aversion [(8.44 ± 2.38) s vs.(14.22 ± 5.07) s, t = 4.618] and negative geotaxis reflex time [(7.26 ± 2.00) s vs. (11.76 ± 3.73) s, t = 4.755] on postnatal 14 days of HIBI+ transplantation group were significantly reduced compared with HIBI+NaCl group (P < 0.01) ; the Morris water maze experiment showed escape latency [ (23.11 ± 6.64) s vs. (34.04 ± 12.95) s, t = 3.356] and swimming distance [ (9.12 ± 1.21) cm vs.(12.70 ± 1.53) cm, t = 17.095] of HIBI+transplantation group were significantly reduced compared with those of HIBI+NaCl group (P < 0.01) ; the residual brain volume on postnatal 10 d [ (75.37 ± 4.53)% vs. (67.17 ± 4.08)%, t = -6.017] and 67 d [ (69.05 ± 3.58)% vs.(60.83 ± 3.69)%, t = -7.148]of HIBI+ transplantation group were significantly larger than those of HIBI+NaCl group (P < 0.01); After human UCBMC transplantation, left cortical edema significantly reduced and nerve cell necrosis of HIBI+ transplantation group is not obvious compared with HIBI+NaCl group. Human UCBMC intraperitoneal transplantation significantly promoted recovery of injured brain cells and neurobehavioral function development.

Hop Distance Symmetry Does Not Indicate Normal Landing Biomechanics in Adolescent Athletes With Recent Anterior Cruciate Ligament Reconstruction.

PubMed

Wren, Tishya A L; Mueske, Nicole M; Brophy, Christopher H; Pace, J Lee; Katzel, Mia J; Edison, Bianca R; VandenBerg, Curtis D; Zaslow, Tracy L

2018-03-30

Study Design Retrospective cohort. Background Return to sport (RTS) protocols after anterior cruciate ligament reconstruction (ACLR) often include assessment of hop distance symmetry. However, it is unclear if movement deficits are present regardless of hop symmetry. Objectives To assess biomechanics and symmetry of adolescent athletes following ACLR during a single leg hop for distance. Methods Forty-six patients with ACLR (5-12 months post-surgery; 27 female; age 15.6, SD 1.7 years) were classified as asymmetric (operative limb hop distance <90% of non-operative limb; n=17) or symmetric (n=29). Lower extremity biomechanics were compared among operative and contralateral limbs and 24 symmetric controls (12 female; age 14.7, SD 1.5 years) using ANOVA. Results Compared to controls, asymmetric patients hopped a shorter distance on their operative limb (P<0.001), while symmetric patients hopped an intermediate distance on both sides (P≥0.12). During landing, operative limbs, regardless of hop distance, exhibited lower knee flexion moments compared to controls and the contralateral side (P≤0.04) with lower knee energy absorption than the contralateral side (P≤0.006). During take-off, both symmetric and asymmetric patients had less hip extension and smaller ankle range of motion on the operative side compared with controls (P≤0.05). Asymmetric patients also had lower hip range of motion on the operative, compared with the contralateral, side (P=0.001). Conclusion Both symmetric and asymmetric patients offloaded the operative knee; symmetric patients achieved symmetry in part by hopping a shorter distance on the contralateral side. Therefore, hop distance symmetry may not be an adequate test of single limb function and RTS readiness. Level of Evidence 2b. J Orthop Sports Phys Ther, Epub 30 Mar 2018. doi:10.2519/jospt.2018.7817.

Using motor behavior during an early critical period to restore skilled limb movement after damage to the corticospinal motor system during development

PubMed Central

Friel, KM; Chakrabarty, S; H-C, Kuo; Martin, JH

2012-01-01

This study investigated requirements for restoring motor function after corticospinal (CS) system damage during early postnatal development. Activity-dependent competition between the CS tracts (CST) of the two hemispheres is imperative for normal development. Blocking primary motor cortex (M1) activity unilaterally during a critical period (postnatal weeks-PW-5–7) produces permanent contralateral motor skill impairments, loss of M1 motor map, aberrant CS terminations, and decreases in CST presynaptic sites and spinal cholinergic interneuron numbers. To repair these motor systems impairments and restore function, we manipulated motor experience in three groups of cats after this CST injury produced by inactivation. One group wore a jacket restraining the limb ipsilateral to inactivation, forcing use of the contralateral, impaired, limb, for the month following M1 inactivation (PW8–13; “Restraint Alone”). A second group wore the restraint during PW8–13, and was also trained for 1 h/day in a reaching task with the contralateral forelimb (“Early Training”). To test the efficacy of intervention during adolescence, a third group wore the restraint and received reach training during PW20–24 (“Delayed Training”). Early training restored CST connections and the M1 motor map; increased cholinergic spinal interneurons numbers on the contralateral, relative to ipsilateral, side; and abrogated limb control impairments. Delayed training restored CST connectivity and the M1 motor map, but not contralateral spinal cholinergic cell counts or motor performance. Restraint alone only restored CST connectivity. Our findings stress the need to reestablish the integrated functions of the CS system at multiple hierarchical levels in restoring skilled motor function after developmental injury. PMID:22764234

Evaluation of contralateral kidney, liver and lung after extracorporeal shock wave lithotripsy in rabbits.

PubMed

Senyucel, M F; Boybeyi, O; Ayva, S; Aslan, M K; Soyer, T; Demet, A I; Kısa, U; Basar, M; Cakmak, M A

2013-10-01

An experimental study was carried out to evaluate the effects of extracorporeal shock wave lithotripsy (ESWL) on contralateral kidney, liver and lung by histopathological and biochemical methods. Twelve New Zealand rabbits were allocated to two groups (n = 6). Tissues of control group (CG, n = 6) were harvested without any intervention. In ESWL group (EG), right kidneys were exposed to 3,000 shock waves at 14 kV energy using electro-hydraulic type ESWL device three times every other day. Both kidneys, liver, and right lobe of lung tissues in EG were harvested on seventh day. Kidneys were examined histopathologically for presence of glomerular and tubular injury, interstitial edema, congestion, inflammation and fibrosis. Livers were examined for hepatocyte vacuolization, congestion, portal inflammation and fibrosis. Lung tissues were examined for loss of normal structure, emphysema, interstitial congestion-edema, prominent alveolar septal vessels, interstitial inflammation, intra-alveolar hemorrhage, intraluminal hemorrhage, peribronchial edema, congestion, inflammation in bronchial wall and epithelial desquamation. Biochemical analysis of tissue samples was performed for oxidative injury markers. Histopathological evaluations revealed that tubular injury was found in both shocked and contralateral kidneys (p < 0.05). EG showed higher grades of portal fibrosis in liver and higher grades of peribronchial congestion in lung when compared to CG (p < 0.05). Biochemical evaluations of both kidneys showed that malondialdehyde levels were higher in EG than in CG (p < 0.05). ESWL causes histopathologic alterations both in shocked and contralateral kidneys. Extrarenal tissues such as liver and lung can be affected by shock waves histopathologically and oxidative injury of contralateral kidney may occur acutely after ESWL.

Short-duration stimulation of the supplementary eye fields perturbs anti-saccade performance while potentiating contralateral head orienting.

PubMed

Chapman, Brendan B; Corneil, Brian D

2014-01-01

Many forms of brain stimulation utilize the notion of state dependency, whereby greater influences are observed when a given area is more engaged at the time of stimulation. Here, by delivering intracortical microstimulation (ICMS) to the supplementary eye fields (SEF) of monkeys performing interleaved pro- and anti-saccades, we show a surprising diversity of state-dependent effects of ICMS-SEF. Short-duration ICMS-SEF passed around cue presentation selectively disrupted anti-saccades by increasing reaction times and error rates bilaterally, and also recruited neck muscles, favoring contralateral head turning to a greater degree on anti-saccade trials. These results are consistent with the functional relevance of the SEF for anti-saccades. The multiplicity of stimulation-evoked effects, with ICMS-SEF simultaneously disrupting anti-saccade performance and facilitating contralateral head orienting, probably reflects both the diversity of cortical and subcortical targets of SEF projections, and the response of this oculomotor network to stimulation. We speculate that the bilateral disruption of anti-saccades arises via feedback loops that may include the thalamus, whereas neck muscle recruitment arises via feedforward polysynaptic pathways to the motor periphery. Consideration of both sets of results reveals a more complete picture of the highly complex and multiphasic response to ICMS-SEF that can play out differently in different effector systems.

Mechanism of Kinect-based virtual reality training for motor functional recovery of upper limbs after subacute stroke.

PubMed

Bao, Xiao; Mao, Yurong; Lin, Qiang; Qiu, Yunhai; Chen, Shaozhen; Li, Le; Cates, Ryan S; Zhou, Shufeng; Huang, Dongfeng

2013-11-05

The Kinect-based virtual reality system for the Xbox 360 enables users to control and interact with the game console without the need to touch a game controller, and provides rehabilitation training for stroke patients with lower limb dysfunctions. However, the underlying mechanism remains unclear. In this study, 18 healthy subjects and five patients after subacute stroke were included. The five patients were scanned using functional MRI prior to training, 3 weeks after training and at a 12-week follow-up, and then compared with healthy subjects. The Fugl-Meyer Assessment and Wolf Motor Function Test scores of the hemiplegic upper limbs of stroke patients were significantly increased 3 weeks after training and at the 12-week follow-up. Functional MRI results showed that contralateral primary sensorimotor cortex was activated after Kinect-based virtual reality training in the stroke patients compared with the healthy subjects. Contralateral primary sensorimotor cortex, the bilateral supplementary motor area and the ipsilateral cerebellum were also activated during hand-clenching in all 18 healthy subjects. Our findings indicate that Kinect-based virtual reality training could promote the recovery of upper limb motor function in subacute stroke patients, and brain reorganization by Kinect-based virtual reality training may be linked to the contralateral sensorimotor cortex.

Mechanism of Kinect-based virtual reality training for motor functional recovery of upper limbs after subacute stroke

PubMed Central

Bao, Xiao; Mao, Yurong; Lin, Qiang; Qiu, Yunhai; Chen, Shaozhen; Li, Le; Cates, Ryan S.; Zhou, Shufeng; Huang, Dongfeng

2013-01-01

The Kinect-based virtual reality system for the Xbox 360 enables users to control and interact with the game console without the need to touch a game controller, and provides rehabilitation training for stroke patients with lower limb dysfunctions. However, the underlying mechanism remains unclear. In this study, 18 healthy subjects and five patients after subacute stroke were included. The five patients were scanned using functional MRI prior to training, 3 weeks after training and at a 12-week follow-up, and then compared with healthy subjects. The Fugl-Meyer Assessment and Wolf Motor Function Test scores of the hemiplegic upper limbs of stroke patients were significantly increased 3 weeks after training and at the 12-week follow-up. Functional MRI results showed that contralateral primary sensorimotor cortex was activated after Kinect-based virtual reality training in the stroke patients compared with the healthy subjects. Contralateral primary sensorimotor cortex, the bilateral supplementary motor area and the ipsilateral cerebellum were also activated during hand-clenching in all 18 healthy subjects. Our findings indicate that Kinect-based virtual reality training could promote the recovery of upper limb motor function in subacute stroke patients, and brain reorganization by Kinect-based virtual reality training may be linked to the contralateral sensorimotor cortex. PMID:25206611

Forelimb training drives transient map reorganization in ipsilateral motor cortex

PubMed Central

Pruitt, David T.; Schmid, Ariel N.; Danaphongse, Tanya T.; Flanagan, Kate E.; Morrison, Robert A.; Kilgard, Michael P.; Rennaker, Robert L.; Hays, Seth A.

2016-01-01

Skilled motor training results in reorganization of contralateral motor cortex movement representations. The ipsilateral motor cortex is believed to play a role in skilled motor control, but little is known about how training influences reorganization of ipsilateral motor representations of the trained limb. To determine whether training results in reorganization of ipsilateral motor cortex maps, rats were trained to perform the isometric pull task, an automated motor task that requires skilled forelimb use. After either 3 or 6 months of training, intracortical microstimulation (ICMS) mapping was performed to document motor representations of the trained forelimb in the hemisphere ipsilateral to that limb. Motor training for 3 months resulted in a robust expansion of right forelimb representation in the right motor cortex, demonstrating that skilled motor training drives map plasticity ipsilateral to the trained limb. After 6 months of training, the right forelimb representation in the right motor cortex was significantly smaller than the representation observed in rats trained for 3 months and similar to untrained controls, consistent with a normalization of motor cortex maps. Forelimb map area was not correlated with performance on the trained task, suggesting that task performance is maintained despite normalization of cortical maps. This study provides new insights into how the ipsilateral cortex changes in response to skilled learning and may inform rehabilitative strategies to enhance cortical plasticity to support recovery after brain injury. PMID:27392641

Forelimb training drives transient map reorganization in ipsilateral motor cortex.

PubMed

Pruitt, David T; Schmid, Ariel N; Danaphongse, Tanya T; Flanagan, Kate E; Morrison, Robert A; Kilgard, Michael P; Rennaker, Robert L; Hays, Seth A

2016-10-15

Skilled motor training results in reorganization of contralateral motor cortex movement representations. The ipsilateral motor cortex is believed to play a role in skilled motor control, but little is known about how training influences reorganization of ipsilateral motor representations of the trained limb. To determine whether training results in reorganization of ipsilateral motor cortex maps, rats were trained to perform the isometric pull task, an automated motor task that requires skilled forelimb use. After either 3 or 6 months of training, intracortical microstimulation (ICMS) mapping was performed to document motor representations of the trained forelimb in the hemisphere ipsilateral to that limb. Motor training for 3 months resulted in a robust expansion of right forelimb representation in the right motor cortex, demonstrating that skilled motor training drives map plasticity ipsilateral to the trained limb. After 6 months of training, the right forelimb representation in the right motor cortex was significantly smaller than the representation observed in rats trained for 3 months and similar to untrained controls, consistent with a normalization of motor cortex maps. Forelimb map area was not correlated with performance on the trained task, suggesting that task performance is maintained despite normalization of cortical maps. This study provides new insights into how the ipsilateral cortex changes in response to skilled learning and may inform rehabilitative strategies to enhance cortical plasticity to support recovery after brain injury. Copyright © 2016 Elsevier B.V. All rights reserved.

BDNF is required for taste axon regeneration following unilateral chorda tympani nerve section.

PubMed

Meng, Lingbin; Huang, Tao; Sun, Chengsan; Hill, David L; Krimm, Robin

2017-07-01

Taste nerves readily regenerate to reinnervate denervated taste buds; however, factors required for regeneration have not yet been identified. When the chorda tympani nerve is sectioned, expression of brain-derived neurotrophic factor (BDNF) remains high in the geniculate ganglion and lingual epithelium, despite the loss of taste buds. These observations suggest that BDNF is present in the taste system after nerve section and may support taste nerve regeneration. To test this hypothesis, we inducibly deleted Bdnf during adulthood in mice. Shortly after Bdnf gene recombination, the chorda tympani nerve was unilaterally sectioned causing a loss of both taste buds and neurons, irrespective of BDNF levels. Eight weeks after nerve section, however, regeneration was differentially affected by Bdnf deletion. In control mice, there was regeneration of the chorda tympani nerve and taste buds reappeared with innervation. In contrast, few taste buds were reinnervated in mice lacking normal Bdnf expression such that taste bud number remained low. In all genotypes, taste buds that were reinnervated were normal-sized, but non-innervated taste buds remained small and atrophic. On the side of the tongue contralateral to the nerve section, taste buds for some genotypes became larger and all taste buds remained innervated. Our findings suggest that BDNF is required for nerve regeneration following gustatory nerve section. Copyright © 2017 Elsevier Inc. All rights reserved.

Contralateral cortical organisation of information in visual short-term memory: evidence from lateralized brain activity during retrieval.

PubMed

Fortier-Gauthier, Ulysse; Moffat, Nicolas; Dell'Acqua, Roberto; McDonald, John J; Jolicœur, Pierre

2012-07-01

We studied brain activity during retention and retrieval phases of two visual short-term memory (VSTM) experiments. Experiment 1 used a balanced memory array, with one color stimulus in each hemifield, followed by a retention interval and a central probe, at the fixation point that designated the target stimulus in memory about which to make a determination of orientation. Retrieval of information from VSTM was associated with an event-related lateralization (ERL) with a contralateral negativity relative to the visual field from which the probed stimulus was originally encoded, suggesting a lateralized organization of VSTM. The scalp distribution of the retrieval ERL was more anterior than what is usually associated with simple maintenance activity, which is consistent with the involvement of different brain structures for these distinct visual memory mechanisms. Experiment 2 was like Experiment 1, but used an unbalanced memory array consisting of one lateral color stimulus in a hemifield and one color stimulus on the vertical mid-line. This design enabled us to separate lateralized activity related to target retrieval from distractor processing. Target retrieval was found to generate a negative-going ERL at electrode sites found in Experiment 1, and suggested representations were retrieved from anterior cortical structures. Distractor processing elicited a positive-going ERL at posterior electrodes sites, which could be indicative of a return to baseline of retention activity for the discarded memory of the now-irrelevant stimulus, or an active inhibition mechanism mediating distractor suppression. Copyright © 2012 Elsevier Ltd. All rights reserved.

Systematization and description of the internal carotid arteries and their main ramifications at the brain base in turtles (Trachemys scripta elegans).

PubMed

Voll, Juliana; Campos, Rui

2016-08-01

Thirty turtle brains (Trachemys scripta elegans) were injected with latex to systematize and describe the internal carotid arteries and their main ramifications at the brain base. The internal carotid arteries had one intercarotid anastomosis. At the level of the tuber cinereum, the internal carotid artery bifurcated into its terminal branches, the rostral and the caudal branches. The rostral branch emitted the rostral choroid artery, the orbital artery, and a series of middle cerebral arteries. After giving off the last middle cerebral artery, the rostral branch continued as the rostral cerebral artery in the cerebral longitudinal fissure, and had one anastomosis with its contralateral homologous artery, the rostral communicating artery, making the first rostral closure of the cerebral arterial circle. Next, the rostral cerebral arteries anastomosed forming a rostral interhemispheric artery, making the second rostral closure of the cerebral arterial circle. The internal carotid artery, after emitting its rostral branch, continued caudally as the caudal branch. The caudal branch ran caudally along the ventral surface of the mesencephalic tegmentum, emitted the caudal cerebral artery and the mesencephalic artery, and continued caudomedially while progressively narrowing, and anastomosed with its contralateral homologous artery, forming the basilar artery. The narrower portion also emitted the trigeminal artery. The anastomosis of the caudal branches closed the cerebral arterial circle caudally. The internal carotid arteries exclusively supplied the cerebral arterial circle of the turtle. Anat Rec, 299:1090-1098, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Functional connectivity evidence of cortico-cortico inhibition in temporal lobe epilepsy.

PubMed

Tracy, Joseph I; Osipowicz, Karol; Spechler, Philip; Sharan, Ashwini; Skidmore, Christopher; Doucet, Gaelle; Sperling, Michael R

2014-01-01

Epileptic seizures can initiate a neural circuit and lead to aberrant neural communication with brain areas outside the epileptogenic region. We focus on interictal activity in focal temporal lobe epilepsy and evaluate functional connectivity (FC) differences that emerge as function of bilateral versus strictly unilateral epileptiform activity. We assess the strength of FC at rest between the ictal and non-ictal temporal lobes, in addition to whole brain connectivity with the ictal temporal lobe. Results revealed strong connectivity between the temporal lobes for both patient groups, but this did not vary as a function of unilateral versus bilateral interictal status. Both the left and right unilateral temporal lobe groups showed significant anti-correlated activity in regions outside the epileptogenic temporal lobe, primarily involving the contralateral (non-ictal/non-pathologic) hemisphere, with precuneus involvement prominent. The bilateral groups did not show this contralateral anti-correlated activity. This anti-correlated connectivity may represent a form of protective and adaptive inhibition, helping to constrain epileptiform activity to the pathologic temporal lobe. The absence of this activity in the bilateral groups may be indicative of flawed inhibitory mechanisms, helping to explain their more widespread epileptiform activity. Our data suggest that the location and build up of epilepsy networks in the brain are not truly random, and are not limited to the formation of strictly epileptogenic networks. Functional networks may develop to take advantage of the regulatory function of structures such as the precuneus to instantiate an anti-correlated network, generating protective cortico-cortico inhibition for the purpose of limiting seizure spread or epileptogenesis. Copyright © 2012 Wiley Periodicals, Inc.

Functional Connectivity Evidence of Cortico-Cortico Inhibition in Temporal Lobe Epilepsy

PubMed Central

Tracy, Joseph I.; Osipowicz, Karol; Spechler, Philip; Sharan, Ashwini; Skidmore, Christopher; Doucet, Gaelle; Sperling, Michael R.

2012-01-01

Epileptic seizures can initiate a neural circuit and lead to aberrant neural communication with brain areas outside the epileptogenic region. We focus on interictal activity in focal temporal lobe epilepsy and evaluate functional connectivity differences that emerge as function of bilateral versus strictly unilateral epileptiform activity. We assess the strength of functional connectivity at rest between the ictal and non-ictal temporal lobes, in addition to whole brain connectivity with the ictal temporal lobe. Results revealed strong connectivity between the temporal lobes for both patient groups, but this did not vary as a function of unilateral versus bilateral interictal status. Both the left and right unilateral temporal lobe groups showed significant anti-correlated activity in regions outside the epileptogenic temporal lobe, primarily involving the contralateral (non-ictal/non-pathologic) hemisphere, with precuneus involvement prominent. The bilateral groups did not show this contralateral anti-correlated activity. This anti-correlated connectivity may represent a form of protective and adaptive inhibition, helping to constrain epileptiform activity to the pathologic temporal lobe. The absence of this activity in the bilateral groups may be indicative of flawed inhibitory mechanisms, helping to explain their more widespread epileptiform activity. Our data suggest that the location and build up of epilepsy networks in the brain are not truly random, and are not limited to the formation of strictly epileptogenic networks. Functional networks may develop to take advantage of the regulatory function of structures such as the precuneus to instantiate an anti-correlated network, generating protective cortico-cortico inhibition for the purpose of limiting seizure spread or epileptogenesis. PMID:22987774

Where one hand meets the other: limb-specific and action-dependent movement plans decoded from preparatory signals in single human frontoparietal brain areas.

PubMed

Gallivan, Jason P; McLean, D Adam; Flanagan, J Randall; Culham, Jody C

2013-01-30

Planning object-directed hand actions requires successful integration of the movement goal with the acting limb. Exactly where and how this sensorimotor integration occurs in the brain has been studied extensively with neurophysiological recordings in nonhuman primates, yet to date, because of limitations of non-invasive methodologies, the ability to examine the same types of planning-related signals in humans has been challenging. Here we show, using a multivoxel pattern analysis of functional MRI (fMRI) data, that the preparatory activity patterns in several frontoparietal brain regions can be used to predict both the limb used and hand action performed in an upcoming movement. Participants performed an event-related delayed movement task whereby they planned and executed grasp or reach actions with either their left or right hand toward a single target object. We found that, although the majority of frontoparietal areas represented hand actions (grasping vs reaching) for the contralateral limb, several areas additionally coded hand actions for the ipsilateral limb. Notable among these were subregions within the posterior parietal cortex (PPC), dorsal premotor cortex (PMd), ventral premotor cortex, dorsolateral prefrontal cortex, presupplementary motor area, and motor cortex, a region more traditionally implicated in contralateral movement generation. Additional analyses suggest that hand actions are represented independently of the intended limb in PPC and PMd. In addition to providing a unique mapping of limb-specific and action-dependent intention-related signals across the human cortical motor system, these findings uncover a much stronger representation of the ipsilateral limb than expected from previous fMRI findings.

Pattern of Corticospinal Projections Defined by Brain Mapping During Resective Epilepsy Surgery in a Patient with Congenital Hemiparesis and Intractable Epilepsy.

PubMed

Yang, Chen-Ya; Chen, Hsin-Hung; Chen, Chien; Chiu, Jan-Wei; Chou, Chen-Liang; Yang, Tsui-Fen

2017-11-01

Congenital or early-onset brain structural lesions often cause contralateral hemiparesis, cognitive deficits, developmental delays, and seizures. Seizure is the most debilitating condition, as it greatly impairs quality of life in both the affected individuals and their caregivers and prevents them from active social participation. A 34-year-old man with hemiparesis and early-onset seizures since childhood owing to a congenital brain lesion developed intractable seizures in the last 2 years and was subsequently admitted for resective epileptic surgery. During the operation, we employed an innovative intraoperative neurophysiologic monitoring technique. In contrast to routine application for transcranial stimulation, we recorded compound muscle action potentials over the bilateral limb muscles simultaneously, instead of over the contralateral muscles only, to determine the patterns of the corticospinal projections. Transcranial stimulation over the bilateral hemispheres was applied before craniotomy, and direct cortical stimulation over the lesioned hemisphere was applied after craniotomy. By integrating both approaches, we could first identify the pattern of corticospinal projections before craniotomy and then accurately define the noneloquent area, which guided the resection to successfully accomplish the surgical goal. This technique is simple because no patient participation is required. We believe that it has the potential to replace conventional preoperative functional magnetic resonance imaging and transcranial magnetic stimulation in resective epilepsy surgery, particularly for young patients. Not only can it improve the safety of surgical procedures, but also it can help predict functional outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Demonstration of elevation and localization of Rho-kinase activity in the brain of a rat model of cerebral infarction.

PubMed

Yano, Kazuo; Kawasaki, Koh; Hattori, Tsuyoshi; Tawara, Shunsuke; Toshima, Yoshinori; Ikegaki, Ichiro; Sasaki, Yasuo; Satoh, Shin-ichi; Asano, Toshio; Seto, Minoru

2008-10-10

Evidence that Rho-kinase is involved in cerebral infarction has accumulated. However, it is uncertain whether Rho-kinase is activated in the brain parenchyma in cerebral infarction. To answer this question, we measured Rho-kinase activity in the brain in a rat cerebral infarction model. Sodium laurate was injected into the left internal carotid artery, inducing cerebral infarction in the ipsilateral hemisphere. At 6 h after injection, increase of activating transcription factor 3 (ATF3) and c-Fos was found in the ipsilateral hemisphere, suggesting that neuronal damage occurs. At 0.5, 3, and 6 h after injection of laurate, Rho-kinase activity in extracts of the cerebral hemispheres was measured by an ELISA method. Rho-kinase activity in extracts of the ipsilateral hemisphere was significantly increased compared with that in extracts of the contralateral hemisphere at 3 and 6 h but not 0.5 h after injection of laurate. Next, localization of Rho-kinase activity was evaluated by immunohistochemical analysis in sections of cortex and hippocampus including infarct area 6 h after injection of laurate. Staining for phosphorylation of myosin-binding subunit (phospho-MBS) and myosin light chain (phospho-MLC), substrates of Rho-kinase, was elevated in neuron and blood vessel, respectively, in ipsilateral cerebral sections, compared with those in contralateral cerebral sections. These findings indicate that Rho-kinase is activated in neuronal and vascular cells in a rat cerebral infarction model, and suggest that Rho-kinase could be an important target in the treatment of cerebral infarction.

Connectivity derived thalamic segmentation in deep brain stimulation for tremor.

PubMed

Akram, Harith; Dayal, Viswas; Mahlknecht, Philipp; Georgiev, Dejan; Hyam, Jonathan; Foltynie, Thomas; Limousin, Patricia; De Vita, Enrico; Jahanshahi, Marjan; Ashburner, John; Behrens, Tim; Hariz, Marwan; Zrinzo, Ludvic

2018-01-01

The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.

Structural Integrity of Normal Appearing White Matter and Sex-Specific Outcomes After Acute Ischemic Stroke.

PubMed

Etherton, Mark R; Wu, Ona; Cougo, Pedro; Giese, Anne-Katrin; Cloonan, Lisa; Fitzpatrick, Kaitlin M; Kanakis, Allison S; Boulouis, Gregoire; Karadeli, Hasan H; Lauer, Arne; Rosand, Jonathan; Furie, Karen L; Rost, Natalia S

2017-12-01

Women have worse poststroke outcomes than men. We evaluated sex-specific clinical and neuroimaging characteristics of white matter in association with functional recovery after acute ischemic stroke. We performed a retrospective analysis of acute ischemic stroke patients with admission brain MRI and 3- to 6-month modified Rankin Scale score. White matter hyperintensity and acute infarct volume were quantified on fluid-attenuated inversion recovery and diffusion tensor imaging MRI, respectively. Diffusivity anisotropy metrics were calculated in normal appearing white matter contralateral to the acute ischemia. Among 319 patients with acute ischemic stroke, women were older (68.0 versus 62.7 years; P =0.004), had increased incidence of atrial fibrillation (21.4% versus 12.2%; P =0.04), and lower rate of tobacco use (21.1% versus 35.9%; P =0.03). There was no sex-specific difference in white matter hyperintensity volume, acute infarct volume, National Institutes of Health Stroke Scale, prestroke modified Rankin Scale score, or normal appearing white matter diffusivity anisotropy metrics. However, women were less likely to have an excellent outcome (modified Rankin Scale score <2: 49.6% versus 67.0%; P =0.005). In logistic regression analysis, female sex and the interaction of sex with fractional anisotropy, radial diffusivity, and axial diffusivity were independent predictors of functional outcome. Female sex is associated with decreased likelihood of excellent outcome after acute ischemic stroke. The correlation between markers of white matter integrity and functional outcomes in women, but not men, suggests a potential sex-specific mechanism. © 2017 American Heart Association, Inc.

Auditory input modulates sleep: an intra-cochlear-implanted human model.

PubMed

Velluti, Ricardo A; Pedemonte, Marisa; Suárez, Hámlet; Bentancor, Claudia; Rodríguez-Servetti, Zulma

2010-12-01

To properly demonstrate the effect of auditory input on sleep of intra-cochlear-implanted patients, the following approach was developed. Four implanted deaf patients were recorded during four nights: two nights with the implant OFF, with no auditory input, and two nights with the implant ON, that is, with normal auditory input, being only the common night sounds present, without any additional auditory stimuli delivered. The sleep patterns of another five deaf people were used as controls, exhibiting normal sleep organization. Moreover, the four experimental patients with intra-cochlear devices and the implant OFF also showed normal sleep patterns. On comparison of the night recordings with the implant ON and OFF, a new sleep organization was observed for the recordings with the implant ON, suggesting that brain plasticity may produce changes in the sleep stage percentages while maintaining the ultradian rhythm. During sleep with the implant ON, the analysis of the electroencephalographic delta, theta and alpha bands in the frequency domain, using the Fast Fourier Transform, revealed a diversity of changes in the power originated in the contralateral cortical temporal region. Different power shifts were observed, perhaps related to the exact position of the implant inside the cochlea and the scalp electrode location. In conclusion, this pilot study shows that the auditory input in humans can introduce changes in central nervous system activity leading to shifts in sleep characteristics, as previously demonstrated in guinea pigs. We are postulating that an intra-cochlear-implanted deaf patient may have a better recovery if the implant is maintained ON during the night, that is, during sleep. © 2010 European Sleep Research Society.

Selective enrichment of hypericin in malignant glioma: pioneering in vivo results.

PubMed

Noell, Susan; Mayer, Daniel; Strauss, Wolfgang S L; Tatagiba, Marcos S; Ritz, Rainer

2011-05-01

Malignant gliomas are diffuse infiltrative growing tumors with a poor prognosis despite treatment with a combination of surgery, radiotherapy and chemotherapy. It has been shown recently that complete tumor resection improves the survival time significantly. Hypericin, a component of St. Johns Wort, is one of the most powerful photosensitizers in nature. The aim of the present study was to investigate accumulation of hypericin in intracerebral implanted malignant glioma in vivo. Rats underwent stereotactic implantation of C6 glioma cells. After intravenous administration of hypericin (5 mg per kg body weight), accumulation of the compound was studied in tumor, the infiltration zone surrounding the tumor and healthy brain (contralateral hemisphere) by fluorescence microscopy between 0 and 48 h after injection. Results were compared by one-way analysis of variance. For post hoc pair-wise comparison the Tukey-Kramer HSD test was used. Accumulation of hypericin was significantly higher in C6 glioma as compared to normal tissue. Maximum hypericin uptake was achieved at 24 h after injection. Ratios of fluorescence intensity between tumor and normal tissue as well as infiltration zone and normal tissue of about 6.1:1 and 1.4:1 were found. Considering tissue auto-fluorescence, fluorescence ratios of about 19.8:1 and 2.5:1 were calculated, respectively. Therefore, hypericin seems to be quite an effective fluorescence marker for the detection of glioma in vivo. To the best of our knowledge, the present study demonstrates for the first time that hypericin accumulates selectively in intracerebral implanted C6 glioma in vivo after systemic (intravenous) administration.

Evaluation of 177Lu[Lu]-CHX-A″-DTPA-6A10 Fab as a radioimmunotherapy agent targeting carbonic anhydrase XII.

PubMed

Fiedler, L; Kellner, M; Gosewisch, A; Oos, R; Böning, G; Lindner, S; Albert, N; Bartenstein, P; Reulen, H-J; Zeidler, R; Gildehaus, F J

2018-05-01

Due to their infiltrative growth behavior, gliomas have, even after surgical resection, a high recurrence tendency. The approach of intracavitary radioimmunotherapy (RIT) is aimed at inhibiting tumor re-growth by directly administering drugs into the resection cavity (RC). Direct application of the radioconjugate into the RC has the advantage of bypassing the blood-brain barrier, which allows the administration of higher radiation doses than systemic application. Carbonic anhydrase XII (CA XII) is highly expressed on glioma cells while being absent from normal brain and thus an attractive target molecule for RIT. We evaluated a CA XII-specific 6A10 Fab (fragment antigen binding) labelled with 177 Lu as an agent for RIT. 6A10 Fab fragment was modified and radiolabelled with 177 Lu and characterized by MALDI-TOF, flow cytometry and radio-TLC. In vitro stability was determined under physiological conditions. Biodistribution studies, autoradiography tumor examinations and planar scintigraphy imaging were performed on SCID-mice bearing human glioma xenografts. The in vitro CA XII binding capacity of the modified Fab was confirmed. Radiochemical purity was determined to be >90% after 72 h of incubation under physiological conditions. Autoradiography experiments proved the specific binding of the Fab to CA XII on tumor cells. Biodistribution studies revealed a tumor uptake of 3.0%ID/g after 6 h and no detectable brain uptake. The tumor-to-contralateral ratio of 10/1 was confirmed by quantitative planar scintigraphy. The radiochemical stability in combination with a successful in vivo tumor uptake shows the potential suitability for future RIT applications with the 6A10 Fab. Copyright © 2018 Elsevier Inc. All rights reserved.

Simulating the Effect of Spectroscopic MRI as a Metric for Radiation Therapy Planning in Patients with Glioblastoma

PubMed Central

Cordova, J. Scott; Kandula, Shravan; Gurbani, Saumya; Zhong, Jim; Tejani, Mital; Kayode, Oluwatosin; Patel, Kirtesh; Prabhu, Roshan; Schreibmann, Eduard; Crocker, Ian; Holder, Chad A.; Shim, Hyunsuk; Shu, Hui-Kuo

2017-01-01

Due to glioblastoma’s infiltrative nature, an optimal radiation therapy (RT) plan requires targeting infiltration not identified by anatomical magnetic resonance imaging (MRI). Here, high-resolution, whole-brain spectroscopic MRI (sMRI) is used to describe tumor infiltration alongside anatomical MRI and simulate the degree to which it modifies RT target planning. In 11 patients with glioblastoma, data from preRT sMRI scans were processed to give high-resolution, whole-brain metabolite maps normalized by contralateral white matter. Maps depicting choline to N-Acetylaspartate (Cho/NAA) ratios were registered to contrast-enhanced T1-weighted RT planning MRI for each patient. Volumes depicting metabolic abnormalities (1.5−, 1.75−, and 2.0-fold increases in Cho/NAA ratios) were compared with conventional target volumes and contrast-enhancing tumor at recurrence. sMRI-modified RT plans were generated to evaluate target volume coverage and organ-at-risk dose constraints. Conventional clinical target volumes and Cho/NAA abnormalities identified significantly different regions of microscopic infiltration with substantial Cho/NAA abnormalities falling outside of the conventional 60 Gy isodose line (41.1, 22.2, and 12.7 cm3, respectively). Clinical target volumes using Cho/NAA thresholds exhibited significantly higher coverage of contrast enhancement at recurrence on average (92.4%, 90.5%, and 88.6%, respectively) than conventional plans (82.5%). sMRI-based plans targeting tumor infiltration met planning objectives in all cases with no significant change in target coverage. In 2 cases, the sMRI-modified plan exhibited better coverage of contrast-enhancing tumor at recurrence than the original plan. Integration of the high-resolution, whole-brain sMRI into RT planning is feasible, resulting in RT target volumes that can effectively target tumor infiltration while adhering to conventional constraints. PMID:28105468

Topographic organization, number, and laminar distribution of callosal cells connecting visual cortical areas 17 and 18 of normally pigmented and Siamese cats.

PubMed

Berman, N E; Grant, S

1992-07-01

The callosal connections between visual cortical areas 17 and 18 in adult normally pigmented and "Boston" Siamese cats were studied using degeneration methods, and by transport of WGA-HRP combined with electrophysiological mapping. In normal cats, over 90% of callosal neurons were located in the supragranular layers. The supragranular callosal cell zone spanned the area 17/18 border and extended, on average, some 2-3 mm into both areas to occupy a territory which was roughly co-extensive with the distribution of callosal terminations in these areas. The region of the visual field adjoining the vertical meridian that was represented by neurons in the supragranular callosal cell zone was shown to increase systematically with decreasing visual elevation. Thus, close to the area centralis, receptive-field centers recorded from within this zone extended only up to 5 deg into the contralateral hemifield but at elevations of -10 deg and -40 deg they extended as far as 8 deg and 14 deg, respectively, into this hemifield. This suggests an element of visual non-correspondence in the callosal pathway between these cortical areas, which may be an essential substrate for "coarse" stereopsis at the visual midline. In the Siamese cats, the callosal cell and termination zones in areas 17 and 18 were expanded in width compared to the normal animals, but the major components were less robust. The area 17/18 border was often devoid of callosal axons and, in particular, the number of supragranular layer neurons participating in the pathway were drastically reduced, to only about 25% of those found in the normally pigmented adults. The callosal zones contained representations of the contralateral and ipsilateral hemifields that were roughly mirror-symmetric about the vertical meridian, and both hemifield representations increased with decreasing visual elevation. The extent and severity of the anomalies observed were similar across individual cats, regardless of whether a strabismus was also present. The callosal pathway between these visual cortical areas in the Siamese cat has been considered "silent," since nearly all neurons within its territory are activated only by the contralateral eye. The paucity of supragranular pyramidal neurons involved in the pathway may explain this silence.

Total hip arthroplasty using a short-stem prosthesis: restoration of hip anatomy.

PubMed

Amenabar, Tomas; Marimuthu, Kanniraj; Hawdon, Gabrielle; Gildone, Alessandro; McMahon, Stephen

2015-04-01

To evaluate hip parameters such as vertical centre of rotation (VCR), horizontal centre of rotation (HCR), femoral offset, and leg length after total hip arthroplasty (THA) using the Nanos short-stem prosthesis. Medical records of 73 men and 74 women aged 25 to 92 (mean, 63) years who underwent THA using the Nanos short-stem prosthesis by a single surgeon were reviewed. Prior to the surgery, the optimal cup and stem size, head length, and level of the neck osteotomy were determined using radiographs. Intra-operatively, the leg length and femoral offset were checked, and the level of neck resection and head length were adjusted. VCR, HCR, femoral offset, and leg length of the operated and contralateral sides were compared. Functional outcomes were assessed using the Harris Hip Score (HHS). Compared with the normal contralateral hips, the operated hips had a mean increase of 0.4 mm in VCR (p=0.032), a mean decrease of 1.4 mm in HCR (p=0.027), a mean increase of 0.6 mm in femoral offset (p=0.043), and a mean increase of 0.36 mm in leg length (p=0.035). For these respective parameters, the difference between the normal contralateral side and the operated side was within 5 mm in 89%, 80%, 71%, and 96% of patients. The HHS improved from a mean of 53 to 91 at one year (p<0.001). THA using the Nanos short-stem prosthesis enabled restoration of hip anatomy (VCR, HCR, femoral offset, and leg length).

Assessment of ureterovesical jet dynamics in obstructed ureter by urinary stone with color Doppler and duplex Doppler examinations.

PubMed

Jandaghi, Ali Babaei; Falahatkar, Siavash; Alizadeh, Ahmad; Kanafi, Alireza Rajabzadeh; Pourghorban, Ramin; Shekarchi, Babak; Zirak, Amin Keshavarz; Esmaeili, Samaneh

2013-04-01

This study was designed to evaluate ureterovesical jet dynamics in obstructed ureter and to compare it with those of contralateral unobstructed side. Forty-six patients with diagnosis of ureteral stone, based on imaging findings in computed tomography were enrolled in this study. The gray-scale ultrasound exam from both kidneys and urinary bladder was performed. Then, ureterovesical jet characteristics including ureteral jet frequency, duration and peak velocity were assessed by color Doppler and duplex Doppler studies in both obstructed and unobstructed ureters by a radiologist, 15-30 min after oral hydration with 750-1,000 mL of water. When compared with contralateral normal side, the ureterovesical jet in obstructed ureter showed less frequency (0.59 vs. 3.04 jets/min; P < 0.05), shorter duration (1.24 vs. 5.26 s; P < 0.05) and lower peak velocity (5.41 vs. 32.09 cm/s; P < 0.05). The cut-off points of 1.5 jets/min, 2.5 s and 19.5 cm/s for difference of ureteral jet frequency, duration and peak velocity between obstructed and contralateral normal ureters yielded sensitivities of 97.8, 95.6 and 100 % and specificities of 87, 87.9 and 97.8 %, respectively for diagnosis of ureteral obstruction. Given the safety of Doppler study and significant differences in flow dynamics of obstructed versus unobstructed ureters, our findings demonstrated the utility of Doppler ultrasound examination as a useful adjunct to gray-scale ultrasound by improving the accuracy of ultrasound exam in diagnosis of ureteral obstruction.

Vascular Dysfunction in Leukoaraiosis.

PubMed

Sam, K; Crawley, A P; Poublanc, J; Conklin, J; Sobczyk, O; Mandell, D M; Duffin, J; Venkatraghavan, L; Fisher, J A; Black, S E; Mikulis, D J

2016-12-01

The pathogenesis of leukoaraiosis has long been debated. This work addresses a less well-studied mechanism, cerebrovascular reactivity, which could play a leading role in the pathogenesis of this disease. Our aim was to evaluate blood flow dysregulation and its relation to leukoaraiosis. Cerebrovascular reactivity, the change in the blood oxygen level-dependent 3T MR imaging signal in response to a consistently applied step change in the arterial partial pressure of carbon dioxide, was measured in white matter hyperintensities and their contralateral spatially homologous normal-appearing white matter in 75 older subjects (age range, 50-91 years; 40 men) with leukoaraiosis. Additional quantitative evaluation of regions of leukoaraiosis was performed by using diffusion (n = 75), quantitative T2 (n = 54), and DSC perfusion MRI metrics (n = 25). When we compared white matter hyperintensities with contralateral normal-appearing white matter, cerebrovascular reactivity was lower by a mean of 61.2% ± 22.6%, fractional anisotropy was lower by 44.9 % ± 6.9%, and CBF was lower by 10.9% ± 11.9%. T2 was higher by 61.7% ± 13.5%, mean diffusivity was higher by 59.0% ± 11.7%, time-to-maximum was higher by 44.4% ± 30.4%, and TTP was higher by 6.8% ± 5.8% (all P < .01). Cerebral blood volume was lower in white matter hyperintensities compared with contralateral normal-appearing white matter by 10.2% ± 15.0% (P = .03). Not only were resting blood flow metrics abnormal in leukoaraiosis but there is also evidence of reduced cerebrovascular reactivity in these areas. Studies have shown that reduced cerebrovascular reactivity is more sensitive than resting blood flow parameters for assessing vascular insufficiency. Future work is needed to examine the sensitivity of resting-versus-dynamic blood flow measures for investigating the pathogenesis of leukoaraiosis. © 2016 by American Journal of Neuroradiology.

Relationship between the blood perfusion values determined by laser speckle imaging and laser Doppler imaging in normal skin and port wine stains.

PubMed

Chen, Defu; Ren, Jie; Wang, Ying; Zhao, Hongyou; Li, Buhong; Gu, Ying

2016-03-01

Laser Doppler imaging (LDI) and laser speckle imaging (LSI) are two major optical techniques aiming at non-invasively imaging the skin blood perfusion. However, the relationship between perfusion values determined by LDI and LSI has not been fully explored. 8 healthy volunteers and 13 PWS patients were recruited. The perfusions in normal skin on the forearm of 8 healthy volunteers were simultaneously measured by both LDI and LSI during post-occlusive reactive hyperemia (PORH). Furthermore, the perfusions of port wine stains (PWS) lesions and contralateral normal skin of 10 PWS patients were also determined. In addition, the perfusions for PWS lesions from 3 PWS patients were successively monitored at 0, 10 and 20min during vascular-targeted photodynamic therapy (V-PDT). The average perfusion values determined by LSI were compared with those of LDI for each subject. In the normal skin during PORH, power function provided better fits of perfusion values than linear function: powers for individual subjects go from 1.312 to 1.942 (R(2)=0.8967-0.9951). There was a linear relationship between perfusion values determined by LDI and LSI in PWS and contralateral normal skin (R(2)=0.7308-0.9623), and in PWS during V-PDT (R(2)=0.8037-0.9968). The perfusion values determined by LDI and LSI correlate closely in normal skin and PWS over a broad range of skin perfusion. However, it still suggests that perfusion range and characteristics of the measured skin should be carefully considered if LDI and LSI measures are compared. Copyright © 2015 Elsevier B.V. All rights reserved.

Idiopathic granulomatous mastitis: magnetic resonance imaging findings with diffusion MRI.

PubMed

Aslan, Hulya; Pourbagher, Aysin; Colakoglu, Tamer

2016-07-01

Idiopathic granulomatous mastitis (IGM) is a rare benign breast disease with unknown etiology which can mimic breast carcinoma, both clinically and radiologically. Magnetic resonance imaging (MRI) findings of IGM have been previously described; however there is no study evaluating diffusion-weighted MRI findings of IGM. To analyze conventional, dynamic contrast-enhanced, and diffusion-weighted MRI signal characteristics of IGM by comparing it with the contralateral normal breast parenchyma. A total of 39 patients were included in the study. On dynamic contrast-enhanced MRI, the distribution and enhancement patterns of the lesions were evaluated. We also detected the frequencies of involving quadrants, retroareolar involvement, accompanying abscess, and skin edema. T2-weighted (T2W) and STIR signal intensities and both mean and minimum apparent diffusion coefficient (ADC) values were compared with the contralateral normal parenchyma. IGM showed significantly lower mean and minimum ADC values when compared with the normal parenchyma. Signal intensities on T2W and STIR sequences of the lesion were significantly higher than the normal parenchyma. On dynamic contrast-enhanced MRI, 7.7% of the patients had mass-like contrast enhancement, 92.3% of the patients had non-mass-like contrast enhancement. Abscess was positive in 33.3% of the patients. As a result, IGM showed commonly non-mass-like lesions with restricted diffusion. Although it is a benign pathology, it may show clustered ring-like enhancement like malignant lesions. © The Foundation Acta Radiologica 2015.

Brain stem origins of spinal projections in the lizard Tupinambis nigropunctatus.

PubMed

Cruce, W L; Newman, D B

1981-05-10

In order to study brainstem origins of spinal projections, ten Tegu lizards (Tupinambis nigropunctatus) received complete or partial hemisections of the spinal cord at the first or second cervical segment. Their brains were processed for conventional Nissl staining. The sections were surveyed for the presence or absence of retrograde chromatolysis. Based on analysis and comparison of results from lesions in the various spinal cord funiculi, the following conclusions were reached: The interstitial nucleus projects ipsilaterally to the spinal cord via the medial longitudinal fasciculus, as does the middle reticular field of the metencephalon. The red nucleus and dorsal vagal motor nucleus both project contralaterally to the spinal cord via the dorsal part of the lateral funiculus. The superior reticular field in the rostral metencephalon and the ventrolateral vestibular nucleus project ipsilaterally to the spinal cord via the ventral funiculus. The dorsolateral metencephalic nucleus and the ventral part of the inferior reticular nucleus of the myelencephalon both project ipsilaterally to the spinal cord via the dorsal part of the lateral funiculus. Several brainstem nuclei in Tupinambis project bilaterally to the spinal cord. The ventrolateral metencephalic nucleus, for example, projects ipsilaterally to the cord via the medial longitudinal fasciculus and contralaterally via the dorsal part of the lateral funiculus. The dorsal part of the inferior reticular nucleus projects bilaterally to the spinal cord via the dorsal part of the lateral funiculus. The nucleus solitarius complex projects contralaterally via the dorsal part of the lateral funiculus but ipsilaterally via the middle of the lateral funiculus. The inferior raphe nucleus projects bilaterally to the spinal cord via the middle part of the lateral funiculus. These data suggest that supraspinal projections in reptiles, especially reticulospinal systems, are more highly differentiated than previously thought. On the other hand, recent findings in cat, opossum, and monkey reveal that the organization of supraspinal pathways in the Tegu lizard bears a striking resemblance to that observed in mammals.

Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

PubMed Central

Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

2014-01-01

Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID:24074493

Neurophysiology of the cortical pain network: revisiting the role of S1 in subjective pain perception via standardized low-resolution brain electromagnetic tomography (sLORETA).

PubMed

Nir, Rony-Reuven; Lev, Rina; Moont, Ruth; Granovsky, Yelena; Sprecher, Elliot; Yarnitsky, David

2008-11-01

Multiple studies have supported the usefulness of standardized low-resolution brain electromagnetic tomography (sLORETA) in localizing generators of scalp-recorded potentials. The current study implemented sLORETA on pain event-related potentials, primarily aiming at validating this technique for pain research by identifying well-known pain-related regions. Subsequently, we pointed at investigating the still-debated and ambiguous topic of pain intensity coding at these regions, focusing on their relative impact on subjective pain perception. sLORETA revealed significant activations of the bilateral primary somatosensory (SI) and anterior cingulate cortices and of the contralateral operculoinsular and dorsolateral prefrontal (DLPFC) cortices (P < .05 for each). Activity of these regions, excluding DLPFC, correlated with subjective numerical pain scores (P < .05 for each). However, a multivariate regression analysis (R = .80; P = .024) distinguished the contralateral SI as the only region whose activation magnitude significantly predicted the subjective perception of noxious stimuli (P = .020), further substantiated by a reduced regression model (R = .75, P = .008). Based on (1) correspondence of the pain-activated regions identified by sLORETA with the acknowledged imaging-based pain-network and (2) the contralateral SI proving to be the most contributing region in pain intensity coding, we found sLORETA to be an appropriate tool for relevant pain research and further substantiated the role of SI in pain perception. Because the literature of pain intensity coding offers inconsistent findings, the current article used a novel tool for revisiting this controversial issue. Results suggest that it is the activation magnitude of SI, which solely establishes the significant correlation with subjective pain ratings, in accordance with the classical clinical thinking, relating SI lesions to diminished perception of pain. Although this study cannot support a causal relation between SI activation magnitude and pain perception, such relation might be insinuated.

Sustained Spatial Attention to Vibrotactile Stimulation in the Flutter Range: Relevant Brain Regions and Their Interaction

PubMed Central

Goltz, Dominique; Pleger, Burkhard; Thiel, Sabrina; Villringer, Arno; Müller, Matthias M.

2013-01-01

The present functional magnetic resonance imaging (fMRI) study was designed to get a better understanding of the brain regions involved in sustained spatial attention to tactile events and to ascertain to what extent their activation was correlated. We presented continuous 20 Hz vibrotactile stimuli (range of flutter) concurrently to the left and right index fingers of healthy human volunteers. An arrow cue instructed subjects in a trial-by-trial fashion to attend to the left or right index finger and to detect rare target events that were embedded in the vibrotactile stimulation streams. We found blood oxygen level-dependent (BOLD) attentional modulation in primary somatosensory cortex (SI), mainly covering Brodmann area 1, 2, and 3b, as well as in secondary somatosensory cortex (SII), contralateral to the to-be-attended hand. Furthermore, attention to the right (dominant) hand resulted in additional BOLD modulation in left posterior insula. All of the effects were caused by an increased activation when attention was paid to the contralateral hand, except for the effects in left SI and insula. In left SI, the effect was related to a mixture of both a slight increase in activation when attention was paid to the contralateral hand as well as a slight decrease in activation when attention was paid to the ipsilateral hand (i.e., the tactile distraction condition). In contrast, the effect in left posterior insula was exclusively driven by a relative decrease in activation in the tactile distraction condition, which points to an active inhibition when tactile information is irrelevant. Finally, correlation analyses indicate a linear relationship between attention effects in intrahemispheric somatosensory cortices, since attentional modulation in SI and SII were interrelated within one hemisphere but not across hemispheres. All in all, our results provide a basis for future research on sustained attention to continuous vibrotactile stimulation in the range of flutter. PMID:24367642

Suppression of Rabbit VX‐2 Subcutaneous Tumor Growth by Gadolinium Neutron Capture Therapy

PubMed Central

Tokita, Nobuhiko; Tokuuye, Koichi; Satoh, Michinao; Churei, Hisahiko; Pechoux, Cécile Le; Kobayashi, Tooru; Kanda, Keiji

1993-01-01

VX‐2 tumors growing in hind legs of New Zealand White rabbits (n=4) were exposed to thermal neutrons for 40 min (2.1 × 1012 neutrons cm−2) while one of two hind leg tumors of each rabbit was infused continuously with meglumine gadopentetate through a branch of the left femoral artery. The contralateral (uninfused) tumors served as controls. Although no differential distribution of gadolinium was achieved between the tumor and its adjacent normal tissue, the gadolinium concentration in the infused tumor was approximately 5–6 fold higher than that in the contralateral tumor. Growth of gadolinium‐infused tumors was significantly inhibited compared to that of control tumors (P<0.05) between the 16th and 23rd days after treatment. PMID:8407547

Does Contralateral Delay Activity Reflect Working Memory Storage or the Current Focus of Spatial Attention within Visual Working Memory?

PubMed

Berggren, Nick; Eimer, Martin

2016-12-01

During the retention of visual information in working memory, event-related brain potentials show a sustained negativity over posterior visual regions contralateral to the side where memorized stimuli were presented. This contralateral delay activity (CDA) is generally believed to be a neural marker of working memory storage. In two experiments, we contrasted this storage account of the CDA with the alternative hypothesis that the CDA reflects the current focus of spatial attention on a subset of memorized items set up during the most recent encoding episode. We employed a sequential loading procedure where participants memorized four task-relevant items that were presented in two successive memory displays (M1 and M2). In both experiments, CDA components were initially elicited contralateral to task-relevant items in M1. Critically, the CDA switched polarity when M2 displays appeared on the opposite side. In line with the attentional activation account, these reversed CDA components exclusively reflected the number of items that were encoded from M2 displays, irrespective of how many M1 items were already held in working memory. On trials where M1 and M2 displays were presented on the same side and on trials where M2 displays appeared nonlaterally, CDA components elicited in the interval after M2 remained sensitive to a residual trace of M1 items, indicating that some activation of previously stored items was maintained across encoding episodes. These results challenge the hypothesis that CDA amplitudes directly reflect the total number of stored objects and suggest that the CDA is primarily sensitive to the activation of a subset of working memory representations within the current focus of spatial attention.

Lateralized delay period activity marks the focus of spatial attention in working memory: evidence from somatosensory event-related brain potentials.

PubMed

Katus, Tobias; Eimer, Martin

2015-04-29

The short-term retention of sensory information in working memory (WM) is known to be associated with a sustained enhancement of neural activity. What remains controversial is whether this neural trace indicates the sustained storage of information or the allocation of attention. To evaluate the storage and attention accounts, we examined sustained tactile contralateral delay activity (tCDA component) of the event-related potential. The tCDA manifests over somatosensory cortex contralateral to task-relevant tactile information during stimulus retention. Two tactile sample sets (S1, S2) were presented sequentially, separated by 1.5 s. Each set comprised two stimuli, one per hand. Human participants memorized the location of one task-relevant stimulus per sample set and judged whether one of these locations was stimulated again at memory test. The two relevant pulses were unpredictably located on the same hand (stay trials) or on different hands (shift trials). Initially, tCDA components emerged contralateral to the relevant S1 pulse. Sequential loading of WM enhanced the tCDA after S2 was presented on stay trials. On shift trials, the tCDA's polarity reversed after S2 presentation, resulting in delay activity that was now contralateral to the task-relevant S2 pulse. The disappearance of a lateralized neural trace for the relevant S1 pulse did not impair memory accuracy for this stimulus on shift trials. These results contradict the storage account and suggest that delay period activity indicates the sustained engagement of an attention-based rehearsal mechanism. In conclusion, somatosensory delay period activity marks the current focus of attention in tactile WM. Copyright © 2015 the authors 0270-6474/15/356689-07$15.00/0.

Effect of intravenous gadolinium-DTPA on diffusion tensor MR imaging for the evaluation of brain tumors.

PubMed

Bae, Min Sun; Jahng, Geon-Ho; Ryu, Chang Woo; Kim, Eui Jong; Choi, Woo Suk; Yang, Dal Mo

2009-12-01

The aim of this study was to investigate whether indices of diffusion tensor MRI (DT-MRI) are altered after contrast medium injection in patients with brain tumors. DT-MRIs at a 3-T unit before and 6 min after gadolinium-diethylenetriamine penta-acetic acid injection were obtained in nine patients (five women, four men) with histologically confirmed brain tumors (four metastases, one glioblastoma multiforme, three meningiomas, and one lymphoma). Fractional anisotropy (FA), trace and mean raw DT-MRI data without (DT_b0, b value = 0 s/mm(2)) and with (DT_b800, b value = 800 s/mm(2)) diffusion-encoded gradients were calculated. Regions of interest (ROIs) were placed in the tumor, peritumoral edema, and normal-appearing symmetric contralateral brain tissue for each patient. The Kruskal-Wallis rank sum test was used to determine the effects of contrast medium and ROI for all of the maps, and the Wilcoxon signed-rank test was performed for either paired t test between pre- and post-contrast values of DTI indices for the ROIs or the post hoc test. Statistically significant differences between pre-contrast and post-contrast DT-MRI are shown in the trace value of the peritumoral edema area (p = 0.0195) and the FA value of the tumor area (p = 0.0273). Trace and FA values of the other areas show no statistically significant differences between pre- and post-contrast (p > 0.05). In addition, we find a significant ROI effect for both FA (chi (2) = 26.514, df = 2, p = 0.0001) and trace (chi (2) = 21.218, df = 2, p = 0.0001). DT-MRI obtained after contrast medium injection of 6 min results in significant changes in diffusion isotropic and anisotropic values. Therefore, clinical applications of DT-MRI after administrating a contrast medium require caution in interpretation.

Three descending interneurons reporting deviation from course in the locust. I. Anatomy.

PubMed

Griss, C; Rowell, C H

1986-06-01

Three descending brain interneurons (DNI, DNM, DNC) are described from Locusta migratoria. All are paired, dorsally situated neurons, with soma in the protocerebrum, input dendrites in the proto- and deuterocerebrum, and a single axon running to the metathoracic ganglion and sometimes further. In DNI the soma and all cerebral arborizations lie ipsilateral to the axon. Discrete regions of arborization lie in the ipsilateral and medial ocellar tracts, the midprotocerebrum and the deuterocerebrum. In the other ganglia the axon branches only ipsilaterally, principally laterally in the flight motor neuropil but also towards the midline. DNC is similarly organized to DNI, but the cell crosses the midline in the brain. Soma, the single projection into a lateral ocellar tract, and the midprotocerebral arborization all lie contralateral to the axon. The deuterocerebral arborization is, however, ipsilateral to the axon. The pattern of projections in the remaining ganglia resembles that of DNI. The soma and all cerebral arborizations of DNM lie ipsilateral to the axon. The arborization is only weakly subdivided into protocerebral, deuterocerebral and medial ocellar tract regions. In the remaining ganglia the arborization extends bilaterally to similar areas of both left and right flight motor neuropil. A table of synonymy is given, equating the various names used for these neurons by previous authors. The morphology correlates well with the known input and output connections. They respond physiologically to deviations from the normal flight posture mediated by ocelli, eyes and wind hairs and connect to the thoracic flight apparatus.

Therapeutic Targeting of P2X7 after TBI

DTIC Science & Technology

2012-11-16

evacuation of acute subdural hematoma : brain shift and the dynamics of extraaxial collections. Neurol Res, 26(7), 763-766. Cold, G. E., & Jensen, F. T...of consecutive bilateral surgeries for patients with acute 31 Kimbler, Donald E N10-P10 subdural hematoma who develop contralateral acute epi...or subdural hematoma . Surg Neurol, 60(1), 23-30; discussion 30. Miller, J. D., Becker, D. P., Ward, J. D., Sullivan, H. G., Adams, W. E., & Rosner, M

Illusion-related brain activations: a new virtual reality mirror box system for use during functional magnetic resonance imaging.

PubMed

Diers, Martin; Kamping, Sandra; Kirsch, Pinar; Rance, Mariela; Bekrater-Bodmann, Robin; Foell, Jens; Trojan, Joerg; Fuchs, Xaver; Bach, Felix; Maaß, Heiko; Cakmak, Hüseyin; Flor, Herta

2015-01-12

Extended viewing of movements of one's intact limb in a mirror as well as motor imagery have been shown to decrease pain in persons with phantom limb pain or complex regional pain syndrome and to increase the movement ability in hemiparesis following stroke. In addition, mirrored movements differentially activate sensorimotor cortex in amputees with and without phantom limb pain. However, using a so-called mirror box has technical limitations, some of which can be overcome by virtual reality applications. We developed a virtual reality mirror box application and evaluated its comparability to a classical mirror box setup. We applied both paradigms to 20 healthy controls and analyzed vividness and authenticity of the illusion as well as brain activation patterns. In both conditions, subjects reported similar intensities for the sensation that movements of the virtual left hand felt as if they were executed by their own left hand. We found activation in the primary sensorimotor cortex contralateral to the actual movement, with stronger activation for the virtual reality 'mirror box' compared to the classical mirror box condition, as well as activation in the primary sensorimotor cortex contralateral to the mirrored/virtual movement. We conclude that a virtual reality application of the mirror box is viable and that it might be useful for future research. Copyright © 2014 Elsevier B.V. All rights reserved.

Dissociated α-band modulations in the dorsal and ventral visual pathways in visuospatial attention and perception.

PubMed

Capilla, Almudena; Schoffelen, Jan-Mathijs; Paterson, Gavin; Thut, Gregor; Gross, Joachim

2014-02-01

Modulations of occipito-parietal α-band (8-14 Hz) power that are opposite in direction (α-enhancement vs. α-suppression) and origin of generation (ipsilateral vs. contralateral to the locus of attention) are a robust correlate of anticipatory visuospatial attention. Yet, the neural generators of these α-band modulations, their interdependence across homotopic areas, and their respective contribution to subsequent perception remain unclear. To shed light on these questions, we employed magnetoencephalography, while human volunteers performed a spatially cued detection task. Replicating previous findings, we found α-power enhancement ipsilateral to the attended hemifield and contralateral α-suppression over occipito-parietal sensors. Source localization (beamforming) analysis showed that α-enhancement and suppression were generated in 2 distinct brain regions, located in the dorsal and ventral visual streams, respectively. Moreover, α-enhancement and suppression showed different dynamics and contribution to perception. In contrast to the initial and transient dorsal α-enhancement, α-suppression in ventro-lateral occipital cortex was sustained and influenced subsequent target detection. This anticipatory biasing of ventro-lateral extrastriate α-activity probably reflects increased receptivity in the brain region specialized in processing upcoming target features. Our results add to current models on the role of α-oscillations in attention orienting by showing that α-enhancement and suppression can be dissociated in time, space, and perceptual relevance.

The neural correlates of learned motor acuity

PubMed Central

Yang, Juemin; Caffo, Brian; Mazzoni, Pietro; Krakauer, John W.

2014-01-01

We recently defined a component of motor skill learning as “motor acuity,” quantified as a shift in the speed-accuracy trade-off function for a task. These shifts are primarily driven by reductions in movement variability. To determine the neural correlates of improvement in motor acuity, we devised a motor task compatible with magnetic resonance brain imaging that required subjects to make finely controlled wrist movements under visual guidance. Subjects were imaged on day 1 and day 5 while they performed this task and were trained outside the scanner on intervening days 2, 3, and 4. The potential confound of performance changes between days 1 and 5 was avoided by constraining movement time to a fixed duration. After training, subjects showed a marked increase in success rate and a reduction in trial-by-trial variability for the trained task but not for an untrained control task, without changes in mean trajectory. The decrease in variability for the trained task was associated with increased activation in contralateral primary motor and premotor cortical areas and in ipsilateral cerebellum. A global nonlocalizing multivariate analysis confirmed that learning was associated with increased overall brain activation. We suggest that motor acuity is acquired through increases in the number of neurons recruited in contralateral motor cortical areas and in ipsilateral cerebellum, which could reflect increased signal-to-noise ratio in motor output and improved state estimation for feedback corrections, respectively. PMID:24848466

Brain-computer interface controlled functional electrical stimulation system for ankle movement.

PubMed

Do, An H; Wang, Po T; King, Christine E; Abiri, Ahmad; Nenadic, Zoran

2011-08-26

Many neurological conditions, such as stroke, spinal cord injury, and traumatic brain injury, can cause chronic gait function impairment due to foot-drop. Current physiotherapy techniques provide only a limited degree of motor function recovery in these individuals, and therefore novel therapies are needed. Brain-computer interface (BCI) is a relatively novel technology with a potential to restore, substitute, or augment lost motor behaviors in patients with neurological injuries. Here, we describe the first successful integration of a noninvasive electroencephalogram (EEG)-based BCI with a noninvasive functional electrical stimulation (FES) system that enables the direct brain control of foot dorsiflexion in able-bodied individuals. A noninvasive EEG-based BCI system was integrated with a noninvasive FES system for foot dorsiflexion. Subjects underwent computer-cued epochs of repetitive foot dorsiflexion and idling while their EEG signals were recorded and stored for offline analysis. The analysis generated a prediction model that allowed EEG data to be analyzed and classified in real time during online BCI operation. The real-time online performance of the integrated BCI-FES system was tested in a group of five able-bodied subjects who used repetitive foot dorsiflexion to elicit BCI-FES mediated dorsiflexion of the contralateral foot. Five able-bodied subjects performed 10 alternations of idling and repetitive foot dorsifiexion to trigger BCI-FES mediated dorsifiexion of the contralateral foot. The epochs of BCI-FES mediated foot dorsifiexion were highly correlated with the epochs of voluntary foot dorsifiexion (correlation coefficient ranged between 0.59 and 0.77) with latencies ranging from 1.4 sec to 3.1 sec. In addition, all subjects achieved a 100% BCI-FES response (no omissions), and one subject had a single false alarm. This study suggests that the integration of a noninvasive BCI with a lower-extremity FES system is feasible. With additional modifications, the proposed BCI-FES system may offer a novel and effective therapy in the neuro-rehabilitation of individuals with lower extremity paralysis due to neurological injuries.

The Effect of Contralateral Acoustic Stimulation on Spontaneous Otoacoustic Emissions

PubMed Central

Dhar, Sumitrajit

2009-01-01

Evoked otoacoustic emissions are often used to study the medial olivocochlear (MOC) efferents in humans. There has been concern that the emission-evoking stimulus may itself elicit efferent activity and alter the evoked otoacoustic emission. Spontaneous otoacoustic emissions (SOAEs) are hence advantageous as no external stimulation is necessary to record the response in the test ear. Contralateral acoustic stimulation (CAS) has been shown to suppress SOAE level and elevate SOAE frequency, but the time course of these effects is largely unknown. By utilizing the Choi–Williams distribution, here we report a gradual adaptation during the presence of CAS and an overshoot following CAS offset in both SOAE magnitude and frequency from six normal-hearing female human subjects. Furthermore, we have quantified the time constants of both magnitude and frequency shifts at the onset, presence, and offset of four levels of CAS. Most studies using contralateral elicitors do not stringently control the middle-ear muscle (MEM) reflex, leaving the results difficult to interpret. In addition to clinically available measures of the MEM reflex, we have incorporated a sensitive laboratory technique to monitor the MEM reflex in our subjects, allowing us to interpret the results with greater confidence. PMID:19798532

Neurocognitive Brain Response to Transient Impairment of Wernicke's Area

PubMed Central

Mason, Robert A.; Prat, Chantel S.; Just, Marcel Adam

2014-01-01

This study examined how the brain system adapts and reconfigures its information processing capabilities to maintain cognitive performance after a key cortical center [left posterior superior temporal gyrus (LSTGp)] is temporarily impaired during the performance of a language comprehension task. By applying repetitive transcranial magnetic stimulation (rTMS) to LSTGp and concurrently assessing the brain response with functional magnetic resonance imaging, we found that adaptation consisted of 1) increased synchronization between compensating regions coupled with a decrease in synchronization within the primary language network and 2) a decrease in activation at the rTMS site as well as in distal regions, followed by their recovery. The compensatory synchronization included 3 centers: The contralateral homolog (RSTGp) of the area receiving rTMS, areas adjacent to the rTMS site, and a region involved in discourse monitoring (medial frontal gyrus). This approach reveals some principles of network-level adaptation to trauma with potential application to traumatic brain injury, stroke, and seizure. PMID:23322403

Neurocognitive brain response to transient impairment of Wernicke's area.

PubMed

Mason, Robert A; Prat, Chantel S; Just, Marcel Adam

2014-06-01

This study examined how the brain system adapts and reconfigures its information processing capabilities to maintain cognitive performance after a key cortical center [left posterior superior temporal gyrus (LSTGp)] is temporarily impaired during the performance of a language comprehension task. By applying repetitive transcranial magnetic stimulation (rTMS) to LSTGp and concurrently assessing the brain response with functional magnetic resonance imaging, we found that adaptation consisted of 1) increased synchronization between compensating regions coupled with a decrease in synchronization within the primary language network and 2) a decrease in activation at the rTMS site as well as in distal regions, followed by their recovery. The compensatory synchronization included 3 centers: The contralateral homolog (RSTGp) of the area receiving rTMS, areas adjacent to the rTMS site, and a region involved in discourse monitoring (medial frontal gyrus). This approach reveals some principles of network-level adaptation to trauma with potential application to traumatic brain injury, stroke, and seizure.

Brain Activity Changes in Somatosensory and Emotion-Related Areas With Medial Patellofemoral Ligament Deficiency.

PubMed

Kadowaki, Masaru; Tadenuma, Taku; Kumahashi, Nobuyuki; Uchio, Yuji

2017-11-01

Patellar instability with medial patellofemoral ligament (MPFL) deficiency is a common sports injury among young people. Although nonoperative and surgical treatment can provide stability of the patella, patients often have anxiety related to the knee. We speculate that neural dysfunction may be related to anxiety in these patients; however, the mechanism in the brain that generates this anxiety remains unknown. (1) How does brain activity in patients with MPFL deficiency change in the areas related to somatic sensation against lateral shift of the patella? (2) How does patella instability, which can lead to continuous fear or apprehension for dislocation, influence brain activity in the areas related to emotion? Nineteen patients with MPFL deficiency underwent surgical reconstruction in our hospital from April 2012 to March 2014. Excluding seven patients with osteochondral lesions, 12 patients (five males and seven females; mean age, 20 years) with MPFL deficiency were sequentially included in this study. Eleven control subjects (four males and seven females; mean age, 23 years) were recruited from medical students who had no history of knee injury. Diagnosis of the MPFL deficiency was made with MR images, which confirmed the rupture, and by proving the instability with a custom-made biomechanical device. Brain activity during passive lateral stress to the patella was assessed by functional MRI. Functional and anatomic images were analyzed using statistical parametric mapping. Differences in functional MRI outcome measures from the detected activated brain regions between the patients with MPFL deficiency and controls were assessed using t tests. Intergroup analysis showed less activity in several sensorimotor cortical areas, including the contralateral primary somatosensory areas (% signal change for MPFL group 0.49% versus 1.1% for the control group; p < 0.001), thalamus (0.2% versus 0.41% for the MPFL versus control, respectively; p < 0.001), ipsilateral thalamus (0.02% versus 0.27% for the MPFL versus control, respectively; p < 0.001), and ipsilateral cerebellum (0.82% versus 1.25% for the MPFL versus control, respectively; p < 0.001) in the MPFL deficiency group than in the control group. In contrast, the MPFL deficiency group showed more activity in several areas, including the contralateral primary motor area (1.06% versus 0.6% for the MPFL versus control, respectively; p < 0.001), supplementary motor area (0.89% versus 0.52% for the MPFL versus control, respectively; p < 0.001), prefrontal cortex (1.09% versus 1.09% for the MPFL versus control, respectively; p < 0.001), inferior parietal lobule (0.89% versus 0.62% for the MPFL versus control, respectively; p < 0.001), anterior cingulate cortex (0.84% versus 0.08% for the MPFL versus control, respectively; p < 0.001), visual cortex (0.86% versus 0.14% for the MPFL versus control, respectively; p < 0.001), vermis (1.18% versus 0.37% for the MPFL versus control, respectively; p < 0.001), and ipsilateral prefrontal cortex (1.1% versus 0.75% for the MPFL versus control, respectively; p < 0.001) than did the control group. Less activity in the contralateral somatosensory cortical areas suggested that MPFL deficiency may lead to diminished somatic sensation against lateral shift of the patella. In contrast, increased activity in the anterior cingulate cortex, prefrontal cortex, and inferior parietal lobule may indicate anxiety or fear resulting from patellar instability, which is recognized as an aversion similar to that toward chronic pain. This study suggests that specific brain-area activity is increased in patients with MPFL deficiency relative to that in controls. Further longitudinal research to assess brain activity and proprioception between patients pre- and postreconstructive knee surgery may reveal more regarding how patella instability is related to brain function. We hope that based on such research, a neural approach to improve patella-instability-related brain function can be developed.

Near-infrared spectroscopy of the human brain during electroconvulsive therapy

NASA Astrophysics Data System (ADS)

Fantini, Sergio; Fabbri, Francesco; Nadgir, Shalini; Henry, Michael E.; Renshaw, Perry F.; Franceschini, Maria-Angela

2003-07-01

We report non-invasive, bilateral measurements of cerebral oxygenation performed with near-infrared spectroscopy (NIRS) on ten patients undergoing right unilateral electro-convulsive therapy (ECT). Right unilateral ECT consists of delivering an electrical current through the right brain hemisphere to induce a seizure, which is associated with significant changes in systemic and regional physiological parameters. In this work, we have examined the regional cerebral oxygenation (StO2) measured with NIRS on the right and left sides of the frontal brain region, and the systemic arterial oxygenation (SaO2) measured with pulse oximetry. On the ten patients examined, we have found that the decrease in the cerebral oxygenation on the side ipsilateral to the ECT electrical discharge (ΔStO2(ipsi)) is consistently stronger than the decrease on the contralateral side (ΔStO2(contra)). The average and standard deviation for the ipsilateral and contralateral oxygenation changes across the ten patients are ΔStO2(ipsi) = -22 +/- 10% and ΔStO2(contra) = -6 +/- 10%, respectively. By contrast, we observed two distinct behaviors in the arterial saturation; in five patients, SaO2 did not significantly change during the ECT procedure, and in three patients, SaO2 decreased by -16+/- 6%, an intermediate value with respect to the changes observed in StO2(ipsi) and StO2(contra) (we do not have the SaO2 recording in the remaining two patients for technical reasons). These results indicate that NIRS monitoring of the cerebral oxygenation during ECT has the potential of being a valuable addition to the standard monitoring of arterial saturation with pulse oximetry.

A pilot study on the optimal speeds for passive wrist movements by a rehabilitation robot of stroke patients: A functional NIRS study.

PubMed

Bae, Sung Jin; Jang, Sung Ho; Seo, Jeong Pyo; Chang, Pyung Hun

2017-07-01

The optimal conditions inducing proper brain activation during performance of rehabilitation robots should be examined to enhance the efficiency of robot rehabilitation based on the concept of brain plasticity. In this study, we attempted to investigate differences in cortical activation according to the speeds of passive wrist movements performed by a rehabilitation robot for stroke patients. 9 stroke patients with right hemiparesis participated in this study. Passive movements of the affected wrist were performed by the rehabilitation robot at three different speeds: 0.25 Hz; slow, 0.5Hz; moderate and 0.75 Hz; fast. We used functional near-infrared spectroscopy to measure the brain activity during the passive movements performed by a robot. Group-average activation map and the relative changes in oxy-hemoglobin (ΔOxyHb) in two regions of interest: the primary sensory-motor cortex (SM1); premotor area (PMA) and region of all channels were measured. In the result of group-averaged activation map, the contralateral SM1, PMA and somatosensory association cortex (SAC) showed the greatest significant activation according to the movements at 0.75 Hz, while there is no significantly activated area at 0.5 Hz. Regarding ΔOxyHb, no significant diiference was observed among three speeds regardless of region. In conclusion, the contralateral SM1, PMA and SAC showed the greatest activation by a fast speed (0.75 Hz) rather than slow (0.25 Hz) and moderate (0. 5 Hz) speed. Our results suggest an optimal speed for execution of the wrist rehabilitation robot. Therefore, we believe that our findings might point to several promising applications for future research regarding useful and empirically-based robot rehabilitation therapy.

Functional anatomy of motor urgency.

PubMed

Thobois, Stéphane; Ballanger, Bénédicte; Baraduc, Pierre; Le Bars, Didier; Lavenne, Franck; Broussolle, Emmanuel; Desmurget, Michel

2007-08-01

This PET H(2)(15)O study uses a reaching task to determine the neural basis of the unconscious motor speed up observed in the context of urgency in healthy subjects. Three conditions were considered: self-initiated (produce the fastest possible movement toward a large plate, when ready), externally-cued (same as self-initiated but in response to an acoustic cue) and temporally-pressing (same as externally-cued with the plate controlling an electromagnet that prevented a rolling ball from falling at the bottom of a tilted ramp). Results show that: (1) Urgent responses (Temporally-pressing versus Externally-cued) engage the left parasagittal and lateral cerebellar hemisphere and the sensorimotor cortex (SMC) bilaterally; (2) Externally-driven responses (Externally-cued versus Self-initiated) recruit executive areas within the contralateral SMC; (3) Volitional responses (Self-initiated versus Externally-cued) involve prefrontal cortical areas. These observations are discussed with respect to the idea that neuromuscular energy is set to a submaximal threshold in self-determined situations. In more challenging tasks, this threshold is raised and the first answer of the nervous system is to optimize the response of the lateral (i.e. crossed) corticospinal tract (contralateral SMC) and ipsilateral cerebellum. In a second step, the anterior (i.e. uncrossed) corticospinal tract (ipsilateral SMC) and the contralateral cerebellum are recruited. This recruitment is akin to the strategy observed during recovery in patients with brain lesions.

Tactile perceptual learning: learning curves and transfer to the contralateral finger.

PubMed

Kaas, Amanda L; van de Ven, Vincent; Reithler, Joel; Goebel, Rainer

2013-02-01

Tactile perceptual learning has been shown to improve performance on tactile tasks, but there is no agreement about the extent of transfer to untrained skin locations. The lack of such transfer is often seen as a behavioral index of the contribution of early somatosensory brain regions. Moreover, the time course of improvements has never been described explicitly. Sixteen subjects were trained on the Ludvigh task (a tactile vernier task) on four subsequent days. On the fifth day, transfer of learning to the non-trained contralateral hand was tested. In five subjects, we explored to what extent training effects were retained approximately 1.5 years after the final training session, expecting to find long-term retention of learning effects after training. Results showed that tactile perceptual learning mainly occurred offline, between sessions. Training effects did not transfer initially, but became fully available to the untrained contralateral hand after a few additional training runs. After 1.5 years, training effects were not fully washed out and could be recuperated within a single training session. Interpreted in the light of theories of visual perceptual learning, these results suggest that tactile perceptual learning is not fundamentally different from visual perceptual learning, but might proceed at a slower pace due to procedural and task differences, thus explaining the apparent divergence in the amount of transfer and long-term retention.

Electrophysiological Evidence for a Sensory Recruitment Model of Somatosensory Working Memory.

PubMed

Katus, Tobias; Grubert, Anna; Eimer, Martin

2015-12-01

Sensory recruitment models of working memory assume that information storage is mediated by the same cortical areas that are responsible for the perceptual processing of sensory signals. To test this assumption, we measured somatosensory event-related brain potentials (ERPs) during a tactile delayed match-to-sample task. Participants memorized a tactile sample set at one task-relevant hand to compare it with a subsequent test set on the same hand. During the retention period, a sustained negativity (tactile contralateral delay activity, tCDA) was elicited over primary somatosensory cortex contralateral to the relevant hand. The amplitude of this component increased with memory load and was sensitive to individual limitations in memory capacity, suggesting that the tCDA reflects the maintenance of tactile information in somatosensory working memory. The tCDA was preceded by a transient negativity (N2cc component) with a similar contralateral scalp distribution, which is likely to reflect selection of task-relevant tactile stimuli at the encoding stage. The temporal sequence of N2cc and tCDA components mirrors previous observations from ERP studies of working memory in vision. The finding that the sustained somatosensory delay period activity varies as a function of memory load supports a sensory recruitment model for spatial working memory in touch. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The cytokine temporal profile in rat cortex after controlled cortical impact

PubMed Central

Dalgard, Clifton L.; Cole, Jeffrey T.; Kean, William S.; Lucky, Jessica J.; Sukumar, Gauthaman; McMullen, David C.; Pollard, Harvey B.; Watson, William D.

2012-01-01

Cerebral inflammatory responses may initiate secondary cascades following traumatic brain injury (TBI). Changes in the expression of both cytokines and chemokines may activate, regulate, and recruit innate and adaptive immune cells associated with secondary degeneration, as well as alter a host of other cellular processes. In this study, we quantified the temporal expression of a large set of inflammatory mediators in rat cortical tissue after brain injury. Following a controlled cortical impact (CCI) on young adult male rats, cortical and hippocampal tissue of the injured hemisphere and matching contralateral material was harvested at early (4, 12, and 24 hours) and extended (3 and 7 days) time points post-procedure. Naïve rats that received only anesthesia were used as controls. Processed brain homogenates were assayed for chemokine and cytokine levels utilizing an electrochemiluminescence-based multiplex ELISA platform. The temporal profile of cortical tissue samples revealed a multi-phasic injury response following brain injury. CXCL1, IFN-γ, TNF-α levels significantly peaked at four hours post-injury compared to levels found in naïve or contralateral tissue. CXCL1, IFN-γ, and TNF-α levels were then observed to decrease at least 3-fold by 12 hours post-injury. IL-1β, IL-4, and IL-13 levels were also significantly elevated at four hours post-injury although their expression did not decrease more than 3-fold for up to 24 hours post-injury. Additionally, IL-1β and IL-4 levels displayed a biphasic temporal profile in response to injury, which may suggest their involvement in adaptive immune responses. Interestingly, peak levels of CCL2 and CCL20 were not observed until after four hours post-injury. CCL2 levels in injured cortical tissue were significantly higher than peak levels of any other inflammatory mediator measured, thus suggesting a possible use as a biomarker. Fully elucidating chemokine and cytokine signaling properties after brain injury may provide increased insight into a number of secondary cascade events that are initiated or regulated by inflammatory responses. PMID:22291617

The cytokine temporal profile in rat cortex after controlled cortical impact.

PubMed

Dalgard, Clifton L; Cole, Jeffrey T; Kean, William S; Lucky, Jessica J; Sukumar, Gauthaman; McMullen, David C; Pollard, Harvey B; Watson, William D

2012-01-01

Cerebral inflammatory responses may initiate secondary cascades following traumatic brain injury (TBI). Changes in the expression of both cytokines and chemokines may activate, regulate, and recruit innate and adaptive immune cells associated with secondary degeneration, as well as alter a host of other cellular processes. In this study, we quantified the temporal expression of a large set of inflammatory mediators in rat cortical tissue after brain injury. Following a controlled cortical impact (CCI) on young adult male rats, cortical and hippocampal tissue of the injured hemisphere and matching contralateral material was harvested at early (4, 12, and 24 hours) and extended (3 and 7 days) time points post-procedure. Naïve rats that received only anesthesia were used as controls. Processed brain homogenates were assayed for chemokine and cytokine levels utilizing an electrochemiluminescence-based multiplex ELISA platform. The temporal profile of cortical tissue samples revealed a multi-phasic injury response following brain injury. CXCL1, IFN-γ, TNF-α levels significantly peaked at four hours post-injury compared to levels found in naïve or contralateral tissue. CXCL1, IFN-γ, and TNF-α levels were then observed to decrease at least 3-fold by 12 hours post-injury. IL-1β, IL-4, and IL-13 levels were also significantly elevated at four hours post-injury although their expression did not decrease more than 3-fold for up to 24 hours post-injury. Additionally, IL-1β and IL-4 levels displayed a biphasic temporal profile in response to injury, which may suggest their involvement in adaptive immune responses. Interestingly, peak levels of CCL2 and CCL20 were not observed until after four hours post-injury. CCL2 levels in injured cortical tissue were significantly higher than peak levels of any other inflammatory mediator measured, thus suggesting a possible use as a biomarker. Fully elucidating chemokine and cytokine signaling properties after brain injury may provide increased insight into a number of secondary cascade events that are initiated or regulated by inflammatory responses.

Dichoptic training enables the adult amblyopic brain to learn.

PubMed

Li, Jinrong; Thompson, Benjamin; Deng, Daming; Chan, Lily Y L; Yu, Minbin; Hess, Robert F

2013-04-22

Adults with amblyopia, a common visual cortex disorder caused primarily by binocular disruption during an early critical period, do not respond to conventional therapy involving occlusion of one eye. But it is now clear that the adult human visual cortex has a significant degree of plasticity, suggesting that something must be actively preventing the adult brain from learning to see through the amblyopic eye. One possibility is an inhibitory signal from the contralateral eye that suppresses cortical inputs from the amblyopic eye. Such a gating mechanism could explain the apparent lack of plasticity within the adult amblyopic visual cortex. Here we provide direct evidence that alleviating suppression of the amblyopic eye through dichoptic stimulus presentation induces greater levels of plasticity than forced use of the amblyopic eye alone. This indicates that suppression is a key gating mechanism that prevents the amblyopic brain from learning to see. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reproductive age modulates the impact of focal ischemia on the forebrain as well as the effects of estrogen treatment in female rats

PubMed Central

Selvamani, Amutha; Sohrabji, Farida

2009-01-01

While human observational studies and animal studies report a neuroprotective role for estrogen therapy in stroke, the multicenter placebo-controlled Women's Health Initiative (WHI) study concluded that hormone therapy increased the risk for stroke in postmenopausal women. The present study therefore tested the hypothesis that estrogen replacement would increase the severity of a stroke-like injury in females when this replacement occurs after a prolonged hypoestrogenic period, such as the menopause or reproductive senescence, but not when given to females that were normally cycling immediately prior to the hormone replacement. Two groups of female rats were used: multiparous females with normal but lengthened estrus cycles (mature adults), and older multiparous females currently in a persistent acyclic state (reproductive senescent). Animals were either used intact, or were bilaterally ovariectomized and immediately replaced with a 17β-estradiol pellet or control pellet. Animals were subject to a forelimb placing test (a test for sensorimotor deficit) and thereafter to middle cerebral artery occlusion (MCAo) by stereotaxic injection of the vasoconstrictive peptide endothelin-1, adjacent to the MCA. One week after stroke, behavioral tests were performed again. Cortical and striatal infarct volume, measured from brain slices, was significantly greater in intact reproductive senescent females as compared to intact mature adults. Furthermore, estrogen treatment to ovariectomized mature adult females significantly reduced the cortical infarct volume. Paradoxically, estrogen treatment to ovariectomized reproductive senescent females significantly increased cortical and striatal infarct volumes as compared to control pellet replaced senescent females. Significant post-stroke behavioral deficit was observed in all groups on the side contralateral to the lesion, while senescent females also exhibited deficits on the ipsilateral side, in the cross-midline forelimb placement test. Using an animal model that approximates the natural ovarian aging process, these findings strongly support the hypothesis that the effectiveness of estrogen therapy in protecting brain health may depend critically on the time of initiation with respect to a female's reproductive status. PMID:18829137

Cooperation Not Competition: Bihemispheric tDCS and fMRI Show Role for Ipsilateral Hemisphere in Motor Learning.

PubMed

Waters, Sheena; Wiestler, Tobias; Diedrichsen, Jörn

2017-08-02

What is the role of ipsilateral motor and premotor areas in motor learning? One view is that ipsilateral activity suppresses contralateral motor cortex and, accordingly, that inhibiting ipsilateral regions can improve motor learning. Alternatively, the ipsilateral motor cortex may play an active role in the control and/or learning of unilateral hand movements. We approached this question by applying double-blind bihemispheric transcranial direct current stimulation (tDCS) over both contralateral and ipsilateral motor cortex in a between-group design during 4 d of unimanual explicit sequence training in human participants. Independently of whether the anode was placed over contralateral or ipsilateral motor cortex, bihemispheric stimulation yielded substantial performance gains relative to unihemispheric or sham stimulation. This performance advantage appeared to be supported by plastic changes in both hemispheres. First, we found that behavioral advantages generalized strongly to the untrained hand, suggesting that tDCS strengthened effector-independent representations. Second, functional imaging during speed-matched execution of trained sequences conducted 48 h after training revealed sustained, polarity-independent increases in activity in both motor cortices relative to the sham group. These results suggest a cooperative rather than competitive interaction of the two motor cortices during skill learning and suggest that bihemispheric brain stimulation during unimanual skill learning may be beneficial because it harnesses plasticity in the ipsilateral hemisphere. SIGNIFICANCE STATEMENT Many neurorehabilitation approaches are based on the idea that is beneficial to boost excitability in the contralateral hemisphere while attenuating that of the ipsilateral cortex to reduce interhemispheric inhibition. We observed that bihemispheric transcranial direct current stimulation (tDCS) with the excitatory anode either over contralateral or ipsilateral motor cortex facilitated motor learning nearly twice as strongly as unihemispheric tDCS. These increases in motor learning were accompanied by increases in fMRI activation in both motor cortices that outlasted the stimulation period, as well as increased generalization to the untrained hand. Collectively, our findings suggest a cooperative rather than a competitive role of the hemispheres and imply that it is most beneficial to harness plasticity in both hemispheres in neurorehabilitation of motor deficits. Copyright © 2017 Waters et al.

Evaluation of radiotherapy techniques for radical treatment of lateralised oropharyngeal cancers : Dosimetry and NTCP.

PubMed

McQuaid, D; Dunlop, A; Nill, S; Franzese, C; Nutting, C M; Harrington, K J; Newbold, K L; Bhide, S A

2016-08-01

The aim of this study was to investigate potential advantages and disadvantages of three-dimensional conformal radiotherapy (3DCRT), multiple fixed-field intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) in terms of dose to the planning target volume (PTV), organs at risk (OARs) and normal tissue complication probability (NTCP) for delivering ipsilateral radiotherapy. 3DCRT, IMRT and VMAT were compared in patients with well-lateralised primary tonsillar cancers who underwent primary radical ipsilateral radiotherapy. The following parameters were compared: conformity index (CI); homogeneity index (HI); dose-volume histograms (DVHs) of PTVs and OARs; NTCP, risk of radiation-induced cancer and dose accumulation during treatment. IMRT and VMAT were superior to 3DCRT in terms of CI, HI and dose to the target volumes, as well as mandible and dose accumulation robustness. The techniques were equivalent in terms of dose and NTCP for the contralateral oral cavity, contralateral submandibular gland and mandible, when specific dose constraint objectives were used on the oral cavity volume. Although the volume of normal tissue exposed to low-dose radiation was significantly higher with IMRT and VMAT, the risk of radiation-induced secondary malignancy was dependant on the mathematical model used. This study demonstrates the superiority of IMRT/VMAT techniques over 3DCRT in terms of dose homogeneity, conformity and consistent dose delivery to the PTV throughout the course of treatment in patients with lateralised oropharyngeal cancers. Dosimetry and NTCP calculations show that these techniques are equivalent to 3DCRT with regard to the risk of acute mucositis when specific dose constraint objectives were used on the contralateral oral cavity OAR.

Descending pathways to the cutaneus trunci muscle motoneuronal cell group in the cat

NASA Technical Reports Server (NTRS)

Holstege, Gert; Blok, Bertil F.

1989-01-01

The descending pathways to the motoneuronal cell group of the cutaneous trunci muscle (CTM) of the cat were investigated by injecting H-3-labeled lucine into the brain stem, the diencephalon, or the C1, C2, C6, and C8 segments of the spinal cord, and examining fixed autoradiographic sections of the spinal cord and brain regions. Results demonstrate presence of specific supraspinal projectons to the CTM motor nucleus originating in the contralateral nucleus retroambiguous and the ipsilateral dorsolateral pontine tegmentum. Results also suggest that propriospinal pathways to the CTM motor nucleus originating in the cervical cord do not exist, although these propriospinal projections to all other motoneuronal cell groups surrounding the CTM nucleus are very strong.

Vocal Fold Vibration Following Surgical Intervention in Three Vocal Pathologies: A Preliminary Study.

PubMed

Chen, Wenli; Woo, Peak; Murry, Thomas

2017-09-01

High-speed videoendoscopy captures the cycle-to-cycle vibratory motion of each individual vocal fold in normal and severely disordered phonation. Therefore, it provides a direct method to examine the specific vibratory changes following vocal fold surgery. The purpose of this study was to examine the vocal fold vibratory pattern changes in the surgically treated pathologic vocal fold and the contralateral vocal fold in three vocal pathologies: vocal polyp (n = 3), paresis or paralysis (n = 3), and scar (n = 3). Digital kymography was used to extract high-speed kymographic vocal fold images at the mid-membranous region of the vocal fold. Spectral analysis was subsequently applied to the digital kymography to quantify the cycle-to-cycle movements of each vocal fold, expressed as a spectrum. Surgical modification resulted in significantly improved spectral power of the treated pathologic vocal fold. Furthermore, the contralateral vocal fold also presented with improved spectral power irrespective of vocal pathology. In comparison with normal vocal fold spectrum, postsurgical vocal fold vibrations continued to demonstrate decreased vibratory amplitude in both vocal folds. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

In vivo, noninvasive functional measurements of bone sarcoma using diffuse optical spectroscopic imaging

NASA Astrophysics Data System (ADS)

Peterson, Hannah M.; Hoang, Bang H.; Geller, David; Yang, Rui; Gorlick, Richard; Berger, Jeremy; Tingling, Janet; Roth, Michael; Gill, Jonathon; Roblyer, Darren

2017-12-01

Diffuse optical spectroscopic imaging (DOSI) is an emerging near-infrared imaging technique that noninvasively measures quantitative functional information in thick tissue. This study aimed to assess the feasibility of using DOSI to measure optical contrast from bone sarcomas. These tumors are rare and pose technical and practical challenges for DOSI measurements due to the varied anatomic locations and tissue depths of presentation. Six subjects were enrolled in the study. One subject was unable to be measured due to tissue contact sensitivity. For the five remaining subjects, the signal-to-noise ratio, imaging depth, optical properties, and quantitative tissue concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipids from tumor and contralateral normal tissues were assessed. Statistical differences between tumor and contralateral normal tissue were found in chromophore concentrations and optical properties for four subjects. Low signal-to-noise was encountered during several subject's measurements, suggesting increased detector sensitivity will help to optimize DOSI for this patient population going forward. This study demonstrates that DOSI is capable of measuring optical properties and obtaining functional information in bone sarcomas. In the future, DOSI may provide a means to stratify treatment groups and monitor chemotherapy response for this disease.

Postrenal acute kidney injury in a patient with unilateral ureteral obstruction caused by urolithiasis: A case report.

PubMed

Kazama, Itsuro; Nakajima, Toshiyuki

2017-10-01

In patients with bilateral ureteral obstruction, the serum creatinine levels are often elevated, sometimes causing postrenal acute kidney injury (AKI). In contrast, those with unilateral ureteral obstruction present normal serum creatinine levels, as long as their contralateral kidneys are preserved intact. However, the unilateral obstruction of the ureter could affect the renal function, as it humorally influences the renal hemodynamics. A 66-year-old man with a past medical history of hypertension and diabetes mellitus came to our outpatient clinic because of right abdominal dullness. Unilateral ureteral obstruction caused by a radio-opaque calculus in the right upper ureter and a secondary renal dysfunction. As oral hydration and the use of calcium antagonists failed to allow the spontaneous stone passage, extracorporeal shock wave lithotripsy (ESWL) was performed. Immediately after the passage of the stone, the number of red blood cells in the urine was dramatically decreased and the serum creatinine level almost returned to the normal range with the significant increase in glomerular filtration rate. Unilateral ureteral obstruction by the calculus, which caused reflex vascular constriction and ureteral spasm in the contralateral kidney, was thought to be responsible for the deteriorating renal function.

Depletion of macrophages in CD11b diphtheria toxin receptor mice induces brain inflammation and enhances inflammatory signaling during traumatic brain injury.

PubMed

Frieler, Ryan A; Nadimpalli, Sameera; Boland, Lauren K; Xie, Angela; Kooistra, Laura J; Song, Jianrui; Chung, Yutein; Cho, Kae W; Lumeng, Carey N; Wang, Michael M; Mortensen, Richard M

2015-10-22

Immune cells have important roles during disease and are known to contribute to secondary, inflammation-induced injury after traumatic brain injury. To delineate the functional role of macrophages during traumatic brain injury, we depleted macrophages using transgenic CD11b-DTR mice and subjected them to controlled cortical impact. We found that macrophage depletion had no effect on lesion size assessed by T2-weighted MRI scans 28 days after injury. Macrophage depletion resulted in a robust increase in proinflammatory gene expression in both the ipsilateral and contralateral hemispheres after controlled cortical impact. Interestingly, this sizeable increase in inflammation did not affect lesion development. We also showed that macrophage depletion resulted in increased proinflammatory gene expression in the brain and kidney in the absence of injury. These data demonstrate that depletion of macrophages in CD11b-DTR mice can significantly modulate the inflammatory response during brain injury without affecting lesion formation. These data also reveal a potentially confounding inflammatory effect in CD11b-DTR mice that must be considered when interpreting the effects of macrophage depletion in disease models. Copyright © 2015 Elsevier B.V. All rights reserved.

Cerebral blood-flow tomography: xenon-133 compared with isopropyl-amphetamine-iodine-123: concise communication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lassen, N.A.; Henriksen, L.; Holm, S.

1983-01-01

Tomographic maps of local cerebral blood flow (CBF) were obtained with xenon-133 and with isopropyl-amphetamine-iodine-123 (IMP) in 11 subjects: one normal, two tumor cases, and eight cerebrovascular cases. A highly sensitive four-face, rapidly rotating, single-photon emission tomograph was used. The Xe-133 flow maps are essentially based on the average Xe-133 concentration over the initial 2 min during and after an inhalation of the inert gas lasting 1 min. These maps agreed very well with the early IMP maps obtained over the initial 10 min following an i.v. bolus injection. The subsequent IMP tomograms showed a slight decrease in contrast amountingmore » to appr. five percentage points in the CBF ratio between diseased and contralateral areas. It is concluded that Xe-133 is more practical: low cost, available on a 7-day basis, easily repeatable, quantifiable without the need for arterial sampling, and with low radiation exposure to patient and personnel. On the other hand, IMP gives an image of slightly higher resolution. It also introduces a new class of iodinated brain-seeking compounds allowing, perhaps, imaging of other functions more important than mere blood flow.« less

Early pathologic findings and long-term improvement in anti-Ma2-associated encephalitis.

PubMed

Blumenthal, D T; Salzman, K L; Digre, K B; Jensen, R L; Dunson, W A; Dalmau, J

2006-07-11

A 67-year-old man sequentially developed anti-Ma2-associated paraneoplastic encephalitis (PNE) and contralateral herpes simplex encephalitis (HSE). Brain biopsy 1 month before HSE revealed extensive infiltrates of T cells, B cells, and plasma cells. Most T cells expressed the cytotoxic granule-associated protein TIA-1 and the membranolytic protein granzyme-B. Although recovery was thought to be unlikely, treatment of the PNE with corticosteroids and resection of the associated lung cancer resulted in dramatic improvement for 21 months.

SU-E-J-87: Ventilation Weighting Effect On Mean Doses of Both Side Lungs for Patients with Advanced Stage Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qu, H; Xia, P; Yu, N

Purpose: To study ventilation weighting effect on radiation doses to both side lungs for patients with advanced stage lung cancer. Methods: Fourteen patients with advanced stage lung cancer were included in this retrospective study. Proprietary software was developed to calculate the lung ventilation map based on 4DCT images acquired for radiation therapy. Two phases of inhale (0%) and exhale (50%) were used for the lung ventilation calculations. For each patient, the CT images were resampled to the same dose calculation resolution of 3mmx3mmx3mm. The ventilation distribution was then normalized by the mean value of the ventilation. The ventilation weighted dosemore » was calculated by applying linearly weighted ventilation to the dose of each pixel. The lung contours were automatically delineated from patient CT image with lung window, excluding the tumor and high density tissues. For contralateral and ipsilateral lungs, the mean lung doses from the original plan and ventilation weighted mean lung doses were compared using two tail t-Test. Results: The average of mean dose was 6.1 ±3.8Gy for the contralateral lungs, and 26.2 ± 14.0Gy for the ipsilateral lungs. The average of ventilation weighted dose was 6.3± 3.8Gy for the contralateral lungs and 24.6 ± 13.1Gy for the ipsilateral lungs. The statistics analysis shows the significance of the mean dose increase (p<0.015) for the contralateral lungs and decrease (p<0.005) for the ipsilateral lungs. Conclusion: Ventilation weighted doses were greater than the un-weighted doses for contralateral lungs and smaller for ipsilateral lungs. This Result may be helpful to understand the radiation dosimetric effect on the lung function and provide planning guidance for patients with advance stage lung cancer.« less

Diagnostic effectiveness of quantitative [18F]flutemetamol PET imaging for detection of fibrillar amyloid β using cortical biopsy histopathology as the standard of truth in subjects with idiopathic normal pressure hydrocephalus

PubMed Central

2014-01-01

Introduction PET imaging of amyloid-β (Aβ) in vivo holds promise for aiding in earlier diagnosis and intervention in Alzheimer’s disease (AD) and mild cognitive impairment. AD-like Aβ pathology is a common comorbidity in patients with idiopathic normal pressure hydrocephalus (iNPH). Fifty patients with iNPH needing ventriculo-peritoneal shunting or intracranial pressure monitoring underwent [18F]flutemetamol PET before (N = 28) or after (N = 22) surgery. Cortical uptake of [18F]flutemetamol was assessed visually by blinded reviewers, and also quantitatively via standard uptake value ratio (SUVR) in specific neocortical regions in relation to either cerebellum or pons reference region: the cerebral cortex of (prospective studies) or surrounding (retrospective studies) the biopsy site, the contralateral homolog, and a calculated composite brain measure. Aβ pathology in the biopsy specimen (standard of truth [SoT]) was measured using Bielschowsky silver and thioflavin S plaque scores, percentage area of grey matter positive for monoclonal antibody to Aβ (4G8), and overall pathology impression. We set out to find (1) which pair(s) of PET SUVR and pathology SoT endpoints matched best, (2) whether quantitative measures of [18F]flutemetamol PET were better for predicting the pathology outcome than blinded image examination (BIE), and (3) whether there was a better match between PET image findings in retrospective vs. prospective studies. Results Of the 24 possible endpoint/SoT combinations, the one with composite-cerebellum SUVR and SoT based on overall pathology had the highest Youden index (1.000), receiver operating characteristic area under the curve (1.000), sensitivity (1.000), specificity (1.000), and sum of sensitivity and specificity for the pooled data as well as for the retrospective and prospective studies separately (2.00, for all 3). The BIE sum of sensitivity and specificity, comparable to that for quantitation, was highest using Bielschowsky silver as SoT for all SUVRs (ipsilateral, contralateral, and composite, for both reference regions). The composite SUVR had a 100% positive predictive value (both reference regions) for the overall pathology diagnosis. All SUVRs had a 100% negative predictive value for the Bielschowsky silver result. Conclusion Bielschowsky silver stain and overall pathology judgment showed the strongest associations with imaging results. PMID:24755237

Supportive Use of Adipose-Derived Stem Cells in Cell-Assisted Lipotransfer for Localized Scleroderma.

PubMed

Chen, Bo; Wang, Xiaojun; Long, Xiao; Zhang, Mingzi; Huang, Jiuzuo; Yu, Nanze; Xu, Jing

2018-06-01

The authors aimed to analyze factors related to lipotransfer for localized scleroderma, and to explore the feasibility of cell-assisted lipotransfer for localized scleroderma treatment. Abdominal fat samples were taken from six scleroderma patients without corticosteroid therapy, five scleroderma patients with corticosteroid therapy, and 10 normal liposuction patients. Their quantity, morphology, and proliferation ability were measured. Blood flow was measured by laser speckle contrast imaging in localized scleroderma lesions and normal contralateral regions for eight localized scleroderma patients. Bleomycin-induced skin fibrosis nude mice were also used to investigate differences between lipotransfer and cell-assisted lipotransfer. Fat weight was measured, and expression of transforming growth factor (TGF)-β1 and type III collagen in the injected skin was determined by immunohistochemistry. The number of stem cells from scleroderma patients with corticosteroid treatment was significantly reduced. Mean blood perfusion in localized scleroderma lesions was not significantly different than in the contralateral normal regions. In normal nude mice, there were no significant changes in TGF-β1 and type III collagen between the control, lipotransfer, and cell-assisted lipotransfer groups, whereas in bleomycin-induced skin fibrosis nude mice, lipotransfer and cell-assisted lipotransfer reduced TGF-β1 and type III collagen expression. For scleroderma patients, fewer adipose-derived stem cells, because of a history of corticosteroid therapy and a local inflammatory microenvironment, are more important factors, whereas blood supply showed no significant change. Therefore, cell-assisted lipotransfer not only improves the survival rate of transplanted fat but also improves skin texture in bleomycin-induced skin fibrosis nude mice.

Brain oscillatory signatures of motor tasks

PubMed Central

Birbaumer, Niels

2015-01-01

Noninvasive brain-computer-interfaces (BCI) coupled with prosthetic devices were recently introduced in the rehabilitation of chronic stroke and other disorders of the motor system. These BCI systems and motor rehabilitation in general involve several motor tasks for training. This study investigates the neurophysiological bases of an EEG-oscillation-driven BCI combined with a neuroprosthetic device to define the specific oscillatory signature of the BCI task. Controlling movements of a hand robotic orthosis with motor imagery of the same movement generates sensorimotor rhythm oscillation changes and involves three elements of tasks also used in stroke motor rehabilitation: passive and active movement, motor imagery, and motor intention. We recorded EEG while nine healthy participants performed five different motor tasks consisting of closing and opening of the hand as follows: 1) motor imagery without any external feedback and without overt hand movement, 2) motor imagery that moves the orthosis proportional to the produced brain oscillation change with online proprioceptive and visual feedback of the hand moving through a neuroprosthetic device (BCI condition), 3) passive and 4) active movement of the hand with feedback (seeing and feeling the hand moving), and 5) rest. During the BCI condition, participants received contingent online feedback of the decrease of power of the sensorimotor rhythm, which induced orthosis movement and therefore proprioceptive and visual information from the moving hand. We analyzed brain activity during the five conditions using time-frequency domain bootstrap-based statistical comparisons and Morlet transforms. Activity during rest was used as a reference. Significant contralateral and ipsilateral event-related desynchronization of sensorimotor rhythm was present during all motor tasks, largest in contralateral-postcentral, medio-central, and ipsilateral-precentral areas identifying the ipsilateral precentral cortex as an integral part of motor regulation. Changes in task-specific frequency power compared with rest were similar between motor tasks, and only significant differences in the time course and some narrow specific frequency bands were observed between motor tasks. We identified EEG features representing active and passive proprioception (with and without muscle contraction) and active intention and passive involvement (with and without voluntary effort) differentiating brain oscillations during motor tasks that could substantially support the design of novel motor BCI-based rehabilitation therapies. The BCI task induced significantly different brain activity compared with the other motor tasks, indicating neural processes unique to the use of body actuators control in a BCI context. PMID:25810484

Contralateral Occlusion Test: The effect of external ear canal occlusion on hearing thresholds.

PubMed

Reis, Luis Roque; Fernandes, Paulo; Escada, Pedro

Bedside testing with tuning forks may decrease turnaround time and improve decision making for a quick qualitative assessment of hearing loss. The purpose of this study was to quantify the effects of ear canal occlusion on hearing, in order to decide which tuning fork frequency is more appropriate to use for quantifying hearing loss with the Contralateral Occlusion Test. Twenty normal-hearing adults (forty ears) underwent sound field pure tone audiometry with and without ear canal occlusion. Each ear was tested with the standard frequencies. The contralateral ear was suppressed with by masking. Ear occlusion was performed by two examiners. Participants aged between 21 and 30 years (25.6±3.03 years) showed an increase in hearing thresholds with increasing frequencies from 19.94dB (250Hz) to 39.25dB (2000Hz). The threshold difference between occluded and unoccluded conditions was statistically significant and increased from 10.69dB (250Hz) to 32.12dB (2000Hz). There were no statistically significant differences according to gender or between the examiners. The occlusion effect increased the hearing thresholds and became more evident with higher frequencies. The occlusion method as performed demonstrated reproducibility. In the Contralateral Occlusion Test, 256Hz or 512Hz tuning forks should be used for diagnosis of mild hearing loss, and a 2048Hz tuning fork should be used for moderate hearing loss. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

Bilateral totally extraperitoneal (TEP) repair of the ultrasound-diagnosed asymptomatic contralateral inguinal hernia.

PubMed

Malouf, Phillip A; Descallar, Joseph; Berney, Christophe R

2018-02-01

The aim of this series is to determine the clinical utility of routine ultrasound (US) of the contralateral, clinically normal groin when a unilateral inguinal hernia is referred for hernia repair-specifically assessing the morbidity and short-term change in quality-of-life (QoL) due to repair of this occult contralateral hernia when also repairing the symptomatic side. TEP inguinal hernia repair affords the opportunity to repair any groin hernia through the same small incisions. US detects 96.6% of groin hernias with 84.4% specificity. 234 consecutive male patients with clinically unilateral and clinically bilateral hernia were enrolled; those with a clinically unilateral hernia were sent for groin US and if positive, a bilateral TEP groin hernia repair was performed (USBH). If negative, a unilateral TEP groin hernia repair was performed (UNIH). Carolina's comfort scales (CCS) and visual analogue scores (VAS) were recorded at 2 and 6 weeks postoperatively, while a modified CCS (MCCS) was recorded for all patients preoperatively. Bilateral TEP repair resulted in higher VAS scores than unilateral repair at 2 weeks but not 6 weeks. CCS were worse in the USBH group than UNIH group at 2 weeks but were similar by 6 weeks. Complications' rates were similar amongst all 3 groups. Factors contributing to worse scores were: smaller hernia, complications, worse preoperative MCCS results, recurrent hernia and bilateral rather than unilateral repair. Bilateral TEP for the clinically unilateral groin hernia with an occult contralateral groin hernia can be performed without increased morbidity, accepting a minor and very temporary impairment of QoL.

The Mirror Illusion Increases Motor Cortex Excitability in Children With and Without Hemiparesis.

PubMed

Grunt, Sebastian; Newman, Christopher J; Saxer, Stefanie; Steinlin, Maja; Weisstanner, Christian; Kaelin-Lang, Alain

2017-03-01

Mirror therapy provides a visual illusion of a normal moving limb by using the mirror reflection of the unaffected arm instead of viewing the paretic limb and is used in rehabilitation to improve hand function. Little is known about the mechanism underlying its effect in children with hemiparesis. To investigate the effect of the mirror illusion (MI) on the excitability of the primary motor cortex (M1) in children and adolescents. Twelve patients with hemiparesis (10-20 years) and 8 typically developing subjects (8-17 years) participated. Corticospinal reorganization was classified as contralateral (projection from contralateral hemisphere to affected hand) or ipsilateral (projection from ipsilateral hemisphere to affected hand). M1 excitability of the hemisphere projecting to the affected (nondominant in typically developing subjects) hand was obtained during 2 different conditions using single-pulse transcranial magnetic stimulation (TMS). Each condition (without/with mirror) consisted of a unimanual and a bimanual task. Motor-evoked potentials (MEPs) were recorded from the abductor pollicis brevis and flexor digitorum superficialis muscles. MEP amplitudes were significantly increased during the mirror condition ( P = .005) in typically developing subjects and in patients with contralateral reorganization. No significant effect of MI was found in subjects with ipsilateral reorganization. MI increased M1 excitability during active movements only. This increase was not correlated to hand function. MI increases the excitability of M1 in hemiparetic patients with contralateral corticospinal organization and in typically developing subjects. This finding provides neurophysiological evidence supporting the application of mirror therapy in selected children and adolescents with hemiparesis.

Task-induced brain activity in aphasic stroke patients: what is driving recovery?

PubMed

Geranmayeh, Fatemeh; Brownsett, Sonia L E; Wise, Richard J S

2014-10-01

The estimated prevalence of aphasia in the UK and the USA is 250 000 and 1 000 000, respectively. The commonest aetiology is stroke. The impairment may improve with behavioural therapy, and trials using cortical stimulation or pharmacotherapy are undergoing proof-of-principle investigation, but with mixed results. Aphasia is a heterogeneous syndrome, and the simple classifications according to the Broca-Wernicke-Lichtheim model inadequately describe the diverse communication difficulties with which patients may present. Greater knowledge of how intact neural networks promote recovery after aphasic stroke, either spontaneously or in response to interventions, will result in clearer hypotheses about how to improve the treatment of aphasia. Twenty-five years ago, a pioneering study on healthy participants heralded the introduction of functional neuroimaging to the study of mechanisms of recovery from aphasia. Over the ensuing decades, such studies have been interpreted as supporting one of three hypotheses, which are not mutually exclusive. The first two predate the introduction of functional neuroimaging: that recovery is the consequence of the reconstitution of domain-specific language systems in tissue around the lesion (the 'perilesional' hypothesis), or by homotopic cortex in the contralateral hemisphere (the 'laterality-shift' hypothesis). The third is that loss of transcallosal inhibition to contralateral homotopic cortex hinders recovery (the 'disinhibition' hypothesis). These different hypotheses at times give conflicting views about rehabilitative intervention; for example, should one attempt to activate or inhibit a contralateral homotopic region with cortical stimulation techniques to promote recovery? This review proposes that although the functional imaging data are statistically valid in most cases, their interpretation has often favoured one explanation while ignoring plausible alternatives. In our view, this is particularly evident when recovery is attributed to activity in 'language networks' occupying sites not observed in healthy participants. In this review we will argue that much of the distribution of what has often been interpreted as language-specific activity, particularly in midline and contralateral cortical regions, is an upregulation of activity in intact domain-general systems for cognitive control and attention, responding in a task-dependent manner to the increased 'effort' when damaged downstream domain-specific language networks are impaired. We further propose that it is an inability fully to activate these systems that may result in sub optimal recovery in some patients. Interpretation of the data in terms of activity in domain-general networks affords insights into novel approaches to rehabilitation. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Serial MR Spectroscopy Reveals a Direct Metabolic Effect of Cediranib in Glioblastoma

PubMed Central

Kim, Heisoog; Catana, Ciprian; Ratai, Eva-Maria; Andronesi, Ovidiu C.; Jennings, D.; Batchelor, Tracy T.; Jain, Rakesh K.; Sorensen, A. Gregory

2011-01-01

Proton magnetic resonance spectroscopy (1H-MRS) is increasingly used in clinical studies of brain tumor to provide information about tissue metabolic profiles. In this study, we evaluated changes in the levels of metabolites predominant in recurrent glioblastoma (rGBM), to characterize the response of rGBM to anti-angiogenic therapy. We examined thirty-one rGBM patients treated with daily doses of cediranib, acquiring serial chemical shift imaging data at specific time points during the treatment regimen. We defined spectra from three regions of interest (ROIs)—enhancing tumor (ET), peritumoral tissue (PT), and normal tissue on the contralateral side (cNT)—in post-contrast T1-weighted images, and normalized the concentrations of N-acetylaspartate (NAA) and choline (Cho) in each ROI to the concentration of creatine in cNT (norCre). We analyzed the ratios of these normalized metabolites (i.e., NAA/Cho, NAA/norCre, and Cho/norCre) by averaging all patients and categorizing two different survival groups. Relative to pre-treatment values, NAA/Cho in ET was unchanged through day 28. However, after day 28, NAA/Cho significantly increased in relation to a significant increase in NAA/norCre and a decrease in Cho/norCre; interestingly, the observed trend was reversed after day 56, consistent with the clinical course of GBM recurrence. Notably, ROC analysis indicated that NAA/Cho in tumor shows a high prediction to 6-month overall survival. These metabolic changes in these rGBM patients strongly suggest a direct metabolic effect of cediranib, and might also reflect an anti-tumor response to anti-angiogenic treatment during the first two months of treatment. Further study is needed to confirm these findings. PMID:21507932

CpG location and methylation level are crucial factors for the early detection of oral squamous cell carcinoma in brushing samples using bisulfite sequencing of a 13-gene panel.

PubMed

Morandi, Luca; Gissi, Davide; Tarsitano, Achille; Asioli, Sofia; Gabusi, Andrea; Marchetti, Claudio; Montebugnoli, Lucio; Foschini, Maria Pia

2017-01-01

Oral squamous cell carcinoma (OSCC) is usually diagnosed at an advanced stage and is commonly preceded by oral premalignant lesions. The mortality rates have remained unchanged (50% within 5 years after diagnosis), and it is related to tobacco smoking and alcohol intake. Novel molecular markers for early diagnosis are urgently needed. The purpose of this study was to evaluate the diagnostic value of methylation level in a set of 18 genes by bisulfite next-generation sequencing. With minimally invasive oral brushing, 28 consecutive OSCC, one squamous cell carcinoma with sarcomatoid features, six high-grade squamous intraepithelial lesions (HGSIL), 30 normal contralateral mucosa from the same patients, and 65 healthy donors were evaluated for DNA methylation analyzing 18 target genes by quantitative bisulfite next-generation sequencing. We further evaluated an independent cohort (validation dataset) made of 20 normal donors, one oral fibroma, 14 oral lichen planus (OLP), three proliferative verrucous leukoplakia (PVL), and two OSCC. Comparing OSCC with normal healthy donors and contralateral mucosa in 355 CpGs, we identified the following epigenetically altered genes: ZAP70 , ITGA4 , KIF1A , PARP15 , EPHX3 , NTM , LRRTM1 , FLI1 , MIR193 , LINC00599 , PAX1 , and MIR137HG showing hypermethylation and MIR296 , TERT , and GP1BB showing hypomethylation . The behavior of ZAP70 , GP1BB , H19 , EPHX3 , and MIR193 fluctuated among different interrogated CpGs. The gap between normal and OSCC samples remained mostly the same (Kruskal-Wallis P values < 0.05), but the absolute values changed conspicuously. ROC curve analysis identified the most informative CpGs, and we correctly stratified OSCC and HGSIL from normal donors using a multiclass linear discriminant analysis in a 13-gene panel (AUC 0.981). Only the OSCC with sarcomatoid features was negative. Three contralateral mucosa were positive, a sign of a possible field cancerization. Among imprinted genes, only MIR296 showed loss of imprinting. DNMT1 , TERC , and H19 together with the global methylation of long interspersed element 1 were unchanged. In the validation dataset, values over the threshold were detected in 2/2 OSCC, in 3/3 PVL, and in 2/14 OLP. Our data highlight the importance of CpG location and correct estimation of DNA methylation level for highly accurate early diagnosis of OSCC.

Radiographic Risk Factors for Contralateral Rupture in Dogs with Unilateral Cranial Cruciate Ligament Rupture

PubMed Central

Chuang, Connie; Ramaker, Megan A.; Kaur, Sirjaut; Csomos, Rebecca A.; Kroner, Kevin T.; Bleedorn, Jason A.; Schaefer, Susan L.; Muir, Peter

2014-01-01

Background Complete cranial cruciate ligament rupture (CR) is a common cause of pelvic limb lameness in dogs. Dogs with unilateral CR often develop contralateral CR over time. Although radiographic signs of contralateral stifle joint osteoarthritis (OA) influence risk of subsequent contralateral CR, this risk has not been studied in detail. Methodology/Principal Findings We conducted a retrospective longitudinal cohort study of client-owned dogs with unilateral CR to determine how severity of radiographic stifle synovial effusion and osteophytosis influence risk of contralateral CR over time. Detailed survival analysis was performed for a cohort of 85 dogs after case filtering of an initial sample population of 513 dogs. This population was stratified based on radiographic severity of synovial effusion (graded on a scale of 0, 1, and 2) and severity of osteophytosis (graded on a scale of 0, 1, 2, and 3) of both index and contralateral stifle joints using a reproducible scoring method. Severity of osteophytosis in the index and contralateral stifles was significantly correlated. Rupture of the contralateral cranial cruciate ligament was significantly influenced by radiographic OA in both the index and contralateral stifles at diagnosis. Odds ratio for development of contralateral CR in dogs with severe contralateral radiographic stifle effusion was 13.4 at one year after diagnosis and 11.4 at two years. Odds ratio for development of contralateral CR in dogs with severe contralateral osteophytosis was 9.9 at one year after diagnosis. These odds ratios were associated with decreased time to contralateral CR. Breed, age, body weight, gender, and tibial plateau angle did not significantly influence time to contralateral CR. Conclusion Subsequent contralateral CR is significantly influenced by severity of radiographic stifle effusion and osteophytosis in the contralateral stifle, suggesting that synovitis and arthritic joint degeneration are significant factors in the disease mechanism underlying the arthropathy. PMID:25254499

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, H; Lan, L; Sennett, C

Purpose: To gain insight into the role of parenchyma stroma in the characterization of breast tumors by incorporating computerized mammographic parenchyma assessment into breast CADx in the task of distinguishing between malignant and benign lesions. Methods: This study was performed on 182 biopsy-proven breast mass lesions, including 76 benign and 106 malignant lesions. For each full-field digital mammogram (FFDM) case, our quantitative imaging analysis was performed on both the tumor and a region-of-interest (ROI) from the normal contralateral breast. The lesion characterization includes automatic lesion segmentation and feature extraction. Radiographic texture analysis (RTA) was applied on the normal ROIs tomore » assess the mammographic parenchymal patterns of these contralateral normal breasts. Classification performance of both individual computer extracted features and the output from a Bayesian artificial neural network (BANN) were evaluated with a leave-one-lesion-out method using receiver operating characteristic (ROC) analysis with area under the curve (AUC) as the figure of merit. Results: Lesion characterization included computer-extracted phenotypes of spiculation, size, shape, and margin. For parenchymal pattern characterization, five texture features were selected, including power law beta, contrast, and edge gradient. Merging of these computer-selected features using BANN classifiers yielded AUC values of 0.79 (SE=0.03) and 0.67 (SE=0.04) in the task of distinguishing between malignant and benign lesions using only tumor phenotypes and texture features from the contralateral breasts, respectively. Incorporation of tumor phenotypes with parenchyma texture features into the BANN yielded improved classification performance with an AUC value of 0.83 (SE=0.03) in the task of differentiating malignant from benign lesions. Conclusion: Combining computerized tumor and parenchyma phenotyping was found to significantly improve breast cancer diagnostic accuracy highlighting the need to consider both tumor and stroma in decision making. Funding: University of Chicago Dean Bridge Fund, NCI U24-CA143848-05, P50-CA58223 Breast SPORE program, and Breast Cancer Research Foundation. COI: MLG is a stockholder in R2 technology/Hologic and receives royalties from Hologic, GE Medical Systems, MEDIAN Technologies, Riverain Medical, Mitsubishi, and Toshiba. MLG is a cofounder and stockholder in Quantitative Insights.« less

Change of Renal Parenchymal Width in Patients with Unilateral Ureteral Stent: A Bicenter Retrospective Study

PubMed Central

Kim, Hee Youn; Lee, Seung-Ju; Yoo, Je Mo; Lee, Joon Ho

2017-01-01

Purpose To determine whether kidney sizes were changed after ureteral stents were instilled, and if so, what parameters were significant. Methods Parenchymal width (PW) of 98 patients with unilateral ureteral stents was measured from the coronal view of CT scans for both stented and unstented contralateral kidney. The mean PW and % change of mean PW were calculated before stenting and at the time of last stent change. Estimated glomerular filtrate rate (eGFR) was recorded as well. Results The mean duration of ureteral stent indwelled was 15.6 ± 10.2 (mean ± SD) months. The change of mean PW of stented kidneys and unstented contralateral kidneys was −16.9 ± 16.4 (mean ± SD)% and 3.6 ± 10.7%, respectively. eGFR before and at the time of the last stent change did not show significant difference (p = 0.294). Duration of ureteral stent indwelled was found to be inversely related to the % change of mean PW (Spearman's correlation coefficient = −0.291, p < 0.001). Conclusions For unilateral ureteral obstruction, kidney size was decreased over time in spite of indwelling ureteral stent. This finding can be overlooked by clinicians due to compensatory growth of contralateral kidney and resultant normal eGFR. PMID:28656136

Relation between measures of speech-in-noise performance and measures of efferent activity

NASA Astrophysics Data System (ADS)

Smith, Brad; Harkrider, Ashley; Burchfield, Samuel; Nabelek, Anna

2003-04-01

Individual differences in auditory perceptual abilities in noise are well documented but the factors causing such variability are unclear. The purpose of this study was to determine if individual differences in responses measured from the auditory efferent system were correlated to individual variations in speech-in-noise performance. The relation between behavioral performance on three speech-in-noise tasks and two objective measures of the efferent auditory system were examined in thirty normal-hearing, young adults. Two of the speech-in-noise tasks measured an acceptable noise level, the maximum level of speech-babble noise that a subject is willing to accept while listening to a story. For these, the acceptable noise level was evaluated using both an ipsilateral (story and noise in same ear) and a contralateral (story and noise in opposite ears) paradigm. The third speech-in-noise task evaluated speech recognition using monosyllabic words presented in competing speech babble. Auditory efferent activity was assessed by examining the resulting suppression of click-evoked otoacoustic emissions following the introduction of a contralateral, broad-band stimulus and the activity of the ipsilateral and contralateral acoustic reflex arc was evaluated using tones and broad-band noise. Results will be discussed relative to current theories of speech in noise performance and auditory inhibitory processes.

Cortical Effects on Ipsilateral Hindlimb Muscles Revealed with Stimulus-Triggered Averaging of EMG Activity

PubMed Central

Messamore, William G.; Van Acker, Gustaf M.; Hudson, Heather M.; Zhang, Hongyu Y.; Kovac, Anthony; Nazzaro, Jules; Cheney, Paul D.

2016-01-01

While a large body of evidence supports the view that ipsilateral motor cortex may make an important contribution to normal movements and to recovery of function following cortical injury (Chollet et al. 1991; Fisher 1992; Caramia et al. 2000; Feydy et al. 2002), relatively little is known about the properties of output from motor cortex to ipsilateral muscles. Our aim in this study was to characterize the organization of output effects on hindlimb muscles from ipsilateral motor cortex using stimulus-triggered averaging of EMG activity. Stimulus-triggered averages of EMG activity were computed from microstimuli applied at 60–120 μA to sites in both contralateral and ipsilateral M1 of macaque monkeys during the performance of a hindlimb push–pull task. Although the poststimulus effects (PStEs) from ipsilateral M1 were fewer in number and substantially weaker, clear and consistent effects were obtained at an intensity of 120 μA. The mean onset latency of ipsilateral poststimulus facilitation was longer than contralateral effects by an average of 0.7 ms. However, the shortest latency effects in ipsilateral muscles were as short as the shortest latency effects in the corresponding contralateral muscles suggesting a minimal synaptic linkage that is equally direct in both cases. PMID:26088970

Effect of cochlear implantation on middle ear function: A three-month prospective study.

PubMed

Wasson, Joseph D; Campbell, Luke; Chambers, Scott; Hampson, Amy; Briggs, Robert J S; O'Leary, Stephen J

2018-05-01

To determine if cochlear implantation has a delayed effect on the middle ear conductive hearing mechanism by measuring laser Doppler vibrometry (LDV) of the tympanic membrane (TM) in both implanted and contralateral control ears preoperatively and 3 months postoperatively, and then comparing the relative change in LDV outcome measures between implanted and control ears. Prospective cohort study. Eleven preoperative adult unilateral cochlear implant recipients in previously unoperated ears with normal anatomy and aerated temporal bones were included in this study. The magnitude and phase angle of umbo velocity transfer function in response to air- conduction (AC) stimulus, and the magnitude of umbo velocity in response to bone- conduction (BC) stimulus were measured in the implant ear and the contralateral control ear preoperatively and 3 months postoperatively and compared. No significant changes in the magnitude or phase angle of TM velocity in response to either AC or BC stimulus were observed in the implanted ear relative to the contralateral control ear 3 months following cochlear implantation. From the results of LDV measurements, it can be said that cochlear implantation has no significant delayed effect on the middle ear conductive mechanism. 4. Laryngoscope, 128:1207-1212, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Long-term effects of enriched environment following neonatal hypoxia-ischemia on behavior, BDNF and synaptophysin levels in rat hippocampus: Effect of combined treatment with G-CSF.

PubMed

Griva, Myrsini; Lagoudaki, Rosa; Touloumi, Olga; Nousiopoulou, Evangelia; Karalis, Filippos; Georgiou, Thomas; Kokaraki, Georgia; Simeonidou, Constantina; Tata, Despina A; Spandou, Evangelia

2017-07-15

Increasing evidence shows that exposure to an enriched environment (EE) is neuroprotective in adult and neonatal animal models of brain ischemia. However, the mechanisms underlying this effect remain unclear. The aim of the current study was to investigate whether post-weaning EE would be effective in preventing functional deficits and brain damage by affecting markers of synaptic plasticity in a neonatal rat model of hypoxia-ischemia (HI). We also examined the possibility that granulocyte-colony stimulating factor (G-CSF), a growth factor with known neuroprotective effects in a variety of experimental brain injury models, combined with EE stimulation could enhance the potential beneficial effect of EE. Seven-day-old Wistar rats of either sex were subjected to permanent ligation of the left common carotid artery followed by 60min of hypoxia (8% O 2 ) and immediately after weaning (postnatal day 21) were housed in enriched conditions for 4weeks. A group of enriched-housed rats had been treated with G-CSF immediately after HI for 5 consecutive days (50μg/kg/day). Behavioral examination took place approximately at three months of age and included assessments of learning and memory (Morris water maze) as well as motor coordination (Rota-Rod). Infarct size and hippocampal area were estimated following behavioral assessment. Synaptic plasticity was evaluated based on BDNF and synaptophysin expression in the dorsal hippocampus. EE resulted in recovery of post-HI motor deficits and partial improvement of memory impairments which was not accompanied by reduced brain damage. Increased synaptophysin expression was observed in the contralateral to carotid ligation hemisphere. Hypoxia-ischemia alone or followed by enriched conditions did not affect BDNF expression which was increased only in enriched-housed normal rats. The combined therapy of G-CSF and EE further enhanced cognitive function compared to EE provided as monotherapy and prevented HI-induced brain damage by altering synaptic plasticity as reflected by increased synaptophysin expression. The above findings demonstrate that combination of neuroprotective treatments may result in increased protection and it might be a more effective strategy for the treatment of neonatal hypoxic-ischemic brain injury. Copyright © 2017. Published by Elsevier B.V.

Prominent hypointense veins on susceptibility weighted image in the cat brain with acute infarction: DWI, SWI, and PWI.

PubMed

Kim, Yong-Woo; Kim, Hak Jin; Choi, Seon Hee; Kim, Dong Chan

2014-10-01

The multiple prominent hypointense veins on susceptibility-weighted imaging (SWI) have been found in the ischemic territory of patients with acute ischemic stroke. Venous side is the unknown area in the hemodynamics of brain infarction. To evaluate the venous aspect in acute brain infarction through an animal study. The acute infarction in cat brains was induced with a bolus infusion of 0.25 mL of triolein through one side of the common carotid artery. The magnetic resonance (MR) images, including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) map, SW, and perfusion-weighted (PWI) images, were obtained serially at 2 h (n = 17), 1 day (n = 11), and 4 days (n = 4) after triolein infusion. The obtained MR images were evaluated qualitatively and quantitatively. For qualitative assessment, the signal intensity of the serial MR images was evaluated. The presence or absence and the location with serial changes of infarction were identified on DWI and ADC map images. The presence or absence of prominent hypointense veins and the serial changes of cortical veins were also evaluated on SWI. Quantitative assessment was performed by comparing the relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transit times (MTT) of the lesions with those of the contralateral normal side calculated on PWI. The serial changes of rCBV, rCBF, and MTT ratio were also evaluated. Acute infarction in the first and second medial gyrus of lesion hemisphere was found by qualitative evaluation of DWI and ADC map images. On the serial evaluation of SWI, the cortical veins of cat brain with infarction were obscured at 2 h and then re-appeared at 1 day. The hemorrhage transformation and prominent hypointense veins were seen at 4 days on SWI. The quantitative evaluation revealed increased MTT ratios and decreased rCBV and rCBF ratios on PWIs in the acute infarction of cat brain. The prominent hypointense veins on SWI were seen in the half of the acute infarction at 4 days. The prominent hypointense veins on SWI may have good agreement with the increased MTT ratio. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

PACAP38 Differentially Effects Genes and CRMP2 Protein Expression in Ischemic Core and Penumbra Regions of Permanent Middle Cerebral Artery Occlusion Model Mice Brain

PubMed Central

Hori, Motohide; Nakamachi, Tomoya; Shibato, Junko; Rakwal, Randeep; Tsuchida, Masachi; Shioda, Seiji; Numazawa, Satoshi

2014-01-01

Pituitary adenylate-cyclase activating polypeptide (PACAP) has neuroprotective and axonal guidance functions, but the mechanisms behind such actions remain unclear. Previously we examined effects of PACAP (PACAP38, 1 pmol) injection intracerebroventrically in a mouse model of permanent middle cerebral artery occlusion (PMCAO) along with control saline (0.9% NaCl) injection. Transcriptomic and proteomic approaches using ischemic (ipsilateral) brain hemisphere revealed differentially regulated genes and proteins by PACAP38 at 6 and 24 h post-treatment. However, as the ischemic hemisphere consisted of infarct core, penumbra, and non-ischemic regions, specificity of expression and localization of these identified molecular factors remained incomplete. This led us to devise a new experimental strategy wherein, ischemic core and penumbra were carefully sampled and compared to the corresponding contralateral (healthy) core and penumbra regions at 6 and 24 h post PACAP38 or saline injections. Both reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to examine targeted gene expressions and the collapsin response mediator protein 2 (CRMP2) protein profiles, respectively. Clear differences in expression of genes and CRMP2 protein abundance and degradation product/short isoform was observed between ischemic core and penumbra and also compared to the contralateral healthy tissues after PACAP38 or saline treatment. Results indicate the importance of region-specific analyses to further identify, localize and functionally analyse target molecular factors for clarifying the neuroprotective function of PACAP38. PMID:25257527

Redundant information encoding in primary motor cortex during natural and prosthetic motor control.

PubMed

So, Kelvin; Ganguly, Karunesh; Jimenez, Jessica; Gastpar, Michael C; Carmena, Jose M

2012-06-01

Redundant encoding of information facilitates reliable distributed information processing. To explore this hypothesis in the motor system, we applied concepts from information theory to quantify the redundancy of movement-related information encoded in the macaque primary motor cortex (M1) during natural and neuroprosthetic control. Two macaque monkeys were trained to perform a delay center-out reaching task controlling a computer cursor under natural arm movement (manual control, 'MC'), and using a brain-machine interface (BMI) via volitional control of neural ensemble activity (brain control, 'BC'). During MC, we found neurons in contralateral M1 to contain higher and more redundant information about target direction than ipsilateral M1 neurons, consistent with the laterality of movement control. During BC, we found that the M1 neurons directly incorporated into the BMI ('direct' neurons) contained the highest and most redundant target information compared to neurons that were not incorporated into the BMI ('indirect' neurons). This effect was even more significant when comparing to M1 neurons of the opposite hemisphere. Interestingly, when we retrained the BMI to use ipsilateral M1 activity, we found that these neurons were more redundant and contained higher information than contralateral M1 neurons, even though ensembles from this hemisphere were previously less redundant during natural arm movement. These results indicate that ensembles most associated to movement contain highest redundancy and information encoding, which suggests a role for redundancy in proficient natural and prosthetic motor control.

Volumetric Analysis of Cerebral Peduncles and Cerebellar Hemispheres for Predicting Hemiparesis After Hemispherectomy.

PubMed

Mullin, Jeffrey P; Soni, Pranay; Lee, Sungho; Jehi, Lara; Naduvil Valappi, Ahsan Moosa; Bingaman, William; Gonzalez-Martinez, Jorge

2016-09-01

In some cases of refractory epilepsy, hemispherectomy is the final invasive treatment option. However, predictors of postoperative hemiparesis in these patients have not been widely studied. To investigate how the volumetric analysis of cerebral peduncles and cerebellar hemispheres in patients who have undergone hemispherectomy may determine prognostic implications for postoperative hemiparesis. Twenty-two patients who underwent hemispherectomy at our institution were retrospectively included. Using iPlan/BrainLAB (BrainLAB, Feldkirchen, Germany) imaging software and a semiautomatic voxel-based segmentation method, we calculated the preoperative cerebral peduncle and cerebellar hemisphere volumes. Cerebral peduncle and cerebellar hemisphere ratios were compared between patients with worsened or unchanged/better hemiparesis postoperatively. The ratios of ipsilateral/contralateral cerebral peduncles (0.570 vs 0.828; P = .02) and contralateral/ipsilateral cerebellar hemispheres (0.885 vs 1.031; P = .009) were significantly lower in patients who had unchanged/improved hemiparesis postoperatively compared with patients who had worsened hemiparesis. Relative risk of worsening hemiparesis was significantly higher in patients with a cerebral peduncle ratio < 0.7 (relative risk, 4.3; P = .03) or a cerebellar ratio < 1.0 (relative risk, 6.4; P = .006). Although patients who undergo hemispherectomy are heterogeneous, we report a method of predicting postoperative hemiparesis using only standard volumetric magnetic resonance imaging. This information could be used in preoperative discussions with patients and families to help better understand that chance of retaining baseline motor function. CST, corticospinal tractfMRI, functional magnetic resonance imagingTMS, transcranial magnetic stimulation.

Comparison of neuromuscular abnormalities between upper and lower extremities in hemiparetic stroke.

PubMed

Mirbagheri, M M; AliBiglou, L; Thajchayapong, M; Lilaonitkul, T; Rymer, W Z

2006-01-01

We studied the neuromuscular mechanical properties of the elbow and ankle joints in chronic, hemiparetic stroke patients and healthy subjects. System identification techniques were used to characterize the mechanical abnormalities of these joints and to identify the contribution of intrinsic and reflex stiffness to these abnormalities. Modulation of intrinsic and reflex stiffness with the joint angle was studied by applying PRBS perturbations to the joint at different joint angles. The experiments were performed for both spastic (stroke) and contralateral (control) sides of stroke patients and one side of healthy (normal) subjects. We found reflex stiffness gain (GR) was significantly larger in the stroke than the control side for both elbow and ankle joints. GR was also strongly position dependent in both joints. However, the modulation of GR with position was slightly different in two joints. GR was also larger in the control than the normal joints but the differences were significant only for the ankle joint. Intrinsic stiffness gain (K) was also significantly larger in the stroke than the control joint at elbow extended positions and at ankle dorsiflexed positions. Modulation of K with the ankle angle was similar for stroke, control and normal groups. In contrast, the position dependency of the elbow was different. K was larger in the control than normal ankle whereas it was lower in the control than normal elbow. However, the differences were not significant for any joint. The findings demonstrate that both reflex and intrinsic stiffness gain increase abnormally in both upper and lower extremities. However, the major contribution of intrinsic and reflex stiffness to the abnormalities is at the end of ROM and at the middle ROM, respectively. The results also demonstrate that the neuromuscular properties of the contralateral limb are not normal suggesting that it may not be used as a suitable control at least for the ankle study.

Subcortical functional reorganization due to early blindness

PubMed Central

Jiang, Fang; Fine, Ione; Watkins, Kate E.; Bridge, Holly

2015-01-01

Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a “visual” subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. PMID:25673746

Subcortical functional reorganization due to early blindness.

PubMed

Coullon, Gaelle S L; Jiang, Fang; Fine, Ione; Watkins, Kate E; Bridge, Holly

2015-04-01

Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a "visual" subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. Copyright © 2015 the American Physiological Society.

Data-driven identification of intensity normalization region based on longitudinal coherency of 18F-FDG metabolism in the healthy brain.

PubMed

Zhang, Huiwei; Wu, Ping; Ziegler, Sibylle I; Guan, Yihui; Wang, Yuetao; Ge, Jingjie; Schwaiger, Markus; Huang, Sung-Cheng; Zuo, Chuantao; Förster, Stefan; Shi, Kuangyu

2017-02-01

In brain 18 F-FDG PET data intensity normalization is usually applied to control for unwanted factors confounding brain metabolism. However, it can be difficult to determine a proper intensity normalization region as a reference for the identification of abnormal metabolism in diseased brains. In neurodegenerative disorders, differentiating disease-related changes in brain metabolism from age-associated natural changes remains challenging. This study proposes a new data-driven method to identify proper intensity normalization regions in order to improve separation of age-associated natural changes from disease related changes in brain metabolism. 127 female and 128 male healthy subjects (age: 20 to 79) with brain 18 F-FDG PET/CT in the course of a whole body cancer screening were included. Brain PET images were processed using SPM8 and were parcellated into 116 anatomical regions according to the AAL template. It is assumed that normal brain 18 F-FDG metabolism has longitudinal coherency and this coherency leads to better model fitting. The coefficient of determination R 2 was proposed as the coherence coefficient, and the total coherence coefficient (overall fitting quality) was employed as an index to assess proper intensity normalization strategies on single subjects and age-cohort averaged data. Age-associated longitudinal changes of normal subjects were derived using the identified intensity normalization method correspondingly. In addition, 15 subjects with clinically diagnosed Parkinson's disease were assessed to evaluate the clinical potential of the proposed new method. Intensity normalizations by paracentral lobule and cerebellar tonsil, both regions derived from the new data-driven coherency method, showed significantly better coherence coefficients than other intensity normalization regions, and especially better than the most widely used global mean normalization. Intensity normalization by paracentral lobule was the most consistent method within both analysis strategies (subject-based and age-cohort averaging). In addition, the proposed new intensity normalization method using the paracentral lobule generates significantly higher differentiation from the age-associated changes than other intensity normalization methods. Proper intensity normalization can enhance the longitudinal coherency of normal brain glucose metabolism. The paracentral lobule followed by the cerebellar tonsil are shown to be the two most stable intensity normalization regions concerning age-dependent brain metabolism. This may provide the potential to better differentiate disease-related changes from age-related changes in brain metabolism, which is of relevance in the diagnosis of neurodegenerative disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Loss of Brain Aerobic Glycolysis in Normal Human Aging.

PubMed

Goyal, Manu S; Vlassenko, Andrei G; Blazey, Tyler M; Su, Yi; Couture, Lars E; Durbin, Tony J; Bateman, Randall J; Benzinger, Tammie L-S; Morris, John C; Raichle, Marcus E

2017-08-01

The normal aging human brain experiences global decreases in metabolism, but whether this affects the topography of brain metabolism is unknown. Here we describe PET-based measurements of brain glucose uptake, oxygen utilization, and blood flow in cognitively normal adults from 20 to 82 years of age. Age-related decreases in brain glucose uptake exceed that of oxygen use, resulting in loss of brain aerobic glycolysis (AG). Whereas the topographies of total brain glucose uptake, oxygen utilization, and blood flow remain largely stable with age, brain AG topography changes significantly. Brain regions with high AG in young adults show the greatest change, as do regions with prolonged developmental transcriptional features (i.e., neoteny). The normal aging human brain thus undergoes characteristic metabolic changes, largely driven by global loss and topographic changes in brain AG. Copyright © 2017 Elsevier Inc. All rights reserved.

Contralateral Supracerebellar-Infratentorial Approach for Resection of Thalamic Cavernous Malformations.

PubMed

Mascitelli, Justin; Burkhardt, Jan-Karl; Gandhi, Sirin; Lawton, Michael T

2018-02-26

Surgical resection of cavernous malformations (CM) in the posterior thalamus, pineal region, and midbrain tectum is technically challenging owing to the presence of adjacent eloquent cortex and critical neurovascular structures. Various supracerebellar infratentorial (SCIT) approaches have been used in the surgical armamentarium targeting lesions in this region, including the median, paramedian, and extreme lateral variants. Surgical view of a posterior thalamic CM from the traditional ipsilateral vantage point may be obscured by occipital lobe and tentorium. To describe a novel surgical approach via a contralateral SCIT (cSCIT) trajectory for resecting posterior thalamic CMs. From 1997 to 2017, 75 patients underwent the SCIT approach for cerebrovascular/oncologic pathology by the senior author. Of these, 30 patients underwent the SCIT approach for CM resection, and 3 patients underwent the cSCIT approach. Historical patient data, radiographic features, surgical technique, and postoperative neurological outcomes were evaluated in each patient. All 3 patients presented with symptomatic CMs within the right posterior thalamus with radiographic evidence of hemorrhage. All surgeries were performed in the sitting position. There were no intraoperative complications. Neuroimaging demonstrated complete CM resection in all cases. There were no new or worsening neurological deficits or evidence of rebleeding/recurrence noted postoperatively. This study establishes the surgical feasibility of a contralateral SCIT approach in resection of symptomatic thalamic CMs It demonstrates the application for this procedure in extending the surgical trajectory superiorly and laterally and maximizing safe resectability of these deep CMs with gravity-assisted brain retraction.

Bilateral versus ipsilesional cortico-subcortical activity patterns in stroke show hemispheric dependence.

PubMed

Vidal, Ana C; Banca, Paula; Pascoal, Augusto G; Cordeiro, Gustavo; Sargento-Freitas, João; Gouveia, Ana; Castelo-Branco, Miguel

2018-01-01

Background Understanding of interhemispheric interactions in stroke patients during motor control is an important clinical neuroscience quest that may provide important clues for neurorehabilitation. In stroke patients bilateral overactivation in both hemispheres has been interpreted as a poor prognostic indicator of functional recovery. In contrast, ipsilesional patterns have been linked with better motor outcomes. Aim We investigated the pathophysiology of hemispheric interactions during limb movement without and with contralateral restraint, to mimic the effects of constraint-induced movement therapy. We used neuroimaging to probe brain activity with such a movement-dependent interhemispheric modulation paradigm. Methods We used a functional magnetic resonance imaging block design during which the plegic/paretic upper limb was recruited/mobilized to perform unilateral arm elevation, as a function of presence versus absence of contralateral limb restriction (n = 20, with balanced left/right lesion sites). Results Analysis of 10 right hemispheric stroke participants yielded bilateral sensorimotor cortex activation in all movement phases in contrast with the unilateral dominance seen in the 10 left hemispheric stroke participants. Superimposition of contralateral restriction led to a prominent shift from activation to deactivation response patterns, in particular in cortical and basal ganglia motor areas in right hemispheric stroke. Left hemispheric stroke was, in general, characterized by reduced activation patterns, even in the absence of restriction, which induced additional cortical silencing. Conclusion The observed hemispheric-dependent activation/deactivation shifts is novel and these pathophysiological observations suggest short-term neuroplasticity that may be useful for hemisphere-tailored neurorehabilitation.

Bilateral versus ipsilesional cortico-subcortical activity patterns in stroke show hemispheric dependence.

PubMed

Vidal, A Cristina; Banca, Paula; Pascoal, Augusto G; Santo, Gustavo C; Sargento-Freitas, João; Gouveia, Ana; Castelo-Branco, Miguel

2017-01-01

Background Understanding of interhemispheric interactions in stroke patients during motor control is an important clinical neuroscience quest that may provide important clues for neurorehabilitation. In stroke patients, bilateral overactivation in both hemispheres has been interpreted as a poor prognostic indicator of functional recovery. In contrast, ipsilesional patterns have been linked with better motor outcomes. Aim We investigated the pathophysiology of hemispheric interactions during limb movement without and with contralateral restraint, to mimic the effects of constraint-induced movement therapy. We used neuroimaging to probe brain activity with such a movement-dependent interhemispheric modulation paradigm. Methods We used an fMRI block design during which the plegic/paretic upper limb was recruited/mobilized to perform unilateral arm elevation, as a function of presence versus absence of contralateral limb restriction ( n = 20, with balanced left/right lesion sites). Results Analysis of 10 right-hemispheric stroke participants yielded bilateral sensorimotor cortex activation in all movement phases in contrast with the unilateral dominance seen in the 10 left-hemispheric stroke participants. Superimposition of contralateral restriction led to a prominent shift from activation to deactivation response patterns, in particular in cortical and basal ganglia motor areas in right-hemispheric stroke. Left-hemispheric stroke was in general characterized by reduced activation patterns, even in the absence of restriction, which induced additional cortical silencing. Conclusion The observed hemispheric-dependent activation/deactivation shifts are novel and these pathophysiological observations suggest short-term neuroplasticity that may be useful for hemisphere-tailored neurorehabilitation.

Structural and functional connectivity mapping of the vestibular circuitry from human brainstem to cortex.

PubMed

Kirsch, V; Keeser, D; Hergenroeder, T; Erat, O; Ertl-Wagner, B; Brandt, T; Dieterich, M

2016-04-01

Structural and functional interconnections of the bilateral central vestibular network have not yet been completely delineated. This includes both ipsilateral and contralateral pathways and crossing sites on the way from the vestibular nuclei via the thalamic relay stations to multiple "vestibular cortex" areas. This study investigated "vestibular" connectivity in the living human brain in between the vestibular nuclei and the parieto-insular vestibular cortex (PIVC) by combined structural and functional connectivity mapping using diffusion tensor imaging and functional connectivity magnetic resonance imaging in 24 healthy right-handed volunteers. We observed a congruent functional and structural link between the vestibular nuclei and the ipsilateral and contralateral PIVC. Five separate and distinct vestibular pathways were identified: three run ipsilaterally, while the two others cross either in the pons or the midbrain. Two of the ipsilateral projections run through the posterolateral or paramedian thalamic subnuclei, while the third bypasses the thalamus to reach the inferior part of the insular cortex directly. Both contralateral pathways travel through the posterolateral thalamus. At the cortical level, the PIVC regions of both hemispheres with a right hemispherical dominance are interconnected transcallosally through the antero-caudal splenium. The above-described bilateral vestibular circuitry in its entirety takes the form of a structure of a rope ladder extending from the brainstem to the cortex with three crossings in the brainstem (vestibular nuclei, pons, midbrain), none at thalamic level and a fourth cortical crossing through the splenium of the corpus callosum.

Resilience to the contralateral visual field bias as a window into object representations

PubMed Central

Garcea, Frank E.; Kristensen, Stephanie; Almeida, Jorge; Mahon, Bradford Z.

2016-01-01

Viewing images of manipulable objects elicits differential blood oxygen level-dependent (BOLD) contrast across parietal and dorsal occipital areas of the human brain that support object-directed reaching, grasping, and complex object manipulation. However, it is unknown which object-selective regions of parietal cortex receive their principal inputs from the ventral object-processing pathway and which receive their inputs from the dorsal object-processing pathway. Parietal areas that receive their inputs from the ventral visual pathway, rather than from the dorsal stream, will have inputs that are already filtered through object categorization and identification processes. This predicts that parietal regions that receive inputs from the ventral visual pathway should exhibit object-selective responses that are resilient to contralateral visual field biases. To test this hypothesis, adult participants viewed images of tools and animals that were presented to the left or right visual fields during functional magnetic resonance imaging (fMRI). We found that the left inferior parietal lobule showed robust tool preferences independently of the visual field in which tool stimuli were presented. In contrast, a region in posterior parietal/dorsal occipital cortex in the right hemisphere exhibited an interaction between visual field and category: tool-preferences were strongest contralateral to the stimulus. These findings suggest that action knowledge accessed in the left inferior parietal lobule operates over inputs that are abstracted from the visual input and contingent on analysis by the ventral visual pathway, consistent with its putative role in supporting object manipulation knowledge. PMID:27160998

Sudden post-traumatic sciatica caused by a thoracic spinal meningioma.

PubMed

Mariniello, Giuseppe; Malacario, Francesca; Dones, Flavia; Severino, Rocco; Ugga, Lorenzo; Russo, Camilla; Elefante, Andrea; Maiuri, Francesco

2016-10-01

Spinal meningiomas usually present with slowly progressive symptoms of cord and root compression, while a sudden clinical onset is very rare. A 35-year-old previously symptom-free woman presented sudden right sciatica and weakness of her right leg following a fall with impact to her left foot. A neurological examination showed paresis of the right quadriceps, tibial and sural muscles, increased bilateral knee and ankle reflexes and positive Babinski sign. Magnetic resonance imaging (MRI) revealed the presence of a spinal T11 meningioma in the left postero-lateral compartment of the spinal canal; at this level, the spinal cord was displaced to the contralateral side with the conus in the normal position. At surgery, a meningioma with dural attachment of the left postero-lateral dural surface was removed. The intervention resulted in rapid remission of both pain and neurological deficits. Spinal meningiomas may exceptionally present with sudden pain and neurological deficits as result of tumour bleeding or post-traumatic injury of the already compressed nervous structures, both in normal patients and in those with conus displacement or tethered cord. In this case, the traumatic impact of the left foot was transmitted to the spine, resulting in stretching of the already compressed cord and of the contralateral lombosacral roots. This case suggests that low thoracic cord compression should be suspected in patients with post-traumatic radicular leg pain with normal lumbar spine MRI. © The Author(s) 2016.

Semiautomated Middle Ear Volume Measurement as a Predictor of Postsurgical Outcomes for Congenital Aural Atresia.

PubMed

Kabadi, S J; Ruhl, D S; Mukherjee, S; Kesser, B W

2018-02-01

Middle ear space is one of the most important components of the Jahrsdoerfer grading system (J-score), which is used to determine surgical candidacy for congenital aural atresia. The purpose of this study was to introduce a semiautomated method for measuring middle ear volume and determine whether middle ear volume, either alone or in combination with the J-score, can be used to predict early postoperative audiometric outcomes. A retrospective analysis was conducted of 18 patients who underwent an operation for unilateral congenital aural atresia at our institution. Using the Livewire Segmentation tool in the Carestream Vue PACS, we segmented middle ear volumes using a semiautomated method for all atretic and contralateral normal ears on preoperative high-resolution CT imaging. Postsurgical audiometric outcome data were then analyzed in the context of these middle ear volumes. Atretic middle ear volumes were significantly smaller than those in contralateral normal ears ( P < .001). Patients with atretic middle ear volumes of >305 mm 3 had significantly better postoperative pure tone average and speech reception thresholds than those with atretic ears below this threshold volume ( P = .01 and P = .006, respectively). Atretic middle ear volume incorporated into the J-score offered the best association with normal postoperative hearing (speech reception threshold ≤ 30 dB; OR = 37.8, P = .01). Middle ear volume, calculated in a semiautomated fashion, is predictive of postsurgical audiometric outcomes, both independently and in combination with the conventional J-score. © 2018 by American Journal of Neuroradiology.

Functional visual acuity in patients with successfully treated amblyopia: a pilot study.

PubMed

Hoshi, Sujin; Hiraoka, Takahiro; Kotsuka, Junko; Sato, Yumiko; Izumida, Shinya; Kato, Atsuko; Ueno, Yuta; Fukuda, Shinichi; Oshika, Tetsuro

2017-06-01

The aim of this study was to use conventional visual acuity measurements to quantify the functional visual acuity (FVA) in eyes with successfully treated amblyopia, and to compare the findings with those for contralateral normal eyes. Nineteen patients (7 boys, 12 girls; age 7.5 ± 2.2 years) with successfully treated unilateral amblyopia and the same conventional decimal visual acuity in both eyes (better than 1.0) were enrolled. FVA, the visual maintenance ratio (VMR), maximum and minimum visual acuity, and the average response time were recorded for both eyes of all patients using an FVA measurement system. The differences in FVA values between eyes were analyzed. The mean LogMAR FVA scores, VMR (p < 0.001 for both), and the LogMAR maximum (p < 0.005) and minimum visual acuity (p < 0.001) were significantly poorer for the eyes with treated amblyopia than for the contralateral normal eyes. There was no significant difference in the average response time. Our results indicate that FVA and VMR were poorer for eyes with treated amblyopia than for normal eyes, even though the treatment for amblyopia was considered successful on the basis of conventional visual acuity measurements. These results suggest that visual function is impaired in eyes with amblyopia, regardless of treatment success, and that FVA measurements can provide highly valuable diagnosis and treatment information that is not readily provided by conventional visual acuity measurements.

Mobile phone types and SAR characteristics of the human brain.

PubMed

Lee, Ae-Kyoung; Hong, Seon-Eui; Kwon, Jong-Hwa; Choi, Hyung-Do; Cardis, Elisabeth

2017-04-07

Mobile phones differ in terms of their operating frequency, outer shape, and form and location of the antennae, all of which affect the spatial distributions of their electromagnetic field and the level of electromagnetic absorption in the human head or brain. For this paper, the specific absorption rate (SAR) was calculated for four anatomical head models at different ages using 11 numerical phone models of different shapes and antenna configurations. The 11 models represent phone types accounting for around 86% of the approximately 1400 commercial phone models released into the Korean market since 2002. Seven of the phone models selected have an internal dual-band antenna, and the remaining four possess an external antenna. Each model was intended to generate an average absorption level equivalent to that of the same type of commercial phone model operating at the maximum available output power. The 1 g peak spatial SAR and ipsilateral and contralateral brain-averaged SARs were reported for all 11 phone models. The effects of the phone type, phone position, operating frequency, and age of head models on the brain SAR were comprehensively determined.

Mobile phone types and SAR characteristics of the human brain

NASA Astrophysics Data System (ADS)

Lee, Ae-Kyoung; Hong, Seon-Eui; Kwon, Jong-Hwa; Choi, Hyung-Do; Cardis, Elisabeth

2017-04-01

Mobile phones differ in terms of their operating frequency, outer shape, and form and location of the antennae, all of which affect the spatial distributions of their electromagnetic field and the level of electromagnetic absorption in the human head or brain. For this paper, the specific absorption rate (SAR) was calculated for four anatomical head models at different ages using 11 numerical phone models of different shapes and antenna configurations. The 11 models represent phone types accounting for around 86% of the approximately 1400 commercial phone models released into the Korean market since 2002. Seven of the phone models selected have an internal dual-band antenna, and the remaining four possess an external antenna. Each model was intended to generate an average absorption level equivalent to that of the same type of commercial phone model operating at the maximum available output power. The 1 g peak spatial SAR and ipsilateral and contralateral brain-averaged SARs were reported for all 11 phone models. The effects of the phone type, phone position, operating frequency, and age of head models on the brain SAR were comprehensively determined.

Some glial progenitors in the neonatal subventricular zone migrate through the corpus callosum to the contralateral cerebral hemisphere.

PubMed

Kakita, Akiyoshi; Zerlin, Marielba; Takahashi, Hitoshi; Goldman, James E

2003-04-14

The great majority of glial cells of the mammalian forebrain are generated in the perinatal period from progenitors in the subventricular zone (SVZ). We investigated the migration of progenitors from the neonatal (postnatal day 0, P0) rat forebrain SVZ by labeling them in vivo with a green fluorescence protein (GFP) retrovirus and monitoring their movements by time-lapse video microscopy in P3 slices. We identified a small number of progenitors that migrated tangentially within the corpus callosum (CC) and crossed the midline. These cells retained a relatively uniform morphology: the leading process was extended toward the contralateral side but showed no process branching or turning away from the migratory direction. Net migration requires the elongation of the leading process and nuclear translocation, and the migrating cells in the CC showed both modes. We confirmed the presence of unmyelinated axon bundles within the P3 CC, but failed to detect any radially directed glial processes (vimentin- or GLAST-immunolabeled fibers) spanning through the CC. Confocal images showed a close proximity between neurofilament-immunolabeled axons and the leading process of the GFP-expressing progenitors in the CC. The destination of the callosal fibers was examined by applying DiI to the right cingulum; the labeled fibers ran throughout the CC and reached the left cingulate and motor areas. The distribution and final fates of the retrovirus-labeled cells were examined in P28 brains. A small proportion of the labeled cells were found in the contralateral hemisphere, where, as oligodendrocytes and astrocytes, they colonized predominantly the cortex and the underlying white matter of the cingulate and secondary motor areas. The distribution pattern appears to coincide well with the projection direction of the callosal fibers. Thus, glial progenitors migrate across the CC, presumably in conjunction with unmyelinated axons, to colonize the contralateral hemisphere. Copyright 2003 Wiley-Liss, Inc.

Variable laterality of corticospinal tract axons that regenerate after spinal cord injury as a result of PTEN deletion or knock-down

PubMed Central

Willenberg, Rafer; Zukor, Katherine; Liu, Kai; He, Zhigang; Steward, Oswald

2016-01-01

Corticospinal tract (CST) axons from one hemisphere normally extend and terminate predominantly in the contralateral spinal cord. We previously showed that deleting PTEN in the sensorimotor cortex enables CST axons to regenerate after spinal cord injury and that some regenerating axons extend along the “wrong” side. Here, we characterize the degree of specificity of regrowth in terms of laterality. PTEN was selectively deleted via cortical AAV-Cre injections in neonatal PTEN-floxed mice. As adults, mice received dorsal hemisection injuries at T12 or complete crush injuries at T9. CST axons from one hemisphere were traced by unilateral BDA injections in PTEN-deleted mice with spinal cord injury and in non-injured PTEN-floxed mice that had not received AAV-Cre. In non-injured mice, 97.9 ± 0.7% of BDA-labeled axons in white matter and 88.5 ± 1.0% of BDA-labeled axons in grey matter were contralateral to the cortex of origin. In contrast, laterality of CST axons that extended past a lesion due to PTEN deletion varied across animals. In some cases, regenerated axons extended predominantly on the ipsilateral side, in other cases, axons extended predominantly contralaterally, and in others, axons were similar in numbers on both sides. Similar results were seen in analyses of cases from previous studies using shRNA-mediated PTEN knock-down. These results indicate that CST axons that extend past a lesion due to PTEN deletion or knock-down do not maintain the contralateral rule of the non-injured CST, highlighting one aspect for how resultant circuitry from regenerating axons may differ from that of the uninjured CST. PMID:26878190

Impairments in prehension produced by early postnatal sensory motor cortex activity blockade.

PubMed

Martin, J H; Donarummo, L; Hacking, A

2000-02-01

This study examined the effects of blocking neural activity in sensory motor cortex during early postnatal development on prehension. We infused muscimol, either unilaterally or bilaterally, into the sensory motor cortex of cats to block activity continuously between postnatal weeks 3-7. After stopping infusion, we trained animals to reach and grasp a cube of meat and tested behavior thereafter. Animals that had not received muscimol infusion (unilateral saline infusion; age-matched) reached for the meat accurately with small end-point errors. They grasped the meat using coordinated digit flexion followed by forearm supination on 82.7% of trials. Performance using either limb did not differ significantly. In animals receiving unilateral muscimol infusion, reaching and grasping using the limb ipsilateral to the infusion were similar to controls. The limb contralateral to infusion showed significant increases in systematic and variable reaching end-point errors, often requiring subsequent corrective movements to contact the meat. Grasping occurred on only 14.8% of trials, replaced on most trials by raking without distal movements. Compensatory adjustments in reach length and angle, to maintain end-point accuracy as movements were started from a more lateral position, were less effective using the contralateral limb than ipsilateral limb. With bilateral inactivations, the form of reaching and grasping impairments was identical to that produced by unilateral inactivation, but the magnitude of the reaching impairments was less. We discuss these results in terms of the differential effects of unilateral and bilateral inactivation on corticospinal tract development. We also investigated the degree to which these prehension impairments after unilateral blockade reflect control by each hemisphere. In animals that had received unilateral blockade between postnatal weeks (PWs) 3 and 7, we silenced on-going activity (after PW 11) during task performance using continuous muscimol infusion. We inactivated the right (previously active) and then the left (previously silenced) sensory motor cortex. Inactivation of the ipsilateral (right) sensory motor cortex produced a further increase in systematic error and less frequent normal grasping. Reinactivation of the contralateral (left) cortex produced larger increases in reaching and grasping impairments than those produced by ipsilateral inactivation. This suggests that the impaired limb receives bilateral sensory motor cortex control but that control by the contralateral (initially silenced) cortex predominates. Our data are consistent with the hypothesis that the normal development of skilled motor behavior requires activity in sensory motor cortex during early postnatal life.

Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit Model of Intrauterine Growth Restriction.

PubMed

Illa, Miriam; Brito, Verónica; Pla, Laura; Eixarch, Elisenda; Arbat-Plana, Ariadna; Batallé, Dafnis; Muñoz-Moreno, Emma; Crispi, Fatima; Udina, Esther; Figueras, Francesc; Ginés, Silvia; Gratacós, Eduard

2017-10-12

The structural correspondence of neurodevelopmental impairments related to intrauterine growth restriction (IUGR) that persists later in life remains elusive. Moreover, early postnatal stimulation strategies have been proposed to mitigate these effects. Long-term brain connectivity abnormalities in an IUGR rabbit model and the effects of early postnatal environmental enrichment (EE) were explored. IUGR was surgically induced in one horn, whereas the contralateral one produced the controls. Postnatally, a subgroup of IUGR animals was housed in an enriched environment. Functional assessment was performed at the neonatal and long-term periods. At the long-term period, structural brain connectivity was evaluated by means of diffusion-weighted brain magnetic resonance imaging and by histological assessment focused on the hippocampus. IUGR animals displayed poorer functional results and presented altered whole-brain networks and decreased median fractional anisotropy in the hippocampus. Reduced density of dendritic spines and perineuronal nets from hippocampal neurons were also observed. Of note, IUGR animals exposed to enriched environment presented an improvement in terms of both function and structure. IUGR is associated with altered brain connectivity at the global and cellular level. A strategy based on early EE has the potential to restore the neurodevelopmental consequences of IUGR. © 2017 S. Karger AG, Basel.

Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction.

PubMed

Xu, Yali; Cui, Hai; Zhu, Qiong; Hua, Xing; Xia, Hongmei; Tan, Kaibin; Gao, Yunhua; Zhao, Jing; Liu, Zheng

2016-01-01

Objective. Blood-brain barrier (BBB) is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p < 0.01). Erythrocytes extravasations were demonstrated in the ultrasound-exposed hemisphere (4 ± 1, grade 2) while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans

DTIC Science & Technology

2014-12-01

airway epithelium [1, 6, 7], and 2) these changes can be detected and serve as biomarker for early detection of lung cancer [8, 9], in the current...biospecimens from seven locations: nasal epithelium , proximal and distal bronchial airway epithelium obtained at bronchoscopy (ipsilateral and...contralateral to the tumor) as well as the tumor/benign lesion, adjacent normal parenchyma, and sub- segmental bronchial epithelium at time of lobectomy

Reduced activation and altered laterality in two neuroleptic-naive catatonic patients during a motor task in functional MRI.

PubMed

Northoff, G; Braus, D F; Sartorius, A; Khoram-Sefat, D; Russ, M; Eckert, J; Herrig, M; Leschinger, A; Bogerts, B; Henn, F A

1999-07-01

Catatonia, a symptom complex with motor, affective and cognitive symptoms seen in a variety of psychotic conditions and with organic disease, was examined using a motor task using functional magnetic resonance imaging (fMRI). Two acute catatonic patients and two age- and sex-matched healthy controls performed sequential finger opposition (SFO) after being medicated with 2 mg of lorazepam (i.v.). Functional magnetic resonance images were collected using a gradient echo pulse sequence (EPI). Patients with catatonia showed reduced motor activation of the contralateral motor cortex during SFO of the right hand, ipsilateral activation was similar for patients and controls. There were no differences in the activation of the SMA. During left hand activation the right-handed catatonic patients showed more activation in the ipsilateral cortex, a reversal from the normal pattern of activation in which the contralateral side shows four to five times more activation than the ipsilateral side. In catatonic patients there is a decreased activation in motor cortex during a motor task compared to matched medicated healthy controls. In addition activation of the non-dominant side, left-handed activity in right-handed patients, results in a total reversal of the normal pattern of lateral activation suggesting a disturbance in hemispheric localization of activity during a catatonic state.

Reconstruction of the first web space in symbrachydactyly using the reverse radial forearm flap.

PubMed

Gülgönen, Ayan; Güdemez, Eftal

2007-02-01

To present a new approach for the reconstruction of severe first web contractures using a distally based reverse radial forearm flap in symbrachydactyly patients. This study included 6 hands in 5 patients. Subjective evaluation included appearance, parent satisfaction (and patient satisfaction when appropriate), and ability to perform daily activities such as thumb-index grasp and pinch at follow-up evaluations. We measured the angle between the first and second rays using a goniometer at maximum radial abduction, and pinch and grasp strengths were evaluated as an objective assessment. The average follow-up period was 2 years. All parents and patients were happy with the aesthetic appearance. They were completely satisfied in their daily living activities. The average first web angle measurement was 56 degrees . An average of 39 degrees of improvement of web measurement was achieved. For the unilateral 4 patients, the average pinch strength measurement was 80% of the normal contralateral hand and the grip strength was 75% of the normal contralateral hand. The reverse radial forearm flap was found to be a safe and simple method in the reconstruction of severe first web contractures in symbrachydactyly patients. This method provided good coverage of appropriate thickness and skin quality, and supple soft tissue that filled the first web space. Therapeutic IV.

Quantification of functional near infrared spectroscopy to assess cortical reorganization in children with cerebral palsy

PubMed Central

Tian, Fenghua; Delgado, Mauricio R.; Dhamne, Sameer C.; Khan, Bilal; Alexandrakis, George; Romero, Mario I.; Smith, Linsley; Reid, Dahlia; Clegg, Nancy J.; Liu, Hanli

2013-01-01

Cerebral palsy (CP) is the most common motor disorder in children. Currently available neuroimaging techniques require complete body confinement and steadiness and thus are extremely difficult for pediatric patients. Here, we report the use and quantification of functional near infrared spectroscopy (fNIRS) to investigate the functional reorganization of the sensorimotor cortex in children with hemiparetic CP. Ten of sixteen children with congenital hemiparesis were measured during finger tapping tasks and compared with eight of sixteen age-matched healthy children, with an overall measurement success rate of 60%. Spatiotemporal analysis was introduced to quantify the motor activation and brain laterality. Such a quantitative approach reveals a consistent, contralateral motor activation in healthy children at 7 years of age or older. In sharp contrast, children with congenital hemiparesis exhibit all three of contralateral, bilateral and ipsilateral motor activations, depending on specific ages of the pediatric subjects. This study clearly demonstrates the feasibility of fNIRS to be utilized for investigating cortical reorganization in children with CP or other cortical disorders. PMID:21164944

Reversed Robin Hood Syndrome in the Light of Nonlinear Model of Cerebral Circulation

NASA Astrophysics Data System (ADS)

Piechna, A.; Cieslicki, K.

2017-05-01

The brain is supplied by the internal carotid and vertebro-basilar systems of vessels interconnected by arterial anastomoses and forming at the base of the brain a structure called the Circle of Willis (CoW). An active intrinsic ability of cerebral vascular bed maintains constant Cerebral Blood Flow (CBF) in a certain range of systemic pressure changes. This ability is called autoregulation and together with the redundant structure of the CoW guarantee maintaining CBF even in partial occlusion of supplying arteries. However, there are some situations when the combination of those two mechanisms causes an opposite effect called the Reversed Robin Hood Syndrome (RRHS). In this work we proposed a model of the CoW with autoregulation mechanism and investigated a RRHS which may occur in the case of Internal Carotid Artery (ICA) stenosis combined with hypercapnia. We showed and analyzed the mechanism of stealing the blood by the contralateral side of the brain. Our results were qualitatively compared with the clinical reports available in the literature.

Multi-channel linear descriptors for event-related EEG collected in brain computer interface.

PubMed

Pei, Xiao-mei; Zheng, Chong-xun; Xu, Jin; Bin, Guang-yu; Wang, Hong-wu

2006-03-01

By three multi-channel linear descriptors, i.e. spatial complexity (omega), field power (sigma) and frequency of field changes (phi), event-related EEG data within 8-30 Hz were investigated during imagination of left or right hand movement. Studies on the event-related EEG data indicate that a two-channel version of omega, sigma and phi could reflect the antagonistic ERD/ERS patterns over contralateral and ipsilateral areas and also characterize different phases of the changing brain states in the event-related paradigm. Based on the selective two-channel linear descriptors, the left and right hand motor imagery tasks are classified to obtain satisfactory results, which testify the validity of the three linear descriptors omega, sigma and phi for characterizing event-related EEG. The preliminary results show that omega, sigma together with phi have good separability for left and right hand motor imagery tasks, which could be considered for classification of two classes of EEG patterns in the application of brain computer interfaces.

In vivo functional neurochemistry of human cortical cholinergic function during visuospatial attention

PubMed Central

Lindner, Michael; Bell, Tiffany; Iqbal, Somya; Mullins, Paul Gerald

2017-01-01

Cortical acetylcholine is involved in key cognitive processes such as visuospatial attention. Dysfunction in the cholinergic system has been described in a number of neuropsychiatric disorders. Levels of brain acetylcholine can be pharmacologically manipulated, but it is not possible to directly measure it in vivo in humans. However, key parts of its biochemical cascade in neural tissue, such as choline, can be measured using magnetic resonance spectroscopy (MRS). There is evidence that levels of choline may be an indirect but proportional measure of acetylcholine availability in brain tissue. In this study, we measured relative choline levels in the parietal cortex using functional (event-related) MRS (fMRS) during performance of a visuospatial attention task, with a modelling approach verified using simulated data. We describe a task-driven interaction effect on choline concentration, specifically driven by contralateral attention shifts. Our results suggest that choline MRS has the potential to serve as a proxy of brain acetylcholine function in humans. PMID:28192451

Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in the Treatment of Dystonia.

PubMed

Lozeron, Pierre; Poujois, Aurélia; Richard, Alexandra; Masmoudi, Sana; Meppiel, Elodie; Woimant, France; Kubis, Nathalie

2016-01-01

Dystonias represent a heterogeneous group of movement disorders responsible for sustained muscle contraction, abnormal postures, and muscle twists. It can affect focal or segmental body parts or be generalized. Primary dystonia is the most common form of dystonia but it can also be secondary to metabolic or structural dysfunction, the consequence of a drug's side-effect or of genetic origin. The pathophysiology is still not elucidated. Based on lesion studies, dystonia has been regarded as a pure motor dysfunction of the basal ganglia loop. However, basal ganglia lesions do not consistently produce dystonia and lesions outside basal ganglia can lead to dystonia; mild sensory abnormalities have been reported in the dystonic limb and imaging studies have shown involvement of multiple other brain regions including the cerebellum and the cerebral motor, premotor and sensorimotor cortices. Transcranial magnetic stimulation (TMS) is a non-invasive technique of brain stimulation with a magnetic field applied over the cortex allowing investigation of cortical excitability. Hyperexcitability of contralateral motor cortex has been suggested to be the trigger of focal dystonia. High or low frequency repetitive TMS (rTMS) can induce excitatory or inhibitory lasting effects beyond the time of stimulation and protocols have been developed having either a positive or a negative effect on cortical excitability and associated with prevention of cell death, γ-aminobutyric acid (GABA) interneurons mediated inhibition and brain-derived neurotrophic factor modulation. rTMS studies as a therapeutic strategy of dystonia have been conducted to modulate the cerebral areas involved in the disease. Especially, when applied on the contralateral (pre)-motor cortex or supplementary motor area of brains of small cohorts of dystonic patients, rTMS has shown a beneficial transient clinical effect in association with restrained motor cortex excitability. TMS is currently a valuable tool to improve our understanding of the pathophysiology of dystonia but large controlled studies using sham stimulation are still necessary to delineate the place of rTMS in the therapeutic strategy of dystonia. In this review, we will focus successively on the use of TMS as a tool to better understand pathophysiology, and the use of rTMS as a therapeutic strategy.

Alterations of the amplitude of low-frequency fluctuation in healthy subjects with theta-burst stimulation of the cortex of the suprahyoid muscles.

PubMed

Ruan, Xiuhang; Xu, Guangqing; Gao, Cuihua; Liu, Lingling; Liu, Yanli; Jiang, Lisheng; Chen, Xin; Yu, Shaode; Jiang, Xinqing; Lan, Yue; Wei, Xinhua

2017-12-04

Theta burst stimulation (TBS) has emerged as a promising tool for the treatment of swallowing disorders; however, the short-term after-effects of brain activation induced by TBS remain unknown. Here, we measured the changes in spontaneous brain activation using the amplitude of low-frequency fluctuation (ALFF) approach in subjects who underwent different TBS protocols. Sixty right-handed healthy participants (male, n=30; female, n=30; mean age=23.5y) were recruited in this study and randomly assigned to three groups that underwent three different TBS protocols. In group 1, continuous TBS (cTBS) was positioned on the left hemisphere of the suprahyoid muscle cortex. For group 2, intermittent TBS (iTBS) was placed on the left hemisphere of the suprahyoid muscle cortex. Group 3 underwent combined cTBS/iTBS protocols in which iTBS on the right hemisphere was performed immediately after completing cTBS on the left suprahyoid muscle cortex. Compared to pre-TBS, post-cTBS showed decreased ALFF in the anterior cingulate gyrus (BA 32); post-iTBS induced an increase in ALFF in the bilateral precuneus (BA 7); and post-cTBS/iTBS induced a decrease in ALFF in the brainstem, and resulted in increased ALFF in the middle cingulate gyrus (BA 24) as well as the left precentral gyrus (BA 6). Compared the effect of post-TBS protocols, increased ALFF was found in left posterior cerebellum lobe and left inferior parietal lobule (BA 40) (post-cTBS vs post-iTBS), and decreased ALFF exhibited in paracentral lobule (BA 4) (post-iTBS vs post-cTBS/iTBS). These findings indicate that multiple brain areas involved in swallowing regulation after stimulation of TBS over the suprahyoid muscles. cTBS induces decreased after-effects while iTBS results in increased after-effects on spontaneous brain activation. Moreover, iTBS can eliminate the after-effects of cTBS applied on the contralateral swallowing cortex and alter the activity of contralateral motor cortex and brainstem. Our findings provide a novel evidence for the short-term effect of TBS on spontaneous brain activation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

NASA Astrophysics Data System (ADS)

Yao, Junjie; Xia, Jun; Maslov, Konstantin; Avanaki, Mohammadreza R. N.; Tsytsarev, Vassiliy; Demchenko, Alexei V.; Wang, Lihong V.

2013-03-01

To control the overall action of the body, brain consumes a large amount of energy in proportion to its volume. In humans and many other species, the brain gets most of its energy from oxygen-dependent metabolism of glucose. An abnormal metabolic rate of glucose and/or oxygen usually reflects a diseased status of brain, such as cancer or Alzheimer's disease. We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood-brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively unmixed by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. The glucose response amplitude was about half that of the hemodynamic response. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area showed a clear vascular pattern and spread about twice as wide as that of the glucose response. The PACT of mouse brain metabolism was validated by high-resolution open-scalp OR-PAM and fluorescence imaging. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism.

Sensitization of cerebral tissue in nude mice with photodynamic therapy induces ADAM17/TACE and promotes glioma cell invasion

PubMed Central

Zheng, Xuguang; Jiang, Feng; Katakowski, Mark; Zhang, Xuepeng; Jiang, Hao; Zhang, Zheng Gang; Chopp, Michael

2008-01-01

In the present study, we tested the hypothesis that a mild cerebral tissue injury promotes subsequent glioma invasion via activation of the ADAM17-EGFR-PI3K-Akt pathway. Mild injury was induced by Photodynamic therapy (PDT), which employs tissue-penetrating laser light exposure following systemic administration of a tumor-localizing photosensitizer. Athymic nude mice were treated with sublethal PDT (80J/cm2 with 2mg/kg Photofrin). Hypoxic stress and ADAM17-EGFR-PI3K-Akt were measured using Western blot and immunostaining. Additional groups with/without pro-sublethal PDT were subsequently implanted with U87 glioma tumor cell. Tumor invasion and ADAM17-EGFR-PI3K-Akt pathway in tumor area were measured. After a sublethal dose of PDT, HIF-1α expression was increased by a factor of three in PDT-treated normal brain tissue compared to contralateral control brain tissue. PDT-treated brain tissue exhibited a significant increase in ADAM17, p-EGFR, p-Akt expression compared to non-treated tissue. ADAM17 positive area significantly increased from 1.78% to 10.89%. The percentage of p-EGFR and p-Akt positive cells significantly increased from 9.50% and 14.50% to 21.31% and 32.29%,respectively, PDT treatment significantly increased subsequent implanted U87 glioma cell invasion by 3.68-fold and increased ADAM17, EGFR, p-EGFR, Akt, p-Akt expression by 178%, 43.9%,152.7%, 89.6%,and 164.2%, respectively, compared to control group. Our data showed that a sublethal sensitization of cerebral tissue with PDT significantly increased U87 cell invasion in nude mice, and that glioma cell invasion is highly correlated with activation of the ADAM17-EGFR-PI3K-Akt pathway (r=0.928, 0.775, 0.870, 0.872, and 0.883, respectively), most likely via HIF-1α. PMID:18358600

A case of schizencephaly has a normal surface EEG but abnormal intracranial EEG: epilepsia partialis continua or dystonia?

PubMed

Lv, Yudan; Ma, Dihui; Meng, Hongmei; Zan, Wang; Li, Cui

2013-10-01

Schizencephaly is a congenital malformation of the cerebral hemispheres, with communication between the lateral ventricle and the subarachnoid space. Marinelli reported that schizencephaly may be associated with continuous involuntary hand movements, such as dystonia or epilepsia partialis continua (EPC). We describe a young Chinese patient with continuous involuntary movements of the contralateral hand affected by schizencephaly. He has a normal scalp electroencephalogram (EEG) but abnormal intracranial EEG, with synchronized periodic lateralized epileptiform discharges. The results obtained from these EEG investigations and the clinical features of the involuntary movements are in favor of a diagnosis of secondary EPC.

Masking overshoot: Effects of ipsilateral, bilateral and contralateral priming

NASA Astrophysics Data System (ADS)

Connington, Maureen Catherine

This study was concerned with masking overshoot, the elevation of the threshold of a brief signal when it is presented at the onset of a masking noise rather than at its temporal center. More specifically, it was concerned with the release from overshoot (i.e., threshold improvement) produced by priming stimuli, presented ipsilaterally, bilaterally and contralaterally at primer- masker gaps of 20, 40 and 80 msec. The more general purpose of the study was to assess the contributions of peripheral and central factors to the overshoot and overshoot-release phenomena. The primers and masking stimuli consisted of white noise bursts of 200 and 400 msec duration, respectively. The probe signal was a 20 msec 4kHz tone. The tone and masker were always presented in one ear. There were, however, 3 modes of primer presentation: ipsilateral, bilateral (identical waveforms to both ears) and contralateral. Three primer-masker gaps of 20, 40 and 80 msec were used. Five normally hearing adults were tested at primer and masker levels of 80 dB HL. Four of the five subjects exhibited significant masking overshoot, when tested without priming. Ipsilateral priming with 20 and 40 msec gaps produced significant masking release from overshoot. Threshold became poorer, however with increasing gap duration and with increasing distance of the perceived primer from the test ear (i.e. ipsilateral priming produced better thresholds than did bilateral priming and bilateral priming produced better thresholds than contralateral priming). There was significant masking enhancement (i.e. threshold was significantly poorer than in the unprimed probe at onset condition) with the contralateral 80 msec primer. The fact that ipsilateral and bilateral primers performed differently does not support the theory that masking overshoot and its release are solely the results of peripheral adaptation. In fact, the group results support the conclusion that masking overshoot is influenced by central factors. However, there were marked inter-subject differences. It seems possible that masking overshoot and its release are influenced by both peripheral adaptation effects and central processes and that the balance between the two is subject-dependent.

Brain-Derived Neurotrophic Factor (BDNF) Promotes Cochlear Spiral Ganglion Cell Survival and Function in Deafened, Developing Cats

PubMed Central

Leake, Patricia A.; Hradek, Gary T.; Hetherington, Alexander M.; Stakhovskaya, Olga

2011-01-01

Postnatal development and survival of spiral ganglion (SG) neurons depend upon both neural activity and neurotrophic support. Our previous studies showed that electrical stimulation from a cochlear implant only partly prevents SG degeneration after early deafness. Thus, neurotrophic agents that might be combined with an implant to improve neural survival are of interest. Recent studies reporting that BDNF promotes SG survival after deafness, have been conducted in rodents and limited to relatively short durations. Our study examined longer duration BDNF treatment in deafened cats that may better model the slow progression of SG degeneration in human cochleae and provides the first study of BDNF in the developing auditory system. Kittens were deafened neonatally, implanted at 4-5 weeks with intracochlear electrodes containing a drug-delivery cannula, and BDNF or artificial perilymph was infused for 10 weeks from a mini-osmotic pump. In BDNF-treated cochleae SG cells grew to normal size and were significantly larger than cells on the contralateral side. However, their morphology was not completely normal and many neurons lacked or had thinned perikaryl myelin. Unbiased stereology was employed to estimate SG cell density, independent of cell size. BDNF was effective in promoting significantly improved survival of SG neurons in these developing animals. BDNF treatment also resulted in higher density and larger size of myelinated radial nerve fibers, sprouting of fibers into the scala tympani, and improvement in electrically-evoked auditory brainstem response thresholds. Although BDNF may have potential therapeutic value in the developing auditory system, many serious obstacles currently preclude clinical application. PMID:21452221

Normative dimensions and symmetry of the lacrimal drainage system on dacryocystography: statistical analysis of morphometric characteristics.

PubMed

Horsburgh, A; Massoud, T F

2013-05-01

Asymmetric lacrimal flow occurs in females more than males. We hypothesised that the normal lacrimal drainage system (LDS) may show subtle left-right asymmetry in morphometry when imaged on dacryocystography (DCG). We retrospectively reviewed 60 normal bilateral LDSs.Images were analysed for 7 parameters: (1) combined length of either the superior or inferior canaliculus plus common canaliculus, (2) angle of insertion of common canaliculus into lacrimal sac (LS), (3, 4) length and width of the LS, (5) length of the naso lacrimal duct (NLD), and (6, 7) width of proximal and distal NLD. We tested the effect of independent variables (age, gender, and side) on each dependent variable (length, width, or angle) using regression analysis. We used a Studentt-test for independent samples to statistically compare bilateral LDSs. Patient median age was 62 years, and male:female ratio was 27:73. Mean dimensions and angles for all LDSs were: (1) 14.5 mm, (2) 57°,(3) 11.6 mm, (4) 2.1 mm, (5) 20.7 mm, (6) 1.4 mm, and (7) 1.8 mm. No independent variable affected variation in length, width, or angle. No significant difference emerged between dimensions of right and left LDSs in both sexes. A degree of affective lateralisation in the brain is known to result in lacrimal flow asymmetry after mood manipulation. We show that this is not reflected in LDS anatomy. Moreover, our detailed morphometric data can aid in therapeutic planning of LDS luminal procedures, especially when DCG images of one LDS are used as a road map for contralateral interventions.

Preoperative ultrasonographic evaluation of the contralateral patent processus vaginalis at the level of the internal inguinal ring is useful for predicting contralateral inguinal hernias in children: a prospective analysis.

PubMed

Kaneda, H; Furuya, T; Sugito, K; Goto, S; Kawashima, H; Inoue, M; Hosoda, T; Masuko, T; Ohashi, K; Ikeda, T; Koshinaga, T; Hoshino, M; Goto, H

2015-08-01

The current study aimed to verify the usefulness of preoperative ultrasonographic evaluation of contralateral patent processus vaginalis (PPV) at the level of the internal inguinal ring. This was a prospective study of patients undergoing unilateral inguinal hernia repair at two institutions during 2010-2011. The sex, age at initial operation, birth weight, initial operation side, and the preoperative diameter of the contralateral PPV as determined using ultrasonography (US) were recorded. We analyzed the incidence of contralateral inguinal hernia, risk factors, and the usefulness of the preoperative major diameter of the contralateral PPV. The follow-up period was 36 months. All 105 patients who underwent unilateral hernia repair completed 36 months of follow-up, during which 11 patients (10.5 %) developed a contralateral hernia. The following covariates were not associated with contralateral hernia development: sex (p = 0.350), age (p = 0.185), birth weight (p = 0.939), and initial operation side (p = 0.350). The preoperative major diameter of the contralateral PPV determined using US was significantly wider among patients with a contralateral hernia than those without a contralateral hernia (p = 0.001). When the 105 patients were divided into two groups according to cut-off values of the preoperative major diameter of the contralateral PPV (wide group, >2.0 mm; narrow group, ≤2.0 mm), a significant association was observed between the preoperative major diameter of the contralateral PPV and patient outcomes (p = 0.001). We used US and confirmed the usefulness of a preoperative evaluation of the major diameter of the contralateral PPV at the level of the internal inguinal ring in pediatric patients with unilateral inguinal hernias.

fMRI and MRS measures of neuroplasticity in the pharyngeal motor cortex

PubMed Central

Michou, Emilia; Williams, Steve; Vidyasagar, Rishma; Downey, Darragh; Mistry, Satish; Edden, Richard A.E.; Hamdy, Shaheen

2016-01-01

Introduction Paired associative stimulation (PAS), is a novel non-invasive technique where two neural substrates are employed in a temporally coordinated manner in order to modulate cortico-motor excitability within the motor cortex (M1). In swallowing, combined pharyngeal electrical and transcranial-magnetic-stimulation induced beneficial neurophysiological and behavioural effects in healthy subjects and dysphagic stroke patients. Here, we aimed to investigate the whole-brain changes in neural activation during swallowing using functional magnetic resonance imaging (fMRI) following PAS application and in parallel assess associated GABA changes with magnetic resonance spectroscopy (MRS). Methods Healthy adults (n = 11, 38 ± 9 years old) were randomised to receive real and sham PAS to the ‘stronger’ motor cortex pharyngeal representation, on 2 separate visits. Following PAS, event-related fMRI was performed to assess changes in brain activation in response to water and saliva swallowing and during rest. Data were analysed (SPM8) at P < .001. MRS data were acquired using MEGA-PRESS before and after the fMRI acquisitions on both visits and GABA concentrations were measured (AMARES, jMRUI). Results Following real PAS, BOLD signal changes (group analyses) increased at the site of stimulation during water and saliva swallowing, compared to sham PAS. It is also evident that PAS induced significant increases in BOLD signal to contralateral (to stimulation) hemispheric areas that are of importance to the swallowing neural network. Following real PAS, GABA: creatine ratio showed a trend to increase contralateral to PAS. Conclusion Targeted PAS applied to the human pharyngeal motor cortex induces local and remote changes in both primary and non-primary areas for water and saliva tasks. There is a possibility that changes of the inhibitory neurotransmitter, GABA, may play a role in the changes in BOLD signal. These findings provide evidence for the mechanisms underlying the beneficial effects of PAS on the brain swallowing network. PMID:25976926

Real color captures attention and overrides spatial cues in grapheme-color synesthetes but not in controls.

PubMed

van Leeuwen, Tessa M; Hagoort, Peter; Händel, Barbara F

2013-08-01

Grapheme-color synesthetes perceive color when reading letters or digits. We investigated oscillatory brain signals of synesthetes vs. controls using magnetoencephalography. Brain oscillations specifically in the alpha band (∼10Hz) have two interesting features: alpha has been linked to inhibitory processes and can act as a marker for attention. The possible role of reduced inhibition as an underlying cause of synesthesia, as well as the precise role of attention in synesthesia is widely discussed. To assess alpha power effects due to synesthesia, synesthetes as well as matched controls viewed synesthesia-inducing graphemes, colored control graphemes, and non-colored control graphemes while brain activity was recorded. Subjects had to report a color change at the end of each trial which allowed us to assess the strength of synesthesia in each synesthete. Since color (synesthetic or real) might allocate attention we also included an attentional cue in our paradigm which could direct covert attention. In controls the attentional cue always caused a lateralization of alpha power with a contralateral decrease and ipsilateral alpha increase over occipital sensors. In synesthetes, however, the influence of the cue was overruled by color: independent of the attentional cue, alpha power decreased contralateral to the color (synesthetic or real). This indicates that in synesthetes color guides attention. This was confirmed by reaction time effects due to color, i.e. faster RTs for the color side independent of the cue. Finally, the stronger the observed color dependent alpha lateralization, the stronger was the manifestation of synesthesia as measured by congruency effects of synesthetic colors on RTs. Behavioral and imaging results indicate that color induces a location-specific, automatic shift of attention towards color in synesthetes but not in controls. We hypothesize that this mechanism can facilitate coupling of grapheme and color during the development of synesthesia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Fluid resuscitation with isotonic or hypertonic saline solution avoids intraneural calcium influx after traumatic brain injury associated with hemorrhagic shock.

PubMed

Balbino, Marcos; Capone Neto, Antonio; Prist, Ricardo; Ferreira, Alice Teixeira; Poli-de-Figueiredo, Luiz F

2010-04-01

Calcium is one of the triggers involved in ischemic neuronal death. Because hypotension is a strong predictor of outcome in traumatic brain injury (TBI), we tested the hypothesis that early fluid resuscitation blunts calcium influx in hemorrhagic shock associated to TBI. Fifteen ketamine-halothane anesthetized mongrel dogs (18.7 kg +/- 1.4 kg) underwent unilateral cryogenic brain injury. Blood was shed in 5 minutes to a target mean arterial pressure of 40 mm Hg to 45 mm Hg and maintained at these levels for 20 minutes (shed blood volume = 26 mL/kg +/- 7 mL/kg). Animals were then randomized into three groups: CT (controls, no fluid resuscitation), HS (7.5% NaCl, 4 mL/kg, in 5 minutes), and LR (lactate Ringer's, 33 mL/kg, in 15 minutes). Twenty minutes later, a craniotomy was performed and cerebral biopsies were obtained next to the lesion ("clinical penumbra") and from the corresponding contralateral side ("lesion's mirror") to determine intracellular calcium by fluorescence signals of Fura-2-loaded cells. Controls remained hypotensive and in a low-flow state, whereas fluid resuscitation improved hemodynamic profile. There was a significant increase in intracellular calcium in the injured hemisphere in CT (1035 nM +/- 782 nM), compared with both HS (457 nM +/- 149 nM, p = 0.028) and LR (392 nM +/- 178 nM, p = 0.017), with no differences between HS and LR (p = 0.38). Intracellular calcium at the contralateral, uninjured hemisphere was 438 nM +/- 192 nM in CT, 510 nM +/- 196 nM in HS, and 311 nM +/- 51 nM in LR, with no significant differences between them. Both small volume hypertonic saline and large volume lactated Ringer's blunts calcium influx in early stages of TBI associated to hemorrhagic shock. No fluid resuscitation strategy promotes calcium influx and further neural damage.

Monocyte galactose/N-acetylgalactosamine-specific C-type lectin receptor stimulant immunotherapy of an experimental glioma. Part II: combination with external radiation improves survival

PubMed Central

Kushchayev, Sergiy V; Sankar, Tejas; Eggink, Laura L; Kushchayeva, Yevgeniya S; Wiener, Philip C; Hoober, J Kenneth; Eschbacher, Jennifer; Liu, Ruolan; Shi, Fu-Dong; Abdelwahab, Mohammed G; Scheck, Adrienne C; Preul, Mark C

2012-01-01

Background A peptide mimetic of a ligand for the galactose/N-acetylgalactosamine-specific C-type lectin receptors (GCLR) exhibited monocyte-stimulating activity, but did not extend survival when applied alone against a syngeneic murine malignant glioma. In this study, the combined effect of GCLRP with radiation was investigated. Methods C57BL/6 mice underwent stereotactic intracranial implantation of GL261 glioma cells. Animals were grouped based on randomized tumor size by magnetic resonance imaging on day seven. One group that received cranial radiation (4 Gy on days seven and nine) only were compared with animals treated with radiation and GCLRP (4 Gy on days seven and nine combined with subcutaneous injection of 1 nmol/g on alternative days beginning on day seven). Magnetic resonance imaging was used to assess tumor growth and correlated with survival rate. Blood and brain tissues were analyzed with regard to tumor and contralateral hemisphere using fluorescence-activated cell sorting analysis, histology, and enzyme-linked immunosorbent assay. Results GCLRP activated peripheral monocytes and was associated with increased blood precursors of dendritic cells. Mean survival increased (P < 0.001) and tumor size was smaller (P < 0.02) in the GCLRP + radiation group compared to the radiation-only group. Accumulation of dendritic cells in both the tumoral hemisphere (P < 0.005) and contralateral tumor-free hemisphere (P < 0.01) was associated with treatment. Conclusion Specific populations of monocyte-derived brain cells develop critical relationships with malignant gliomas. The biological effect of GCLRP in combination with radiation may be more successful because of the damage incurred by tumor cells by radiation and the enhanced or preserved presentation of tumor cell antigens by GCLRP-activated immune cells. Monocyte-derived brain cells may be important targets for creating effective immunological modalities such as employing the receptor system described in this study. PMID:23049281

Monocyte galactose/N-acetylgalactosamine-specific C-type lectin receptor stimulant immunotherapy of an experimental glioma. Part II: combination with external radiation improves survival.

PubMed

Kushchayev, Sergiy V; Sankar, Tejas; Eggink, Laura L; Kushchayeva, Yevgeniya S; Wiener, Philip C; Hoober, J Kenneth; Eschbacher, Jennifer; Liu, Ruolan; Shi, Fu-Dong; Abdelwahab, Mohammed G; Scheck, Adrienne C; Preul, Mark C

2012-01-01

A peptide mimetic of a ligand for the galactose/N-acetylgalactosamine-specific C-type lectin receptors (GCLR) exhibited monocyte-stimulating activity, but did not extend survival when applied alone against a syngeneic murine malignant glioma. In this study, the combined effect of GCLRP with radiation was investigated. C57BL/6 mice underwent stereotactic intracranial implantation of GL261 glioma cells. Animals were grouped based on randomized tumor size by magnetic resonance imaging on day seven. One group that received cranial radiation (4 Gy on days seven and nine) only were compared with animals treated with radiation and GCLRP (4 Gy on days seven and nine combined with subcutaneous injection of 1 nmol/g on alternative days beginning on day seven). Magnetic resonance imaging was used to assess tumor growth and correlated with survival rate. Blood and brain tissues were analyzed with regard to tumor and contralateral hemisphere using fluorescence-activated cell sorting analysis, histology, and enzyme-linked immunosorbent assay. GCLRP activated peripheral monocytes and was associated with increased blood precursors of dendritic cells. Mean survival increased (P < 0.001) and tumor size was smaller (P < 0.02) in the GCLRP + radiation group compared to the radiation-only group. Accumulation of dendritic cells in both the tumoral hemisphere (P < 0.005) and contralateral tumor-free hemisphere (P < 0.01) was associated with treatment. Specific populations of monocyte-derived brain cells develop critical relationships with malignant gliomas. The biological effect of GCLRP in combination with radiation may be more successful because of the damage incurred by tumor cells by radiation and the enhanced or preserved presentation of tumor cell antigens by GCLRP-activated immune cells. Monocyte-derived brain cells may be important targets for creating effective immunological modalities such as employing the receptor system described in this study.

Structural white-matter connections mediating distinct behavioral components of spatial neglect in right brain-damaged patients.

PubMed

Vaessen, Maarten J; Saj, Arnaud; Lovblad, Karl-Olof; Gschwind, Markus; Vuilleumier, Patrik

2016-04-01

Spatial neglect is a neuropsychological syndrome in which patients fail to perceive and orient to stimuli located in the space contralateral to the lesioned hemisphere. It is characterized by a wide heterogeneity in clinical symptoms which can be grouped into distinct behavioral components correlating with different lesion sites. Moreover, damage to white-matter (WM) fiber tracts has been suggested to disconnect brain networks that mediate different functions associated with spatial cognition and attention. However, it remains unclear what WM pathways are associated with functionally dissociable neglect components. In this study we examined nine patients with a focal right hemisphere stroke using a series of neuropsychological tests and diffusion tensor imaging (DTI) in order to disentangle the role of specific WM pathways in neglect symptoms. First, following previous work, the behavioral test scores of patients were factorized into three independent components reflecting perceptual, exploratory, and object-centered deficits in spatial awareness. We then examined the structural neural substrates of these components by correlating indices of WM integrity (fractional anisotropy) with the severity of deficits along each profile. Several locations in the right parietal and frontal WM correlated with neuropsychological scores. Fiber tracts projecting from these locations indicated that posterior parts of the superior longitudinal fasciculus (SLF), as well as nearby callosal fibers connecting ipsilateral and contralateral parietal areas, were associated with perceptual spatial deficits, whereas more anterior parts of SLF and inferior fronto-occipital fasciculus (IFOF) were predominantly associated with object-centered deficits. In addition, connections between frontal areas and superior colliculus were found to be associated with the exploratory deficits. Our results provide novel support to the view that neglect may result from disconnection lesions in distributed brain networks, but also extend these notions by highlighting the role of dissociable circuits in different functional components of the neglect syndrome. However these preliminary findings require replication with larger samples of patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stab wound injury of the zebrafish adult telencephalon: a method to investigate vertebrate brain neurogenesis and regeneration.

PubMed

Schmidt, Rebecca; Beil, Tanja; Strähle, Uwe; Rastegar, Sepand

2014-08-04

Adult zebrafish have an amazing capacity to regenerate their central nervous system after injury. To investigate the cellular response and the molecular mechanisms involved in zebrafish adult central nervous system (CNS) regeneration and repair, we developed a zebrafish model of adult telencephalic injury. In this approach, we manually generate an injury by pushing an insulin syringe needle into the zebrafish adult telencephalon. At different post injury days, fish are sacrificed, their brains are dissected out and stained by immunohistochemistry and/or in situ hybridization (ISH) with appropriate markers to observe cell proliferation, gliogenesis, and neurogenesis. The contralateral unlesioned hemisphere serves as an internal control. This method combined for example with RNA deep sequencing can help to screen for new genes with a role in zebrafish adult telencephalon neurogenesis, regeneration, and repair.

Parry-Romberg syndrome: intracranial MRI appearances.

PubMed

Moko, Sheree Bernadette; Mistry, Yezdi; Blandin de Chalain, Tristan Maurice

2003-10-01

To gain further insight into the pathogenesis of Parry-Romberg syndrome, a sporadic disease of unknown aetiology characterized by progressive wasting of one side of the face. Cranial MRI was performed in 10 patients with Parry-Romberg syndrome. The central nervous system findings are correlated to clinical findings and a review of the literature. Three patients with a history of migraine had abnormal brain findings confined to the cerebral hemisphere ipsilateral to the facial hemiatrophy. Two patients without CNS symptoms had intracranial changes, one ipsilateral, the other both ipsilateral and contralateral to the facial hemiatrophy, on MRI. These changes consisted of either intracerebral atrophy or white matter hyperintensity. Five patients without CNS symptoms had no pathological intracranial MRI appearances. A significant number of patients with Parry-Romberg syndrome may have underlying brain involvement. These findings are consistent with previous reports.

Descending pathways to the cutaneus trunci muscle motoneuronal cell group in the cat

NASA Technical Reports Server (NTRS)

Holstege, Gert; Blok, Bertil F.

1989-01-01

Pathways involved in the cutaneous trunci muscle (CTM) reflex in the cat were investigated. Experimental animals were injected with tritium-labeled L-leucine into their spinal cord, brain stem, or diencephalon and, after six weeks, perfused with 10-percent formalin. The brains and spinal cords were postfixed in formalin and were cut into transverse 25-micron-thick frozen sections for autoradiography. Results based on injections in the C1, C2, C6, and C8 segments suggest that propriospinal pathways to the CTM motor nucleus originating in the cervical cord do no exist, although these propriospinal projections are very strong to all other motoneuronal cell groups surrounding the CTM motor nucleus. The results also demonstrate presence of specific supraspinal projections to the CTM motor nucleus, originating in the contralateral nucleus retroambiguous and the ipsilateral dorsolateral pontine tegmentum.

Neural correlates of lower limbs proprioception: An fMRI study of foot position matching.

PubMed

Iandolo, Riccardo; Bellini, Alessandro; Saiote, Catarina; Marre, Ilaria; Bommarito, Giulia; Oesingmann, Niels; Fleysher, Lazar; Mancardi, Giovanni Luigi; Casadio, Maura; Inglese, Matilde

2018-05-01

Little is known about the neural correlates of lower limbs position sense, despite the impact that proprioceptive deficits have on everyday life activities, such as posture and gait control. We used fMRI to investigate in 30 healthy right-handed and right-footed subjects the regional distribution of brain activity during position matching tasks performed with the right dominant and the left nondominant foot. Along with the brain activation, we assessed the performance during both ipsilateral and contralateral matching tasks. Subjects had lower errors when matching was performed by the left nondominant foot. The fMRI analysis suggested that the significant regions responsible for position sense are in the right parietal and frontal cortex, providing a first characterization of the neural correlates of foot position matching. © 2018 Wiley Periodicals, Inc.

Muscle metastasis from non-small cell lung cancer: two cases and literature review.

PubMed

Tezcan, Y; Koc, M

2014-08-01

Non-small cell lung cancers (NSCLC) is the most commonly observed group among lung cancers. Adenocancers are histopathologically more common. Males are more affected than females, an effect which is directly related to smoking. They generally cause distant haematogenous and lymphatic metastasis. Distant haematogenous metastases are often seen in contralateral lung, brain, bone, adrenals, and liver. Muscle metastases from NSCLC are quite rare and male cases are more frequently affected compared to female cases. NSCLC cases with muscle metastasis are at the same time accompanied by distant organ metastases such as bone, brain, and liver. All treatment approaches are considered to be palliative in these cases, which are symptomatologically quite severe. In the present study, we presented the rarely observed cases of two male patients with muscle metastasis from NSCLC together with the related literature.

Effects of monocular viewing and eye dominance on spatial attention.

PubMed

Roth, Heidi L; Lora, Andrea N; Heilman, Kenneth M

2002-09-01

Observations in primates and patients with unilateral spatial neglect have suggested that patching of the eye ipsilateral to the injury and contralateral to the neglected space can sometimes improve attention to the neglected space. Investigators have generally attributed the effects of monocular eye patching to activation of subcortical centers that interact with cortical attentional systems. Eye patching is thought to produce preferential activation of attentional systems contralateral to the viewing eye. In this study we examined the effect of monocular eye patching on attentional biases in normal subjects. When normal subjects bisect vertical (radial) lines using both eyes, they demonstrate a far attentional bias, misbisecting lines away from their body. In a monocular viewing experiment, we found that the majority of subjects, who were right eye dominant, had relatively nearer bisections and a diminished far bias when they used their right eye (left eye covered) compared with when they used their left eye (right eye covered). The smaller group of subjects who were left eye dominant had relatively nearer bisections and a diminished far bias when they used their left eye compared with when they used their right eye. In the hemispatial placement experiment, we directly manipulated hemispheric engagement by having subjects perform the same task in right and left hemispace. We found that right eye dominant subjects had a diminished far bias in right hemispace relative to left hemispace. Left eye dominant subjects showed the opposite pattern and had a diminished far bias in left hemispace. For both groups, spatial presentation affected performance more for the non-dominant eye. The results suggest that monocular viewing is associated with preferential activation of attentional systems in the contralateral hemisphere, and that the right hemisphere (at least in right eye dominant subjects) is biased towards far space. Finally, the results suggest that the poorly understood phenomenon of eye dominance may be related to hemispheric specialization for visual attention.

A nitric oxide donor reduces brain injury and enhances recovery of cerebral blood flow after hypoxia-ischemia in the newborn rat.

PubMed

Wainwright, Mark S; Grundhoefer, Dava; Sharma, Shruti; Black, Stephen M

2007-03-26

Nitric oxide (NO) released in response to hypoxia-ischemia (HI) in the newborn brain may mediate both protective and pathologic responses. We sought to determine whether pharmacologic increase of NO using an NO donor would reduce neurologic injury resulting from HI in the postnatal day 7 rat. We measured NO levels and CBF in the presence of either a NOS inhibitor, N-nitro-l-arginine methyl ester (L-NAME) or an NO donor (Z)-1-[N-(2-amino-ethyl)-N-(2-ammonio-ethyl)amino]diazen-1-ium-1,2-diolate (DETANONOate). Both inhibition of NOS and administration of an NO donor reduced neuropathologic injury after 7-day recovery. NO levels decreased in both ischemic and contralateral hemispheres during HI. This response was prevented by treatment with DETANONOate. Despite the decrease in NO, CBF increased during ischemia in the contralateral hemisphere but decreased when combined with brief hypoxia. Treatment with L-NAME abolished these increases, which were not altered by DETANONOate. Reduction of cellular metabolism by mild hypothermia also reduced both NO and CBF. Following prolonged HI, CBF remained decreased in the ischemic hemisphere up to 24-h recovery. This decrease was prevented by treatment with DETANONOate. These data show that administration of an NO donor reduces neurologic injury following HI in the newborn rat. This mechanism of this protection, in part, is due to an increase in the rate of recovery of CBF compared to vehicle-treated animals. Augmentation of NO-dependent increases in CBF may serve to improve neurologic outcome after perinatal asphyxia.

A NITRIC OXIDE DONOR REDUCES BRAIN INJURY AND ENHANCES RECOVERY OF CEREBRAL BLOOD FLOW AFTER HYPOXIA-ISCHEMIA IN THE NEWBORN RAT

PubMed Central

Wainwright, Mark S.; Grundhoefer, Dava; Sharma, Shruti; Black, Stephen M.

2007-01-01

Nitric oxide (NO) released in response to hypoxia-ischemia (HI) in the newborn brain may mediate both protective and pathologic responses. We sought to determine whether pharmacologic increase of NO using an NO donor would reduce neurologic injury resulting from HI in the postnatal day 7 rat. We measured NO levels and CBF in the presence of either a NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME) or an NO donor (Z)-1-[N-(2aminoethyl)-N-(2-ammonio-ethyl)amino]diazen-1-ium-1,2-diolate (DETANONOate). Both inhibition of NOS and administration of an NO donor reduced neuropathologic injury after 7-day recovery. NO levels decreased in both ischemic and contralateral hemispheres during HI. This response was prevented by treatment with DETANONOate. Despite the decrease in NO, CBF increased during ischemia in the contralateral hemisphere but decreased when combined with brief hypoxia. Treatment with L-NAME abolished these increases, which were not altered by DETANONOate. Reduction of cellular metabolism by mild hypothermia also reduced both NO and CBF. Following prolonged HI, CBF remained decreased in the ischemic hemisphere up to 24-hour recovery. This decrease was prevented by treatment with DETANONOate. These data show that administration of an NO donor reduces neurologic injury following HI in the newborn rat. This mechanism of this protection, in part, is due to an increase in the rate of recovery of CBF compared to vehicle-treated animals. Augmentation of NO-dependent increases in CBF may serve to improve neurologic outcome after perinatal asphyxia. PMID:17270345

Effects of subjective preference of colors on attention-related occipital theta oscillations.

PubMed

Kawasaki, Masahiro; Yamaguchi, Yoko

2012-01-02

Human daily behaviors are often affected by subjective preferences. Studies have shown that physical responses are affected by unconscious preferences before conscious decision making. Accordingly, attention-related neural activities could be influenced by unconscious preferences. However, few neurological data exist on the relationship between visual attention and subjective preference. To address this issue, we focused on lateralization during visual attention and investigated the effects of subjective color preferences on visual attention-related brain activities. We recorded electroencephalograph (EEG) data during a preference judgment task that required 19 participants to choose their preferred color from 2 colors simultaneously presented to the right and left hemifields. In addition, to identify oscillatory activity during visual attention, we conducted a control experiment in which the participants focused on either the right or the left color without stating their preference. The EEG results showed enhanced theta (4-6 Hz) and decreased alpha (10-12 Hz) activities in the right and left occipital electrodes when the participants focused on the color in the opposite hemifield. Occipital theta synchronizations also increased contralaterally to the hemifield to which the preferred color was presented, whereas the alpha desynchronizations showed no lateralization. The contralateral occipital theta activity lasted longer than the ipsilateral occipital theta activity. Interestingly, theta lateralization was observed even when the preferred color was presented to the unattended side in the control experiment, revealing the strength of the preference-related theta-modulation effect irrespective of visual attention. These results indicate that subjective preferences modulate visual attention-related brain activities. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Effective Connectivity Reveals Right-Hemisphere Dominance in Audiospatial Perception: Implications for Models of Spatial Neglect

PubMed Central

Friston, Karl J.; Mattingley, Jason B.; Roepstorff, Andreas; Garrido, Marta I.

2014-01-01

Detecting the location of salient sounds in the environment rests on the brain's ability to use differences in sounds arriving at both ears. Functional neuroimaging studies in humans indicate that the left and right auditory hemispaces are coded asymmetrically, with a rightward attentional bias that reflects spatial attention in vision. Neuropsychological observations in patients with spatial neglect have led to the formulation of two competing models: the orientation bias and right-hemisphere dominance models. The orientation bias model posits a symmetrical mapping between one side of the sensorium and the contralateral hemisphere, with mutual inhibition of the ipsilateral hemisphere. The right-hemisphere dominance model introduces a functional asymmetry in the brain's coding of space: the left hemisphere represents the right side, whereas the right hemisphere represents both sides of the sensorium. We used Dynamic Causal Modeling of effective connectivity and Bayesian model comparison to adjudicate between these alternative network architectures, based on human electroencephalographic data acquired during an auditory location oddball paradigm. Our results support a hemispheric asymmetry in a frontoparietal network that conforms to the right-hemisphere dominance model. We show that, within this frontoparietal network, forward connectivity increases selectively in the hemisphere contralateral to the side of sensory stimulation. We interpret this finding in light of hierarchical predictive coding as a selective increase in attentional gain, which is mediated by feedforward connections that carry precision-weighted prediction errors during perceptual inference. This finding supports the disconnection hypothesis of unilateral neglect and has implications for theories of its etiology. PMID:24695717

A New Analysis of Resting State Connectivity and Graph Theory Reveals Distinctive Short-Term Modulations due to Whisker Stimulation in Rats.

PubMed

Kreitz, Silke; de Celis Alonso, Benito; Uder, Michael; Hess, Andreas

2018-01-01

Resting state (RS) connectivity has been increasingly studied in healthy and diseased brains in humans and animals. This paper presents a new method to analyze RS data from fMRI that combines multiple seed correlation analysis with graph-theory (MSRA). We characterize and evaluate this new method in relation to two other graph-theoretical methods and ICA. The graph-theoretical methods calculate cross-correlations of regional average time-courses, one using seed regions of the same size (SRCC) and the other using whole brain structure regions (RCCA). We evaluated the reproducibility, power, and capacity of these methods to characterize short-term RS modulation to unilateral physiological whisker stimulation in rats. Graph-theoretical networks found with the MSRA approach were highly reproducible, and their communities showed large overlaps with ICA components. Additionally, MSRA was the only one of all tested methods that had the power to detect significant RS modulations induced by whisker stimulation that are controlled by family-wise error rate (FWE). Compared to the reduced resting state network connectivity during task performance, these modulations implied decreased connectivity strength in the bilateral sensorimotor and entorhinal cortex. Additionally, the contralateral ventromedial thalamus (part of the barrel field related lemniscal pathway) and the hypothalamus showed reduced connectivity. Enhanced connectivity was observed in the amygdala, especially the contralateral basolateral amygdala (involved in emotional learning processes). In conclusion, MSRA is a powerful analytical approach that can reliably detect tiny modulations of RS connectivity. It shows a great promise as a method for studying RS dynamics in healthy and pathological conditions.

A New Analysis of Resting State Connectivity and Graph Theory Reveals Distinctive Short-Term Modulations due to Whisker Stimulation in Rats

PubMed Central

Kreitz, Silke; de Celis Alonso, Benito; Uder, Michael; Hess, Andreas

2018-01-01

Resting state (RS) connectivity has been increasingly studied in healthy and diseased brains in humans and animals. This paper presents a new method to analyze RS data from fMRI that combines multiple seed correlation analysis with graph-theory (MSRA). We characterize and evaluate this new method in relation to two other graph-theoretical methods and ICA. The graph-theoretical methods calculate cross-correlations of regional average time-courses, one using seed regions of the same size (SRCC) and the other using whole brain structure regions (RCCA). We evaluated the reproducibility, power, and capacity of these methods to characterize short-term RS modulation to unilateral physiological whisker stimulation in rats. Graph-theoretical networks found with the MSRA approach were highly reproducible, and their communities showed large overlaps with ICA components. Additionally, MSRA was the only one of all tested methods that had the power to detect significant RS modulations induced by whisker stimulation that are controlled by family-wise error rate (FWE). Compared to the reduced resting state network connectivity during task performance, these modulations implied decreased connectivity strength in the bilateral sensorimotor and entorhinal cortex. Additionally, the contralateral ventromedial thalamus (part of the barrel field related lemniscal pathway) and the hypothalamus showed reduced connectivity. Enhanced connectivity was observed in the amygdala, especially the contralateral basolateral amygdala (involved in emotional learning processes). In conclusion, MSRA is a powerful analytical approach that can reliably detect tiny modulations of RS connectivity. It shows a great promise as a method for studying RS dynamics in healthy and pathological conditions. PMID:29875622

Sustained maintenance of somatotopic information in brain regions recruited by tactile working memory.

PubMed

Katus, Tobias; Müller, Matthias M; Eimer, Martin

2015-01-28

To adaptively guide ongoing behavior, representations in working memory (WM) often have to be modified in line with changing task demands. We used event-related potentials (ERPs) to demonstrate that tactile WM representations are stored in modality-specific cortical regions, that the goal-directed modulation of these representations is mediated through hemispheric-specific activation of somatosensory areas, and that the rehearsal of somatotopic coordinates in memory is accomplished by modality-specific spatial attention mechanisms. Participants encoded two tactile sample stimuli presented simultaneously to the left and right hands, before visual retro-cues indicated which of these stimuli had to be retained to be matched with a subsequent test stimulus on the same hand. Retro-cues triggered a sustained tactile contralateral delay activity component with a scalp topography over somatosensory cortex contralateral to the cued hand. Early somatosensory ERP components to task-irrelevant probe stimuli (that were presented after the retro-cues) and to subsequent test stimuli were enhanced when these stimuli appeared at the currently memorized location relative to other locations on the cued hand, demonstrating that a precise focus of spatial attention was established during the selective maintenance of tactile events in WM. These effects were observed regardless of whether participants performed the matching task with uncrossed or crossed hands, indicating that WM representations in this task were based on somatotopic rather than allocentric spatial coordinates. In conclusion, spatial rehearsal in tactile WM operates within somatotopically organized sensory brain areas that have been recruited for information storage. Copyright © 2015 Katus et al.

TLR4 Gene Expression and Pro-Inflammatory Cytokines in Alzheimer's Disease and in Response to Hippocampal Deafferentation in Rodents.

PubMed

Miron, Justin; Picard, Cynthia; Frappier, Josée; Dea, Doris; Théroux, Louise; Poirier, Judes

2018-01-01

One important aspect in Alzheimer's disease pathology is the presence of chronic inflammation. Considering its role as a key receptor in the microglial innate immune system, TLR4 was shown to regulate the binding and phagocytosis of amyloid plaques by microglia in several mouse models of amyloidosis, as well as the production of pro-inflammatory cytokines. To our knowledge, TLR4 and its association with cytokines have not been thoroughly examined in the brains of subjects affected with Alzheimer's disease. Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in postmortem human brains, we observed increased expression for the TLR4 and TNF genes (p = 0.001 and p = 0.025, respectively), as well as a trend for higher IL6 gene expression in the frontal cortex of AD subjects when compared to age-matched controls. Similarly, using a mouse model of hippocampal deafferentation without amyloidosis, (i.e., the entorhinal cortex lesioned mouse), we observed significant increases in the expression of both the Tlr4 (p = 0.0367 and p = 0.0193 compared to sham-lesioned mice or to the contralateral side, respectively) and Il1b (p = 0.0055 and p = 0.0066 compared to sham-lesioned mice or to the contralateral side, respectively) genes in the deafferentation phase, but not during the ensuing reinnervation process. In conclusion, we suggest that the modulation of cytokines by TLR4 is differentially regulated whether by the presence of amyloid plaques or by the ongoing deafferentation process.

Scaling of movement is related to pallidal γ oscillations in patients with dystonia.

PubMed

Brücke, Christof; Huebl, Julius; Schönecker, Thomas; Neumann, Wolf-Julian; Yarrow, Kielan; Kupsch, Andreas; Blahak, Christian; Lütjens, Goetz; Brown, Peter; Krauss, Joachim K; Schneider, Gerd-Helge; Kühn, Andrea A

2012-01-18

Neuronal synchronization in the gamma (γ) band is considered important for information processing through functional integration of neuronal assemblies across different brain areas. Movement-related γ synchronization occurs in the human basal ganglia where it is centered at ~70 Hz and more pronounced contralateral to the moved hand. However, its functional significance in motor performance is not yet well understood. Here, we assessed whether event-related γ synchronization (ERS) recorded from the globus pallidus internus in patients undergoing deep brain stimulation for medically intractable primary focal and segmental dystonia might code specific motor parameters. Pallidal local field potentials were recorded in 22 patients during performance of a choice-reaction-time task. Movement amplitude of the forearm pronation-supination movements was parametrically modulated with an angular degree of 30°, 60°, and 90°. Only patients with limbs not affected by dystonia were tested. A broad contralateral γ band (35-105 Hz) ERS occurred at movement onset with a maximum reached at peak velocity of the movement. The pallidal oscillatory γ activity correlated with movement parameters: the larger and faster the movement, the stronger was the synchronization in the γ band. In contrast, the event-related decrease in beta band activity was similar for all movements. Gamma band activity did not change with movement direction and did not occur during passive movements. The stepwise increase of γ activity with movement size and velocity suggests a role of neuronal synchronization in this frequency range in basal ganglia control of the scaling of ongoing movements.

Temporal Sequence of Ictal discharges Propagation in the Corticolimbic Basal Ganglia System during Amygdala Kindled Seizures in Freely Moving Rats

PubMed Central

Shi, Li-Hong; Luo, Fei; Woodward, Donald J.; McIntyre, Dan C.; Chang, Jing-Yu

2007-01-01

We used a multiple channel, single unit recording technique to investigate the neural activity in different corticolimbic and basal ganglia regions in freely moving rats before and during generalized amygdala kindled seizures. Neural activity was recorded simultaneously in the sensorimotor cortex (Ctx), hippocampus, amygdala, substantia nigra pars reticulata (SNr) and the subthalamic nucleus (STN). We observed massive synchronized activity among neurons of different brain regions during seizure episodes. Neurons in the kindled amygdala led other regions in synchronized firing, revealed by time lags of neurons in other regions in crosscorrelogram analysis. While there was no obvious time lag between Ctx and SNr, the STN and hippocampus did lag behind the Ctx and SNr in correlated firing. Activity in the amygdala and SNr contralateral to the kindling stimulation site lagged behind their ipsilateral counterparts. However no time lag was found between the kindling and contralateral sides of Ctx, hippocampus and STN. Our data confirm that the amygdala is an epileptic focus that emits ictal discharges to other brain regions. The observed temporal pattern indicates that ictal discharges from the amygdala arrive first at Ctx and SNr, and then spread to the hippocampus and STN. The simultaneous activation of both sides of the Ctx suggests that the neocortex participates in kindled seizures as a unisonant entity to provoke the clonic motor seizures. Early activation of the SNr (before the STN and hippocampus) points to an important role of the SNr in amygdala kindled seizures and supports the view that different SNr manipulations may be effective ways to control seizures. PMID:17049434

Neural dynamics in motor preparation: From phase-mediated global computation to amplitude-mediated local computation.

PubMed

Kajihara, Takafumi; Anwar, Muhammad Nabeel; Kawasaki, Masahiro; Mizuno, Yuji; Nakazawa, Kimitaka; Kitajo, Keiichi

2015-09-01

Oscillatory activity plays a critical role in the brain. Here, we illustrate the dynamics of neural oscillations in the motor system of the brain. We used a non-directional cue to instruct participants to prepare a motor response with either the left or the right hand and recorded electroencephalography during the preparation of the response. Consistent with previous findings, the amplitude of alpha-band (8-14Hz) oscillations significantly decreased over the motor region contralateral to the hand prepared for the response. Prior to this decrease, there were a number of inter-regional phase synchronies at lower frequencies (2-4Hz; delta band). Cross-frequency coupling was quantified to further explore the direct link between alpha amplitudes and delta synchrony. The cross-frequency coupling of showed response-specific modulation, whereby the motor region contralateral to the preparation hand exhibited an increase in coupling relative to the baseline. The amplitude of alpha oscillations had an unpreferred and a preferred delta phase, in which the amplitude was modulated negatively and positively, respectively. Given the amplitude of alpha-band oscillations decreased over the analyzed period, the alpha amplitude might be down-regulated by the phase-amplitude coupling, although we do not have direct evidence for that. Taken together, these results show global-to-local computation in the motor system, which started from inter-regional delta phase synchrony and ended at an effector-specific decrease in the amplitude of alpha-band oscillations, with phase-amplitude coupling connecting both computations. Copyright © 2015. Published by Elsevier Inc.

Functional plasticity of regenerated and intact taste receptors in adult rats unmasked by dietary sodium restriction.

PubMed

Hill, D L; Phillips, L M

1994-05-01

Unilateral chorda tympani nerve sectioning was combined with institution of a sodium-restricted diet in adult rats to determine the role that environment has on the functional properties of regenerating taste receptor cells. Rats receiving chorda tympani sectioning but no dietary manipulation (cut controls) and rats receiving only the dietary manipulation (diet controls) had normal responses to a concentration series of NaCl, sodium acetate (NaAc), and NH4Cl. However, responses from the regenerated nerve in NaCl-restricted rats (40-120 d postsectioning) to NaCl and NaAc were reduced by as much as 30% compared to controls, indicating that regenerating taste receptors are influenced by environmental (dietary) factors. Responses to NH4Cl were normal; therefore, the effect appears specific to sodium salts. Surprisingly, in the same rats, NaCl responses from the contralateral, intact chorda tympani were up to 40% greater than controls. Thus, in the same rat, there was over a twofold difference in sodium responses between the right and left chorda tympani nerves. A study of the time course of the functional alterations in the intact nerve revealed that responses to NaCl were extremely low immediately following sectioning (about 20% of the normal response), and then increased monotonically during the following 50 d until relative response magnitudes became supersensitive. This function occurred even when the cut chorda tympani was prevented from reinnervating lingual epithelia, demonstrating that events related to regeneration do not play a role in the functional properties of the contralateral side of the tongue.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of short malunion of the clavicle on in vivo scapular kinematics.

PubMed

Kim, DooSup; Lee, DongWoo; Jang, YoungHwan; Yeom, JunSeop; Banks, Scott A

2017-09-01

Short malunion of the clavicle after fracture can change scapular kinematics and alter clinical outcome. However, the effects of malunion on kinematics and outcomes remains poorly understood because there have been no in vivo studies measuring changes during active motion with malunion. This study aimed to measure and to compare in vivo 3-dimensional (3D) scapular kinematics between normal shoulders and shoulders with short malunion using 3D-2-dimensional model image registration techniques. Fifteen patients with clavicle fracture who had been treated conservatively were enrolled in this study. In these patients, the angle of scapular upward rotation, posterior tilting, and external rotation were compared between shoulders with short malunion and contralateral, normal shoulders. A 3D-2-dimensional model image registration technique was used to determine the 3D orientation of the scapula. Scapular upward rotation increased following increase of the arm elevation angle and also showed a significant difference by arm elevation in both groups (P = .04). Posterior tilting of the scapula gradually increased as the arm abduction angle increased, and this varied significantly between groups (P = .01). Shoulders with short malunion also showed a more internally rotated position than the contralateral, normal shoulders between 100° and the maximum abduction angle (P = .04). Our results suggest that clavicle shortening of >10% greatly affects scapular kinematics in vivo. Further studies will be needed to determine the clinical implications of short malunion of the clavicle. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of reconstruction of the anterior cruciate ligament on proprioception of the knee and the heel strike transient.

PubMed

Co, F H; Skinner, H B; Cannon, W D

1993-09-01

Abnormal proprioception of the knee joint has been documented after rupture of the anterior cruciate ligament (ACL) and may result in the loss of muscular reflexes. Excessive loading from the lack of muscular control may predispose the joint to osteoarthrosis. To investigate this problem, 10 patients were studied at an average of 31.6 months after ACL reconstruction. Three tests of joint proprioception and measurements of the vertical component of heel strike force during normal gait were used. A normal control group also was studied. For two of the proprioception tests (reproduction of passive motion and relative reproduction), there were no statistical differences among the uninjured (control) limbs, the normal contralateral limb of patients with a reconstructed ACL, and the extremity with a reconstructed ACL. In the third test (threshold of detection of motion), which previously has been shown to be adversely affected by ACL injury, the measurements for both extremities of patients with a reconstructed ACL were more accurate than those for the control group. The reconstructed extremity performed less accurately than the contralateral extremity (p < 0.05). The heel strike transient (vertical component of ground reaction force at heel strike) for uninjured and ACL-reconstructed limbs was not significantly different. In fact, the extremity with the reconstructed ACL had a lower transient than the uninjured extremity. Heel strike transients in patients with a reconstructed ACL were higher than those in the controls, but the differences were significant only when corrected for velocity of gait.(ABSTRACT TRUNCATED AT 250 WORDS)

Contralateral Anterior Interhemispheric Transparaterminal Gyrus Approach for Thalamopeduncular Pilocytic Astrocytoma in an Adult: Technical Report.

PubMed

Kumar, Amandeep; Sharma, Raghavendra; Garg, Ajay; Sharma, Bhawani S

2016-03-01

Thalamopeduncular gliomas arise at the junction of the thalamus and cerebral peduncle and constitute a subgroup of thalamic gliomas. These are surgically challenging lesions because of close proximity to important neural structures including corticospinal tracts (CSTs) and the thalamus. These tumors usually displace CSTs anterolaterally or extend to the lateral ventricular surface. Such tumors can be removed by either temporal or transventricular approaches. However, if CSTs cover the entire lateral surface of tumor and tumor does not extend to the ventricular surface, temporal and transventricular approaches cannot be used because the trajectories of both approaches would pass through normal eloquent structures (CSTs and thalamus), and consequently there would be a very high risk of postoperative neurologic deficits developing. A 50-year-old woman presented with contralateral hemiparesis. Radiologic evaluation revealed a right Thalamopeduncular glioma that displaced CSTs laterally and was covered by normal thalamus superiorly. Some CST fibers passed through the tumor. Because both lateral and superior surfaces were covered by eloquent structures, we used an anterior interhemispheric transparaterminal gyrus approach to access the tumor successfully and achieved subtotal excision. The patient had transient neurologic deterioration postoperatively that recovered to preoperative level within 2 weeks. The anterior interhemispheric transparaterminal gyrus approach has not been described previously for accessing brainstem lesions. This approach can be used to access tumors of the cerebral peduncle that displace CSTs laterally and are covered by normal thalamus superiorly. The anterior interhemispheric transparaterminal gyrus approach adds to the armamentarium of neurosurgeons for treatment of cerebral peduncular lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

Differences in neural responses to ipsilateral stimuli in wide-view fields between face- and house-selective areas

PubMed Central

Li, Ting; Niu, Yan; Xiang, Jie; Cheng, Junjie; Liu, Bo; Zhang, Hui; Yan, Tianyi; Kanazawa, Susumu; Wu, Jinglong

2018-01-01

Category-selective brain areas exhibit varying levels of neural activity to ipsilaterally presented stimuli. However, in face- and house-selective areas, the neural responses evoked by ipsilateral stimuli in the peripheral visual field remain unclear. In this study, we displayed face and house images using a wide-view visual presentation system while performing functional magnetic resonance imaging (fMRI). The face-selective areas (fusiform face area (FFA) and occipital face area (OFA)) exhibited intense neural responses to ipsilaterally presented images, whereas the house-selective areas (parahippocampal place area (PPA) and transverse occipital sulcus (TOS)) exhibited substantially smaller and even negative neural responses to the ipsilaterally presented images. We also found that the category preferences of the contralateral and ipsilateral neural responses were similar. Interestingly, the face- and house-selective areas exhibited neural responses to ipsilateral images that were smaller than the responses to the contralateral images. Multi-voxel pattern analysis (MVPA) was implemented to evaluate the difference between the contralateral and ipsilateral responses. The classification accuracies were much greater than those expected by chance. The classification accuracies in the FFA were smaller than those in the PPA and TOS. The closer eccentricities elicited greater classification accuracies in the PPA and TOS. We propose that these ipsilateral neural responses might be interpreted by interhemispheric communication through intrahemispheric connectivity of white matter connection and interhemispheric connectivity via the corpus callosum and occipital white matter connection. Furthermore, the PPA and TOS likely have weaker interhemispheric communication than the FFA and OFA, particularly in the peripheral visual field. PMID:29451872

Response properties of single units in the dorsal nucleus of the lateral lemniscus of decerebrate cats.

PubMed

Davis, Kevin A; Lomakin, Oleg; Pesavento, Michael J

2007-09-01

The dorsal nucleus of the lateral lemniscus (DNLL) receives afferent inputs from many brain stem nuclei and, in turn, is a major source of inhibitory inputs to the inferior colliculus (IC). The goal of this study was to characterize the monaural and binaural response properties of neurons in the DNLL of unanesthetized decerebrate cat. Monaural responses were classified according to the patterns of excitation and inhibition observed in contralateral and ipsilateral frequency response maps. Binaural classification was based on unit sensitivity to interaural level differences. The results show that units in the DNLL can be grouped into three distinct types. Type v units produce contralateral response maps that show a wide V-shaped excitatory area and no inhibition. These units receive ipsilateral excitation and exhibit binaural facilitation. The contralateral maps of type i units show a more restricted I-shaped region of excitation that is flanked by inhibition. Type o maps display an O-shaped island of excitation at low stimulus levels that is bounded by inhibition at higher levels. Both type i and type o units receive ipsilateral inhibition and exhibit binaural inhibition. Units that produce type v maps have a low best frequency (BF), whereas type i and type o units have high BFs. Type v and type i units give monotonic rate-level responses for both BF tones and broadband noise. Type o units are inhibited by tones at high levels, but are excited by high-level noise. These results show that the DNLL can exert strong, differential effects in the IC.

Infundibulopelvic stenosis in children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lucaya, J.; Enriquez, G.; Delgado, R.

1984-03-01

Of 11,500 children who underwent excretory urography during a 17-year period, three were found to have the rare renal malformation infundibulopelvic stenosis, characterized by caliceal dilatation, infundibular stenosis, and hypoplasia or stenosis of the renal pelvis. The contralateral kidney was absent in two cases and normal in the other. Voiding cystourethrograms were normal in all three. Renal sonography showed a variable degree of caliceal dilatation without associated pelvic dilatation. The diagnosis was confirmed by retrograde ureteropyelography in one case. Two patients were followed for 12 and 18 months, respectively; both remained asymptomatic with normal renal function, and sequential sonographic examinationsmore » of their kidneys have shown no significant changes. The third patient died of an unrelated condition. Infundibulopelvic stenosis has highly characteristic radiographic features, and prognosis is good for most affected patients.« less

Risk of contralateral avascular necrosis (AVN) after total hip arthroplasty (THA) for non-traumatic AVN.

PubMed

Goker, Berna; Block, Joel A

2006-01-01

The risk of developing bilateral disease progressing to total hip arthroplasty (THA) among patients who undergo unilateral THA for non-traumatic avascular necrosis (AVN) remains poorly understood. An analysis of the time-course to contralateral THA, as well as the effects of underlying AVN risk factors, is presented. Forty-seven consecutive patients who underwent THA for AVN were evaluated. Peri-operative and annual post-operative antero-posterior pelvis radiographs were examined for evidence of contralateral involvement. Patient age, weight, height, underlying AVN risk factor(s), date of onset of contralateral hip pain if occurred, and date of contralateral THA if performed, were recorded. Bone scan, computerized tomography and magnetic resonance imaging data were utilized when available. Twenty-one patients (46.6%) underwent contralateral THA for AVN within a median of 9 months after the initial THA (range 0-93, interquartile range 28.5 months). The median follow-up for patients without contralateral THA was 75 months (range 3-109, interquartile range 69 months). Thirty-four patients had radiographic findings of contralateral AVN at study entry; 25 were symptomatic bilaterally at entry and 7 developed contralateral symptoms within a mean time of 12 months (median 10 months, interquartile range 12 months). None of the 13 patients who were free of radiographic evidence of contralateral AVN at study entry developed evidence of AVN during the follow-up. AVN associated with glucocorticoid use was more likely to manifest as bilateral disease than either idiopathic AVN or ethanol-associated AVN (P=0.02 and P=0.03 respectively). Radiographically-evident AVN in the contralateral hip at THA is unlikely to remain asymptomatic for a prolonged period of time. Conversely, asymptomatic contralateral hips without radiographic evidence of AVN are unlikely to develop clinically significant AVN.

Adaptive functional change of the contralateral kidney after partial nephrectomy.

PubMed

Choi, Se Young; Yoo, Sangjun; You, Dalsan; Jeong, In Gab; Song, Cheryn; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung-Soo

2017-08-01

Partial nephrectomy aims to maintain renal function by nephron sparing; however, functional changes in the contralateral kidney remain unknown. We evaluate the functional change in the contralateral kidney using a diethylene triamine penta-acetic acid (DTPA) renal scan and determine factors predicting contralateral kidney function after partial nephrectomy. A total of 699 patients underwent partial nephrectomy, with a DTPA scan before and after surgery to assess the separate function of each kidney. Patients were divided into three groups according to initial contralateral glomerular filtration rate (GFR; group 1 : <30 ml·min -1 ·1.73 m -2 , group 2 : 30-45 ml·min -1 ·1.73 m -2 , and group 3 : ≥45 ml·min -1 ·1.73 m -2 ). Multiple-regression analysis was used to identify the factors associated with increased GFR of the contralateral kidney over a 4-yr postoperative period. Patients in group 1 had a higher mean age and hypertension history, worse American Society of Anesthesiologists score, and larger tumor size than in the other two groups. The ipsilateral GFR changes at 4 yr after partial nephrectomy were -18.9, -3.6, and 3.9% in groups 1 , 2 , and 3 , respectively, whereas the contralateral GFR changes were 10.8, 25.7, and 38.8%. Age [β: -0.105, 95% confidence interval (CI): -0.213; -0.011, P < 0.05] and preoperative contralateral GFR (β: -0.256, 95% CI: -0.332; -0.050, P < 0.01) were significant predictive factors for increased GFR of the contralateral kidney after 4 yr. The contralateral kidney compensated for the functional loss of the ipsilateral kidney. The increase of GFR in contralateral kidney is more prominent in younger patients with decreased contralateral renal function. Copyright © 2017 the American Physiological Society.

Abnormal Injury Response in Spontaneous Mild Ventriculomegaly Wistar Rat Brains: A Pathological Correlation Study of Diffusion Tensor and Magnetization Transfer Imaging in Mild Traumatic Brain Injury.

PubMed

Tu, Tsang-Wei; Lescher, Jacob D; Williams, Rashida A; Jikaria, Neekita; Turtzo, L Christine; Frank, Joseph A

2017-01-01

Spontaneous mild ventriculomegaly (MVM) was previously reported in ∼43% of Wistar rats in association with vascular anomalies without phenotypic manifestation. This mild traumatic brain injury (TBI) weight drop model study investigates whether MVM rats (n = 15) have different injury responses that could inadvertently complicate the interpretation of imaging studies compared with normal rats (n = 15). Quantitative MRI, including diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), and immunohistochemistry (IHC) analysis were used to examine the injury pattern up to 8 days post-injury in MVM and normal rats. Prior to injury, the MVM brain showed significant higher mean diffusivity, axial diffusivity, and radial diffusivity, and lower fractional anisotropy (FA) and magnetization transfer ratio (MTR) in the corpus callosum than normal brain (p < 0.05). Following TBI, normal brains exhibited significant decreases of FA in the corpus callosum, whereas MVM brains demonstrated insignificant changes in FA, suggesting less axonal injury. At day 8 after mild TBI, MTR of the normal brains significantly decreased whereas the MTR of the MVM brains significantly increased. IHC staining substantiated the MRI findings, demonstrating limited axonal injury with significant increase of microgliosis and astrogliosis in MVM brain compared with normal animals. The radiological-pathological correlation data showed that both DTI and MTI were sensitive in detecting mild diffuse brain injury, although DTI metrics were more specific in correlating with histologically identified pathologies. Compared with the higher correlation levels reflecting axonal injury pathology in the normal rat mild TBI, the DTI and MTR metrics were more affected by the increased inflammation in the MVM rat mild TBI. Because MVM Wistar rats appear normal, there was a need to screen rats prior to TBI research to rule out the presence of ventriculomegaly, which may complicate the interpretation of imaging and IHC observations.

Abnormal Injury Response in Spontaneous Mild Ventriculomegaly Wistar Rat Brains: A Pathological Correlation Study of Diffusion Tensor and Magnetization Transfer Imaging in Mild Traumatic Brain Injury

PubMed Central

Lescher, Jacob D.; Williams, Rashida A.; Jikaria, Neekita; Turtzo, L. Christine; Frank, Joseph A.

2017-01-01

Abstract Spontaneous mild ventriculomegaly (MVM) was previously reported in ∼43% of Wistar rats in association with vascular anomalies without phenotypic manifestation. This mild traumatic brain injury (TBI) weight drop model study investigates whether MVM rats (n = 15) have different injury responses that could inadvertently complicate the interpretation of imaging studies compared with normal rats (n = 15). Quantitative MRI, including diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), and immunohistochemistry (IHC) analysis were used to examine the injury pattern up to 8 days post-injury in MVM and normal rats. Prior to injury, the MVM brain showed significant higher mean diffusivity, axial diffusivity, and radial diffusivity, and lower fractional anisotropy (FA) and magnetization transfer ratio (MTR) in the corpus callosum than normal brain (p < 0.05). Following TBI, normal brains exhibited significant decreases of FA in the corpus callosum, whereas MVM brains demonstrated insignificant changes in FA, suggesting less axonal injury. At day 8 after mild TBI, MTR of the normal brains significantly decreased whereas the MTR of the MVM brains significantly increased. IHC staining substantiated the MRI findings, demonstrating limited axonal injury with significant increase of microgliosis and astrogliosis in MVM brain compared with normal animals. The radiological-pathological correlation data showed that both DTI and MTI were sensitive in detecting mild diffuse brain injury, although DTI metrics were more specific in correlating with histologically identified pathologies. Compared with the higher correlation levels reflecting axonal injury pathology in the normal rat mild TBI, the DTI and MTR metrics were more affected by the increased inflammation in the MVM rat mild TBI. Because MVM Wistar rats appear normal, there was a need to screen rats prior to TBI research to rule out the presence of ventriculomegaly, which may complicate the interpretation of imaging and IHC observations. PMID:26905805

Replacement of the ureter by an ileal loop. Quantitative aspects of long-term morphological alterations in minipigs.

PubMed

Pabst, R; Kamran, D

1983-06-01

In minipigs 1 ureter was replaced by a loop of the terminal ileum and the contralateral kidney removed. After 2.5 to 3 years the morphology of the replaced ureter was compared with the normal ileum. Independent of the 3 different operative techniques used, in about half of the pigs there was loss or flattening of the villi. In the other pigs the morphometrically determined number of intraepithelial lymphocytes, the cell density in the lamina propria and the length of the villi did not differ significantly compared with the normal ileum. There was no increase in goblet cells in the crypts. The transitional epithelium covered only a short distance at the anastomotic junctions. Peyer's patches of normal age-related size were found in the replaced ureter. Despite the long-term contact with urine instead of gut contents, in many pigs a normal amount of lymphocytes remained in the "ileal ureter".

Contralateral Cruciate Survival in Dogs with Unilateral Non-Contact Cranial Cruciate Ligament Rupture

PubMed Central

Muir, Peter; Schwartz, Zeev; Malek, Sarah; Kreines, Abigail; Cabrera, Sady Y.; Buote, Nicole J.; Bleedorn, Jason A.; Schaefer, Susan L.; Holzman, Gerianne; Hao, Zhengling

2011-01-01

Background Non-contact cranial cruciate ligament rupture (CrCLR) is an important cause of lameness in client-owned dogs and typically occurs without obvious injury. There is a high incidence of bilateral rupture at presentation or subsequent contralateral rupture in affected dogs. Although stifle synovitis increases risk of contralateral CrCLR, relatively little is known about risk factors for subsequent contralateral rupture, or whether therapeutic intervention may modify this risk. Methodology/Principal Findings We conducted a longitudinal study examining survival of the contralateral CrCL in client-owned dogs with unilateral CrCLR in a large baseline control population (n = 380), and a group of dogs that received disease-modifying therapy with arthroscopic lavage, intra-articular hyaluronic acid and oral doxycycline (n = 16), and were followed for one year. Follow-up in treated dogs included analysis of mobility, radiographic evaluation of stifle effusion and arthritis, and quantification of biomarkers of synovial inflammation. We found that median survival of the contralateral CrCL was 947 days. Increasing tibial plateau angle decreased contralateral ligament survival, whereas increasing age at diagnosis increased survival. Contralateral ligament survival was reduced in neutered dogs. Our disease-modifying therapy did not significantly influence contralateral ligament survival. Correlative analysis of clinical and biomarker variables with development of subsequent contralateral rupture revealed few significant results. However, increased expression of T lymphocyte-associated genes in the index unstable stifle at diagnosis was significantly related to development of subsequent non-contact contralateral CrCLR. Conclusion Subsequent contralateral CrCLR is common in client-owned dogs, with a median ligament survival time of 947 days. In this naturally occurring model of non-contact cruciate ligament rupture, cranial tibial translation is preceded by development of synovial inflammation. However, treatment with arthroscopic lavage, intra-articular hyaluronic acid and oral doxycycline does not significantly influence contralateral CrCL survival. PMID:21998650

A novel pre-clinical in vivo mouse model for malignant brain tumor growth and invasion.

PubMed

Shelton, Laura M; Mukherjee, Purna; Huysentruyt, Leanne C; Urits, Ivan; Rosenberg, Joshua A; Seyfried, Thomas N

2010-09-01

Glioblastoma multiforme (GBM) is a rapidly progressive disease of morbidity and mortality and is the most common form of primary brain cancer in adults. Lack of appropriate in vivo models has been a major roadblock to developing effective therapies for GBM. A new highly invasive in vivo GBM model is described that was derived from a spontaneous brain tumor (VM-M3) in the VM mouse strain. Highly invasive tumor cells could be identified histologically on the hemisphere contralateral to the hemisphere implanted with tumor cells or tissue. Tumor cells were highly expressive for the chemokine receptor CXCR4 and the proliferation marker Ki-67 and could be identified invading through the pia mater, the vascular system, the ventricular system, around neurons, and over white matter tracts including the corpus callosum. In addition, the brain tumor cells were labeled with the firefly luciferase gene, allowing for non-invasive detection and quantitation through bioluminescent imaging. The VM-M3 tumor has a short incubation time with mortality occurring in 100% of the animals within approximately 15 days. The VM-M3 brain tumor model therefore can be used in a pre-clinical setting for the rapid evaluation of novel anti-invasive therapies.

Insights into Intrinsic Brain Networks based on Graph Theory and PET in right- compared to left-sided Temporal Lobe Epilepsy.

PubMed

Vanicek, Thomas; Hahn, Andreas; Traub-Weidinger, Tatjana; Hilger, Eva; Spies, Marie; Wadsak, Wolfgang; Lanzenberger, Rupert; Pataraia, Ekaterina; Asenbaum-Nan, Susanne

2016-06-28

The human brain exhibits marked hemispheric differences, though it is not fully understood to what extent lateralization of the epileptic focus is relevant. Preoperative [(18)F]FDG-PET depicts lateralization of seizure focus in patients with temporal lobe epilepsy and reveals dysfunctional metabolic brain connectivity. The aim of the present study was to compare metabolic connectivity, inferred from inter-regional [(18)F]FDG PET uptake correlations, in right-sided (RTLE; n = 30) and left-sided TLE (LTLE; n = 32) with healthy controls (HC; n = 31) using graph theory based network analysis. Comparing LTLE and RTLE and patient groups separately to HC, we observed higher lobar connectivity weights in RTLE compared to LTLE for connections of the temporal and the parietal lobe of the contralateral hemisphere (CH). Moreover, especially in RTLE compared to LTLE higher local efficiency were found in the temporal cortices and other brain regions of the CH. The results of this investigation implicate altered metabolic networks in patients with TLE specific to the lateralization of seizure focus, and describe compensatory mechanisms especially in the CH of patients with RTLE. We propose that graph theoretical analysis of metabolic connectivity using [(18)F]FDG-PET offers an important additional modality to explore brain networks.

Contralateral radiculopathy after transforaminal lumbar interbody fusion in the treatment of lumbar degenerative diseases: A Case Series.

PubMed

Hu, Hong-Tao; Ren, Liang; Sun, Xian-Ze; Liu, Feng-Yu; Yu, Jin-He; Gu, Zhen-Fang

2018-04-01

Transforaminal lumbar interbody fusion (TLIF) is an effective treatment for patients with degenerative lumbar disc disorder. Contralateral radiculopathy, as a complication of TLIF, has been recognized in this institution, but is rarely reported in the literature. In this article, we report 2 cases of contralateral radiculopathy after TLIF in our institution and its associated complications. In the 2 cases, the postoperative computed tomography (CT) and magnetic resonance image (MRI) showed obvious upward movement of the superior articular process, leading to contralateral foraminal stenosis. Revision surgery was done at once to partially resect the opposite superior facet and to relieve nerve root compression. After revision surgery, the contralateral radiculopathy disappeared. Contralateral radiculopathy is an avoidable potential complication. It is very important to create careful preoperative plans and to conscientiously plan the use of intraoperative techniques. In case of postoperative contralateral leg pain, the patients should be examined by CT and MRI. If CT and MRI show that the superior articular process significantly migrated upwards, which leads to contralateral foraminal stenosis, revision surgery should be done at once to partially resect the contralateral superior facet so as to relieve nerve root compression and avoid possible long-term impairment.

Lesions of entorhinal cortex produce a calpain-mediated degradation of brain spectrin in dentate gyrus. I. Biochemical studies.

PubMed

Seubert, P; Ivy, G; Larson, J; Lee, J; Shahi, K; Baudry, M; Lynch, G

1988-09-06

Lesions of the rat entorhinal cortex cause extensive synaptic restructuring and perturbation of calcium regulation in the dentate gyrus of hippocampus. Calpain is a calcium-activated protease which has been implicated in degenerative phenomena in muscles and in peripheral nerves. In addition, calpain degrades several major structural neuronal proteins and has been proposed to play a critical role in the morphological changes observed following deafferentation. In this report we present evidence that lesions of the entorhinal cortex produce a marked increase in the breakdown of brain spectrin, a substrate for calpain, in the dentate gyrus. Two lines of evidence indicate that this effect is due to calpain activation: (i) the spectrin breakdown products observed following the lesion are indistinguishable from calpain-generated spectrin fragments in vitro; and (ii) their appearance can be reduced by prior intraventricular in fusion of leupeptin, a calpain inhibitor. Levels of spectrin breakdown products are increased as early as 4 h post-lesion, reach maximal values at 2 days, and remain above normal to some degree for at least 27 days. In addition, a small but significant increase in spectrin proteolysis is also observed in the hippocampus contralateral to the lesioned side in the first week postlesion. At 2 days postlesion the total spectrin immunoreactivity (native polypeptide plus breakdown products) increases by 40%, suggesting that denervation of the dentate gyrus produces not only an increased rate of spectrin degradation but also an increased rate of spectrin synthesis. These results indicate that calpain activation and spectrin degradation are early biochemical events following deafferentation and might well participate in the remodelling of postsynaptic structures. Finally, the magnitude of the observed effects as well as the stable nature of the breakdown products provide a sensitive assay for neuronal pathology.

The affective modulation of motor awareness in anosognosia for hemiplegia: Behavioural and lesion evidence

PubMed Central

Besharati, Sahba; Forkel, Stephanie J.; Kopelman, Michael; Solms, Mark; Jenkinson, Paul M.; Fotopoulou, Aikaterini

2014-01-01

The possible role of emotion in anosognosia for hemiplegia (i.e., denial of motor deficits contralateral to a brain lesion), has long been debated between psychodynamic and neurocognitive theories. However, there are only a handful of case studies focussing on this topic, and the precise role of emotion in anosognosia for hemiplegia requires empirical investigation. In the present study, we aimed to investigate how negative and positive emotions influence motor awareness in anosognosia. Positive and negative emotions were induced under carefully-controlled experimental conditions in right-hemisphere stroke patients with anosognosia for hemiplegia (n = 11) and controls with clinically normal awareness (n = 10). Only the negative, emotion induction condition resulted in a significant improvement of motor awareness in anosognosic patients compared to controls; the positive emotion induction did not. Using lesion overlay and voxel-based lesion-symptom mapping approaches, we also investigated the brain lesions associated with the diagnosis of anosognosia, as well as with performance on the experimental task. Anatomical areas that are commonly damaged in AHP included the right-hemisphere motor and sensory cortices, the inferior frontal cortex, and the insula. Additionally, the insula, putamen and anterior periventricular white matter were associated with less awareness change following the negative emotion induction. This study suggests that motor unawareness and the observed lack of negative emotions about one's disabilities cannot be adequately explained by either purely motivational or neurocognitive accounts. Instead, we propose an integrative account in which insular and striatal lesions result in weak interoceptive and motivational signals. These deficits lead to faulty inferences about the self, involving a difficulty to personalise new sensorimotor information, and an abnormal adherence to premorbid beliefs about the body. PMID:25481471

The affective modulation of motor awareness in anosognosia for hemiplegia: behavioural and lesion evidence.

PubMed

Besharati, Sahba; Forkel, Stephanie J; Kopelman, Michael; Solms, Mark; Jenkinson, Paul M; Fotopoulou, Aikaterini

2014-12-01

The possible role of emotion in anosognosia for hemiplegia (i.e., denial of motor deficits contralateral to a brain lesion), has long been debated between psychodynamic and neurocognitive theories. However, there are only a handful of case studies focussing on this topic, and the precise role of emotion in anosognosia for hemiplegia requires empirical investigation. In the present study, we aimed to investigate how negative and positive emotions influence motor awareness in anosognosia. Positive and negative emotions were induced under carefully-controlled experimental conditions in right-hemisphere stroke patients with anosognosia for hemiplegia (n = 11) and controls with clinically normal awareness (n = 10). Only the negative, emotion induction condition resulted in a significant improvement of motor awareness in anosognosic patients compared to controls; the positive emotion induction did not. Using lesion overlay and voxel-based lesion-symptom mapping approaches, we also investigated the brain lesions associated with the diagnosis of anosognosia, as well as with performance on the experimental task. Anatomical areas that are commonly damaged in AHP included the right-hemisphere motor and sensory cortices, the inferior frontal cortex, and the insula. Additionally, the insula, putamen and anterior periventricular white matter were associated with less awareness change following the negative emotion induction. This study suggests that motor unawareness and the observed lack of negative emotions about one's disabilities cannot be adequately explained by either purely motivational or neurocognitive accounts. Instead, we propose an integrative account in which insular and striatal lesions result in weak interoceptive and motivational signals. These deficits lead to faulty inferences about the self, involving a difficulty to personalise new sensorimotor information, and an abnormal adherence to premorbid beliefs about the body. Copyright © 2014 Elsevier Ltd. All rights reserved.

A novel mouse model for neurotrophic keratopathy: trigeminal nerve stereotactic electrolysis through the brain.

PubMed

Ferrari, Giulio; Chauhan, Sunil K; Ueno, Hiroki; Nallasamy, Nambi; Gandolfi, Stefano; Borges, Lawrence; Dana, Reza

2011-04-01

To develop a mouse model of neurotrophic keratopathy by approaching the trigeminal nerve through the brain and to evaluate changes in corneal cell apoptosis and proliferation. Six- to 8-week-old male C57BL/6 mice underwent trigeminal stereotactic electrolysis (TSE) to destroy the ophthalmic branch of the trigeminal nerve. Clinical follow-up using biomicroscopy of the cornea was performed at days 2, 4, 5, and 7. To confirm the effectiveness of the procedure, we examined the gross nerve pathology, blink reflex, and immunohistochemistry of the corneal nerves. TUNEL-positive apoptotic and Ki-67-positive proliferating corneal cells were evaluated to detect changes from the contralateral normal eye. TSE was confirmed by gross histology of the trigeminal nerve and was considered effective if the corneal blink reflex was completely abolished. TSE totally abolished the blink reflex in 70% of mice and significantly reduced it in the remaining 30%. Animals with absent blink reflex were used for subsequent experiments. In these mice, a progressive corneal degeneration developed, with thinning of the corneal epithelium and eventually perforation after 7 days. In all mice, 48 hours after TSE, corneal nerves were not recognizable histologically. Seven days after TSE, an increase in cellular apoptosis in all the corneal layers and a reduction in proliferation in basal epithelial cells were detected consistently in all mice. TSE was able, in most cases, to induce a disease state that reflected clinical neurotrophic keratitis without damaging the periocular structures. Moreover, corneal denervation led to increased apoptosis and reduced proliferation of epithelial cells, formally implicating intact nerve function in regulating epithelial survival and turnover.

A Novel Mouse Model for Neurotrophic Keratopathy: Trigeminal Nerve Stereotactic Electrolysis through the Brain

PubMed Central

Ferrari, Giulio; Chauhan, Sunil K.; Ueno, Hiroki; Nallasamy, Nambi; Gandolfi, Stefano; Borges, Lawrence

2011-01-01

Purpose. To develop a mouse model of neurotrophic keratopathy by approaching the trigeminal nerve through the brain and to evaluate changes in corneal cell apoptosis and proliferation. Methods. Six- to 8-week-old male C57BL/6 mice underwent trigeminal stereotactic electrolysis (TSE) to destroy the ophthalmic branch of the trigeminal nerve. Clinical follow-up using biomicroscopy of the cornea was performed at days 2, 4, 5, and 7. To confirm the effectiveness of the procedure, we examined the gross nerve pathology, blink reflex, and immunohistochemistry of the corneal nerves. TUNEL-positive apoptotic and Ki-67–positive proliferating corneal cells were evaluated to detect changes from the contralateral normal eye. Results. TSE was confirmed by gross histology of the trigeminal nerve and was considered effective if the corneal blink reflex was completely abolished. TSE totally abolished the blink reflex in 70% of mice and significantly reduced it in the remaining 30%. Animals with absent blink reflex were used for subsequent experiments. In these mice, a progressive corneal degeneration developed, with thinning of the corneal epithelium and eventually perforation after 7 days. In all mice, 48 hours after TSE, corneal nerves were not recognizable histologically. Seven days after TSE, an increase in cellular apoptosis in all the corneal layers and a reduction in proliferation in basal epithelial cells were detected consistently in all mice. Conclusions. TSE was able, in most cases, to induce a disease state that reflected clinical neurotrophic keratitis without damaging the periocular structures. Moreover, corneal denervation led to increased apoptosis and reduced proliferation of epithelial cells, formally implicating intact nerve function in regulating epithelial survival and turnover. PMID:21071731

Use of Brain MRI Atlases to Determine Boundaries of Age-Related Pathology: The Importance of Statistical Method

PubMed Central

Dickie, David Alexander; Job, Dominic E.; Gonzalez, David Rodriguez; Shenkin, Susan D.; Wardlaw, Joanna M.

2015-01-01

Introduction Neurodegenerative disease diagnoses may be supported by the comparison of an individual patient’s brain magnetic resonance image (MRI) with a voxel-based atlas of normal brain MRI. Most current brain MRI atlases are of young to middle-aged adults and parametric, e.g., mean ±standard deviation (SD); these atlases require data to be Gaussian. Brain MRI data, e.g., grey matter (GM) proportion images, from normal older subjects are apparently not Gaussian. We created a nonparametric and a parametric atlas of the normal limits of GM proportions in older subjects and compared their classifications of GM proportions in Alzheimer’s disease (AD) patients. Methods Using publicly available brain MRI from 138 normal subjects and 138 subjects diagnosed with AD (all 55–90 years), we created: a mean ±SD atlas to estimate parametrically the percentile ranks and limits of normal ageing GM; and, separately, a nonparametric, rank order-based GM atlas from the same normal ageing subjects. GM images from AD patients were then classified with respect to each atlas to determine the effect statistical distributions had on classifications of proportions of GM in AD patients. Results The parametric atlas often defined the lower normal limit of the proportion of GM to be negative (which does not make sense physiologically as the lowest possible proportion is zero). Because of this, for approximately half of the AD subjects, 25–45% of voxels were classified as normal when compared to the parametric atlas; but were classified as abnormal when compared to the nonparametric atlas. These voxels were mainly concentrated in the frontal and occipital lobes. Discussion To our knowledge, we have presented the first nonparametric brain MRI atlas. In conditions where there is increasing variability in brain structure, such as in old age, nonparametric brain MRI atlases may represent the limits of normal brain structure more accurately than parametric approaches. Therefore, we conclude that the statistical method used for construction of brain MRI atlases should be selected taking into account the population and aim under study. Parametric methods are generally robust for defining central tendencies, e.g., means, of brain structure. Nonparametric methods are advisable when studying the limits of brain structure in ageing and neurodegenerative disease. PMID:26023913

An fMRI compatible wrist robotic interface to study brain development in neonates.

PubMed

Allievi, A G; Melendez-Calderon, A; Arichi, T; Edwards, A D; Burdet, E

2013-06-01

A comprehensive understanding of the mechanisms that underlie brain development in premature infants and newborns is crucial for the identification of interventional therapies and rehabilitative strategies. fMRI has the potential to identify such mechanisms, but standard techniques used in adults cannot be implemented in infant studies in a straightforward manner. We have developed an MR safe wrist stimulating robot to systematically investigate the functional brain activity related to both spontaneous and induced wrist movements in premature babies using fMRI. We present the technical aspects of this development and the results of validation experiments. Using the device, the cortical activity associated with both active and passive finger movements were reliably identified in a healthy adult subject. In two preterm infants, passive wrist movements induced a well localized positive BOLD response in the contralateral somatosensory cortex. Furthermore, in a single preterm infant, spontaneous wrist movements were found to be associated with an adjacent cluster of activity, at the level of the infant's primary motor cortex. The described device will allow detailed and objective fMRI studies of somatosensory and motor system development during early human life and following neonatal brain injury.

Test-retest assessment of cortical activation induced by repetitive transcranial magnetic stimulation with brain atlas-guided optical topography

NASA Astrophysics Data System (ADS)

Tian, Fenghua; Kozel, F. Andrew; Yennu, Amarnath; Croarkin, Paul E.; McClintock, Shawn M.; Mapes, Kimberly S.; Husain, Mustafa M.; Liu, Hanli

2012-11-01

Repetitive transcranial magnetic stimulation (rTMS) is a technology that stimulates neurons with rapidly changing magnetic pulses with demonstrated therapeutic applications for various neuropsychiatric disorders. Functional near-infrared spectroscopy (fNIRS) is a suitable tool to assess rTMS-evoked brain responses without interference from the magnetic or electric fields generated by the TMS coil. We have previously reported a channel-wise study of combined rTMS/fNIRS on the motor and prefrontal cortices, showing a robust decrease of oxygenated hemoglobin concentration (Δ[HbO2]) at the sites of 1-Hz rTMS and the contralateral brain regions. However, the reliability of this putative clinical tool is unknown. In this study, we develop a rapid optical topography approach to spatially characterize the rTMS-evoked hemodynamic responses on a standard brain atlas. A hemispherical approximation of the brain is employed to convert the three-dimensional topography on the complex brain surface to a two-dimensional topography in the spherical coordinate system. The test-retest reliability of the combined rTMS/fNIRS is assessed using repeated measurements performed two to three days apart. The results demonstrate that the Δ[HbO2] amplitudes have moderate-to-high reliability at the group level; and the spatial patterns of the topographic images have high reproducibility in size and a moderate degree of overlap at the individual level.

SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Hildebrand, K; Ahmad, S

Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targetsmore » were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery.« less

Dependence of normal brain integral dose and normal tissue complication probability on the prescription isodose values for γ-knife radiosurgery

NASA Astrophysics Data System (ADS)

Ma, Lijun

2001-11-01

A recent multi-institutional clinical study suggested possible benefits of lowering the prescription isodose lines for stereotactic radiosurgery procedures. In this study, we investigate the dependence of the normal brain integral dose and the normal tissue complication probability (NTCP) on the prescription isodose values for γ-knife radiosurgery. An analytical dose model was developed for γ-knife treatment planning. The dose model was commissioned by fitting the measured dose profiles for each helmet size. The dose model was validated by comparing its results with the Leksell gamma plan (LGP, version 5.30) calculations. The normal brain integral dose and the NTCP were computed and analysed for an ensemble of treatment cases. The functional dependence of the normal brain integral dose and the NCTP versus the prescribing isodose values was studied for these cases. We found that the normal brain integral dose and the NTCP increase significantly when lowering the prescription isodose lines from 50% to 35% of the maximum tumour dose. Alternatively, the normal brain integral dose and the NTCP decrease significantly when raising the prescribing isodose lines from 50% to 65% of the maximum tumour dose. The results may be used as a guideline for designing future dose escalation studies for γ-knife applications.

Real-time monitoring of human blood-brain barrier disruption

PubMed Central

Kiviniemi, Vesa; Korhonen, Vesa; Kortelainen, Jukka; Rytky, Seppo; Keinänen, Tuija; Tuovinen, Timo; Isokangas, Matti; Sonkajärvi, Eila; Siniluoto, Topi; Nikkinen, Juha; Alahuhta, Seppo; Tervonen, Osmo; Turpeenniemi-Hujanen, Taina; Myllylä, Teemu; Kuittinen, Outi; Voipio, Juha

2017-01-01

Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 μV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery. PMID:28319185

Expression of hypoxia-inducible carbonic anhydrases in brain tumors

PubMed Central

Proescholdt, Martin A.; Mayer, Christina; Kubitza, Marion; Schubert, Thomas; Liao, Shu-Yuan; Stanbridge, Eric J.; Ivanov, Sergey; Oldfield, Edward H.; Brawanski, Alexander; Merrill, Marsha J.

2005-01-01

Malignant brain tumors exhibit distinct metabolic characteristics. Despite high levels of lactate, the intracellular pH of brain tumors is more alkaline than normal brain. Additionally, with increasing malignancy, brain tumors display intratumoral hypoxia. Carbonic anhydrase (CA) IX and XII are transmembrane isoenzymes that are induced by tissue hypoxia. They participate in regulation of pH homeostasis by catalyzing the reversible hydration of carbon dioxide. The aim of our study was to investigate whether brain tumors of different histology and grade of malignancy express elevated levels of CA IX and XII as compared to normal brain. We analyzed 120 tissue specimens from brain tumors (primary and metastatic) and normal brain for CA IX and XII expression by immunohistochemistry, Western blot, and in situ hybridization. Whereas normal brain tissue showed minimal levels of CA IX and XII expression, expression in tumors was found to be upregulated with increased level of malignancy. Hemangioblastomas, from patients with von Hippel–Lindau disease, also displayed high levels of CA IX and XII expression. Comparison of CA IX and XII staining with HIF-1α staining revealed a similar microanatomical distribution, indicating hypoxia as a major, but not the only, induction factor. The extent of CA IX and XII staining correlated with cell proliferation, as indicated by Ki67 labeling. The results demonstrate that CA IX and XII are upregulated in intrinsic and metastatic brain tumors as compared to normal brain tissue. This may contribute to the management of tumor-specific acid load and provide a therapeutic target. PMID:16212811

Twenty-first century brain banking. Processing brains for research: the Columbia University methods

PubMed Central

del Amaya, Maria Pilar; Keller, Christian E.

2007-01-01

Carefully categorized postmortem human brains are crucial for research. The lack of generally accepted methods for processing human postmortem brains for research persists. Thus, brain banking is essential; however, it cannot be achieved at the cost of the teaching mission of the academic institution by routing brains away from residency programs, particularly when the autopsy rate is steadily decreasing. A consensus must be reached whereby a brain can be utilizable for diagnosis, research, and teaching. The best diagnostic categorization possible must be secured and the yield of samples for basic investigation maximized. This report focuses on integrated, novel methods currently applied at the New York Brain Bank, Columbia University, New York, which are designed to reach accurate neuropathological diagnosis, optimize the yield of samples, and process fresh-frozen samples suitable for a wide range of modern investigations. The brains donated for research are processed as soon as possible after death. The prosector must have a good command of the neuroanatomy, neuropathology, and the protocol. One half of each brain is immersed in formalin for performing the thorough neuropathologic evaluation, which is combined with the teaching task. The contralateral half is extensively dissected at the fresh state. The anatomical origin of each sample is recorded using the map of Brodmann for the cortical samples. The samples are frozen at −160°C, barcode labeled, and ready for immediate disbursement once categorized diagnostically. A rigorous organization of freezer space, coupled to an electronic tracking system with its attached software, fosters efficient access for retrieval within minutes of any specific frozen samples in storage. This report describes how this achievement is feasible with emphasis on the actual processing of brains donated for research. PMID:17985145

Testis sparing surgery for treatment of small testicular lesions: Is it feasible even in germ cell tumors?

PubMed

Bojanic, Nebojsa; Bumbasirevic, Uros; Bojanic, Gordana; Vukovic, Ivan; Milojevic, Bogomir; Pekmezovic, Tatjana

2017-03-01

To evaluate the results of testis-sparing surgery (TSS) in patients, with small testicular lesions and a normal contralateral testicle. In all, 28 patients were treated with TSS for small testicular lesions and a normal contralateral testicle. TSS was considered in patients with testicular lesions smaller than 2 cm and no evidence of metastatic disease. The mean age of patients was 35.3 ± 7.3 years, while the mean diameter of the testicular lesions was 11.4 ± 3.7 mm. After pathological examination, 18 patients (64.3%) were diagnosed with stromal tumors and miscellaneous lesions, while 10 (35.7%) had a germ cell tumor. The median follow-up time for the former group was 33 months and no recurrences were observed. In one patient with germ cell tumor, immediate orchiectomy was performed, while the remaining nine were followed-up (median time, 45 months). One patient developed local recurrence after 39 months. Excellent outcomes for benign lesions could be achieved using TSS. TSS could be offered safely in highly selected patients with germ cell tumors, specifically within a clinical trial but there is more data needed regarding the potential risks and benefits. J. Surg. Oncol. 2017;115:287-290. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Pencil beam scanning proton therapy vs rotational arc radiation therapy: A treatment planning comparison for postoperative oropharyngeal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Apinorasethkul, Ontida, E-mail: Ontida.a@gmail.com; Kirk, Maura; Teo, Kevin

Patients diagnosed with head and neck cancer are traditionally treated with photon radiotherapy. Proton therapy is currently being used clinically and may potentially reduce treatment-related toxicities by minimizing the dose to normal organs in the treatment of postoperative oropharyngeal cancer. The finite range of protons has the potential to significantly reduce normal tissue toxicity compared to photon radiotherapy. Seven patients were planned with both proton and photon modalities. The planning goal for both modalities was achieving the prescribed dose to 95% of the planning target volume (PTV). Dose-volume histograms were compared in which all cases met the target coverage goals.more » Mean doses were significantly lower in the proton plans for the oral cavity (1771 cGy photon vs 293 cGy proton, p < 0.001), contralateral parotid (1796 cGy photon vs 1358 proton, p < 0.001), and the contralateral submandibular gland (3608 cGy photon vs 3251 cGy proton, p = 0.03). Average total integral dose was 9.1% lower in proton plans. The significant dosimetric sparing seen with proton therapy may lead to reduced side effects such as pain, weight loss, taste changes, and dry mouth. Prospective comparisons of protons vs photons for disease control, toxicity, and patient-reported outcomes are therefore warranted and currently being pursued.« less

Second cancer incidence risk estimates using BEIR VII models for standard and complex external beam radiotherapy for early breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donovan, E. M.; James, H.; Bonora, M.

2012-10-15

Purpose: To compare organ specific cancer incidence risks for standard and complex external beam radiotherapy (including cone beam CT verification) following breast conservation surgery for early breast cancer.Method: Doses from breast radiotherapy and kilovoltage cone beam CT (CBCT) exposures were obtained from thermoluminescent dosimeter measurements in an anthropomorphic phantom in which the positions of radiosensitive organs were delineated. Five treatment deliveries were investigated: (i) conventional tangential field whole breast radiotherapy (WBRT), (ii) noncoplanar conformal delivery applicable to accelerated partial beast irradiation (APBI), (iii) two-volume simultaneous integrated boost (SIB) treatment, (iv) forward planned three-volume SIB, and (v) inverse-planned three volume SIB.more » Conformal and intensity modulated radiotherapy methods were used to plan the complex treatments. Techniques spanned the range from simple methods appropriate for patient cohorts with a low cancer recurrence risk to complex plans relevant to cohorts with high recurrence risk. Delineated organs at risk included brain, salivary glands, thyroid, contralateral breast, left and right lung, esophagus, stomach, liver, colon, and bladder. Biological Effects of Ionizing Radiation (BEIR) VII cancer incidence models were applied to the measured mean organ doses to determine lifetime attributable risk (LAR) for ages at exposure from 35 to 80 yr according to radiotherapy techniques, and included dose from the CBCT imaging. Results: All LAR decreased with age at exposure and were lowest for brain, thyroid, liver, and bladder (<0.1%). There was little dependence of LAR on radiotherapy technique for these organs and for colon and stomach. LAR values for the lungs for the three SIB techniques were two to three times those from WBRT and APBI. Uncertainties in the LAR models outweigh any differences in lung LAR between the SIB methods. Constraints in the planning of the SIB methods ensured that contralateral breast doses and LAR were comparable to WBRT, despite their added complexity. The smaller irradiated volume of the ABPI plan contributed to a halving of LAR for contralateral breast compared with the other plan types. Daily image guided radiotherapy (IGRT) for a left breast protocol using kilovoltage CBCT contributed <10% to LAR for the majority of organs, and did not exceed 22% of total organ dose. Conclusions: Phantom measurements and calculations of LAR from the BEIR VII models predict that complex breast radiotherapy techniques do not increase the theoretical risk of second cancer incidence for organs distant from the treated breast, or the contralateral breast where appropriate plan constraints are applied. Complex SIB treatments are predicted to increase the risk of second cancer incidence in the lungs compared to standard whole breast radiotherapy; this is outweighed by the threefold reduction in 5 yr local recurrence risk for patients of high risk of recurrence, and young age, from the use of radiotherapy. APBI may have a favorable impact on risk of second cancer in the contralateral breast and lung for older patients at low risk of recurrence. Intensive use of IGRTincreased the estimated values of LAR but these are dominated by the effect of the dose from the radiotherapy, and any increase in LAR from IGRT is much lower than the models' uncertainties.« less

Developmental thyroid hormone insufficiency and brain development: A role for brain-derived neurotrophic factor (BDNF)?*

EPA Science Inventory

Thyroid hormones (TH) are essential for normal brain development. Even subclinical hypothyroidism experienced in utero can result in neuropsychological deficits in children despite normal thyroid status at birth. Neurotrophins have been implicated in a host of brain cellular func...

Neuroimaging Studies of Normal Brain Development and Their Relevance for Understanding Childhood Neuropsychiatric Disorders

ERIC Educational Resources Information Center

Marsh, Rachel; Gerber, Andrew J.; Peterson, Bradley S.

2008-01-01

Neuroimaging findings which identify normal brain development trajectories are presented. Results show that early brain development begins with the neural tube formation and ends with myelintation. How disturbances in brain development patterns are related to childhood psychiatric disorders is examined.

A brain imaging repository of normal structural MRI across the life course: Brain Images of Normal Subjects (BRAINS).

PubMed

Job, Dominic E; Dickie, David Alexander; Rodriguez, David; Robson, Andrew; Danso, Sammy; Pernet, Cyril; Bastin, Mark E; Boardman, James P; Murray, Alison D; Ahearn, Trevor; Waiter, Gordon D; Staff, Roger T; Deary, Ian J; Shenkin, Susan D; Wardlaw, Joanna M

2017-01-01

The Brain Images of Normal Subjects (BRAINS) Imagebank (http://www.brainsimagebank.ac.uk) is an integrated repository project hosted by the University of Edinburgh and sponsored by the Scottish Imaging Network: A Platform for Scientific Excellence (SINAPSE) collaborators. BRAINS provide sharing and archiving of detailed normal human brain imaging and relevant phenotypic data already collected in studies of healthy volunteers across the life-course. It particularly focusses on the extremes of age (currently older age, and in future perinatal) where variability is largest, and which are under-represented in existing databanks. BRAINS is a living imagebank where new data will be added when available. Currently BRAINS contains data from 808 healthy volunteers, from 15 to 81years of age, from 7 projects in 3 centres. Additional completed and ongoing studies of normal individuals from 1st to 10th decades are in preparation and will be included as they become available. BRAINS holds several MRI structural sequences, including T1, T2, T2* and fluid attenuated inversion recovery (FLAIR), available in DICOM (http://dicom.nema.org/); in future Diffusion Tensor Imaging (DTI) will be added where available. Images are linked to a wide range of 'textual data', such as age, medical history, physiological measures (e.g. blood pressure), medication use, cognitive ability, and perinatal information for pre/post-natal subjects. The imagebank can be searched to include or exclude ranges of these variables to create better estimates of 'what is normal' at different ages. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Comparison of analytical methods of brain [18F]FDG-PET after severe traumatic brain injury.

PubMed

Madsen, Karine; Hesby, Sara; Poulsen, Ingrid; Fuglsang, Stefan; Graff, Jesper; Larsen, Karen B; Kammersgaard, Lars P; Law, Ian; Siebner, Hartwig R

2017-11-01

Loss of consciousness has been shown to reduce cerebral metabolic rates of glucose (CMRglc) measured by brain [ 18 F]FDG-PET. Measurements of regional metabolic patterns by normalization to global cerebral metabolism or cerebellum may underestimate widespread reductions. The aim of this study was to compare quantification methods of whole brain glucose metabolism, including whole brain [18F]FDG uptake normalized to uptake in cerebellum, normalized to injected activity, normalized to plasma tracer concentration, and two methods for estimating CMRglc. Six patients suffering from severe traumatic brain injury (TBI) and ten healthy controls (HC) underwent a 10min static [ 18 F]FDG-PET scan and venous blood sampling. Except from normalizing to cerebellum, all quantification methods found significant lower level of whole brain glucose metabolism of 25-33% in TBI patients compared to HC. In accordance these measurements correlated to level of consciousness. Our study demonstrates that the analysis method of the [ 18 F]FDG PET data has a substantial impact on the estimated whole brain cerebral glucose metabolism in patients with severe TBI. Importantly, the SUVR method which is often used in a clinical setting was not able to distinguish patients with severe TBI from HC at the whole-brain level. We recommend supplementing a static [ 18 F]FDG scan with a single venous blood sample in future studies of patients with severe TBI or reduced level of consciousness. This can be used for simple semi-quantitative uptake values by normalizing brain activity uptake to plasma tracer concentration, or quantitative estimates of CMRglc. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative study of nonlinear properties of EEG signals of normal persons and epileptic patients

PubMed Central

2009-01-01

Background Investigation of the functioning of the brain in living systems has been a major effort amongst scientists and medical practitioners. Amongst the various disorder of the brain, epilepsy has drawn the most attention because this disorder can affect the quality of life of a person. In this paper we have reinvestigated the EEGs for normal and epileptic patients using surrogate analysis, probability distribution function and Hurst exponent. Results Using random shuffled surrogate analysis, we have obtained some of the nonlinear features that was obtained by Andrzejak et al. [Phys Rev E 2001, 64:061907], for the epileptic patients during seizure. Probability distribution function shows that the activity of an epileptic brain is nongaussian in nature. Hurst exponent has been shown to be useful to characterize a normal and an epileptic brain and it shows that the epileptic brain is long term anticorrelated whereas, the normal brain is more or less stochastic. Among all the techniques, used here, Hurst exponent is found very useful for characterization different cases. Conclusion In this article, differences in characteristics for normal subjects with eyes open and closed, epileptic subjects during seizure and seizure free intervals have been shown mainly using Hurst exponent. The H shows that the brain activity of a normal man is uncorrelated in nature whereas, epileptic brain activity shows long range anticorrelation. PMID:19619290

Adaptive remodeling at the pedicle due to pars fracture: a finite element analysis study.

PubMed

İnceoğlu, Serkan; Mageswaran, Prasath; Modic, Michael T; Benzel, Edward C

2014-09-01

Spondylolysis is a common condition among the general population and a major cause of back pain in young athletes. This condition can be difficult to detect with plain radiography and has been reported to lead to contralateral pars fracture or pedicle fracture in the terminal stages. Interestingly, some patients with late-stage spondylolysis are observed to have radiographic or CT evidence of a sclerotic pedicle on the side contralateral to the spondylolysis. Although computational studies have shown stress elevation in the contralateral pedicle after a pars fracture, it is not known if these changes would cause sclerotic changes in the contralateral pedicle. The objective of this study was to investigate the adaptive remodeling process at the pedicle due to a contralateral spondylolysis using finite element analysis. A multiscale finite element model of a vertebra was obtained by combining a continuum model of the posterior elements with a voxel-based pedicle section. Extension loading conditions were applied with or without a fracture at the contralateral pars to analyze the stresses in the contralateral pedicle. A remodeling algorithm was used to simulate and assess density changes in the contralateral pedicle. The remodeling algorithm demonstrated an increase in bone formation around the perimeter of the contralateral pedicle with some localized loss of mass in the region of cancellous bone. The authors' results indicated that a pars fracture results in sclerotic changes in the contralateral pedicle. Such a remodeling process could increase overall bone mass. However, focal bone loss in the region of the cancellous bone of the pedicle might predispose the pedicle to microfractures. This phenomenon explains, at least in part, the origin of pedicle stress fractures in the sclerotic contralateral pedicles of patients with unilateral spondylolysis.

The value of preoperative 18F-FDG PET/CT for the assessing contralateral neck in head and neck cancer patients with unilateral node metastasis (N1-3).

PubMed

Joo, Y-H; Yoo, I-R; Cho, K-J; Park, J-O; Nam, I-C; Kim, C-S; Kim, S-Y; Kim, M-S

2014-12-01

The purpose of this study was to determine whether preoperative (18) F-FDG PET/CT is useful in assessing contralateral lymph node metastasis in the neck. A retrospective review of medical records was performed. Patients treated at a single institute. One hundred and fifty-seven patients whose pathology results were positive for unilateral node metastasis (N1-3) involvement and underwent preoperative (18) F-FDG PET/CT for head and neck squamous cell carcinoma (HNSCC) were reviewed. Prognostic factors and nodal SUVmax were studied to identify the risk of contralateral disease. Thirty-six (22.9%) patients had contralateral cervical lymph node metastases. The (18) F-FDG PET/CT had a sensitivity of 80% and a specificity of 96% in identifying the contralateral cervical lymph node metastases on a level-by-level basis. The median SUVmax values of the ipsilateral and contralateral lymph nodes were 3.99 ± 3.36 (range, 0-20.4) and 2.94 ± 2.04 (range, 0-8.7), respectively (P = 0.001). There was a significant difference in the median SUVmax of contralateral nodes between the benign and malignant cervical lymph nodes (2.31 ± 0.62 versus 3.28 ± 2.43, P = 0.014). The cut-off value of contralateral median SUVmax in the context of contralateral cervical metastasis was 2.5 with the sensitivity of 75% and the specificity of 94%. A median contralateral lymph node SUVmax  ≥ 2.5 was associated with 5-year disease-specific survival (P = 0.038). (18) F-FDG PET/CT median SUVmax cut-off values of contralateral lymph nodes ≥2.5 were associated with contralateral cervical lymph node metastases and 5-year disease-specific survival in HNSCC patients with unilateral metastases. © 2014 John Wiley & Sons Ltd.

Effect of intravenous gadolinium-DTPA on diffusion-weighted imaging of brain tumors: a short temporal interval assessment.

PubMed

Li, Xiang; Qu, Jin-Rong; Luo, Jun-Peng; Li, Jing; Zhang, Hong-Kai; Shao, Nan-Nan; Kwok, Keith; Zhang, Shou-Ning; Li, Yan-le; Liu, Cui-Cui; Zee, Chi-Shing; Li, Hai-Liang

2014-09-01

To determine the effect of intravenous administration of gadolinium (Gd) contrast medium (Gd-DTPA) on diffusion-weighted imaging (DWI) for the evaluation of normal brain parenchyma vs. brain tumor following a short temporal interval. Forty-four DWI studies using b values of 0 and 1000 s/mm(2) were performed before, immediately after, 1 min after, 3 min after, and 5 min after the administration of Gd-DTPA on 62 separate lesions including 15 meningioma, 17 glioma and 30 metastatic lesions. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and apparent diffusion coefficient (ADC) values of the brain tumor lesions and normal brain tissues were measured on pre- and postcontrast images. Statistical analysis using paired t-test between precontrast and postcontrast data were obtained on three brain tumors and normal brain tissue. The SNR and CNR of brain tumors and the SNR of normal brain tissue showed no statistical differences between pre- and postcontrast (P > 0.05). The ADC values on the three cases of brain tumors demonstrated significant initial increase on the immediate time point (P < 0.01) and decrease on following the 1 min time point (P < 0.01) after contrast. Significant decrease of ADC value was still found at 3min and 5min time point in the meningioma group (P < 0.01) with gradual normalization over time. The ADC values of normal brain tissues demonstrated significant initial elevation on the immediately postcontrast DWI sequence (P < 0.01). Contrast medium can cause a slight but statistically significant change on the ADC value within a short temporal interval after the contrast administration. The effect is both time and lesion-type dependent. © 2013 Wiley Periodicals, Inc.

Cortical-basal ganglionic degeneration.

PubMed

Riley, D E; Lang, A E; Lewis, A; Resch, L; Ashby, P; Hornykiewicz, O; Black, S

1990-08-01

We report our experience with 15 patients believed to have cortical-basal ganglionic degeneration. The clinical picture is distinctive, comprising features referable to both cortical and basal ganglionic dysfunction. Characteristic manifestations include cortical sensory loss, focal reflex myoclonus, "alien limb" phenomena, apraxia, rigidity and akinesia, a postural-action tremor, limb dystonia, hyperreflexia, and postural instability. The asymmetry of symptoms and signs is often striking. Brain imaging may demonstrate greater abnormalities contralateral to the more affected side. Postmortem studies in 2 patients revealed the characteristic pathologic features of swollen, poorly staining (achromatic) neurons and degeneration of cerebral cortex and substantia nigra. Biochemical analysis of 1 brain showed a severe, diffuse loss of dopamine in the striatum. This condition is more frequent than previously believed, and the diagnosis can be predicted during life on the basis of clinical findings. However, as with other "degenerative" diseases of the nervous system, a definitive diagnosis of cortical-basal ganglionic degeneration requires confirmation by autopsy.

Somatosensory responses in a human motor cortex

PubMed Central

Donoghue, John P.; Hochberg, Leigh R.

2013-01-01

Somatic sensory signals provide a major source of feedback to motor cortex. Changes in somatosensory systems after stroke or injury could profoundly influence brain computer interfaces (BCI) being developed to create new output signals from motor cortex activity patterns. We had the unique opportunity to study the responses of hand/arm area neurons in primary motor cortex to passive joint manipulation in a person with a long-standing brain stem stroke but intact sensory pathways. Neurons responded to passive manipulation of the contralateral shoulder, elbow, or wrist as predicted from prior studies of intact primates. Thus fundamental properties and organization were preserved despite arm/hand paralysis and damage to cortical outputs. The same neurons were engaged by attempted arm actions. These results indicate that intact sensory pathways retain the potential to influence primary motor cortex firing rates years after cortical outputs are interrupted and may contribute to online decoding of motor intentions for BCI applications. PMID:23343902

Role of the superior colliculus in choosing mixed-strategy saccades.

PubMed

Thevarajah, Dhushan; Mikulić, Areh; Dorris, Michael C

2009-02-18

Game theory outlines optimal response strategies during mixed-strategy competitions. The neural processes involved in choosing individual strategic actions, however, remain poorly understood. Here, we tested whether the superior colliculus (SC), a brain region critical for generating sensory-guided saccades, is also involved in choosing saccades under strategic conditions. Monkeys were free to choose either of two saccade targets as they competed against a computer opponent during the mixed-strategy game "matching pennies." The accuracy with which presaccadic SC activity predicted upcoming choice gradually increased in the time leading up to the saccade. Probing the SC with suprathreshold stimulation demonstrated that these evolving signals were functionally involved in preparing strategic saccades. Finally, subthreshold stimulation of the SC increased the likelihood that contralateral saccades were selected. Together, our results suggest that motor regions of the brain play an active role in choosing strategic actions rather than passively executing those prespecified by upstream executive regions.

Accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue.

PubMed

Zhang, Jing; Fan, Yimeng; He, Min; Ma, Xuelei; Song, Yanlin; Liu, Ming; Xu, Jianguo

2017-05-30

Raman spectroscopy could be applied to distinguish tumor from normal tissues. This meta-analysis was conducted to assess the accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue. PubMed and Embase were searched to identify suitable studies prior to Jan 1st, 2016. We estimated the pooled sensitivity, specificity, positive and negative likelihood ratios (LR), diagnostic odds ratio (DOR), and constructed summary receiver operating characteristics (SROC) curves to identity the accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue. A total of six studies with 1951 spectra were included. For glioma, the pooled sensitivity and specificity of Raman spectroscopy were 0.96 (95% CI 0.94-0.97) and 0.99 (95% CI 0.98-0.99), respectively. The area under the curve (AUC) was 0.9831. For meningioma, the pooled sensitivity and specificity were 0.98 (95% CI 0.94-1.00) and 1.00 (95% CI 0.98-1.00), respectively. The AUC was 0.9955. This meta-analysis suggested that Raman spectroscopy could be an effective and accurate tool for differentiating glioma and meningioma from normal brain tissue, which would help us both avoid removal of normal tissue and minimize the volume of residual tumor.

SU-E-T-331: Dosimetric Impact of Multileaf Collimator Leaf Width On Stereotactic Radiosurgery (SRS) RapidArc Treatment Plans for Single and Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Keeling, V; Ahmad, S

Purpose: To determine the effects of multileaf collimator (MLC) leaf width on normal-brain-tissue doses and dose conformity of SRS RapidArc treatment plans for brain tumors. Methods: Ten patients with 24 intracranial tumors (seven with 1–2 and three with 4–6 lesions) were planned using RapidArc for both Varian Millennium 120 MLC (5 mm leaf width) and high definition (HD) MLC (2.5 mm leaf width). Between 2 and 8 arcs were used with two full coplanar arcs and the rest non-coplanar half arcs. 6 MV beams were used and plans were optimized with a high priority to the Normal Tissue Objective (tomore » achieve dose conformity and sharp dose fall-off) and normal brain tissue. Calculation was done using AAA on a 1 mm grid size. The prescription dose ranged from 14–22 Gy. Plans were normalized such that 99% of the target received the prescription dose. Identical beam geometries, optimizations, calculations, and normalizations were used for both plans. Paddick Conformity Index (PCI), V4, V8 and V12 Gy for normal brain tissue and Integral Dose were used for analysis. Results: In all cases, HD MLC plans performed better in sparing normal brain tissue, achieving a higher PCI with a lower Integral Dose. The average PCI for all 24 targets was 0.75±0.23 and 0.70±0.23 (p ≤0.0015) for HD MLC and Millennium MLC plans, respectively. The average ratio of normal brain doses for Millennium MLC to HD MLC plans was 1.30±0.16, 1.27±0.15, and 1.31±0.18 for the V4, V8, and V12, respectively. The differences in normal brain dose for all criteria were statistically significant with p-value < 0.02. On average Millennium MLC plans had a 16% higher integral dose than HD MLC plans. Conclusion: Significantly better dose conformity with reduced volume of normal brain tissue and integral dose was achieved with HD MLC plans compared to Millennium MLC plans.« less

1H Magnetic resonance spectroscopy of the internal capsule in human brain: a feasibility study to detect lactate following contralateral motor activity.

PubMed

Mostert, Jop P; Sijens, Paul E; Oudkerk, Matthijs; De Keyser, Jacques

2005-07-01

Animal experiments suggest that astrocytic glycogen may act as an energy source for axons especially during heightened activity. In this model astrocytic glycogen breaks down to lactate that is shuttled to axons where it is metabolized oxidatively to generate ATP. The aim of this study was to investigate whether (1)H-magnetic resonance spectroscopy could be used to detect a rise in lactate levels in human white matter during enhanced axonal activation. Six healthy volunteers (four women and two men; age range 21-38 years) participated in the study. We were unable to detect any significant MR spectral change, i.e. neither in the peak areas of inositol, choline, creatine, glutamate and N-acetylaspartate nor in the lactate level, in the contralateral posterior limb of the internal capsule during intense motor activation of the hand (four successive episodes of squeezing a soft ball for 7 min followed by 7 min rest). Possible explanations are that the technique is not sensitive enough to detect a small rise in lactate, or lactate turnover is too fast to be detected, or that another monocarboxylate different from lactate may be involved in axonal energy metabolism.

Columnar alterations of NADH fluorescence during hypoxia-ischemia in immature rat brain.

PubMed

Welsh, F A; Vannucci, R C; Brierley, J B

1982-01-01

Cerebral hypoxia-ischemia was produced in 7-day postnatal rats by unilateral carotid artery ligation combined with systemic hypoxia (8% O2). Levels of high energy phosphates, which were only slightly altered in the contralateral hemisphere, were nearly depleted in the ipsilateral hemisphere during the 3-h hypoxic insult. With hypoxia of between 1 and 3 hours' duration, columnar alterations of cortical NADH fluorescence occurred in the same location and regional pattern as did histologic damage demonstrated previously (Rice et al., 1981). In regions exhibiting columns of NADH fluorescence, there was no evidence of a columnar reduction of high energy phosphates as levels of ATP and phosphocreatine were nearly zero. Recovery from 3 h of hypoxia was accompanied by partial and regionally heterogeneous restoration of ATP within the ipsilateral hemisphere. Columnar variations of NADH fluorescence were not detected in the recovery period; rather, regions with impaired restitution of high energy phosphates exhibited NADH fluorescence that was diminished diffusely compared to the contralateral hemisphere. The correlation between depressed NADH fluorescence and depleted ATP, present as cortical columns during hypoxia and as larger regions during recovery, suggests that decreased formation of NADH may be limiting the resynthesis of high energy phosphates.

Blood-Brain Glucose Transfer: Repression in Chronic Hyperglycemia

NASA Astrophysics Data System (ADS)

Gjedde, Albert; Crone, Christian

1981-10-01

Diabetic patients with increased plasma glucose concentrations may develop cerebral symptoms of hypoglycemia when their plasma glucose is rapidly lowered to normal concentrations. The symptoms may indicate insufficient transport of glucose from blood to brain. In rats with chronic hyperglycemia the maximum glucose transport capacity of the blood-brain barrier decreased from 400 to 290 micromoles per 100 grams per minute. When plasma glucose was lowered to normal values, the glucose transport rate into brain was 20 percent below normal. This suggests that repressive changes of the glucose transport mechanism occur in brain endothelial cells in response to increased plasma glucose.

Temporal lobe epilepsy patients with severe hippocampal neuron loss but normal hippocampal volume: Extracellular matrix molecules are important for the maintenance of hippocampal volume.

PubMed

Peixoto-Santos, Jose Eduardo; Velasco, Tonicarlo Rodrigues; Galvis-Alonso, Orfa Yineth; Araujo, David; Kandratavicius, Ludmyla; Assirati, Joao Alberto; Carlotti, Carlos Gilberto; Scandiuzzi, Renata Caldo; Santos, Antonio Carlos dos; Leite, Joao Pereira

2015-10-01

Hippocampal sclerosis is a common finding in patients with temporal lobe epilepsy (TLE), and magnetic resonance imaging (MRI) studies associate the reduction of hippocampal volume with the neuron loss seen on histologic evaluation. Astrogliosis and increased levels of chondroitin sulfate, a major component of brain extracellular matrix, are also seen in hippocampal sclerosis. Our aim was to evaluate the association between hippocampal volume and chondroitin sulfate, as well as neuronal and astroglial populations in the hippocampus of patients with TLE. Patients with drug-resistant TLE were subdivided, according to hippocampal volume measured by MRI, into two groups: hippocampal atrophy (HA) or normal volume (NV) cases. Hippocampi from TLE patients and age-matched controls were submitted to immunohistochemistry to evaluate neuronal population, astroglial population, and chondroitin sulfate expression with antibodies against neuron nuclei protein (NeuN), glial fibrillary acidic protein (GFAP), and chondroitin sulfate (CS-56) antigens, respectively. Both TLE groups were clinically similar. NV cases had higher hippocampal volume, both ipsilateral and contralateral, when compared to HA. Compared to controls, NV and HA patients had reduced neuron density, and increased GFAP and CS-56 immunopositive area. There was no statistical difference between NV and HA groups in neuron density or immunopositive areas for GFAP and CS-56. Hippocampal volume correlated positively with neuron density in CA1 and prosubiculum, and with immunopositive areas for CS-56 in CA1, and negatively with immunopositive area for GFAP in CA1. Multiple linear regression analysis indicated that both neuron density and CS-56 immunopositive area in CA1 were statistically significant predictors of hippocampal volume. Our findings indicate that neuron density and chondroitin sulfate immunopositive area in the CA1 subfield are crucial for the hippocampal volume, and that chondroitin sulfate is important for the maintenance of a normal hippocampal volume in some cases with severe neuron loss. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Multichannel optical mapping: investigation of depth information

NASA Astrophysics Data System (ADS)

Sase, Ichiro; Eda, Hideo; Seiyama, Akitoshi; Tanabe, Hiroki C.; Takatsuki, Akira; Yanagida, Toshio

2001-06-01

Near infrared (NIR) light has become a powerful tool for non-invasive imaging of human brain activity. Many systems have been developed to capture the changes in regional brain blood flow and hemoglobin oxygenation, which occur in the human cortex in response to neural activity. We have developed a multi-channel reflectance imaging system, which can be used as a `mapping device' and also as a `multi-channel spectrophotometer'. In the present study, we visualized changes in the hemodynamics of the human occipital region in multiple ways. (1) Stimulating left and right primary visual cortex independently by showing sector shaped checkerboards sequentially over the contralateral visual field, resulted in corresponding changes in the hemodynamics observed by `mapping' measurement. (2) Simultaneous measurement of functional-MRI and NIR (changes in total hemoglobin) during visual stimulation showed good spatial and temporal correlation with each other. (3) Placing multiple channels densely over the occipital region demonstrated spatial patterns more precisely, and depth information was also acquired by placing each pair of illumination and detection fibers at various distances. These results indicate that optical method can provide data for 3D analysis of human brain functions.

Cortico-muscular coherence on artifact corrected EEG-EMG data recorded with a MRI scanner.

PubMed

Muthuraman, M; Galka, A; Hong, V N; Heute, U; Deuschl, G; Raethjen, J

2013-01-01

Simultaneous recording of electroencephalogram (EEG) and electromyogram (EMG) with magnetic resonance imaging (MRI) provides great potential for studying human brain activity with high temporal and spatial resolution. But, due to the MRI, the recorded signals are contaminated with artifacts. The correction of these artifacts is important to use these signals for further spectral analysis. The coherence can reveal the cortical representation of peripheral muscle signal in particular motor tasks, e.g. finger movements. The artifact correction of these signals was done by two different algorithms the Brain vision analyzer (BVA) and the Matlab FMRIB plug-in for EEGLAB. The Welch periodogram method was used for estimating the cortico-muscular coherence. Our analysis revealed coherence with a frequency of 5Hz in the contralateral side of the brain. The entropy is estimated for the calculated coherence to get the distribution of coherence in the scalp. The significance of the paper is to identify the optimal algorithm to rectify the MR artifacts and as a first step to use both these signals EEG and EMG in conjunction with MRI for further studies.

Poster - Thur Eve - 16: Four-dimensional x-ray computed tomography and hyperpolarized 3 He magnetic resonance imaging of gas distribution in lung cancer.

PubMed

Mathew, L; Castillo, R; Castillo, E; Yaremko, B; Rodrigues, G; Etemad-Rezai, R; Guerrero, T; Parraga, G

2012-07-01

Dynamic imaging methods such as four-dimensional computed tomography (4DCT) and static imaging methods such as noble gas magnetic resonance imaging (MRI) deliver direct and regional measurements of lung function even in lung cancer patients in whom global lung function measurements are dominated by tumour burden. The purpose of this study was to directly compare quantitative measurements of gas distribution from static hyperpolarized 3 He MRI and dynamic 4DCT in a small group of lung cancer patients. MRI and 4DCT were performed in 11 subjects prior to radiation therapy. MRI was performed at 3.0T in breath-hold after inhalation 1L of hyperpolarized 3 He gas. Gas distribution in 3 He MRI was quantified using a semi-automated segmentation algorithm to generate percent-ventilated volume (PVV), reflecting the volume of gas in the lung normalized to the thoracic cavity volume. 4DCT pulmonary function maps were generated using deformable image registration of six expiratory phase images. The correspondence between identical tissue elements at inspiratory and expiratory phases was used to estimate regional gas distribution and PVV was quantified from these images. After accounting for differences in lung volumes between 3 He MRI (1.9±0.5L ipsilateral, 2.3±0.7 contralateral) and 4DCT (1.2±0.3L ipsilateral, 1.3±0.4L contralateral) during image acquisition, there was no statistically significant difference in PVV between 3 He MRI (72±11% ipsilateral, 79±12% contralateral) and 4DCT (74±3% ipsilateral, 75±4% contralateral). Our results indicate quantitative agreement in the regional distribution of inhaled gas in both static and dynamic imaging methods. PVV may be considered as a regional surrogate measurement of lung function or ventilation. © 2012 American Association of Physicists in Medicine.

Contralateral posterior interhemispheric approach to deep medial parietooccipital vascular malformations: surgical technique and results.

PubMed

Burkhardt, Jan-Karl; Winkler, Ethan A; Lawton, Michael T

2017-07-21

OBJECTIVE Deep medial parietooccipital arteriovenous malformations (AVMs) and cerebral cavernous malformations (CCMs) are traditionally resected through an ipsilateral posterior interhemispheric approach (IPIA), which creates a deep, perpendicular perspective with limited access to the lateral margins of the lesion. The contralateral posterior interhemispheric approach (CPIA) flips the positioning, with the midline positioned horizontally for retraction due to gravity, but with the AVM on the upper side and the approach from the contralateral, lower side. The aim of this paper was to analyze whether the perpendicular angle of attack that is used in IPIA would convert to a parallel angle of attack with the CPIA, with less retraction, improved working angles, and no significant increase in risk. METHODS A retrospective review of pre- and postoperative clinical and radiographic data was performed in 8 patients who underwent a CPIA. RESULTS Three AVMs and 5 CCMs were resected using the CPIA, with an average nidus size of 2.3 cm and CCM diameter of 1.7 cm. All lesions were resected completely, as confirmed on postoperative catheter angiography or MRI. All patients had good neurological outcomes, with either stable or improved modified Rankin Scale scores at last follow-up. CONCLUSIONS The CPIA is a safe alternative approach to the IPIA for deep medial parietooccipital vascular malformations that extend 2 cm or more off the midline. Contralaterality and retraction due to gravity optimize the interhemispheric corridor, the surgical trajectory to the lesion, and the visualization of the lateral margin, without resection or retraction of adjacent normal cortex. Although the falx is a physical barrier to accessing the lesion, it stabilizes the ipsilateral hemisphere while gravity delivers the dissected lesion through the transfalcine window. Patient positioning, CSF drainage, venous preservation, and meticulous dissection of the deep margins are critical to the safety of this approach.

Ipsilateral irradiation for well lateralized carcinomas of the oral cavity and oropharynx: results on tumor control and xerostomia

PubMed Central

Cerezo, Laura; Martín, Margarita; López, Mario; Marín, Alicia; Gómez, Alberto

2009-01-01

Background In head and neck cancer, bilateral neck irradiation is the standard approach for many tumor locations and stages. Increasing knowledge on the pattern of nodal invasion leads to more precise targeting and normal tissue sparing. The aim of the present study was to evaluate the morbidity and tumor control for patients with well lateralized squamous cell carcinomas of the oral cavity and oropharynx treated with ipsilateral radiotherapy. Methods Twenty consecutive patients with lateralized carcinomas of the oral cavity and oropharynx were treated with a prospective management approach using ipsilateral irradiation between 2000 and 2007. This included 8 radical oropharyngeal and 12 postoperative oral cavity carcinomas, with Stage T1-T2, N0-N2b disease. The actuarial freedom from contralateral nodal recurrence was determined. Late xerostomia was evaluated using the European Organization for Research and Treatment of Cancer QLQ-H&N35 questionnaire and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3. Results At a median follow-up of 58 months, five-year overall survival and loco-regional control rates were 82.5% and 100%, respectively. No local or contralateral nodal recurrences were observed. Mean dose to the contralateral parotid gland was 4.72 Gy and to the contralateral submandibular gland was 15.30 Gy. Mean score for dry mouth was 28.1 on the 0-100 QLQ-H&N35 scale. According to CTCAE v3 scale, 87.5% of patients had grade 0-1 and 12.5% grade 2 subjective xerostomia. The unstimulated salivary flow was > 0.2 ml/min in 81.2% of patients and 0.1-0.2 ml/min in 19%. None of the patients showed grade 3 xerostomia. Conclusion In selected patients with early and moderate stages, well lateralized oral and oropharyngeal carcinomas, ipsilateral irradiation treatment of the primary site and ipsilateral neck spares salivary gland function without compromising loco-regional control. PMID:19723329

Phantom-to-clinic development of hypofractionated stereotactic body radiotherapy for early-stage glottic laryngeal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, Chuxiong; Chun, Stephen G.; Sumer, Baran D.

The purpose of this study was to commission and clinically test a robotic stereotactic delivery system (CyberKnife, Sunnyvale, CA) to treat early-stage glottic laryngeal cancer. We enrolled 15 patients with cTis-T2N0M0 carcinoma of the glottic larynx onto an institutional review board (IRB)-approved clinical trial. Stereotactic body radiotherapy (SBRT) plans prescribed 45 Gy/10 fractions to the involved hemilarynx. SBRT dosimetry was compared with (1) standard carotid-sparing laryngeal intensity-modulated radiation therapy (IMRT) and (2) selective hemilaryngeal IMRT. Our results demonstrate that SBRT plans improved sparing of the contralateral arytenoid (mean 20.0 Gy reduction, p <0.001), ipsilateral carotid D{sub max} (mean 20.6 Gy reduction, p <0.001), contralateral carotidmore » D{sub max} (mean 28.1 Gy reduction, p <0.001), and thyroid D{sub mean} (mean 15.0 Gy reduction, p <0.001) relative to carotid-sparing IMRT. SBRT also modestly improved dose sparing to the contralateral arytenoid (mean 4.8 Gy reduction, p = 0.13) and spinal cord D{sub max} (mean 4.9 Gy reduction, p = 0.015) relative to selective hemilaryngeal IMRT plans. This “phantom-to-clinic” feasibility study confirmed that hypofractionated SBRT treatment for early-stage laryngeal cancer can potentially spare dose to adjacent normal tissues relative to current IMRT standards. Clinical efficacy and toxicity correlates continue to be collected through an ongoing prospective trial.« less

Targeted Gene Transfer to the Brain via the Delivery of Brain-Penetrating DNA Nanoparticles with Focused Ultrasound

PubMed Central

Mead, Brian P.; Mastorakos, Panagiotis; Suk, Jung Soo; Klibanov, Alexander L.; Hanes, Justin; Price, Richard J.

2016-01-01

Gene therapy holds promise for the treatment of many pathologies of the central nervous system (CNS), including brain tumors and neurodegenerative diseases. However, the delivery of systemically administered gene carriers to the CNS is hindered by both the blood-brain barrier (BBB) and the nanoporous and electrostatically charged brain extracelluar matrix (ECM), which acts as a steric and adhesive barrier. We have previously shown that these physiological barriers may be overcome by, respectively, opening the BBB with MR image-guided focused ultrasound (FUS) and microbubbles and using highly compact “brain penetrating” nanoparticles (BPN) coated with a dense polyethylene glycol corona that prevents adhesion to ECM components. Here, we tested whether this combined approach could be utilized to deliver systemically administered DNA-bearing BPN (DNA-BPN) across the BBB and mediate localized, robust, and sustained transgene expression in the rat brain. Systemically administered DNA-BPN delivered through the BBB with FUS led to dose-dependent transgene expression only in the FUS-treated region that was evident as early as 24 h post administration and lasted for at least 28 days. In the FUS-treated region ~42% of all cells, including neurons and astrocytes, were transfected, while less than 6% were transfected in the contralateral non-FUS treated hemisphere. Importantly, this was achieved without any sign of toxicity or astrocyte activation. We conclude that the image-guided delivery of DNA-BPN with FUS and microbubbles constitutes a safe and non-invasive strategy for targeted gene therapy to the brain. PMID:26732553

The effect of midline crossing of lateral supraglottic cancer on contralateral cervical lymph node metastasis.

PubMed

Yılmaz, Taner; Süslü, Nilda; Atay, Gamze; Günaydın, Rıza Önder; Bajin, Münir Demir; Özer, Serdar

2015-05-01

The degree of midline crossing of lateral supraglottic cancer does not significantly change its rate of contralateral cervical metastasis. The rate of occult metastasis is too high to take the risk of contralateral regional recurrence. We support routine bilateral neck dissection even in lateral supraglottic cancers with no or minimal midline crossing. Data on the rate of contralateral cervical metastasis of laterally located supraglottic cancer, the effect of its degree of midline crossing on contralateral cervical metastasis, and its treatment are still controversial. This was a retrospective cohort, chart review involving 305 surgically treated patients with T1-3 squamous cell carcinoma of the supraglottic larynx. In all, 184 patients had bilateral neck dissection; 86 N0 contralateral necks were followed up. Thirty-five patients who needed postoperative radiation therapy because of the primary tumor or ipsilateral neck dissection specimen also received radiation therapy to the contralateral neck. The degree of midline crossing at the epiglottis was measured on a laryngectomy specimen with a ruler and expressed as 'no,' '<5 mm' or '≥5 mm.' The rates of occult and overall contralateral metastasis in our series were 16% and 28%, respectively. There was no statistically significant difference between contralateral neck metastasis and recurrence rates in the neck dissection, follow-up, and irradiation groups according to the degree of midline crossing.

Study of Methylene Blue Ototoxicity in the Guinea Pig.

PubMed

Belhassen, Sarah; Alzahrani, Musaed; Nader, Marc-Elie; Gaboury, Louis; Saliba, Issam

2017-11-01

Methylene blue is widely used in the medical field, especially as a blue dye for staining. It is also used as a photosensitizing agent in antimicrobial photodynamic therapy, which once photoactivated is effective for the eradication of several multi-resistant bacteria. The objective of this study was to investigate the ototoxic potential of methylene blue and precise its use in otology. It was a prospective animal study performed on guinea pigs in our tertiary medical center. We divided the animals into two groups: an experimental group and a control group, who underwent a series of three intratympanic (IT) injections. In the control group (n = 10), they received injections of gentamicin in one ear (positive control) and normal saline in the contralateral ear (negative control). The experimental group (n = 10) received injections of methylene blue in one ear, compared to injections of normal saline in the contralateral ear. We conducted auditory-evoked brainstem response (ABR) before and 1 week after the injection series. Once this is completed, the cochlea was dissected and caspase-3 was analyzed by immunohistochemistry. The mean difference of hearing loss in the methylene blue group compared to normal saline was 1.50 dB, and it was not shown to be statistically significant (P = 0.688). For the positive control group, which received IT injections of gentamicin, the mean threshold of hearing loss difference for all the frequencies combined was 66.25 dB (P < 0.001). Furthermore, uptake of caspase-3 by immunohistochemistry (apoptotic marker) was negative in our group, which received injections of methylene blue. In light of our results, IT injections of methylene blue did not demonstrate an ototoxic potential. We recommend further studies to precise its use in the otologic field.

Whisker motor cortex reorganization after superior colliculus output suppression in adult rats.

PubMed

Veronesi, Carlo; Maggiolini, Emma; Franchi, Gianfranco

2013-10-01

The effect of unilateral superior colliculus (SC) output suppression on the ipsilateral whisker motor cortex (WMC) was studied at different time points after tetrodotoxin and quinolinic acid injections, in adult rats. The WMC output was assessed by mapping the movement evoked by intracortical microstimulation (ICMS) and by recording the ICMS-evoked electromyographic (EMG) responses from contralateral whisker muscles. At 1 h after SC injections, the WMC showed: (i) a strong decrease in contralateral whisker sites, (ii) a strong increase in ipsilateral whisker sites and in ineffective sites, and (iii) a strong increase in threshold current values. At 6 h after injections, the WMC size had shrunk to 60% of the control value and forelimb representation had expanded into the lateral part of the normal WMC. Thereafter, the size of the WMC recovered, returning to nearly normal 12 h later (94% of control) and persisted unchanged over time (1-3 weeks). The ICMS-evoked EMG response area decreased at 1 h after SC lesion and had recovered its baseline value 12 h later. Conversely, the latency of ICMS-evoked EMG responses had increased by 1 h and continued to increase for as long as 3 weeks following the lesion. These findings provide physiological evidence that SC output suppression persistently withdrew the direct excitatory drive from whisker motoneurons and induced changes in the WMC. We suggest that the changes in the WMC are a form of reversible short-term reorganization that is induced by SC lesion. The persistent latency increase in the ICMS-evoked EMG response suggested that the recovery of basic WMC excitability did not take place with the recovery of normal explorative behaviour. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Degree of corneal anaesthesia after topical application of 0.4% oxybuprocaine hydrochloride and 0.5% proparacaine hydrochloride ophthalmic solution in clinically normal cattle.

PubMed

Little, W B; Jean, G St; Sithole, F; Little, E; Jean, K Yvorchuk-St

2016-06-01

The use of corneal anaesthesia is necessary for a range of clinical purposes. Therefore, we assessed and compared the efficacy of corneal anaesthesia after application of 0.4% oxybuprocaine hydrochloride and 0.5% proparacaine hydrochloride ophthalmic solution in clinically normal cattle. The 24 clinically normal cows were allocated into two groups. Cows in group 1 (n = 12) received 0.2 mL of 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mL of sterile saline (0.9% NaCl) with fluorescein in the contralateral eye (control). Group 2 (n = 12) received 0.2 mL of 0.4% oxybuprocaine hydrochloride with fluorescein ophthalmic solution in one eye and 0.2 mL of 0.5% proparacaine hydrochloride with fluorescein in the contralateral eye (control). In each group, corneal touch threshold was determined by Cochet-Bonnet aesthesiometer for both eyes immediately prior to topical administration of solutions, at 1 min and 5 min after administration of topical solutions and every 5 min thereafter for a total of 75 min. Significant corneal anaesthesia was noted immediately following topical application of both oxybuprocaine and proparacaine as compared with controls, with maximal corneal anaesthesia noted 1 min after administration. Both oxybuprocaine and proparacaine produced significant corneal anaesthesia for the duration of the 75-min study. Neither oxybuprocaine hydrochloride nor proparacaine hydrochloride treatment resulted in visible adverse effects. There are limited data available demonstrating the efficacy and duration of corneal anaesthetic agents in cattle. Both oxybuprocaine hydrochloride and proparacaine hydrochloride should be considered practical options for providing corneal anaesthesia in cattle in a clinical setting. © 2016 Australian Veterinary Association.

Study of Methylene Blue Ototoxicity in the Guinea Pig

PubMed Central

Belhassen, Sarah; Alzahrani, Musaed; Nader, Marc-Elie; Gaboury, Louis; Saliba, Issam

2017-01-01

Background Methylene blue is widely used in the medical field, especially as a blue dye for staining. It is also used as a photosensitizing agent in antimicrobial photodynamic therapy, which once photoactivated is effective for the eradication of several multi-resistant bacteria. The objective of this study was to investigate the ototoxic potential of methylene blue and precise its use in otology. Methods It was a prospective animal study performed on guinea pigs in our tertiary medical center. We divided the animals into two groups: an experimental group and a control group, who underwent a series of three intratympanic (IT) injections. In the control group (n = 10), they received injections of gentamicin in one ear (positive control) and normal saline in the contralateral ear (negative control). The experimental group (n = 10) received injections of methylene blue in one ear, compared to injections of normal saline in the contralateral ear. We conducted auditory-evoked brainstem response (ABR) before and 1 week after the injection series. Once this is completed, the cochlea was dissected and caspase-3 was analyzed by immunohistochemistry. Results The mean difference of hearing loss in the methylene blue group compared to normal saline was 1.50 dB, and it was not shown to be statistically significant (P = 0.688). For the positive control group, which received IT injections of gentamicin, the mean threshold of hearing loss difference for all the frequencies combined was 66.25 dB (P < 0.001). Furthermore, uptake of caspase-3 by immunohistochemistry (apoptotic marker) was negative in our group, which received injections of methylene blue. Conclusion In light of our results, IT injections of methylene blue did not demonstrate an ototoxic potential. We recommend further studies to precise its use in the otologic field. PMID:29038666

Three-dimensional shoulder kinematics normalize after rotator cuff repair.

PubMed

Kolk, Arjen; de Witte, Pieter Bas; Henseler, Jan Ferdinand; van Zwet, Erik W; van Arkel, Ewoud R A; van der Zwaal, Peer; Nelissen, Rob G H H; de Groot, Jurriaan H

2016-06-01

Patients with a rotator cuff (RC) tear often exhibit scapular dyskinesia with increased scapular lateral rotation and decreased glenohumeral elevation with arm abduction. We hypothesized that in patients with an RC tear, scapular lateral rotation, and thus glenohumeral elevation, will be restored to normal after RC repair. Shoulder kinematics were quantitatively analyzed in 26 patients with an electromagnetic tracking device (Flock of Birds) before and 1 year after RC repair in this observational case series. We focused on humeral range of motion and scapular kinematics during abduction. The asymptomatic contralateral shoulder was used as the control. Changes in scapular kinematics were associated with the gain in range of motion. Shoulder kinematics were analyzed using a linear mixed model. Mean arm abduction and forward flexion improved after surgery by 20° (95% confidence interval [CI], 2.7°-36.5°; P = .025) and 13° (95% CI, 1.2°-36.5°; P = .044), respectively. Kinematic analyses showed decreases in mean scapular protraction (ie, internal rotation) and lateral rotation (ie, upward rotation) during abduction by 3° (95% CI, 0.0°-5.2°; P = .046) and 4° (95% CI, 1.6°-8.4°; P = .042), respectively. Glenohumeral elevation increased by 5° (95% CI, 0.6°-9.7°; P = .028) at 80°. Humeral range of motion increased when scapular lateral rotation decreased and posterior tilt increased. Scapular kinematics normalize after RC repair toward a symmetrical scapular motion pattern as observed in the asymptomatic contralateral shoulder. The observed changes in scapular kinematics are associated with an increased overall range of motion and suggest restored function of shoulder muscles. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Impact of parenchymal loss on renal function after laparoscopic partial nephrectomy under warm ischemia.

PubMed

Bagheri, Fariborz; Pusztai, Csaba; Farkas, László; Kallidonis, Panagiotis; Buzogány, István; Szabó, Zsuzsanna; Lantos, János; Imre, Marianna; Farkas, Nelli; Szántó, Árpád

2016-12-01

To elucidate the impact of renal parenchymal loss and the ischemic reperfusion injury (RI) on the renal function after laparoscopic partial nephrectomy (LPN) under warm ischemia (WI). Thirty-five patients with a single polar renal mass ≤4 cm and normal contralateral kidney underwent LPN. Transperitoneal LPN with WI using en bloc hilar occlusion was performed. The total differential renal function (T-DRF) using 99m Tc-dimercaptosuccinic acid was evaluated preoperatively and postoperatively over a period of 1 year. A special region of interest (ROI) was selected on the non-tumorous pole of the involved kidney, and was compared with the same ROI in the contralateral kidney. The latter comparison was defined as partial differential renal function (P-DRF). Any postoperative decline in the P-DRF of the operated kidney was attributed to the RI. Subtraction of the P-DRF decline from the T-DRF decline was attributed to the parenchymal loss caused by the resection of the tumor and suturing of the normal parenchyma. The mean WI time was 22 min, and the mean weight of resected specimen was 18 g. The mean postoperative eGFR declined to 87 ml/min/1.73 m 2 from its baseline mean value of 97 ml/min/1.73 m 2 (p value = 0.075). Mean postoperative T-DRF and P-DRF of the operated kidney declined by 7 and 3 %, respectively. After LPN of small renal mass, decline in renal function is primarily attributed to parenchymal loss caused by tumor resection and suturing of the normal parenchyma rather than the RI.

Quantitative Analysis of Diffusion-Weighted Imaging for Diagnosis of Puerperal Breast Abscess After Polyacrylamide Hydrogel Augmentation Mammoplasty: Compared with Other Conventional Modalities.

PubMed

Liu, Lihua; Long, Miaomiao; Wang, Junping; Liu, Ning; Ge, Xihong; Hu, Zhandong; Shen, Wen

2015-02-01

Puerperal breast abscess after polyacrylamide hydrogel (PAAG) augmentation mammoplasty can induce breast auto-inflation resulting in serious consequences. Mammography, ultrasound, and conventional MRI are poor at detecting related PAAG abnormality histologically. We evaluated the value of diffusion-weighted imaging (DWI) in the quantitative analysis of puerperal PAAG abscess after augmentation mammoplasty. This was a retrospective study, and a waiver for informed consent was granted. Sixteen puerperal women with breast discomfort underwent conventional breast non-enhanced MRI and axial DWI using a 3T MR scanner. Qualitative analysis of the signal intensity on DWI and conventional sequences was performed. The apparent diffusion coefficient (ADC) values of the affected and contralateral normal PAAG cysts were measured quantitatively. Paired t test was used to evaluate whether there was significant difference. Both affected and normal PAAG cysts showed equal signal intensity on conventional T1WI and fat saturation T2WI, which were not helpful in detecting puerperal PAAG abscess. However, the affected PAAG cysts had a significantly decreased ADC value of 1.477 ± 0.332 × 10(-3)mm(2)/s and showed obvious hypo-intensity on the ADC map and increased signal intensity on DWI compared with the ADC value of 2.775 ± 0.233 × 10(-3)mm(2)/s of the contralateral normal PAAG cysts. DWI and quantitative measurement of ADC values are of great value for the diagnosis of puerperal PAAG abscess. Standardized MRI should be suggested to these puerperal women with breast discomfort or just for the purpose of check up. DWI should be selected as the essential MRI sequence.

Stratum corneum integrity as a predictor for peristomal skin problems in ostomates.

PubMed

Nybaek, H; Lophagen, S; Karlsmark, T; Bang Knudsen, D; Jemec, G B E

2010-02-01

Peristomal skin problems are common, most often the result is disruption of the skin barrier and this may account for more than one in three visits to ostomy nurses. Therefore a specific assessment of individual risk factors relating to the skin barrier function would be of great interest. Skin barrier integrity in ostomy patients with peristomal skin problems (PSP) was compared with that of ostomy patients with normal skin (controls) using transepidermal water loss (TEWL). Mechanical barrier disruption was determined by a tape stripping test and chemical barrier disruption [sodium lauryl sulphate (SLS) 0.25%]. Patients and controls had a highly significant increase in TEWL value in the peristomal area compared with nonperistomal contralateral abdominal skin (P < 0.0001 for both groups). The skin barrier of normal-looking contralateral skin of ostomates was found to be borderline impaired in patients with PSP compared with those without. A linear association was seen between the number of tape strips removed and TEWL for both cases and controls. Tape stripping suggested that patients with PSP had less resilient skin (P = 0.002). A significant difference in TEWL value between cases and controls was also seen for the SLS patch test on the dorsal skin (P = 0.02). Successive tape stripping, a situation analogous to the normal use of a pouching system, caused a higher degree of barrier damage more rapidly in patients with PSP, indicating an impaired mechanical quality of the barrier. The SLS exposure test suggested a generally increased susceptibility to irritant dermatitis as assessed by TEWL. Our findings suggest tape stripping and SLS testing may have a role as predictive tests to identify patients at risk of PSP.

Favorable surgical outcomes of aldosterone-producing adenoma based on lateralization by CT imaging and hypokalemia: a non-AVS-based strategy.

PubMed

Li, Hai; Liu, Jianbin; Feng, Xiujuan; Liu, Liehua; Wei, Guohong; Cao, Xiaopei; Li, Yanbing

2017-12-01

To test the efficacy of a strategy based on CT imaging and clinical characteristics on lateralizing origin of excess aldosterone secretion in primary aldosteronism. Consecutive patients with diagnosed primary hyperaldosteronism from June 2006 to July 2012 in our center underwent adrenal surgeries without pre-operational adrenal venous sampling (AVS) if all the three criteria were met: (1) round- or oval-shaped occupational lesion of low density after contrast enhancement with diameter >1 cm on CT scan was located in one adrenal gland; (2) unequivocally normal contralateral adrenal gland; (3) serum potassium level lower than 3.5 mmol/L. Subjects who had received operation were taken into analysis and follow-ups. One hundred and twenty-five patients fulfilled the criteria and were recruited into our research. One hundred and twenty-two operated patients (97.6%) experienced complete resolution of hypokalemia as well as resolution or improvement in hypertension with reduction in antihypertensive medication, while 3 patients (2.4%) failed to obtain normal kalemia and continued on spironolactone therapy. At a median of 65-month (range 21-93) follow-up of these 122 subjects, 27 patients dropped out (22.1%). The 95 responding patients reported no episodes of paralysis or confirmed hypokalemia or any supplementation of potassium. Multivariate linear correlation analysis showed that plasma potassium level was correlated inversely with tumor diameter (r = -0.258, 95% CI -0.076, -0.514, p = 0.037) and basal plasma aldosterone level (r = -0.251, 95% CI -0.040, -0.464, p = 0.042). Most patients with typical unilateral adrenal macroadenomas, normal contralateral glands and hypokalemia could attain favorable surgical therapeutic outcomes without pre-operational AVS lateralization.

Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

NASA Astrophysics Data System (ADS)

Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

2016-03-01

In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

Does unilateral basal ganglia activity functionally influence the contralateral side? What we can learn from STN stimulation in patients with Parkinson's disease.

PubMed

Brun, Yohann; Karachi, Carine; Fernandez-Vidal, Sara; Jodoin, Nicolas; Grabli, David; Bardinet, Eric; Mallet, Luc; Agid, Yves; Yelnik, Jerome; Welter, Marie-Laure

2012-09-01

In humans, the control of voluntary movement, in which the corticobasal ganglia (BG) circuitry participates, is mainly lateralized. However, several studies have suggested that both the contralateral and ipsilateral BG systems are implicated during unilateral movement. Bilateral improvement of motor signs in patients with Parkinson's disease (PD) has been reported with unilateral lesion or high-frequency stimulation (HFS) of the internal part of the globus pallidus or the subthalamic nucleus (STN-HFS). To decipher the mechanisms of production of ipsilateral movements induced by the modulation of unilateral BG circuitry activity, we recorded left STN neuronal activity during right STN-HFS in PD patients operated for bilateral deep brain stimulation. Left STN single cells were recorded in the operating room during right STN-HFS while patients experienced, or did not experience, right stimulation-induced dyskinesias. Most of the left-side STN neurons (64%) associated with the presence of right dyskinesias were inhibited, with a significant decrease in burst and intraburst frequencies. In contrast, left STN neurons not associated with right dyskinesias were mainly activated (48%), with a predominant increase 4-5 ms after the stimulation pulse and a decrease in oscillatory activity. This suggests that unilateral neuronal STN modulation is associated with changes in the activity of the contralateral STN. The fact that one side of the BG system can influence the functioning of the other could explain the occurrence of bilateral dyskinesias and motor improvement observed in PD patients during unilateral STN-HFS, as a result of a bilateral disruption of the pathological activity in the corticosubcortical circuitry.

Is the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex important for motor recovery in rats with photochemically induced cortical lesions?

PubMed

Takata, Kotaro; Yamauchi, Hideki; Tatsuno, Hisashi; Hashimoto, Keiji; Abo, Masahiro

2006-01-01

To determine whether the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex is important for motor recovery after brain damage in the photochemically initiated thrombosis (PIT) model. We induced PIT in the sensorimotor cortex in rats and examined the recovery of motor function using the beam-walking test. In 24 rats, the right sensorimotor cortex was lesioned after 2 days of training for the beam-walking test (group 1). After 10 days, PIT was induced in the left sensorimotor cortex. Eight additional rats (group 2) received 2 days training in beam walking, then underwent the beam-walking test to evaluate function. After 10 days of testing, the left sensorimotor cortex was lesioned and recovery was monitored by the beam-walking test for 8 days. In group 1 animals, left hindlimb function caused by a right sensorimotor cortex lesion recovered within 10 days after the operation. Right hindlimb function caused by the left-side lesion recovered within 6 days. In group 2, right hindlimb function caused by induction of the left-side lesion after a total of 12 days of beam-walking training and testing recovered within 6 days as with the double PIT model. The training effect may be relevant to reorganization and neuromodulation. Motor recovery patterns did not indicate whether motor recovery was dependent on the ipsilateral cortex surrounding the lesion or the cortex of the contralateral side. The results emphasize the need for selection of appropriate programs tailored to the area of cortical damage in order to enhance motor functional recovery in this model. Copyright 2006 S. Karger AG, Basel.

Switching handedness: fMRI study of hand motor control in right-handers, left-handers and converted left-handers.

PubMed

Grabowska, Anna; Gut, Malgorzata; Binder, Marek; Forsberg, Lars; Rymarczyk, Krystyna; Urbanik, Andrzej

2012-01-01

The purpose of this study was to investigate the differences in the brain organization of motor control in left- and right-handers and to study whether early left-to-right handwriting switch changes the cortical representation of finger movements in the left and right hemispheres. Echo-planar MR imaging was performed in 52 subjects: consistent right-handers (RH), consistent left-handers (LH), and subjects who had been forced at an early age to switch their left-hand preferences toward the right side. The scanning was performed during simple (flexion/extension of the index finger) and complex (successive finger-thumb opposition) tasks. Subjects performed the tasks using both the preferred and non-preferred hand. In right-handers, there was a general predominance of left-hemisphere activation relative to right hemisphere activation. In lefthanders this pattern was reversed. The switched subjects showed no such volumetric asymmetry. Increasing levels of complexity of motor activity resulted in an increase in the volume of consistently activated areas and the involvement of the ipsilateral in addition to contralateral activations. In both right- and left-handers, movements of the preferred hand activated mainly the contralateral hemisphere, whereas movements of the non-preferred hand resulted in a more balanced pattern of activation in the two hemispheres, indicating greater involvement of the ipsilateral activations. Overall, this study shows that in both left- and right-handed subjects, the preferred hand is controlled mainly by the hemisphere contralateral to that hand, whereas the non-preferred hand is controlled by both hemispheres. The switched individuals share features of both lefthanders and right-handers regarding their motor control architectures.

Cortical compression rapidly trimmed transcallosal projections and altered axonal anterograde transport machinery.

PubMed

Chen, Li-Jin; Wang, Yueh-Jan; Tseng, Guo-Fang

2017-10-24

Trauma and tumor compressing the brain distort underlying cortical neurons. Compressed cortical neurons remodel their dendrites instantly. The effects on axons however remain unclear. Using a rat epidural bead implantation model, we studied the effects of unilateral somatosensory cortical compression on its transcallosal projection and the reversibility of the changes following decompression. Compression reduced the density, branching profuseness and boutons of the projection axons in the contralateral homotopic cortex 1week and 1month post-compression. Projection fiber density was higher 1-month than 1-week post-compression, suggesting adaptive temporal changes. Compression reduced contralateral cortical synaptophysin, vesicular glutamate transporter 1 (VGLUT1) and postsynaptic density protein-95 (PSD95) expressions in a week and the first two marker proteins further by 1month. βIII-tubulin and kinesin light chain (KLC) expressions in the corpus callosum (CC) where transcallosal axons traveled were also decreased. Kinesin heavy chain (KHC) level in CC was temporarily increased 1week after compression. Decompression increased transcallosal axon density and branching profuseness to higher than sham while bouton density returned to sham levels. This was accompanied by restoration of synaptophysin, VGLUT1 and PSD95 expressions in the contralateral cortex of the 1-week, but not the 1-month, compression rats. Decompression restored βIII-tubulin, but not KLC and KHC expressions in CC. However, KLC and KHC expressions in the cell bodies of the layer II/III pyramidal neurons partially recovered. Our results show cerebral compression compromised cortical axonal outputs and reduced transcallosal projection. Some of these changes did not recover in long-term decompression. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Disconnection of basolateral amygdala and insular cortex disrupts conditioned approach in Pavlovian lever autoshaping.

PubMed

Nasser, Helen M; Lafferty, Danielle S; Lesser, Ellen N; Bacharach, Sam Z; Calu, Donna J

2018-01-01

Previously established individual differences in appetitive approach and devaluation sensitivity observed in goal- and sign-trackers may be attributed to differences in the acquisition, modification, or use of associative information in basolateral amygdala (BLA) pathways. Here, we sought to determine the extent to which communication of associative information between BLA and anterior portions of insular cortex (IC) supports ongoing Pavlovian conditioned approach behaviors in sign- and goal-tracking rats, in the absence of manipulations to outcome value. We hypothesized that the BLA mediates goal-, but not sign- tracking approach through interactions with the IC, a brain region involved in supporting flexible behavior. We first trained rats in Pavlovian lever autoshaping to determine their sign- or goal-tracking tendency. During alternating test sessions, we gave unilateral intracranial injections of vehicle or a cocktail of gamma-aminobutyric acid (GABA) receptor agonists, baclofen and muscimol, unilaterally into the BLA and contralaterally or ipsilaterally into the IC prior to reinforced lever autoshaping sessions. Consistent with our hypothesis we found that contralateral inactivation of BLA and IC increased the latency to approach the food cup and decreased the number of food cup contacts in goal-trackers. While contralateral inactivation of BLA and IC did not affect the total number of lever contacts in sign-trackers, this manipulation increased the latency to approach the lever. Ipsilateral inactivation of BLA and IC did not impact approach behaviors in Pavlovian lever autoshaping. These findings, contrary to our hypothesis, suggest that communication between BLA and IC maintains a representation of initially learned appetitive associations that commonly support the initiation of Pavlovian conditioned approach behavior regardless of whether it is directed at the cue or the location of reward delivery. Copyright © 2017 Elsevier Inc. All rights reserved.

Digital atlas of fetal brain MRI.

PubMed

Chapman, Teresa; Matesan, Manuela; Weinberger, Ed; Bulas, Dorothy I

2010-02-01

Fetal MRI can be performed in the second and third trimesters. During this time, the fetal brain undergoes profound structural changes. Interpretation of appropriate development might require comparison with normal age-based models. Consultation of a hard-copy atlas is limited by the inability to compare multiple ages simultaneously. To provide images of normal fetal brains from weeks 18 through 37 in a digital format that can be reviewed interactively. This will facilitate recognition of abnormal brain development. T2-W images for the atlas were obtained from fetal MR studies of normal brains scanned for other indications from 2005 to 2007. Images were oriented in standard axial, coronal and sagittal projections, with laterality established by situs. Gestational age was determined by last menstrual period, earliest US measurements and sonogram performed on the same day as the MR. The software program used for viewing the atlas, written in C#, permits linked scrolling and resizing the images. Simultaneous comparison of varying gestational ages is permissible. Fetal brain images across gestational ages 18 to 37 weeks are provided as an interactive digital atlas and are available for free download from http://radiology.seattlechildrens.org/teaching/fetal_brain . Improved interpretation of fetal brain abnormalities can be facilitated by the use of digital atlas cataloging of the normal changes throughout fetal development. Here we provide a description of the atlas and a discussion of normal fetal brain development.

Choosing the appropriate side for subcutaneous port catheter placement in patients with mastectomy: ipsilateral or contralateral?

PubMed

Nas, Omer Fatih; Hacikurt, Kadir; Kaya, Ahmet; Dogan, Nurullah; Sanal, Bekir; Ozkaya, Guven; Dundar, Halit Ziya; Erdogan, Cuneyt

2017-06-01

To evaluate long-term clinical follow-up results of implanting subcutaneous port catheters (SPCs) on ipsilateral or contralateral with mastectomy side in patients with axillary lymph node dissection. A total of 73 patients composed of ipsilateral (34 catheters) and contralateral (39 catheters) groups, with SPCs were included. All patients had lumpectomy or modified radical mastectomy for breast cancer. Ipsilateral and contralateral groups had similar patient characteristics. Five late complications were seen in the ipsilateral group and 2 late complications in the contralateral group. No statistical significant difference was seen between two groups in regard to late complications. Four complications of the ipsilateral group were classified as major group C and 1 as major group D, while 1 complication of the contralateral group was classified as minor group B and 1 as major group C according to Society of Interventional Radiology (SIR) classification. No statistical significant difference was seen between complication rates of two groups in regard to SIR classification. SPC related complications do not differ in regard to ipsilateral or contralateral side selection on mastectomized patients with breast cancer and lymph node dissection. SPCs can be implanted on ipsilateral or contralateral sides of the operation in these patients.