Brain cholinesterase activity of apparently normal wild birds

USGS Publications Warehouse

Hill, E.F.

1988-01-01

Organophosphorus and carbamate pesticides are potent anticholinesterase substances that have killed large numbers of wild birds of various species. Cause of death is diagnosed by demonstration of depressed brain cholinesterase (ChE) activity in combination with chemical detection of anticholinesterase residue in the affected specimen. ChE depression is determined by comparison of the affected specimen to normal ChE activity for a sample of control specimens of the same species, but timely procurement of controls is not always possible. Therefore, a reference file of normal whole brain ChE activity is provided for 48 species of wild birds from North America representing 11 orders and 23 families for use as emergency substitutes in diagnosis of anticholinesterase poisoning. The ChE values, based on 83 sets of wild control specimens from across the United States, are reproducible provided the described procedures are duplicated. Overall, whole brain ChE activity varied nearly three-fold among the 48 species represented, but it was usually similar for closely related species. However, some species were statistically separable in most families and some species of the same genus differed as much as 50%.

X-ray diffraction evidence for myelin disorder in brain from humans with Alzheimer's disease.

PubMed

Chia, L S; Thompson, J E; Moscarello, M A

1984-09-05

Wide-angle X-ray diffraction studies revealed that the lipid phase transition temperature of myelin from brain tissue of humans with Alzheimer's disease was about 12 degrees C lower than that of normal age-matched controls, indicating differences in the physical organization of the myelin lipid bilayer. Elevated levels of malondialdehyde and conjugated diene were found in brain tissue from humans with Alzheimer's disease, indicating an increased amount of lipid peroxidation over the controls. An increase in myelin disorder and in lipid peroxidation can both be correlated with aging in human brain, but the changes in myelin from humans with Alzheimer's disease are more pronounced than in normal aging. These changes might represent severe or accelerated aging.

Terahertz spectroscopy of brain tissue from a mouse model of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Shi, Lingyan; Shumyatsky, Pavel; Rodríguez-Contreras, Adrián; Alfano, Robert

2016-01-01

The terahertz (THz) absorption and index of refraction of brain tissues from a mouse model of Alzheimer's disease (AD) and a control wild-type (normal) mouse were compared using THz time-domain spectroscopy (THz-TDS). Three dominating absorption peaks associated to torsional-vibrational modes were observed in AD tissue, at about 1.44, 1.8, and 2.114 THz, closer to the peaks of free tryptophan molecules than in normal tissue. A possible reason is that there is more free tryptophan in AD brain tissue, while in normal brain tissue more tryptophan is attached to other molecules. Our study suggests that THz-absorption modes may be used as an AD biomarker fingerprint in brain, and that THz-TDS is a promising technique for early diagnosis of AD.

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.

Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure

PubMed Central

Treit, Sarah; Zhou, Dongming; Chudley, Albert E.; Andrew, Gail; Rasmussen, Carmen; Nikkel, Sarah M.; Samdup, Dawa; Hanlon-Dearman, Ana; Loock, Christine; Beaulieu, Christian

2016-01-01

Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5–19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol exposure, but raise concerns about the predictive value of this metric at an individual-subject level. PMID:26928125

Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure.

PubMed

Treit, Sarah; Zhou, Dongming; Chudley, Albert E; Andrew, Gail; Rasmussen, Carmen; Nikkel, Sarah M; Samdup, Dawa; Hanlon-Dearman, Ana; Loock, Christine; Beaulieu, Christian

2016-01-01

Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5-19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol exposure, but raise concerns about the predictive value of this metric at an individual-subject level.

Role of 5-hydroxytryptamine in the regulation of brain neuropeptides in normal and diabetic rat

NASA Technical Reports Server (NTRS)

Kolta, Malak G.; Williams, Byron B.; Soliman, Karam F. A.

1986-01-01

The effect of 5-hydroxytryptamine (5-HT) alteration on brain dopamine (DA), norepinephrine (NE), beta-endorphin (beta-E), and immunoreactive insulin was studied in Sprague-Dawley diabetic and control rats. Diabetes was induced using alloxan (45 mg/kg), 15 days prior to sacrificing. Both control and diabetic animals were treated with either p-chlorophenylalanine (PCPA, 300 mg/kg) three days prior to sacrificing or fluoxetine (10 mg/kg) twice daily for three days. PCPA treatment significantly decreased brain content of 5-HT and 5-hydroxyindolel acetic acid, while it caused significant increase and decrease in brain beta-E and insulin levels, respectively, in both normal and diabetic rat. Meanwhile, the administration of fluoxetine resulted in significant increase in brain content of 5-HT, DA, NE and insulin but significant decline of beta-E in diabetic and saline control rats. The results of this experiment indicate that 5-HT may be regulating both beta-E and insulin regardless of the availability of pancreatic insulin.

Photodynamic therapy: a review of applications in neurooncology and neuropathology

NASA Astrophysics Data System (ADS)

Uzdensky, Anatoly B.; Berezhnaya, Elena; Kovaleva, Vera; Neginskaya, Marya; Rudkovskii, Mikhail; Sharifulina, Svetlana

2015-06-01

Photodynamic therapy (PDT) effect is a promising adjuvant modality for diagnosis and treatment of brain cancer. It is of importance that the bright fluorescence of most photosensitizers provides visualization of brain tumors. This is successfully used for fluorescence-guided tumor resection according to the principle "to see and to treat." Non-oncologic application of PDT effect for induction of photothrombotic infarct of the brain tissue is a well-controlled and reproducible stroke model, in which a local brain lesion is produced in the predetermined brain area. Since normal neurons and glial cells may also be damaged by PDT and this can lead to unwanted neurological consequences, PDT effects on normal neurons and glial cells should be comprehensively studied. We overviewed the current literature data on the PDT effect on a range of signaling and epigenetic proteins that control various cell functions, survival, necrosis, and apoptosis. We hypothesize that using cell-specific inhibitors or activators of some signaling proteins, one can selectively protect normal neurons and glia, and simultaneously exacerbate photodynamic damage of malignant gliomas.

Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome.

PubMed

Abu-Judeh, H H; Levine, S; Kumar, M; el-Zeftawy, H; Naddaf, S; Lou, J Q; Abdel-Dayem, H M

1998-11-01

Chronic fatigue syndrome is a clinically defined condition of uncertain aetiology. We compared 99Tcm-HMPAO single photon emission tomography (SPET) brain perfusion with dual-head 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Eighteen patients (14 females, 4 males), who fulfilled the diagnostic criteria of the Centers for Disease Control for chronic fatigue syndrome, were investigated. Thirteen patients had abnormal SPET brain perfusion scans and five had normal scans. Fifteen patients had normal glucose brain metabolism scans and three had abnormal scans. We conclude that, in chronic fatigue syndrome patients, there is discordance between SPET brain perfusion and 18F-FDG brain uptake. It is possible to have brain perfusion abnormalities without corresponding changes in glucose uptake.

The iconic memory skills of brain injury survivors and non-brain injured controls after visual scanning training.

PubMed

McClure, J T; Browning, R T; Vantrease, C M; Bittle, S T

1994-01-01

Previous research suggests that traumatic brain injury (TBI) results in impairment of iconic memory abilities.We would like to acknowledge the contribution of Jeffrey D. Vantrease, who wrote the software program for the Iconic Memory procedure and measurement. This raises serious implications for brain injury rehabilitation. Most cognitive rehabilitation programs do not include iconic memory training. Instead it is common for cognitive rehabilitation programs to focus on attention and concentration skills, memory skills, and visual scanning skills.This study compared the iconic memory skills of brain-injury survivors and control subjects who all reached criterion levels of visual scanning skills. This involved previous training for the brain-injury survivors using popular visual scanning programs that allowed them to visually scan with response time and accuracy within normal limits. Control subjects required only minimal training to reach normal limits criteria. This comparison allows for the dissociation of visual scanning skills and iconic memory skills.The results are discussed in terms of their implications for cognitive rehabilitation and the relationship between visual scanning training and iconic memory skills.

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.

Patterns of brain structural connectivity differentiate normal weight from overweight subjects

PubMed Central

Gupta, Arpana; Mayer, Emeran A.; Sanmiguel, Claudia P.; Van Horn, John D.; Woodworth, Davis; Ellingson, Benjamin M.; Fling, Connor; Love, Aubrey; Tillisch, Kirsten; Labus, Jennifer S.

2015-01-01

Background Alterations in the hedonic component of ingestive behaviors have been implicated as a possible risk factor in the pathophysiology of overweight and obese individuals. Neuroimaging evidence from individuals with increasing body mass index suggests structural, functional, and neurochemical alterations in the extended reward network and associated networks. Aim To apply a multivariate pattern analysis to distinguish normal weight and overweight subjects based on gray and white-matter measurements. Methods Structural images (N = 120, overweight N = 63) and diffusion tensor images (DTI) (N = 60, overweight N = 30) were obtained from healthy control subjects. For the total sample the mean age for the overweight group (females = 32, males = 31) was 28.77 years (SD = 9.76) and for the normal weight group (females = 32, males = 25) was 27.13 years (SD = 9.62). Regional segmentation and parcellation of the brain images was performed using Freesurfer. Deterministic tractography was performed to measure the normalized fiber density between regions. A multivariate pattern analysis approach was used to examine whether brain measures can distinguish overweight from normal weight individuals. Results 1. White-matter classification: The classification algorithm, based on 2 signatures with 17 regional connections, achieved 97% accuracy in discriminating overweight individuals from normal weight individuals. For both brain signatures, greater connectivity as indexed by increased fiber density was observed in overweight compared to normal weight between the reward network regions and regions of the executive control, emotional arousal, and somatosensory networks. In contrast, the opposite pattern (decreased fiber density) was found between ventromedial prefrontal cortex and the anterior insula, and between thalamus and executive control network regions. 2. Gray-matter classification: The classification algorithm, based on 2 signatures with 42 morphological features, achieved 69% accuracy in discriminating overweight from normal weight. In both brain signatures regions of the reward, salience, executive control and emotional arousal networks were associated with lower morphological values in overweight individuals compared to normal weight individuals, while the opposite pattern was seen for regions of the somatosensory network. Conclusions 1. An increased BMI (i.e., overweight subjects) is associated with distinct changes in gray-matter and fiber density of the brain. 2. Classification algorithms based on white-matter connectivity involving regions of the reward and associated networks can identify specific targets for mechanistic studies and future drug development aimed at abnormal ingestive behavior and in overweight/obesity. PMID:25737959

Convergence, Degeneracy, and Control

ERIC Educational Resources Information Center

Green, David W.; Crinion, Jenny; Price, Cathy J.

2006-01-01

Understanding the neural representation and control of language in normal bilingual speakers provides insights into the factors that constrain the acquisition of another language, insights into the nature of language expertise, and an understanding of the brain as an adaptive system. We illustrate both functional and structural brain changes…

Benefits of Docosahexaenoic Acid, Folic Acid, Vitamin D and Iodine on Foetal and Infant Brain Development and Function Following Maternal Supplementation during Pregnancy and Lactation

PubMed Central

Morse, Nancy L.

2012-01-01

Scientific literature is increasingly reporting on dietary deficiencies in many populations of some nutrients critical for foetal and infant brain development and function. Purpose: To highlight the potential benefits of maternal supplementation with docosahexaenoic acid (DHA) and other important complimentary nutrients, including vitamin D, folic acid and iodine during pregnancy and/or breast feeding for foetal and/or infant brain development and/or function. Methods: English language systematic reviews, meta-analyses, randomised controlled trials, cohort studies, cross-sectional and case-control studies were obtained through searches on MEDLINE and the Cochrane Register of Controlled Trials from January 2000 through to February 2012 and reference lists of retrieved articles. Reports were selected if they included benefits and harms of maternal supplementation of DHA, vitamin D, folic acid or iodine supplementation during pregnancy and/or lactation. Results: Maternal DHA intake during pregnancy and/or lactation can prolong high risk pregnancies, increase birth weight, head circumference and birth length, and can enhance visual acuity, hand and eye co-ordination, attention, problem solving and information processing. Vitamin D helps maintain pregnancy and promotes normal skeletal and brain development. Folic acid is necessary for normal foetal spine, brain and skull development. Iodine is essential for thyroid hormone production necessary for normal brain and nervous system development during gestation that impacts childhood function. Conclusion: Maternal supplementation within recommended safe intakes in populations with dietary deficiencies may prevent many brain and central nervous system malfunctions and even enhance brain development and function in their offspring. PMID:22852064

Disruptions of brain structural network in end-stage renal disease patients with long-term hemodialysis and normal-appearing brain tissues.

PubMed

Chou, Ming-Chung; Ko, Chih-Hung; Chang, Jer-Ming; Hsieh, Tsyh-Jyi

2018-05-04

End-stage renal disease (ESRD) patients on hemodialysis were demonstrated to exhibit silent and invisible white-matter alterations which would likely lead to disruptions of brain structural networks. Therefore, the purpose of this study was to investigate the disruptions of brain structural network in ESRD patients. Thiry-three ESRD patients with normal-appearing brain tissues and 29 age- and gender-matched healthy controls were enrolled in this study and underwent both cognitive ability screening instrument (CASI) assessment and diffusion tensor imaging (DTI) acquisition. Brain structural connectivity network was constructed using probabilistic tractography with automatic anatomical labeling template. Graph-theory analysis was performed to detect the alterations of node-strength, node-degree, node-local efficiency, and node-clustering coefficient in ESRD patients. Correlational analysis was performed to understand the relationship between network measures, CASI score, and dialysis duration. Structural connectivity, node-strength, node-degree, and node-local efficiency were significantly decreased, whereas node-clustering coefficient was significantly increased in ESRD patients as compared with healthy controls. The disrupted local structural networks were generally associated with common neurological complications of ESRD patients, but the correlational analysis did not reveal significant correlation between network measures, CASI score, and dialysis duration. Graph-theory analysis was helpful to investigate disruptions of brain structural network in ESRD patients with normal-appearing brain tissues. Copyright © 2018. Published by Elsevier Masson SAS.

A PML/Slit Axis Controls Physiological Cell Migration and Cancer Invasion in the CNS.

PubMed

Amodeo, Valeria; A, Deli; Betts, Joanne; Bartesaghi, Stefano; Zhang, Ying; Richard-Londt, Angela; Ellis, Matthew; Roshani, Rozita; Vouri, Mikaella; Galavotti, Sara; Oberndorfer, Sarah; Leite, Ana Paula; Mackay, Alan; Lampada, Aikaterini; Stratford, Eva Wessel; Li, Ningning; Dinsdale, David; Grimwade, David; Jones, Chris; Nicotera, Pierluigi; Michod, David; Brandner, Sebastian; Salomoni, Paolo

2017-07-11

Cell migration through the brain parenchyma underpins neurogenesis and glioblastoma (GBM) development. Since GBM cells and neuroblasts use the same migratory routes, mechanisms underlying migration during neurogenesis and brain cancer pathogenesis may be similar. Here, we identify a common pathway controlling cell migration in normal and neoplastic cells in the CNS. The nuclear scaffold protein promyelocytic leukemia (PML), a regulator of forebrain development, promotes neural progenitor/stem cell (NPC) and neuroblast migration in the adult mouse brain. The PML pro-migratory role is active also in transformed mouse NPCs and in human primary GBM cells. In both normal and neoplastic settings, PML controls cell migration via Polycomb repressive complex 2 (PRC2)-mediated repression of Slits, key regulators of axon guidance. Finally, a PML/SLIT1 axis regulates sensitivity to the PML-targeting drug arsenic trioxide in primary GBM cells. Taken together, these findings uncover a drug-targetable molecular axis controlling cell migration in both normal and neoplastic cells. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Regional CBF in chronic stable TBI treated with hyperbaric oxygen.

PubMed

Barrett, K F; Masel, B; Patterson, J; Scheibel, R S; Corson, K P; Mader, J T

2004-01-01

To investigate whether Hyperbaric Oxygen Therapy (HBO2) could improve neurologic deficits and regional cerebral blood flow (rCBF) in chronic traumatic brain injuries (TBI), the authors employed a nonrandomized control pilot trial. Five subjects, at least three years post head injury, received HBO2. Five head injured controls (HIC) were matched for age, sex, and type of injury. Five healthy subjects served as normal controls. Sixty-eight normal volunteers comprised a reference data bank against which to compare SPECT brain scans. HBO2 subjects received 120 HBO2 in blocks of 80 and 40 treatments with an interval five-month break. Normal controls underwent a single SPECT brain scan, HBO2, and repeat SPECT battery. TBI subjects were evaluated by neurologic, neuropsychometric, exercise testing, and pre and post study MRIs, or CT scans if MRI was contraindicated. Statistical Parametric Mapping was applied to SPECT scans for rCBF analysis. There were no significant objective changes in neurologic, neuropsychometric, exercise testing, MRIs, or rCBF. In this small pilot study, HBO2 did not effect clinical or regional cerebral blood flow improvement in TBI subjects.

Use of EPO as an adjuvant in PDT of brain tumors to reduce damage to normal brain

NASA Astrophysics Data System (ADS)

Rendon, Cesar A.; Lilge, Lothar

2004-10-01

In order to reduce damage to surrounding normal brain in the treatment of brain tumors with photodynamic therapy (PDT), we have investigated the use of the cytokine erythropoietin (EPO) to exploit its well-established role as a neuroprotective agent. In vitro experiments demonstrated that EPO does not confer protection from PDT to rat glioma cells. In vivo testing of the possibility of EPO protecting normal brain tissue was carried out. The normal brains of Lewis rats were treated with Photofrin mediated PDT (6.25 mg/Kg B.W. 22 hours pre irradiation) and the outcome of the treatment compared between animals that received EPO (5000 U/Kg B.W. 22 hours pre irradiation) and controls. This comparison was made based on the volume of necrosis, as measured with the viability stain 2,3,5- Triphenyl tetrazoium chloride (TTC), and incidence of apoptosis, as measured with in situ end labeling assay (ISEL). Western blotting showed that EPO reaches the normal brain and activates the anti-apoptotic protein PKB/AKT1 within the brain cortex. The comparison based on volume of necrosis showed no statistical significance between the two groups. No clear difference was observed in the ISEL staining between the groups. A possible lack of responsivity in the assays that give rise to these results is discussed and future corrections are described.

Functional brain response to food images in successful adolescent weight losers compared with normal-weight and overweight controls.

PubMed

Jensen, Chad D; Kirwan, C Brock

2015-03-01

Research conducted with adults suggests that successful weight losers demonstrate greater activation in brain regions associated with executive control in response to viewing high-energy foods. No previous studies have examined these associations in adolescents. Functional neuroimaging was used to assess brain response to food images among groups of overweight (OW), normal-weight (NW), and successful weight-losing (SWL) adolescents. Eleven SWL, 12 NW, and 11 OW participants underwent functional magnetic resonance imaging while viewing images of high- and low-energy foods. When viewing high-energy food images, SWLs demonstrated greater activation in the dorsolateral prefrontal cortex (DLPFC) compared with OW and NW controls. Compared with NW and SWL groups, OW individuals demonstrated greater activation in the ventral striatum and anterior cingulate in response to food images. Adolescent SWLs demonstrated greater neural activation in the DLPFC compared with OW/NW controls when viewing high-energy food stimuli, which may indicate enhanced executive control. OW individuals' brain responses to food stimuli may indicate greater reward incentive processes than either SWL or NW groups. © 2015 The Obesity Society.

Interhemispheric and Intrahemispheric Control of Emotion: A Focus on Unilateral Brain Damage.

ERIC Educational Resources Information Center

Borod, Joan C.

1992-01-01

Discusses neocortical contributions to emotional processing. Examines parameters critical to neuropsychological study of emotion: interhemispheric and intrahemispheric factors, processing mode, and communication channel. Describes neuropsychological theories of emotion. Reviews studies of right-brain-damaged, left-brain-damaged, and normal adults,…

C145 as a short-latency electrophysiological index of cognitive compensation in Alzheimer's disease

PubMed Central

Chapman, Robert M.; Porsteinsson, Anton P.; Gardner, Margaret N.; Mapstone, Mark; McCrary, John W.; Sandoval, Tiffany C.; Guillily, Maria D.; DeGrush, Elizabeth; Reilly, Lindsey A.

2012-01-01

Brain plasticity and cognitive compensation in the elderly are of increasing interest, and Alzheimer's disease (AD) offers an opportunity to elucidate how the brain may overcome damage. We provide neurophysiological evidence of a short-latency ERP component (C145) linked to stimulus relevancy that may reflect cognitive compensation in early-stage Alzheimer's disease (AD). Thirty-six subjects with early-stage, mild AD and 36 like-aged normal elderly (Controls) had their EEG recorded while performing our Number-Letter task, a cognitive/perceptual paradigm that manipulates stimulus relevancies. ERP components, including C145, were extracted from ERPs using Principal Components Analysis. C145 amplitudes and spatial distributions were compared among Controls, AD subjects with high performance on the Number-Letter task, and AD subjects with low performance. Compared to AD subjects, Control subjects showed enhanced C145 processing of visual stimuli in the occipital region where differential processing of relevant stimuli occurred. AD high performers recruited central brain areas in processing task relevancy. Controls and AD low performers did not show a significant task relevancy effect in these areas. We conclude that short-latency ERP components can detect electrophysiological differences in early-stage AD that reflect altered cognition. Differences in C145 amplitudes between AD and normal elderly groups regarding brain locations and types of task effects suggest compensatory mechanisms can occur in the AD brain to overcome loss of normal functionality, and this early compensation may have a profound effect on the cognitive efficiency of AD individuals. PMID:22886016

Lateralization of Egocentric and Allocentric Spatial Processing after Parietal Brain Lesions

ERIC Educational Resources Information Center

Iachini, Tina; Ruggiero, Gennaro; Conson, Massimiliano; Trojano, Luigi

2009-01-01

The purpose of this paper was to verify whether left and right parietal brain lesions may selectively impair egocentric and allocentric processing of spatial information in near/far spaces. Two Right-Brain-Damaged (RBD), 2 Left-Brain-Damaged (LBD) patients (not affected by neglect or language disturbances) and eight normal controls were submitted…

Investment behavior and the negative side of emotion.

PubMed

Shiv, Baba; Loewenstein, George; Bechara, Antoine; Damasio, Hanna; Damasio, Antonio R

2005-06-01

Can dysfunction in neural systems subserving emotion lead, under certain circumstances, to more advantageous decisions? To answer this question, we investigated how normal participants, patients with stable focal lesions in brain regions related to emotion (target patients), and patients with stable focal lesions in brain regions unrelated to emotion (control patients) made 20 rounds of investment decisions. Target patients made more advantageous decisions and ultimately earned more money from their investments than the normal participants and control patients. When normal participants and control patients either won or lost money on an investment round, they adopted a conservative strategy and became more reluctant to invest on the subsequent round; these results suggest that they were more affected than target patients by the outcomes of decisions made in the previous rounds.

[Study of dopamine transporter imaging on the brain of children with autism].

PubMed

Sun, Xiaomian; Yue, Jing; Zheng, Chongxun

2008-04-01

This study was conducted to evaluate the applicability of 99mTc-2beta-[ N, N'-bis (2-mercaptoethyl) ethylenediamino]methyl,3beta(4-chlorophenyl)tropane(TRODAT-1) dopamine transporter(DAT) SPECT imaging in children with autism, and thus to provide an academic basis for the etiology, mechanism and clinical therapy of autism. Ten autistic children and ten healthy controls were examined with 99mTc-TRODAT-1 DAT SPECT imaging. Striatal specific uptake of 99mTc-TRODAT-1 was calculated with region of interest analysis according to the ratics between striatum and cerebellum [(STR-BKG)/BKG]. There was no statistically significant difference in semiquantitative dopamine transporter between the bilateral striata of autistic children (P=0.562), and between those of normal controls (p=0.573); Dopamine transporter in the brain of patients with autism increased significantly as compared with that in the brain of normal controls (P=0.017). Dopaminergic nervous system is dysfunctioning in the brain of children with autism, and DAT 99mTc-TRODAT-1 SPECT imaging on the brain will help the imaging diagnosis of childhcod autism.

FMRI Brain Activation in a Finnish Family with Specific Language Impairment Compared with a Normal Control Group

ERIC Educational Resources Information Center

Hugdahl, Kenneth; Gundersen, Hilde; Brekke, Cecilie; Thomsen, Tormod; Rimol, Lars Morten; Ersland, Lars; Niemi, Jussi

2004-01-01

The aim of the present study was to investigate differences in brain activation in a family with SLI as compared to intact individuals with normally developed language during processing of language stimuli. Functional magnetic resonance imaging (fMRI) was used to monitor changes in neuronal activation in temporal and frontal lobe areas in 5…

Magnetic Resonance Elastography Demonstrates Increased Brain Stiffness in Normal Pressure Hydrocephalus

PubMed Central

N, Fattahi; A, Arani; A, Perry; F, Meyer; A, Manduca; K, Glaser; ML, Senjem; RL, Ehman; J, Huston

2015-01-01

Introduction Normal pressure hydrocephalus (NPH) is a reversible neurologic disorder characterized by a triad of cognitive impairment, gait abnormality and urinary incontinence that is commonly treated with ventriculoperitoneal shunt placement. However, there are multiple overlapping symptoms which often make it difficult to differentiate NPH from other types of dementia and improved diagnostic techniques would help patient management. MR elastography (MRE) is a novel diagnostic tool that could potentially identify patients with NPH. The purpose of this study was to assess brain stiffness changes in NPH patients compared with age- and sex-matched cognitively normal individuals. Methods MRE was performed on 10 NPH patients and 21 age- and sex-matched volunteers with no known neurologic disorders. Image acquisition was conducted on a 3T MRI scanner. Shear waves with 60Hz vibration frequency were transmitted into the brain by a pillow-like passive driver. A novel postprocessing technique resistant to noise and edge artifacts was implemented to determine regional brain stiffness. The Wilcoxon rank sum test and linear regression were used for statistical analysis. Results A significant increase in stiffness was observed in the cerebrum (p = 0.001), occipital lobe (p = 0.0002), parietal lobe (p= 0.001), and the temporal lobe (p = 0.02) in the NPH group compared with normal controls. However, no significant difference was noted in other regions of the brain including the frontal lobe (p = 0.07), deep gray and white matter (p = 0.43), or the cerebellum (p = 0.20). Conclusion This study demonstrates increased brain stiffness in NPH patients compared to age- and sex-matched normal controls which motivates future studies investigating the use of MRE for NPH diagnosis and efficacy of shunt therapy. PMID:26542235

Back to the future: estimating pre-injury brain volume in patients with traumatic brain injury.

PubMed

Ross, David E; Ochs, Alfred L; D Zannoni, Megan; Seabaugh, Jan M

2014-11-15

A recent meta-analysis by Hedman et al. allows for accurate estimation of brain volume changes throughout the life span. Additionally, Tate et al. showed that intracranial volume at a later point in life can be used to estimate reliably brain volume at an earlier point in life. These advancements were combined to create a model which allowed the estimation of brain volume just prior to injury in a group of patients with mild or moderate traumatic brain injury (TBI). This volume estimation model was used in combination with actual measurements of brain volume to test hypotheses about progressive brain volume changes in the patients. Twenty six patients with mild or moderate TBI were compared to 20 normal control subjects. NeuroQuant® was used to measure brain MRI volume. Brain volume after the injury (from MRI scans performed at t1 and t2) was compared to brain volume just before the injury (volume estimation at t0) using longitudinal designs. Groups were compared with respect to volume changes in whole brain parenchyma (WBP) and its 3 major subdivisions: cortical gray matter (GM), cerebral white matter (CWM) and subcortical nuclei+infratentorial regions (SCN+IFT). Using the normal control data, the volume estimation model was tested by comparing measured brain volume to estimated brain volume; reliability ranged from good to excellent. During the initial phase after injury (t0-t1), the TBI patients had abnormally rapid atrophy of WBP and CWM, and abnormally rapid enlargement of SCN+IFT. Rates of volume change during t0-t1 correlated with cross-sectional measures of volume change at t1, supporting the internal reliability of the volume estimation model. A logistic regression analysis using the volume change data produced a function which perfectly predicted group membership (TBI patients vs. normal control subjects). During the first few months after injury, patients with mild or moderate TBI have rapid atrophy of WBP and CWM, and rapid enlargement of SCN+IFT. The magnitude and pattern of the changes in volume may allow for the eventual development of diagnostic tools based on the volume estimation approach. Copyright © 2014 Elsevier Inc. All rights reserved.

Control of hepatic glucose metabolism by islet and brain.

PubMed

Rojas, J M; Schwartz, M W

2014-09-01

Dysregulation of hepatic glucose uptake (HGU) and inability of insulin to suppress hepatic glucose production (HGP) contribute to hyperglycaemia in patients with type 2 diabetes (T2D). Growing evidence suggests that insulin can inhibit HGP not only through a direct effect on the liver but also through a mechanism involving the brain. Yet, the notion that insulin action in the brain plays a physiological role in the control of HGP continues to be controversial. Although studies in dogs suggest that the direct hepatic effect of insulin is sufficient to explain day-to-day control of HGP, a surprising outcome has been revealed by recent studies in mice, investigating whether the direct hepatic action of insulin is necessary for normal HGP: when the hepatic insulin signalling pathway was genetically disrupted, HGP was maintained normally even in the absence of direct input from insulin. Here, we present evidence that points to a potentially important role of the brain in the physiological control of both HGU and HGP in response to input from insulin as well as other hormones and nutrients. © 2014 John Wiley & Sons Ltd.

Functional brain development in growth-restricted and constitutionally small fetuses: a fetal magnetoencephalography case-control study.

PubMed

Morin, E C; Schleger, F; Preissl, H; Braendle, J; Eswaran, H; Abele, H; Brucker, S; Kiefer-Schmidt, I

2015-08-01

Fetal magnetoencephalography records fetal brain activity non-invasively. Delayed brain responses were reported for fetuses weighing below the tenth percentile. To investigate whether this delay indicates delayed brain maturation resulting from placental insufficiency, this study distinguished two groups of fetuses below the tenth percentile: growth-restricted fetuses with abnormal umbilical artery Doppler velocity (IUGR) and constitutionally small-for-gestational-age fetuses with normal umbilical artery Doppler findings (SGA) were compared with fetuses of adequate weight for gestational age (AGA), matched for age and behavioural state. A case-control study of matched pairs. Fetal magnetoencephalography-Center at the University Hospital of Tuebingen. Fourteen IUGR fetuses and 23 SGA fetuses were matched for gestational age and fetal behavioural state with 37 healthy, normal-sized fetuses. A 156-channel fetal magentoencephalography system was used to record fetal brain activity. Light flashes as visual stimulation were applied to the fetus. The Student's t-test for paired groups was performed. Latency of fetal visual evoked magnetic responses (VER). The IUGR fetuses showed delayed VERs compared with controls (IUGR, 233.1 ms; controls, 184.6 ms; P = 0.032). SGA fetuses had similar evoked response latencies compared with controls (SGA, 216.1 ms; controls, 219.9 ms; P = 0.828). Behavioural states were similarly distributed. Visual evoked responses are delayed in IUGR fetuses, but not in SGA. Fetal behavioural state as an influencing factor of brain response latency was accounted for in the comparison. This reinforces that delayed brain maturation is the result of placental insufficiency. © 2015 Royal College of Obstetricians and Gynaecologists.

Protective effects of melatonin against 12C6+ beam irradiation-induced oxidative stress and DNA injury in the mouse brain

NASA Astrophysics Data System (ADS)

Wu, Z. H.; Zhang, H.; Wang, X. Y.; Yang, R.; Liu, B.; Liu, Y.; Zhao, W. P.; Feng, H. Y.; Xue, L. G.; Hao, J. F.; Niu, B. T.; Wang, Z. H.

2012-01-01

The purpose of this experiment was to estimate the protective effects of melatonin against radiation-induced brain damages in mice induced by heavy ion beams. Kun-Ming mice were randomly divided into five groups: normal control group, irradiation control group, and three different doses of melatonin (5, 10, and 20 mg/kg, i.p.) treated groups. Apart from the normal control group, the other four groups were exposed to whole-body 4.0 Gy carbon ion beam irradiation (approximately 0.5 Gy/min) after i.p. administration of normal saline or melatonin 1 h before irradiation. The oxidative redox status of brain tissue was assessed by measurement of malondiadehyde (MDA) levels, total superoxide dismutase (T-SOD), cytosolic superoxide dismutase (Cu/ZnSOD, SOD1) and mitochondrial superoxide dismutase (MnSOD, SOD2) activities at 8 h after irradiation. DNA damages were determined using the Comet assay and apoptosis and cell cycle distribution were detected by flow cytometric analyses. A dramatic dose-dependent decrease in MDA levels, tail moment, rates of tailing cells, and apoptosis, and a dose-dependent increase in T-SOD and SOD2 activities, in brain tissues in the melatonin-treated groups were detected compared with the irradiation only group. Furthermore, flow cytometric analysis demonstrated that the percentage of brain cells in the G0/G1 phase decreased significantly, while those in the S and G2/M stage increased dramatically, with mice pretreated with melatonin compared to the irradiation control group. These data indicate that melatonin has protective effects against irradiation-induced brain injury, and that its underlying protective mechanisms may relate to modulation of oxidative stress induced by heavy ionirradiation.

Cranial irradiation increases tumor growth in experimental breast cancer brain metastasis.

PubMed

Hamilton, Amanda M; Wong, Suzanne M; Wong, Eugene; Foster, Paula J

2018-05-01

Whole-brain radiotherapy is the standard of care for patients with breast cancer with multiple brain metastases and, although this treatment has been essential in the management of existing brain tumors, there are many known negative consequences associated with the irradiation of normal brain tissue. In our study, we used in vivo magnetic resonance imaging analysis to investigate the influence of radiotherapy-induced damage of healthy brain on the arrest and growth of metastatic breast cancer cells in a mouse model of breast cancer brain metastasis. We observed that irradiated, but otherwise healthy, neural tissue had an increased propensity to support metastatic growth compared with never-irradiated controls. The elucidation of the impact of irradiation on normal neural tissue could have implications in clinical patient management, particularly in patients with residual systemic disease or with residual radio-resistant brain cancer. Copyright © 2018 John Wiley & Sons, Ltd.

Development of a cerebral circulation model for the automatic control of brain physiology.

PubMed

Utsuki, T

2015-01-01

In various clinical guidelines of brain injury, intracranial pressure (ICP), cerebral blood flow (CBF) and brain temperature (BT) are essential targets for precise management for brain resuscitation. In addition, the integrated automatic control of BT, ICP, and CBF is required for improving therapeutic effects and reducing medical costs and staff burden. Thus, a new model of cerebral circulation was developed in this study for integrative automatic control. With this model, the CBF and cerebral perfusion pressure of a normal adult male were regionally calculated according to cerebrovascular structure, blood viscosity, blood distribution, CBF autoregulation, and ICP. The analysis results were consistent with physiological knowledge already obtained with conventional studies. Therefore, the developed model is potentially available for the integrative control of the physiological state of the brain as a reference model of an automatic control system, or as a controlled object in various control simulations.

Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease.

PubMed

Kanoto, Masafumi; Hosoya, Takaaki; Toyoguchi, Yuuki; Oda, Atsuko

2013-01-01

Chronic progressive neuro-Behçet's disease (CPNBD) resembles multiple sclerosis (MS) on patient background and image findings, and therefore is difficult to diagnose. The purpose is to identify the characteristic magnetic resonance imaging (MRI) findings of CPNBD and to clarify the differences between the MRI findings of CPNBD and those of MS. The subjects consist of a CPNBD group (n=4; 1 male and 3 females; mean age, 51 y.o.), a MS group (n=19; 3 males and 16 females; mean age, 45 y.o.) and a normal control group (n=23; 10 males and 13 females; mean age, 45 y.o.). Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were retrospectively evaluated in each subjects. In middle sagittal brain MR images, the prepontine distance was measured as an indirect index of brain stem and cerebellar atrophy and the pontine and mesencephalic distance was measured as a direct index of brain stem atrophy. These indexes were statistically analyzed. Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were seen in all CPNBD cases. Prepontine distance was significantly different between the CPNBD group and the MS group (p<0.05), and between the CPNBD group and the normal control group (p<0.001). Pontine and mesencephalic distance were significantly different between the CPNBD group and the MS group (p<0.001, p<0.01 respectively), and between the CPNBD group and the normal control group (p<0.001). Chronic progressive neuro-Behçet's disease should be considered in patients with brain stem and cerebellar atrophy in addition to leukoencephalopathy similar to that seen in multiple sclerosis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Normalization of aberrant resting state functional connectivity in fibromyalgia patients following a three month physical exercise therapy

PubMed Central

Flodin, P.; Martinsen, S.; Mannerkorpi, K.; Löfgren, M.; Bileviciute-Ljungar, I.; Kosek, E.; Fransson, P.

2015-01-01

Physical exercise is one of the most efficient interventions to mitigate chronic pain symptoms in fibromyalgia (FM). However, little is known about the neurophysiological mechanisms mediating these effects. In this study we investigated resting-state connectivity using functional magnetic resonance imaging (fMRI) before and after a 15 week standardized exercise program supervised by physical therapists. Our aim was to gain an understanding of how physical exercise influences previously shown aberrant patterns of intrinsic brain activity in FM. Fourteen FM patients and eleven healthy controls successfully completed the physical exercise treatment. We investigated post- versus pre-treatment changes of brain connectivity, as well as changes in clinical symptoms in the patient group. FM patients reported improvements in symptom severity. Although several brain regions showed a treatment-related change in connectivity, only the connectivity between the right anterior insula and the left primary sensorimotor area was significantly more affected by the physical exercise among the fibromyalgia patients compared to healthy controls. Our results suggest that previously observed aberrant intrinsic brain connectivity patterns in FM are partly normalized by the physical exercise therapy. However, none of the observed normalizations in intrinsic brain connectivity were significantly correlated with symptom changes. Further studies conducted in larger cohorts are warranted to investigate the precise relationship between improvements in fibromyalgia symptoms and changes in intrinsic brain activity. PMID:26413476

Normalization of aberrant resting state functional connectivity in fibromyalgia patients following a three month physical exercise therapy.

PubMed

Flodin, P; Martinsen, S; Mannerkorpi, K; Löfgren, M; Bileviciute-Ljungar, I; Kosek, E; Fransson, P

2015-01-01

Physical exercise is one of the most efficient interventions to mitigate chronic pain symptoms in fibromyalgia (FM). However, little is known about the neurophysiological mechanisms mediating these effects. In this study we investigated resting-state connectivity using functional magnetic resonance imaging (fMRI) before and after a 15 week standardized exercise program supervised by physical therapists. Our aim was to gain an understanding of how physical exercise influences previously shown aberrant patterns of intrinsic brain activity in FM. Fourteen FM patients and eleven healthy controls successfully completed the physical exercise treatment. We investigated post- versus pre-treatment changes of brain connectivity, as well as changes in clinical symptoms in the patient group. FM patients reported improvements in symptom severity. Although several brain regions showed a treatment-related change in connectivity, only the connectivity between the right anterior insula and the left primary sensorimotor area was significantly more affected by the physical exercise among the fibromyalgia patients compared to healthy controls. Our results suggest that previously observed aberrant intrinsic brain connectivity patterns in FM are partly normalized by the physical exercise therapy. However, none of the observed normalizations in intrinsic brain connectivity were significantly correlated with symptom changes. Further studies conducted in larger cohorts are warranted to investigate the precise relationship between improvements in fibromyalgia symptoms and changes in intrinsic brain activity.

Multimodality Instrument for Tissue Characterization

NASA Technical Reports Server (NTRS)

Mah, Robert W. (Inventor); Andrews, Russell J. (Inventor)

2000-01-01

A system with multimodality instrument for tissue identification includes a computer-controlled motor driven heuristic probe with a multisensory tip is discussed. For neurosurgical applications, the instrument is mounted on a stereotactic frame for the probe to penetrate the brain in a precisely controlled fashion. The resistance of the brain tissue being penetrated is continually monitored by a miniaturized strain gauge attached to the probe tip. Other modality sensors may be mounted near the probe tip to provide real-time tissue characterizations and the ability to detect the proximity of blood vessels, thus eliminating errors normally associated with registration of pre-operative scans, tissue swelling, elastic tissue deformation, human judgement, etc., and rendering surgical procedures safer, more accurate, and efficient. A neural network, program adaptively learns the information on resistance and other characteristic features of normal brain tissue during the surgery and provides near real-time modeling. A fuzzy logic interface to the neural network program incorporates expert medical knowledge in the learning process. Identification of abnormal brain tissue is determined by the detection of change and comparison with previously learned models of abnormal brain tissues. The operation of the instrument is controlled through a user friendly graphical interface. Patient data is presented in a 3D stereographics display. Acoustic feedback of selected information may optionally be provided. Upon detection of the close proximity to blood vessels or abnormal brain tissue, the computer-controlled motor immediately stops probe penetration.

Correlation between 99Tcm-HMPAO-SPECT brain image and a history of decompression illness or extent of diving experience in commercial divers.

PubMed Central

Shields, T G; Duff, P M; Evans, S A; Gemmell, H G; Sharp, P F; Smith, F W; Staff, R T; Wilcock, S E

1997-01-01

OBJECTIVES: To explore the use of 99technetiumm-hexamethyl propylene amine oxime single photon computed tomography (HMPAO-SPECT) of the brain as a means of detecting nervous tissue damage in divers and to determine if there is any correlation between brain image and a diver's history of diving or decompression illness (DCI). METHODS: 28 commercial divers with a history of DCI, 26 divers with no history of DCI, and 19 non-diving controls were examined with brain HMPAO-SPECT. Results were classified by observer assessment as normal (I) or as a pattern variants (II-V). The brain images of a subgroup of these divers (n = 44) and the controls (n = 17) were further analysed with a first order texture analysis technique based on a grey level histogram. RESULTS: 15 of 54 commercial divers (28%) were visually assessed as having HMPAO-SPECT images outside normal limits compared with 15.8% in appropriately identified non-diver control subjects. 18% of divers with a history of DCI were classified as having a pattern different from the normal image compared with 38% with no history of DCI. No association was established between the presence of a pattern variant from the normal image and history of DCI, diving, or other previous possible neurological insult. On texture analysis of the brain images, divers had a significantly lower mean grey level (MGL) than non-divers. Divers with a history of DCI (n = 22) had a significantly lower MGL when compared with divers with no history of DCI (n = 22). Divers with > 14 years professional diving or > 100 decompression days a year had a significantly lower MGL value. CONCLUSIONS: Observer assessment of HMPAO-SPECT brain images can lead to disparity in results. Texture analysis of the brain images supplies both an objective and consistent method of measurement. A significant correlation was found between a low measure of MGL and a history of DCI. There was also an indication that diving itself had an effect on texture measurement, implying that it had caused subclinical nervous tissue damage. PMID:9166130

Integrin suppresses neurogenesis and regulates brain tissue assembly in planarian regeneration.

PubMed

Bonar, Nicolle A; Petersen, Christian P

2017-03-01

Animals capable of adult regeneration require specific signaling to control injury-induced cell proliferation, specification and patterning, but comparatively little is known about how the regeneration blastema assembles differentiating cells into well-structured functional tissues. Using the planarian Schmidtea mediterranea as a model, we identify β1-integrin as a crucial regulator of blastema architecture. β1-integrin(RNAi) animals formed small head blastemas with severe tissue disorganization, including ectopic neural spheroids containing differentiated neurons normally found in distinct organs. By mimicking aspects of normal brain architecture but without normal cell-type regionalization, these spheroids bore a resemblance to mammalian tissue organoids synthesized in vitro We identified one of four planarian integrin-alpha subunits inhibition of which phenocopied these effects, suggesting that a specific receptor controls brain organization through regeneration. Neoblast stem cells and progenitor cells were mislocalized in β1-integrin(RNAi) animals without significantly altered body-wide patterning. Furthermore, tissue disorganization phenotypes were most pronounced in animals undergoing brain regeneration and not homeostatic maintenance or regeneration-induced remodeling of the brain. These results suggest that integrin signaling ensures proper progenitor recruitment after injury, enabling the generation of large-scale tissue organization within the regeneration blastema. © 2017. Published by The Company of Biologists Ltd.

William's syndrome: gene expression is related to parental origin and regional coordinate control

PubMed Central

Collette, Jeremy C; Chen, Xiao-Ning; Mills, Debra L; Galaburda, Albert M; Reiss, Allan L; Bellugi, Ursula; Korenberg, Julie R

2013-01-01

William's syndrome (WS) features a spectrum of neurocognitive and behavioral abnormalities due to a rare 1.5MB deletion that includes about 24–28 genes on chromosome band 7q11.23. Study of the expression of these genes from the single normal copy provides an opportunity to elucidate the genetic and epigenetic controls on these genes as well as their roles in both WS and normal brain development and function. We used quantitative RT-PCR to determine the transcriptional level of 14 WS gene markers in a cohort of 77 persons with WS and 48 normal controls. Results reported here: (1) show that the expression of the genes deleted in WS is decreased in some but not all cases, (2) demonstrate that the parental origin of the deletion contributes to the level of expression of GTF2I independently of age and gender and (3) indicate that the correlation of expression between GTF2I and some other genes in the WS region differs in WS subjects and normal controls, which in turn points toward a regulatory role for this gene. Interspecies comparisons suggest GTF2I may play a key role in normal brain development. PMID:19282872

Brain injury following trial of hypothermia for neonatal hypoxic–ischaemic encephalopathy

PubMed Central

Shankaran, Seetha; Barnes, Patrick D; Hintz, Susan R; Laptook, Abbott R; Zaterka-Baxter, Kristin M; McDonald, Scott A; Ehrenkranz, Richard A; Walsh, Michele C; Tyson, Jon E; Donovan, Edward F; Goldberg, Ronald N; Bara, Rebecca; Das, Abhik; Finer, Neil N; Sanchez, Pablo J; Poindexter, Brenda B; Van Meurs, Krisa P; Carlo, Waldemar A; Stoll, Barbara J; Duara, Shahnaz; Guillet, Ronnie; Higgins, Rosemary D

2013-01-01

Objective The objective of our study was to examine the relationship between brain injury and outcome following neonatal hypoxic–ischaemic encephalopathy treated with hypothermia. Design and patients Neonatal MRI scans were evaluated in the National Institute of Child Health and Human Development (NICHD) randomised controlled trial of whole-body hypothermia and each infant was categorised based upon the pattern of brain injury on the MRI findings. Brain injury patterns were assessed as a marker of death or disability at 18–22 months of age. Results Scans were obtained on 136 of 208 trial participants (65%); 73 in the hypothermia and 63 in the control group. Normal scans were noted in 38 of 73 infants (52%) in the hypothermia group and 22 of 63 infants (35%) in the control group. Infants in the hypothermia group had fewer areas of infarction (12%) compared to infants in the control group (22%). Fifty-one of the 136 infants died or had moderate or severe disability at 18 months. The brain injury pattern correlated with outcome of death or disability and with disability among survivors. Each point increase in the severity of the pattern of brain injury was independently associated with a twofold increase in the odds of death or disability. Conclusions Fewer areas of infarction and a trend towards more normal scans were noted in brain MRI following whole-body hypothermia. Presence of the NICHD pattern of brain injury is a marker of death or moderate or severe disability at 18–22 months following hypothermia for neonatal encephalopathy. PMID:23080477

A computed tomography-based spatial normalization for the analysis of [18F] fluorodeoxyglucose positron emission tomography of the brain.

PubMed

Cho, Hanna; Kim, Jin Su; Choi, Jae Yong; Ryu, Young Hoon; Lyoo, Chul Hyoung

2014-01-01

We developed a new computed tomography (CT)-based spatial normalization method and CT template to demonstrate its usefulness in spatial normalization of positron emission tomography (PET) images with [(18)F] fluorodeoxyglucose (FDG) PET studies in healthy controls. Seventy healthy controls underwent brain CT scan (120 KeV, 180 mAs, and 3 mm of thickness) and [(18)F] FDG PET scans using a PET/CT scanner. T1-weighted magnetic resonance (MR) images were acquired for all subjects. By averaging skull-stripped and spatially-normalized MR and CT images, we created skull-stripped MR and CT templates for spatial normalization. The skull-stripped MR and CT images were spatially normalized to each structural template. PET images were spatially normalized by applying spatial transformation parameters to normalize skull-stripped MR and CT images. A conventional perfusion PET template was used for PET-based spatial normalization. Regional standardized uptake values (SUV) measured by overlaying the template volume of interest (VOI) were compared to those measured with FreeSurfer-generated VOI (FSVOI). All three spatial normalization methods underestimated regional SUV values by 0.3-20% compared to those measured with FSVOI. The CT-based method showed slightly greater underestimation bias. Regional SUV values derived from all three spatial normalization methods were correlated significantly (p < 0.0001) with those measured with FSVOI. CT-based spatial normalization may be an alternative method for structure-based spatial normalization of [(18)F] FDG PET when MR imaging is unavailable. Therefore, it is useful for PET/CT studies with various radiotracers whose uptake is expected to be limited to specific brain regions or highly variable within study population.

Brain structural correlates of reward sensitivity and impulsivity in adolescents with normal and excess weight.

PubMed

Moreno-López, Laura; Soriano-Mas, Carles; Delgado-Rico, Elena; Rio-Valle, Jacqueline S; Verdejo-García, Antonio

2012-01-01

Neuroscience evidence suggests that adolescent obesity is linked to brain dysfunctions associated with enhanced reward and somatosensory processing and reduced impulse control during food processing. Comparatively less is known about the role of more stable brain structural measures and their link to personality traits and neuropsychological factors on the presentation of adolescent obesity. Here we aimed to investigate regional brain anatomy in adolescents with excess weight vs. lean controls. We also aimed to contrast the associations between brain structure and personality and cognitive measures in both groups. Fifty-two adolescents (16 with normal weight and 36 with excess weight) were scanned using magnetic resonance imaging and completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), the UPPS-P scale, and the Stroop task. Voxel-based morphometry (VBM) was used to assess possible between-group differences in regional gray matter (GM) and to measure the putative differences in the way reward and punishment sensitivity, impulsivity and inhibitory control relate to regional GM volumes, which were analyzed using both region of interest (ROI) and whole brain analyses. The ROIs included areas involved in reward/somatosensory processing (striatum, somatosensory cortices) and motivation/impulse control (hippocampus, prefrontal cortex). Excess weight adolescents showed increased GM volume in the right hippocampus. Voxel-wise volumes of the second somatosensory cortex (SII) were correlated with reward sensitivity and positive urgency in lean controls, but this association was missed in excess weight adolescents. Moreover, Stroop performance correlated with dorsolateral prefrontal cortex volumes in controls but not in excess weight adolescents. Adolescents with excess weight have structural abnormalities in brain regions associated with somatosensory processing and motivation.

Increased Steady-State Mutant Huntingtin mRNA in Huntington's Disease Brain.

PubMed

Liu, Wanzhao; Chaurette, Joanna; Pfister, Edith L; Kennington, Lori A; Chase, Kathryn O; Bullock, Jocelyn; Vonsattel, Jean Paul G; Faull, Richard L M; Macdonald, Douglas; DiFiglia, Marian; Zamore, Phillip D; Aronin, Neil

2013-01-01

Huntington's disease is caused by expansion of CAG trinucleotide repeats in the first exon of the huntingtin gene, which is essential for both development and neurogenesis. Huntington's disease is autosomal dominant. The normal allele contains 6 to 35 CAG triplets (average, 18) and the mutant, disease-causing allele contains >36 CAG triplets (average, 42). We examined 279 postmortem brain samples, including 148 HD and 131 non-HD controls. A total of 108 samples from 87 HD patients that are heterozygous at SNP rs362307, with a normal allele (18 to 27 CAG repeats) and a mutant allele (39 to 73 CAG repeats) were used to measure relative abundance of mutant and wild-type huntingtin mRNA. We used allele-specific, quantitative RT-PCR based on SNP heterozygosity to estimate the relative amount of mutant versus normal huntingtin mRNA in postmortem brain samples from patients with Huntington's disease. In the cortex and striatum, the amount of mRNA from the mutant allele exceeds that from the normal allele in 75% of patients. In the cerebellum, no significant difference between the two alleles was evident. Brain tissues from non-HD controls show no significant difference between two alleles of huntingtin mRNAs. Allelic differences were more pronounced at early neuropathological grades (grades 1 and 2) than at late grades (grades 3 and 4). More mutant HTT than normal could arise from increased transcription of mutant HTT allele, or decreased clearance of mutant HTT mRNA, or both. An implication is that equimolar silencing of both alleles would increase the mutant HTT to normal HTT ratio.

Cross-entropy optimization for neuromodulation.

PubMed

Brar, Harleen K; Yunpeng Pan; Mahmoudi, Babak; Theodorou, Evangelos A

2016-08-01

This study presents a reinforcement learning approach for the optimization of the proportional-integral gains of the feedback controller represented in a computational model of epilepsy. The chaotic oscillator model provides a feedback control systems view of the dynamics of an epileptic brain with an internal feedback controller representative of the natural seizure suppression mechanism within the brain circuitry. Normal and pathological brain activity is simulated in this model by adjusting the feedback gain values of the internal controller. With insufficient gains, the internal controller cannot provide enough feedback to the brain dynamics causing an increase in correlation between different brain sites. This increase in synchronization results in the destabilization of the brain dynamics, which is representative of an epileptic seizure. To provide compensation for an insufficient internal controller an external controller is designed using proportional-integral feedback control strategy. A cross-entropy optimization algorithm is applied to the chaotic oscillator network model to learn the optimal feedback gains for the external controller instead of hand-tuning the gains to provide sufficient control to the pathological brain and prevent seizure generation. The correlation between the dynamics of neural activity within different brain sites is calculated for experimental data to show similar dynamics of epileptic neural activity as simulated by the network of chaotic oscillators.

Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients.

PubMed

Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

2016-01-01

Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM.

Bladder control, urgency, and urge incontinence: evidence from functional brain imaging.

PubMed

Griffiths, Derek; Tadic, Stasa D

2008-01-01

To review brain imaging studies of bladder control in subjects with normal control and urge incontinence; to define a simple model of supraspinal bladder control; and to propose a neural correlate of urgency and possible origins of urge incontinence. Review of published reports of brain imaging relevant to urine storage, and secondary analyses of our own recent observations. In a simple model of normal urine storage, bladder and urethral afferents received in the periaqueductal gray (PAG) are mapped in the insula, forming the basis of sensation; the anterior cingulate gyrus (ACG) provides monitoring and control; the prefrontal cortex makes voiding decisions. The net result, as the bladder fills, is inhibition of the pontine micturition center (PMC) and of voiding, together with gradual increase in insular response, corresponding to increasing desire to void. In urge-incontinent subjects, brain responses differ. At large bladder volumes and strong sensation, but without detrusor overactivity (DO), most cortical responses become exaggerated, especially in ACG. This may be both a learned reaction to previous incontinence episodes and the neural correlate of urgency. The neural signature of DO itself seems to be prefrontal deactivation. Possible causes of urge incontinence include dysfunction of prefrontal cortex or limbic system, suggested by weak responses and/or deactivation, as well as abnormal afferent signals or re-emergence of infantile reflexes. Bladder control depends on an extensive network of brain regions. Dysfunction in various parts may contribute to urge incontinence, suggesting that there are different phenotypes requiring different treatments. (c) 2007 Wiley-Liss, Inc.

Normalizing motor-related brain activity: subthalamic nucleus stimulation in Parkinson disease.

PubMed

Grafton, S T; Turner, R S; Desmurget, M; Bakay, R; Delong, M; Vitek, J; Crutcher, M

2006-04-25

To test whether therapeutic unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson disease (PD) leads to normalization in the pattern of brain activation during movement execution and control of movement extent. Six patients with PD were imaged off medication by PET during performance of a visually guided tracking task with the DBS voltage programmed for therapeutic (effective) or subtherapeutic (ineffective) stimulation. Data from patients with PD during ineffective stimulation were compared with a group of 13 age-matched control subjects to identify sites with abnormal patterns of activation. Conjunction analysis was used to identify those areas in patients with PD where activity normalized when they were treated with effective stimulation. For movement execution, effective DBS caused an increase of activation in the supplementary motor area (SMA), superior parietal cortex, and cerebellum toward a more normal pattern. At rest, effective stimulation reduced overactivity of SMA. Therapeutic stimulation also induced reductions of movement related "overactivity" compared with healthy subjects in prefrontal, temporal lobe, and basal ganglia circuits, consistent with the notion that many areas are recruited to compensate for ineffective motor initiation. Normalization of activity related to the control of movement extent was associated with reductions of activity in primary motor cortex, SMA, and basal ganglia. Effective subthalamic nucleus stimulation leads to task-specific modifications with appropriate recruitment of motor areas as well as widespread, nonspecific reductions of compensatory or competing cortical activity.

Alterations in Sociability and Functional Brain Connectivity Caused by Early-Life Seizures is Reversed by Bumetanide

PubMed Central

Holmes, Gregory L.; Tian, Chengju; Hernan, Amanda E.; Flynn, Sean; Camp, Devon; Barry, Jeremy

2015-01-01

There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced seizures from postnatal (P) day 5-14 and then tested, along with controls, for developmental alterations of development brain oscillatory activity from P18-25. Specifically we wished to understand how normal changes in rhythmicity in and between brain regions change as a function of age and if this rhythmicity is altered or interrupted by early life seizures. In rat pups with early-life seizures, field recordings from dorsal and ventral hippocampus and prefrontal cortex demonstrated marked increase in coherence as well as a decrease in voltage correlation at all bandwidths compared to controls while there were minimal differences in total power and relative power spectral densities. Rats with early-life seizures had resulting impairment in the sociability and social novelty tests but demonstrated no evidence of increased activity or generalized anxiety as measured in the open field. In addition, rats with early-life seizures had lower seizure thresholds than controls, indicating long-standing alterations in the excitatory/inhibition balance. Bumetanide, a pharmacological agent that blocks the activity of NKCC1 and induces a significant shift of ECl toward more hyperpolarized values, administration at the time of the seizures precluded the subsequent abnormalities in coherence and voltage correlation and resulted in normal sociability and seizure threshold. Taken together these findings indicate that early-life seizures alter the development of oscillations and result in autistic-like behaviors. The altered communication between these brain regions could reflect the physiological underpinnings underlying social cognitive deficits seen in autism spectrum disorders. PMID:25766676

Onset of multiple sclerosis before adulthood leads to failure of age-expected brain growth

PubMed Central

Aubert-Broche, Bérengère; Fonov, Vladimir; Narayanan, Sridar; Arnold, Douglas L.; Araujo, David; Fetco, Dumitru; Till, Christine; Sled, John G.; Collins, D. Louis

2014-01-01

Objective: To determine the impact of pediatric-onset multiple sclerosis (MS) on age-expected brain growth. Methods: Whole brain and regional volumes of 36 patients with relapsing-remitting MS onset prior to 18 years of age were segmented in 185 longitudinal MRI scans (2–11 scans per participant, 3-month to 2-year scan intervals). MRI scans of 25 age- and sex-matched healthy normal controls (NC) were also acquired at baseline and 2 years later on the same scanner as the MS group. A total of 874 scans from 339 participants from the NIH-funded MRI study of normal brain development acquired at 2-year intervals were used as an age-expected healthy growth reference. All data were analyzed with an automatic image processing pipeline to estimate the volume of brain and brain substructures. Mixed-effect models were built using age, sex, and group as fixed effects. Results: Significant group and age interactions were found with the adjusted models fitting brain volumes and normalized thalamus volumes (p < 10−4). These findings indicate a failure of age-normative brain growth for the MS group, and an even greater failure of thalamic growth. In patients with MS, T2 lesion volume correlated with a greater reduction in age-expected thalamic volume. To exclude any scanner-related influence on our data, we confirmed no significant interaction of group in the adjusted models between the NC and NIH MRI Study of Normal Brain Development groups. Conclusions: Our results provide evidence that the onset of MS during childhood and adolescence limits age-expected primary brain growth and leads to subsequent brain atrophy, implicating an early onset of the neurodegenerative aspect of MS. PMID:25378667

Brain Microstructural Correlates of Cognitive Dysfunction in Clinically and Biochemically Normal Hepatitis C Virus Infection.

PubMed

Kumar, Ajay; Deep, Amar; Gupta, Rakesh K; Atam, Virendra; Mohindra, Samir

2017-09-01

This study examined correlates of the brain's neurocognitive performance among clinically and biochemically normal adult patient with hepatitis C virus (HCV). We hypothesized that anti-HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using diffusion tensor tractrography (DTT) metrics. Anti-HCV positive patient ( n  = 40), and healthy controls ( n  = 31), fulfilling inclusion criteria (incidentally detected anti-HCV positive) and able to provide informed consent were screened and recruited for the study. All these subjects and controls underwent subjective assessment of their quality of life related symptoms, neuropsychometric tests (NPT) and magnetic resonance imaging. The patients were subjected to neuroimaging as well as psychological testing. There was no significant difference in basic laboratory parameters in these two groups. Independent t -test reveals significantly lower neuropsychological functioning as compared to healthy control. A significantly decreased FA values and myoinsitol were observed in HCV subjects on sensory, inferior longitudinal fascicules, and STR fiber bundles as compared to healthy control. Bivariate correlation analysis reveals that neuropsychological scores are significantly positive. Our result show that HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using DTT metrics.

Physiological Correlates of Intellectual Function in Children with Sickle Cell Disease: Hypoxaemia, Hyperaemia and Brain Infarction

ERIC Educational Resources Information Center

Hogan, Alexandra M.; Pit-ten Cate, Ineke M.; Vargha-Khadem, Faraneh; Prengler, Mara; Kirkham, Fenella J.

2006-01-01

Lowered intelligence relative to controls is evident by mid-childhood in children with sickle cell disease. There is consensus that brain infarct contributes to this deficit, but the subtle lowering of IQ in children with normal MRI scans might be accounted for by chronic systemic complications leading to insufficient oxygen delivery to the brain.…

Processing of Basic Speech Acts Following Localized Brain Damage: A New Light on the Neuroanatomy of Language

ERIC Educational Resources Information Center

Soroker, N.; Kasher, A.; Giora, R.; Batori, G.; Corn, C.; Gil, M.; Zaidel, E.

2005-01-01

We examined the effect of localized brain lesions on processing of the basic speech acts (BSAs) of question, assertion, request, and command. Both left and right cerebral damage produced significant deficits relative to normal controls, and left brain damaged patients performed worse than patients with right-sided lesions. This finding argues…

Early embryonic brain development in rats requires the trophic influence of cerebrospinal fluid.

PubMed

Martin, C; Alonso, M I; Santiago, C; Moro, J A; De la Mano, A; Carretero, R; Gato, A

2009-11-01

Cerebrospinal fluid has shown itself to be an essential brain component during development. This is particularly evident at the earliest stages of development where a lot of research, performed mainly in chick embryos, supports the evidence that cerebrospinal fluid is involved in different mechanisms controlling brain growth and morphogenesis, by exerting a trophic effect on neuroepithelial precursor cells (NPC) involved in controlling the behaviour of these cells. Despite it being known that cerebrospinal fluid in mammals is directly involved in corticogenesis at fetal stages, the influence of cerebrospinal fluid on the activity of NPC at the earliest stages of brain development has not been demonstrated. Here, using "in vitro" organotypic cultures of rat embryo brain neuroepithelium in order to expose NPC to or deprive them of cerebrospinal fluid, we show that the neuroepithelium needs the trophic influence of cerebrospinal fluid to undergo normal rates of cell survival, replication and neurogenesis, suggesting that NPC are not self-sufficient to induce their normal activity. This data shows that cerebrospinal fluid is an essential component in chick and rat early brain development, suggesting that its influence could be constant in higher vertebrates.

WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions

NASA Astrophysics Data System (ADS)

Lee, Kendall H.; Lujan, J. Luis; Trevathan, James K.; Ross, Erika K.; Bartoletta, John J.; Park, Hyung Ook; Paek, Seungleal Brian; Nicolai, Evan N.; Lee, Jannifer H.; Min, Hoon-Ki; Kimble, Christopher J.; Blaha, Charles D.; Bennet, Kevin E.

2017-04-01

There has been significant progress in understanding the role of neurotransmitters in normal and pathologic brain function. However, preclinical trials aimed at improving therapeutic interventions do not take advantage of real-time in vivo neurochemical changes in dynamic brain processes such as disease progression and response to pharmacologic, cognitive, behavioral, and neuromodulation therapies. This is due in part to a lack of flexible research tools that allow in vivo measurement of the dynamic changes in brain chemistry. Here, we present a research platform, WINCS Harmoni, which can measure in vivo neurochemical activity simultaneously across multiple anatomical targets to study normal and pathologic brain function. In addition, WINCS Harmoni can provide real-time neurochemical feedback for closed-loop control of neurochemical levels via its synchronized stimulation and neurochemical sensing capabilities. We demonstrate these and other key features of this platform in non-human primate, swine, and rodent models of deep brain stimulation (DBS). Ultimately, systems like the one described here will improve our understanding of the dynamics of brain physiology in the context of neurologic disease and therapeutic interventions, which may lead to the development of precision medicine and personalized therapies for optimal therapeutic efficacy.

Towards hyperpolarized 13C-succinate imaging of brain cancer

PubMed Central

Bhattacharya, Pratip; Chekmenev, Eduard Y.; Perman, William H.; Harris, Kent C.; Lin, Alexander P.; Norton, Valerie A.; Tan, Chou T.; Ross, Brian D.; Weitekamp, Daniel P.

2009-01-01

We describe a novel 13C enriched precursor molecule, sodium 1-13C acetylenedicarboxylate, which after hydrogenation by PASADE-NA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized 13C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized 13C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized 13C sodium succinate, contained significant concentrations of the injected substrate, 13C sodium succinate, together with 13C maleate and succinate metabolites 1-13C-glutamate, 5-13C-glutamate, 1-13C-glutamine and 5-13C-glutamine. The 13C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood–brain barrier. These ex vivo results indicate that hyperpolarized 13C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in 13C MR spectral-spatial images. PMID:17303454

Towards hyperpolarized 13C-succinate imaging of brain cancer

NASA Astrophysics Data System (ADS)

Bhattacharya, Pratip; Chekmenev, Eduard Y.; Perman, William H.; Harris, Kent C.; Lin, Alexander P.; Norton, Valerie A.; Tan, Chou T.; Ross, Brian D.; Weitekamp, Daniel P.

2007-05-01

We describe a novel 13C enriched precursor molecule, sodium 1- 13C acetylenedicarboxylate, which after hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized 13C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized 13C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized 13C sodium succinate, contained significant concentrations of the injected substrate, 13C sodium succinate, together with 13C maleate and succinate metabolites 1- 13C-glutamate, 5- 13C-glutamate, 1- 13C-glutamine and 5- 13C-glutamine. The 13C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood-brain barrier. These ex vivo results indicate that hyperpolarized 13C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in 13C MR spectral-spatial images.

[Effects of N-butylphthalide on the expressions of ZO-1 and claudin-5 in blood-brain barrier of rats with acute carbon monoxide poisoning].

PubMed

Wang, Li; Ding, Xiaoyu; Bi, Mingjun; Wang, Jinglin; Zou, Yong; Tang, Jiyou; Li, Qin

2018-05-01

To explore the effects of N-butylphthalide on the expressions of ZO-1 and claudin-5 in blood-brain barrier (BBB) in rats with acute carbon monoxide (CO) poisoning. A total of 144 adult healthy male Sprague-Dawley (SD) rats were randomly divided into normal control group, CO poisoning group, and NBP treatment group, with 48 rats in each group. The acute CO poisoning model was reproduced in hyperbaric oxygen chamber, and all model rats were given hyperbaric oxygen therapy once daily. The rats in the normal control group were free to breathe fresh air. The rats in NBP treatment group were administered orally NBP 60 mg/kg twice a day at 2 hours after poisoning until death. The rats in normal control group and CO poisoning group were treated with equal amount of pure olive oil. Four rats were sacrificed from each group at 1, 3, 7, 14 days after model reproducing, respectively. The changes in ultrastructure of BBB were observed under transmission electron microscope. The expressions of ZO-1 and claudin-5 proteins were determined by immunofluorescence staining and Western Blot. The localization of the two target proteins was observed by immunofluorescence double staining. The correlation between the two proteins was analyzed by linear regression. The ultrastructure of BBB was normal in normal control group, some ZO-1 and a large number of claudin-5 positive cells were observed. The ultrastructure of BBB was seriously injured, ZO-1 and claudin-5 positive cells in brain tissue were significantly decreased, and the expressions of ZO-1 and claudin-5 proteins in brain tissue at 1 day after poisoning in CO poisoning group were significantly lower than those of normal control group (ZO-1 protein: 3.38±0.30 vs. 24.50±5.62, claudin-5 protein: 11.38±0.93 vs. 46.35±6.88, both P < 0.05), and although gradually restored, they were maintained at relatively lower levels until 14 days as compared with those in normal control group (ZO-1 protein: 10.35±0.80 vs. 24.63±3.57, claudin-5 protein: 32.35±3.11 vs. 46.43±7.20, both P < 0.05). NBP treatment could significantly alleviate the ultrastructure injury of BBB induced by acute CO poisoning, the amount of ZO-1 and claudin-5 positive cells in brain tissue were significantly increased, as well as the expressions of ZO-1 and claudin-5 proteins were significantly increased, which were significantly higher than those of CO poisoning group from 1 day and 3 days on, respectively (1-day ZO-1 protein: 7.57±0.69 vs. 3.38±0.30, 3-day claudin-5 protein: 20.46±1.42 vs. 11.43±0.86, both P < 0.05), and which showed an increase tendency with time prolongation. The results of immunofluorescence double staining showed that ZO-1 and claudin-5 proteins could not only coexist in the same cell, but also could be expressed separately in different cells. Linear regression analysis showed the positive correlation between the expressions of ZO-1 and claudin-5 proteins in brain tissue of rats with acute CO poisoning (R 2 = 0.917, P = 0.022). NBP could markedly improve the ultrastructure and functional integrity of BBB through up-regulating the expressions of ZO-1 and claudin-5 proteins, and then reduce brain damage caused by CO poisoning.

Default, Cognitive and Affective Brain Networks in Human Tinnitus

DTIC Science & Technology

Tinnitus is a major health problem among those currently and formerly in military service. This project hypothesizes that many of the clinically...significant, non-auditory aspects of the tinnitus condition involve two major brain networks: the cognitive control network (CCN) and the default mode...function can be assessed. Subjects in three groups are being compared: (1) control subjects with clinically-normal hearing thresholds and no tinnitus

Physiology and molecular biology of barrier mechanisms in the fetal and neonatal brain.

PubMed

Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld; Habgood, Mark D

2018-05-17

Properties of the local internal environment of the adult brain are tightly controlled providing a stable milieu essential for its normal function. The mechanisms involved in this complex control are structural, molecular and physiological (influx and efflux transporters) frequently referred to as the "blood-brain barrier". These mechanisms include regulation of ion levels in brain interstitial fluid essential for normal neuronal function, supply of nutrients, removal of metabolic products and prevention of entry or elimination of toxic agents. A key feature is cerebrospinal fluid secretion and turnover. This is much less during development, allowing greater accumulation of permeating molecules. The overall effect of these mechanisms is to tightly control the exchange of molecules into and out of the brain. This review presents experimental evidence currently available on the status of these mechanisms in developing brain. It has been frequently stated for over nearly a century that the blood-brain barrier is not present or at least is functionally deficient in the embryo, fetus and newborn. We suggest the alternative hypothesis that the barrier mechanisms in developing brain are likely to be appropriately matched to each stage of its development. The contributions of different barrier mechanisms, such as changes in constituents of cerebrospinal fluid in relation to specific features of brain development, for example neurogenesis, are only beginning to be studied. The evidence on this previously neglected aspect of brain barrier function is outlined. We also suggest future directions this field could follow with special emphasis on potential applications in a clinical setting. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Posterior brain in fetuses with open spina bifida at 11 to 13 weeks.

PubMed

Lachmann, Robert; Chaoui, Rabih; Moratalla, Jose; Picciarelli, Gemma; Nicolaides, Kypros H

2011-01-01

To measure the changes in the posterior fossa in first-trimester fetuses with open spina bifida (OSB). The brain stem diameter and brain stem to occipital bone (BSOB) diameter were measured in stored images of the mid-sagittal view of the fetal face at 11(+0) to 13(+6) weeks from 30 fetuses with OSB and 1000 normal controls. In the control group, the brain stem and BSOB diameter increased significantly with crown-rump length (CRL) and the brain stem to BSOB ratio decreased. In the spina bifida group, the brain stem diameter was above the 95th percentile of the control group in 29 (96.7%) cases, the BSOB diameter was below the 5th percentile in 26 (86.7%) and the brain stem to BSOB ratio was above the 95th percentile in all cases. At 11 to 13 weeks the majority of fetuses with OSB have measurable abnormalities in the posterior brain.

Immunopathological Changes in the Brain of Immunosuppressed Mice Experimentally Infected with Toxocara canis

PubMed Central

Eid, Mohamed M.; El-Kowrany, Samy I.; Othman, Ahmad A.; Gendy, Dina I. El; Saied, Eman M.

2015-01-01

Toxocariasis is a soil-transmitted helminthozoonosis due to infection of humans by larvae of Toxocara canis. The disease could produce cognitive and behavioral disturbances especially in children. Meanwhile, in our modern era, the incidence of immunosuppression has been progressively increasing due to increased incidence of malignancy as well as increased use of immunosuppressive agents. The present study aimed at comparing some of the pathological and immunological alterations in the brain of normal and immunosuppressed mice experimentally infected with T. canis. Therefore, 180 Swiss albino mice were divided into 4 groups including normal (control) group, immunocompetent T. canis-infected group, immunosuppressed group (control), and immunosuppressed infected group. Infected mice were subjected to larval counts in the brain, and the brains from all mice were assessed for histopathological changes, astrogliosis, and IL-5 mRNA expression levels in brain tissues. The results showed that under immunosuppression, there were significant increase in brain larval counts, significant enhancement of reactive gliosis, and significant reduction in IL-5 mRNA expression. All these changes were maximal in the chronic stage of infection. In conclusion, the immunopathological alterations in the brains of infected animals were progressive over time, and were exaggerated under the effect of immunosuppression as did the intensity of cerebral infection. PMID:25748709

Brain surface contraction mapped in first-episode schizophrenia: a longitudinal magnetic resonance imaging study

PubMed Central

Sun, D; Stuart, GW; Jenkinson, M; Wood, SJ; McGorry, PD; Velakoulis, D; van Erp, TGM; Thompson, PM; Toga, AW; Smith, DJ; Cannon, TD; Pantelis, C

2009-01-01

Schizophrenia is associated with structural brain abnormalities, but the timing of onset and course of these changes remains unclear. Longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive brain volume decreases in patients around and after the onset of illness, although considerable discrepancies exist regarding which brain regions are affected. The anatomical pattern of these progressive changes in schizophrenia is largely unknown. In this study, MRI scans were acquired repeatedly from 16 schizophrenia patients approximately 2 years apart following their first episode of illness, and also from 14 age-matched healthy subjects. Cortical Pattern Matching, in combination with Structural Image Evaluation, using Normalisation, of Atrophy, was applied to compare the rates of cortical surface contraction between patients and controls. Surface contraction in the dorsal surfaces of the frontal lobe was significantly greater in patients with first-episode schizophrenia (FESZ) compared with healthy controls. Overall, brain surface contraction in patients and healthy controls showed similar anatomical patterns, with that of the former group exaggerated in magnitude across the entire brain surface. That the pattern of structural change in the early course of schizophrenia corresponds so closely to that associated with normal development is consistent with the hypothesis that a schizophrenia-related factor interacts with normal adolescent brain developmental processes in the pathophysiology of schizophrenia. The exaggerated progressive changes seen in patients with schizophrenia may reflect an increased rate of synaptic pruning, resulting in excessive loss of neuronal connectivity, as predicted by the late neurodevelopmental hypothesis of the illness. PMID:18607377

Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?

PubMed

Nugent, S; Castellano, C A; Bocti, C; Dionne, I; Fulop, T; Cunnane, S C

2016-02-01

Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized.

Unravelling the influence of mild traumatic brain injury (MTBI) on cognitive-linguistic processing: a comparative group analysis.

PubMed

Barwood, Caroline H S; Murdoch, Bruce E

2013-06-01

Cognitive-linguistic deficits often accompany traumatic brain injury (TBI) and can negatively impact communicative competency. The linguistic sequelae underpinning mild TBI (MTBI) remain largely unexplored in contemporary literature. The present research methods aim to provide group evidence pertaining to the influence of MTBI on linguistic and higher-level language processing. Extrapolating on the findings of recent case reports, it is hypothesized that performance of the MTBI patients will be significantly reduced compared to normal controls performance on the employed high-level linguistic tasks. Sixteen patients with MTBI and 16 age- and education-matched normal control participants were assessed using a comprehensive battery of cognitive-linguistic assessments. The results demonstrated statistically significant differences between MTBI and normal control group performance across a number of higher-level linguistic, general cognitive and general language tasks. MTBI group performance was significantly lower than the normal control group on tasks requiring complex lexical semantic operations and memory demands, including: Recall, organization, making inferences, naming and perception/discrimination. These outcomes confer that post-MTBI, cognitive, high-level language and isolated general language performance (e.g. naming) is significantly reduced in MTBI patients, compared to normal controls. Furthermore, the detailed cognitive-linguistic profile offered provides a necessary direction for the identification of areas of linguistic decline in MTBI and targets for therapeutic intervention of impaired cognitive-linguistic processes to ultimately improve communicative outcomes in MTBI.

Preliminary study of Alzheimer's Disease diagnosis based on brain electrical signals using wireless EEG

NASA Astrophysics Data System (ADS)

Handayani, N.; Akbar, Y.; Khotimah, S. N.; Haryanto, F.; Arif, I.; Taruno, W. P.

2016-03-01

This research aims to study brain's electrical signals recorded using EEG as a basis for the diagnosis of patients with Alzheimer's Disease (AD). The subjects consisted of patients with AD, and normal subjects are used as the control. Brain signals are recorded for 3 minutes in a relaxed condition and with eyes closed. The data is processed using power spectral analysis, brain mapping and chaos test to observe the level of complexity of EEG's data. The results show a shift in the power spectral in the low frequency band (delta and theta) in AD patients. The increase of delta and theta occurs in lobus frontal area and lobus parietal respectively. However, there is a decrease of alpha activity in AD patients where in the case of normal subjects with relaxed condition, brain alpha wave dominates the posterior area. This is confirmed by the results of brain mapping. While the results of chaos analysis show that the average value of MMLE is lower in AD patients than in normal subjects. The level of chaos associated with neural complexity in AD patients with lower neural complexity is due to neuronal damage caused by the beta amyloid plaques and tau protein in neurons.

Brain iron concentrations in regions of interest and relation with serum iron levels in Parkinson disease.

PubMed

Costa-Mallen, Paola; Gatenby, Christopher; Friend, Sally; Maravilla, Kenneth R; Hu, Shu-Ching; Cain, Kevin C; Agarwal, Pinky; Anzai, Yoshimi

2017-07-15

Brain iron has been previously found elevated in the substantia nigra pars compacta (SNpc), but not in other brain regions, of Parkinson's disease (PD) patients. However, iron in circulation has been recently observed to be lower than normal in PD patients. The regional selectivity of iron deposition in brain as well as the relationship between SNpc brain iron and serum iron within PD patients has not been completely elucidated. In this pilot study we measured brain iron in six regions of interest (ROIs) as well as serum iron and serum ferritin, in 24 PD patients and 27 age- gender-matched controls. Brain iron was measured on magnetic resonance imaging (MRI) with a T2 prime (T2') method. Difference in brain iron deposition between PD cases and controls for the six ROIs were calculated. SNpc/white matter brain iron ratios and SNpc/serum iron ratios were calculated for each study participant, and differences between PD patients and controls were tested. PD patients overall had higher brain iron than controls in the SNpc. PD patients had significantly higher SNpc/white matter brain iron ratios than controls, and significantly higher brain SNpc iron/serum iron ratios than controls. These results indicate that PD patients' iron metabolism is disrupted toward a higher partitioning of iron to the brain SNpc at the expenses of iron in the circulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Absence of gender effect on children with attention-deficit/hyperactivity disorder as assessed by optimized voxel-based morphometry.

PubMed

Yang, Pinchen; Wang, Pei-Ning; Chuang, Kai-Hsiang; Jong, Yuh-Jyh; Chao, Tzu-Cheng; Wu, Ming-Ting

2008-12-30

Brain abnormalities, as determined by structural magnetic resonance imaging (MRI), have been reported in patients with attention-deficit hyperactivity disorder (ADHD); however, female subjects have been underrepresented in previous reports. In this study, we used optimized voxel-based morphometry to compare the total and regional gray matter volumes between groups of 7- to 17-year-old ADHD and healthy children (total 114 subjects). Fifty-seven children with ADHD (n=57, 35 males and 22 females) and healthy children (n=57) received MRI scans. Segmented brain MRI images were normalized into standardized stereotactic space, modulated to allow volumetric analysis, smoothed and compared at the voxel level with statistical parametric mapping. Global volumetric comparisons between groups revealed that the total brain volumes of ADHD children were smaller than those of the control children. As for the regional brain analysis, the brain volumes of ADHD children were found to be bilaterally smaller in the following regions as compared with normal control values: the caudate nucleus and the cerebellum. There were two clusters of regional decrease in the female brain, left posterior cingulum and right precuneus, as compared with the male brain. Brain regions showing the interaction effect of diagnosis and gender were negligible. These results were consistent with the hypothesized dysfunctional systems in ADHD, and they also suggested that neuroanatomical abnormalities in ADHD were not influenced by gender.

A Unique Four-Hub Protein Cluster Associates to Glioblastoma Progression

PubMed Central

Simeone, Pasquale; Trerotola, Marco; Urbanella, Andrea; Lattanzio, Rossano; Ciavardelli, Domenico; Di Giuseppe, Fabrizio; Eleuterio, Enrica; Sulpizio, Marilisa; Eusebi, Vincenzo; Pession, Annalisa; Piantelli, Mauro; Alberti, Saverio

2014-01-01

Gliomas are the most frequent brain tumors. Among them, glioblastomas are malignant and largely resistant to available treatments. Histopathology is the gold standard for classification and grading of brain tumors. However, brain tumor heterogeneity is remarkable and histopathology procedures for glioma classification remain unsatisfactory for predicting disease course as well as response to treatment. Proteins that tightly associate with cancer differentiation and progression, can bear important prognostic information. Here, we describe the identification of protein clusters differentially expressed in high-grade versus low-grade gliomas. Tissue samples from 25 high-grade tumors, 10 low-grade tumors and 5 normal brain cortices were analyzed by 2D-PAGE and proteomic profiling by mass spectrometry. This led to identify 48 differentially expressed protein markers between tumors and normal samples. Protein clustering by multivariate analyses (PCA and PLS-DA) provided discrimination between pathological samples to an unprecedented extent, and revealed a unique network of deranged proteins. We discovered a novel glioblastoma control module centered on four major network hubs: Huntingtin, HNF4α, c-Myc and 14-3-3ζ. Immunohistochemistry, western blotting and unbiased proteome-wide meta-analysis revealed altered expression of this glioblastoma control module in human glioma samples as compared with normal controls. Moreover, the four-hub network was found to cross-talk with both p53 and EGFR pathways. In summary, the findings of this study indicate the existence of a unifying signaling module controlling glioblastoma pathogenesis and malignant progression, and suggest novel targets for development of diagnostic and therapeutic procedures. PMID:25050814

Alterations in L-Glutamate Binding in Alzheimer's and Huntington's Diseases

NASA Astrophysics Data System (ADS)

Greenamyre, J. Timothy; Penney, John B.; Young, Anne B.; D'Amato, Constance J.; Hicks, Samuel P.; Shoulson, Ira

1985-03-01

Brain sections from patients who had died with senile dementia of the Alzheimer's type (SDAT), Huntington's disease (HD), or no neurologic disease were studied by autoradiography to measure sodium-independent L-[3H]glutamate binding. In brain sections from SDAT patients, glutamate binding was normal in the caudate, putamen, and claustrum but was lower than normal in the cortex. The decreased cortical binding represented a reduction in numbers of binding sites, not a change in binding affinity, and appeared to be the result of a specific decrease in numbers of the low-affinity quisqualate binding site. No significant changes in cortical binding of other ligands were observed. In brains from Huntington's disease patients, glutamate binding was lower in the caudate and putamen than in the same regions of brains from control and SDAT patients but was normal in the cortex. It is possible that development of positron-emitting probes for glutamate receptors may permit diagnosis of SDAT in vivo by means of positron emission tomographic scanning.

Increased determinism in brain electrical activity occurs in association with multiple sclerosis.

PubMed

Carrubba, Simona; Minagar, Alireza; Chesson, Andrew L; Frilot, Clifton; Marino, Andrew A

2012-04-01

Increased determinism (decreased complexity) of brain electrical activity has been associated with some brain diseases. Our objective was to determine whether a similar association occurred for multiple sclerosis (MS). Ten subjects with a relapsing-remitting course of MS who were in remission were studied; the controls were age- and gender-matched clinically normal subjects. Recurrence plots were calculated using representative electroencephalogram (EEG) epochs (1-7 seconds) from six derivations; the plots were quantified using the nonlinear variables percent recurrence (%R) and percent determinism (%D). The results were averaged over all derivations for each participant, and the means were compared between the groups. As a linear control procedure the groups were also compared using spectral analysis. The mean±SD of %R for the MS subjects was 6·6±1·3%, compared with 5·1±1·3% in the normal group (P = 0·017), indicating that brain activity in the subjects with MS was less complex, as hypothesized. The groups were not distinguishable using %D or spectral analysis. Taken together with our earlier report that %R could be used to discriminate between MS and normal subjects based on the ability to exhibit evoked potentials, the evidence suggests that complexity analysis of the EEG has potential for development as a diagnostic test for MS.

Default network connectivity decodes brain states with simulated microgravity.

PubMed

Zeng, Ling-Li; Liao, Yang; Zhou, Zongtan; Shen, Hui; Liu, Yadong; Liu, Xufeng; Hu, Dewen

2016-04-01

With great progress of space navigation technology, it becomes possible to travel beyond Earth's gravity. So far, it remains unclear whether the human brain can function normally within an environment of microgravity and confinement. Particularly, it is a challenge to figure out some neuroimaging-based markers for rapid screening diagnosis of disrupted brain function in microgravity environment. In this study, a 7-day -6° head down tilt bed rest experiment was used to simulate the microgravity, and twenty healthy male participants underwent resting-state functional magnetic resonance imaging scans at baseline and after the simulated microgravity experiment. We used a multivariate pattern analysis approach to distinguish the brain states with simulated microgravity from normal gravity based on the functional connectivity within the default network, resulting in an accuracy of no less than 85 % via cross-validation. Moreover, most discriminative functional connections were mainly located between the limbic system and cortical areas and were enhanced after simulated microgravity, implying a self-adaption or compensatory enhancement to fulfill the need of complex demand in spatial navigation and motor control functions in microgravity environment. Overall, the findings suggest that the brain states in microgravity are likely different from those in normal gravity and that brain connectome could act as a biomarker to indicate the brain state in microgravity.

Plasma serotonin in autism.

PubMed

Connors, Susan L; Matteson, Karla J; Sega, Gary A; Lozzio, Carmen B; Carroll, Roger C; Zimmerman, Andrew W

2006-09-01

Serotonin is necessary for normal fetal brain development. Administration of serotonin inhibitors to pregnant rats results in offspring with abnormal behaviors, brain morphology, and serotonin receptor numbers. Low maternal plasma serotonin may contribute to abnormal brain development in autism. In this study, plasma serotonin levels in autism mothers and control mothers of typically developing children were compared, and plasma serotonin levels in children with autism (n = 17) and their family members were measured. Plasma serotonin levels in autism mothers were significantly lower than in mothers of normal children (P = 0.002). Plasma serotonin levels correlated between autism mothers and their children, but differed between autistic children and their fathers (P = 0.028) and siblings (P = 0.063). Low maternal plasma serotonin may be a risk factor for autism through effects on fetal brain development.

Higher resting-state activity in reward-related brain circuits in obese versus normal-weight females independent of food intake.

PubMed

Hogenkamp, P S; Zhou, W; Dahlberg, L S; Stark, J; Larsen, A L; Olivo, G; Wiemerslage, L; Larsson, E-M; Sundbom, M; Benedict, C; Schiöth, H B

2016-11-01

In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals-that is, resting-state brain activity-in the context of food intake are, however, less well studied. To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese and normal-weight females, as assessed by functional magnetic resonance imaging (fMRI). Fractional amplitude of low-frequency fluctuations were measured in the morning following an overnight fast in 17 obese (age: 39±11 years, body mass index (BMI): 42.3±4.8 kg m - 2 ) and 12 normal-weight females (age: 36±12 years, BMI: 22.7±1.8 kg m - 2 ), both before and 30 min after consumption of a standardized meal (~260 kcal). Compared with normal-weight controls, obese females had increased low-frequency activity in clusters located in the putamen, claustrum and insula (P<0.05). This group difference was not altered by food intake. Self-reported hunger dropped and plasma glucose concentrations increased after food intake (P<0.05); however, these changes did not differ between the BMI groups. Reward-related brain regions are more active under resting-state conditions in obese than in normal-weight females. This difference was independent of food intake under the experimental settings applied in the current study. Future studies involving males and females, as well as utilizing repeated post-prandial resting-state fMRI scans and various types of meals are needed to further investigate how food intake alters resting-state brain activity in obese humans.

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study.

PubMed

Yuan, Hong; Zhang, Lei; Frank, Jonathan E; Inscoe, Christina R; Burk, Laurel M; Hadsell, Mike; Lee, Yueh Z; Lu, Jianping; Chang, Sha; Zhou, Otto

2015-09-01

Microbeam radiation treatment (MRT) using synchrotron radiation has shown great promise in the treatment of brain tumors, with a demonstrated ability to eradicate the tumor while sparing normal tissue in small animal models. With the goal of expediting the advancement of MRT research beyond the limited number of synchrotron facilities in the world, we recently developed a compact laboratory-scale microbeam irradiator using carbon nanotube (CNT) field emission-based X-ray source array technology. The focus of this study is to evaluate the effects of the microbeam radiation generated by this compact irradiator in terms of tumor control and normal tissue damage in a mouse brain tumor model. Mice with U87MG human glioblastoma were treated with sham irradiation, low-dose MRT, high-dose MRT or 10 Gy broad-beam radiation treatment (BRT). The microbeams were 280 μm wide and spaced at 900 μm center-to-center with peak dose at either 48 Gy (low-dose MRT) or 72 Gy (high-dose MRT). Survival studies showed that the mice treated with both MRT protocols had a significantly extended life span compared to the untreated control group (31.4 and 48.5% of life extension for low- and high-dose MRT, respectively) and had similar survival to the BRT group. Immunostaining on MRT mice demonstrated much higher DNA damage and apoptosis level in tumor tissue compared to the normal brain tissue. Apoptosis in normal tissue was significantly lower in the low-dose MRT group compared to that in the BRT group at 48 h postirradiation. Interestingly, there was a significantly higher level of cell proliferation in the MRT-treated normal tissue compared to that in the BRT-treated mice, indicating rapid normal tissue repairing process after MRT. Microbeam radiation exposure on normal brain tissue causes little apoptosis and no macrophage infiltration at 30 days after exposure. This study is the first biological assessment on MRT effects using the compact CNT-based irradiator. It provides an alternative technology that can enable widespread MRT research on mechanistic studies using a preclinical model, as well as further translational research towards clinical applications.

Reversible changes in brain glucose metabolism following thyroid function normalization in hyperthyroidism.

PubMed

Miao, Q; Zhang, S; Guan, Y H; Ye, H Y; Zhang, Z Y; Zhang, Q Y; Xue, R D; Zeng, M F; Zuo, C T; Li, Y M

2011-01-01

Patients with hyperthyroidism frequently present with regional cerebral metabolic changes, but the consequences of endocrine-induced brain changes after thyroid function normalization are unclear. We hypothesized that the changes of regional cerebral glucose metabolism are related to thyroid hormone levels in patients with hyperthyroid, and some of these changes can be reversed with antithyroid therapy. Relative regional cerebral glucose metabolism was compared between 10 new-onset untreated patients with hyperthyroidism and 20 healthy control participants by using brain FDG-PET scans. Levels of emotional distress were evaluated by using the SAS and SDS. Patients were treated with methimazole. A follow-up PET scan was performed to assess metabolic changes of the brain when thyroid functions normalized. Compared with controls, patients exhibited lower activity in the limbic system, frontal lobes, and temporal lobes before antithyroid treatment. There were positive correlations between scores of depression and regional metabolism in the cingulate and paracentral lobule. The severity of depression and anxiety covaried negatively with pretreatment activity in the inferior temporal and inferior parietal gyri respectively. Compared with the hyperthyroid status, patients with normalized thyroid functions showed an increased metabolism in the left parahippocampal, fusiform, and right superior frontal gyri. The decrease in both FT3 and FT4 was associated with increased activity in the left parahippocampal and right superior frontal gyri. The changes of regional cerebral glucose metabolism are related to thyroid hormone levels in patients with hyperthyroidism, and some cerebral hypometabolism can be improved after antithyroid therapy.

OP17MICRORNA PROFILING USING SMALL RNA-SEQ IN PAEDIATRIC LOW GRADE GLIOMAS

PubMed Central

Jeyapalan, Jennie N.; Jones, Tania A.; Tatevossian, Ruth G.; Qaddoumi, Ibrahim; Ellison, David W.; Sheer, Denise

2014-01-01

INTRODUCTION: MicroRNAs regulate gene expression by targeting mRNAs for translational repression or degradation at the post-transcriptional level. In paediatric low-grade gliomas a few key genetic mutations have been identified, including BRAF fusions, FGFR1 duplications and MYB rearrangements. Our aim in the current study is to profile aberrant microRNA expression in paediatric low-grade gliomas and determine the role of epigenetic changes in the aetiology and behaviour of these tumours. METHOD: MicroRNA profiling of tumour samples (6 pilocytic, 2 diffuse, 2 pilomyxoid astrocytomas) and normal brain controls (4 adult normal brain samples and a primary glial progenitor cell-line) was performed using small RNA sequencing. Bioinformatic analysis included sequence alignment, analysis of the number of reads (CPM, counts per million) and differential expression. RESULTS: Sequence alignment identified 695 microRNAs, whose expression was compared in tumours v. normal brain. PCA and hierarchical clustering showed separate groups for tumours and normal brain. Computational analysis identified approximately 400 differentially expressed microRNAs in the tumours compared to matched location controls. Our findings will then be validated and integrated with extensive genetic and epigenetic information we have previously obtained for the full tumour cohort. CONCLUSION: We have identified microRNAs that are differentially expressed in paediatric low-grade gliomas. As microRNAs are known to target genes involved in the initiation and progression of cancer, they provide critical information on tumour pathogenesis and are an important class of biomarkers.

Microglia: new roles for the synaptic stripper.

PubMed

Kettenmann, Helmut; Kirchhoff, Frank; Verkhratsky, Alexei

2013-01-09

Any pathologic event in the brain leads to the activation of microglia, the immunocompetent cells of the central nervous system. In recent decades diverse molecular pathways have been identified by which microglial activation is controlled and by which the activated microglia affects neurons. In the normal brain microglia were considered "resting," but it has recently become evident that they constantly scan the brain environment and contact synapses. Activated microglia can remove damaged cells as well as dysfunctional synapses, a process termed "synaptic stripping." Here we summarize evidence that molecular pathways characterized in pathology are also utilized by microglia in the normal and developing brain to influence synaptic development and connectivity, and therefore should become targets of future research. Microglial dysfunction results in behavioral deficits, indicating that microglia are essential for proper brain function. This defines a new role for microglia beyond being a mere pathologic sensor. Copyright © 2013 Elsevier Inc. All rights reserved.

Preserved pontine glucose metabolism in Alzheimer disease: A reference region for functional brain image (PET) analysis

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

Minoshima, Satoshi; Frey, K.A.; Foster, N.L.

1995-07-01

Our goal was to examine regional preservation of energy metabolism in Alzheimer disease (AD) and to evaluate effects of PET data normalization to reference regions. Regional metabolic rates in the pons, thalamus, putamen, sensorimotor cortex, visual cortex, and cerebellum (reference regions) were determined stereotaxically and examined in 37 patients with probable AD and 22 normal controls based on quantitative {sup 18}FDG-PET measurements. Following normalization of metabolic rates of the parietotemporal association cortex and whole brain to each reference region, distinctions of the two groups were assessed. The pons showed the best preservation of glucose metabolism in AD. Other reference regionsmore » showed relatively preserved metabolism compared with the parietotemporal association cortex and whole brain, but had significant metabolic reduction. Data normalization to the pons not only enhanced statistical significance of metabolic reduction in the parietotemporal association cortex, but also preserved the presence of global cerebral metabolic reduction indicated in analysis of the quantitative data. Energy metabolism in the pons in probable AD is well preserved. The pons is a reliable reference for data normalization and will enhance diagnostic accuracy and efficiency of quantitative and nonquantitative functional brain imaging. 39 refs., 2 figs., 3 tabs.« less

Compelling Evidence that Exposure Therapy for PTSD Normalizes Brain Function.

PubMed

Roy, Michael J; Costanzo, Michelle E; Blair, James R; Rizzo, Albert A

2014-01-01

Functional magnetic resonance imaging (fMRI) is helping us better understand the neurologic pathways involved in posttraumatic stress disorder (PTSD). We previously reported that military service members with PTSD after deployment to Iraq or Afghanistan demonstrated significant improvement, or normalization, in the fMRI-measured activation of the amygdala, prefrontal cortex and anterior cingulate gyrus following exposure therapy for PTSD. However, our original study design did not include repeat scans of control participants, rendering it difficult to discern how much of the observed normalization in brain activity is attributable to treatment, rather than merely a practice effect. Using the same Affective Stroop task paradigm, we now report on a larger sample of PTSD-positive combat veterans that we treated with exposure therapy, as well as a combat-exposed control group of service members who completed repeat scans at 3-4 month intervals. Findings from the treatment group are similar to our prior report. Combat controls showed no significant change on repeat scanning, indicating that the observed differences in the intervention group were in fact due to treatment. We continue to scan additional study participants, in order to determine whether virtual reality exposure therapy has a different impact on regional brain activation than other therapies for PTSD.

Brain structure characteristics in intellectually superior schizophrenia.

PubMed

Vaskinn, Anja; Hartberg, Cecilie B; Sundet, Kjetil; Westlye, Lars T; Andreassen, Ole A; Melle, Ingrid; Agartz, Ingrid

2015-04-30

The current study aims to fill a gap in the knowledge base by investigating the structural brain characteristics of individuals with schizophrenia and superior intellectual abilities. Subcortical volumes, cortical thickness and cortical surface area were examined in intellectually normal and intellectually superior participants with schizophrenia and their IQ-matched healthy controls, as well as in intellectually low schizophrenia participants. We replicated significant diagnostic group effects on hippocampal and ventricular size after correction for multiple comparisons. There were no statistically significant effects of intellectual level or of the interaction between diagnostic group and intellectual level. Effect sizes indicated that differences between schizophrenia and healthy control participants were of similar magnitude at both intellectual levels for all three types of morphological data. A secondary analysis within the schizophrenia group, including participants with low intellectual abilities, yielded numerical, but no statistically significant differences on any structural brain measure. The present findings indicate that the brain structure abnormalities in schizophrenia are present at all intellectual levels, and individuals with schizophrenia and superior intellectual abilities have brain structure abnormalities of the same magnitude as individuals with schizophrenia and normal intellectual abilities. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Blood-brain barrier transport of drugs for the treatment of brain diseases.

PubMed

Gabathuler, Reinhard

2009-06-01

The central nervous system is a sanctuary protected by barriers that regulate brain homeostasis and control the transport of endogenous compounds into the brain. The blood-brain barrier, formed by endothelial cells of the brain capillaries, restricts access to brain cells allowing entry only to amino acids, glucose and hormones needed for normal brain cell function and metabolism. This very tight regulation of brain cell access is essential for the survival of neurons which do not have a significant capacity to regenerate, but also prevents therapeutic compounds, small and large, from reaching the brain. As a result, various strategies are being developed to enhance access of drugs to the brain parenchyma at therapeutically meaningful concentrations to effectively manage disease.

The Role of Neuronal Signaling in Controlling Cerebral Blood Flow

ERIC Educational Resources Information Center

Drake, Carrie T.; Iadecola, Costantino

2007-01-01

Well-regulated blood flow within the brain is vital to normal function. The brain's requirement for sufficient blood flow is ensured by a tight link between neural activity and blood flow. The link between regional synaptic activity and regional cerebral blood flow, termed functional hyperemia, is the basis for several modern imaging techniques…

Cognitive Impairment and Whole Brain Diffusion in Patients with Neuromyelitis Optica after Acute Relapse

ERIC Educational Resources Information Center

He, Diane; Wu, Qizhu; Chen, Xiuying; Zhao, Daidi; Gong, Qiyong; Zhou, Hongyu

2011-01-01

The objective of this study investigated cognitive impairments and their correlations with fractional anisotropy (FA) and mean diffusivity (MD) in patients with neuromyelitis optica (NMO) without visible lesions on conventional brain MRI during acute relapse. Twenty one patients with NMO and 21 normal control subjects received several cognitive…

PET imaging and quantitation of Internet-addicted patients and normal controls

NASA Astrophysics Data System (ADS)

Jeong, Ha-Kyu; Kim, Hee-Joung; Jung, Haijo; Son, Hye-Kyung; Kim, Dong-Hyeon; Yun, Mijin; Shin, Yee-Jin; Lee, Jong-Doo

2002-04-01

Internet addicted patients (IAPs) have widely been increased, as Internet games are becoming very popular in daily life. The purpose of this study was to investigate regional brain activation patterns associated with excessive use of Internet games in adolescents. Six normal controls (NCs) and eight IAPs who were classified as addiction group by adapted version of DSM-IV for pathologic gambling were participated. 18F-FDG PET studies were performed for all adolescents at their rest and activated condition after 20 minutes of each subject's favorite Internet game. To investigate quantitative metabolic differences in both groups, all possible combinations of group comparison were carried out using Statistical Parametric Mapping (SPM 99). Regional brain activation foci were identified on Talairach coordinate. SPM results showed increased metabolic activation in occipital lobes for both groups. Higher metabolisms were seen at resting condition in IAPs than that of in NCs. In comparison to both groups, IAPs showed different patterns of regional brain metabolic activation compared with that of NCs. It suggests that addictive use of Internet games may result in functional alteration of developing brain in adolescents.

The muscle protein dysferlin accumulates in the Alzheimer brain

PubMed Central

Palamand, Divya; Strider, Jeff; Milone, Margherita; Pestronk, Alan

2006-01-01

Dysferlin is a transmembrane protein that is highly expressed in muscle. Dysferlin mutations cause limb-girdle dystrophy type 2B, Miyoshi myopathy and distal anterior compartment myopathy. Dysferlin has also been described in neural tissue. We studied dysferlin distribution in the brains of patients with Alzheimer disease (AD) and controls. Twelve brains, staged using the Clinical Dementia Rating were examined: 9 AD cases (mean age: 85.9 years and mean disease duration: 8.9 years), and 3 age-matched controls (mean age: 87.5 years). Dysferlin is a cytoplasmic protein in the pyramidal neurons of normal and AD brains. In addition, there were dysferlin-positive dystrophic neurites within Aβ plaques in the AD brain, distinct from tau-positive neurites. Western blots of total brain protein (RIPA) and sequential extraction buffers (high salt, high salt/Triton X-100, SDS and formic acid) of increasing protein extraction strength were performed to examine solubility state. In RIPA fractions, dysferlin was seen as 230–272 kDa bands in normal and AD brains. In serial extractions, there was a shift of dysferlin from soluble phase in high salt/Triton X-100 to the more insoluble SDS fraction in AD. Dysferlin is a new protein described in the AD brain that accumulates in association with neuritic plaques. In muscle, dysferlin plays a role in the repair of muscle membrane damage. The accumulation of dysferlin in the AD brain may be related to the inability of neurons to repair damage due to Aβ deposits accumulating in the AD brain. PMID:17024495

Disrupted Sleep in Narcolepsy: Exploring the Integrity of Galanin Neurons in the Ventrolateral Preoptic Area.

PubMed

Gavrilov, Yury V; Ellison, Brian A; Yamamoto, Mihoko; Reddy, Hasini; Haybaeck, Johannes; Mignot, Emmanuel; Baumann, Christian R; Scammell, Thomas E; Valko, Philipp O

2016-05-01

To examine the integrity of sleep-promoting neurons of the ventrolateral preoptic nucleus (VLPO) in postmortem brains of narcolepsy type 1 patients. Postmortem examination of five narcolepsy and eight control brains. VLPO galanin neuron count did not differ between narcolepsy patients (11,151 ± 3,656) and controls (13,526 ± 9,544). A normal number of galanin-immunoreactive VLPO neurons in narcolepsy type 1 brains at autopsy suggests that VLPO cell loss is an unlikely explanation for the sleep fragmentation that often accompanies the disease. © 2016 Associated Professional Sleep Societies, LLC.

A Comparison of Oxidative Lactate Metabolism in Traumatically Injured Brain and Control Brain.

PubMed

Jalloh, Ibrahim; Helmy, Adel; Howe, Duncan J; Shannon, Richard J; Grice, Peter; Mason, Andrew; Gallagher, Clare N; Murphy, Michael P; Pickard, John D; Menon, David K; Carpenter, T Adrian; Hutchinson, Peter J; Carpenter, Keri L H

2018-05-18

Metabolic abnormalities occur after traumatic brain injury (TBI). Glucose is conventionally regarded as the major energy substrate, although lactate can also be an energy source. We compared 3- 13 C lactate metabolism in TBI with "normal" control brain and muscle, measuring 13 C-glutamine enrichment to assess tricarboxylic acid (TCA) cycle metabolism. Microdialysis catheters in brains of nine patients with severe TBI, five non-TBI brain surgical patients, and five resting muscle (non-TBI) patients were perfused (24 h in brain, 8 h in muscle) with 8 mmol/L sodium 3- 13 C lactate. Microdialysate analysis employed ISCUS and nuclear magnetic resonance. In TBI, with 3- 13 C lactate perfusion, microdialysate glucose concentration increased nonsignificantly (mean +11.9%, p = 0.463), with significant increases (p = 0.028) for lactate (+174%), pyruvate (+35.8%), and lactate/pyruvate ratio (+101.8%). Microdialysate 13 C-glutamine fractional enrichments (median, interquartile range) were: for C4 5.1 (0-11.1) % in TBI and 5.7 (4.6-6.8) % in control brain, for C3 0 (0-5.0) % in TBI and 0 (0-0) % in control brain, and for C2 2.9 (0-5.7) % in TBI and 1.8 (0-3.4) % in control brain. 13 C-enrichments were not statistically different between TBI and control brain, showing both metabolize 3- 13 C lactate via TCA cycle, in contrast to muscle. Several patients with TBI exhibited 13 C-glutamine enrichment above the non-TBI control range, suggesting lactate oxidative metabolism as a TBI "emergency option."

The diffusion tensor imaging (DTI) component of the NIH MRI study of normal brain development (PedsDTI).

PubMed

Walker, Lindsay; Chang, Lin-Ching; Nayak, Amritha; Irfanoglu, M Okan; Botteron, Kelly N; McCracken, James; McKinstry, Robert C; Rivkin, Michael J; Wang, Dah-Jyuu; Rumsey, Judith; Pierpaoli, Carlo

2016-01-01

The NIH MRI Study of normal brain development sought to characterize typical brain development in a population of infants, toddlers, children and adolescents/young adults, covering the socio-economic and ethnic diversity of the population of the United States. The study began in 1999 with data collection commencing in 2001 and concluding in 2007. The study was designed with the final goal of providing a controlled-access database; open to qualified researchers and clinicians, which could serve as a powerful tool for elucidating typical brain development and identifying deviations associated with brain-based disorders and diseases, and as a resource for developing computational methods and image processing tools. This paper focuses on the DTI component of the NIH MRI study of normal brain development. In this work, we describe the DTI data acquisition protocols, data processing steps, quality assessment procedures, and data included in the database, along with database access requirements. For more details, visit http://www.pediatricmri.nih.gov. This longitudinal DTI dataset includes raw and processed diffusion data from 498 low resolution (3 mm) DTI datasets from 274 unique subjects, and 193 high resolution (2.5 mm) DTI datasets from 152 unique subjects. Subjects range in age from 10 days (from date of birth) through 22 years. Additionally, a set of age-specific DTI templates are included. This forms one component of the larger NIH MRI study of normal brain development which also includes T1-, T2-, proton density-weighted, and proton magnetic resonance spectroscopy (MRS) imaging data, and demographic, clinical and behavioral data. Published by Elsevier Inc.

Blindness alters the microstructure of the ventral but not the dorsal visual stream.

PubMed

Reislev, Nina L; Kupers, Ron; Siebner, Hartwig R; Ptito, Maurice; Dyrby, Tim B

2016-07-01

Visual deprivation from birth leads to reorganisation of the brain through cross-modal plasticity. Although there is a general agreement that the primary afferent visual pathways are altered in congenitally blind individuals, our knowledge about microstructural changes within the higher-order visual streams, and how this is affected by onset of blindness, remains scant. We used diffusion tensor imaging and tractography to investigate microstructural features in the dorsal (superior longitudinal fasciculus) and ventral (inferior longitudinal and inferior fronto-occipital fasciculi) visual pathways in 12 congenitally blind, 15 late blind and 15 normal sighted controls. We also studied six prematurely born individuals with normal vision to control for the effects of prematurity on brain connectivity. Our data revealed a reduction in fractional anisotropy in the ventral but not the dorsal visual stream for both congenitally and late blind individuals. Prematurely born individuals, with normal vision, did not differ from normal sighted controls, born at term. Our data suggest that although the visual streams are structurally developing without normal visual input from the eyes, blindness selectively affects the microstructure of the ventral visual stream regardless of the time of onset. We suggest that the decreased fractional anisotropy of the ventral stream in the two groups of blind subjects is the combined result of both degenerative and cross-modal compensatory processes, affecting normal white matter development.

Compensatory brain activation in children with attention deficit/hyperactivity disorder during a simplified Go/No-go task.

PubMed

Ma, Jun; Lei, Du; Jin, Xingming; Du, Xiaoxia; Jiang, Fan; Li, Fei; Zhang, Yiwen; Shen, Xiaoming

2012-05-01

Given that a number of recent studies have shown attenuated brain activation in prefrontal regions in children with ADHD, it has been recognized as a disorder in executive function. However, fewer studies have focused exclusively on the compensatory brain activation in ADHD. The present study objective was to investigate the compensatory brain activation patterns during response inhibition (RI) processing in ADHD children. In this study, 15 ADHD children and 15 sex-, age-, and IQ-matched control children were scanned with a 3-T MRI equipment while performing a simplified letter Go/No-go task. The results showed more brain activation in the ADHD group compared with the control group, whereas the accuracy and reaction time of behavioral performance were the same. Children with ADHD did not activate the normal RI brain circuits, which are thought to be predominantly located in the right middle/inferior frontal gyrus (BA46/44), right inferior parietal regions (BA40), and pre-SMA(BA6), but instead, activated brain regions, such as the left inferior frontal cortex, the right inferior temporal cortex, the right precentral gyrus, the left postcentral gyrus, the inferior occipital cortex, the middle occipital cortex, the right calcarine, the right hippocampus, the right midbrain, and the cerebellum. Our conclusion is that children with ADHD tend to compensatorily use more posterior and diffusive brain regions to sustain normal RI function. © Springer-Verlag 2011

Regional brain glucose metabolism in patients with brain tumors before and after radiotherapy

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

Wang, G.J.; Volkow, N.D.; Lau, Y.H.

1994-05-01

This study was performed to measure regional glucose metabolism in nonaffected brain regions of patients with primary or metastatic brain tumors. Seven female and four male patients (mean age 51.5{plus_minus}14.0 years old) were compared with eleven age and sex matched normal subjects. None of the patients had hydrocephalus and/or increased intracranial pressure. Brain glucose metabolism was measured using FDG-PET scan. Five of the patients were reevaluated one week after receiving radiation treatment (RT) to the brain. Patients were on Decadron and/or Dilantin at the time of both scan. PET images were analyzed with a template of 115 nonoverlapping regions ofmore » interest and then grouped into eight gray matter regions on each hemisphere. Brain regions with tumors and edema shown in MR imaging were excluded. Z scores were used to compare individual patients` regional values with those of normal subjects. The number of regional values with Z scores of less than - 3.0 were considered abnormal and were quantified. The mean global glucose metabolic rate (mean of all regions) in nonaffected brain regions of patients was significantly lower than that of normal controls (32.1{plus_minus}9.0 versus 44.8{plus_minus}6.3 {mu}mol/100g/min, p<0.001). Analyses of individual subjects revealed that none of the controls and 8 of the 11 patients had at least one abnormal region. In these 8 patients the regions which were abnormal were most frequently localized in right (n=5) and left occipital (n=6) and right orbital frontal cortex (n=7) whereas the basal ganglia was not affected. Five of the patients who had repeated scans following RT showed decrements in tumor metabolism (41{plus_minus}20.5%) and a significant increase in whole brain metabolism (8.6{plus_minus}5.3%, p<0.001). The improvement in whole brain metabolism after RT suggests that the brain metabolic decrements in the patients were related to the presence of tumoral tissue and not just a medication effect.« less

Voxel-based statistical analysis of cerebral blood flow using Tc-99m ECD brain SPECT in patients with traumatic brain injury: group and individual analyses.

PubMed

Shin, Yong Beom; Kim, Seong-Jang; Kim, In-Ju; Kim, Yong-Ki; Kim, Dong-Soo; Park, Jae Heung; Yeom, Seok-Ran

2006-06-01

Statistical parametric mapping (SPM) was applied to brain perfusion single photon emission computed tomography (SPECT) images in patients with traumatic brain injury (TBI) to investigate regional cerebral abnormalities compared to age-matched normal controls. Thirteen patients with TBI underwent brain perfusion SPECT were included in this study (10 males, three females, mean age 39.8 +/- 18.2, range 21 - 74). SPM2 software implemented in MATLAB 5.3 was used for spatial pre-processing and analysis and to determine the quantitative differences between TBI patients and age-matched normal controls. Three large voxel clusters of significantly decreased cerebral blood perfusion were found in patients with TBI. The largest clusters were area including medial frontal gyrus (voxel number 3642, peak Z-value = 4.31, 4.27, p = 0.000) in both hemispheres. The second largest clusters were areas including cingulated gyrus and anterior cingulate gyrus of left hemisphere (voxel number 381, peak Z-value = 3.67, 3.62, p = 0.000). Other clusters were parahippocampal gyrus (voxel number 173, peak Z-value = 3.40, p = 0.000) and hippocampus (voxel number 173, peak Z-value = 3.23, p = 0.001) in the left hemisphere. The false discovery rate (FDR) was less than 0.04. From this study, group and individual analyses of SPM2 could clearly identify the perfusion abnormalities of brain SPECT in patients with TBI. Group analysis of SPM2 showed hypoperfusion pattern in the areas including medial frontal gyrus of both hemispheres, cingulate gyrus, anterior cingulate gyrus, parahippocampal gyrus and hippocampus in the left hemisphere compared to age-matched normal controls. Also, left parahippocampal gyrus and left hippocampus were additional hypoperfusion areas. However, these findings deserve further investigation on a larger number of patients to be performed to allow a better validation of objective SPM analysis in patients with TBI.

The effect of ingested sulfite on visual evoked potentials, lipid peroxidation, and antioxidant status of brain in normal and sulfite oxidase-deficient aged rats.

PubMed

Ozsoy, Ozlem; Aras, Sinem; Ozkan, Ayse; Parlak, Hande; Aslan, Mutay; Yargicoglu, Piraye; Agar, Aysel

2016-07-01

Sulfite, commonly used as a preservative in foods, beverages, and pharmaceuticals, is a very reactive and potentially toxic molecule which is detoxified by sulfite oxidase (SOX). Changes induced by aging may be exacerbated by exogenous chemicals like sulfite. The aim of this study was to investigate the effects of ingested sulfite on visual evoked potentials (VEPs) and brain antioxidant statuses by measuring superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. Brain lipid oxidation status was also determined via thiobarbituric acid reactive substances (TBARS) in normal- and SOX-deficient aged rats. Rats do not mimic the sulfite responses seen in humans because of their relatively high SOX activity level. Therefore this study used SOX-deficient rats since they are more appropriate models for studying sulfite toxicity. Forty male Wistar rats aged 24 months were randomly assigned to four groups: control (C), sulfite (S), SOX-deficient (D) and SOX-deficient + sulfite (DS). SOX deficiency was established by feeding rats with low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg kg(-1) day(-1)) was given by gavage. Treatment continued for 6 weeks. At the end of the experimental period, flash VEPs were recorded. Hepatic SOX activity was measured to confirm SOX deficiency. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with the normal rats. The activity of SOX in deficient rats was thus in the range of humans. There was no significant difference between control and treated groups in either latence or amplitude of VEP components. Brain SOD, CAT, and GPx activities and brain TBARS levels were similar in all experimental groups compared with the control group. Our results indicate that exogenous administration of sulfite does not affect VEP components and the antioxidant/oxidant status of aged rat brains. © The Author(s) 2014.

Volunteers for biomedical research. Recruitment and screening of normal controls.

PubMed

Shtasel, D L; Gur, R E; Mozley, P D; Richards, J; Taleff, M M; Heimberg, C; Gallacher, F; Gur, R C

1991-11-01

We examined the process of accruing healthy control subjects for biomedical research on brain function. Of 1670 responders to newspaper advertising, 23.1% were uninterested when learning more about the studies, and 50.9% of those remaining were found by structured telephone screening to meet exclusionary criteria for having a history of psychiatric, neurologic, or medical disease that might affect brain function. Of 312 volunteers passing the telephone screening who came to an in-person evaluation by a physician and agreed to participate, 49.7% were found to meet exclusionary criteria, and only 157 were admitted to the study. This underscores the importance of attending to the issue of screening and assessment of "normal volunteers." Alternative strategies should be considered for enriching the pool.

Pomegranate polyphenols and extract inhibit nuclear factor of activated T-cell activity and microglial activation in vitro and in a transgenic mouse model of Alzheimer disease.

PubMed

Rojanathammanee, Lalida; Puig, Kendra L; Combs, Colin K

2013-05-01

Alzheimer disease (AD) brain is characterized by extracellular plaques of amyloid β (Aβ) peptide with reactive microglia. This study aimed to determine whether a dietary intervention could attenuate microgliosis. Memory was assessed in 12-mo-old male amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice via Barnes maze testing followed by division into either a control-fed group provided free access to normal chow and water or a treatment group provided free access to normal chow and drinking water supplemented with pomegranate extract (6.25 mL/L) for 3 mo followed by repeat Barnes maze testing for both groups. Three months of pomegranate feeding decreased the path length to escape of mice compared with their initial 12-mo values (P < 0.05) and their control-fed counterparts (P < 0.05). Brains of the 3-mo study pomegranate-fed mice had lower tumor necrosis factor α (TNF-α) concentrations (P < 0.05) and lower nuclear factor of activated T-cell (NFAT) transcriptional activity (P < 0.05) compared with controls. Brains of the 3-mo pomegranate or control mice were also compared with an additional control group of 12-mo-old mice for histologic analysis. Immunocytochemistry showed that pomegranate- but not control-fed mice had attenuated microgliosis (P < 0.05) and Aβ plaque deposition (P < 0.05) compared with 12-mo-old mice. An additional behavioral study again used 12-mo-old male APP/PS1 mice tested by T-maze followed by division into a control group provided with free access to normal chow and sugar supplemented drinking water or a treatment group provided with normal chow and pomegranate extract-supplemented drinking water (6.25 mL/L) for 1 mo followed by repeat T-maze testing in both groups. One month of pomegranate feeding increased spontaneous alternations versus control-fed mice (P < 0.05). Cell culture experiments verified that 2 polyphenol components of pomegranate extract, punicalagin and ellagic acid, attenuated NFAT activity in a reporter cell line (P < 0.05) and decreased Aβ-stimulated TNF-α secretion by murine microglia (P < 0.05). These data indicate that dietary pomegranate produces brain antiinflammatory effects that may attenuate AD progression.

Pomegranate Polyphenols and Extract Inhibit Nuclear Factor of Activated T-Cell Activity and Microglial Activation In Vitro and in a Transgenic Mouse Model of Alzheimer Disease123

PubMed Central

Rojanathammanee, Lalida; Puig, Kendra L.; Combs, Colin K.

2013-01-01

Alzheimer disease (AD) brain is characterized by extracellular plaques of amyloid β (Aβ) peptide with reactive microglia. This study aimed to determine whether a dietary intervention could attenuate microgliosis. Memory was assessed in 12-mo-old male amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice via Barnes maze testing followed by division into either a control-fed group provided free access to normal chow and water or a treatment group provided free access to normal chow and drinking water supplemented with pomegranate extract (6.25 mL/L) for 3 mo followed by repeat Barnes maze testing for both groups. Three months of pomegranate feeding decreased the path length to escape of mice compared with their initial 12-mo values (P < 0.05) and their control-fed counterparts (P < 0.05). Brains of the 3-mo study pomegranate-fed mice had lower tumor necrosis factor α (TNF-α) concentrations (P < 0.05) and lower nuclear factor of activated T-cell (NFAT) transcriptional activity (P < 0.05) compared with controls. Brains of the 3-mo pomegranate or control mice were also compared with an additional control group of 12-mo-old mice for histologic analysis. Immunocytochemistry showed that pomegranate- but not control-fed mice had attenuated microgliosis (P < 0.05) and Aβ plaque deposition (P < 0.05) compared with 12-mo-old mice. An additional behavioral study again used 12-mo-old male APP/PS1 mice tested by T-maze followed by division into a control group provided with free access to normal chow and sugar supplemented drinking water or a treatment group provided with normal chow and pomegranate extract–supplemented drinking water (6.25 mL/L) for 1 mo followed by repeat T-maze testing in both groups. One month of pomegranate feeding increased spontaneous alternations versus control-fed mice (P < 0.05). Cell culture experiments verified that 2 polyphenol components of pomegranate extract, punicalagin and ellagic acid, attenuated NFAT activity in a reporter cell line (P < 0.05) and decreased Aβ-stimulated TNF-α secretion by murine microglia (P < 0.05). These data indicate that dietary pomegranate produces brain antiinflammatory effects that may attenuate AD progression. PMID:23468550

Increased brain edema following 5-aminolevulinic acid mediated photodynamic in normal and tumor bearing rats

NASA Astrophysics Data System (ADS)

Hirschberg, Henry; Angell-Petersen, Even; Spetalen, Signe; Mathews, Marlon; Madsen, Steen J.

2007-02-01

Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to both tumor cells as well as cerebral blood vessels leading to degradation of the blood brain barrier with subsequent increase of brain edema. The increase in brain edema following ALA-PDT was evaluated in terms of animal survival, histopatological changes in normal brain and tumor tissue and MRI scanning. The effect of steroid treatment, to reduce post-treatment PDT induced edema, was also examined. Methods:Tumors were established in the brains of inbred BD-IX and Fisher rats. At various times following tumor induction the animals were injected with ALA ip. and four hours later light treatment at escalating fluences and fluence rates were given. Nontumor bearing control animals were also exposed to ALA-PDT in a similar manner to evaluate damage to normal brain and degree of blood brain barrier (BBB) disruption. Results: Despite a very low level of PpIX production in normal brain, with a 200:1 tumor to normal tissue selectivity ratio measured at a distance of 2 mm from the tumor border, many animals succumbed shortly after treatment. A total radiant energy of 54 J to non-tumor bearing animals resulted in 50% mortality within 5 days of treatment. Treatment of tumor bearing animals with moderate fluence levels produced similar brain edema compared to higher fluence levels. ALA PDT in nontumor bearing animals produced edema that was light dose dependent. PDT appeared to open the BBB for a period of 24-48 hrs after which it was restored. The addition of post operative steroid treatment reduced the incident of post treatment morbidity and mortality. Conclusions: T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and non-evasive modality in following the development of the edema reaction and the degree and time course of BBB dysfunction thus allowing the use of fewer animals.

Glial dysfunction in abstinent methamphetamine abusers

PubMed Central

Sailasuta, Napapon; Abulseoud, Osama; Harris, Kent C; Ross, Brian D

2010-01-01

Persistent neurochemical abnormalities in frontal brain structures are believed to result from methamphetamine use. We developed a localized 13C magnetic resonance spectroscopy (MRS) assay on a conventional MR scanner, to quantify selectively glial metabolic flux rate in frontal brain of normal subjects and a cohort of recovering abstinent methamphetamine abusers. Steady-state bicarbonate concentrations were similar, between 11 and 15 mmol/L in mixed gray-white matter of frontal brain of normal volunteers and recovering methamphetamine-abusing subjects (P>0.1). However, glial 13C-bicarbonate production rate from [1-13C]acetate, equating with glial tricarboxylic acid (TCA) cycle rate, was significantly reduced in frontal brain of abstinent methamphetamine-addicted women (methamphetamine 0.04 μmol/g per min (N=5) versus controls 0.11 μmol/g per min (N=5), P=0.001). This is equivalent to 36% of the normal glial TCA cycle rate. Severe reduction in glial TCA cycle rate that normally comprises 10% of total cerebral metabolic rate may impact operation of the neuronal glial glutamate cycle and result in accumulation of frontal brain glutamate, as observed in these recovering methamphetamine abusers. Although these are the first studies to define directly an abnormality in glial metabolism in human methamphetamine abuse, sequential studies using analogous 13C MRS methods may determine ‘cause and effect' between glial failure and neuronal injury. PMID:20040926

Rivastigmine is Associated with Restoration of Left Frontal Brain Activity in Parkinson’s Disease

PubMed Central

Possin, Katherine L.; Kang, Gail A.; Guo, Christine; Fine, Eric M.; Trujillo, Andrew J.; Racine, Caroline A.; Wilheim, Reva; Johnson, Erica T.; Witt, Jennifer L.; Seeley, William W.; Miller, Bruce L.; Kramer, Joel H.

2013-01-01

Objective To investigate how acetylcholinesterase inhibitor (ChEI) treatment impacts brain function in Parkinson’s disease (PD). Methods Twelve patients with PD and either dementia or mild cognitive impairment underwent task-free functional magnetic resonance imaging before and after three months of ChEI treatment and were compared to 15 age and sex matched neurologically healthy controls. Regional spontaneous brain activity was measured using the fractional amplitude of low frequency fluctuations. Results At baseline, patients showed reduced spontaneous brain activity in regions important for motor control (e.g., caudate, supplementary motor area, precentral gyrus, thalamus), attention and executive functions (e.g., lateral prefrontal cortex), and episodic memory (e.g., precuneus, angular gyrus, hippocampus). After treatment, the patients showed a similar but less extensive pattern of reduced spontaneous brain activity relative to controls. Spontaneous brain activity deficits in the left premotor cortex, inferior frontal gyrus, and supplementary motor area were restored such that the activity was increased post-treatment compared to baseline and was no longer different from controls. Treatment-related increases in left premotor and inferior frontal cortex spontaneous brain activity correlated with parallel reaction time improvement on a test of controlled attention. Conclusions PD patients with cognitive impairment show numerous regions of decreased spontaneous brain function compared to controls, and rivastigmine is associated with performance-related normalization in left frontal cortex function. PMID:23847120

The Effect of Early Intervention and Rehabilitation in the Expression of Aquaporin-4; and Ultrastructure Changes on Rat's Offspring's Damaged Brain Caused by Intrauterine Infection

PubMed Central

Rajesh, Kumar; Xiangying, Kong

2015-01-01

Objective To study the effect of early intervention and rehabilitation in the expression of aquaporin-4 and ultrastructure changes on cerebral palsy pups model induced by intrauterine infection. Methods 20 pregnant Wistar rats were consecutively injected with lipopolysaccharide intraperitoneally. 60 Pups born from lipopolysaccharide group were randomly divided into intervention group (n=30) and non-intervention group (n=30); intervention group further divided into early intervention and rehabilitation group (n=10), acupuncture group (n=10) and consolidate group (n=10). Another 5 pregnant rats were injected with normal saline intraperitoneally; 30 pups born from the normal saline group were taken as control group. The intervention group received early intervention, rehabilitation and acupuncture treatment. The motor functions of all pups were assessed via suspension test and modified BBB locomotor score. Aquaporin-4 expression in brain tissue was studied through immunohistochemical and western-blot analysis. Ultrastructure changes in damaged brain and control group were studied electron-microscopically. Results The scores of suspension test and modified BBB locomotor test were significantly higher in the control group than the intervention and non intervention group (p<0.01); higher in the intervention group than the non-intervention group (p<0.01). The expression of Aquaporin-4 was lower in intervention and non intervention group than in the control group (p<0.01); also lower in non-intervention group than the intervention group (p<0.01). Marked changes were observed in ultrastructure of cortex and hippocampus CAI in brain damaged group. Conclusion Early intervention and rehabilitation training can improve the motor function in offspring with brain injury and reduce the expression of aquaporin-4 in damaged brain. PMID:26279808

Multimodality instrument for tissue characterization

NASA Technical Reports Server (NTRS)

Mah, Robert W. (Inventor); Andrews, Russell J. (Inventor)

2004-01-01

A system with multimodality instrument for tissue identification includes a computer-controlled motor driven heuristic probe with a multisensory tip. For neurosurgical applications, the instrument is mounted on a stereotactic frame for the probe to penetrate the brain in a precisely controlled fashion. The resistance of the brain tissue being penetrated is continually monitored by a miniaturized strain gauge attached to the probe tip. Other modality sensors may be mounted near the probe tip to provide real-time tissue characterizations and the ability to detect the proximity of blood vessels, thus eliminating errors normally associated with registration of pre-operative scans, tissue swelling, elastic tissue deformation, human judgement, etc., and rendering surgical procedures safer, more accurate, and efficient. A neural network program adaptively learns the information on resistance and other characteristic features of normal brain tissue during the surgery and provides near real-time modeling. A fuzzy logic interface to the neural network program incorporates expert medical knowledge in the learning process. Identification of abnormal brain tissue is determined by the detection of change and comparison with previously learned models of abnormal brain tissues. The operation of the instrument is controlled through a user friendly graphical interface. Patient data is presented in a 3D stereographics display. Acoustic feedback of selected information may optionally be provided. Upon detection of the close proximity to blood vessels or abnormal brain tissue, the computer-controlled motor immediately stops probe penetration. The use of this system will make surgical procedures safer, more accurate, and more efficient. Other applications of this system include the detection, prognosis and treatment of breast cancer, prostate cancer, spinal diseases, and use in general exploratory surgery.

Acute pharmacologically induced shifts in serotonin availability abolish emotion-selective responses to negative face emotions in distinct brain networks.

PubMed

Grady, Cheryl L; Siebner, Hartwig R; Hornboll, Bettina; Macoveanu, Julian; Paulson, Olaf B; Knudsen, Gitte M

2013-05-01

Pharmacological manipulation of serotonin availability can alter the processing of facial expressions of emotion. Using a within-subject design, we measured the effect of serotonin on the brain's response to aversive face emotions with functional MRI while 20 participants judged the gender of neutral, fearful and angry faces. In three separate and counterbalanced sessions, participants received citalopram (CIT) to raise serotonin levels, underwent acute tryptophan depletion (ATD) to lower serotonin, or were studied without pharmacological challenge (Control). An analysis designed to identify distributed brain responses identified two brain networks with modulations of activity related to face emotion and serotonin level. The first network included the left amygdala, bilateral striatum, and fusiform gyri. During the Control session this network responded only to fearful faces; increasing serotonin decreased this response to fear, whereas reducing serotonin enhanced the response of this network to angry faces. The second network involved bilateral amygdala and ventrolateral prefrontal cortex, and these regions also showed increased activity to fear during the Control session. Both drug challenges enhanced the neural response of this set of regions to angry faces, relative to Control, and CIT also enhanced activity for neutral faces. The net effect of these changes in both networks was to abolish the selective response to fearful expressions. These results suggest that a normal level of serotonin is critical for maintaining a differentiated brain response to threatening face emotions. Lower serotonin leads to a broadening of a normally fear-specific response to anger, and higher levels reduce the differentiated brain response to aversive face emotions. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

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

Khatoon, S.; Slevin, J.T.; Haley, B.E.

A decrease occurs (80-100%) in the (/sup 32/P)8N/sub 3/GTP photoinsertion into a cytosolic protein (55K M/sub r/) of Alzheimer's (AD) brain, tentatively identified as the ..beta..-subunit of tubulin (co-migration with purified tubulin, concentration dependence of interaction with GTP, ATP and their 8-azido photoprobes, and similar effects of Ca/sup 2 +/ and EDTA on photoinsertion). This agrees with prior observations of (/sup 32/P)8N/sub 3/GTP interactions with brain tubulin and a recent report on faulty microtubular assembly in AD brain. The decrease in (/sup 32/P)8N/sub 3/GTP photoinsertion into the 55K M/sub r/ protein of AD brain was in contrast with other photolabeledmore » proteins, which remained at equal levels in AD and age-matched normal brain tissues. The 55K and 45K M/sub r/ were the two major (/sup 32/P)8N/sub 3/GTP photoinsertion species in non-AD brain. Of 5 AD brains, the photoinsertion of (/sup 32/P)8N/sub 3/GTP into the 55K M/sub r/ region was low or absent in 4 (55K/45K=0.1); one was 75% below normals (55K/45K=0.24). Total protein migrating at 55K M/sub r/ was similar in AD and controls. AD brain tubulin, while present, has its exchangeable GTP binding site on ..beta..-tubulin blocked/modified such that (/sup 32/P)8N/sub 3/GTP cannot interact normally with this site.« less

Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome.

PubMed

Mutch, W Alan C; Ellis, Michael J; Ryner, Lawrence N; Ruth Graham, M; Dufault, Brenden; Gregson, Brian; Hall, Thomas; Bunge, Martin; Essig, Marco; Fisher, Joseph A; Duffin, James; Mikulis, David J

2016-09-01

OBJECT A neuroimaging assessment tool to visualize global and regional impairments in cerebral blood flow (CBF) and cerebrovascular responsiveness in individual patients with concussion remains elusive. Here the authors summarize the safety, feasibility, and results of brain CO2 stress testing in adolescents with postconcussion syndrome (PCS) and healthy controls. METHODS This study was approved by the Biomedical Research Ethics Board at the University of Manitoba. Fifteen adolescents with PCS and 17 healthy control subjects underwent anatomical MRI, pseudo-continuous arterial spin labeling MRI, and brain stress testing using controlled CO2 challenge and blood oxygen level-dependent (BOLD) MRI. Post hoc processing was performed using statistical parametric mapping to determine voxel-by-voxel regional resting CBF and cerebrovascular responsiveness of the brain to the CO2 stimulus (increase in BOLD signal) or the inverse (decrease in BOLD signal). Receiver operating characteristic (ROC) curves were generated to compare voxel counts categorized by control (0) or PCS (1). RESULTS Studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study participants. No differences in CO2 stimuli were seen between the 2 participant groups. No group differences in global mean CBF were detected between PCS patients and healthy controls. Patient-specific differences in mean regional CBF and CO2 BOLD responsiveness were observed in all PCS patients. The ROC curve analysis for brain regions manifesting a voxel response greater than and less than the control atlas (that is, abnormal voxel counts) produced an area under the curve of 0.87 (p < 0.0001) and 0.80 (p = 0.0003), respectively, consistent with a clinically useful predictive model. CONCLUSIONS Adolescent PCS is associated with patient-specific abnormalities in regional mean CBF and BOLD cerebrovascular responsiveness that occur in the setting of normal global resting CBF. Future prospective studies are warranted to examine the utility of brain MRI CO2 stress testing in the longitudinal assessment of acute sports-related concussion and PCS.

Brain acetycholinesterase activity in botulism-intoxicated mallards

USGS Publications Warehouse

Rocke, T.E.; Samuel, M.D.

1991-01-01

Brain acetylcholinesterase (AChE) activity in captive-reared mallards (Anas platyrhynchos) that died of botulism was compared with euthanized controls. AChE levels for both groups were within the range reported for normal mallards, and there was no significant difference in mean AChE activity between birds that ingested botulism toxin and died and those that did not.

Effects of high-pressure oxygen therapy on brain tissue water content and AQP4 expression in rabbits with cerebral hemorrhage.

PubMed

Wu, Jing; Chen, Jiong; Guo, Hua; Peng, Fang

2014-12-01

To investigate the effects of different atmosphere absolutes (ATA) of high-pressure oxygen (HPO) on brain tissue water content and Aquaporin-4 (AQP4) expression in rabbits with cerebral hemorrhage. 180 New Zealand white rabbits were selected and randomly divided into normal group (n = 30), control group (n = 30) and cerebral hemorrhage group (n = 120), and cerebral hemorrhage group was divided into group A, B, C and D with 30 rabbits in each group. The groups received 1.0, 1.8, 2.0 and 2.2 ATA of HPO treatments, respectively. Ten rabbits in each group were killed at first, third and fifth day to detect the brain tissue water content and change of AQP4 expression. In cerebral hemorrhage group, brain tissue water content and AQP4 expression after model establishment were first increased, then decreased and reached the maximum on third day (p < 0.05). Brain tissue water content and AQP4 expression in control group and cerebral hemorrhage group were significantly higher than normal group at different time points (p < 0.05). In contrast, brain tissue water content and AQP4 expression in group C were significantly lower than in group A, group B, group D and control group (p < 0.05). In control group, AQP4-positive cells significantly increased after model establishment, which reached maximum on third day, and positive cells in group C were significantly less than in group A, group B and group D. We also found that AQP4 expression were positively correlated with brain tissue water content (r = 0.719, p < 0.05) demonstrated by significantly increased AQP4 expression along with increased brain tissue water content. In conclusion, HPO can decrease AQP4 expression in brain tissue of rabbits with cerebral hemorrhage to suppress the progression of brain edema and promote repairing of injured tissue. 2.0 ATA HPO exerts best effects, which provides an experimental basis for ATA selection of HPO in treating cerebral hemorrhage.

HIGHER SERUM TOTAL CHOLESTEROL LEVELS IN LATE MIDDLE AGE ARE ASSOCIATED WITH GLUCOSE HYPOMETABOLISM IN BRAIN REGIONS AFFECTED BY ALZHEIMER’S DISEASE AND NORMAL AGING

PubMed Central

Reiman, Eric M.; Chen, Kewei; Langbaum, Jessica B.S.; Lee, Wendy; Reschke, Cole; Bandy, Daniel; Alexander, Gene E.; Caselli, Richard J.

2010-01-01

Epidemiological studies suggest that higher midlife serum total cholesterol levels are associated with an increased risk of Alzheimer’s disease (AD). Using fluorodeoxyglucose positron emission tomography (PET) in the study of cognitively normal late-middle-aged people, we demonstrated an association between apolipoprotein E (APOE) ε4 gene dose, the major genetic risk factor for late-onset AD, and lower measurements of the cerebral metabolic rate for glucose (CMRgl) in AD-affected brain regions, we proposed using PET as a presymptomatic endophenotype to evaluate other putative AD risk modifiers, and we then used it to support an aggregate cholesterol-related genetic risk score in the risk of AD. In the present study, we used PET to investigate the association between serum total cholesterol levels and cerebral metabolic rate for glucose metabolism (CMRgl) in 117 cognitively normal late middle-aged APOE ε4 homozygotes, heterozygotes and noncarriers. Higher serum total cholesterol levels were associated with lower CMRgl bilaterally in precuneus, parietotemporal and prefrontal regions previously found to be preferentially affected by AD, and in additional frontal regions previously found to be preferentially affected by normal aging. The associations were greater in APOE ε4 carriers than non-carriers in some of the AD-affected brain regions. We postulate the higher midlife serum total cholesterol levels accelerate brain processes associated with normal aging and conspire with other risk factors in the predisposition to AD. We propose using PET in proof-of-concept randomized controlled trials to rapidly evaluate the effects of midlife cholesterol-lowering treatments on the brain changes associated with normal aging and AD. PMID:19631758

Unable or Unwilling to Exercise Self-control? The Impact of Neuroscience on Perceptions of Impulsive Offenders

PubMed Central

Blakey, Robert; Kremsmayer, Tobias P.

2018-01-01

In growing numbers of court cases, neuroscience is presented to document the mental state of the offender at the level of the brain. While a small body of research has documented the effects of describing the brain state of psychotic offenders, this study tested the impact of neuroscience that could apply to far more offenders; that is the neuroscience of impulse control. In this online vignette experiment, 759 participants sentenced a normally controlled or normally impulsive actor, who committed a violent offense on impulse, explained in either cognitive or neurobiological terms. Although participants considered the neurobiological actor less responsible for his impulsive disposition than the cognitive actor, the neuroscientific testimony did not affect attributions of choice, blame, dangerousness, or punishment for the criminal act. In fact, the neuroscientific testimony exacerbated the perception that the offender offended consciously and “really wanted” to offend. The described disposition of the actor was also influential: participants attributed more capacity for reform, more free choice and consequently, more blame to the normally controlled actor. Participants also attributed this actor's offending more to his social life experiences and less to his genes and brain. However, this shift in attributions was unable to explain the greater blame directed at this offender. Together, such findings suggest that even when neuroscience changes attributions for impulsive character, attributions for impulsive offending may remain unchanged. Hence this study casts doubt on the mitigating and aggravating potential of neuroscientific testimony in court. PMID:29354076

Fluid dynamics vascular theory of brain and inner-ear function in traumatic brain injury: a translational hypothesis for diagnosis and treatment.

PubMed

Shulman, Abraham; Strashun, Arnold M

2009-01-01

It is hypothesized that in all traumatic brain injury (TBI) patients with a clinical history of closed or penetrating head injury, the initial head trauma is associated with a vibratory sensation and noise exposure, with resultant alteration in vascular supply to the structures and contents of the fluid compartments of brain and ear (i.e., the fluid dynamics vascular theory of brain-inner-ear function [FDVTBE]). The primary etiology-head trauma-results in an initial fluctuation, interference, or interaction in the normal fluid dynamics between brain and labyrinth of the inner ear, with a resultant clinical diversity of complaints varying in time of onset and severity. Normal function of the brain and ear is a reflection of a normal state of homeostasis between the fluid compartments in the brain of cerebrospinal fluid and perilymph-endolymph in the labyrinth of the ear. The normal homeostasis in the structures and contents between the two fluid compartment systems--intracerebral and intralabyrinthine--is controlled by mechanisms involved in the maintenance of normal pressures, water and electrolyte content, and neurotransmitter activities. The initial pathophysiology (a reflection of an alteration in the vascular supply to the brain-ear) is hypothesized to be an initial acute inflammatory response, persistence of which results in ischemia and an irreversible alteration in the involved neural substrates of brain-ear. Clinically, a chronic multisymptom complex becomes manifest. The multisymptom complex, individual for each TBI patient regardless of the diagnostic TBI category (i.e., mild, moderate, or severe), initially reflects processes of inflammation and ischemia which, in brain, result in brain volume loss identified as neurodegeneration and hydrocephalus ex vacuo or an alteration in cerebrospinal fluid production (i.e., pseudotumor cerebri) and, in ear, secondary endolymphatic hydrops with associated cochleovestibular complaints of hearing loss, tinnitus, vertigo, ear blockage, and hyperacusis. The FDVTBE integrates and translates a neurovascular hypothesis for Alzheimer's disease to TBI. This study presents an FDVTBE hypothesis of TBI to explain the clinical association of head trauma (TBI) and central nervous system neurodegeneration with multisensory complaints, highlighted by and focusing on cochleovestibular complaints. A clinical case report, previously published for demonstration of the cerebrovascular medical significance of a particular type of tinnitus, and evidence-based basic science and clinical medicine are cited to provide objective evidence in support and demonstration of the FDVTBE.

Maternal high-fat feeding leads to alterations of brain glucose metabolism in the offspring: positron emission tomography study in a porcine model.

PubMed

Sanguinetti, Elena; Liistro, Tiziana; Mainardi, Marco; Pardini, Silvia; Salvadori, Piero A; Vannucci, Alessandro; Burchielli, Silvia; Iozzo, Patricia

2016-04-01

Maternal obesity negatively affects fetal development. Abnormalities in brain glucose metabolism are predictive of metabolic-cognitive disorders. We studied the offspring (aged 0, 1, 6, 12 months) of minipigs fed a normal vs high-fat diet (HFD), by positron emission tomography (PET) to measure brain glucose metabolism, and ex vivo assessments of brain insulin receptors (IRβ) and GLUT4. At birth, brain glucose metabolism and IRβ were twice as high in the offspring of HFD-fed than control mothers. During infancy and youth, brain glucose uptake, GLUT4 and IRβ increased in the offspring of control mothers and decreased in those of HFD-fed mothers, leading to a 40-85% difference (p < 0.05), and severe glycogen depletion, lasting until adulthood. Maternal high-fat feeding leads to brain glucose overexposure during fetal development, followed by long-lasting depression in brain glucose metabolism in minipigs. These features may predispose the offspring to develop metabolic-neurodegenerative diseases.

Brain metabolism in patients with vegetative state after post-resuscitated hypoxic-ischemic brain injury: statistical parametric mapping analysis of F-18 fluorodeoxyglucose positron emission tomography.

PubMed

Kim, Yong Wook; Kim, Hyoung Seop; An, Young-sil

2013-03-01

Hypoxic-ischemic brain injury (HIBI) after cardiopulmonary resuscitation is one of the most devastating neurological conditions that causing the impaired consciousness. However, there were few studies investigated the changes of brain metabolism in patients with vegetative state (VS) after post-resuscitated HIBI. This study aimed to analyze the change of overall brain metabolism and elucidated the brain area correlated with the level of consciousness (LOC) in patients with VS after post-resuscitated HIBI. We consecutively enrolled 17 patients with VS after HIBI, who experienced cardiopulmonary resuscitation. Overall brain metabolism was measured by F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) and we compared regional brain metabolic patterns from 17 patients with those from 15 normal controls using voxel-by-voxel based statistical parametric mapping analysis. Additionally, we correlated the LOC measured by the JFK-coma recovery scale-revised of each patient with brain metabolism by covariance analysis. Compared with normal controls, the patients with VS after post-resuscitated HIBI revealed significantly decreased brain metabolism in bilateral precuneus, bilateral posterior cingulate gyrus, bilateral middle frontal gyri, bilateral superior parietal gyri, bilateral middle occipital gyri, bilateral precentral gyri (PFEW correctecd < 0.0001), and increased brain metabolism in bilateral insula, bilateral cerebella, and the brainstem (PFEW correctecd < 0.0001). In covariance analysis, the LOC was significantly correlated with brain metabolism in bilateral fusiform and superior temporal gyri (Puncorrected < 0.005). Our study demonstrated that the precuneus, the posterior cingulate area and the frontoparietal cortex, which is a component of neural correlate for consciousness, may be relevant structure for impaired consciousness in patient with VS after post-resuscitated HIBI. In post-resuscitated HIBI, measurement of brain metabolism using PET images may be helpful for investigating the brain function that cannot be obtained by morphological imaging and can be used to assess the brain area responsible for consciousness.

Region-specific Alterations in Glucocorticoid Receptor Expression in the Postmortem Brain of Teenage Suicide Victims

PubMed Central

Pandey, Ghanshyam N.; Rizavi, Hooriyah S.; Ren, Xinguo; Dwivedi, Yogesh; Palkovits, Miklós

2013-01-01

Introduction Abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and suicide. The purpose of this study was to test the hypothesis that the reported dysregulation of the HPA axis in suicide may be related to a disturbed feedback inhibition caused by decreased corticoid receptors in the brain. We therefore determined the protein and gene expression of glucocorticoid (GR) and mineralocorticoid receptors (MR) in the postmortem brain of teenage suicide victims and matched normal controls. Methods Protein and mRNA expression of GR (GR-α and GR-β) and MR and the mRNA expression of glucocorticoid-induced leucine zipper (GILZ), a target gene for GR were determined by immunolabeling using Western blot technique and the real-time RT-polymerase chain reaction (qPCR) technique in the prefrontal cortex (PFC), hippocampus, subiculum, and amygdala obtained from 24 teenage suicide victims and 24 teenage control subjects. Results We observed that protein and gene expression of GR-α was significantly decreased in the PFC and amygdala, but not in the hippocampus or subiculum, of teenage suicide victims compared with normal control subjects. Also, the mRNA levels of GR inducible target gene GILZ was significantly decreased in PFC and amygdaloid nuclei but not in hippocampus compared with controls. In contrast, no significant differences were observed in protein or gene expression of MR in any of the areas studied between teenage suicide victims and normal control subjects. There was no difference in the expression of GR-β in the PFC between suicide victims and normal controls. Conclusions These results suggested that the observed dysregulation of the HPA axis in suicide may be related to a decreased expression of GR-α and GR inducible genes in the PFC and amygdala of teenage suicide victims. The reason why GR receptors are not dysregulated in the hippocampus or subiculum, presumably two sites of stress action, are not clear at this time. PMID:23845513

Altered Blood-Brain Barrier Permeability in Patients With Systemic Lupus Erythematosus: A Novel Imaging Approach.

PubMed

Gulati, Gaurav; Jones, Jordan T; Lee, Gregory; Altaye, Mekibib; Beebe, Dean W; Meyers-Eaton, Jamie; Wiley, Kasha; Brunner, Hermine I; DiFrancesco, Mark W

2017-02-01

To evaluate a safe, noninvasive magnetic resonance imaging (MRI) method to measure regional blood-brain barrier integrity and investigate its relationship with neurocognitive function and regional gray matter volume in juvenile-onset systemic lupus erythematosus (SLE). In this cross-sectional, case-control study, capillary permeability was measured as a marker of blood-brain barrier integrity in juvenile SLE patients and matched healthy controls, using a combination of arterial spin labeling and diffusion-weighted brain MRI. Regional gray matter volume was measured by voxel-based morphometry. Correlation analysis was done to investigate the relationship between regional capillary permeability and regional gray matter volume. Formal neurocognitive testing was completed (measuring attention, visuoconstructional ability, working memory, and psychomotor speed), and scores were regressed against regional blood-brain barrier integrity among juvenile SLE patients. Formal cognitive testing confirmed normal cognitive ability in all juvenile SLE subjects (n = 11) included in the analysis. Regional capillary permeability was negatively associated (P = 0.026) with neurocognitive performance concerning psychomotor speed in the juvenile SLE cohort. Compared with controls (n = 11), juvenile SLE patients had significantly greater capillary permeability involving Brodmann's areas 19, 28, 36, and 37 and caudate structures (P < 0.05 for all). There is imaging evidence of increased regional capillary permeability in juvenile SLE patients with normal cognitive performance using a novel noninvasive MRI technique. These blood-brain barrier outcomes appear consistent with functional neuronal network alterations and gray matter volume loss previously observed in juvenile SLE patients with overt neurocognitive deficits, supporting the notion that blood-brain barrier integrity loss precedes the loss of cognitive ability in juvenile SLE. Longitudinal studies are needed to confirm the findings of this pilot study. © 2016, American College of Rheumatology.

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.

On children's dyslexia with NIRS

NASA Astrophysics Data System (ADS)

Gan, Zhuo; Li, Chengjun; Gong, Hui; Luo, Qingming; Yao, Bin; Song, Ranran; Wu, Hanrong

2003-12-01

Developmental dyslexia is a kind of prevalent psychologic disease. Some functional imaging technologies, such as FMRI and PET, have been used to study the brain activities of dyslexics. NIRS is a kind of novel technology which is more and more widely being used for study of the cognitive psychology. However, there aren"t reports about the dyslexic research using NIRS to be found until now. This paper introduces a NIRS system of four measuring channels. Brain activities of dyslexic subjects and normal subjects during reading task were studied with the NIRS system. Two groups of subjects, the group of dyslexia and the group of normal, were appointed to perform two reading tasks. At the same time, their cortical activities were measured with the NIRS system. This experimental result indicates that the brain activities of the dyslexic group were significantly higher than the control group in BA 48 and that NIRS can be used for the study of human brain activity.

Brain antibodies in the cortex and blood of people with schizophrenia and controls

PubMed Central

Glass, L J; Sinclair, D; Boerrigter, D; Naude, K; Fung, S J; Brown, D; Catts, V S; Tooney, P; O'Donnell, M; Lenroot, R; Galletly, C; Liu, D; Weickert, T W; Shannon Weickert, C

2017-01-01

The immune system is implicated in the pathogenesis of schizophrenia, with elevated proinflammatory cytokine mRNAs found in the brains of ~40% of individuals with the disorder. However, it is not clear if antibodies (specifically immunoglobulin-γ (IgG)) can be found in the brain of people with schizophrenia and if their abundance relates to brain inflammatory cytokine mRNA levels. Therefore, we investigated the localization and abundance of IgG in the frontal cortex of people with schizophrenia and controls, and the impact of proinflammatory cytokine status on IgG abundance in these groups. Brain IgGs were detected surrounding blood vessels in the human and non-human primate frontal cortex by immunohistochemistry. IgG levels did not differ significantly between schizophrenia cases and controls, or between schizophrenia cases in ‘high’ and ‘low’ proinflammatory cytokine subgroups. Consistent with the existence of IgG in the parenchyma of human brain, mRNA and protein of the IgG transporter (FcGRT) were present in the brain, and did not differ according to diagnosis or inflammatory status. Finally, brain-reactive antibody presence and abundance was investigated in the blood of living people. The plasma of living schizophrenia patients and healthy controls contained antibodies that displayed positive binding to Rhesus macaque cerebellar tissue, and the abundance of these antibodies was significantly lower in patients than controls. These findings suggest that antibodies in the brain and brain-reactive antibodies in the blood are present under normal circumstances. PMID:28786974

Brain antibodies in the cortex and blood of people with schizophrenia and controls.

PubMed

Glass, L J; Sinclair, D; Boerrigter, D; Naude, K; Fung, S J; Brown, D; Catts, V S; Tooney, P; O'Donnell, M; Lenroot, R; Galletly, C; Liu, D; Weickert, T W; Shannon Weickert, C

2017-08-08

The immune system is implicated in the pathogenesis of schizophrenia, with elevated proinflammatory cytokine mRNAs found in the brains of ~40% of individuals with the disorder. However, it is not clear if antibodies (specifically immunoglobulin-γ (IgG)) can be found in the brain of people with schizophrenia and if their abundance relates to brain inflammatory cytokine mRNA levels. Therefore, we investigated the localization and abundance of IgG in the frontal cortex of people with schizophrenia and controls, and the impact of proinflammatory cytokine status on IgG abundance in these groups. Brain IgGs were detected surrounding blood vessels in the human and non-human primate frontal cortex by immunohistochemistry. IgG levels did not differ significantly between schizophrenia cases and controls, or between schizophrenia cases in 'high' and 'low' proinflammatory cytokine subgroups. Consistent with the existence of IgG in the parenchyma of human brain, mRNA and protein of the IgG transporter (FcGRT) were present in the brain, and did not differ according to diagnosis or inflammatory status. Finally, brain-reactive antibody presence and abundance was investigated in the blood of living people. The plasma of living schizophrenia patients and healthy controls contained antibodies that displayed positive binding to Rhesus macaque cerebellar tissue, and the abundance of these antibodies was significantly lower in patients than controls. These findings suggest that antibodies in the brain and brain-reactive antibodies in the blood are present under normal circumstances.

Apicobasal polarity of brain endothelial cells

PubMed Central

Worzfeld, Thomas

2015-01-01

Normal brain homeostasis depends on the integrity of the blood–brain barrier that controls the access of nutrients, humoral factors, and immune cells to the CNS. The blood–brain barrier is composed mainly of brain endothelial cells. Forming the interface between two compartments, they are highly polarized. Apical/luminal and basolateral/abluminal membranes differ in their lipid and (glyco-)protein composition, allowing brain endothelial cells to secrete or transport soluble factors in a polarized manner and to maintain blood flow. Here, we summarize the basic concepts of apicobasal cell polarity in brain endothelial cells. To address potential molecular mechanisms underlying apicobasal polarity in brain endothelial cells, we draw on investigations in epithelial cells and discuss how polarity may go awry in neurological diseases. PMID:26661193

Multicentre imaging measurements for oncology and in the brain

PubMed Central

Tofts, P S; Collins, D J

2011-01-01

Multicentre imaging studies of brain tumours (and other tumour and brain studies) can enable a large group of patients to be studied, yet they present challenging technical problems. Differences between centres can be characterised, understood and minimised by use of phantoms (test objects) and normal control subjects. Normal white matter forms an excellent standard for some MRI parameters (e.g. diffusion or magnetisation transfer) because the normal biological range is low (<2–3%) and the measurements will reflect this, provided the acquisition sequence is controlled. MR phantoms have benefits and they are necessary for some parameters (e.g. tumour volume). Techniques for temperature monitoring and control are given. In a multicentre study or treatment trial, between-centre variation should be minimised. In a cross-sectional study, all groups should be represented at each centre and the effect of centre added as a covariate in the statistical analysis. In a serial study of disease progression or treatment effect, individual patients should receive all of their scans at the same centre; the power is then limited by the within-subject reproducibility. Sources of variation that are generic to any imaging method and analysis parameters include MR sequence mismatch, B1 errors, CT effective tube potential, region of interest generation and segmentation procedure. Specific tissue parameters are analysed in detail to identify the major sources of variation and the most appropriate phantoms or normal studies. These include dynamic contrast-enhanced and dynamic susceptibility contrast gadolinium imaging, T1, diffusion, magnetisation transfer, spectroscopy, tumour volume, arterial spin labelling and CT perfusion. PMID:22433831

A combination of lipidomics, MS imaging, and PET scan imaging reveals differences in cerebral activity in rat pups according to the lipid quality of infant formulas.

PubMed

Aidoud, Nacima; Delplanque, Bernadette; Baudry, Charlotte; Garcia, Cyrielle; Moyon, Anais; Balasse, Laure; Guillet, Benjamin; Antona, Claudine; Darmaun, Dominique; Fraser, Karl; Ndiaye, Sega; Leruyet, Pascale; Martin, Jean-Charles

2018-03-22

We evaluated the effect of adding docosahexaenoic:arachidonic acids (3:2) (DHA+ARA) to 2 representative commercial infant formulas on brain activity and brain and eye lipids in an artificially reared rat pup model. The formula lipid background was either a pure plant oil blend, or dairy fat with a plant oil blend (1:1). Results at weaning were compared to breast milk-fed pups. Brain functional activity was determined by positron emission tomography scan imaging, the brain and eye fatty acid and lipid composition by targeted and untargeted lipidomics, and DHA brain regional location by mass-spectrometry imaging. The brain functional activity was normalized to controls with DHA+ARA added to the formulas. DHA in both brain and eyes was influenced by formula intake, but more than two-thirds of tissue DHA-glycerolipids remained insensitive to the dietary challenge. However, the DHA lipidome correlated better with brain function than sole DHA content ( r = 0.70 vs. r = 0.48; P < 0.05). Brain DHA regional distribution was more affected by the formula lipid background than the provision of PUFAs. Adding DHA+ARA to formulas alters the DHA content and lipidome of nervous tissue in the neonate, making it closer to dam milk-fed controls, and normalizes brain functional activity.-Aidoud, N., Delplanque, B., Baudry, C., Garcia, C., Moyon, A., Balasse, L., Guillet, B., Antona, C., Darmaun, D., Fraser, K., Ndiaye, S., Leruyet, P., Martin, J.-C. A combination of lipidomics, MS imaging, and PET scan imaging reveals differences in cerebral activity in rat pups according to the lipid quality of infant formulas.

Reduced hemispheric asymmetry of brain anatomical networks in attention deficit hyperactivity disorder.

PubMed

Li, Dandan; Li, Ting; Niu, Yan; Xiang, Jie; Cao, Rui; Liu, Bo; Zhang, Hui; Wang, Bin

2018-05-11

Despite many studies reporting a variety of alterations in brain networks in patients with attention deficit hyperactivity disorder (ADHD), alterations in hemispheric anatomical networks are still unclear. In this study, we investigated topology alterations in hemispheric white matter in patients with ADHD and the relationship between these alterations and clinical features of the illness. Weighted hemispheric brain anatomical networks were first constructed for each of 40 right-handed patients with ADHD and 53 matched normal controls. Then, graph theoretical approaches were utilized to compute hemispheric topological properties. The small-world property was preserved in the hemispheric network. Furthermore, a significant group-by-hemisphere interaction was revealed in global efficiency, local efficiency and characteristic path length, attributed to the significantly reduced hemispheric asymmetry of global and local integration in patients with ADHD compared with normal controls. Specifically, reduced asymmetric regional efficiency was found in three regions. Finally, we found that the abnormal asymmetry of hemispheric brain anatomical network topology and regional efficiency were both associated with clinical features (the Adult ADHD Self-Report Scale and Wechsler Adult Intelligence Scale) in patients. Our findings provide new insights into the lateralized nature of hemispheric dysconnectivity and highlight the potential for using brain network measures of hemispheric asymmetry as neural biomarkers for ADHD and its clinical features.

EGFR-directed Affibody for fluorescence-guided glioma surgery: time-dose analysis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Ribeiro de Souza, Ana Luiza; Marra, Kayla; Gunn, Jason R.; Elliott, Jonathan T.; Samkoe, Kimberley S.; Paulsen, Keith D.; Draney, Daniel R.; Feldwisch, Joachim

2016-03-01

The key to fluorescence guided surgical oncology is the ability to create specific contrast between normal and glioma tissue. The blood brain barrier that limits the delivery of substances to the normal brain is broken in tumors, allowing accumulation of agents in the tumor interior. However, for a clinical success, imaging agents should be in the infiltrative edges to minimize the resection of normal brain while enable the removal of tumor. The aberrant overexpression and/or activation of EGFR is associated with many types of cancers, including glioblastoma and the injection of a fluorescent molecule targeted to these receptors would improve tumor contrast during fluorescence guided surgery. Affibody molecules have intentional medium affinity and high potential specificity, which are the desirable features of a good surgical imaging agent. The aim of this study was evaluate the brain/glioma uptake of ABY029 labeled with near-infrared dye IRDye800CW after intravenous injection. Rats were either inoculated with orthotopic implantations of U251 human glioma cell line or PBS (shams control) in the brain. The tumors were allowed to grow for 2-3 weeks before carrying out fluorescent tracer experiments. Fluorescent imaging of ex vivo brain slices from rats was acquired at different time points after infection of fluorescently labeled EGFR-specific affibody to verify which time provided maximal contrast tumor to normal brain. Although the tumor was most clearly visualized after 1h of IRDye800CW-labeled ABY029 injection, the tumor location could be identified from the background after 48h. These results suggest that the NIR-labeled affibody examined shows excellent potential to increase surgical visualization for confirmed EGFR positive tumors.

Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

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

Rumsey, J.M.; Duara, R.; Grady, C.

The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic ratesmore » (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions.« less

Estimating brain age using high-resolution pattern recognition: Younger brains in long-term meditation practitioners.

PubMed

Luders, Eileen; Cherbuin, Nicolas; Gaser, Christian

2016-07-01

Normal aging is known to be accompanied by loss of brain substance. The present study was designed to examine whether the practice of meditation is associated with a reduced brain age. Specific focus was directed at age fifty and beyond, as mid-life is a time when aging processes are known to become more prominent. We applied a recently developed machine learning algorithm trained to identify anatomical correlates of age in the brain translating those into one single score: the BrainAGE index (in years). Using this validated approach based on high-dimensional pattern recognition, we re-analyzed a large sample of 50 long-term meditators and 50 control subjects estimating and comparing their brain ages. We observed that, at age fifty, brains of meditators were estimated to be 7.5years younger than those of controls. In addition, we examined if the brain age estimates change with increasing age. While brain age estimates varied only little in controls, significant changes were detected in meditators: for every additional year over fifty, meditators' brains were estimated to be an additional 1month and 22days younger than their chronological age. Altogether, these findings seem to suggest that meditation is beneficial for brain preservation, effectively protecting against age-related atrophy with a consistently slower rate of brain aging throughout life. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain-Derived Neurotrophic Factor Gene Expression in Pediatric Bipolar Disorder: Effects of Treatment and Clinical Response

ERIC Educational Resources Information Center

Pandey, Ghanshyam N.; Rizavi, Hooriyah S.; Dwivedi, Yogesh; Pavuluri, Mani N.

2008-01-01

The study determines the gene expression of brain-derived neurotrophic factor (BDNF) in the lymphocytes of subjects with pediatric bipolar disorder (PBD) before and during treatment with mood stabilizers and in drug-free normal control subjects. Results indicate the potential of BDNF levels as a biomarker for PBD and as a treatment predictor and…

Fluid intelligence and brain functional organization in aging yoga and meditation practitioners

PubMed Central

Gard, Tim; Taquet, Maxime; Dixit, Rohan; Hölzel, Britta K.; de Montjoye, Yves-Alexandre; Brach, Narayan; Salat, David H.; Dickerson, Bradford C.; Gray, Jeremy R.; Lazar, Sara W.

2014-01-01

Numerous studies have documented the normal age-related decline of neural structure, function, and cognitive performance. Preliminary evidence suggests that meditation may reduce decline in specific cognitive domains and in brain structure. Here we extended this research by investigating the relation between age and fluid intelligence and resting state brain functional network architecture using graph theory, in middle-aged yoga and meditation practitioners, and matched controls. Fluid intelligence declined slower in yoga practitioners and meditators combined than in controls. Resting state functional networks of yoga practitioners and meditators combined were more integrated and more resilient to damage than those of controls. Furthermore, mindfulness was positively correlated with fluid intelligence, resilience, and global network efficiency. These findings reveal the possibility to increase resilience and to slow the decline of fluid intelligence and brain functional architecture and suggest that mindfulness plays a mechanistic role in this preservation. PMID:24795629

L-Phenylalanine preloading reduces the (10)B(n, α)(7)Li dose to the normal brain by inhibiting the uptake of boronophenylalanine in boron neutron capture therapy for brain tumours.

PubMed

Watanabe, Tsubasa; Tanaka, Hiroki; Fukutani, Satoshi; Suzuki, Minoru; Hiraoka, Masahiro; Ono, Koji

2016-01-01

Boron neutron capture therapy (BNCT) is a cellular-level particle radiation therapy that combines the selective delivery of boron compounds to tumour tissue with neutron irradiation. Previously, high doses of one of the boron compounds used for BNCT, L-BPA, were found to reduce the boron-derived irradiation dose to the central nervous system. However, injection with a high dose of L-BPA is not feasible in clinical settings. We aimed to find an alternative method to improve the therapeutic efficacy of this therapy. We examined the effects of oral preloading with various analogues of L-BPA in a xenograft tumour model and found that high-dose L-phenylalanine reduced the accumulation of L-BPA in the normal brain relative to tumour tissue. As a result, the maximum irradiation dose in the normal brain was 19.2% lower in the L-phenylalanine group relative to the control group. This study provides a simple strategy to improve the therapeutic efficacy of conventional boron compounds for BNCT for brain tumours and the possibility to widen the indication of BNCT to various kinds of other tumours. Copyright © 2015. Published by Elsevier Ireland Ltd.

Influence of chronobiology on the nanoparticle-mediated drug uptake into the brain.

PubMed

Kreuter, Jörg

2015-02-03

Little attention so-far has been paid to the influence of chronobiology on the processes of nanoparticle uptake and transport into the brain, even though this transport appears to be chronobiologically controlled to a significant degree. Nanoparticles with specific surface properties enable the transport across the blood-brain barrier of many drugs that normally cannot cross this barrier. A clear dependence of the central antinociceptive (analgesic) effects of a nanoparticle-bound model drug, i.e., the hexapeptide dalargin, on the time of day was observable after intravenous injection in mice. In addition to the strongly enhanced antinociceptive effect due to the binding to the nanoparticles, the minima and maxima of the pain reaction with the nanoparticle-bound drug were shifted by almost half a day compared to the normal circadian nociception: The maximum in the pain reaction after i.v. injection of the nanoparticle-bound dalargin occurred during the later rest phase of the animals whereas the normal pain reaction and that of a dalargin solution was highest during the active phase of the mice in the night. This important shift could be caused by an enhanced endo- and exocytotic particulates transport activity of the brain capillary endothelial cells or within the brain during the rest phase.

A SPECT study of language and brain reorganization three years after pediatric brain injury.

PubMed

Chiu Wong, Stephanie B; Chapman, Sandra B; Cook, Lois G; Anand, Raksha; Gamino, Jacquelyn F; Devous, Michael D

2006-01-01

Using single photon emission computed tomography (SPECT), we investigated brain plasticity in children 3 years after sustaining a severe traumatic brain injury (TBI). First, we assessed brain perfusion patterns (i.e., the extent of brain blood flow to regions of the brain) at rest in eight children who suffered severe TBI as compared to perfusion patterns in eight normally developing children. Second, we examined differences in perfusion between children with severe TBI who showed good versus poor recovery in complex discourse skills. Specifically, the children were asked to produce and abstract core meaning for two stories in the form of a lesson. Inconsistent with our predictions, children with severe TBI showed areas of increased perfusion as compared to normally developing controls. Adult studies have shown the reverse pattern with TBI associated with reduced perfusion. With regard to the second aim and consistent with previously identified brain-discourse relations, we found a strong positive association between perfusion in right frontal regions and discourse abstraction abilities, with higher perfusion linked to better discourse outcomes and lower perfusion linked to poorer discourse outcomes. Furthermore, brain-discourse patterns of increased perfusion in left frontal regions were associated with lower discourse abstraction ability. The results are discussed in terms of how brain changes may represent adaptive and maladaptive plasticity. The findings offer direction for future studies of brain plasticity in response to neurocognitive treatments.

Weight Perturbation Alters Leptin Signal Transduction in a Region-Specific Manner throughout the Brain

PubMed Central

Morabito, Michael V.; Ravussin, Yann; Mueller, Bridget R.; Skowronski, Alicja A.; Watanabe, Kazuhisa; Foo, Kylie S.; Lee, Samuel X.; Lehmann, Anders; Hjorth, Stephan; Zeltser, Lori M.; LeDuc, Charles A.; Leibel, Rudolph L.

2017-01-01

Diet-induced obesity (DIO) resulting from consumption of a high fat diet (HFD) attenuates normal neuronal responses to leptin and may contribute to the metabolic defense of an acquired higher body weight in humans; the molecular bases for the persistence of this defense are unknown. We measured the responses of 23 brain regions to exogenous leptin in 4 different groups of weight- and/or diet-perturbed mice. Responses to leptin were assessed by quantifying pSTAT3 levels in brain nuclei 30 minutes following 3 mg/kg intraperitoneal leptin. HFD attenuated leptin sensing throughout the brain, but weight loss did not restore central leptin signaling to control levels in several brain regions important in energy homeostasis, including the arcuate and dorsomedial hypothalamic nuclei. Effects of diet on leptin signaling varied by brain region, with results dependent on the method of weight loss (restriction of calories of HFD, ad lib intake of standard mouse chow). High fat diet attenuates leptin signaling throughout the brain, but some brain regions maintain their ability to sense leptin. Weight loss restores leptin sensing to some degree in most (but not all) brain regions, while other brain regions display hypersensitivity to leptin following weight loss. Normal leptin sensing was restored in several brain regions, with the pattern of restoration dependent on the method of weight loss. PMID:28107353

Alternative Polyadenylation in Glioblastoma Multiforme and Changes in Predicted RNA Binding Protein Profiles

PubMed Central

Shao, Jiaofang; Zhang, Jing; Zhang, Zengming; Jiang, Huawei; Lou, Xiaoyan; Foltz, Gregory; Lan, Qing; Huang, Qiang

2013-01-01

Abstract Alternative polyadenylation (APA) is widely present in the human genome and plays a key role in carcinogenesis. We conducted a comprehensive analysis of the APA products in glioblastoma multiforme (GBM, one of the most lethal brain tumors) and normal brain tissues and further developed a computational pipeline, RNAelements (http://sysbio.zju.edu.cn/RNAelements/), using covariance model from known RNA binding protein (RBP) targets acquired by RNA Immunoprecipitation (RIP) analysis. We identified 4530 APA isoforms for 2733 genes in GBM, and found that 182 APA isoforms from 148 genes showed significant differential expression between normal and GBM brain tissues. We then focused on three genes with long and short APA isoforms that show inconsistent expression changes between normal and GBM brain tissues. These were myocyte enhancer factor 2D, heat shock factor binding protein 1, and polyhomeotic homolog 1 (Drosophila). Using the RNAelements program, we found that RBP binding sites were enriched in the alternative regions between the first and the last polyadenylation sites, which would result in the short APA forms escaping regulation from those RNA binding proteins. To the best of our knowledge, this report is the first comprehensive APA isoform dataset for GBM and normal brain tissues. Additionally, we demonstrated a putative novel APA-mediated mechanism for controlling RNA stability and translation for APA isoforms. These observations collectively lay a foundation for novel diagnostics and molecular mechanisms that can inform future therapeutic interventions for GBM. PMID:23421905

Structural changes of the corpus callosum in tinnitus

PubMed Central

Diesch, Eugen; Schummer, Verena; Kramer, Martin; Rupp, Andre

2012-01-01

Objectives: In tinnitus, several brain regions seem to be structurally altered, including the medial partition of Heschl's gyrus (mHG), the site of the primary auditory cortex. The mHG is smaller in tinnitus patients than in healthy controls. The corpus callosum (CC) is the main interhemispheric commissure of the brain connecting the auditory areas of the left and the right hemisphere. Here, we investigate whether tinnitus status is associated with CC volume. Methods: The midsagittal cross-sectional area of the CC was examined in tinnitus patients and healthy controls in which an examination of the mHG had been carried out earlier. The CC was extracted and segmented into subregions which were defined according to the most common CC morphometry schemes introduced by Witelson (1989) and Hofer and Frahm (2006). Results: For both CC segmentation schemes, the CC posterior midbody was smaller in male patients than in male healthy controls and the isthmus, the anterior midbody, and the genou were larger in female patients than in female controls. With CC size normalized relative to mHG volume, the normalized CC splenium was larger in male patients than male controls and the normalized CC splenium, the isthmus and the genou were larger in female patients than female controls. Normalized CC segment size expresses callosal interconnectivity relative to auditory cortex volume. Conclusion: It may be argued that the predominant function of the CC is excitatory. The stronger callosal interconnectivity in tinnitus patients, compared to healthy controls, may facilitate the emergence and maintenance of a positive feedback loop between tinnitus generators located in the two hemispheres. PMID:22470322

Brain Perfusion and Diffusion Abnormalities in Children Treated for Posterior Fossa Brain Tumors.

PubMed

Li, Matthew D; Forkert, Nils D; Kundu, Palak; Ambler, Cheryl; Lober, Robert M; Burns, Terry C; Barnes, Patrick D; Gibbs, Iris C; Grant, Gerald A; Fisher, Paul G; Cheshier, Samuel H; Campen, Cynthia J; Monje, Michelle; Yeom, Kristen W

2017-06-01

To compare cerebral perfusion and diffusion in survivors of childhood posterior fossa brain tumor with neurologically normal controls and correlate differences with cognitive dysfunction. We analyzed retrospectively arterial spin-labeled cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) in 21 patients with medulloblastoma (MB), 18 patients with pilocytic astrocytoma (PA), and 64 neurologically normal children. We generated ANCOVA models to evaluate treatment effects on the cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, and cerebral white matter at time points an average of 5.7 years after original diagnosis. A retrospective review of patient charts identified 12 patients with neurocognitive data and in whom the relationship between IQ and magnetic resonance imaging variables was assessed for each brain structure. Patients with MB (all treated with surgery, chemotherapy, and radiation) had significantly lower global CBF relative to controls (10%-23% lower, varying by anatomic region, all adjusted P?

Liver transplantation nearly normalizes brain spontaneous activity and cognitive function at 1 month: a resting-state functional MRI study.

PubMed

Cheng, Yue; Huang, Lixiang; Zhang, Xiaodong; Zhong, Jianhui; Ji, Qian; Xie, Shuangshuang; Chen, Lihua; Zuo, Panli; Zhang, Long Jiang; Shen, Wen

2015-08-01

To investigate the short-term brain activity changes in cirrhotic patients with Liver transplantation (LT) using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. Twenty-six cirrhotic patients as transplant candidates and 26 healthy controls were included in this study. The assessment was repeated for a sub-group of 12 patients 1 month after LT. ReHo values were calculated to evaluate spontaneous brain activity and whole brain voxel-wise analysis was carried to detect differences between groups. Correlation analyses were performed to explore the relationship between the change of ReHo with the change of clinical indexes pre- and post-LT. Compared to pre-LT, ReHo values increased in the bilateral inferior frontal gyrus (IFG), right inferior parietal lobule (IPL), right supplementary motor area (SMA), right STG and left middle frontal gyrus (MFG) in patients post-LT. Compared to controls, ReHo values of post-LT patients decreased in the right precuneus, right SMA and increased in bilateral temporal pole, left caudate, left MFG, and right STG. The changes of ReHo in the right SMA, STG and IFG were correlated with change of digit symbol test (DST) scores (P < 0.05 uncorrected). This study found that, at 1 month after LT, spontaneous brain activity of most brain regions with decreased ReHo in pre-LT was substantially improved and nearly normalized, while spontaneous brain activity of some brain regions with increased ReHo in pre-LT continuously increased. ReHo may provide information on the neural mechanisms of LT' effects on brain function.

Normal variation in early parental sensitivity predicts child structural brain development.

PubMed

Kok, Rianne; Thijssen, Sandra; Bakermans-Kranenburg, Marian J; Jaddoe, Vincent W V; Verhulst, Frank C; White, Tonya; van IJzendoorn, Marinus H; Tiemeier, Henning

2015-10-01

Early caregiving can have an impact on brain structure and function in children. The influence of extreme caregiving experiences has been demonstrated, but studies on the influence of normal variation in parenting quality are scarce. Moreover, no studies to date have included the role of both maternal and paternal sensitivity in child brain maturation. This study examined the prospective relation between mothers' and fathers' sensitive caregiving in early childhood and brain structure later in childhood. Participants were enrolled in a population-based prenatal cohort. For 191 families, maternal and paternal sensitivity was repeatedly observed when the child was between 1 year and 4 years of age. Head circumference was assessed at 6 weeks, and brain structure was assessed using magnetic resonance imaging (MRI) measurements at 8 years of age. Higher levels of parental sensitivity in early childhood were associated with larger total brain volume (adjusted β = 0.15, p = .01) and gray matter volume (adjusted β = 0.16, p = .01) at 8 years, controlling for infant head size. Higher levels of maternal sensitivity in early childhood were associated with a larger gray matter volume (adjusted β = 0.13, p = .04) at 8 years, independent of infant head circumference. Associations with maternal versus paternal sensitivity were not significantly different. Normal variation in caregiving quality is related to markers of more optimal brain development in children. The results illustrate the important role of both mothers and fathers in child brain development. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects

PubMed Central

Millard, Steven P.; Lutz, Franziska; Li, Ge; Galasko, Douglas R.; Farlow, Martin R.; Quinn, Joseph F.; Kaye, Jeffrey A.; Leverenz, James B.; Tsuang, Debby; Yu, Chang-En; Peskind, Elaine R.; Bekris, Lynn M.

2013-01-01

Low cerebrospinal fluid (CSF) Aβ42 levels correlate with increased brain Aβ deposition in Alzheimer’s disease (AD), which suggests a disruption in the degradation and clearance of Aβ from the brain. In addition, APOE ε4 carriers have lower CSF Aβ42 levels than non-carriers. The hypothesis of this investigation was that CSF Aβ42 levels correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of Aβ from the brain. CSF Aβ42 levels were tested for associations with Aβ degradation and clearance genes and APOE ε4. Twenty-four SNPs located within the 5′ and 3′ regions of 12 genes were analyzed. The study sample consisted of 99 AD patients and 168 cognitively normal control subjects. CSF Aβ42 levels were associated with APOE ε4 status in controls but not in AD patients; A2M regulatory region SNPs were also associated with CSF Aβ42 levels in controls, but not in AD patients, even after adjusting for APOE ε4. These results suggest that genetic variation within the A2M gene influences CSF Aβ42 levels. PMID:24011543

Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain.

PubMed

Al-Mashhadi, Sufana; Simpson, Julie E; Heath, Paul R; Dickman, Mark; Forster, Gillian; Matthews, Fiona E; Brayne, Carol; Ince, Paul G; Wharton, Stephen B

2015-09-01

White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2'-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. © 2014 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

Some Kinds of Cancer Kids Get

MedlinePlus

... normal grow too fast and spread out of control. A group or mass of growing cells is called a ... person, these white blood cells multiply out of control. They fill up the bone ... Cancer A brain tumor is a group or clump of fast-growing cells that can ...

Treatment effectiveness of brain-computer interface training for patients with focal hand dystonia: A double-case study.

PubMed

Hashimoto, Yasunari; Ota, Tetsuo; Mukaino, Masahiko; Ushiba, Junichi

2013-01-01

Neuronal mechanism underlying dystonia is poorly understood. Dystonia can be treated with botulinum toxin injections or deep brain stimulation but these methods are not available for every patient therefore we need to consider other methods Our study aimed to develop a novel rehabilitation training using brain-computer interface system that decreases neural overexcitation in the sensorimotor cortex by bypassing brain and external world without the normal neuromuscular pathway. To achieve this purpose, we recorded electroencephalograms (10 channels) and forearm electromyograms (3 channels) from 2 patients with the diagnosis of writer's cramp and healthy control participants as a preliminary experiment. The patients were trained to control amplitude of their electroencephalographic signal using feedback from the brain-computer interface for 1 hour a day and then continued the training twice a month. After the 5-month training, a patient clearly showed reduction of dystonic movement during writing.

The neural basis of impaired self-awareness after traumatic brain injury

PubMed Central

Ham, Timothy E.; Bonnelle, Valerie; Hellyer, Peter; Jilka, Sagar; Robertson, Ian H.; Leech, Robert

2014-01-01

Self-awareness is commonly impaired after traumatic brain injury. This is an important clinical issue as awareness affects long-term outcome and limits attempts at rehabilitation. It can be investigated by studying how patients respond to their errors and monitor their performance on tasks. As awareness is thought to be an emergent property of network activity, we tested the hypothesis that impaired self-awareness is associated with abnormal brain network function. We investigated a group of subjects with traumatic brain injury (n = 63) split into low and high performance-monitoring groups based on their ability to recognize and correct their own errors. Brain network function was assessed using resting-state and event-related functional magnetic resonance imaging. This allowed us to investigate baseline network function, as well as the evoked response of networks to specific events including errors. The low performance-monitoring group underestimated their disability and showed broad attentional deficits. Neural activity within what has been termed the fronto-parietal control network was abnormal in patients with impaired self-awareness. The dorsal anterior cingulate cortex is a key part of this network that is involved in performance-monitoring. This region showed reduced functional connectivity to the rest of the fronto-parietal control network at ‘rest’. In addition, the anterior insulae, which are normally tightly linked to the dorsal anterior cingulate cortex, showed increased activity following errors in the impaired group. Interestingly, the traumatic brain injury patient group with normal performance-monitoring showed abnormally high activation of the right middle frontal gyrus, putamen and caudate in response to errors. The impairment of self-awareness was not explained either by the location of focal brain injury, or the amount of traumatic axonal injury as demonstrated by diffusion tensor imaging. The results suggest that impairments of self-awareness after traumatic brain injury result from breakdown of functional interactions between nodes within the fronto-parietal control network. PMID:24371217

The neural basis of impaired self-awareness after traumatic brain injury.

PubMed

Ham, Timothy E; Bonnelle, Valerie; Hellyer, Peter; Jilka, Sagar; Robertson, Ian H; Leech, Robert; Sharp, David J

2014-02-01

Self-awareness is commonly impaired after traumatic brain injury. This is an important clinical issue as awareness affects long-term outcome and limits attempts at rehabilitation. It can be investigated by studying how patients respond to their errors and monitor their performance on tasks. As awareness is thought to be an emergent property of network activity, we tested the hypothesis that impaired self-awareness is associated with abnormal brain network function. We investigated a group of subjects with traumatic brain injury (n = 63) split into low and high performance-monitoring groups based on their ability to recognize and correct their own errors. Brain network function was assessed using resting-state and event-related functional magnetic resonance imaging. This allowed us to investigate baseline network function, as well as the evoked response of networks to specific events including errors. The low performance-monitoring group underestimated their disability and showed broad attentional deficits. Neural activity within what has been termed the fronto-parietal control network was abnormal in patients with impaired self-awareness. The dorsal anterior cingulate cortex is a key part of this network that is involved in performance-monitoring. This region showed reduced functional connectivity to the rest of the fronto-parietal control network at 'rest'. In addition, the anterior insulae, which are normally tightly linked to the dorsal anterior cingulate cortex, showed increased activity following errors in the impaired group. Interestingly, the traumatic brain injury patient group with normal performance-monitoring showed abnormally high activation of the right middle frontal gyrus, putamen and caudate in response to errors. The impairment of self-awareness was not explained either by the location of focal brain injury, or the amount of traumatic axonal injury as demonstrated by diffusion tensor imaging. The results suggest that impairments of self-awareness after traumatic brain injury result from breakdown of functional interactions between nodes within the fronto-parietal control network.

Rifaximin, but not growth factor 1, reduces brain edema in cirrhotic rats

PubMed Central

Òdena, Gemma; Miquel, Mireia; Serafín, Anna; Galan, Amparo; Morillas, Rosa; Planas, Ramon; Bartolí, Ramon

2012-01-01

AIM: To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion. METHODS: Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups: Cirrhosis; Cirrhosis + IGF-1; Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin. An oral glutamine-challenge test was performed, and plasma and cerebral ammonia, glucose, bilirubin, transaminases, endotoxemia, brain water content and ileocecal cultures were measured and liver histology was assessed. RESULTS: Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups, and improved some liver function parameters (bilirubin, alanine aminotransferase and aspartate aminotransferase). These effects were associated with a significant reduction in cerebral water content. Blood and cerebral ammonia levels, and area-under-the-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals. By contrast, IGF-1 administration failed to improve most alterations observed in cirrhosis. CONCLUSION: By reducing gut bacterial overgrowth, only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema, alterations associated with hepatic encephalopathy. PMID:22563196

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.

Microglial activation as a measure of stress in mouse brains exposed acutely (60 minutes) and long-term (2 years) to mobile telephone radiofrequency fields.

PubMed

Finnie, John W; Cai, Zhao; Manavis, Jim; Helps, Stephen; Blumbergs, Peter C

2010-02-01

To determine whether acute or long-term exposure of the brain to mobile telephone radiofrequency (RF) fields produces activation of microglia, which normally respond rapidly to any change in their microenvironment. Using a purpose designed exposure system at 900 MHz, mice were given a single, far-field whole body exposure at a specific absorption rate (SAR) of 4 W/kg for 60 min (acute) or on five successive days per week for 104 weeks (long-term). Control mice were sham-exposed or freely mobile in a cage to control for any stress caused by immobilisation in the exposure module. Positive control brains subjected to a stab wound were also included to confirm the ability of microglia to react to any neural stress. Brains were perfusion-fixed with 4% paraformaldehyde and representative regions of the cerebral cortex and hippocampus immunostained for ionised calcium binding adaptor molecule (Iba1), a specific microglial marker. There was no increase in microglial Iba1 expression in brains short or long-term exposed to mobile telephony microwaves compared to control (sham-exposed or freely moving caged mice) brains, while substantial microglial activation occurred in damaged positive control neural tissue. Acute (60 minutes) or longer duration (2 years) exposure of murine brains to mobile telephone RF fields did not produce any microglial activation detectable by Iba1 immunostaining.

Role of Lactobacillus plantarum MTCC1325 in membrane-bound transport ATPases system in Alzheimer’s disease-induced rat brain

PubMed Central

Mallikarjuna, Nimgampalle; Praveen, Kukkarasapalli; Yellamma, Kuna

2016-01-01

Introduction: Alzheimer’s disease (AD) is a neurodegenerative disorder, clinically characterized by memory dysfunction and progressive loss of cognition. No curative therapeutic or drug is available for the complete cure of this disease. The present study was aimed to evaluate the efficacy of Lactobacillus plantarum MTCC1325 in ATPases activity in the selected brain regions of rats induced with Alzheimer’s. Methods: For the study, 48 healthy Wistar rats were divided into four groups: group I as control group, group II as AD model (AD induced by intraperitoneal injection of D-Galactose, 120 mg/kg body weight for 6 weeks), group III as normal control rats which were orally administered only with L. plantarum MTCC1325 for 60 days, and group IV where the AD-induced rats simultaneously received oral treatment of L. plantarum MTCC1325 (10ml/kg body weight, 12×108 CFU/mL) for 60 days. The well known membrane bound transport enzymes including Na+, K+-ATPases, Ca2+-ATPases, and Mg2+-ATPases were assayed in the selected brain regions of hippocampus and cerebral cortex in all four groups of rats at selected time intervals. Results: Chronic injection of D-Galactose caused lipid peroxidation, oxidative stress, and mitochondrial dysfunction leading to the damage of neurons in the brain, finally bringing a significant decrease (-20%) in the brain total membrane bound ATPases over the controls. Contrary to this, treatment of AD-induced rats with L. plantarum MTCC1325 reverted all the constituents of ATPase enzymes to near normal levels within 30 days. Conclusion: Lactobacillus plantarum MTCC1325 exerted a beneficial action on the entire ATPases system in AD-induced rat brain by delaying neurodegeneration. PMID:28265536

Abnormal neural activities of directional brain networks in patients with long-term bilateral hearing loss.

PubMed

Xu, Long-Chun; Zhang, Gang; Zou, Yue; Zhang, Min-Feng; Zhang, Dong-Sheng; Ma, Hua; Zhao, Wen-Bo; Zhang, Guang-Yu

2017-10-13

The objective of the study is to provide some implications for rehabilitation of hearing impairment by investigating changes of neural activities of directional brain networks in patients with long-term bilateral hearing loss. Firstly, we implemented neuropsychological tests of 21 subjects (11 patients with long-term bilateral hearing loss, and 10 subjects with normal hearing), and these tests revealed significant differences between the deaf group and the controls. Then we constructed the individual specific virtual brain based on functional magnetic resonance data of participants by utilizing effective connectivity and multivariate regression methods. We exerted the stimulating signal to the primary auditory cortices of the virtual brain and observed the brain region activations. We found that patients with long-term bilateral hearing loss presented weaker brain region activations in the auditory and language networks, but enhanced neural activities in the default mode network as compared with normally hearing subjects. Especially, the right cerebral hemisphere presented more changes than the left. Additionally, weaker neural activities in the primary auditor cortices were also strongly associated with poorer cognitive performance. Finally, causal analysis revealed several interactional circuits among activated brain regions, and these interregional causal interactions implied that abnormal neural activities of the directional brain networks in the deaf patients impacted cognitive function.

Visual feature integration with an attention deficit.

PubMed

Arguin, M; Cavanagh, P; Joanette, Y

1994-01-01

Treisman's feature integration theory proposes that the perception of illusory conjunctions of correctly encoded visual features is due to the failure of an attentional process. This hypothesis was examined by studying brain-damaged subjects who had previously been shown to have difficulty in attending to contralesional stimulation. These subjects exhibited a massive feature integration deficit for contralesional stimulation relative to ipsilesional displays. In contrast, both normal age-matched controls and brain-damaged subjects who did not exhibit any evidence of an attention deficit showed comparable feature integration performance with left- and right-hemifield stimulation. These observations indicate the crucial function of attention for visual feature integration in normal perception.

Multiple feature extraction and classification of electroencephalograph signal for Alzheimers' with spectrum and bispectrum

NASA Astrophysics Data System (ADS)

Wang, Ruofan; Wang, Jiang; Li, Shunan; Yu, Haitao; Deng, Bin; Wei, Xile

2015-01-01

In this paper, we have combined experimental neurophysiologic recording and statistical analysis to investigate the nonlinear characteristic and the cognitive function of the brain. Spectrum and bispectrum analyses are proposed to extract multiple effective features of electroencephalograph (EEG) signals from Alzheimer's disease (AD) patients and further applied to distinguish AD patients from the normal controls. Spectral analysis based on autoregressive Burg method is first used to quantify the power distribution of EEG series in the frequency domain. Compared to the control group, the relative power spectral density of AD group is significantly higher in the theta frequency band, while lower in the alpha frequency bands. In addition, median frequency of spectrum is decreased, and spectral entropy ratio of these two frequency bands undergoes drastic changes at the P3 electrode in the central-parietal brain region, implying that the electrophysiological behavior in AD brain is much slower and less irregular. In order to explore the nonlinear high order information, bispectral analysis which measures the complexity of phase-coupling is further applied to P3 electrode in the whole frequency band. It is demonstrated that less bispectral peaks appear and the amplitudes of peaks fall, suggesting a decrease of non-Gaussianity and nonlinearity of EEG in ADs. Notably, the application of this method to five brain regions shows higher concentration of the weighted center of bispectrum and lower complexity reflecting phase-coupling by bispectral entropy. Based on spectrum and bispectrum analyses, six efficient features are extracted and then applied to discriminate AD from the normal in the five brain regions. The classification results indicate that all these features could differentiate AD patients from the normal controls with a maximum accuracy of 90.2%. Particularly, different brain regions are sensitive to different features. Moreover, the optimal combination of features obtained by discriminant analysis may improve the classification accuracy. These results demonstrate the great promise for scape EEG spectral and bispectral features as a potential effective method for detection of AD, which may facilitate our understanding of the pathological mechanism of the disease.

Multiple feature extraction and classification of electroencephalograph signal for Alzheimers' with spectrum and bispectrum.

PubMed

Wang, Ruofan; Wang, Jiang; Li, Shunan; Yu, Haitao; Deng, Bin; Wei, Xile

2015-01-01

In this paper, we have combined experimental neurophysiologic recording and statistical analysis to investigate the nonlinear characteristic and the cognitive function of the brain. Spectrum and bispectrum analyses are proposed to extract multiple effective features of electroencephalograph (EEG) signals from Alzheimer's disease (AD) patients and further applied to distinguish AD patients from the normal controls. Spectral analysis based on autoregressive Burg method is first used to quantify the power distribution of EEG series in the frequency domain. Compared to the control group, the relative power spectral density of AD group is significantly higher in the theta frequency band, while lower in the alpha frequency bands. In addition, median frequency of spectrum is decreased, and spectral entropy ratio of these two frequency bands undergoes drastic changes at the P3 electrode in the central-parietal brain region, implying that the electrophysiological behavior in AD brain is much slower and less irregular. In order to explore the nonlinear high order information, bispectral analysis which measures the complexity of phase-coupling is further applied to P3 electrode in the whole frequency band. It is demonstrated that less bispectral peaks appear and the amplitudes of peaks fall, suggesting a decrease of non-Gaussianity and nonlinearity of EEG in ADs. Notably, the application of this method to five brain regions shows higher concentration of the weighted center of bispectrum and lower complexity reflecting phase-coupling by bispectral entropy. Based on spectrum and bispectrum analyses, six efficient features are extracted and then applied to discriminate AD from the normal in the five brain regions. The classification results indicate that all these features could differentiate AD patients from the normal controls with a maximum accuracy of 90.2%. Particularly, different brain regions are sensitive to different features. Moreover, the optimal combination of features obtained by discriminant analysis may improve the classification accuracy. These results demonstrate the great promise for scape EEG spectral and bispectral features as a potential effective method for detection of AD, which may facilitate our understanding of the pathological mechanism of the disease.

Quantitative Magnetic Resonance Diffusion-Weighted Imaging Evaluation of the Supratentorial Brain Regions in Patients Diagnosed with Brainstem Variant of Posterior Reversible Encephalopathy Syndrome: A Preliminary Study.

PubMed

Chen, Tai-Yuan; Wu, Te-Chang; Ko, Ching-Chung; Feng, I-Jung; Tsui, Yu-Kun; Lin, Chien-Jen; Chen, Jeon-Hor; Lin, Ching-Po

2017-07-01

Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic entity with several causes, characterized by rapid onset of symptoms and typical neuroimaging features, which usually resolve if promptly recognized and treated. Brainstem variant of PRES presents with vasogenic edema in brainstem regions on magnetic resonance (MR) images and there is sparing of the supratentorial regions. Because PRES is usually caused by a hypertensive crisis, which would likely have a systemic effect and global manifestations on the brain tissue, we thus proposed that some microscopic abnormalities of the supratentorial regions could be detected with diffusion-weighted imaging (DWI) using apparent diffusion coefficient (ADC) analysis in brainstem variant of PRES and hypothesized that "normal-looking" supratentorial regions will increase water diffusion. We retrospectively identified patients with PRES who underwent brain magnetic resonance imaging studies. We identified 11 brainstem variants of PRES patients, who formed the study cohort, and 11 typical PRES patients and 20 normal control subjects as the comparison cohorts for this study. Nineteen regions of interest were drawn and systematically placed. The mean ADC values were measured and compared among these 3 groups. ADC values of the typical PRES group were consistently elevated compared with those in normal control subjects. ADC values of the brainstem variant group were consistently elevated compared with those in normal control subjects. ADC values of the typical PRES group and brainstem variant group did not differ significantly, except for the pons area. Quantitative MR DWI may aid in the evaluation of supratentorial microscopic abnormalities in brainstem variant of PRES patients. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Temporal and spatial profile of brain diffusion-weighted MRI after cardiac arrest

PubMed Central

Mlynash, M.; Campbell, D.M.; Leproust, E.M.; Fischbein, N.J.; Bammer, R.; Eyngorn, I.; Hsia, A.W.; Moseley, M.; Wijman, C.A.C.

2010-01-01

Background and Purpose Diffusion-weighted MRI (DWI) of the brain is a promising technique to help predict functional outcome in comatose survivors of cardiac arrest. We aimed to evaluate prospectively the temporal-spatial profile of brain apparent diffusion coefficient (ADC) changes in comatose survivors during the first 8 days after cardiac arrest. Methods ADC values were measured by two independent and blinded investigators in predefined brain regions in 18 good and 15 poor outcome patients with 38 brain MRIs, and compared with 14 normal controls. The same brain regions were also assessed qualitatively by two other independent and blinded investigators. Results In poor outcome patients, cortical structures, in particular the occipital and temporal lobes, and the putamen exhibited the most profound ADC reductions, which were noted as early as 1.5 days and reached nadir between 3 to 5 days after the arrest. Conversely, when compared to normal controls, good outcome patients exhibited increased diffusivity, in particular in the hippocampus, temporal and occipital lobes, and corona radiata. By the qualitative MRI readings, one or more cortical gray matter structures were read as moderately-to-severely abnormal in all poor outcome patients imaged beyond 54 hours after the arrest, but not in the three patients imaged earlier. Conclusions Brain DWI changes in comatose post-cardiac arrest survivors in the first week after the arrest are region- and time-dependent and differ between good and poor outcome patients. With the increasing use of MRI in this context, it is important to be aware of these relationships. PMID:20595666

Diagnostic Validity of an Automated Probabilistic Tractography in Amnestic Mild Cognitive Impairment

PubMed Central

Jung, Won Sang; Um, Yoo Hyun; Kang, Dong Woo; Lee, Chang Uk; Woo, Young Sup; Bahk, Won-Myong

2018-01-01

Objective Although several prior works showed the white matter (WM) integrity changes in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease, it is still unclear the diagnostic accuracy of the WM integrity measurements using diffusion tensor imaging (DTI) in discriminating aMCI from normal controls. The aim of this study is to explore diagnostic validity of whole brain automated probabilistic tractography in discriminating aMCI from normal controls. Methods One hundred-two subjects (50 aMCI and 52 normal controls) were included and underwent DTI scans. Whole brain WM tracts were reconstructed with automated probabilistic tractography. Fractional anisotropy (FA) and mean diffusivity (MD) values of the memory related WM tracts were measured and compared between the aMCI and the normal control groups. In addition, the diagnostic validities of these WM tracts were evaluated. Results Decreased FA and increased MD values of memory related WM tracts were observed in the aMCI group compared with the control group. Among FA and MD value of each tract, the FA value of left cingulum angular bundle showed the highest area under the curve (AUC) of 0.85 with a sensitivity of 88.2%, a specificity of 76.9% in differentiating MCI patients from control subjects. Furthermore, the combination FA values of WM integrity measures of memory related WM tracts showed AUC value of 0.98, a sensitivity of 96%, a specificity of 94.2%. Conclusion Our results with good diagnostic validity of WM integrity measurements suggest DTI might be promising neuroimaging tool for early detection of aMCI and AD patients. PMID:29739127

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.

Alterations of whole-brain cortical area and thickness in mild cognitive impairment and Alzheimer's disease.

PubMed

Li, Chuanming; Wang, Jian; Gui, Li; Zheng, Jian; Liu, Chen; Du, Hanjian

2011-01-01

Gray matter volume and density of several brain regions, determined by magnetic resonance imaging (MRI), are decreased in Alzheimer's disease (AD). Animal studies have indicated that changes in cortical area size is relevant to thinking and behavior, but alterations of cortical area and thickness in the brains of individuals with AD or its likely precursor, mild cognitive impairment (MCI), have not been reported. In this study, 25 MCI subjects, 30 AD subjects, and 30 age-matched normal controls were recruited for brain MRI scans and Functional Activities Questionnaire (FAQ) assessments. Based on the model using FreeSurfer software, two brain lobes were divided into various regions according to the Desikan-Killiany atlas and the cortical area and thickness of every region was compared and analyzed. We found a significant increase in cortical area of several regions in the frontal and temporal cortices, which correlated negatively with MMSE scores, and a significant decrease in cortical area of several regions in the parietal cortex and the cingulate gyrus in AD subjects. Increased cortical area was also seen in some regions of the frontal and temporal cortices in MCI subjects, whereas the cortical thickness of the same regions was decreased. Our observations suggest characteristic differences of the cortical area and thickness in MCI, AD, and normal control subjects, and these changes may help diagnose both MCI and AD.

Disrupted topological organization in whole-brain functional networks of heroin-dependent individuals: a resting-state FMRI study.

PubMed

Jiang, Guihua; Wen, Xue; Qiu, Yingwei; Zhang, Ruibin; Wang, Junjing; Li, Meng; Ma, Xiaofen; Tian, Junzhang; Huang, Ruiwang

2013-01-01

Neuroimaging studies have shown that heroin addiction is related to abnormalities in widespread local regions and in the functional connectivity of the brain. However, little is known about whether heroin addiction changes the topological organization of whole-brain functional networks. Seventeen heroin-dependent individuals (HDIs) and 15 age-, gender-matched normal controls (NCs) were enrolled, and the resting-state functional magnetic resonance images (RS-fMRI) were acquired from these subjects. We constructed the brain functional networks of HDIs and NCs, and compared the between-group differences in network topological properties using graph theory method. We found that the HDIs showed decreases in the normalized clustering coefficient and in small-worldness compared to the NCs. Furthermore, the HDIs exhibited significantly decreased nodal centralities primarily in regions of cognitive control network, including the bilateral middle cingulate gyrus, left middle frontal gyrus, and right precuneus, but significantly increased nodal centralities primarily in the left hippocampus. The between-group differences in nodal centralities were not corrected by multiple comparisons suggesting these should be considered as an exploratory analysis. Moreover, nodal centralities in the left hippocampus were positively correlated with the duration of heroin addiction. Overall, our results indicated that disruptions occur in the whole-brain functional networks of HDIs, findings which may be helpful in further understanding the mechanisms underlying heroin addiction.

Prolonged fasting impairs neural reactivity to visual stimulation.

PubMed

Kohn, N; Wassenberg, A; Toygar, T; Kellermann, T; Weidenfeld, C; Berthold-Losleben, M; Chechko, N; Orfanos, S; Vocke, S; Laoutidis, Z G; Schneider, F; Karges, W; Habel, U

2016-01-01

Previous literature has shown that hypoglycemia influences the intensity of the BOLD signal. A similar but smaller effect may also be elicited by low normal blood glucose levels in healthy individuals. This may not only confound the BOLD signal measured in fMRI, but also more generally interact with cognitive processing, and thus indirectly influence fMRI results. Here we show in a placebo-controlled, crossover, double-blind study on 40 healthy subjects, that overnight fasting and low normal levels of glucose contrasted to an activated, elevated glucose condition have an impact on brain activation during basal visual stimulation. Additionally, functional connectivity of the visual cortex shows a strengthened association with higher-order attention-related brain areas in an elevated blood glucose condition compared to the fasting condition. In a fasting state visual brain areas show stronger coupling to the inferior temporal gyrus. Results demonstrate that prolonged overnight fasting leads to a diminished BOLD signal in higher-order occipital processing areas when compared to an elevated blood glucose condition. Additionally, functional connectivity patterns underscore the modulatory influence of fasting on visual brain networks. Patterns of brain activation and functional connectivity associated with a broad range of attentional processes are affected by maturation and aging and associated with psychiatric disease and intoxication. Thus, we conclude that prolonged fasting may decrease fMRI design sensitivity in any task involving attentional processes when fasting status or blood glucose is not controlled.

Effects of CPAP-therapy on brain electrical activity in obstructive sleep apneic patients: a combined EEG study using LORETA and Omega complexity : reversible alterations of brain activity in OSAS.

PubMed

Toth, Marton; Faludi, Bela; Kondakor, Istvan

2012-10-01

Effects of initiation of continuous positive airway pressure (CPAP) therapy on EEG background activity were investigated in patients with obstructive sleep apnea syndrome (OSAS, N = 25) to test possible reversibility of alterations of brain electrical activity caused by chronic hypoxia. Normal control group (N = 14) was also examined. Two EEG examinations were done in each groups: at night and in the next morning. Global and regional (left vs. right, anterior vs. posterior) measures of spatial complexity (Omega complexity) were used to characterize the degree of spatial synchrony of EEG. Low resolution electromagnetic tomography (LORETA) was used to localize generators of EEG activity in separate frequency bands. Before CPAP-treatment, a significantly lower Omega complexity was found globally and over the right hemisphere. Due to CPAP-treatment, these significant differences vanished. Significantly decreased Omega complexity was found in the anterior region after treatment. LORETA showed a decreased activity in all of the beta bands after therapy in the right hippocampus, premotor and temporo-parietal cortex, and bilaterally in the precuneus, paracentral and posterior cingulate cortex. No significant changes were seen in control group. Comparing controls and patients before sleep, an increased alpha2 band activity was seen bilaterally in the precuneus, paracentral and posterior cingulate cortex, while in the morning an increased beta3 band activity in the left precentral and bilateral premotor cortex and a decreased delta band activity in the right temporo-parietal cortex and insula were observed. These findings indicate that effect of sleep on EEG background activity is different in OSAS patients and normal controls. In OSAS patients, significant changes lead to a more normal EEG after a night under CPAP-treatment. Compensatory alterations of brain electrical activity in regions associated with influencing sympathetic outflow, visuospatial abilities, long-term memory and motor performances caused by chronic hypoxia could be reversed by CPAP-therapy.

Functional MRI and intraoperative brain mapping to evaluate brain plasticity in patients with brain tumours and hemiparesis

PubMed Central

Roux, F; Boulanouar, K; Ibarrola, D; Tremoulet, M; Chollet, F; Berry, I

2000-01-01

OBJECTIVE—To support the hypothesis about the potential compensatory role of ipsilateral corticofugal pathways when the contralateral pathways are impaired by brain tumours.
METHODS—Retrospective analysis was carried out on the results of functional MRI (fMRI) of a selected group of five paretic patients with Rolandic brain tumours who exhibited an abnormally high ipsilateral/contralateral ratio of activation—that is, movements of the paretic hand activated predominately the ipsilateral cortex. Brain activation was achieved with a flexion extension of the fingers. Statistical parametric activation was obtained using a t test and a threshold of p<0.001. These patients, candidates for tumour resection, also underwent cortical intraoperative stimulation that was correlated to the fMRI spatial data using three dimensional reconstructions of the brain. Three patients also had postoperative control fMRI.
RESULTS—The absence of fMRI activation of the primary sensorimotor cortex normally innervating the paretic hand for the threshold chosen, was correlated with completely negative cortical responses of the cortical hand area during the operation. The preoperative fMRI activation of these patients predominantly found in the ipsilateral frontal and primary sensorimotor cortices could be related to the residual ipsilateral hand function. Postoperatively, the fMRI activation returned to more classic patterns of activation, reflecting the consequences of therapy.
CONCLUSION—In paretic patients with brain tumours, ipsilateral control could be implicated in the residual hand function, when the normal primary pathways are impaired. The possibility that functional tissue still remains in the peritumorous sensorimotor cortex even when the preoperative fMRI and the cortical intraoperative stimulations are negative, should be taken into account when planning the tumour resection and during the operation.

 PMID:10990503

Novel strategies of Raman imaging for brain tumor research.

PubMed

Anna, Imiela; Bartosz, Polis; Lech, Polis; Halina, Abramczyk

2017-10-17

Raman diagnostics and imaging have been shown to be an effective tool for the analysis and discrimination of human brain tumors from normal structures. Raman spectroscopic methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n= 5), low-grade astrocytoma (grades I-II WHO) (n =4), ependymoma (n=3) and metastatic brain tumors (n= 1) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma, low grade astrocytoma and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational features and Raman images we provide a real-time feedback method that is label-free to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, proteins, DNA and RNA. Our results indicate marked metabolic differences between low and high grade brain tumors. We discuss molecular mechanisms causing these metabolic changes, particularly lipid alterations in malignant medulloblastoma and low grade gliomas that may shed light on the mechanisms driving tumor recurrence thereby revealing new approaches for the treatment of malignant glioma. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have found that almost all tumors studied in the paper have increased Raman signals of nucleic acids. This increase can be interpreted as increased DNA/RNA turnover in brain tumors. We have shown that the ratio of Raman intensities I 2930 /I 2845 at 2930 and 2845 cm -1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the different lipid and protein contents of cancerous brain tissue compared to the non-tumor tissue. We found that levels of the saturated fatty acids were significantly reduced in the high grade medulloblastoma samples compared with non-tumor brain samples and low grade astrocytoma. Differences were also noted in the n-6/n-3 polyunsaturated fatty acids (PUFA) content between medulloblastoma and non-tumor brain samples. The content of the oleic acid (OA) was significantly smaller in almost all brain high grade brain tumors than that observed in the control samples. It indicates that the fatty acid composition of human brain tumors differs from that found in non-tumor brain tissue. The iodine number N I for the normal brain tissue is 60. For comparison OA has 87, docosahexaenoic acid (DHA) 464, α-linolenic acid (ALA) 274. The high grade tumors have the iodine numbers between that for palmitic acid, stearic acid, arachidic acid (N I =0) and oleic acid (N I =87). Most low grade tumors have N I similar to that of OA. The iodine number for arachidonic acid (AA) (N I =334) is much higher than those observed for all studied samples.

Novel strategies of Raman imaging for brain tumor research

PubMed Central

Anna, Imiela; Bartosz, Polis; Lech, Polis; Halina, Abramczyk

2017-01-01

Raman diagnostics and imaging have been shown to be an effective tool for the analysis and discrimination of human brain tumors from normal structures. Raman spectroscopic methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n= 5), low-grade astrocytoma (grades I-II WHO) (n =4), ependymoma (n=3) and metastatic brain tumors (n= 1) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma, low grade astrocytoma and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational features and Raman images we provide a real–time feedback method that is label-free to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, proteins, DNA and RNA. Our results indicate marked metabolic differences between low and high grade brain tumors. We discuss molecular mechanisms causing these metabolic changes, particularly lipid alterations in malignant medulloblastoma and low grade gliomas that may shed light on the mechanisms driving tumor recurrence thereby revealing new approaches for the treatment of malignant glioma. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have found that almost all tumors studied in the paper have increased Raman signals of nucleic acids. This increase can be interpreted as increased DNA/RNA turnover in brain tumors. We have shown that the ratio of Raman intensities I2930/I2845 at 2930 and 2845 cm-1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the different lipid and protein contents of cancerous brain tissue compared to the non-tumor tissue. We found that levels of the saturated fatty acids were significantly reduced in the high grade medulloblastoma samples compared with non-tumor brain samples and low grade astrocytoma. Differences were also noted in the n-6/n-3 polyunsaturated fatty acids (PUFA) content between medulloblastoma and non-tumor brain samples. The content of the oleic acid (OA) was significantly smaller in almost all brain high grade brain tumors than that observed in the control samples. It indicates that the fatty acid composition of human brain tumors differs from that found in non-tumor brain tissue. The iodine number NI for the normal brain tissue is 60. For comparison OA has 87, docosahexaenoic acid (DHA) 464, α-linolenic acid (ALA) 274. The high grade tumors have the iodine numbers between that for palmitic acid, stearic acid, arachidic acid (NI=0) and oleic acid (NI=87). Most low grade tumors have NI similar to that of OA. The iodine number for arachidonic acid (AA) (NI=334) is much higher than those observed for all studied samples. PMID:29156720

Motor prediction in Brain-Computer Interfaces for controlling mobile robots.

PubMed

Geng, Tao; Gan, John Q

2008-01-01

EEG-based Brain-Computer Interface (BCI) can be regarded as a new channel for motor control except that it does not involve muscles. Normal neuromuscular motor control has two fundamental components: (1) to control the body, and (2) to predict the consequences of the control command, which is called motor prediction. In this study, after training with a specially designed BCI paradigm based on motor imagery, two subjects learnt to predict the time course of some features of the EEG signals. It is shown that, with this newly-obtained motor prediction skill, subjects can use motor imagery of feet to directly control a mobile robot to avoid obstacles and reach a small target in a time-critical scenario.

Reduced spontaneous but relatively normal deliberate vicarious representations in psychopathy

PubMed Central

Meffert, Harma; Gazzola, Valeria; den Boer, Johan A.; Bartels, Arnold A. J.

2013-01-01

Psychopathy is a personality disorder associated with a profound lack of empathy. Neuroscientists have associated empathy and its interindividual variation with how strongly participants activate brain regions involved in their own actions, emotions and sensations while viewing those of others. Here we compared brain activity of 18 psychopathic offenders with 26 control subjects while viewing video clips of emotional hand interactions and while experiencing similar interactions. Brain regions involved in experiencing these interactions were not spontaneously activated as strongly in the patient group while viewing the video clips. However, this group difference was markedly reduced when we specifically instructed participants to feel with the actors in the videos. Our results suggest that psychopathy is not a simple incapacity for vicarious activations but rather reduced spontaneous vicarious activations co-existing with relatively normal deliberate counterparts. PMID:23884812

Cerebral glucose uptake in patients with chronic mental and cognitive sequelae following a single blunt mild TBI without visible brain lesions.

PubMed

Komura, Akifumi; Kawasaki, Tomohiro; Yamada, Yuichi; Uzuyama, Shiho; Asano, Yoshitaka; Shinoda, Jun

2018-06-19

The aim of this study is to investigate glucose uptake on FDG-PET in patients with chronic mental and cognitive symptoms following a single blunt mild traumatic brain injury (TBI) and without visible brain lesions on CT/MRI. Eighty-nine consecutive patients (mean age 43.8±10.75) who had a single blunt mild TBI from a traffic accident and suffering from chronic mental and cognitive symptoms without visible brain lesions on CT/MRI were enrolled in the study. Patients underwent FDG-PET imaging, and the mean interval between the TBI and FDG-PET was 50.0 months. The Wechsler Adult Intelligence Scale version III testing was performed within one month of the FDG-PET. A control group consisting of 93 healthy adult volunteers (mean age 42.2±14.3 years) also underwent FDG-PET. The glucose uptake pattern from FDG-PET in the patient group was compared to that from normal controls using statistical parametric mapping. Glucose uptake was significantly decreased in the bilateral prefrontal area and significantly increased around the limbic system in the patient group compared to normal controls. This topographical pattern of glucose uptake is different from that reported previously in patients with diffuse axonal injury (DAI), but may be similar to that seen in patients with major depression disorder. These results suggest that the pathological mechanism causing chronic mental and cognitive symptoms in patients with a single blunt mild TBI and without visible brain lesions might be different from that due to primary axonopathy in patients with DAI.

Attention Performance in Autism and Regional Brain Metabolic Rate Assessed by Positron Emission Tomography. Brief Report.

ERIC Educational Resources Information Center

Buchsbaum, M. S.; And Others

1992-01-01

This evaluation of seven high functioning adults with autism utilized positron emission tomography on a visual vigilance task. Although the subjects, as a group, did as well as normal controls on the task, there was a lack of normal hemispheric asymmetry in glucose metabolic rate. A heterogeneous etiology for autism is suggested to explain…

Loss of pons-to-hypothalamic white matter tracks in brainstem obesity.

PubMed

Purnell, J Q; Lahna, D L; Samuels, M H; Rooney, W D; Hoffman, W F

2014-12-01

Hyperphagia and obesity have been reported following damage to the hypothalamus in humans. Other brain sites are also postulated to be involved in the control of food intake and body weight regulation, such as the amygdala and brainstem. The brainstem, however, is thought to primarily integrate short-term meal-related signals but not affect long-term alterations in body weight, which is controlled by higher centers. The objective of this study was to identify structural pathways damaged in a patient with a brainstem cavernoma who experienced sudden onset of hyperphagia and >50 kg weight gain in <1 year following surgical drainage via a midline suboccipital craniotomy. Diffusion tensor imaging revealed loss of nerve fiber connections between her brainstem, hypothalamus and higher brain centers with preservation of motor tracks. Imaging and endocrine testing confirmed normal hypothalamic structure and function. Gastric bypass surgery restored normal appetite and body weight to baseline. This is the first report of 'brainstem obesity' and adds to the brain regions that can determine the long-term body weight set point in humans.

Intrinsic sensory deprivation induced by neonatal capsaicin treatment induces changes in rat brain and behaviour of possible relevance to schizophrenia

PubMed Central

Newson, Penny; Lynch-Frame, Ann; Roach, Rebecca; Bennett, Sarah; Carr, Vaughan; Chahl, Loris A

2005-01-01

Schizophrenia is considered to be a neurodevelopmental disorder with origins in the prenatal or neonatal period. Brains from subjects with schizophrenia have enlarged ventricles, reduced cortical thickness (CT) and increased neuronal density in the prefrontal cortex compared with those from normal subjects. Subjects with schizophrenia have reduced pain sensitivity and niacin skin flare responses, suggesting that capsaicin-sensitive primary afferent neurons might be abnormal in schizophrenia. This study tested the hypothesis that intrinsic somatosensory deprivation, induced by neonatal capsaicin treatment, causes changes in the brains of rats similar to those found in schizophrenia. Wistar rats were treated with capsaicin, 50 mg kg−1 subcutaneously, or vehicle (control) at 24–36 h of life. At 5–7 weeks behavioural observations were made, and brains removed, fixed and sectioned. The mean body weight of capsaicin-treated rats was not significantly different from control, but the mean brain weight of male, but not female, rats, was significantly lower than control. Capsaicin-treated rats were hyperactive compared with controls. The hyperactivity was abolished by haloperidol. Coronal brain sections of capsaicin-treated rats had smaller cross-sectional areas, reduced CT, larger ventricles and aqueduct, smaller hippocampal area and reduced corpus callosum thickness, than brain sections from control rats. Neuronal density was increased in several cortical areas and the caudate putamen, but not in the visual cortex. It is concluded that neonatal capsaicin treatment of rats produces brain changes that are similar to those found in brains of subjects with schizophrenia. PMID:16041396

An automated normative-based fluorodeoxyglucose positron emission tomography image-analysis procedure to aid Alzheimer disease diagnosis using statistical parametric mapping and interactive image display

NASA Astrophysics Data System (ADS)

Chen, Kewei; Ge, Xiaolin; Yao, Li; Bandy, Dan; Alexander, Gene E.; Prouty, Anita; Burns, Christine; Zhao, Xiaojie; Wen, Xiaotong; Korn, Ronald; Lawson, Michael; Reiman, Eric M.

2006-03-01

Having approved fluorodeoxyglucose positron emission tomography (FDG PET) for the diagnosis of Alzheimer's disease (AD) in some patients, the Centers for Medicare and Medicaid Services suggested the need to develop and test analysis techniques to optimize diagnostic accuracy. We developed an automated computer package comparing an individual's FDG PET image to those of a group of normal volunteers. The normal control group includes FDG-PET images from 82 cognitively normal subjects, 61.89+/-5.67 years of age, who were characterized demographically, clinically, neuropsychologically, and by their apolipoprotein E genotype (known to be associated with a differential risk for AD). In addition, AD-affected brain regions functionally defined as based on a previous study (Alexander, et al, Am J Psychiatr, 2002) were also incorporated. Our computer package permits the user to optionally select control subjects, matching the individual patient for gender, age, and educational level. It is fully streamlined to require minimal user intervention. With one mouse click, the program runs automatically, normalizing the individual patient image, setting up a design matrix for comparing the single subject to a group of normal controls, performing the statistics, calculating the glucose reduction overlap index of the patient with the AD-affected brain regions, and displaying the findings in reference to the AD regions. In conclusion, the package automatically contrasts a single patient to a normal subject database using sound statistical procedures. With further validation, this computer package could be a valuable tool to assist physicians in decision making and communicating findings with patients and patient families.

Clinical applications of image guided-intensity modulated radiation therapy (IG-IMRT) for conformal avoidance of normal tissue

NASA Astrophysics Data System (ADS)

Gutierrez, Alonso Navar

2007-12-01

Recent improvements in imaging technology and radiation delivery have led to the development of advanced treatment techniques in radiotherapy which have opened the door for novel therapeutic approaches to improve the efficacy of radiation cancer treatments. Among these advances is image-guided, intensity modulated radiation therapy (IG-IMRT), in which imaging is incorporated to aid in inter-/intra-fractional target localization and to ensure accurate delivery of precise and highly conformal dose distributions. In principle, clinical implementation of IG-IMRT should improve normal tissue sparing and permit effective biological dose escalation thus widening the radiation therapeutic window and lead to increases in survival through improved local control of primary neoplastic diseases. Details of the development of three clinical applications made possible solely with IG-IMRT radiation delivery techniques are presented: (1) Laparoscopically implanted tissue expander radiotherapy (LITE-RT) has been developed to enhance conformal avoidance of normal tissue during the treatment of intra-abdominopelvic cancers. LITE-RT functions by geometrically displacing surrounding normal tissue and isolating the target volume through the interfractional inflation of a custom-shaped tissue expander throughout the course of treatment. (2) The unique delivery geometry of helical tomotherapy, a novel form of IG-IMRT, enables the delivery of composite treatment plan m which whole brain radiotherapy (WBRT) with hippocampal avoidance, hypothesized to reduce the risk of memory function decline and improve the patient's quality of life, and simultaneously integrated boost to multiple brain metastases to improve intracranial tumor control is achieved. (3) Escalation of biological dose to targets through integrated, selective subvolume boosts have been shown to efficiently increase tumor dose without significantly increasing normal tissue dose. Helical tomotherapy was used to investigate the feasibility of delivering a simultaneously integrated subvolume boost to canine nasal tumors and was found to dramatically increase estimated 1-year tumor control probability (TCP) without increasing the dose to the eyes, so as to preserve vision, and to the brain, so as to prevent neuropathy.

Changes of Brain Glucose Metabolism in the Pretreatment Patients with Non-Small Cell Lung Cancer: A Retrospective PET/CT Study.

PubMed

Zhang, Weishan; Ning, Ning; Li, Xianjun; Niu, Gang; Bai, Lijun; Guo, Youmin; Yang, Jian

2016-01-01

The tumor-to-brain communication has been emphasized by recent converging evidences. This study aimed to compare the difference of brain glucose metabolism between patients with non-small cell lung cancer (NSCLC) and control subjects. NSCLC patients prior to oncotherapy and control subjects without malignancy confirmed by 6 months follow-up were collected and underwent the resting state 18F-fluoro-D-glucose (FDG) PET/CT. Normalized FDG metabolism was calculated by a signal intensity ratio of each brain region to whole brain. Brain glucose metabolism was compared between NSCLC patients and control group using two samples t-test and multivariate test by statistical parametric maps (SPM) software. Compared with the control subjects (n = 76), both brain glucose hyper- and hypometabolism regions with significant statistical differences (P<0.01) were found in the NSCLC patients (n = 83). The hypermetabolism regions (bilateral insula, putamen, pallidum, thalamus, hippocampus and amygdala, the right side of cerebellum, orbital part of right inferior frontal gyrus and vermis) were component parts of visceral to brain signal transduction pathways, and the hypometabolism regions (the left superior parietal lobule, bilateral inferior parietal lobule and left fusiform gyrus) lied in dorsal attention network and visuospatial function areas. The changes of brain glucose metabolism exist in NSCLC patients prior to oncotherapy, which might be attributed to lung-cancer related visceral sympathetic activation and decrease of dorsal attention network function.

Closed-loop control of targeted ultrasound drug delivery across the blood–brain/tumor barriers in a rat glioma model

PubMed Central

Sun, Tao; Zhang, Yongzhi; Power, Chanikarn; Alexander, Phillip M.; Sutton, Jonathan T.; Aryal, Muna; Vykhodtseva, Natalia; Miller, Eric L.; McDannold, Nathan J.

2017-01-01

Cavitation-facilitated microbubble-mediated focused ultrasound therapy is a promising method of drug delivery across the blood–brain barrier (BBB) for treating many neurological disorders. Unlike ultrasound thermal therapies, during which magnetic resonance thermometry can serve as a reliable treatment control modality, real-time control of modulated BBB disruption with undetectable vascular damage remains a challenge. Here a closed-loop cavitation controlling paradigm that sustains stable cavitation while suppressing inertial cavitation behavior was designed and validated using a dual-transducer system operating at the clinically relevant ultrasound frequency of 274.3 kHz. Tests in the normal brain and in the F98 glioma model in vivo demonstrated that this controller enables reliable and damage-free delivery of a predetermined amount of the chemotherapeutic drug (liposomal doxorubicin) into the brain. The maximum concentration level of delivered doxorubicin exceeded levels previously shown (using uncontrolled sonication) to induce tumor regression and improve survival in rat glioma. These results confirmed the ability of the controller to modulate the drug delivery dosage within a therapeutically effective range, while improving safety control. It can be readily implemented clinically and potentially applied to other cavitation-enhanced ultrasound therapies. PMID:29133392

Brain-Derived Neurotrophic Factor Expression in Individuals With Schizophrenia and Healthy Aging: Testing the Accelerated Aging Hypothesis of Schizophrenia.

PubMed

Islam, Farhana; Mulsant, Benoit H; Voineskos, Aristotle N; Rajji, Tarek K

2017-07-01

Schizophrenia has been hypothesized to be a syndrome of accelerated aging. Brain plasticity is vulnerable to the normal aging process and affected in schizophrenia: brain-derived neurotrophic factor (BDNF) is an important neuroplasticity molecule. The present review explores the accelerated aging hypothesis of schizophrenia by comparing changes in BDNF expression in schizophrenia with aging-associated changes. Individuals with schizophrenia show patterns of increased overall mortality, metabolic abnormalities, and cognitive decline normally observed later in life in the healthy population. An overall decrease is observed in BDNF expression in schizophrenia compared to healthy controls and in older individuals compared to a younger cohort. There is a marked decrease in BDNF levels in the frontal regions and in the periphery among older individuals and those with schizophrenia; however, data for BDNF expression in the occipital, parietal, and temporal cortices and the hippocampus is inconclusive. Accelerated aging hypothesis is supported based on frontal regions and peripheral studies; however, further studies are needed in other brain regions.

Influence of acute and chronic treadmill exercise on rat plasma lactate and brain NPY, L-ENK, DYN A1-13.

PubMed

Chen, Jia-Xu; Zhao, Xin; Yue, Guang-Xin; Wang, Zhu-Feng

2007-02-01

This study was designed to investigate the effect of acute and chronic high-intensity treadmill exercise on changes in plasma lactate and brain neuropeptide (NPY), leucine-enkephalin (L-ENK), and dynorphin A(1-13) (DYN A(1-13)). Avidin-biotin complex (ABC) immunohistochemistry and image pattern analysis were used to observe the effect of chronic (total 7 weeks) and acute treadmill exercise (an initial speed of 15 m min(-1) gradually increased to 35 m min(-1) with 0 degrees, 20-25 min per day duration) on the changes of NPY, L-ENK, and DYN A(1-13) in different areas of rat brain. Plasma lactate was also measured in response to such exercise. Compared with preexercise control (P < 0.01), plasma lactate concentration significantly increased in the immediate postexercise; but it returned to the normal level soon after the 30 min postexercise. The content of NPY in paraventricular (PVN), dorsomedial (DMN), and ventromedial (VMN) hypothalamic nuclei continued to increase in 0, 30, and 180 min postexercise compared with preexercise control (P < 0.01). The content of L-ENK in caudate-putamen (CPu) significantly increased in the immediate postexercise compared with preexercise control (P < 0.01), but it gradually returned to the normal level after the 180 min postexercise. However, the content of DYN A(1-13) in PVN rose substantially only in 30 min postexercise in comparison with the preexercise control (P < 0.01). Thus, different changes of NPY, L-ENK, and DYN A(1-13) in response to such high-intensity exercise depend on the brain region and the time examined, especially, the contents of NPY in different brain regions continuously remain at a high level after such high-intensity exercise. And this high level might reduce energy expenditure and thus contribute to the stimulation of brain NPY neurons.

Consequences of Traumatic Brain Injury for Human Vergence Dynamics

PubMed Central

Tyler, Christopher W.; Likova, Lora T.; Mineff, Kristyo N.; Elsaid, Anas M.; Nicholas, Spero C.

2015-01-01

Purpose: Traumatic brain injury involving loss of consciousness has focal effects in the human brainstem, suggesting that it may have particular consequences for eye movement control. This hypothesis was investigated by measurements of vergence eye movement parameters. Methods: Disparity vergence eye movements were measured for a population of 123 normally sighted individuals, 26 of whom had suffered diffuse traumatic brain injury (dTBI) in the past, while the remainder served as controls. Vergence tracking responses were measured to sinusoidal disparity modulation of a random-dot field. Disparity vergence step responses were characterized in terms of their dynamic parameters separately for the convergence and divergence directions. Results: The control group showed notable differences between convergence and divergence dynamics. The dTBI group showed significantly abnormal vergence behavior on many of the dynamic parameters. Conclusion: The results support the hypothesis that occult injury to the oculomotor control system is a common residual outcome of dTBI. PMID:25691880

A methodology for generating normal and pathological brain perfusion SPECT images for evaluation of MRI/SPECT fusion methods: application in epilepsy

NASA Astrophysics Data System (ADS)

Grova, C.; Jannin, P.; Biraben, A.; Buvat, I.; Benali, H.; Bernard, A. M.; Scarabin, J. M.; Gibaud, B.

2003-12-01

Quantitative evaluation of brain MRI/SPECT fusion methods for normal and in particular pathological datasets is difficult, due to the frequent lack of relevant ground truth. We propose a methodology to generate MRI and SPECT datasets dedicated to the evaluation of MRI/SPECT fusion methods and illustrate the method when dealing with ictal SPECT. The method consists in generating normal or pathological SPECT data perfectly aligned with a high-resolution 3D T1-weighted MRI using realistic Monte Carlo simulations that closely reproduce the response of a SPECT imaging system. Anatomical input data for the SPECT simulations are obtained from this 3D T1-weighted MRI, while functional input data result from an inter-individual analysis of anatomically standardized SPECT data. The method makes it possible to control the 'brain perfusion' function by proposing a theoretical model of brain perfusion from measurements performed on real SPECT images. Our method provides an absolute gold standard for assessing MRI/SPECT registration method accuracy since, by construction, the SPECT data are perfectly registered with the MRI data. The proposed methodology has been applied to create a theoretical model of normal brain perfusion and ictal brain perfusion characteristic of mesial temporal lobe epilepsy. To approach realistic and unbiased perfusion models, real SPECT data were corrected for uniform attenuation, scatter and partial volume effect. An anatomic standardization was used to account for anatomic variability between subjects. Realistic simulations of normal and ictal SPECT deduced from these perfusion models are presented. The comparison of real and simulated SPECT images showed relative differences in regional activity concentration of less than 20% in most anatomical structures, for both normal and ictal data, suggesting realistic models of perfusion distributions for evaluation purposes. Inter-hemispheric asymmetry coefficients measured on simulated data were found within the range of asymmetry coefficients measured on corresponding real data. The features of the proposed approach are compared with those of other methods previously described to obtain datasets appropriate for the assessment of fusion methods.

Functional network centrality in obesity: A resting-state and task fMRI study.

PubMed

García-García, Isabel; Jurado, María Ángeles; Garolera, Maite; Marqués-Iturria, Idoia; Horstmann, Annette; Segura, Bàrbara; Pueyo, Roser; Sender-Palacios, María José; Vernet-Vernet, Maria; Villringer, Arno; Junqué, Carme; Margulies, Daniel S; Neumann, Jane

2015-09-30

Obesity is associated with structural and functional alterations in brain areas that are often functionally distinct and anatomically distant. This suggests that obesity is associated with differences in functional connectivity of regions distributed across the brain. However, studies addressing whole brain functional connectivity in obesity remain scarce. Here, we compared voxel-wise degree centrality and eigenvector centrality between participants with obesity (n=20) and normal-weight controls (n=21). We analyzed resting state and task-related fMRI data acquired from the same individuals. Relative to normal-weight controls, participants with obesity exhibited reduced degree centrality in the right middle frontal gyrus in the resting-state condition. During the task fMRI condition, obese participants exhibited less degree centrality in the left middle frontal gyrus and the lateral occipital cortex along with reduced eigenvector centrality in the lateral occipital cortex and occipital pole. Our results highlight the central role of the middle frontal gyrus in the pathophysiology of obesity, a structure involved in several brain circuits signaling attention, executive functions and motor functions. Additionally, our analysis suggests the existence of task-dependent reduced centrality in occipital areas; regions with a role in perceptual processes and that are profoundly modulated by attention. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Control of Abnormal Synchronization in Neurological Disorders

PubMed Central

Popovych, Oleksandr V.; Tass, Peter A.

2014-01-01

In the nervous system, synchronization processes play an important role, e.g., in the context of information processing and motor control. However, pathological, excessive synchronization may strongly impair brain function and is a hallmark of several neurological disorders. This focused review addresses the question of how an abnormal neuronal synchronization can specifically be counteracted by invasive and non-invasive brain stimulation as, for instance, by deep brain stimulation for the treatment of Parkinson’s disease, or by acoustic stimulation for the treatment of tinnitus. On the example of coordinated reset (CR) neuromodulation, we illustrate how insights into the dynamics of complex systems contribute to successful model-based approaches, which use methods from synergetics, non-linear dynamics, and statistical physics, for the development of novel therapies for normalization of brain function and synaptic connectivity. Based on the intrinsic multistability of the neuronal populations induced by spike timing-dependent plasticity (STDP), CR neuromodulation utilizes the mutual interdependence between synaptic connectivity and dynamics of the neuronal networks in order to restore more physiological patterns of connectivity via desynchronization of neuronal activity. The very goal is to shift the neuronal population by stimulation from an abnormally coupled and synchronized state to a desynchronized regime with normalized synaptic connectivity, which significantly outlasts the stimulation cessation, so that long-lasting therapeutic effects can be achieved. PMID:25566174

Increased brain lysosomal pepstatin-insensitive proteinase activity in patients with neurodegenerative diseases.

PubMed

Junaid, M A; Pullarkat, R K

1999-04-02

A recent study has shown mutations in CLN2 gene, that encodes a novel lysosomal pepstatin-insensitive proteinase (LPIP), in the pathophysiology of late-infantile neuronal ceroid lipofuscinosis (LINCL). We have measured the LPIP activities in brains from various forms of human neuronal ceroid lipofuscinoses (NCL), canine ceroid lipofuscinosis and other neurodegenerative disorders with a highly sensitive assay using a tetrapeptide Gly-Phe-Phe-Leu-amino-trifluoromethyl coumarin (AFC) as substrate. Brain LPIP has a pH optimum of 3.5 and an apparent km of 100 microM for the crude enzyme. The enzyme activity is totally absent in LINCL patients. Pronounced increase in the LPIP activity was seen in patients suffering from infantile (INCL), juvenile (JNCL) and adult (ANCL) forms of neuronal ceroid lipofuscinoses. LPIP activity was also found to be increased about two-fold in Alzheimer's disease when compared with normal or age-matched controls, while in globoidal-cell leukodystrophy (Krabbe's disease) it was similar to the normal controls. Although mannose-6-phosphorylated LPIP is increased 13-fold in brains of patients with JNCL, this form of LPIP did not have any enzyme activity. The mechanism by which LPIP activities are increased in a wide range of neurodegenerative diseases is unknown, although neuronal loss, followed by gliosis are common characteristics of these diseases.

Does gender matter? Differences in social-emotional behavior among infants and toddlers before and after mild traumatic brain injury: a preliminary study.

PubMed

Kaldoja, Mari-Liis; Kolk, Anneli

2015-06-01

Traumatic brain injury is a common cause of acquired disability in childhood. While much is known about cognitive sequelae of brain trauma, gender-specific social-emotional problems in children with mild traumatic brain injury is far less understood. The aims of the study were to investigate gender differences in social-emotional behavior before and after mild traumatic brain injury. Thirty-five 3- to 65-month-old children with mild traumatic brain injury and 70 controls were assessed with Ages and Stages Questionnaires: Social-Emotional. Nine months later, 27 of 35 patients and 54 of 70 controls were reassessed. We found that before injury, boys had more self-regulation and autonomy difficulties and girls had problems with adaptive functioning. Nine months after injury, boys continued to struggle with self-regulation and autonomy and new difficulties with interaction had emerged, whereas in girls, problems in interaction had evolved. Even mild traumatic brain injury in early childhood disrupts normal social-emotional development having especially devastating influence on interaction skills. © The Author(s) 2014.

Narrative discourse in children with early focal brain injury.

PubMed

Reilly, J S; Bates, E A; Marchman, V A

1998-02-15

Children with early brain damage, unlike adult stroke victims, often go on to develop nearly normal language. However, the route and extent of their linguistic development are still unclear, as is the relationship between lesion site and patterns of delay and recovery. Here we address these questions by examining narratives from children with early brain damage. Thirty children (ages 3:7-10:10) with pre- or perinatal unilateral focal brain damage and their matched controls participated in a storytelling task. Analyses focused on linguistic proficiency and narrative competence. Overall, children with brain damage scored significantly lower than their age-matched controls on both linguistic (morphological and syntactic) indices and those targeting broader narrative qualities. Rather than indicating that children with brain damage fully catch up, these data suggest that deficits in linguistic abilities reassert themselves as children face new linguistic challenges. Interestingly, after age 5, site of lesion does not appear to be a significant factor and the delays we have witnessed do not map onto the lesion profiles observed in adults with analogous brain injuries.

Brief report: Preliminary study on evaluation of spasticity in patients with brain lesions using mechanomyography.

PubMed

Jun, Sang Woo; Yong, Suk Joong; Jo, Min; Kim, Young Ho; Kim, Sung Hoon

2018-05-01

Electromyography and the modified Ashworth scale (MAS) are among the most effective methods for evaluating spasticity; however, these are often inappropriate for clinical use, owing to the complicated procedure and subjective evaluation outcomes. A passive stretch reflex test was performed on 10 subjects with brain lesions. Furthermore, mechanomyography and electromyography were conducted on the vastus lateralis muscle (agonist) and semitendinosus muscle (antagonist) of the subjects with brain lesions. A new equation to define the normalized hull area; that is, the mechanomyography (MMG) ratio, was applied to quantify the triaxial motion of the agonist muscle versus antagonist muscles, reflecting the electromyographic firing point of the spastic muscle. The MMG ratio was proposed, which statistically distinguishes the spastic and normal muscles (p = 0.01) and exhibits a concordance with the conventional mean MAS (r = 0.69, p = 0.01). Patients suspected to have spasticity of 0 to 1+ grade can be quantitatively evaluated using the normalized hull area ratio, which can be used as an additional clinical indicator for spasticity evaluation. The study was conducted in conformity with the Helsinki declaration principles and performed in the Korea Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea); 2010; KCT0002385; A new approach of spasticity measurement using mechanomyography in patients with brain lesions: A randomized pilot study for a parallel randomized controlled trial; October 8, 2015 [Cited on July 21, 2017]; [1 screen]. Available from: https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=7805<ype=&rtype=. Copyright © 2018. Published by Elsevier Ltd.

Fingolimod against endotoxin-induced fetal brain injury in a rat model.

PubMed

Yavuz, And; Sezik, Mekin; Ozmen, Ozlem; Asci, Halil

2017-11-01

Fingolimod is a sphingosine-1-phosphate receptor modulator used for multiple sclerosis treatment and acts on cellular processes such as apoptosis, endothelial permeability, and inflammation. We hypothesized that fingolimod has a positive effect on alleviating preterm fetal brain injury. Sixteen pregnant rats were divided into four groups of four rats each. On gestational day 17, i.p. endotoxin was injected to induce fetal brain injury, followed by i.p. fingolimod (4 mg/kg maternal weight). Hysterotomy for preterm delivery was performed 6 h after fingolimod. The study groups included (i) vehicle controls (i.p. normal saline only); (ii) positive controls (endotoxin plus saline); (iii) saline plus fingolimod; and (iv) endotoxin plus fingolimod treatment. Brain tissues of the pups were dissected for evaluation of interleukin (IL)-6, caspase-3, and S100β on immunohistochemistry. Maternal fingolimod treatment attenuated endotoxin-related fetal brain injury and led to lower immunoreactions for IL-6, caspase-3, and S100β compared with endotoxin controls (P < 0.0001 for all comparisons). Antenatal maternal fingolimod therapy had fetal neuroprotective effects by alleviating preterm birth-related fetal brain injury with inhibitory effects on inflammation and apoptosis. © 2017 Japan Society of Obstetrics and Gynecology.

Reward-based hypertension control by a synthetic brain-dopamine interface.

PubMed

Rössger, Katrin; Charpin-El Hamri, Ghislaine; Fussenegger, Martin

2013-11-05

Synthetic biology has significantly advanced the design of synthetic trigger-controlled devices that can reprogram mammalian cells to interface with complex metabolic activities. In the brain, the neurotransmitter dopamine coordinates communication with target neurons via a set of dopamine receptors that control behavior associated with reward-driven learning. This dopamine transmission has recently been suggested to increase central sympathetic outflow, resulting in plasma dopamine levels that correlate with corresponding brain activities. By functionally rewiring the human dopamine receptor D1 (DRD1) via the second messenger cyclic adenosine monophosphate (cAMP) to synthetic promoters containing cAMP response element-binding protein 1(CREB1)-specific cAMP-responsive operator modules, we have designed a synthetic dopamine-sensitive transcription controller that reversibly fine-tunes specific target gene expression at physiologically relevant brain-derived plasma dopamine levels. Following implantation of circuit-transgenic human cell lines insulated by semipermeable immunoprotective microcontainers into mice, the designer device interfaced with dopamine-specific brain activities and produced a systemic expression response when the animal's reward system was stimulated by food, sexual arousal, or addictive drugs. Reward-triggered brain activities were able to remotely program peripheral therapeutic implants to produce sufficient amounts of the atrial natriuretic peptide, which reduced the blood pressure of hypertensive mice to the normal physiologic range. Seamless control of therapeutic transgenes by subconscious behavior may provide opportunities for treatment strategies of the future.

Altered respiratory response to substance P in capsaicin-treated rats.

PubMed

Towle, A C; Mueller, R A; Breese, G R; Lauder, J

1985-01-01

The present investigation sought to examine the importance of substance P in the altered respiratory activity after neonatal capsaicin administration. Halothane-anesthetized adult rats given capsaicin neonatally exhibit a decreased basal minute ventilation with PaCO2 equal to and PaO2 greater than vehicle injected controls. In addition, the minute ventilation-PaCO2 curve was displaced to the right. Acute bilateral cervical vagotomy severely blunted the minute ventilation response to PaCO2 and abolished the differences in ventilation between capsaicin treated and control rats. Neonatal capsaicin significantly reduced pons-medulla substance P content but not TRH, serotonin or 5-hydroxyindole acetic acid. Immunohistochemical studies revealed that substance P fibers of the trigeminal spinal nucleus were the most severely affected in the brain stem and that substance P fibers in the lung were totally absent. The intracerebroventricular administration of substance P increased minute ventilation similarly in both control and capsaicin treated rats, largely as a result of increases in tidal volume. The minute ventilation-PaCO2 curve was similar in both groups after substance P administration. Simultaneous administration of the peptidase inhibitor captopril with substance P increased the respiratory response to substance P in normal rats. Administration of captopril to capsaicin treated rats restored the ventilation-PaCO2 curve to the position observed in normal rats. The hypotensive response to intracerebroventricular captopril alone in control rats was less profound in rats given neonatal capsaicin. These results are consistent with the thesis that respiratory depression after capsaicin treatment is at least in part due to the loss of substance P primary afferent nerve terminals in the brain stem, suggesting that substance P fibers in the brain stem may participate in the normal modulation of respiratory activity.

Relationships among neuroscore, magnetic resonance imaging features, and intracranial pressure in sheep affected by slow-growing brain lesions.

PubMed

Evangelisti, Maria A; Deiana, Roberta; Melosu, Valentino; Burrai, Giovanni P; Ballocco, Isabella; Varcasia, Antonio; Scala, Antonio; Manunta, Maria L

2018-05-01

Diagnosing high intracranial pressure by clinical and diagnostic imaging is particularly challenging for chronic or slow-growing lesions. The aim of this prospective case-control study is to determine whether the neuroscore and brain magnetic resonance imaging (MRI) are related to the direct measurement of intracranial pressure in sheep affected by intracranial slow-growing lesions due to chronic cerebral coenurosis (Coenurus cerebralis). Seventeen affected and 10 control sheep were included. All animals underwent a neurological examination, MRI of the brain, and direct measurement of intracranial pressure. The severity of clinical signs and MRI findings were scored. Data were statistically analyzed. The invasive intracranial pressure value was higher in affected animals. A severely altered neuroscore is related to an increased intracranial pressure beyond the normal threshold (P < 0.05). The volume of the calvarium was larger in affected animals than in control animals (P = 0.0001) and was positively influenced by the presence and volume of the parasitic cyst (r = 0.7881, P < 0.01). Several degrees of deviation and deformation of both the ventricular system and brain parenchyma were detected by MRI. Subjective MRI findings were not associated with intracranial hypertension. In conclusion, this study shows that in sheep affected by slow-growing lesions, severe alterations in the neuroscore and the results of objective MRI are related to an increased intracranial pressure beyond the normal threshold. © 2017 American College of Veterinary Radiology.

The amusic brain: in tune, out of key, and unaware.

PubMed

Peretz, Isabelle; Brattico, Elvira; Järvenpää, Miika; Tervaniemi, Mari

2009-05-01

Like language, music engagement is universal, complex and present early in life. However, approximately 4% of the general population experiences a lifelong deficit in music perception that cannot be explained by hearing loss, brain damage, intellectual deficiencies or lack of exposure. This musical disorder, commonly known as tone-deafness and now termed congenital amusia, affects mostly the melodic pitch dimension. Congenital amusia is hereditary and is associated with abnormal grey and white matter in the auditory cortex and the inferior frontal cortex. In order to relate these anatomical anomalies to the behavioural expression of the disorder, we measured the electrical brain activity of amusic subjects and matched controls while they monitored melodies for the presence of pitch anomalies. Contrary to current reports, we show that the amusic brain can track quarter-tone pitch differences, exhibiting an early right-lateralized negative brain response. This suggests near-normal neural processing of musical pitch incongruities in congenital amusia. It is important because it reveals that the amusic brain is equipped with the essential neural circuitry to perceive fine-grained pitch differences. What distinguishes the amusic from the normal brain is the limited awareness of this ability and the lack of responsiveness to the semitone changes that violate musical keys. These findings suggest that, in the amusic brain, the neural pitch representation cannot make contact with musical pitch knowledge along the auditory-frontal neural pathway.

Adolescent Cannabis Use: What is the Evidence for Functional Brain Alteration?

PubMed

Lorenzetti, Valentina; Alonso-Lana, Silvia; Youssef, George J; Verdejo-Garcia, Antonio; Suo, Chao; Cousijn, Janna; Takagi, Michael; Yücel, Murat; Solowij, Nadia

2016-01-01

Cannabis use typically commences during adolescence, a period during which the brain undergoes profound remodeling in areas that are high in cannabinoid receptors and that mediate cognitive control and emotion regulation. It is therefore important to determine the impact of adolescent cannabis use on brain function. We investigate the impact of adolescent cannabis use on brain function by reviewing the functional magnetic resonance imaging studies in adolescent samples. We systematically reviewed the literature and identified 13 functional neuroimaging studies in adolescent cannabis users (aged 13 to 18 years) performing working memory, inhibition and reward processing tasks. The majority of the studies found altered brain function, but intact behavioural task performance in adolescent cannabis users versus controls. The most consistently reported differences were in the frontal-parietal network, which mediates cognitive control. Heavier use was associated with abnormal brain function in most samples. A minority of studies controlled for the influence of confounders that can also undermine brain function, such as tobacco and alcohol use, psychopathology symptoms, family history of psychiatric disorders and substance use. Emerging evidence shows abnormal frontal-parietal network activity in adolescent cannabis users, particularly in heavier users. Brain functional alterations may reflect a compensatory neural mechanism that enables normal behavioural performance. It remains unclear if cannabis exposure drives these alterations, as substance use and mental health confounders have not been systematically examined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Diffusion abnormalities in adolescents and young adults with a history of heavy cannabis use.

PubMed

Ashtari, Manzar; Cervellione, Kelly; Cottone, John; Ardekani, Babak A; Sevy, Serge; Kumra, Sanjiv

2009-01-01

There is growing evidence that adolescence is a key period for neuronal maturation. Despite the high prevalence of marijuana use among adolescents and young adults in the United States and internationally, very little is known about its impact on the developing brain. Based on neuroimaging literature on normal brain developmental during adolescence, we hypothesized that individuals with heavy cannabis use (HCU) would have brain structure abnormalities in similar brain regions that undergo development during late adolescence, particularly the fronto-temporal connection. Fourteen young adult males in residential treatment for cannabis dependence and 14 age-matched healthy male control subjects were recruited. Patients had a history of HCU throughout adolescence; 5 had concurrent alcohol abuse. Subjects underwent structural and diffusion tensor magnetic resonance imaging. White matter integrity was compared between subject groups using voxelwise and fiber tractography analysis. Voxelwise and tractography analyses revealed that adolescents with HCU had reduced fractional anisotropy, increased radial diffusivity, and increased trace in the homologous areas known to be involved in ongoing development during late adolescence, particularly in the fronto-temporal connection via arcuate fasciculus. Our results support the hypothesis that heavy cannabis use during adolescence may affect the trajectory of normal brain maturation. Due to concurrent alcohol consumption in five HCU subjects, conclusions from this study should be considered preliminary, as the DTI findings reported here may be reflective of the combination of alcohol and marijuana use. Further research in larger samples, longitudinal in nature, and controlling for alcohol consumption is needed to better understand the pathophysiology of the effect of cannabis on the developing brain.

Quantitative susceptibility map analysis in preterm neonates with germinal matrix-intraventricular hemorrhage.

PubMed

Tortora, Domenico; Severino, Mariasavina; Sedlacik, Jan; Toselli, Benedetta; Malova, Mariya; Parodi, Alessandro; Morana, Giovanni; Fato, Marco Massimo; Ramenghi, Luca Antonio; Rossi, Andrea

2018-05-10

Germinal matrix-intraventricular hemorrhage (GMH-IVH) is a common form of intracranial hemorrhage occurring in preterm neonates that may affect normal brain development. Although the primary lesion is easily identified on MRI by the presence of blood products, its exact extent may not be recognizable with conventional sequences. Quantitative susceptibility mapping (QSM) quantify the spatial distribution of magnetic susceptibility within biological tissues, including blood degradation products. To evaluate magnetic susceptibility of normal-appearing white (WM) and gray matter regions in preterm neonates with and without GMH-IVH. Retrospective case-control. A total of 127 preterm neonates studied at term equivalent age: 20 had mild GMH-IVH (average gestational age 28.7 ± 2.1 weeks), 15 had severe GMH-IVH (average gestational age 29.3 ± 1.8 weeks), and 92 had normal brain MRI (average gestational age 29.8 ± 1.8 weeks). QSM at 1.5 Tesla. QSM analysis was performed for each brain hemisphere with a region of interest-based approach including five WM regions (centrum semiovale, frontal, parietal, temporal, and cerebellum), and a subcortical gray matter region (basal ganglia/thalami). Changes in magnetic susceptibility were explored using a one-way analysis of covariance, according to GMH-IVH severity (P < 0.05). In preterm neonates with normal brain MRI, all white and subcortical gray matter regions had negative magnetic susceptibility values (diamagnetic). Neonates with severe GMH-IVH showed higher positive magnetic susceptibility values (i.e. paramagnetic) in the centrum semiovale (0.0019 versus -0.0014 ppm; P < 0.001), temporal WM (0.0011 versus -0.0012 ppm; P = 0.037), and parietal WM (0.0005 versus -0.0001 ppm; P = 0.002) compared with controls. No differences in magnetic susceptibility were observed between neonates with mild GMH-IVH and controls (P = 0.236). Paramagnetic susceptibility changes occur in several normal-appearing WM regions of neonates with severe GMH-IVH, likely related to the accumulation of hemosiderin/ferritin iron secondary to diffusion of extracellular hemoglobin from the ventricle into the periventricular WM. 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Evidence of Altered Brain Responses to Nicotine in an Animal Model of Attention Deficit/Hyperactivity Disorder.

PubMed

Poirier, Guillaume L; Huang, Wei; Tam, Kelly; DiFranza, Joseph R; King, Jean A

2017-09-01

Individuals with attention deficit/hyperactivity disorder (ADHD) are susceptible to earlier and more severe nicotine addiction. To shed light on the relationship between nicotine and ADHD, we examined nicotine's effects on functional brain networks in an animal model of ADHD. Awake magnetic resonance imaging was used to compare functional connectivity in adolescent (post-natal day 44 ± 2) males of the spontaneously hypertensive rat (SHR) strain and two control strains, Wistar-Kyoto and Sprague-Dawley (n = 16 each). We analyzed functional connectivity immediately before and after nicotine exposure (0.4 mg/kg base) in naïve animals, using a region-of-interest approach focussing on 16 regions previously implicated in reward and addiction. Relative to the control groups, the SHR strain demonstrated increased functional connectivity between the ventral tegmental area (VTA) and retrosplenial cortex in response to nicotine, suggesting an aberrant response to nicotine. In contrast, increased VTA-substantia nigra connectivity in response to a saline injection in the SHR was absent following a nicotine injection, suggesting that nicotine normalized function in this circuit. In the SHR, nicotine triggered an atypical response in one VTA circuit while normalizing activity in another. The VTA has been widely implicated in drug reward. Our data suggest that increased susceptibility to nicotine addiction in individuals with ADHD may involve altered responses to nicotine involving VTA circuits. Nicotine addiction is more common among individuals with ADHD. We found that two circuits involving the VTA responded differently to nicotine in animals that model ADHD in comparison to two control strains. In one circuit, nicotine normalized activity that was abnormal in the ADHD animals, while in the other circuit nicotine caused an atypical brain response in the ADHD animals. The VTA has been implicated in drug reward. Our results would be consistent with an interpretation that nicotine may normalize abnormal brain activity in ADHD, and that nicotine may be more rewarding for individuals with ADHD. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Personality and complex brain networks: The role of openness to experience in default network efficiency

PubMed Central

Kaufman, Scott Barry; Benedek, Mathias; Jung, Rex E.; Kenett, Yoed N.; Jauk, Emanuel; Neubauer, Aljoscha C.; Silvia, Paul J.

2015-01-01

Abstract The brain's default network (DN) has been a topic of considerable empirical interest. In fMRI research, DN activity is associated with spontaneous and self‐generated cognition, such as mind‐wandering, episodic memory retrieval, future thinking, mental simulation, theory of mind reasoning, and creative cognition. Despite large literatures on developmental and disease‐related influences on the DN, surprisingly little is known about the factors that impact normal variation in DN functioning. Using structural equation modeling and graph theoretical analysis of resting‐state fMRI data, we provide evidence that Openness to Experience—a normally distributed personality trait reflecting a tendency to engage in imaginative, creative, and abstract cognitive processes—underlies efficiency of information processing within the DN. Across two studies, Openness predicted the global efficiency of a functional network comprised of DN nodes and corresponding edges. In Study 2, Openness remained a robust predictor—even after controlling for intelligence, age, gender, and other personality variables—explaining 18% of the variance in DN functioning. These findings point to a biological basis of Openness to Experience, and suggest that normally distributed personality traits affect the intrinsic architecture of large‐scale brain systems. Hum Brain Mapp 37:773–779, 2016. © 2015 Wiley Periodicals, Inc. PMID:26610181

Brain Cell Swelling During Hypocapnia Increases with Hyperglycemia or Ketosis

PubMed Central

Glaser, Nicole; Bundros, Angeliki; Anderson, Steve; Tancredi, Daniel; Lo, Weei; Orgain, Myra; O'Donnell, Martha

2014-01-01

Severe hypocapnia increases the risk of DKA-related cerebral injury in children, but the reason for this association is unclear. To determine whether the effects of hypocapnia on the brain are altered during hyperglycemia or ketosis, we induced hypocapnia (pCO2 20 ± 3 mmHg) via mechanical ventilation in three groups of juvenile rats: 25 controls, 22 hyperglycemic rats (serum glucose 451± 78 mg/dL) and 15 ketotic rats (beta-hydroxy butyrate 3.0 ± 1.0 mmol/L). We used magnetic resonance imaging to measure cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) values in these groups and in 17 ventilated rats with normal pCO2 (40±3 mmHg). In a subset (n=35), after 2 hrs of hypocapnia, pCO2 levels were normalized (40±3 mmHg) and ADC and CBF measurements repeated. Declines in CBF with hypocapnia occurred in all groups. Normalization of pCO2 after hypocapnia resulted in striatal hyperemia. These effects were not substantially altered by hyperglycemia or ketosis, however, declines in ADC during hypocapnia were greater during both hyperglycemia and ketosis. We conclude that brain cell swelling associated with hypocapnia is increased by both hyperglycemia and ketosis, suggesting that these metabolic conditions may make the brain more vulnerable to injury during hypocapnia. PMID:24443981

Loss of astrocyte cholesterol synthesis disrupts neuronal function and alters whole-body metabolism.

PubMed

Ferris, Heather A; Perry, Rachel J; Moreira, Gabriela V; Shulman, Gerald I; Horton, Jay D; Kahn, C Ronald

2017-01-31

Cholesterol is important for normal brain function. The brain synthesizes its own cholesterol, presumably in astrocytes. We have previously shown that diabetes results in decreased brain cholesterol synthesis by a reduction in sterol regulatory element-binding protein 2 (SREBP2)-regulated transcription. Here we show that coculture of control astrocytes with neurons enhances neurite outgrowth, and this is reduced with SREBP2 knockdown astrocytes. In vivo, mice with knockout of SREBP2 in astrocytes have impaired brain development and behavioral and motor defects. These mice also have altered energy balance, altered body composition, and a shift in metabolism toward carbohydrate oxidation driven by increased glucose oxidation by the brain. Thus, SREBP2-mediated cholesterol synthesis in astrocytes plays an important role in brain and neuronal development and function, and altered brain cholesterol synthesis may contribute to the interaction between metabolic diseases, such as diabetes and altered brain function.

Loss of astrocyte cholesterol synthesis disrupts neuronal function and alters whole-body metabolism

PubMed Central

Ferris, Heather A.; Perry, Rachel J.; Moreira, Gabriela V.; Shulman, Gerald I.; Horton, Jay D.; Kahn, C. Ronald

2017-01-01

Cholesterol is important for normal brain function. The brain synthesizes its own cholesterol, presumably in astrocytes. We have previously shown that diabetes results in decreased brain cholesterol synthesis by a reduction in sterol regulatory element-binding protein 2 (SREBP2)-regulated transcription. Here we show that coculture of control astrocytes with neurons enhances neurite outgrowth, and this is reduced with SREBP2 knockdown astrocytes. In vivo, mice with knockout of SREBP2 in astrocytes have impaired brain development and behavioral and motor defects. These mice also have altered energy balance, altered body composition, and a shift in metabolism toward carbohydrate oxidation driven by increased glucose oxidation by the brain. Thus, SREBP2-mediated cholesterol synthesis in astrocytes plays an important role in brain and neuronal development and function, and altered brain cholesterol synthesis may contribute to the interaction between metabolic diseases, such as diabetes and altered brain function. PMID:28096339

Characterization of a new model of GM2-gangliosidosis (Sandhoff's disease) in Korat cats.

PubMed Central

Neuwelt, E A; Johnson, W G; Blank, N K; Pagel, M A; Maslen-McClure, C; McClure, M J; Wu, P M

1985-01-01

We have detected a disorder in Korat cats (initially imported from Thailand) that is analogous to human Sandhoff's disease. Pedigree analysis indicates that this disease in an autosomal recessive disorder in the American Korat. Postmortem studies on one affected cat showed hepatomegaly that was not reported in the only other known feline model of GM2-gangliosidosis type II. Histologic and ultra-structural evaluation revealed typical storage vacuoles. There was a marked deficiency in the activity of hexosaminidase (HEX) A and B in affected brain and liver as compared to controls. Electrophoresis of a liver extract revealed a deficiency of normal HEX A and B in the affected animals. The blocking primary enzyme immunoassay verified the presence of antigenically reactive HEX present in affected cat livers in quantities slightly elevated with respect to the normal HEX concentration in control cats. In leukocytes, obligate heterozygotes had intermediate levels of total HEX activity with a slight increase in the percent activity due to HEX A. Indeed, 4 of 11 phenotypically normal animals in addition to four obligate heterozygotes appear to be carriers using this assay. Affected brain and liver compared with control brain and liver contained a great excess of bound N-acetylneuraminic acid in the Folch upper-phase solids; thin-layer chromatography showed a marked increase in GM2-ganglioside. In summary, we have characterized the pedigree, pathology, and biochemistry of a new feline model of GM2-gangliosidosis which is similar to but different from the only other known feline model. Images PMID:4040927

Characterization of a new model of GM2-gangliosidosis (Sandhoff's disease) in Korat cats.

PubMed

Neuwelt, E A; Johnson, W G; Blank, N K; Pagel, M A; Maslen-McClure, C; McClure, M J; Wu, P M

1985-08-01

We have detected a disorder in Korat cats (initially imported from Thailand) that is analogous to human Sandhoff's disease. Pedigree analysis indicates that this disease in an autosomal recessive disorder in the American Korat. Postmortem studies on one affected cat showed hepatomegaly that was not reported in the only other known feline model of GM2-gangliosidosis type II. Histologic and ultra-structural evaluation revealed typical storage vacuoles. There was a marked deficiency in the activity of hexosaminidase (HEX) A and B in affected brain and liver as compared to controls. Electrophoresis of a liver extract revealed a deficiency of normal HEX A and B in the affected animals. The blocking primary enzyme immunoassay verified the presence of antigenically reactive HEX present in affected cat livers in quantities slightly elevated with respect to the normal HEX concentration in control cats. In leukocytes, obligate heterozygotes had intermediate levels of total HEX activity with a slight increase in the percent activity due to HEX A. Indeed, 4 of 11 phenotypically normal animals in addition to four obligate heterozygotes appear to be carriers using this assay. Affected brain and liver compared with control brain and liver contained a great excess of bound N-acetylneuraminic acid in the Folch upper-phase solids; thin-layer chromatography showed a marked increase in GM2-ganglioside. In summary, we have characterized the pedigree, pathology, and biochemistry of a new feline model of GM2-gangliosidosis which is similar to but different from the only other known feline model.

Evidence for widespread, severe brain copper deficiency in Alzheimer's dementia.

PubMed

Xu, Jingshu; Church, Stephanie J; Patassini, Stefano; Begley, Paul; Waldvogel, Henry J; Curtis, Maurice A; Faull, Richard L M; Unwin, Richard D; Cooper, Garth J S

2017-08-16

Datasets comprising simultaneous measurements of many essential metals in Alzheimer's disease (AD) brain are sparse, and available studies are not entirely in agreement. To further elucidate this matter, we employed inductively-coupled-plasma mass spectrometry to measure post-mortem levels of 8 essential metals and selenium, in 7 brain regions from 9 cases with AD (neuropathological severity Braak IV-VI), and 13 controls who had normal ante-mortem mental function and no evidence of brain disease. Of the regions studied, three undergo severe neuronal damage in AD (hippocampus, entorhinal cortex and middle-temporal gyrus); three are less-severely affected (sensory cortex, motor cortex and cingulate gyrus); and one (cerebellum) is relatively spared. Metal concentrations in the controls differed among brain regions, and AD-associated perturbations in most metals occurred in only a few: regions more severely affected by neurodegeneration generally showed alterations in more metals, and cerebellum displayed a distinctive pattern. By contrast, copper levels were substantively decreased in all AD-brain regions, to 52.8-70.2% of corresponding control values, consistent with pan-cerebral copper deficiency. This copper deficiency could be pathogenic in AD, since levels are lowered to values approximating those in Menkes' disease, an X-linked recessive disorder where brain-copper deficiency is the accepted cause of severe brain damage. Our study reinforces others reporting deficient brain copper in AD, and indicates that interventions aimed at safely and effectively elevating brain copper could provide a new experimental-therapeutic approach.

Disrupted functional connectome in antisocial personality disorder.

PubMed

Jiang, Weixiong; Shi, Feng; Liao, Jian; Liu, Huasheng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen; Wang, Wei; Shen, Dinggang

2017-08-01

Studies on antisocial personality disorder (ASPD) subjects focus on brain functional alterations in relation to antisocial behaviors. Neuroimaging research has identified a number of focal brain regions with abnormal structures or functions in ASPD. However, little is known about the connections among brain regions in terms of inter-regional whole-brain networks in ASPD patients, as well as possible alterations of brain functional topological organization. In this study, we employ resting-state functional magnetic resonance imaging (R-fMRI) to examine functional connectome of 32 ASPD patients and 35 normal controls by using a variety of network properties, including small-worldness, modularity, and connectivity. The small-world analysis reveals that ASPD patients have increased path length and decreased network efficiency, which implies a reduced ability of global integration of whole-brain functions. Modularity analysis suggests ASPD patients have decreased overall modularity, merged network modules, and reduced intra- and inter-module connectivities related to frontal regions. Also, network-based statistics show that an internal sub-network, composed of 16 nodes and 16 edges, is significantly affected in ASPD patients, where brain regions are mostly located in the fronto-parietal control network. These results suggest that ASPD is associated with both reduced brain integration and segregation in topological organization of functional brain networks, particularly in the fronto-parietal control network. These disruptions may contribute to disturbances in behavior and cognition in patients with ASPD. Our findings may provide insights into a deeper understanding of functional brain networks of ASPD.

Disrupted functional connectome in antisocial personality disorder

PubMed Central

Jiang, Weixiong; Shi, Feng; Liao, Jian; Liu, Huasheng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen

2017-01-01

Studies on antisocial personality disorder (ASPD) subjects focus on brain functional alterations in relation to antisocial behaviors. Neuroimaging research has identified a number of focal brain regions with abnormal structures or functions in ASPD. However, little is known about the connections among brain regions in terms of inter-regional whole-brain networks in ASPD patients, as well as possible alterations of brain functional topological organization. In this study, we employ resting-state functional magnetic resonance imaging (R-fMRI) to examine functional connectome of 32 ASPD patients and 35 normal controls by using a variety of network properties, including small-worldness, modularity, and connectivity. The small-world analysis reveals that ASPD patients have increased path length and decreased network efficiency, which implies a reduced ability of global integration of whole-brain functions. Modularity analysis suggests ASPD patients have decreased overall modularity, merged network modules, and reduced intra- and inter-module connectivities related to frontal regions. Also, network-based statistics show that an internal sub-network, composed of 16 nodes and 16 edges, is significantly affected in ASPD patients, where brain regions are mostly located in the fronto-parietal control network. These results suggest that ASPD is associated with both reduced brain integration and segregation in topological organization of functional brain networks, particularly in the fronto-parietal control network. These disruptions may contribute to disturbances in behavior and cognition in patients with ASPD. Our findings may provide insights into a deeper understanding of functional brain networks of ASPD. PMID:27541949

Long term imaging of living brain cancer cells

NASA Astrophysics Data System (ADS)

Farias, Patricia M. A.; Galembeck, André; Milani, Raquel; Andrade, Arnaldo C. D. S.; Stingl, Andreas

2018-02-01

QDs synthesized in aqueous medium and functionalized with polyethylene glycol were used as fluorescent probes. They label and monitor living healthy and cancer brain glial cells in culture. Physical-chemical characterization was performed. Toxicological studies were performed by in vivo short and long-term inhalation in animal models. Healthy and cancer glial living cells were incubated in culture media with highly controlled QDs. Specific features of glial cancer cells were enhanced by QD labelling. Cytoplasmic labelling pattern was clearly distinct for healthy and cancer cells. Labelled cells kept their normal activity for same period as non-labelled control samples.

Clinical review: Brain-body temperature differences in adults with severe traumatic brain injury

PubMed Central

2013-01-01

Surrogate or 'proxy' measures of brain temperature are used in the routine management of patients with brain damage. The prevailing view is that the brain is 'hotter' than the body. The polarity and magnitude of temperature differences between brain and body, however, remains unclear after severe traumatic brain injury (TBI). The focus of this systematic review is on the adult patient admitted to intensive/neurocritical care with a diagnosis of severe TBI (Glasgow Coma Scale score of less than 8). The review considered studies that measured brain temperature and core body temperature. Articles published in English from the years 1980 to 2012 were searched in databases, CINAHL, PubMed, Scopus, Web of Science, Science Direct, Ovid SP, Mednar and ProQuest Dissertations & Theses Database. For the review, publications of randomised controlled trials, non-randomised controlled trials, before and after studies, cohort studies, case-control studies and descriptive studies were considered for inclusion. Of 2,391 records identified via the search strategies, 37 were retrieved for detailed examination (including two via hand searching). Fifteen were reviewed and assessed for methodological quality. Eleven studies were included in the systematic review providing 15 brain-core body temperature comparisons. The direction of mean brain-body temperature differences was positive (brain higher than body temperature) and negative (brain lower than body temperature). Hypothermia is associated with large brain-body temperature differences. Brain temperature cannot be predicted reliably from core body temperature. Concurrent monitoring of brain and body temperature is recommended in patients where risk of temperature-related neuronal damage is a cause for clinical concern and when deliberate induction of below-normal body temperature is instituted. PMID:23680353

Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain

PubMed Central

Al-Mashhadi, Sufana; Simpson, Julie E.; Heath, Paul R.; Dickman, Mark; Forster, Gillian; Matthews, Fiona E.; Brayne, Carol; Ince, Paul G.; Wharton, Stephen B.

2016-01-01

White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2′-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. PMID:25311358

Differentiating pediatric epileptic brain tissue from normal brain tissue by using time-dependent diffuse reflectance spectroscopy in vivo: comprehensive data analysis method in the time domain

NASA Astrophysics Data System (ADS)

Oh, Sanghoon; Fernald, Bradley; Bhatia, Sanjiv; Ragheb, John; Sandberg, David; Johnson, Mahlon; Lin, Wei-Chiang

2009-05-01

This research investigated the feasibility of using time-dependent diffuse reflectance spectroscopy to differentiate pediatric epileptic brain tissue from normal brain tissue. The optical spectroscopic technique monitored the dynamic optical properties of the cerebral cortex that are associated with its physiological, morphological, and compositional characteristics. Due to the transient irregular epileptic discharge activity within the epileptic brain tissue it was hypothesized that the lesion would express abnormal dynamic optical behavior that would alter normal dynamic behavior. Thirteen pediatric epilepsy patients and seven pediatric brain tumor patients (normal controls) were recruited for this clinical study. Dynamic optical properties were obtained from the cortical surface intraoperatively using a timedependent diffuse reflectance spectroscopy system. This system consisted of a fiber-optic probe, a tungsten-halogen light source, and a spectrophotometer. It acquired diffuse reflectance spectra with a spectral range of 204 nm to 932 nm at a rate of 33 spectra per second for approximately 12 seconds. Biopsy samples were taken from electrophysiologically abnormal cortex and evaluated by a neuropathologist, which served as a gold standard for lesion classification. For data analysis, spectral intensity changes of diffuse reflectance in the time domain at two different wavelengths from each investigated site were compared. Negative correlation segment, defined by the periods where the intensity changes at the two wavelengths were opposite in their slope polarity, were extracted. The total duration of negative correlation, referred to as the "negative correlation time index", was calculated by integrating the negative correlation segments. The negative correlation time indices from all investigated sites were sub-grouped according to the corresponding histological classifications. The difference between the mean indices of two subgroups was evaluated by standard t-test. These comparison and calculation procedures were carried out for all possible wavelength combinations between 400 nm and 800 nm with 2 nm increments. The positive group consisted of seven pathologically abnormal test sites, and the negative group consisted of 13 normal test sites from non-epileptic tumor patients. A standard t-test showed significant difference between negative correlation time indices from the two groups at the wavelength combinations of 700-760 nm versus 550-580 nm. An empirical discrimination algorithm based on the negative correlation time indices in this range produced 100% sensitivity and 85% specificity. Based on these results time-dependent diffuse reflectance spectroscopy with optimized data analysis methods differentiates epileptic brain tissue from normal brain tissue adequately, therefore can be utilized for surgical guidance, and may enhance the surgical outcome of pediatric epilepsy surgery.

Brain tumor modeling: glioma growth and interaction with chemotherapy

NASA Astrophysics Data System (ADS)

Banaem, Hossein Y.; Ahmadian, Alireza; Saberi, Hooshangh; Daneshmehr, Alireza; Khodadad, Davood

2011-10-01

In last decade increasingly mathematical models of tumor growths have been studied, particularly on solid tumors which growth mainly caused by cellular proliferation. In this paper we propose a modified model to simulate the growth of gliomas in different stages. Glioma growth is modeled by a reaction-advection-diffusion. We begin with a model of untreated gliomas and continue with models of polyclonal glioma following chemotherapy. From relatively simple assumptions involving homogeneous brain tissue bounded by a few gross anatomical landmarks (ventricles and skull) the models have been expanded to include heterogeneous brain tissue with different motilities of glioma cells in grey and white matter. Tumor growth is characterized by a dangerous change in the control mechanisms, which normally maintain a balance between the rate of proliferation and the rate of apoptosis (controlled cell death). Result shows that this model closes to clinical finding and can simulate brain tumor behavior properly.

The impact of junk foods on the adolescent brain.

PubMed

Reichelt, Amy C; Rank, Michelle M

2017-12-01

Adolescence is a significant period of physical, social, and emotional development, and is characterized by prominent neurobiological changes in the brain. The maturational processes that occur in brain regions responsible for cognitive control and reward seeking may underpin excessive consumption of palatable high fat and high sugar "junk" foods during adolescence. Recent studies have highlighted the negative impact of these foods on brain function, resulting in cognitive impairments and altered reward processing. The increased neuroplasticity during adolescence may render the brain vulnerable to the negative effects of these foods on cognition and behavior. In this review, we describe the mechanisms by which junk food diets influence neurodevelopment during adolescence. Diet can lead to alterations in dopamine-mediated reward signaling, and inhibitory neurotransmission controlled by γ-aminobutyric acid (GABA), two major neurotransmitter systems that are under construction across adolescence. We propose that poor dietary choices may derail the normal adolescent maturation process and influence neurodevelopmental trajectories, which can predispose individuals to dysregulated eating and impulsive behaviors. © 2017 Wiley Periodicals, Inc.

Role of the brain stem in tibial inhibition of the micturition reflex in cats.

PubMed

Ferroni, Matthew C; Slater, Rick C; Shen, Bing; Xiao, Zhiying; Wang, Jicheng; Lee, Andy; Roppolo, James R; de Groat, William C; Tai, Changfeng

2015-08-01

This study examined the role of the brain stem in inhibition of bladder reflexes induced by tibial nerve stimulation (TNS) in α-chloralose-anesthetized decerebrate cats. Repeated cystometrograms (CMGs) were performed by infusing saline or 0.25% acetic acid (AA) to elicit normal or overactive bladder reflexes, respectively. TNS (5 or 30 Hz) at three times the threshold (3T) intensity for inducing toe movement was applied for 30 min between CMGs to induce post-TNS inhibition or applied during the CMGs to induce acute TNS inhibition. Inhibition was evident as an increase in bladder capacity without a change in amplitude of bladder contractions. TNS applied for 30 min between saline CMGs elicited prolonged (>2 h) poststimulation inhibition that significantly (P < 0.05) increased bladder capacity to 30-60% above control; however, TNS did not produce this effect during AA irritation. TNS applied during CMGs at 5 Hz but not 30 Hz significantly (P < 0.01) increased bladder capacity to 127.3 ± 6.1% of saline control or 187.6 ± 5.0% of AA control. During AA irritation, naloxone (an opioid receptor antagonist) administered intravenously (1 mg/kg) or directly to the surface of the rostral brain stem (300-900 μg) eliminated acute TNS inhibition and significantly (P < 0.05) reduced bladder capacity to 62.8 ± 22.6% (intravenously) or 47.6 ± 25.5% (brain stem application). Results of this and previous studies indicate 1) forebrain circuitry rostral to the pons is not essential for TNS inhibition; and 2) opioid receptors in the brain stem have a critical role in TNS inhibition of overactive bladder reflexes but are not involved in inhibition of normal bladder reflexes. Copyright © 2015 the American Physiological Society.

High prevalence of brain pathology in violent prisoners: a qualitative CT and MRI scan study.

PubMed

Schiltz, Kolja; Witzel, Joachim G; Bausch-Hölterhoff, Josef; Bogerts, Bernhard

2013-10-01

The aim of this study was to determine the frequency and extent of brain anomalies in a large sample of incarcerated violent offenders not previously considered neuropsychiatrically ill, in comparison with non-violent offenders and non-offending controls. MRI and CT brain scans from 287 male prison inmates (162 violent and 125 non-violent) not diagnosed as mentally ill before that were obtained due to headache, vertigo or psychological complaints during imprisonment were assessed and compared to 52 non-criminal controls. Brain scans were rated qualitatively with respect to evidence of structural brain damage. Each case received a semiquantitative rating of "normal" (=0), "questionably abnormal" (=1) or "definitely abnormal" (=2) for the lateral ventricles, frontal/parietal cortex and medial temporal structures bilaterally as well as third ventricle. Overall, offenders displayed a significantly higher rate of morphological abnormality, with the violent offenders scoring significantly higher than non-violent offenders and controls. This difference was statistically detectable for frontal/parietal cortex, medial temporal structures, third ventricle and the left but not the right lateral ventricle. The remarkable prevalence of brain pathology in convicted violent prisoners detectable by neuroradiological routine assessment not only highlights the importance of frontal and temporal structures in the control of social, and specifically of violent behaviour, but also raises questions on the legal culpability of violent offenders with brain abnormalities. The high proportion of undetected presence of structural brain damage emphasizes the need that in violent criminals, the comprehensive routine neuropsychiatric assessment usually performed in routine forensic psychiatric expertises should be complemented with brain imaging.

Brain reward system's alterations in response to food and monetary stimuli in overweight and obese individuals.

PubMed

Verdejo-Román, Juan; Vilar-López, Raquel; Navas, Juan F; Soriano-Mas, Carles; Verdejo-García, Antonio

2017-02-01

The brain's reward system is crucial to understand obesity in modern society, as increased neural responsivity to reward can fuel the unhealthy food choices that are driving the growing obesity epidemic. Brain's reward system responsivity to food and monetary rewards in individuals with excessive weight (overweight and obese) versus normal weight controls, along with the relationship between this responsivity and body mass index (BMI) were tested. The sample comprised 21 adults with obesity (BMI > 30), 21 with overweight (BMI between 25 and 30), and 39 with normal weight (BMI < 25). Participants underwent a functional magnetic resonance imaging (fMRI) session while performing two tasks that involve the processing of food (Willing to Pay) and monetary rewards (Monetary Incentive Delay). Neural activations within the brain reward system were compared across the three groups. Curve fit analyses were conducted to establish the association between BMI and brain reward system's response. Individuals with obesity had greater food-evoked responsivity in the dorsal and ventral striatum compared with overweight and normal weight groups. There was an inverted U-shape association between BMI and monetary-evoked responsivity in the ventral striatum, medial frontal cortex, and amygdala; that is, individuals with BMIs between 27 and 32 had greater responsivity to monetary stimuli. Obesity is associated with greater food-evoked responsivity in the ventral and dorsal striatum, and overweight is associated with greater monetary-evoked responsivity in the ventral striatum, the amygdala, and the medial frontal cortex. Findings suggest differential reactivity of the brain's reward system to food versus monetary rewards in obesity and overweight. Hum Brain Mapp 38:666-677, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Quantitative assessment of cerebral glucose metabolic rates after blood-brain barrier disruption induced by focused ultrasound using FDG-MicroPET.

PubMed

Yang, Feng-Yi; Chang, Wen-Yuan; Chen, Jyh-Cheng; Lee, Lin-Chien; Hung, Yi-Shun

2014-04-15

The goal of this study was to evaluate the pharmacokinetics of (18)F-2-fluoro-2-deoxy-d-glucose ((18)F-FDG) and the expression of glucose transporter 1 (GLUT1) protein after blood-brain barrier (BBB) disruption of normal rat brains by focused ultrasound (FUS). After delivery of an intravenous bolus of ~37 MBq (1 mCi) (18)F-FDG, dynamic positron emission tomography scans were performed on rats with normal brains and those whose BBBs had been disrupted by FUS. Arterial blood sampling was collected throughout the scanning procedure. A 2-tissue compartmental model was used to estimate (18)F-FDG kinetic parameters in brain tissues. The rate constants Ki, K1, and k3 were assumed to characterize the uptake, transport, and hexokinase activity, respectively, of (18)F-FDG. The uptake of (18)F-FDG in brains significantly decreased immediately after the blood-brain barrier was disrupted. At the same time, the derived values of Ki, K1, and k3 for the sonicated brains were significantly lower than those for the control brains. In agreement with the reduction in glucose, Western blot analyses confirmed that focused ultrasound exposure significantly reduced the expression of GLUT1 protein in the brains. Furthermore, the effect of focused ultrasound on glucose uptake was transient and reversible 24h after sonication. Our results indicate that focused ultrasound may inhibit GLUT1 expression to decrease the glucose uptake in brain tissue during the period of BBB disruption. Copyright © 2013 Elsevier Inc. All rights reserved.

EEG topography and tomography (LORETA) in the classification and evaluation of the pharmacodynamics of psychotropic drugs.

PubMed

Saletu, Bernd; Anderer, Peter; Saletu-Zyhlarz, Gerda M

2006-04-01

By multi-lead computer-assisted quantitative analyses of human scalp-recorded electroencephalogram (QEEG) in combination with certain statistical procedures (quantitative pharmaco-EEG) and mapping techniques (pharmaco-EEG mapping or topography), it is possible to classify psychotropic substances and objectively evaluate their bioavailability at the target organ, the human brain. Specifically, one may determine at an early stage of drug development whether a drug is effective on the central nervous system (CNS) compared with placebo, what its clinical efficacy will be like, at which dosage it acts, when it acts and the equipotent dosages of different galenic formulations. Pharmaco-EEG maps of neuroleptics, antidepressants, tranquilizers, hypnotics, psychostimulants and nootropics/cognition-enhancing drugs will be described. Methodological problems, as well as the relationships between acute and chronic drug effects, alterations in normal subjects and patients, CNS effects and therapeutic efficacy will be discussed. Imaging of drug effects on the regional brain electrical activity of healthy subjects by means of EEG tomography such as low-resolution electromagnetic tomography (LORETA) has been used for identifying brain areas predominantly involved in psychopharmacological action. This will be shown for the representative drugs of the four main psychopharmacological classes, such as 3 mg haloperidol for neuroleptics, 20 mg citalopram for antidepressants, 2 mg lorazepam for tranquilizers and 20 mg methylphenidate for psychostimulants. LORETA demonstrates that these psychopharmacological classes affect brain structures differently. By considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a key-lock principle, since the drug should normalize the deviant brain function. Thus, pharmaco-EEG topography and tomography are valuable methods in human neuropsychopharmacology, clinical psychiatry and neurology.

The biochemical, nanomechanical and chemometric signatures of brain cancer

NASA Astrophysics Data System (ADS)

Abramczyk, Halina; Imiela, Anna

2018-01-01

Raman spectroscopy and imaging combined with AFM topography and mechanical indentation by AFM have been shown to be an effective tool for analysis and discrimination of human brain tumors from normal structures. Raman methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n = 5) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma (IV grade), and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational spectra and Raman images we provide a real-time feedback that is label-free method to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, and proteins. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have shown that the ratio of Raman intensities I2930/I2845 at 2930 and 2845 cm- 1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the lipid and protein contents of tumorous brain tissue compared to the non-tumor tissue. Almost all brain tumors have the Raman intensity ratios significantly higher (1.99 ± 0.026) than that found in non-tumor brain tissue, which is 1.456 ± 0.02, and indicates that the relative amount of lipids compared to proteins is significantly higher in the normal brain tissue. Mechanical indentation using AFM on sliced human brain tissues (medulloblastoma, grade IV) revealed that the mechanical properties of this tissue are strongly heterogeneous, between 1.8 and 75.7 kPa, and the mean of 27.16 kPa. The sensitivity and specificity obtained directly from PLSDA and cross validation gives a sensitivity and specificity of 98.5% and 96% and 96.3% and 92% for cross-validation, respectively. The high sensitivity and specificity demonstrates usefulness for a proper decision for a Raman diagnostic test on biochemical alterations monitored by Raman spectroscopy related to brain cancer development.

Anticholinesterase Effect on Motor Kinematic Measures and Brain Activation in Parkinson’s Disease

PubMed Central

Mentis, Marc J.; Delalot, Dominique; Naqvi, Hassan; Gordon, Mark F.; Gudesblatt, Mark; Edwards, Christine; Donatelli, Luke; Dhawan, Vijay; Eidelberg, David

2015-01-01

Anticholinesterase (AChE) drugs are being prescribed off label for nonmotor symptoms in Parkinson’s disease (PD). Theoretically, these drugs can impair motor function. A small literature suggests AChE therapy has little effect on clinical motor evaluation; however, no study has made objective motor kinematic measures or evaluated brain function. We hypothesized that even if clinical examination was normal in PD patients on dopamine therapy, (1) sensitive kinematic measures would be abnormal during AChE therapy or (2) normal kinematic measures would be maintained by compensatory brain activation. We carried out a randomized, double-blind, placebo-controlled trial of 8 weeks donepezil (10 mg/day) in 17 PD subjects. Subjects carried out a computerized motor task during a positron emission tomography (PET) scan before starting the drug and again after 8 weeks of donepezil or placebo. Kinematic measures of motor function and PET scans were analyzed to compare the effects of donepezil and placebo. Neither placebo nor donepezil altered motor kinematic measures. Furthermore, movement integrity while on donepezil was maintained without compensatory brain activity. Donepezil 10 mg/day can be given for nonmotor symptoms in PD without adverse motor effects or compensatory brain activity. PMID:16228997

Effect of time period after boric acid injection on 10B absorption in different regions of adult male rat's brain.

PubMed

Khojasteh, Nasrin Baghban; Pazirandeh, Ali; Jameie, Behnam; Goodarzi, Samereh

2012-06-01

Distribution of (10)B in different regions of rat normal brain was studied. Two groups were chosen as control and trial. Trial group received 2 ml of neutral boron compound. 2, 4 and 6 h after the injection brain removed, coronal sections of forebrain, midbrain and hindbrain were sandwiched between two pieces of polycarbonate. Autoradiography plots of (10)B distribution showed significant differences in three regions with the highest (10)B concentration in the forebrain during 4 h after injection. Copyright © 2012 Elsevier Ltd. All rights reserved.

Singing ability after right and left sided brain damage. A research note.

PubMed

Kinsella, G; Prior, M R; Murray, G

1988-03-01

Capacity to sing following brain damage was investigated in a series of 15 right sided and 15 left sided lesioned subjects and 15 normal control subjects. All subjects were asked to sing the same well-known song and performance was judged by independent expert musicians using criteria of ability to pitch the melody, accurately produce the rhythm, and overall quality of the production. There was a lack of support for differential effect of right and left cerebral damage on pitch and rhythm aspects of singing, but a generalized effect of brain damage was found.

Pathology of non-thermal irreversible electroporation (N-TIRE)-induced ablation of the canine brain.

PubMed

Rossmeisl, John H; Garcia, Paulo A; Roberston, John L; Ellis, Thomas L; Davalos, Rafael V

2013-01-01

This study describes the neuropathologic features of normal canine brain ablated with non-thermal irreversible electroporation (N-TIRE). The parietal cerebral cortices of four dogs were treated with N-TIRE using a dose-escalation protocol with an additional dog receiving sham treatment. Animals were allowed to recover following N-TIRE ablation and the effects of treatment were monitored with clinical and magnetic resonance imaging examinations. Brains were subjected to histopathologic and ultrastructural assessment along with Bcl-2, caspase-3, and caspase-9 immunohistochemical staining following sacrifice 72 h post-treatment. Adverse clinical effects of N-TIRE were only observed in the dog treated at the upper energy tier. MRI and neuropathologic examinations indicated that N-TIRE ablation resulted in focal regions of severe cytoarchitectural and blood-brain-barrier disruption. Lesion size correlated to the intensity of the applied electrical field. N-TIRE-induced lesions were characterized by parenchymal necrosis and hemorrhage; however, large blood vessels were preserved. A transition zone containing parenchymal edema, perivascular inflammatory cuffs, and reactive gliosis was interspersed between the necrotic focus and normal neuropil. Apoptotic labeling indices were not different between the N-TIRE-treated and control brains. This study identified N-TIRE pulse parameters that can be used to safely create circumscribed foci of brain necrosis while selectively preserving major vascular structures.

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

COUP-TF1 Modulates Thyroid Hormone Action in an Embryonic Stem-Cell Model of Cortical Pyramidal Neuronal Differentiation.

PubMed

Teng, Xiaochun; Liu, Yan-Yun; Teng, Weiping; Brent, Gregory A

2018-05-01

Thyroid hormone is critical for normal brain development and acts in a spatial and temporal specific pattern. Thyroid hormone excess, or deficiency, can lead to irreversible impairment of brain and sensory development. Chicken ovalbumin upstream-transcription factor 1 (COUP-TF1), expressed early in neuronal development, is essential to achieve normal brain structure. Thyroid hormone stimulation of gene expression is inversely correlated with the level of COUP-TF1 expression. An in vitro method of differentiating mouse embryonic stem (mES) cells into cortical neurons was utilized to study the influence of COUP-TF1 on thyroid hormone signaling in brain development. mES cells were cultured and differentiated in specific conditioned media, and a high percentage of nestin-positive progenitor neurons in the first stage, and cortical neurons in the second stage, was obtained with characteristic neuronal firing. The number of nestin-positive progenitors, as determined by fluorescence-activated cell sorting analysis, was significantly greater with triiodothyronine (T3) treatment compared to control (p < 0.05). T3 enhanced the expression of cortical neuron marker (Tbr1 and Rc3) mRNAs. After COUP-TF1 knockdown, the number of nestin-positive progenitors was reduced compared to control (p < 0.05), but the number increased with T3 treatment. The mRNA of cortical neuronal gene markers was measured after COUP-TF1 knockdown. In the presence of T3, the peak expression of neuron markers Emx1, Tbr1, Camkiv, and Rc3 mRNA was earlier, at day 18 of differentiation, compared to control cells, at day 22. Furthermore, after COUP-TF1 knockdown, T3 induction of Rc3 and Tbr1 mRNA was significantly enhanced compared to cells expressing COUP-TF1. These results indicate that COUP-TF1 plays an important role in modulating the timing and magnitude of T3-stimulated gene expression required for normal corticogenesis.

Cumulative Brain Injury from Motor Vehicle-Induced Whole-Body Vibration and Prevention by Human Apolipoprotein A-I Molecule Mimetic (4F) Peptide (an Apo A-I Mimetic)

PubMed Central

Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; Yan, Yuhui; LoGiudice, John; Sanger, James R.; Matloub, Hani S.; Pritchard, Kirkwood A.; Jaradeh, Safwan S.; Havlik, Robert

2017-01-01

Background Insidious cumulative brain injury from motor vehicle-induced whole-body vibration (MV-WBV) has not yet been studied. The objective of the present study is to validate whether whole-body vibration for long periods causes cumulative brain injury and impairment of the cerebral function. We also explored a preventive method for MV-WBV injury. Methods A study simulating whole-body vibration was conducted in 72 male Sprague-Dawley rats divided into 9 groups (N = 8): (1) 2-week normal control; (2) 2-week sham control (in the tube without vibration); (3) 2-week vibration (exposed to whole-body vibration at 30 Hz and .5 G acceleration for 4 hours/day, 5 days/week for 2 weeks; vibration parameters in the present study are similar to the most common driving conditions); (4) 4-week sham control; (5) 4-week vibration; (6) 4-week vibration with human apolipoprotein A-I molecule mimetic (4F)-preconditioning; (7) 8-week sham control; (8) 8-week vibration; and (9) 8-week 4F-preconditioning group. All the rats were evaluated by behavioral, physiological, and histological studies of the brain. Results Brain injury from vibration is a cumulative process starting with cerebral vasoconstriction, squeezing of the endothelial cells, increased free radicals, decreased nitric oxide, insufficient blood supply to the brain, and repeated reperfusion injury to brain neurons. In the 8-week vibration group, which indicated chronic brain edema, shrunken neuron numbers increased and whole neurons atrophied, which strongly correlated with neural functional impairment. There was no prominent brain neuronal injury in the 4F groups. Conclusions The present study demonstrated cumulative brain injury from MV-WBV and validated the preventive effects of 4F preconditioning. PMID:26433438

Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion.

PubMed

Daly, Eileen; Ecker, Christine; Hallahan, Brian; Deeley, Quinton; Craig, Michael; Murphy, Clodagh; Johnston, Patrick; Spain, Debbie; Gillan, Nicola; Gudbrandsen, Maria; Brammer, Michael; Giampietro, Vincent; Lamar, Melissa; Page, Lisa; Toal, Fiona; Schmitz, Nicole; Cleare, Anthony; Robertson, Dene; Rubia, Katya; Murphy, Declan G M

2014-09-01

It has been suggested that the restricted, stereotyped and repetitive behaviours typically found in autism are underpinned by deficits of inhibitory control. The biological basis of this is unknown but may include differences in the modulatory role of neurotransmitters, such as serotonin, which are implicated in the condition. However, this has never been tested directly. We therefore assessed the modifying role of serotonin on inhibitory brain function during a Go/No-Go task in 14 adults with autism and normal intelligence and 14 control subjects that did not differ in gender, age and intelligence. We undertook a double-blind, placebo-controlled, crossover trial of acute tryptophan depletion using functional magnetic resonance imaging. Following sham, adults with autism relative to controls had reduced activation in key inhibitory regions of inferior frontal cortex and thalamus, but increased activation of caudate and cerebellum. However, brain activation was modulated in opposite ways by depletion in each group. Within autistic individuals depletion upregulated fronto-thalamic activations and downregulated striato-cerebellar activations toward control sham levels, completely 'normalizing' the fronto-cerebellar dysfunctions. The opposite pattern occurred in controls. Moreover, the severity of autism was related to the degree of differential modulation by depletion within frontal, striatal and thalamic regions. Our findings demonstrate that individuals with autism have abnormal inhibitory networks, and that serotonin has a differential, opposite, effect on them in adults with and without autism. Together these factors may partially explain the severity of autistic behaviours and/or provide a novel (tractable) treatment target. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Apelin targets gut contraction to control glucose metabolism via the brain

PubMed Central

Fournel, Audren; Drougard, Anne; Duparc, Thibaut; Marlin, Alysson; Brierley, Stuart M; Castro, Joel; Le-Gonidec, Sophie; Masri, Bernard; Colom, André; Lucas, Alexandre; Rousset, Perrine; Cenac, Nicolas; Vergnolle, Nathalie; Valet, Philippe; Cani, Patrice D; Knauf, Claude

2017-01-01

Objective The gut–brain axis is considered as a major regulatory checkpoint in the control of glucose homeostasis. The detection of nutrients and/or hormones in the duodenum informs the hypothalamus of the host's nutritional state. This process may occur via hypothalamic neurons modulating central release of nitric oxide (NO), which in turn controls glucose entry into tissues. The enteric nervous system (ENS) modulates intestinal contractions in response to various stimuli, but the importance of this interaction in the control of glucose homeostasis via the brain is unknown. We studied whether apelin, a bioactive peptide present in the gut, regulates ENS-evoked contractions, thereby identifying a new physiological partner in the control of glucose utilisation via the hypothalamus. Design We measured the effect of apelin on electrical and mechanical duodenal responses via telemetry probes and isotonic sensors in normal and obese/diabetic mice. Changes in hypothalamic NO release, in response to duodenal contraction modulated by apelin, were evaluated in real time with specific amperometric probes. Glucose utilisation in tissues was measured with orally administrated radiolabeled glucose. Results In normal and obese/diabetic mice, glucose utilisation is improved by the decrease of ENS/contraction activities in response to apelin, which generates an increase in hypothalamic NO release. As a consequence, glucose entry is significantly increased in the muscle. Conclusions Here, we identify a novel mode of communication between the intestine and the hypothalamus that controls glucose utilisation. Moreover, our data identified oral apelin administration as a novel potential target to treat metabolic disorders. PMID:26565000

Neural systemic impairment from whole-body vibration.

PubMed

Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; LoGiudice, John; Sanger, James R; Matloub, Hani S; Havlik, Robert

2015-05-01

Insidious brain microinjury from motor vehicle-induced whole-body vibration (WBV) has not yet been investigated. For a long time we have believed that WBV would cause cumulative brain microinjury and impair cerebral function, which suggests an important risk factor for motor vehicle accidents and secondary cerebral vascular diseases. Fifty-six Sprague-Dawley rats were divided into seven groups (n = 8): 1) 2-week normal control group, 2) 2-week sham control group (restrained in the tube without vibration), 3) 2-week vibration group (exposed to whole-body vibration at 30 Hz and 0.5g acceleration for 4 hr/day, 5 days/week, for 2 weeks), 4) 4-week sham control group, 5) 4-week vibration group, 6) 8-week sham control group, and 7) 8-week vibration group. At the end point, all rats were evaluated in behavior, physiological, and brain histopathological studies. The cerebral injury from WBV is a cumulative process starting with vasospasm squeezing of the endothelial cells, followed by constriction of the cerebral arteries. After the 4-week vibration, brain neuron apoptosis started. After the 8-week vibration, vacuoles increased further in the brain arteries. Brain capillary walls thickened, mean neuron size was obviously reduced, neuron necrosis became prominent, and wide-ranging chronic cerebral edema was seen. These pathological findings are strongly correlated with neural functional impairments. © 2014 Wiley Periodicals, Inc.

Change of Brain Functional Connectivity in Patients With Spinal Cord Injury: Graph Theory Based Approach.

PubMed

Min, Yu-Sun; Chang, Yongmin; Park, Jang Woo; Lee, Jong-Min; Cha, Jungho; Yang, Jin-Ju; Kim, Chul-Hyun; Hwang, Jong-Moon; Yoo, Ji-Na; Jung, Tae-Du

2015-06-01

To investigate the global functional reorganization of the brain following spinal cord injury with graph theory based approach by creating whole brain functional connectivity networks from resting state-functional magnetic resonance imaging (rs-fMRI), characterizing the reorganization of these networks using graph theoretical metrics and to compare these metrics between patients with spinal cord injury (SCI) and age-matched controls. Twenty patients with incomplete cervical SCI (14 males, 6 females; age, 55±14.1 years) and 20 healthy subjects (10 males, 10 females; age, 52.9±13.6 years) participated in this study. To analyze the characteristics of the whole brain network constructed with functional connectivity using rs-fMRI, graph theoretical measures were calculated including clustering coefficient, characteristic path length, global efficiency and small-worldness. Clustering coefficient, global efficiency and small-worldness did not show any difference between controls and SCIs in all density ranges. The normalized characteristic path length to random network was higher in SCI patients than in controls and reached statistical significance at 12%-13% of density (p<0.05, uncorrected). The graph theoretical approach in brain functional connectivity might be helpful to reveal the information processing after SCI. These findings imply that patients with SCI can build on preserved competent brain control. Further analyses, such as topological rearrangement and hub region identification, will be needed for better understanding of neuroplasticity in patients with SCI.

CONTROL OF SLEEP AND WAKEFULNESS

PubMed Central

Brown, Ritchie E.; Basheer, Radhika; McKenna, James T.; Strecker, Robert E.; McCarley, Robert W.

2013-01-01

This review summarizes the brain mechanisms controlling sleep and wakefulness. Wakefulness promoting systems cause low-voltage, fast activity in the electroencephalogram (EEG). Multiple interacting neurotransmitter systems in the brain stem, hypothalamus, and basal forebrain converge onto common effector systems in the thalamus and cortex. Sleep results from the inhibition of wake-promoting systems by homeostatic sleep factors such as adenosine and nitric oxide and GABAergic neurons in the preoptic area of the hypothalamus, resulting in large-amplitude, slow EEG oscillations. Local, activity-dependent factors modulate the amplitude and frequency of cortical slow oscillations. Non-rapid-eye-movement (NREM) sleep results in conservation of brain energy and facilitates memory consolidation through the modulation of synaptic weights. Rapid-eye-movement (REM) sleep results from the interaction of brain stem cholinergic, aminergic, and GABAergic neurons which control the activity of glutamatergic reticular formation neurons leading to REM sleep phenomena such as muscle atonia, REMs, dreaming, and cortical activation. Strong activation of limbic regions during REM sleep suggests a role in regulation of emotion. Genetic studies suggest that brain mechanisms controlling waking and NREM sleep are strongly conserved throughout evolution, underscoring their enormous importance for brain function. Sleep disruption interferes with the normal restorative functions of NREM and REM sleep, resulting in disruptions of breathing and cardiovascular function, changes in emotional reactivity, and cognitive impairments in attention, memory, and decision making. PMID:22811426

Encoding-related brain activity and accelerated forgetting in transient epileptic amnesia.

PubMed

Atherton, Kathryn E; Filippini, Nicola; Zeman, Adam Z J; Nobre, Anna C; Butler, Christopher R

2018-05-17

The accelerated forgetting of newly learned information is common amongst patients with epilepsy and, in particular, in the syndrome of transient epileptic amnesia (TEA). However, the neural mechanisms underlying accelerated forgetting are poorly understood. It has been hypothesised that interictal epileptiform activity during longer retention intervals disrupts normally established memory traces. Here, we tested a distinct hypothesis-that accelerated forgetting relates to the abnormal encoding of memories. We studied a group of 15 patients with TEA together with matched, healthy control subjects. Despite normal performance on standard anterograde memory tasks, patients showed accelerated forgetting of a word list over one week. We used a subsequent memory paradigm to compare encoding-related brain activity in patients and controls. Participants studied a series of visually presented scenes whilst undergoing functional MRI scanning. Recognition memory for these scenes was then probed outside the scanner after delays of 45 min and of 4 days. Patients showed poorer memory for the scenes compared with controls. In the patients but not the controls, subsequently forgotten stimuli were associated with reduced hippocampal activation at encoding. Furthermore, patients demonstrated reduced deactivation of posteromedial cortex regions upon viewing subsequently remembered stimuli as compared to subsequently forgotten ones. These data suggest that abnormal encoding-related activity in key memory areas of the brain contributes to accelerated forgetting in TEA. We propose that abnormally encoded memory traces may be particularly vulnerable to interference from subsequently encountered material and hence be forgotten more rapidly. Our results shed light on the mechanisms underlying memory impairment in epilepsy, and offer support to the proposal that accelerated forgetting may be a useful marker of subtle dysfunction in memory-related brain systems. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Long-term effects of boxing and judo-choking techniques on brain function.

PubMed

Rodriguez, G; Vitali, P; Nobili, F

1998-12-01

Regional cerebral blood flow (rCBF) was measured by 133-xenon inhalation in 24 amateur and 20 professional boxers, and in 10 judoka. Results were compared with those from age- and sex-matched healthy controls. Eighteen boxers (9 amateurs and 9 professionals) and all judoka also underwent electroencephalography (EEG). Mean rCBF values did not differ between either amateur boxers orjudoka and controls, whereas in professional boxers rCBF was significantly (p<.001) reduced in the whole brain, especially in the frontocentral regions. Healthy subjects, judoka, and amateur boxers showed a similar distribution of global CBF (gCBF, the mean of 32 probes) values, although 12.5% of amateurs had a significantly lower gCBF than controls. Among professional boxers, 25% showed a significantly low gCBF value; in the remaining 75%, gCBF was below the mean value of controls but did not reach statistical significance. Regional hypoperfusion, mainly in the frontocentral regions of both sides, was found in 35% of professional and in 29% of amateur boxers. A correlation between gCBF values and number of official matches was not found in boxers. EEG was normal in all judoka and amateur boxers, but it was abnormal in 3 professionals. This study shows the relevance of the neurophysiological assessment of athletes engaged in violent sports which can cause brain impairment. In fact, while professional boxers may show brain functional impairment in comparison to normal subjects, judoka do not. The lack of correlation between CBF values in boxers and the number of official matches points to the difficulty of taking into account variables, such as the number and the severity of matches during training.

Aberrant brain stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer's disease.

PubMed

Lee, Ji Han; Jung, Won Sang; Choi, Woo Hee; Lim, Hyun Kook

2016-01-01

Among patients with Alzheimer's disease (AD), sleep disturbances are common and serious noncognitive symptoms. Previous studies of AD patients have identified deformations in the brain stem, which may play an important role in the regulation of sleep. The aim of this study was to further investigate the relationship between sleep disturbances and alterations in brain stem morphology in AD. In 44 patients with AD and 40 healthy elderly controls, sleep disturbances were measured using the Neuropsychiatry Inventory sleep subscale. We employed magnetic resonance imaging-based automated segmentation tools to examine the relationship between sleep disturbances and changes in brain stem morphology. Analyses of the data from AD subjects revealed significant correlations between the Neuropsychiatry Inventory sleep-subscale scores and structural alterations in the left posterior lateral region of the brain stem, as well as normalized brain stem volumes. In addition, significant group differences in posterior brain stem morphology were observed between the AD group and the control group. This study is the first to analyze an association between sleep disturbances and brain stem morphology in AD. In line with previous findings, this study lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD. Further longitudinal research is needed to confirm these findings.

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

The road to LOAD: late-onset Alzheimer's disease and a possible way to block it.

PubMed

Whitfield, James F

2007-10-01

The ageing brain becomes increasingly less able to destroy or eject toxic amyloid (A) beta42 peptide byproducts of normal neuronal activity that consequently accumulate to induce Alzheimer's disease (AD). Therefore, the various components of the Abeta-clearing machinery are prime targets for AD therapeutics. In this connection, there are reports that taking statins to lower circulating cholesterol to prevent cardiovascular disease can also prevent late-onset AD (LOAD) the most common form of the disease. However, it seems unlikely that statins would prevent LOAD by lowering the very long-lived brain cholesterol that is controlled independently from the very much shorter-lived circulating cholesterol. In fact, reducing the ability of the brain astrocytes to make cholesterol for their closely associated neuron clients' synaptogenesis could damage the brain rather than protect it. However, a plausible way statins might prevent LOAD is to target a main component of the clearance machinery, low-density lipoprotein receptor-related protein 1 (LRP1), the brain's powerful Abeta-efflux driver. This is indicated by a reported ability of micromolar concentrations of lovastatin and simvastatin to strongly stimulate brain vascular endothelial cells to make this Abeta ejector. Therefore, if this holds up, taking a statin over the years would prevent the normal decline of LRP1 in the ageing brain and a LOAD-driving accumulation of Abeta.

Alpha-Hydroxylation of lignoceric and nervonic acids in the brain. Effects of altered thyroid function on postnatal development of the hydroxylase activity.

PubMed

Murad, S; Strycharz, G D; Kishimoto, Y

1976-09-10

Rat brain postnuclear preparations catalyzed the alpha-hydroxylation of nervonic acid with an apparent Km of 3 muM. Evidence has been presented which suggests that nervonic acid in the brain is hydroxylated by the same enzyme system which hydroxylates lignoceric acid. The hydroxylase activity in brains of normal (euthyroid) rats increased rapidly from a low in the period immediately following birth to a maximum at the 23rd day and then declined to a low level characteristic of the mature brain. Neonatal hypothyroidism retarded the development of the activity and shifted its peak to the 39th day after birth. Conversely, neonatal hyperthyroidism accelerated the entire developmental pattern and shifted the peak to the 16th day after birth. The hydroxylase activity in mouse brain was also increased by thyroid hormone administration from the 13th through the 18th day after birth. Unlike normal mice, the low activity in jimpy mice was not affected by this treatment. It is concluded that thyroid hormones play an important role in the control of brain fatty acid alpha-hydroxylation. The stimulation of alpha-hydroxy fatty acid synthesis in response to hyperthyroidism during the early postnatal period may be one of the major effects of thyroid hormones in accelerating myelination of the central nervous system.

Developmental pattern of diacylglycerol lipase-α (DAGLα) immunoreactivity in brain regions important for song learning and control in the zebra finch (Taeniopygia guttata).

PubMed

Soderstrom, Ken; Wilson, Ashley R

2013-11-01

Zebra finch song is a learned behavior dependent upon successful progress through a sensitive period of late-postnatal development. This learning is associated with maturation of distinct brain nuclei and the fiber tract interconnections between them. We have previously found remarkably distinct and dense CB1 cannabinoid receptor expression within many of these song control brain regions, implying a normal role for endocannabinoid signaling in vocal learning. Activation of CB1 receptors via daily treatments with exogenous agonist during sensorimotor stages of song learning (but not in adulthood) results in persistent alteration of song patterns. Now we are working to understand physiological changes responsible for this cannabinoid-altered vocal learning. We have found that song-altering developmental treatments are associated with changes in expression of endocannabinoid signaling elements, including CB1 receptors and the principal CNS endogenous agonist, 2-AG. Within CNS, 2-AG is produced largely through activity of the α isoform of the enzyme diacylglycerol lipase (DAGLα). To better appreciate the role of 2-AG production in normal vocal development we have determined the spatial distribution of DAGLα expression within zebra finch CNS during vocal development. Early during vocal development at 25 days, DAGLα staining is typically light and of fibroid processes. Staining peaks late in the sensorimotor stage of song learning at 75 days and is characterized by fiber, neuropil and some staining of both small and large cell somata. Results provide insight to the normal role for endocannabinoid signaling in the maturation of brain regions responsible for song learning and vocal-motor output, and suggest mechanisms by which exogenous cannabinoid exposure alters acquisition of this form of vocal communication. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of experimental suppression of active (REM) sleep during early development upon adult brain and behavior in the rat.

PubMed

Mirmiran, M; Scholtens, J; van de Poll, N E; Uylings, H B; van der Gugten, J; Boer, G J

1983-04-01

In order to test the hypothesis that active sleep (AS) is important for the normal development of the central nervous system, 3 different deprivation methods were applied to male Wistar rat pups during the first month of life. Daily injection of clomipramine from 8 to 21 days of age reduced the high level of AS to less than the adult value throughout most of the experimental period. Administration of clonidine from 8 to 21 days of life induced an almost total suppression of AS. Instrumental deprivation, using the 'pendulum' method, led to a significant (but less severe) AS reduction during 2-4 weeks of postnatal age. Open-field behavior testing in adulthood revealed a higher than normal level of ambulation in all 3 experimental groups. Masculine sexual responses were deficient, due to a low level of both mounts and ejaculations, in both clomipramine- and clonidine-treated animals. Neither passive avoidance learning nor dark preference tests revealed any differences between the experimental and control rats. Sleep observations showed that there was an abnormally high incidence of large myoclonic jerks during AS in both clomipramine- and clonidine-treated rats. Subsequent measurement of regional brain weights showed a significant reduction in the cerebral cortex and medulla oblongata, as compared with the respective control groups, in both the clomipramine- and the clonidine-treated rats. In addition, DNA and protein determination in the affected brain areas showed a proportional reduction in the cortex and in the medulla. These results demonstrate that interference with normal functioning either of AS per se or of specific monoaminergic transmitter systems during early development can produce long-lasting behavioral as well as brain morphological and biochemical abnormalities in later life.

Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity

PubMed Central

Volkow, Nora D.; Wang, Gene-Jack; Telang, Frank; Fowler, Joanna S.; Alexoff, David; Logan, Jean; Jayne, Millard; Wong, Christopher; Tomasi, Dardo

2014-01-01

Moves to legalize marijuana highlight the urgency to investigate effects of chronic marijuana in the human brain. Here, we challenged 48 participants (24 controls and 24 marijuana abusers) with methylphenidate (MP), a drug that elevates extracellular dopamine (DA) as a surrogate for probing the reactivity of the brain to DA stimulation. We compared the subjective, cardiovascular, and brain DA responses (measured with PET and [11C]raclopride) to MP between controls and marijuana abusers. Although baseline (placebo) measures of striatal DA D2 receptor availability did not differ between groups, the marijuana abusers showed markedly blunted responses when challenged with MP. Specifically, compared with controls, marijuana abusers had significantly attenuated behavioral (“self-reports” for high, drug effects, anxiety, and restlessness), cardiovascular (pulse rate and diastolic blood pressure), and brain DA [reduced decreases in distribution volumes (DVs) of [11C]raclopride, although normal reductions in striatal nondisplaceable binding potential (BPND)] responses to MP. In ventral striatum (key brain reward region), MP-induced reductions in DVs and BPND (reflecting DA increases) were inversely correlated with scores of negative emotionality, which were significantly higher for marijuana abusers than controls. In marijuana abusers, DA responses in ventral striatum were also inversely correlated with addiction severity and craving. The attenuated responses to MP, including reduced decreases in striatal DVs, are consistent with decreased brain reactivity to the DA stimulation in marijuana abusers that might contribute to their negative emotionality (increased stress reactivity and irritability) and addictive behaviors. PMID:25024177

Evaluating effects of methylphenidate on brain activity in cocaine addiction: a machine-learning approach

NASA Astrophysics Data System (ADS)

Rish, Irina; Bashivan, Pouya; Cecchi, Guillermo A.; Goldstein, Rita Z.

2016-03-01

The objective of this study is to investigate effects of methylphenidate on brain activity in individuals with cocaine use disorder (CUD) using functional MRI (fMRI). Methylphenidate hydrochloride (MPH) is an indirect dopamine agonist commonly used for treating attention deficit/hyperactivity disorders; it was also shown to have some positive effects on CUD subjects, such as improved stop signal reaction times associated with better control/inhibition,1 as well as normalized task-related brain activity2 and resting-state functional connectivity in specific areas.3 While prior fMRI studies of MPH in CUDs have focused on mass-univariate statistical hypothesis testing, this paper evaluates multivariate, whole-brain effects of MPH as captured by the generalization (prediction) accuracy of different classification techniques applied to features extracted from resting-state functional networks (e.g., node degrees). Our multivariate predictive results based on resting-state data from3 suggest that MPH tends to normalize network properties such as voxel degrees in CUD subjects, thus providing additional evidence for potential benefits of MPH in treating cocaine addiction.

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.

Microbiota Dysbiosis Controls the Neuroinflammatory Response after Stroke.

PubMed

Singh, Vikramjeet; Roth, Stefan; Llovera, Gemma; Sadler, Rebecca; Garzetti, Debora; Stecher, Bärbel; Dichgans, Martin; Liesz, Arthur

2016-07-13

Acute brain ischemia induces a local neuroinflammatory reaction and alters peripheral immune homeostasis at the same time. Recent evidence has suggested a key role of the gut microbiota in autoimmune diseases by modulating immune homeostasis. Therefore, we investigated the mechanistic link among acute brain ischemia, microbiota alterations, and the immune response after brain injury. Using two distinct models of acute middle cerebral artery occlusion, we show by next-generation sequencing that large stroke lesions cause gut microbiota dysbiosis, which in turn affects stroke outcome via immune-mediated mechanisms. Reduced species diversity and bacterial overgrowth of bacteroidetes were identified as hallmarks of poststroke dysbiosis, which was associated with intestinal barrier dysfunction and reduced intestinal motility as determined by in vivo intestinal bolus tracking. Recolonizing germ-free mice with dysbiotic poststroke microbiota exacerbates lesion volume and functional deficits after experimental stroke compared with the recolonization with a normal control microbiota. In addition, recolonization of mice with a dysbiotic microbiome induces a proinflammatory T-cell polarization in the intestinal immune compartment and in the ischemic brain. Using in vivo cell-tracking studies, we demonstrate the migration of intestinal lymphocytes to the ischemic brain. Therapeutic transplantation of fecal microbiota normalizes brain lesion-induced dysbiosis and improves stroke outcome. These results support a novel mechanism in which the gut microbiome is a target of stroke-induced systemic alterations and an effector with substantial impact on stroke outcome. We have identified a bidirectional communication along the brain-gut microbiota-immune axis and show that the gut microbiota is a central regulator of immune homeostasis. Acute brain lesions induced dysbiosis of the microbiome and, in turn, changes in the gut microbiota affected neuroinflammatory and functional outcome after brain injury. The microbiota impact on immunity and stroke outcome was transmissible by microbiota transplantation. Our findings support an emerging concept in which the gut microbiota is a key regulator in priming the neuroinflammatory response to brain injury. These findings highlight the key role of microbiota as a potential therapeutic target to protect brain function after injury. Copyright © 2016 the authors 0270-6474/16/367428-13$15.00/0.

Hyperintense White Matter Lesions in 50 High-Altitude Pilots with Neurologic Decompression Sickness

DTIC Science & Technology

2012-12-01

Environ Med 2004 ; 75 : 969 – 72 . 4. Bartzokis G, Tishler TA, Shin IS, Lu PH, Cummings JL . Brain ferritin iron as a risk factor for...Coyle T, Lancaster J, et al. Can structural MRI indices of cerebral integrity track cognitive trends in executive control function during normal...Digital brain atlases . Trends Neurosci 1995 ; 18 : 210 – 1 . 28. Miura K, Soyama Y, Morikawa Y, Nishijo M, Nakanishi Y, et al

Measurement of cerebral oxidative glucose consumption in patients with type 1 diabetes and hypoglycemia unawareness using 13C nuclear magnetic resonance spectroscopy

PubMed Central

Henry, Pierre-Gilles; Criego, Amy B.; Kumar, Anjali; Seaquist, Elizabeth R.

2009-01-01

The aim of the present study was to use 13C NMR to measure the cerebral oxidative metabolic rate of glucose (CMRglc(ox)) in patients with diabetes and to compare these measurements with those collected from matched controls. We elected to study a group with type 1 diabetes and hypoglycemia unawareness, since we had previously found such patients to have higher brain glucose concentrations than normal volunteers under steady state conditions. We sought to determine if this difference in steady-state brain concentrations could be explained by a difference in CMRglc(ox). Time courses of 13C label incorporation in brain amino acids were measured in occipital cortex during infusion of [1-13C]glucose. These time courses were fitted using a one-compartment metabolic model to determine CMRglc(ox). Our results show that the TCA cycle rate (VTCA, which is twice CMRglc(ox)) in subjects with type 1 diabetes was not significantly different from normal controls (0.84 ± 0.03 vs 0.79 ± 0.03 μmol/gm/min, n=5 in each group, mean ± SEM). We conclude that the changes in steady-state brain glucose concentrations that we observed in patients with type 1 diabetes in a previous study (1) cannot be explained by changes in oxidative glucose consumption PMID:19766263

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.

Pathological changes in Alzheimer"s brain evaluated with fluorescence emission analysis (FEA)

NASA Astrophysics Data System (ADS)

Christov, Alexander; Ottman, Todd; Grammas, Paula

2004-07-01

Development of AD is associated with cerebrovascular deposition of amyloid beta (Aβ) as well as a progressive increase in vasular collagen content. Both AΒ and collagen are naturally fluorescent compounds when exposed to UV light. We analyzed autofluorescence emitted from brain tissue samples and isolated brain resistance vessels harvested postmortem from patients with Alzheimer's disease (AD) and age-matched controls. Fluorescence emission, excited at 355 nm with an Nd:YAG laser, was measured using a fiber-optic based fluorescence spectroscopic system for tissue analysis. Significantly higher values of fluorescence emission intensity (P<0.001) in the spectral region from 465 to 490 nm were detected in brain resistance vessel samples from AD patients compared to the normal individuals. Results from western blot analysis showed elevated levels of type I and type III collagen, and reduced levels of type IV collagen in resistance vessels from AD patients, compared to control samples. In addition, using direct scanning of the cortical suface for fluoresxcence emission by the laser-induced fluorescence spectroscopy system we detected a significantly (P<0.05) higher level of apoptosis in AD brain tissue compared to age-matched controls. Fluorescence emission analysis (FEA) appears to be a sensitive technique for detecting structural changes in AD brain tissue.

Gamma-aminobutyric acid (GABA)-B receptor 1 in cerebellar cortex of essential tremor.

PubMed

Luo, C; Rajput, A H; Robinson, C A; Rajput, A

2012-06-01

Some reports suggest cerebellar dysfunction as the basis of essential tremor (ET). Several drugs with the action of gamma-aminobutyric acid (GABA) are known to improve ET. Autopsy studies were performed on brains from nine former patients followed at the Movement Disorders Clinic Saskatchewan, Canada, and compared with five normal control brains. We aimed to measure the concentration of GABA B receptor 1 (GBR1) in the brains of patients who had had ET and to compare them to the GABA concentration in brains of controls. Western blot was used to determine the expression of GBR1 in cerebellar cortex tissue. We found that compared to the controls, the ET brains had three different patterns of GBR1 protein concentration--two with high, four comparable, and three with marginally low levels. There was no association between the age of onset, severity or duration of tremor, the response to alcohol or other drugs and GBR1 level. Thus, we conclude that our study does not support that GBR1 is involved in ET. Further studies are needed to verify these results. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

Estimating the brain pathological age of Alzheimer’s disease patients from MR image data based on the separability distance criterion

NASA Astrophysics Data System (ADS)

Li, Yongming; Li, Fan; Wang, Pin; Zhu, Xueru; Liu, Shujun; Qiu, Mingguo; Zhang, Jingna; Zeng, Xiaoping

2016-10-01

Traditional age estimation methods are based on the same idea that uses the real age as the training label. However, these methods ignore that there is a deviation between the real age and the brain age due to accelerated brain aging. This paper considers this deviation and searches for it by maximizing the separability distance value rather than by minimizing the difference between the estimated brain age and the real age. Firstly, set the search range of the deviation as the deviation candidates according to prior knowledge. Secondly, use the support vector regression (SVR) as the age estimation model to minimize the difference between the estimated age and the real age plus deviation rather than the real age itself. Thirdly, design the fitness function based on the separability distance criterion. Fourthly, conduct age estimation on the validation dataset using the trained age estimation model, put the estimated age into the fitness function, and obtain the fitness value of the deviation candidate. Fifthly, repeat the iteration until all the deviation candidates are involved and get the optimal deviation with maximum fitness values. The real age plus the optimal deviation is taken as the brain pathological age. The experimental results showed that the separability was apparently improved. For normal control-Alzheimer’s disease (NC-AD), normal control-mild cognition impairment (NC-MCI), and MCI-AD, the average improvements were 0.178 (35.11%), 0.033 (14.47%), and 0.017 (39.53%), respectively. For NC-MCI-AD, the average improvement was 0.2287 (64.22%). The estimated brain pathological age could be not only more helpful to the classification of AD but also more precisely reflect accelerated brain aging. In conclusion, this paper offers a new method for brain age estimation that can distinguish different states of AD and can better reflect the extent of accelerated aging.

Revealing pathologies in the liquid crystalline structures of the brain by polarimetric studies (Presentation Recording)

NASA Astrophysics Data System (ADS)

Bakhshetyan, Karen; Melkonyan, Gurgen G.; Galstian, Tigran V.; Saghatelyan, Armen

2015-10-01

Natural or "self" alignment of molecular complexes in living tissue represents many similarities with liquid crystals (LC), which are anisotropic liquids. The orientational characteristics of those complexes may be related to many important functional parameters and their study may reveal important pathologies. The know-how, accumulated thanks to the study of LC materials, may thus be used to this end. One of the traditionally used methods, to characterize those materials, is the polarized light imaging (PLI) that allows for label-free analysis of anisotropic structures in the brain tissue and can be used, for example, for the analysis of myelinated fiber bundles. In the current work, we first attempted to apply the PLI on the mouse histological brain sections to create a map of anisotropic structures using cross-polarizer transmission light. Then we implemented the PLI for comparative study of histological sections of human postmortem brain samples under normal and pathological conditions, such as Parkinson's disease (PD). Imaging the coronal, sagittal and horizontal sections of mouse brain allowed us to create a false color-coded fiber orientation map under polarized light. In human brain datasets for both control and PD groups we measured the pixel intensities in myelin-rich subregions of internal capsule and normalized these to non-myelinated background signal from putamen and caudate nucleus. Quantification of intensities revealed a statistically significant reduction of fiber intensity of PD compared to control subjects (2.801 +/- 0.303 and 3.724 +/- 0.07 respectively; *p < 0.05). Our study confirms the validity of PLI method for visualizing myelinated axonal fibers. This relatively simple technique can become a promising tool for study of neurodegenerative diseases where labeling-free imaging is an important benefit.

TRACTOGRAPHY DENSITY AND NETWORK MEASURES IN ALZHEIMER'S DISEASE.

PubMed

Prasad, Gautam; Nir, Talia M; Toga, Arthur W; Thompson, Paul M

2013-04-01

Brain connectivity declines in Alzheimer's disease (AD), both functionally and structurally. Connectivity maps and networks derived from diffusion-based tractography offer new ways to track disease progression and to understand how AD affects the brain. Here we set out to identify (1) which fiber network measures show greatest differences between AD patients and controls, and (2) how these effects depend on the density of fibers extracted by the tractography algorithm. We computed brain networks from diffusion-weighted images (DWI) of the brain, in 110 subjects (28 normal elderly, 56 with early and 11 with late mild cognitive impairment, and 15 with AD). We derived connectivity matrices and network topology measures, for each subject, from whole-brain tractography and cortical parcellations. We used an ODF lookup table to speed up fiber extraction, and to exploit the full information in the orientation distribution function (ODF). This made it feasible to compute high density connectivity maps. We used accelerated tractography to compute a large number of fibers to understand what effect fiber density has on network measures and in distinguishing different disease groups in our data. We focused on global efficiency, transitivity, path length, mean degree, density, modularity, small world, and assortativity measures computed from weighted and binary undirected connectivity matrices. Of all these measures, the mean nodal degree best distinguished diagnostic groups. High-density fiber matrices were most helpful for picking up the more subtle clinical differences, e.g. between mild cognitively impaired (MCI) and normals, or for distinguishing subtypes of MCI (early versus late). Care is needed in clinical analyses of brain connectivity, as the density of extracted fibers may affect how well a network measure can pick up differences between patients and controls.

Intrinsic Brain Activity of Cognitively Normal Older Persons Resembles More That of Patients Both with and at Risk for Alzheimer's Disease Than That of Healthy Younger Persons

PubMed Central

Pasquini, Lorenzo; Tonch, Annika; Plant, Claudia; Zherdin, Andrew; Ortner, Marion; Kurz, Alexander; Förstl, Hans; Zimmer, Claus; Grimmer, Timo; Wohlschäger, Afra; Riedl, Valentin

2014-01-01

Abstract In Alzheimer's disease (AD), recent findings suggest that amyloid-β (Aβ)-pathology might start 20–30 years before first cognitive symptoms arise. To account for age as most relevant risk factor for sporadic AD, it has been hypothesized that lifespan intrinsic (i.e., ongoing) activity of hetero-modal brain areas with highest levels of functional connectivity triggers Aβ-pathology. This model induces the simple question whether in older persons without any cognitive symptoms intrinsic activity of hetero-modal areas is more similar to that of symptomatic patients with AD or to that of younger healthy persons. We hypothesize that due to advanced age and therefore potential impact of pre-clinical AD, intrinsic activity of older persons resembles more that of patients than that of younger controls. We tested this hypothesis in younger (ca. 25 years) and older healthy persons (ca. 70 years) and patients with mild cognitive impairment and AD-dementia (ca. 70 years) by the use of resting-state functional magnetic resonance imaging, distinct measures of intrinsic brain activity, and different hierarchical clustering approaches. Independently of applied methods and involved areas, healthy older persons' intrinsic brain activity was consistently more alike that of patients than that of younger controls. Our result provides evidence for larger similarity in intrinsic brain activity between healthy older persons and patients with or at-risk for AD than between older and younger ones, suggesting a significant proportion of pre-clinical AD cases in the group of cognitively normal older people. The observed link of aging and AD with intrinsic brain activity supports the view that lifespan intrinsic activity may contribute critically to the pathogenesis of AD. PMID:24689864

Proximal and distal esophageal sensitivity is decreased in patients with Barrett’s esophagus

PubMed Central

Krarup, Anne L; Olesen, Søren S; Funch-Jensen, Peter; Gregersen, Hans; Drewes, Asbjørn M

2011-01-01

AIM: To investigate sensations to multimodal pain stimulation in the metaplastic and normal parts of the esophagus in patients with Barrett’s esophagus (BE). METHODS: Fifteen patients with BE and 15 age-matched healthy volunteers were subjected to mechanical, thermal and electrical pain stimuli of the esophagus. Both the metaplastic part and the normal part (4 and 14 cm, respectively, above the esophago-gastric junction) were examined. At sensory thresholds the stimulation intensity, referred pain areas, and evoked brain potentials were recorded. RESULTS: Patients were hyposensitive to heat stimulation both in the metaplastic part [median stimulation time to reach the pain detection threshold: 15 (12-34) s vs 14 (6-23) s in controls; F = 4.5, P = 0.04] and the normal part of the esophagus [median 17 (6-32) s vs 13 (8-20) s in controls; F = 6.2, P = 0.02]. Furthermore, patients were hyposensitive in the metaplastic part of the esophagus to mechanical distension [median volume at moderate pain: 50 (20-50) mL vs 33 (13-50) mL in controls; F = 5.7, P = 0.02]. No indication of central nervous system abnormalities was present, as responses were comparable between groups to electrical pain stimuli in the metaplastic part [median current evoking moderate pain: 13 (6-26) mA vs 12 (9-24) mA in controls; F = 0.1, P = 0.7], and in the normal part of the esophagus [median current evoking moderate pain: 9 (6-16) mA, vs 11 (5-11) mA in controls; F = 3.4, P = 0.07]. Furthermore, no differences were seen for the referred pain areas (P-values all > 0.3) or latencies and amplitudes for the evoked brain potentials (P-values all > 0.1). CONCLUSION: Patients with BE are hyposensitive both in the metaplastic and normal part of esophagus likely as a result of abnormalities affecting peripheral nerve pathways. PMID:21274382

Neurocognitive findings in Prader-Willi syndrome and early-onset morbid obesity.

PubMed

Miller, Jennifer; Kranzler, John; Liu, Yijun; Schmalfuss, Ilona; Theriaque, Douglas W; Shuster, Jonathan J; Hatfield, Ann; Mueller, O Thomas; Goldstone, Anthony P; Sahoo, Trilochan; Beaudet, Arthur L; Driscoll, Daniel J

2006-08-01

To examine whether early-onset morbid obesity is associated with cognitive impairment, neuropathologic changes, and behavioral problems. This case-control study compared head MRI scans and cognitive, achievement, and behavioral evaluations of subjects with Prader-Willi syndrome (PWS), early-onset morbid obesity (EMO), and normal-weight sibling control subjects from both groups. Head MRI was done on 17 PWS, 18 EMO, and 21 siblings, and cognitive, achievement, and behavioral evaluations were done on 19 PWS, 17 EMO, and 24 siblings. The mean General Intellectual Ability score of the EMO group was 77.4 +/- 17.8; PWS, 63.3 +/- 14.2; and control subjects, 106.4 +/- 13.0. Achievement scores for the three groups were EMO, 78.7 +/- 18.8; PWS, 71.2 +/- 17.0; and control subjects, 104.8 +/- 17.0. Significant negative behaviors and poor adaptive skills were found in the EMO group. White matter lesions were noted on brain MRI in 6 subjects with PWS and 5 with EMO. None of the normal-weight control subjects had these findings. Individuals with EMO have significantly lower cognitive function and more behavioral problems than control subjects with no history of childhood obesity. Both EMO and PWS subjects have white matter lesions on brain MRI that have not previously been described.

Cerebral utilization of glucose, ketone bodies and oxygen in starving infant rats and the effect of intrauterine growth retardation.

PubMed

Dahlquist, G

1976-10-01

Cerebral arteriovenous differences of acetoacetate, D-beta-hydroxybutyrate, glucose, lactate and oxygen and brain DNA content was measured at 20 days of age in intrauterine growth retarded (IUGR) rats and normal littermates after 48 and 72 h of starvation. Cerebral blood flow (CBF) was measured with labeled microspheres in other comparable groups of IUGR and control rats. CBF was similar in IUGR and normal littermates (0.57+/-0.09 and 0.58+/-0.10 ml/min respectively). After 48 h of starvation, arterial glucose was significantly lower in IUGR than control animals but the arterial concentrations of ketone bodies were similar. After 48 h of starvation, cerebral arteriovenous difference of beta-hydroxybutyrate was significantly higher in control than IUGR rats also when expressed per mg brain DNA as was the fractional uptake of D-beta-hydroxybutyrate. After 72 h of starvation, arterial concentrations of ketone bodies were significantly lower in IUGR rats than controls but the fractional uptake of D-beta-hydroxybutyrate was increased compared to IUGR rats starved for 48 h. The average percentage of calculated total substrate uptake (mumol/min) accounted for by ketone bodies increased in control animals from 31.1% after 48 h of starvation to 41.0% after 72 h of starvation. In IUGR rats these percentage values were 26.5 and 25.7 respectively. After 72 h of starvation the fraction of total cerebral uptake of substrates accounted for by ketone bodies was significantly higher in control that IUGR rats. As total cerebral uptake of substrates was similar between IUGR and control animals it is concluded that IUGR rats are more dependent on glucose as a substrate for the brain during starvation.

Structural MRI markers of brain aging early after ischemic stroke.

PubMed

Werden, Emilio; Cumming, Toby; Li, Qi; Bird, Laura; Veldsman, Michele; Pardoe, Heath R; Jackson, Graeme; Donnan, Geoffrey A; Brodtmann, Amy

2017-07-11

To examine associations between ischemic stroke, vascular risk factors, and MRI markers of brain aging. Eighty-one patients (mean age 67.5 ± 13.1 years, 31 left-sided, 61 men) with confirmed first-ever (n = 66) or recurrent (n = 15) ischemic stroke underwent 3T MRI scanning within 6 weeks of symptom onset (mean 26 ± 9 days). Age-matched controls (n = 40) completed identical testing. Multivariate regression analyses examined associations between group membership and MRI markers of brain aging (cortical thickness, total brain volume, white matter hyperintensity [WMH] volume, hippocampal volume), normalized against intracranial volume, and the effects of vascular risk factors on these relationships. First-ever stroke was associated with smaller hippocampal volume ( p = 0.025) and greater WMH volume ( p = 0.004) relative to controls. Recurrent stroke was in turn associated with smaller hippocampal volume relative to both first-ever stroke ( p = 0.017) and controls ( p = 0.001). These associations remained significant after adjustment for age, sex, education, and, in stroke patients, infarct volume. Total brain volume was not significantly smaller in first-ever stroke patients than in controls ( p = 0.056), but the association became significant after further adjustment for atrial fibrillation ( p = 0.036). Cortical thickness and brain volumes did not differ as a function of stroke type, infarct volume, or etiology. Brain structure is likely to be compromised before ischemic stroke by vascular risk factors. Smaller hippocampal and total brain volumes and increased WMH load represent proxies for underlying vascular brain injury. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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.

CSF Flow in the Brain in the Context of Normal Pressure Hydrocephalus.

PubMed

Bradley, W G

2015-05-01

CSF normally flows back and forth through the aqueduct during the cardiac cycle. During systole, the brain and intracranial vasculature expand and compress the lateral and third ventricles, forcing CSF craniocaudad. During diastole, they contract and flow through the aqueduct reverses. Hyperdynamic CSF flow through the aqueduct is seen when there is ventricular enlargement without cerebral atrophy. Therefore, patients presenting with clinical normal pressure hydrocephalus who have hyperdynamic CSF flow have been found to respond better to ventriculoperitoneal shunting than those with normal or decreased CSF flow. Patients with normal pressure hydrocephalus have also been found to have larger intracranial volumes than sex-matched controls, suggesting that they may have had benign external hydrocephalus as infants. While their arachnoidal granulations clearly have decreased CSF resorptive capacity, it now appears that this is fixed and that the arachnoidal granulations are not merely immature. Such patients appear to develop a parallel pathway for CSF to exit the ventricles through the extracellular space of the brain and the venous side of the glymphatic system. This pathway remains functional until late adulthood when the patient develops deep white matter ischemia, which is characterized histologically by myelin pallor (ie, loss of lipid). The attraction between the bare myelin protein and the CSF increases resistance to the extracellular outflow of CSF, causing it to back up, resulting in hydrocephalus. Thus idiopathic normal pressure hydrocephalus appears to be a "2 hit" disease: benign external hydrocephalus in infancy followed by deep white matter ischemia in late adulthood. © 2015 by American Journal of Neuroradiology.

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.

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

Short-Term Effects of Binaural Beats on EEG Power, Functional Connectivity, Cognition, Gait and Anxiety in Parkinson's Disease.

PubMed

Gálvez, Gerardo; Recuero, Manuel; Canuet, Leonides; Del-Pozo, Francisco

2018-06-01

We applied rhythmic binaural sound to Parkinson's Disease (PD) patients to investigate its influence on several symptoms of this disease and on Electrophysiology (Electrocardiography and Electroencephalography (EEG)). We conducted a double-blind, randomized controlled study in which rhythmic binaural beats and control were administered over two randomized and counterbalanced sessions (within-subjects repeated-measures design). Patients ([Formula: see text], age [Formula: see text], stage I-III Hoehn & Yahr scale) participated in two sessions of sound stimulation for 10[Formula: see text]min separated by a minimum of 7 days. Data were collected immediately before and after both stimulations with the following results: (1) a decrease in theta activity, (2) a general decrease in Functional Connectivity (FC), and (3) an improvement in working memory performance. However, no significant changes were identified in the gait performance, heart rate or anxiety level of the patients. With regard to the control stimulation, we did not identify significant changes in the variables analyzed. The use of binaural-rhythm stimulation for PD, as designed in this study, seems to be an effective, portable, inexpensive and noninvasive method to modulate brain activity. This influence on brain activity did not induce changes in anxiety or gait parameters; however, it resulted in a normalization of EEG power (altered in PD), normalization of brain FC (also altered in PD) and working memory improvement (a normalizing effect). In summary, we consider that sound, particularly binaural-rhythmic sound, may be a co-assistant tool in the treatment of PD, however more research is needed to consider the use of this type of stimulation as an effective therapy.

The prebiotics 3′Sialyllactose and 6′Sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations: evidence for effects on the gut-brain axis

PubMed Central

Tarr, Andrew J.; Galley, Jeffrey D.; Fisher, Sydney; Chichlowski, Maciej; Berg, Brian M.; Bailey, Michael T.

2015-01-01

There are extensive bidirectional interactions between the gut microbiota and the central nervous system (CNS), and studies demonstrate that stressor exposure significantly alters gut microbiota community structure. We tested whether oligosaccharides naturally found in high levels in human milk, which have been reported to impact brain development and enhance the growth of beneficial commensal microbes, would prevent stressor-induced alterations in gut microbial community composition and attenuate stressor-induced anxiety-like behavior. Mice were fed standard laboratory diet, or laboratory diet containing the human milk oligosaccharides 3′Sialyllactose (3′SL) or 6′Sialyllactose (6′SL) for two weeks prior to being exposed to either a social disruption stressor or a non-stressed control condition. Stressor exposure significantly changed the structure of the colonic mucosa-associated microbiota in control mice, as indicated by changes in beta diversity. The stressor resulted in anxiety-like behavior in both the light/dark preference and open field tests in control mice. This effect was associated with a reduction in immature neurons in the dentate gyrus as indicated by doublecortin (DCX) immunostaining. These effects were not evident in mice fed milk oligosaccharides; stressor exposure did not significantly change microbial community structure in mice fed 3′SL or 6′SL. In addition, 3′SL and 6′SL helped maintain normal behavior on tests of anxiety-like behavior and normal numbers of DCX+ immature neurons. These studies indicate that milk oligosaccharides support normal microbial communities and behavioral responses during stressor exposure, potentially through effects on the gut microbiota-brain axis. PMID:26144888

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.

Comparison between Alzheimer's disease and subcortical vascular dementia: attentional cortex study in functional magnetic resonance imaging.

PubMed

Li, C; Zheng, J; Wang, J; Gui, L

2011-01-01

Blood oxygen level dependent functional magnetic resonance imaging (fMRI) and the Stroop test were used to assess attentional cortex activation in patients with Alzheimer's disease, subcortical vascular dementia, and normal control subjects. Patients with Alzheimer's disease and subcortical vascular dementia demonstrated similar locations of cortical activation, including the bilateral middle and inferior frontal gyri, anterior cingulate and inferior parietal lobule in response to Stroop colour word stimuli. This activation was distinctly decreased in patients with dementia compared with normal control subjects. Different regions of the brain were activated in patients with Alzheimer's disease and subcortical vascular dementia compared with normal controls. fMRI is a useful tool for the study of dementia in humans and has some potential diagnostic value. Further studies with larger numbers of participants are required.

Inhibitory Control in Mind and Brain: An Interactive Race Model of Countermanding Saccades

ERIC Educational Resources Information Center

Boucher, Leanne; Palmeri, Thomas J.; Logan, Gordon D.; Schall, Jeffrey D.

2007-01-01

The stop-signal task has been used to study normal cognitive control and clinical dysfunction. Its utility is derived from a race model that accounts for performance and provides an estimate of the time it takes to stop a movement. This model posits a race between go and stop processes with stochastically independent finish times. However,…

To rise and to fall: functional connectivity in cognitively normal and cognitively impaired patients with Parkinson's disease.

PubMed

Gorges, Martin; Müller, Hans-Peter; Lulé, Dorothée; Pinkhardt, Elmar H; Ludolph, Albert C; Kassubek, Jan

2015-04-01

Cognitive decline is a burdensome extra-motor symptom associated with Parkinson's disease (PD). This study aimed at investigating intrinsic functional connectivity (iFC) of the brain in cognitively unimpaired (PD-CU) and impaired PD patients (PD-CI) compared with age-matched healthy controls. "Resting-state" functional magnetic resonance imaging was acquired in 53 subjects, that is, 14 PD-CU patients, 17 PD-CI patients, and 22 control subjects. Cognition and cognitive status for patient classification were assessed using detailed neuropsychological testing. In PD-CU patients versus controls, we demonstrated significantly increased iFC (hyperconnectivity) presenting as network expansions in cortical, limbic, and basal ganglia-thalamic areas. Significantly, decreased iFC in PD-CI patients compared with control subjects was observed, predominantly between major nodes of the default mode network. In conclusion, the increased iFC might be the initial manifestation of altered brain function preceding cognitive deficits. Hyperconnectivity could be an adaptive (compensatory) mechanism by recruiting additional resources to maintain normal cognitive performance. As PD-related pathology progresses, functional disruptions within the default mode networks seem to be considerably associated with cognitive decline. Copyright © 2015 Elsevier Inc. All rights reserved.

Increased frequency of brain pathology in inmates of a high-security forensic institution: a qualitative CT and MRI scan study.

PubMed

Witzel, Joachim G; Bogerts, Bernhard; Schiltz, Kolja

2016-09-01

This study aimed to assess whether brain pathology might be more abundant in forensic inpatients in a high-security setting than in non-criminal individuals. By using a previously used reliable approach, we explored the frequency and extent of brain pathology in a large group of institutionalized offenders who had not previously been considered to be suffering from structural brain damage and compare it to healthy, non-offending subjects. MRI and CT brain scans from 148 male inpatients of a high-security mental health institution (offense type: 51 sex, 80 violent, 9 arson, and 8 nonviolent) that were obtained due to headache, vertigo, or psychological complaints during imprisonment were assessed and compared to 52 non-criminal healthy controls. Brain scans were assessed qualitatively with respect to evidence of structural brain damage. Each case received a semiquantitative rating of "normal" (=0), "questionably abnormal" (=1), or "definitely abnormal" (=2) for the lateral ventricles, frontal/parietal cortex, and medial temporal structures bilaterally as well as third ventricle. Forensic inpatients displayed signs of brain damage to a significantly higher degree than healthy controls (p < 0.001). Even after adjustment for age, in the patients, being younger than the controls (p < 0.05), every offender type group displayed a higher proportion of subjects with brain regions categorized as definitely abnormal than the non-criminal controls. Within the forensic inpatients, offense type groups did not significantly differ in brain pathology. The astonishingly high prevalence of brain pathology in institutionalized inmates of a high-security mental health institution who previously had not been considered to be suffering from an organic brain syndrome raises questions on whether such neuroradiological assessment might be considered as a routine procedure in newly admitted patients. Furthermore, it highlights that organic changes, detectable under clinical routine conditions, may play a role in the development of legally relevant behavioral disturbances which might be underestimated.

Neuropathological findings processed by artificial neural networks (ANNs) can perfectly distinguish Alzheimer's patients from controls in the Nun Study

PubMed Central

Grossi, Enzo; Buscema, Massimo P; Snowdon, David; Antuono, Piero

2007-01-01

Background Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT) can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old. The aim of this study is to discover the hidden and non-linear associations among AD pathognomonic brain lesions and the clinical diagnosis of AD in participants in the Nun Study through Artificial Neural Networks (ANNs) analysis Methods The analyses were based on 26 clinically- and pathologically-confirmed AD cases and 36 controls who had normal cognitive function. The inputs used for the analyses were just NFT and neuritic plaques counts in neocortex and hippocampus, for which, despite substantial differences in mean lesions counts between AD cases and controls, there was a substantial overlap in the range of lesion counts. Results By taking into account the above four neuropathological features, the overall predictive capability of ANNs in sorting out AD cases from normal controls reached 100%. The corresponding accuracy obtained with Linear Discriminant Analysis was 92.30%. These results were consistently obtained in ten independent experiments. The same experiments were carried out with ANNs on a subgroup of 13 non severe AD patients and on the same 36 controls. The results obtained in terms of prediction accuracy with ANNs were exactly the same. Input relevance analysis confirmed the relative dominance of NFT in neocortex in discriminating between AD patients and controls and indicated the lesser importance played by NP in the hippocampus. Conclusion The results of this study suggest that: a) cortical NFT represent the key variable in AD neuropathology; b) the neuropathologic profile of AD subjects is complex, however, c) ANNs can analyze neuropathologic features and differentiate AD cases from controls. PMID:17584929

Neuropathological findings processed by artificial neural networks (ANNs) can perfectly distinguish Alzheimer's patients from controls in the Nun Study.

PubMed

Grossi, Enzo; Buscema, Massimo P; Snowdon, David; Antuono, Piero

2007-06-21

Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT) can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old. The aim of this study is to discover the hidden and non-linear associations among AD pathognomonic brain lesions and the clinical diagnosis of AD in participants in the Nun Study through Artificial Neural Networks (ANNs) analysis The analyses were based on 26 clinically- and pathologically-confirmed AD cases and 36 controls who had normal cognitive function. The inputs used for the analyses were just NFT and neuritic plaques counts in neocortex and hippocampus, for which, despite substantial differences in mean lesions counts between AD cases and controls, there was a substantial overlap in the range of lesion counts. By taking into account the above four neuropathological features, the overall predictive capability of ANNs in sorting out AD cases from normal controls reached 100%. The corresponding accuracy obtained with Linear Discriminant Analysis was 92.30%. These results were consistently obtained in ten independent experiments. The same experiments were carried out with ANNs on a subgroup of 13 non severe AD patients and on the same 36 controls. The results obtained in terms of prediction accuracy with ANNs were exactly the same. Input relevance analysis confirmed the relative dominance of NFT in neocortex in discriminating between AD patients and controls and indicated the lesser importance played by NP in the hippocampus. The results of this study suggest that: a) cortical NFT represent the key variable in AD neuropathology; b) the neuropathologic profile of AD subjects is complex, however, c) ANNs can analyze neuropathologic features and differentiate AD cases from controls.

Brain enlargement is associated with regression in preschool-age boys with autism spectrum disorders

PubMed Central

Nordahl, Christine Wu; Lange, Nicholas; Li, Deana D.; Barnett, Lou Ann; Lee, Aaron; Buonocore, Michael H.; Simon, Tony J.; Rogers, Sally; Ozonoff, Sally; Amaral, David G.

2011-01-01

Autism is a heterogeneous disorder with multiple behavioral and biological phenotypes. Accelerated brain growth during early childhood is a well-established biological feature of autism. Onset pattern, i.e., early onset or regressive, is an intensely studied behavioral phenotype of autism. There is currently little known, however, about whether, or how, onset status maps onto the abnormal brain growth. We examined the relationship between total brain volume and onset status in a large sample of 2- to 4-y-old boys and girls with autism spectrum disorder (ASD) [n = 53, no regression (nREG); n = 61, regression (REG)] and a comparison group of age-matched typically developing controls (n = 66). We also examined retrospective head circumference measurements from birth through 18 mo of age. We found that abnormal brain enlargement was most commonly found in boys with regressive autism. Brain size in boys without regression did not differ from controls. Retrospective head circumference measurements indicate that head circumference in boys with regressive autism is normal at birth but diverges from the other groups around 4–6 mo of age. There were no differences in brain size in girls with autism (n = 22, ASD; n = 24, controls). These results suggest that there may be distinct neural phenotypes associated with different onsets of autism. For boys with regressive autism, divergence in brain size occurs well before loss of skills is commonly reported. Thus, rapid head growth may be a risk factor for regressive autism. PMID:22123952

Design and Rationale of the Cognitive Intervention to Improve Memory in Heart Failure Patients Study.

PubMed

Pressler, Susan J; Giordani, Bruno; Titler, Marita; Gradus-Pizlo, Irmina; Smith, Dean; Dorsey, Susan G; Gao, Sujuan; Jung, Miyeon

Memory loss is an independent predictor of mortality among heart failure patients. Twenty-three percent to 50% of heart failure patients have comorbid memory loss, but few interventions are available to treat the memory loss. The aims of this 3-arm randomized controlled trial were to (1) evaluate efficacy of computerized cognitive training intervention using BrainHQ to improve primary outcomes of memory and serum brain-derived neurotrophic factor levels and secondary outcomes of working memory, instrumental activities of daily living, and health-related quality of life among heart failure patients; (2) evaluate incremental cost-effectiveness of BrainHQ; and (3) examine depressive symptoms and genomic moderators of BrainHQ effect. A sample of 264 heart failure patients within 4 equal-sized blocks (normal/low baseline cognitive function and gender) will be randomly assigned to (1) BrainHQ, (2) active control computer-based crossword puzzles, and (3) usual care control groups. BrainHQ is an 8-week, 40-hour program individualized to each patient's performance. Data collection will be completed at baseline and at 10 weeks and 4 and 8 months. Descriptive statistics, mixed model analyses, and cost-utility analysis using intent-to-treat approach will be computed. This research will provide new knowledge about the efficacy of BrainHQ to improve memory and increase serum brain-derived neurotrophic factor levels in heart failure. If efficacious, the intervention will provide a new therapeutic approach that is easy to disseminate to treat a serious comorbid condition of heart failure.

The Whole-Brain “Global” Signal from Resting State fMRI as a Potential Biomarker of Quantitative State Changes in Glucose Metabolism

PubMed Central

Thompson, Garth J.; Grimmer, Timo; Drzezga, Alexander; Herman, Peter

2016-01-01

Abstract The evolution of functional magnetic resonance imaging to resting state (R-fMRI) allows measurement of changes in brain networks attributed to state changes, such as in neuropsychiatric diseases versus healthy controls. Since these networks are observed by comparing normalized R-fMRI signals, it is difficult to determine the metabolic basis of such group differences. To investigate the metabolic basis of R-fMRI network differences within a normal range, eyes open versus eyes closed in healthy human subjects was used. R-fMRI was recorded simultaneously with fluoro-deoxyglucose positron emission tomography (FDG-PET). Higher baseline FDG was observed in the eyes open state. Variance-based metrics calculated from R-fMRI did not match the baseline shift in FDG. Functional connectivity density (FCD)-based metrics showed a shift similar to the baseline shift of FDG, however, this was lost if R-fMRI “nuisance signals” were regressed before FCD calculation. Average correlation with the mean R-fMRI signal across the whole brain, generally regarded as a “nuisance signal,” also showed a shift similar to the baseline of FDG. Thus, despite lacking a baseline itself, changes in whole-brain correlation may reflect changes in baseline brain metabolism. Conversely, variance-based metrics may remain similar between states due to inherent region-to-region differences overwhelming the differences between normal physiological states. As most previous studies have excluded the spatial means of R-fMRI metrics from their analysis, this work presents the first evidence of a potential R-fMRI biomarker for baseline shifts in quantifiable metabolism between brain states. PMID:27029438

The Whole-Brain "Global" Signal from Resting State fMRI as a Potential Biomarker of Quantitative State Changes in Glucose Metabolism.

PubMed

Thompson, Garth J; Riedl, Valentin; Grimmer, Timo; Drzezga, Alexander; Herman, Peter; Hyder, Fahmeed

2016-07-01

The evolution of functional magnetic resonance imaging to resting state (R-fMRI) allows measurement of changes in brain networks attributed to state changes, such as in neuropsychiatric diseases versus healthy controls. Since these networks are observed by comparing normalized R-fMRI signals, it is difficult to determine the metabolic basis of such group differences. To investigate the metabolic basis of R-fMRI network differences within a normal range, eyes open versus eyes closed in healthy human subjects was used. R-fMRI was recorded simultaneously with fluoro-deoxyglucose positron emission tomography (FDG-PET). Higher baseline FDG was observed in the eyes open state. Variance-based metrics calculated from R-fMRI did not match the baseline shift in FDG. Functional connectivity density (FCD)-based metrics showed a shift similar to the baseline shift of FDG, however, this was lost if R-fMRI "nuisance signals" were regressed before FCD calculation. Average correlation with the mean R-fMRI signal across the whole brain, generally regarded as a "nuisance signal," also showed a shift similar to the baseline of FDG. Thus, despite lacking a baseline itself, changes in whole-brain correlation may reflect changes in baseline brain metabolism. Conversely, variance-based metrics may remain similar between states due to inherent region-to-region differences overwhelming the differences between normal physiological states. As most previous studies have excluded the spatial means of R-fMRI metrics from their analysis, this work presents the first evidence of a potential R-fMRI biomarker for baseline shifts in quantifiable metabolism between brain states.

Functional Connectivity Associated with Acoustic Stability During Vowel Production: Implications for Vocal-Motor Control

PubMed Central

2015-01-01

Abstract Vowels provide the acoustic foundation of communication through speech and song, but little is known about how the brain orchestrates their production. Positron emission tomography was used to study regional cerebral blood flow (rCBF) during sustained production of the vowel /a/. Acoustic and blood flow data from 13, normal, right-handed, native speakers of American English were analyzed to identify CBF patterns that predicted the stability of the first and second formants of this vowel. Formants are bands of resonance frequencies that provide vowel identity and contribute to voice quality. The results indicated that formant stability was directly associated with blood flow increases and decreases in both left- and right-sided brain regions. Secondary brain regions (those associated with the regions predicting formant stability) were more likely to have an indirect negative relationship with first formant variability, but an indirect positive relationship with second formant variability. These results are not definitive maps of vowel production, but they do suggest that the level of motor control necessary to produce stable vowels is reflected in the complexity of an underlying neural system. These results also extend a systems approach to functional image analysis, previously applied to normal and ataxic speech rate that is solely based on identifying patterns of brain activity associated with specific performance measures. Understanding the complex relationships between multiple brain regions and the acoustic characteristics of vocal stability may provide insight into the pathophysiology of the dysarthrias, vocal disorders, and other speech changes in neurological and psychiatric disorders. PMID:25295385

Differences in Regional Brain Responses to Food Ingestion After Roux-en-Y Gastric Bypass and the Role of Gut Peptides: A Neuroimaging Study.

PubMed

Hunt, Katharine F; Dunn, Joel T; le Roux, Carel W; Reed, Laurence J; Marsden, Paul K; Patel, Ameet G; Amiel, Stephanie A

2016-10-01

Improved appetite control, possibly mediated by exaggerated gut peptide responses to eating, may contribute to weight loss after Roux-en-Y gastric bypass (RYGB). This study compared brain responses to food ingestion between post-RYGB (RYGB), normal weight (NW), and obese (Ob) unoperated subjects and explored the role of gut peptide responses in RYGB. Neuroimaging with [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography was performed in 12 NW, 21 Ob, and 9 RYGB (18 ± 13 months postsurgery) subjects after an overnight fast, once FED (400 kcal mixed meal), and once FASTED, in random order. RYGB subjects repeated the studies with somatostatin infusion and basal insulin replacement. Fullness, sickness, and postscan ad libitum meal consumption were measured. Regional brain FDG uptake was compared using statistical parametric mapping. RYGB subjects had higher overall fullness and food-induced sickness and lower ad libitum consumption. Brain responses to eating differed in the hypothalamus and pituitary (exaggerated activation in RYGB), left medial orbital cortex (OC) (activation in RYGB, deactivation in NW), right dorsolateral frontal cortex (deactivation in RYGB and NW, absent in Ob), and regions mapping to the default mode network (exaggerated deactivation in RYGB). Somatostatin in RYGB reduced postprandial gut peptide responses, sickness, and medial OC activation. RYGB induces weight loss by augmenting normal brain responses to eating in energy balance regions, restoring lost inhibitory control, and altering hedonic responses. Altered postprandial gut peptide responses primarily mediate changes in food-induced sickness and OC responses, likely to associate with food avoidance. © 2016 by the American Diabetes Association.

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

Cholinesterase activity in Japanese quail dusted with carbaryl

USGS Publications Warehouse

Hill, E.F.

1979-01-01

Japanese quail (Coturnix coturnix japonica) were dusted with 5% carbaryl to determine if this topical treatment would alter plasma and brain cholinesterase activities. Within 6 hours after dusting, plasma cholinesterase activity was depressed compared with controls, the depression averaging 20% for females and 27% for males. By 24 hours the cholinesterase activity of females had returned to normal, but the cholinesterase activity of males remained depressed. Brain cholinesterase activity was not affected by the treatment, and there were no overt toxic signs.

Effects of BDNF Val66Met polymorphism on brain metabolism in Alzheimer's disease.

PubMed

Xu, Cunlu; Wang, Zhenhua; Fan, Ming; Liu, Bing; Song, Ming; Zhen, Xiantong; Jiang, Tianzi

2010-08-23

Earlier studies showed that the Val66Met polymorphisms of the brain-derived neurotrophic factor differentially affect gray matter volume and brain region activities. This study used resting positron emission tomography to investigate the relationship between the polymorphisms of Val66Met and the regional cerebral metabolic rate in the brain. We analyzed the positron emission tomography images of 215 patients from the Alzheimer's Disease Neuroimaging Initiative and found significant differences in the parahippocampal gyrus, superior temporal gyrus, prefrontal cortex, and inferior parietal lobule when comparing Met carriers with noncarriers among both the normal controls and those with mild cognitive impairment. For those with Alzheimer's disease, we also found additional differences in the bilateral insula between the carriers and noncarriers.

Structural and Functional Consequences of Increased Tubulin Glycosylation in Diabetes Mellitus

NASA Astrophysics Data System (ADS)

Williams, Stuart K.; Howarth, Nancy L.; Devenny, James J.; Bitensky, Mark W.

1982-11-01

The extent of in vitro nonenzymatic glycosylation of purified rat brain tubulin was dependent on time and glucose concentration. Tubulin glycosylation profoundly inhibited GTP-dependent tubulin polymerization. Electron microscopy and NaDodSO4/polyacrylamide gel electrophoresis showed that glycosylated tubulin forms high molecular weight amorphous aggregates that are not disrupted by detergents or reducing agents. The amount of covalently bound NaB3H4-reducible sugars in tubulin recovered from brain of streptozotocin-induced diabetic rats was dramatically increased as compared with tubulin recovered from normal rat brain. Moreover, tubulin recovered from diabetic rat brain exhibited less GTP-induced polymerization than tubulin from nondiabetic controls. The possible implications of these data for diabetic neuropathy are discussed.

Molecular networks and the evolution of human cognitive specializations.

PubMed

Fontenot, Miles; Konopka, Genevieve

2014-12-01

Inroads into elucidating the origins of human cognitive specializations have taken many forms, including genetic, genomic, anatomical, and behavioral assays that typically compare humans to non-human primates. While the integration of all of these approaches is essential for ultimately understanding human cognition, here, we review the usefulness of coexpression network analysis for specifically addressing this question. An increasing number of studies have incorporated coexpression networks into brain expression studies comparing species, disease versus control tissue, brain regions, or developmental time periods. A clearer picture has emerged of the key genes driving brain evolution, as well as the developmental and regional contributions of gene expression patterns important for normal brain development and those misregulated in cognitive diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

Glutamate-glutamine and GABA in brain of normal aged and patients with cognitive impairment.

PubMed

Huang, Dandan; Liu, Dan; Yin, Jianzhong; Qian, Tianyi; Shrestha, Susan; Ni, Hongyan

2017-07-01

To explore the changes of glutamate-glutamine (Glx) and gamma-aminobutyric acid (GABA) in the brain in normal old age and cognitive impairment using magnetic resonance spectroscopy (MRS). Seventeen normal young controls (NYC), 15 normal elderly controls (NEC), 21 patients with mild cognitive impairment (MCI) and 17 with Alzheimer disease (AD) patients were included in this study. Glx and GABA+ levels in the anterior cingulate cortex (ACC) and right hippocampus (rHP) were measured by using a MEGA-PRESS sequence. Glx/Cr and GABA+/Cr ratios were compared between NYC and NEC and between the three elderly groups using analysis of covariance (ANCOVA); the tissue fractions of voxels were used as covariates. The relationships between metabolite ratios and cognitive performance were analysed using Spearman correlation coefficients. For NEC and NYC groups, Glx/Cr and GABA+/Cr ratios were lower in NEC in ACC and rHP. For the three elderly groups, Glx/Cr ratio was lower in AD in ACC compared to NEC and MCI; Glx/Cr ratio was lower in AD in rHP compared to NEC. There was no significant decrease for GABA+/Cr ratio. Glx and GABA levels may decrease simultaneously in normal aged, and Glx level decreased predominantly in AD, and it is helpful in the early diagnosis of AD. • Glx and GABA levels may decrease simultaneously in normal aged. • Glx level may decrease predominantly in Alzheimer disease. • The balance in excitatory-inhibitory systems may be broken in AD. • Decreased Glx level may be helpful in early diagnosis of AD.

Glymphatic clearance controls state-dependent changes in brain lactate concentration.

PubMed

Lundgaard, Iben; Lu, Minh Lon; Yang, Ezra; Peng, Weiguo; Mestre, Humberto; Hitomi, Emi; Deane, Rashid; Nedergaard, Maiken

2017-06-01

Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep-wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport.

Glymphatic clearance controls state-dependent changes in brain lactate concentration

PubMed Central

Lu, Minh Lon; Yang, Ezra; Peng, Weiguo; Mestre, Humberto; Hitomi, Emi; Deane, Rashid; Nedergaard, Maiken

2016-01-01

Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep–wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport. PMID:27481936

Type 1 Diabetes Modifies Brain Activation in Young Patients While Performing Visuospatial Working Memory Tasks

PubMed Central

González-Garrido, Andrés A.; Gudayol-Ferré, Esteban; Guàrdia-Olmos, Joan

2015-01-01

In recent years, increasing attention has been paid to the effects of Type 1 Diabetes (T1D) on cognitive functions. T1D onset usually occurs during childhood, so it is possible that the brain could be affected during neurodevelopment. We selected young patients of normal intelligence with T1D onset during neurodevelopment, no complications from diabetes, and adequate glycemic control. The purpose of this study was to compare the neural BOLD activation pattern in a group of patients with T1D versus healthy control subjects while performing a visuospatial working memory task. Sixteen patients and 16 matched healthy control subjects participated. There was no significant statistical difference in behavioral performance between the groups, but, in accordance with our hypothesis, results showed distinct brain activation patterns. Control subjects presented the expected activations related to the task, whereas the patients had greater activation in the prefrontal inferior cortex, basal ganglia, posterior cerebellum, and substantia nigra. These different patterns could be due to compensation mechanisms that allow them to maintain a behavioral performance similar to that of control subjects. PMID:26266268

Attention and Working Memory in Adolescents with Autism Spectrum Disorder: A Functional MRI Study.

PubMed

Rahko, Jukka S; Vuontela, Virve A; Carlson, Synnöve; Nikkinen, Juha; Hurtig, Tuula M; Kuusikko-Gauffin, Sanna; Mattila, Marja-Leena; Jussila, Katja K; Remes, Jukka J; Jansson-Verkasalo, Eira M; Aronen, Eeva T; Pauls, David L; Ebeling, Hanna E; Tervonen, Osmo; Moilanen, Irma K; Kiviniemi, Vesa J

2016-06-01

The present study examined attention and memory load-dependent differences in the brain activation and deactivation patterns between adolescents with autism spectrum disorders (ASDs) and typically developing (TD) controls using functional magnetic resonance imaging. Attentional (0-back) and working memory (WM; 2-back) processing and load differences (0 vs. 2-back) were analysed. WM-related areas activated and default mode network deactivated normally in ASDs as a function of task load. ASDs performed the attentional 0-back task similarly to TD controls but showed increased deactivation in cerebellum and right temporal cortical areas and weaker activation in other cerebellar areas. Increasing task load resulted in multiple responses in ASDs compared to TD and in inadequate modulation of brain activity in right insula, primary somatosensory, motor and auditory cortices. The changes during attentional task may reflect compensatory mechanisms enabling normal behavioral performance. The inadequate memory load-dependent modulation of activity suggests diminished compensatory potential in ASD.

Axonal abnormalities in vanishing white matter.

PubMed

Klok, Melanie D; Bugiani, Marianna; de Vries, Sharon I; Gerritsen, Wouter; Breur, Marjolein; van der Sluis, Sophie; Heine, Vivi M; Kole, Maarten H P; Baron, Wia; van der Knaap, Marjo S

2018-04-01

We aimed to study the occurrence and development of axonal pathology and the influence of astrocytes in vanishing white matter. Axons and myelin were analyzed using electron microscopy and immunohistochemistry on Eif2b4 and Eif2b5 single- and double-mutant mice and patient brain tissue. In addition, astrocyte-forebrain co-culture studies were performed. In the corpus callosum of Eif2b5- mutant mice, myelin sheath thickness, axonal diameter, and G-ratio developed normally up to 4 months. At 7 months, however, axons had become thinner, while in control mice axonal diameters had increased further. Myelin sheath thickness remained close to normal, resulting in an abnormally low G-ratio in Eif2b5- mutant mice. In more severely affected Eif2b4-Eif2b5 double-mutants, similar abnormalities were already present at 4 months, while in milder affected Eif2b4 mutants, few abnormalities were observed at 7 months. Additionally, from 2 months onward an increased percentage of thin, unmyelinated axons and increased axonal density were present in Eif2b5 -mutant mice. Co-cultures showed that Eif2b5 mutant astrocytes induced increased axonal density, also in control forebrain tissue, and that control astrocytes induced normal axonal density, also in mutant forebrain tissue. In vanishing white matter patient brains, axons and myelin sheaths were thinner than normal in moderately and severely affected white matter. In mutant mice and patients, signs of axonal transport defects and cytoskeletal abnormalities were minimal. In vanishing white matter, axons are initially normal and atrophy later. Astrocytes are central in this process. If therapy becomes available, axonal pathology may be prevented with early intervention.

Central exogenous nitric oxide decreases cardiac sympathetic drive and improves baroreflex control of heart rate in ovine heart failure.

PubMed

Ramchandra, Rohit; Hood, Sally G; May, Clive N

2014-08-01

Heart failure (HF) is associated with increased cardiac and renal sympathetic drive, which are both independent predictors of poor prognosis. A candidate mechanism for the centrally mediated sympathoexcitation in HF is reduced synthesis of the inhibitory neuromodulator nitric oxide (NO), resulting from downregulation of neuronal NO synthase (nNOS). Therefore, we investigated the effects of increasing the levels of NO in the brain, or selectively in the paraventricular nucleus of the hypothalamus (PVN), on cardiac sympathetic nerve activity (CSNA) and baroreflex control of CSNA and heart rate in ovine pacing-induced HF. The resting level of CSNA was significantly higher in the HF than in the normal group, but the resting level of RSNA was unchanged. Intracerebroventricular infusion of the NO donor sodium nitroprusside (SNP; 500 μg · ml(-1)· h(-1)) in conscious normal sheep and sheep in HF inhibited CSNA and restored baroreflex control of heart rate, but there was no change in RSNA. Microinjection of SNP into the PVN did not cause a similar cardiac sympathoinhibition in either group, although the number of nNOS-positive cells was decreased in the PVN of sheep in HF. Reduction of endogenous NO with intracerebroventricular infusion of N(ω)-nitro-l-arginine methyl ester decreased CSNA in normal but not in HF sheep and caused no change in RSNA in either group. These findings indicate that endogenous NO in the brain provides tonic excitatory drive to increase resting CSNA in the normal state, but not in HF. In contrast, exogenously administered NO inhibited CSNA in both the normal and HF groups via an action on sites other than the PVN. Copyright © 2014 the American Physiological Society.

Disrupted Sleep in Narcolepsy: Exploring the Integrity of Galanin Neurons in the Ventrolateral Preoptic Area

PubMed Central

Gavrilov, Yury V.; Ellison, Brian A.; Yamamoto, Mihoko; Reddy, Hasini; Haybaeck, Johannes; Mignot, Emmanuel; Baumann, Christian R.; Scammell, Thomas E.; Valko, Philipp O.

2016-01-01

Study Objectives: To examine the integrity of sleep-promoting neurons of the ventrolateral preoptic nucleus (VLPO) in postmortem brains of narcolepsy type 1 patients. Methods: Postmortem examination of five narcolepsy and eight control brains. Results: VLPO galanin neuron count did not differ between narcolepsy patients (11,151 ± 3,656) and controls (13,526 ± 9,544). Conclusions: A normal number of galanin-immunoreactive VLPO neurons in narcolepsy type 1 brains at autopsy suggests that VLPO cell loss is an unlikely explanation for the sleep fragmentation that often accompanies the disease. Citation: Gavrilov YV, Ellison BA, Yamamoto M, Reddy H, Haybaeck J, Mignot E, Baumann CR, Scammell TE, Valko PO. Disrupted sleep in narcolepsy: exploring the integrity of galanin neurons in the ventrolateral preoptic area. SLEEP 2016;39(5):1059–1062. PMID:26951397

Freesurfer-initialized large deformation diffeomorphic metric mapping with application to Parkinson's disease

NASA Astrophysics Data System (ADS)

Chen, Jingyun; Palmer, Samantha J.; Khan, Ali R.; Mckeown, Martin J.; Beg, Mirza Faial

2009-02-01

We apply a recently developed automated brain segmentation method, FS+LDDMM, to brain MRI scans from Parkinson's Disease (PD) subjects, and normal age-matched controls and compare the results to manual segmentation done by trained neuroscientists. The data set consisted of 14 PD subjects and 12 age-matched control subjects without neurologic disease and comparison was done on six subcortical brain structures (left and right caudate, putamen and thalamus). Comparison between automatic and manual segmentation was based on Dice Similarity Coefficient (Overlap Percentage), L1 Error, Symmetrized Hausdorff Distance and Symmetrized Mean Surface Distance. Results suggest that FS+LDDMM is well-suited for subcortical structure segmentation and further shape analysis in Parkinson's Disease. The asymmetry of the Dice Similarity Coefficient over shape change is also discussed based on the observation and measurement of FS+LDDMM segmentation results.

Neural Control of the Cardiovascular System in Space

NASA Technical Reports Server (NTRS)

Levine, Benjamin D.; Pawelczyk, James A.; Zuckerman, Julie; Zhang, Rong; Fu, Qi; Iwasaki, Kenichi; Ray, Chet; Blomqvist, C. Gunnar; Lane, Lynda D.; Giller, Cole A.

2003-01-01

During the acute transition from lying supine to standing upright, a large volume of blood suddenly moves from the chest into the legs. To prevent fainting, the blood pressure control system senses this change immediately, and rapidly adjusts flow (by increasing heart rate) and resistance to flow (by constricting the blood vessels) to restore blood pressure and maintain brain blood flow. If this system is inadequate, the brain has a backup plan. Blood vessels in the brain can adjust their diameter to keep blood flow constant. If blood pressure drops, the brain blood vessels dilate; if blood pressure increases, the brain blood vessels constrict. This process, which is called autoregulation, allows the brain to maintain a steady stream of oxygen, even when blood pressure changes. We examined what changes in the blood pressure control system or cerebral autoregulation contribute to the blood pressure control problems seen after spaceflight. We asked: (1) does the adaptation to spaceflight cause an adaptation in the blood pressure control system that impairs the ability of the system to constrict blood vessels on return to Earth?; (2) if such a defect exists, could we pinpoint the neural pathways involved?; and (3) does cerebral autoregulation become abnormal during spaceflight, impairing the body s ability to maintain constant brain blood flow when standing upright on Earth? We stressed the blood pressure control system using lower body negative pressure, upright tilt, handgrip exercise, and cold stimulation of the hand. Standard cardiovascular parameters were measured along with sympathetic nerve activity (the nerve activity causing blood vessels to constrict) and brain blood flow. We confirmed that the primary cardiovascular effect of spaceflight was a postflight reduction in upright stroke volume (the amount of blood the heart pumps per beat). Heart rate increased appropriately for the reduction in stroke volume, thereby showing that changes in heart rate regulation alone cannot be responsible for orthostatic hypotension after spaceflight. All of the astronauts in our study had an increase in sympathetic nerve activity during upright tilting on Earth postflight. This increase was well calibrated for the reduction in stroke volume induced by the upright posture. The results obtained from stimulating the sympathetic nervous system using handgrip exercise or cold stress were also entirely normal during and after spaceflight. No astronaut had reduced cerebral blood flow during upright tilt, and cerebral autoregulation was normal or even enhanced inflight. These experiments show that the cardiovascular adaptation to spaceflight does not lead to a defect in the regulation of blood vessel constriction via sympathetic nerve activity. In addition, cerebral autoregulation is well-maintained. It is possible that despite the increased sympathetic nerve activity, blood vessels did not respond with a greater degree of constriction than occurred preflight, possibly uncovering a limit of vasoconstrictor reserve.

Intrinsic brain networks normalize with treatment in pediatric complex regional pain syndrome

PubMed Central

Becerra, Lino; Sava, Simona; Simons, Laura E.; Drosos, Athena M.; Sethna, Navil; Berde, Charles; Lebel, Alyssa A.; Borsook, David

2014-01-01

Pediatric complex regional pain syndrome (P-CRPS) offers a unique model of chronic neuropathic pain as it either resolves spontaneously or through therapeutic interventions in most patients. Here we evaluated brain changes in well-characterized children and adolescents with P-CRPS by measuring resting state networks before and following a brief (median = 3 weeks) but intensive physical and psychological treatment program, and compared them to matched healthy controls. Differences in intrinsic brain networks were observed in P-CRPS compared to controls before treatment (disease state) with the most prominent differences in the fronto-parietal, salience, default mode, central executive, and sensorimotor networks. Following treatment, behavioral measures demonstrated a reduction of symptoms and improvement of physical state (pain levels and motor functioning). Correlation of network connectivities with spontaneous pain measures pre- and post-treatment indicated concomitant reductions in connectivity in salience, central executive, default mode and sensorimotor networks (treatment effects). These results suggest a rapid alteration in global brain networks with treatment and provide a venue to assess brain changes in CRPS pre- and post-treatment, and to evaluate therapeutic effects. PMID:25379449

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.

Focal epidural cooling reduces the infarction volume of permanent middle cerebral artery occlusion in swine.

PubMed

Zhang, Lihua; Cheng, Huilin; Shi, Jixin; Chen, Jun

2007-02-01

The protective effect against ischemic stroke by systemic hypothermia is limited by the cooling rate and it has severe complications. This study was designed to evaluate the effect of SBH induced by epidural cooling on infarction volume in a swine model of PMCAO. Permanent middle cerebral artery occlusion was performed in 12 domestic swine assigned to groups A and B. In group A, the cranial and rectal temperatures were maintained at normal range (37 degrees C-39 degrees C) for 6 hours after PMCAO. In group B, cranial temperature was reduced to moderate (deep brain, <30 degrees C) and deep (brain surface, <20 degrees C) temperature and maintained at that level for 5 hours after 1 hour after PMCAO, by the epidural cooling method. All animals were euthanized 6 hours after MCAO; their brains were sectioned and stained with 2,3,5-triphenyltetrazolium chloride and their infarct volumes were calculated. The moderate and deep brain temperature (at deep brain and brain surface) can be induced by rapid epidural cooling, whereas the rectal temperature was maintained within normal range. The infarction volume after PMCAO was significantly reduced by epidural cooling compared with controls (13.73% +/- 1.82% vs 5.62% +/- 2.57%, P < .05). The present study has demonstrated, with histologic confirmation, that epidural cooling may be a useful strategy for reducing infarct volume after the onset of ischemia.

Between destiny and disease: genetics and molecular pathways of human central nervous system aging.

PubMed

Glorioso, Christin; Sibille, Etienne

2011-02-01

Aging of the human brain is associated with "normal" functional, structural, and molecular changes that underlie alterations in cognition, memory, mood and motor function, amongst other processes. Normal aging also imposes a robust constraint on the onset of many neurological diseases, ranging from late onset neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's diseases (PD), to early onset psychiatric disorders, such as bipolar disorder (BPD) and schizophrenia (SCZ). The molecular mechanisms and genetic underpinnings of age-related changes in the brain are understudied, and, while they share some overlap with peripheral mechanisms of aging, many are unique to the largely non-mitotic brain. Hence, understanding mechanisms of brain aging and identifying associated modulators may have profound consequences for the prevention and treatment of age-related impairments and diseases. Here we review current knowledge on age-related functional and structural changes, their molecular and genetic underpinnings, and discuss how these pathways may contribute to the vulnerability to develop age-related neurological diseases. We highlight recent findings from human post-mortem brain microarray studies, which we hypothesize, point to a potential genetically controlled transcriptional program underlying molecular changes and age-gating of neurological diseases. Finally, we discuss the implications of this model for understanding basic mechanisms of brain aging and for the future investigation of therapeutic approaches. Copyright © 2010 Elsevier Ltd. All rights reserved.

Comparison of Automated Brain Volume Measures obtained with NeuroQuant and FreeSurfer.

PubMed

Ochs, Alfred L; Ross, David E; Zannoni, Megan D; Abildskov, Tracy J; Bigler, Erin D

2015-01-01

To examine intermethod reliabilities and differences between FreeSurfer and the FDA-cleared congener, NeuroQuant, both fully automated methods for structural brain MRI measurements. MRI scans from 20 normal control subjects, 20 Alzheimer's disease patients, and 20 mild traumatically brain-injured patients were analyzed with NeuroQuant and with FreeSurfer. Intermethod reliability was evaluated. Pairwise correlation coefficients, intraclass correlation coefficients, and effect size differences were computed. NeuroQuant versus FreeSurfer measures showed excellent to good intermethod reliability for the 21 regions evaluated (r: .63 to .99/ICC: .62 to .99/ES: -.33 to 2.08) except for the pallidum (r/ICC/ES = .31/.29/-2.2) and cerebellar white matter (r/ICC/ES = .31/.31/.08). Volumes reported by NeuroQuant were generally larger than those reported by FreeSurfer with the whole brain parenchyma volume reported by NeuroQuant 6.50% larger than the volume reported by FreeSurfer. There was no systematic difference in results between the 3 subgroups. NeuroQuant and FreeSurfer showed good to excellent intermethod reliability in volumetric measurements for all brain regions examined with the only exceptions being the pallidum and cerebellar white matter. This finding was robust for normal individuals, patients with Alzheimer's disease, and patients with mild traumatic brain injury. Copyright © 2015 by the American Society of Neuroimaging.

Brain, body, and cognition: Neural, physiological and self-report correlates of phobic and normative fear

PubMed Central

Schaefer, Hillary S.; Larson, Christine L.; Davidson, Richard J.; Coan, James A.

2014-01-01

The phobic fear response appears to resemble an intense form of normal threat responding that can be induced in a nonthreatening situation. However, normative and phobic fear are rarely contrasted directly, thus the degree to which these two types of fear elicit similar neural and bodily responses is not well understood. To examine biological correlates of normal and phobic fear, 21 snake phobic and 21 nonphobic controls saw videos of slithering snakes, attacking snakes and fish in an event-related fMRI design. Simultaneous eletrodermal, pupillary, and self-reported affective responses were collected. Nonphobic fear activated a network of threat-responsive brain regions and involved pupillary dilation, electrodermal response and self-reported affect selective to the attacking snakes. Phobic fear recruited a large array of brain regions including those active in normal fear plus additional structures and also engendered increased pupil dilation, electrodermal and self-reported responses that were greater to any snake versus fish. Importantly, phobics showed greater between- and within-subject concordance among neural, electrodermal, pupillary, and subjective report measures. These results suggest phobic responses recruit overlapping but more strongly activated and more extensive networks of brain activity as compared to normative fear, and are characterized by greater concordance among neural activation, peripheral physiology and self-report. It is yet unclear whether concordance is unique to psychopathology, or rather simply an indicator of the intense fear seen in the phobic response, but these results underscore the importance of synchrony between brain, body, and cognition during the phobic reaction. PMID:24561099

Reversing pathologically increased EEG power by acoustic coordinated reset neuromodulation

PubMed Central

Adamchic, Ilya; Toth, Timea; Hauptmann, Christian; Tass, Peter Alexander

2014-01-01

Acoustic Coordinated Reset (CR) neuromodulation is a patterned stimulation with tones adjusted to the patient's dominant tinnitus frequency, which aims at desynchronizing pathological neuronal synchronization. In a recent proof-of-concept study, CR therapy, delivered 4–6 h/day more than 12 weeks, induced a significant clinical improvement along with a significant long-lasting decrease of pathological oscillatory power in the low frequency as well as γ band and an increase of the α power in a network of tinnitus-related brain areas. As yet, it remains unclear whether CR shifts the brain activity toward physiological levels or whether it induces clinically beneficial, but nonetheless abnormal electroencephalographic (EEG) patterns, for example excessively decreased δ and/or γ. Here, we compared the patients' spontaneous EEG data at baseline as well as after 12 weeks of CR therapy with the spontaneous EEG of healthy controls by means of Brain Electrical Source Analysis source montage and standardized low-resolution brain electromagnetic tomography techniques. The relationship between changes in EEG power and clinical scores was investigated using a partial least squares approach. In this way, we show that acoustic CR neuromodulation leads to a normalization of the oscillatory power in the tinnitus-related network of brain areas, most prominently in temporal regions. A positive association was found between the changes in tinnitus severity and the normalization of δ and γ power in the temporal, parietal, and cingulate cortical regions. Our findings demonstrate a widespread CR-induced normalization of EEG power, significantly associated with a reduction of tinnitus severity. PMID:23907785

Brain, body, and cognition: neural, physiological and self-report correlates of phobic and normative fear.

PubMed

Schaefer, Hillary S; Larson, Christine L; Davidson, Richard J; Coan, James A

2014-04-01

The phobic fear response appears to resemble an intense form of normal threat responding that can be induced in a nonthreatening situation. However, normative and phobic fear are rarely contrasted directly, thus the degree to which these two types of fear elicit similar neural and bodily responses is not well understood. To examine biological correlates of normal and phobic fear, 21 snake phobic and 21 nonphobic controls saw videos of slithering snakes, attacking snakes and fish in an event-related fMRI design. Simultaneous eletrodermal, pupillary, and self-reported affective responses were collected. Nonphobic fear activated a network of threat-responsive brain regions and involved pupillary dilation, electrodermal response and self-reported affect selective to the attacking snakes. Phobic fear recruited a large array of brain regions including those active in normal fear plus additional structures and also engendered increased pupil dilation, electrodermal and self-reported responses that were greater to any snake versus fish. Importantly, phobics showed greater between- and within-subject concordance among neural, electrodermal, pupillary, and subjective report measures. These results suggest phobic responses recruit overlapping but more strongly activated and more extensive networks of brain activity as compared to normative fear, and are characterized by greater concordance among neural activation, peripheral physiology and self-report. It is yet unclear whether concordance is unique to psychopathology, or rather simply an indicator of the intense fear seen in the phobic response, but these results underscore the importance of synchrony between brain, body, and cognition during the phobic reaction. Copyright © 2014. Published by Elsevier B.V.

Apelin targets gut contraction to control glucose metabolism via the brain.

PubMed

Fournel, Audren; Drougard, Anne; Duparc, Thibaut; Marlin, Alysson; Brierley, Stuart M; Castro, Joel; Le-Gonidec, Sophie; Masri, Bernard; Colom, André; Lucas, Alexandre; Rousset, Perrine; Cenac, Nicolas; Vergnolle, Nathalie; Valet, Philippe; Cani, Patrice D; Knauf, Claude

2017-02-01

The gut-brain axis is considered as a major regulatory checkpoint in the control of glucose homeostasis. The detection of nutrients and/or hormones in the duodenum informs the hypothalamus of the host's nutritional state. This process may occur via hypothalamic neurons modulating central release of nitric oxide (NO), which in turn controls glucose entry into tissues. The enteric nervous system (ENS) modulates intestinal contractions in response to various stimuli, but the importance of this interaction in the control of glucose homeostasis via the brain is unknown. We studied whether apelin, a bioactive peptide present in the gut, regulates ENS-evoked contractions, thereby identifying a new physiological partner in the control of glucose utilisation via the hypothalamus. We measured the effect of apelin on electrical and mechanical duodenal responses via telemetry probes and isotonic sensors in normal and obese/diabetic mice. Changes in hypothalamic NO release, in response to duodenal contraction modulated by apelin, were evaluated in real time with specific amperometric probes. Glucose utilisation in tissues was measured with orally administrated radiolabeled glucose. In normal and obese/diabetic mice, glucose utilisation is improved by the decrease of ENS/contraction activities in response to apelin, which generates an increase in hypothalamic NO release. As a consequence, glucose entry is significantly increased in the muscle. Here, we identify a novel mode of communication between the intestine and the hypothalamus that controls glucose utilisation. Moreover, our data identified oral apelin administration as a novel potential target to treat metabolic disorders. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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.

The androgen receptor governs the execution, but not programming, of male sexual and territorial behaviors

PubMed Central

Juntti, Scott A; Tollkuhn, Jessica; Wu, Melody V; Fraser, Eleanor J; Soderborg, Taylor; Tan, Stella; Honda, Shin-Ichiro; Harada, Nobuhiro; Shah, Nirao M

2010-01-01

SUMMARY Testosterone and estrogen are essential for male behaviors in vertebrates. How these two signaling pathways interact to control masculinization of the brain and behavior remains to be established. Circulating testosterone activates the androgen receptor (AR) and also serves as the source of estrogen in the brain. We have used a genetic strategy to delete AR specifically in the mouse nervous system. This approach permits us to determine the function of AR in sexually dimorphic behaviors in males while maintaining circulating testosterone levels within the normal range. We find that AR mutant males exhibit masculine sexual and territorial displays, but they have striking deficits in specific components of these behaviors. Taken together with the surprisingly limited expression of AR in the developing brain, our findings indicate that testosterone acts as a precursor to estrogen to masculinize the brain and behavior, and signals via AR to control the levels of male behavioral displays. PMID:20435002

EEG Brain Wave Activity at Rest and during Evoked Attention in Children with Attention-Deficit/Hyperactivity Disorder and Effects of Methylphenidate.

PubMed

Thomas, Bianca Lee; Viljoen, Margaretha

2016-01-01

The aim of this study was to assess baseline EEG brain wave activity in children with attention-deficit/hyperactivity disorder (ADHD) and to examine the effects of evoked attention and methylphenidate on this activity. Children with ADHD (n = 19) were tested while they were stimulant free and during a period in which they were on stimulant (methylphenidate) medication. Control subjects (n = 18) were tested once. EEG brain wave activity was tested both at baseline and during focussed attention. Attention was evoked and EEG brain wave activity was determined by means of the BioGraph Infiniti biofeedback apparatus. The main finding of this study was that control subjects and stimulant-free children with ADHD exhibited the expected reactivity in high alpha-wave activity (11-12 Hz) from baseline to focussed attention; however, methylphenidate appeared to abolish this reactivity. Methylphenidate attenuates the normal cortical response to a cognitive challenge. © 2016 S. Karger AG, Basel.

Zolpidem efficacy and safety in disorders of consciousness.

PubMed

Machado, Calixto; Estévez, Mario; Rodriguez-Rojas, Rafael

2018-01-01

Sutton and Clauss presented a detailed review about the effectiveness of zolpidem, discussing recoveries from brain damage due to strokes, trauma and hypoxia. A significant finding has been the unexpected and paradoxical increment of brain activity in vegetative state/unresponsive wakefulness syndrome (VS/UWS). On the contrary, zolpidem is considered one of the best sleep inducers in normal subjects. We have studied series of VS/UWS cases after zolpidem intake. We have demonstrated EEG activation, increment of BOLD signal in different brain regions, and an autonomic influence, mainly characterized by a vagolytic chronotropic effect without a significant increment of the vasomotor sympathetic tone. As this autonomic imbalance might induce cardio- circulatory complications, which we didn't find in any of our patients, we suggest developing future trials under control of physiological indices by bedside monitoring. However, considering that the paradoxical arousing zolpidem effect might be certainly related to brain function improvement, we agree with Sutton and Clauss that future multicentre and multinational clinical trials should be developed, but under control of physiological indices.

The effect of electromagnetic radiation on the rat brain: an experimental study.

PubMed

Eser, Olcay; Songur, Ahmet; Aktas, Cevat; Karavelioglu, Ergun; Caglar, Veli; Aylak, Firdevs; Ozguner, Fehmi; Kanter, Mehmet

2013-01-01

The aim of this study is to determine the structural changes of electromagnetic waves in the frontal cortex, brain stem and cerebellum. 24 Wistar Albino adult male rats were randomly divided into four groups: group I consisted of control rats, and groups II-IV comprised electromagnetically irradiated (EMR) with 900, 1800 and 2450 MHz. The heads of the rats were exposed to 900, 1800 and 2450 MHz microwaves irradiation for 1h per day for 2 months. While the histopathological changes in the frontal cortex and brain stem were normal in the control group, there were severe degenerative changes, shrunken cytoplasm and extensively dark pyknotic nuclei in the EMR groups. Biochemical analysis demonstrated that the Total Antioxidative Capacity level was significantly decreased in the EMR groups and also Total Oxidative Capacity and Oxidative Stress Index levels were significantly increased in the frontal cortex, brain stem and cerebellum. IL-1β level was significantly increased in the EMR groups in the brain stem. EMR causes to structural changes in the frontal cortex, brain stem and cerebellum and impair the oxidative stress and inflammatory cytokine system. This deterioration can cause to disease including loss of these areas function and cancer development.

Information flow dynamics in the brain

NASA Astrophysics Data System (ADS)

Rabinovich, Mikhail I.; Afraimovich, Valentin S.; Bick, Christian; Varona, Pablo

2012-03-01

Timing and dynamics of information in the brain is a hot field in modern neuroscience. The analysis of the temporal evolution of brain information is crucially important for the understanding of higher cognitive mechanisms in normal and pathological states. From the perspective of information dynamics, in this review we discuss working memory capacity, language dynamics, goal-dependent behavior programming and other functions of brain activity. In contrast with the classical description of information theory, which is mostly algebraic, brain flow information dynamics deals with problems such as the stability/instability of information flows, their quality, the timing of sequential processing, the top-down cognitive control of perceptual information, and information creation. In this framework, different types of information flow instabilities correspond to different cognitive disorders. On the other hand, the robustness of cognitive activity is related to the control of the information flow stability. We discuss these problems using both experimental and theoretical approaches, and we argue that brain activity is better understood considering information flows in the phase space of the corresponding dynamical model. In particular, we show how theory helps to understand intriguing experimental results in this matter, and how recent knowledge inspires new theoretical formalisms that can be tested with modern experimental techniques.

Current approaches to the treatment of metastatic brain tumours

PubMed Central

Owonikoko, Taofeek K.; Arbiser, Jack; Zelnak, Amelia; Shu, Hui-Kuo G.; Shim, Hyunsuk; Robin, Adam M.; Kalkanis, Steven N.; Whitsett, Timothy G.; Salhia, Bodour; Tran, Nhan L.; Ryken, Timothy; Moore, Michael K.; Egan, Kathleen M.; Olson, Jeffrey J.

2014-01-01

Metastatic tumours involving the brain overshadow primary brain neoplasms in frequency and are an important complication in the overall management of many cancers. Importantly, advances are being made in understanding the molecular biology underlying the initial development and eventual proliferation of brain metastases. Surgery and radiation remain the cornerstones of the therapy for symptomatic lesions; however, image-based guidance is improving surgical technique to maximize the preservation of normal tissue, while more sophisticated approaches to radiation therapy are being used to minimize the long-standing concerns over the toxicity of whole-brain radiation protocols used in the past. Furthermore, the burgeoning knowledge of tumour biology has facilitated the entry of systemically administered therapies into the clinic. Responses to these targeted interventions have ranged from substantial toxicity with no control of disease to periods of useful tumour control with no decrement in performance status of the treated individual. This experience enables recognition of the limits of targeted therapy, but has also informed methods to optimize this approach. This Review focuses on the clinically relevant molecular biology of brain metastases, and summarizes the current applications of these data to imaging, surgery, radiation therapy, cytotoxic chemotherapy and targeted therapy. PMID:24569448

Brain extraction from normal and pathological images: A joint PCA/Image-Reconstruction approach.

PubMed

Han, Xu; Kwitt, Roland; Aylward, Stephen; Bakas, Spyridon; Menze, Bjoern; Asturias, Alexander; Vespa, Paul; Van Horn, John; Niethammer, Marc

2018-08-01

Brain extraction from 3D medical images is a common pre-processing step. A variety of approaches exist, but they are frequently only designed to perform brain extraction from images without strong pathologies. Extracting the brain from images exhibiting strong pathologies, for example, the presence of a brain tumor or of a traumatic brain injury (TBI), is challenging. In such cases, tissue appearance may substantially deviate from normal tissue appearance and hence violates algorithmic assumptions for standard approaches to brain extraction; consequently, the brain may not be correctly extracted. This paper proposes a brain extraction approach which can explicitly account for pathologies by jointly modeling normal tissue appearance and pathologies. Specifically, our model uses a three-part image decomposition: (1) normal tissue appearance is captured by principal component analysis (PCA), (2) pathologies are captured via a total variation term, and (3) the skull and surrounding tissue is captured by a sparsity term. Due to its convexity, the resulting decomposition model allows for efficient optimization. Decomposition and image registration steps are alternated to allow statistical modeling of normal tissue appearance in a fixed atlas coordinate system. As a beneficial side effect, the decomposition model allows for the identification of potentially pathological areas and the reconstruction of a quasi-normal image in atlas space. We demonstrate the effectiveness of our approach on four datasets: the publicly available IBSR and LPBA40 datasets which show normal image appearance, the BRATS dataset containing images with brain tumors, and a dataset containing clinical TBI images. We compare the performance with other popular brain extraction models: ROBEX, BEaST, MASS, BET, BSE and a recently proposed deep learning approach. Our model performs better than these competing approaches on all four datasets. Specifically, our model achieves the best median (97.11) and mean (96.88) Dice scores over all datasets. The two best performing competitors, ROBEX and MASS, achieve scores of 96.23/95.62 and 96.67/94.25 respectively. Hence, our approach is an effective method for high quality brain extraction for a wide variety of images. Copyright © 2018 Elsevier Inc. All rights reserved.

Brain abnormalities in cognition, anxiety, and depression regulatory regions in adolescents with single ventricle heart disease.

PubMed

Pike, Nancy A; Roy, Bhaswati; Gupta, Ritika; Singh, Sadhana; Woo, Mary A; Halnon, Nancy J; Lewis, Alan B; Kumar, Rajesh

2018-06-01

Single ventricle heart disease (SVHD) adolescents show cognitive impairments and anxiety and depressive symptoms, indicating the possibility of brain injury in regions that control these functions. However, brain tissue integrity in cognition, anxiety, and depression regulatory sites in SVHD remains unclear. We examined brain tissue changes in SVHD compared to controls using T2-relaxometry procedures, which measure free water content and show tissue injury. Proton-density and T2-weighted images, using a 3.0-Tesla MRI, as well as anxiety (Beck anxiety inventory [BAI]), depressive symptoms (patient health questionnaire-9 [PHQ-9]), and cognition (wide range assessment of memory and learning 2 [WRAML2] and Montreal cognitive assessment [MoCA]) data were collected from 20 SVHD (age: 15.8 ± 1.1 years, male/female: 11/9) and 36 controls (age: 16.0 ± 1.1 years, male/female: 19/17). Whole-brain T2-relaxation maps were calculated, normalized to a common space, smoothed, and compared between groups and sexes (analysis of covariance; covariates: age, sex; p < 0.001). SVHD subjects showed significantly increased BAI and PHQ-9 and reduced MoCA and WRAML2 scores over controls. Several brain regions in SVHD showed increased T2-relaxation values (chronic injury), including the cingulate, and insula, hippocampus/para-hippocampal gyrus, thalamus, hypothalamus, amygdala, frontal white matter, corpus callosum, brainstem, and cerebellar areas. Decreased T2-relaxation values (acute injury) emerged in a few regions, including the prefrontal and cerebellar cortices in SVHD over controls. In addition, male SVHD showed more brain changes over female SVHD. Adolescents with SVHD showed significant brain injury with variable male-female differences in areas that control cognition, anxiety, and depression, which may contribute to functional deficits found in the condition. © 2018 Wiley Periodicals, Inc.

Long-term influence of normal variation in neonatal characteristics on human brain development

PubMed Central

Walhovd, Kristine B.; Fjell, Anders M.; Brown, Timothy T.; Kuperman, Joshua M.; Chung, Yoonho; Hagler, Donald J.; Roddey, J. Cooper; Erhart, Matthew; McCabe, Connor; Akshoomoff, Natacha; Amaral, David G.; Bloss, Cinnamon S.; Libiger, Ondrej; Schork, Nicholas J.; Darst, Burcu F.; Casey, B. J.; Chang, Linda; Ernst, Thomas M.; Frazier, Jean; Gruen, Jeffrey R.; Kaufmann, Walter E.; Murray, Sarah S.; van Zijl, Peter; Mostofsky, Stewart; Dale, Anders M.; Jernigan, Terry L.; McCabe, Connor; Chang, Linda; Akshoomoff, Natacha; Newman, Erik; Dale, Anders M.; Ernst, Thomas; Dale, Anders M.; Van Zijl, Peter; Kuperman, Joshua; Murray, Sarah; Bloss, Cinnamon; Schork, Nicholas J.; Appelbaum, Mark; Gamst, Anthony; Thompson, Wesley; Bartsch, Hauke; Jernigan, Terry L.; Dale, Anders M.; Akshoomoff, Natacha; Chang, Linda; Ernst, Thomas; Keating, Brian; Amaral, David; Sowell, Elizabeth; Kaufmann, Walter; Van Zijl, Peter; Mostofsky, Stewart; Casey, B.J.; Ruberry, Erika J.; Powers, Alisa; Rosen, Bruce; Kenet, Tal; Frazier, Jean; Kennedy, David; Gruen, Jeffrey

2012-01-01

It is now recognized that a number of cognitive, behavioral, and mental health outcomes across the lifespan can be traced to fetal development. Although the direct mediation is unknown, the substantial variance in fetal growth, most commonly indexed by birth weight, may affect lifespan brain development. We investigated effects of normal variance in birth weight on MRI-derived measures of brain development in 628 healthy children, adolescents, and young adults in the large-scale multicenter Pediatric Imaging, Neurocognition, and Genetics study. This heterogeneous sample was recruited through geographically dispersed sites in the United States. The influence of birth weight on cortical thickness, surface area, and striatal and total brain volumes was investigated, controlling for variance in age, sex, household income, and genetic ancestry factors. Birth weight was found to exert robust positive effects on regional cortical surface area in multiple regions as well as total brain and caudate volumes. These effects were continuous across birth weight ranges and ages and were not confined to subsets of the sample. The findings show that (i) aspects of later child and adolescent brain development are influenced at birth and (ii) relatively small differences in birth weight across groups and conditions typically compared in neuropsychiatric research (e.g., Attention Deficit Hyperactivity Disorder, schizophrenia, and personality disorders) may influence group differences observed in brain parameters of interest at a later stage in life. These findings should serve to increase our attention to early influences. PMID:23169628

Long-term influence of normal variation in neonatal characteristics on human brain development.

PubMed

Walhovd, Kristine B; Fjell, Anders M; Brown, Timothy T; Kuperman, Joshua M; Chung, Yoonho; Hagler, Donald J; Roddey, J Cooper; Erhart, Matthew; McCabe, Connor; Akshoomoff, Natacha; Amaral, David G; Bloss, Cinnamon S; Libiger, Ondrej; Schork, Nicholas J; Darst, Burcu F; Casey, B J; Chang, Linda; Ernst, Thomas M; Frazier, Jean; Gruen, Jeffrey R; Kaufmann, Walter E; Murray, Sarah S; van Zijl, Peter; Mostofsky, Stewart; Dale, Anders M

2012-12-04

It is now recognized that a number of cognitive, behavioral, and mental health outcomes across the lifespan can be traced to fetal development. Although the direct mediation is unknown, the substantial variance in fetal growth, most commonly indexed by birth weight, may affect lifespan brain development. We investigated effects of normal variance in birth weight on MRI-derived measures of brain development in 628 healthy children, adolescents, and young adults in the large-scale multicenter Pediatric Imaging, Neurocognition, and Genetics study. This heterogeneous sample was recruited through geographically dispersed sites in the United States. The influence of birth weight on cortical thickness, surface area, and striatal and total brain volumes was investigated, controlling for variance in age, sex, household income, and genetic ancestry factors. Birth weight was found to exert robust positive effects on regional cortical surface area in multiple regions as well as total brain and caudate volumes. These effects were continuous across birth weight ranges and ages and were not confined to subsets of the sample. The findings show that (i) aspects of later child and adolescent brain development are influenced at birth and (ii) relatively small differences in birth weight across groups and conditions typically compared in neuropsychiatric research (e.g., Attention Deficit Hyperactivity Disorder, schizophrenia, and personality disorders) may influence group differences observed in brain parameters of interest at a later stage in life. These findings should serve to increase our attention to early influences.

Goal selection versus process control in a brain-computer interface based on sensorimotor rhythms.

PubMed

Royer, Audrey S; He, Bin

2009-02-01

In a brain-computer interface (BCI) utilizing a process control strategy, the signal from the cortex is used to control the fine motor details normally handled by other parts of the brain. In a BCI utilizing a goal selection strategy, the signal from the cortex is used to determine the overall end goal of the user, and the BCI controls the fine motor details. A BCI based on goal selection may be an easier and more natural system than one based on process control. Although goal selection in theory may surpass process control, the two have never been directly compared, as we are reporting here. Eight young healthy human subjects participated in the present study, three trained and five naïve in BCI usage. Scalp-recorded electroencephalograms (EEG) were used to control a computer cursor during five different paradigms. The paradigms were similar in their underlying signal processing and used the same control signal. However, three were based on goal selection, and two on process control. For both the trained and naïve populations, goal selection had more hits per run, was faster, more accurate (for seven out of eight subjects) and had a higher information transfer rate than process control. Goal selection outperformed process control in every measure studied in the present investigation.

Metabolic brain networks in aging and preclinical Alzheimer's disease.

PubMed

Arnemann, Katelyn L; Stöber, Franziska; Narayan, Sharada; Rabinovici, Gil D; Jagust, William J

2018-01-01

Metabolic brain networks can provide insight into the network processes underlying progression from healthy aging to Alzheimer's disease. We explore the effect of two Alzheimer's disease risk factors, amyloid-β and ApoE ε4 genotype, on metabolic brain networks in cognitively normal older adults (N = 64, ages 69-89) compared to young adults (N = 17, ages 20-30) and patients with Alzheimer's disease (N = 22, ages 69-89). Subjects underwent MRI and PET imaging of metabolism (FDG) and amyloid-β (PIB). Normal older adults were divided into four subgroups based on amyloid-β and ApoE genotype. Metabolic brain networks were constructed cross-sectionally by computing pairwise correlations of metabolism across subjects within each group for 80 regions of interest. We found widespread elevated metabolic correlations and desegregation of metabolic brain networks in normal aging compared to youth and Alzheimer's disease, suggesting that normal aging leads to widespread loss of independent metabolic function across the brain. Amyloid-β and the combination of ApoE ε4 led to less extensive elevated metabolic correlations compared to other normal older adults, as well as a metabolic brain network more similar to youth and Alzheimer's disease. This could reflect early progression towards Alzheimer's disease in these individuals. Altered metabolic brain networks of older adults and those at the highest risk for progression to Alzheimer's disease open up novel lines of inquiry into the metabolic and network processes that underlie normal aging and Alzheimer's disease.

Transport mechanism of L-[14C]glutamate in cortical slices and synaptosomes of rabbits exposed to brain ischemia and reperfusion.

PubMed

Solyakov, L; Dobrota, D; Drany, O; Vachova, M; Machac, S; Mezesova, V; Bachurin, S; Lombardi, V

1995-01-01

Changes in the functioning of the glutamatergic system in rabbit brain were studied after partial brain ischemia and reperfusion. In vitro studies were conducted relating to the release of L-[14C]glutamate from cortical brain slices, L-[14C]glutamate uptake in synaptosomes, and 45Ca uptake in synaptosomes. It was found that basal release of L-[14C]glutamate from rabbit brain cortical slices after 30 min of partial ischemia and 1 d of reperfusion was essentially without change compared to the control values. After 3 d of reperfusion, there was an increase in basal release of L-[14C]glutamate from rabbit brain cortical slices. K+ stimulated release of L-[14C]glutamate in normal Krebs-Ringer medium was essentially the same in the control group and in the experimental group after 30 min of ischemia. The K+ stimulated release of L-[14C]glutamate independent of calcium was increased to 145% after 30 min of ischemia and 1 d of reperfusion. The decreased Km value at the glutamate transporter may have contributed to this difference. Kinetic parameters of the L-[14C]glutamate uptake (Km and Vmax) in synaptosomes from rabbit brain were significantly lower after 30 min of ischemia. The authors discovered that during the reperfusion period, Vmax was almost the same as in the control group. The activity of the Na+/Ca2+ exchanger in synaptosomes of rat brain was about 70% of the control values after 30 min of ischemia and 72 h of reperfusion. According to our results, increased L-[14C]glutamate release after 30 min of ischemia appears to be the result of higher intracellular calcium concentration and possibly also of a higher uptake of glutamate.

Abnormalities of hippocampal-cortical connectivity in temporal lobe epilepsy patients with hippocampal sclerosis

NASA Astrophysics Data System (ADS)

Li, Wenjing; He, Huiguang; Lu, Jingjing; Wang, Chunheng; Li, Meng; Lv, Bin; Jin, Zhengyu

2011-03-01

Hippocampal sclerosis (HS) is the most common damage seen in the patients with temporal lobe epilepsy (TLE). In the present study, the hippocampal-cortical connectivity was defined as the correlation between the hippocampal volume and cortical thickness at each vertex throughout the whole brain. We aimed to investigate the differences of ipsilateral hippocampal-cortical connectivity between the unilateral TLE-HS patients and the normal controls. In our study, the bilateral hippocampal volumes were first measured in each subject, and we found that the ipsilateral hippocampal volume significantly decreased in the left TLE-HS patients. Then, group analysis showed significant thinner average cortical thickness of the whole brain in the left TLE-HS patients compared with the normal controls. We found significantly increased ipsilateral hippocampal-cortical connectivity in the bilateral superior temporal gyrus, the right cingulate gyrus and the left parahippocampal gyrus of the left TLE-HS patients, which indicated structural vulnerability related to the hippocampus atrophy in the patient group. However, for the right TLE-HS patients, no significant differences were found between the patients and the normal controls, regardless of the ipsilateral hippocampal volume, the average cortical thickness or the patterns of hippocampal-cortical connectivity, which might be related to less atrophies observed in the MRI scans. Our study provided more evidence for the structural abnormalities in the unilateral TLE-HS patients.

β-Amyloid Deposition Is Associated with Decreased Right Prefrontal Activation during Task Switching among Cognitively Normal Elderly

PubMed Central

Steffener, Jason; Razlighi, Qolamreza R.; Habeck, Christian; Stern, Yaakov

2016-01-01

The accumulation of β-amyloid (Aβ) peptides, a pathological hallmark of Alzheimer's disease (AD), has been associated with functional alterations, often in an episodic memory system with a particular emphasis on medial temporal lobe function. The topography of Aβ deposition, however, largely overlaps with frontoparietal control (FPC) regions implicated in cognitive control that has been shown to be impaired in early mild AD. To understand the neural mechanism underlying early changes in cognitive control with AD, we examined the impact of Aβ deposition on task-evoked FPC activation using functional magnetic resonance imaging (fMRI) in humans. Forty-three young and 62 cognitively normal older adults underwent an fMRI session during an executive contextual task in which task difficulty varied: single (either letter case or vowel/consonant judgment task) vs dual (switching between letter case and vowel/consonant decisions) task. Older subjects additionally completed 18F-florbetaben positron emission tomography scans and were classified as either amyloid positive (Aβ+) or negative (Aβ−). Consistent with previous reports, age-related increases in brain activity were found in FPC regions commonly identified across groups. For both task conditions, Aβ-related increases in brain activity were found compared with baseline activity. For higher cognitive control load, however, Aβ+ elderly showed reduced task-switching activation in the right inferior frontal cortex. Our findings suggest that with Aβ deposition, brain activation in the cognitive control region reaches a maximum with lower control demand and decreases with higher control demand, which may underlie early impairment in cognitive control with AD progression. SIGNIFICANCE STATEMENT The accumulation of β-amyloid (Aβ) peptides, a pathological hallmark of Alzheimer's disease, spatially overlaps with frontoparietal control (FPC) regions implicated in cognitive control, but the impact of Aβ deposition on FPC regions is largely unknown. Using functional magnetic resonance imaging with a task-switching task, we found Aβ-related increases in FPC regions compared with baseline activity. For higher cognitive control load, however, Aβ-related hypoactivity was found in the right inferior frontal cortex, a region highly implicated in cognitive control. The findings suggest that with Aβ deposition, task-related brain activity may reach a plateau early and undergo downstream pathways of neural dysfunction, which may relate to the early impairment of cognitive control seen in the progression of Aβ pathology. PMID:26865619

Gallium Maltolate Disrupts Tumor Iron Metabolism and Retards the Growth of Glioblastoma by Inhibiting Mitochondrial Function and Ribonucleotide Reductase.

PubMed

Chitambar, Christopher R; Al-Gizawiy, Mona M; Alhajala, Hisham S; Pechman, Kimberly R; Wereley, Janine P; Wujek, Robert; Clark, Paul A; Kuo, John S; Antholine, William E; Schmainda, Kathleen M

2018-06-01

Gallium, a metal with antineoplastic activity, binds transferrin (Tf) and enters tumor cells via Tf receptor1 (TfR1); it disrupts iron homeostasis leading to cell death. We hypothesized that TfR1 on brain microvascular endothelial cells (BMEC) would facilitate Tf-Ga transport into the brain enabling it to target TfR-bearing glioblastoma. We show that U-87 MG and D54 glioblastoma cell lines and multiple glioblastoma stem cell (GSC) lines express TfRs, and that their growth is inhibited by gallium maltolate (GaM) in vitro After 24 hours of incubation with GaM, cells displayed a loss of mitochondrial reserve capacity followed by a dose-dependent decrease in oxygen consumption and a decrease in the activity of the iron-dependent M2 subunit of ribonucleotide reductase (RRM2). IHC staining of rat and human tumor-bearing brains showed that glioblastoma, but not normal glial cells, expressed TfR1 and RRM2, and that glioblastoma expressed greater levels of H- and L-ferritin than normal brain. In an orthotopic U-87 MG glioblastoma xenograft rat model, GaM retarded the growth of brain tumors relative to untreated control ( P = 0.0159) and reduced tumor mitotic figures ( P = 0.045). Tumors in GaM-treated animals displayed an upregulation of TfR1 expression relative to control animals, thus indicating that gallium produced tumor iron deprivation. GaM also inhibited iron uptake and upregulated TfR1 expression in U-87 MG and D54 cells in vitro We conclude that GaM enters the brain via TfR1 on BMECs and targets iron metabolism in glioblastoma in vivo, thus inhibiting tumor growth. Further development of novel gallium compounds for brain tumor treatment is warranted. Mol Cancer Ther; 17(6); 1240-50. ©2018 AACR . ©2018 American Association for Cancer Research.

Sexual dimorphism of the planum temporale in schizophrenia: A MRI study.

PubMed

Delvecchio, Giuseppe; Pigoni, Alessandro; Perlini, Cinzia; Barillari, Marco; Ruggeri, Mirella; Altamura, Alfredo Carlo; Bellani, Marcella; Brambilla, Paolo

2017-10-01

Anatomical alterations in the superior temporal gyrus have been consistently reported in patients with schizophrenia, and they have mostly been linked to positive symptoms, including hallucinations and thought disorders. The superior temporal gyrus is considered one of the most asymmetric and lateralized structure of the human brain, and the process of lateralization seems to vary according to gender in the normal population. However, although it has been consistently suggested that patients with schizophrenia did not show normal brain lateralization in several regions, only few studies investigated it in the superior temporal gyrus and its sub-regions considering the effects of gender. In this context, the aim of this study was to evaluate sexual dimorphism in superior temporal gyrus volumes in a sample of patients with schizophrenia compared to age- and gender-matched healthy controls. A total of 72 right/left-handed males (40 schizophrenia patients and 32 healthy controls) and 45 right/left-handed females (18 schizophrenia patients and 27 healthy controls) underwent clinical evaluation and a 1.5T magnetic resonance imaging scan. Gray and white matter volumes of regions of interest within the superior temporal gyrus were manually detected, including the Heschl's gyrus and the planum temporale. Female patients with schizophrenia presented a reduction in left planum temporale gray matter volumes ( F = 4.58, p = 0.03) and a lack of the normal planum temporale asymmetry index ( t = 0.27; p = 0.79) compared to female controls ( t = 5.47; p = 0.001). No differences were found between males for any volumes or laterality indices. Finally, in female patients with schizophrenia, Heschl's gyrus gray and white matter volumes negatively correlated with positive symptoms ( r = -0.56, p = 0.01). Our results showed that sexual dimorphism plays a key role on planum temporale in schizophrenia, underlining the importance of gender as a modulator of brain morphology and lateralization of schizophrenia.

Right Hemisphere Dominance in Visual Statistical Learning

ERIC Educational Resources Information Center

Roser, Matthew E.; Fiser, Jozsef; Aslin, Richard N.; Gazzaniga, Michael S.

2011-01-01

Several studies report a right hemisphere advantage for visuospatial integration and a left hemisphere advantage for inferring conceptual knowledge from patterns of covariation. The present study examined hemispheric asymmetry in the implicit learning of new visual feature combinations. A split-brain patient and normal control participants viewed…

Type 1 Diabetes and Impaired Awareness of Hypoglycemia Are Associated with Reduced Brain Gray Matter Volumes.

PubMed

Bednarik, Petr; Moheet, Amir A; Grohn, Heidi; Kumar, Anjali F; Eberly, Lynn E; Seaquist, Elizabeth R; Mangia, Silvia

2017-01-01

In this study, we retrospectively analyzed the anatomical MRI data acquired from 52 subjects with type 1 diabetes (26M/26F, 36 ± 11 years old, A1C = 7.2 ± 0.9%) and 50 age, sex and BMI frequency-matched non-diabetic controls (25M/25F, 36 ± 14 years old). The T1D group was further sub-divided based on whether subjects had normal, impaired, or indeterminate awareness of hypoglycemia ( n = 31, 20, and 1, respectively). Our goals were to test whether the gray matter (GM) volumes of selected brain regions were associated with diabetes status as well as with the status of hypoglycemia awareness. T1D subjects were found to have slightly smaller volume of the whole cortex as compared to controls (-2.7%, p = 0.016), with the most affected brain region being the frontal lobe (-3.6%, p = 0.024). Similar differences of even larger magnitude were observed among the T1D subjects based on their hypoglycemia awareness status. Indeed, compared to the patients with normal awareness of hypoglycemia, patients with impaired awareness had smaller volume of the whole cortex (-7.9%, p = 0.0009), and in particular of the frontal lobe (-9.1%, p = 0.006), parietal lobe (-8.0%, p = 0.015) and temporal lobe (-8.2%, p = 0.009). Such differences were very similar to those observed between patients with impaired awareness and controls (-7.6%, p = 0.0002 in whole cortex, -9.1%, p = 0.0003 in frontal lobe, -7.8%, p = 0.002 in parietal lobe, and -6.4%, p = 0.019 in temporal lobe). On the other hand, patients with normal awareness did not present significant volume differences compared to controls. No group-differences were observed in the occipital lobe or in the anterior cingulate, posterior cingulate, hippocampus, and thalamus. We conclude that diabetes status is associated with a small but statistically significant reduction of the whole cortex volume, mainly in the frontal lobe. The most prominent structural effects occurred in patients with impaired awareness of hypoglycemia (IAH) as compared to those with normal awareness, perhaps due to the long-term exposure to recurrent episodes of hypoglycemia. Future studies aimed at quantifying relationships of structural outcomes with functional outcomes, with cognitive performance, as well as with parameters describing glucose variability and severity of hypoglycemia episodes, will be necessary to further understand the impact of T1D on the brain.

An fMRI study of acupuncture-induced brain activation of aphasia stroke patients.

PubMed

Li, Geng; Yang, Edward S

2011-01-01

This investigation aims to test the effect of acupuncture on word generation activation (WGA) in post-stroke aphasia patients. Seven vascular aphasia patients and 14 control subjects were studied using functional magnetic resonance imaging (fMRI). Each performed: (1) a word generation (WG) task alone, followed by (2) repeating WG after insertion of acupuncture needles (WGN) into SJ 8 (a language-implicated acupoint), followed by (3) repeating WGN reinforced by electrical stimulation (WGA) of SJ 8, and finally (4) electrical stimulation (ES) of SJ 8 alone. Significant activation was found in the opercular, triangular, or insula during the ES stimulation in patients when comparing each patient to 14 normal controls. For the WG task, significant activation was found in the inferior frontal gyrus when comparing each patient to 14 normal controls. The signal induced by acupuncture was larger than that of the WG task in the left middle frontal gyrus with the comparison of WGA vs. WGN in seven patients. Further, main significant effects in the right insula in patients were observed when comparing seven patients to 14 normal controls. The activation induced by ES stimulation was only found on the left side in controls. This activation was observed on the lesion side of superior and middle frontal gyrus (SMFG) in patients. This study demonstrates for the first time that language-deficit-implicated acupoint stimulation can selectively activate the brain on the lesion side in post-stroke aphasia patients. These results suggest that acupuncture may have therapeutic benefits in post-stroke aphasia patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

Extended findings of Brain Metabolite Normalization in MA-Dependent Subjects Across Sustained Abstinence: A Proton MRS Study

PubMed Central

Salo, Ruth; Buonocore, Michael H.; Leamon, Martin; Natsuaki, Yutaka; Waters, Christy; Moore, Charles D.; Galloway, Gantt P.; Nordahl, Thomas E.

2010-01-01

Objective The goal of the present study was to extend our previous findings on long-term methamphetamine (MA) use and drug abstinence on brain metabolite levels in an expanded group of MA-dependent individuals. Methods Seventeen MA abusers with sustained drug abstinence (1 year to 5 years), 30 MA abusers with short-term drug abstinence (1 month to 6 months) and 24 non-substance using controls were studied using MR spectroscopy (MRS). MRS measures of NAA/Cr, Cho/Cr and Cho/NAA were obtained in the anterior cingulate cortex (ACC) and in the primary visual cortex (PVC). Results ACC-Cho/NAA values were abnormally high in the short-term abstinent group compared to controls [F(1,52)=18.76, p<0.0001]. No differences were observed between controls and the long-term abstinent group [F(1,39)=0.97, p=0.97]. New evidence of lower ACC-NAA/Cr levels were observed in the short-term abstinent MA abusers compared to controls [F(1,52)=23.05, p<0.0001] and long-term abstinent MA abusers [F(1,45)=7.06, p=0.01]. No differences were observed between long-term abstinent MA abusers and controls [F(1,39)=0.48, p=0.49]. Conclusions The new findings of relative NAA/Cr normalization across periods of abstinence suggest that adaptive changes following cessation of MA abuse may be broader than initially thought. These changes may contribute to some degree of normalization of neuronal function in the ACC. PMID:20739127

The biochemical, nanomechanical and chemometric signatures of brain cancer.

PubMed

Abramczyk, Halina; Imiela, Anna

2018-01-05

Raman spectroscopy and imaging combined with AFM topography and mechanical indentation by AFM have been shown to be an effective tool for analysis and discrimination of human brain tumors from normal structures. Raman methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n=5) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma (IV grade), and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational spectra and Raman images we provide a real-time feedback that is label-free method to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, and proteins. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have shown that the ratio of Raman intensities I2930/I2845 at 2930 and 2845cm -1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the lipid and protein contents of tumorous brain tissue compared to the non-tumor tissue. Almost all brain tumors have the Raman intensity ratios significantly higher (1.99±0.026) than that found in non-tumor brain tissue, which is 1.456±0.02, and indicates that the relative amount of lipids compared to proteins is significantly higher in the normal brain tissue. Mechanical indentation using AFM on sliced human brain tissues (medulloblastoma, grade IV) revealed that the mechanical properties of this tissue are strongly heterogeneous, between 1.8 and 75.7kPa, and the mean of 27.16kPa. The sensitivity and specificity obtained directly from PLSDA and cross validation gives a sensitivity and specificity of 98.5% and 96% and 96.3% and 92% for cross-validation, respectively. The high sensitivity and specificity demonstrates usefulness for a proper decision for a Raman diagnostic test on biochemical alterations monitored by Raman spectroscopy related to brain cancer development. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Towards mapping the brain connectome in depression: functional connectivity by perfusion SPECT.

PubMed

Gardner, Ann; Åstrand, Disa; Öberg, Johanna; Jacobsson, Hans; Jonsson, Cathrine; Larsson, Stig; Pagani, Marco

2014-08-30

Several studies have demonstrated altered brain functional connectivity in the resting state in depression. However, no study has investigated interregional networking in patients with persistent depressive disorder (PDD). The aim of this study was to assess differences in brain perfusion distribution and connectivity between large groups of patients and healthy controls. Participants comprised 91 patients with PDD and 65 age- and sex-matched healthy controls. Resting state perfusion was investigated by single photon emission computed tomography, and group differences were assessed by Statistical Parametric Mapping. Brain connectivity was explored through a voxel-wise interregional correlation analysis using as covariate of interest the normalized values of clusters of voxels in which perfusion differences were found in group analysis. Significantly increased regional brain perfusion distribution covering a large part of the cerebellum was observed in patients as compared with controls. Patients showed a significant negative functional connectivity between the cerebellar cluster and caudate, bilaterally. This study demonstrated inverse relative perfusion between the cerebellum and the caudate in PDD. Functional uncoupling may be associated with a dysregulation between the role of the cerebellum in action control and of the caudate in action selection, initiation and decision making in the patients. The potential impact of the resting state condition and the possibility of mitochondrial impairment are discussed. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

A computational model of prefrontal control in free recall: strategic memory use in the California Verbal Learning Task.

PubMed

Becker, Suzanna; Lim, Jean

2003-08-15

Several decades of research into the function of the frontal lobes in brain-damaged patients, and more recently in intact individuals using function brain imaging, has delineated the complex executive functions of the frontal cortex. And yet, the mechanisms by which the brain achieves these functions remain poorly understood. Here, we present a computational model of the role of the prefrontal cortex (PFC) in controlled memory use that may help to shed light on the mechanisms underlying one aspect of frontal control: the development and deployment of recall strategies. The model accounts for interactions between the PFC and medial temporal lobe in strategic memory use. The PFC self-organizes its own mnemonic codes using internally derived performance measures. These mnemonic codes serve as retrieval cues by biasing retrieval in the medial temporal lobe memory system. We present data from three simulation experiments that demonstrate strategic encoding and retrieval in the free recall of categorized lists of words. Experiment 1 compares the performance of the model with two control networks to evaluate the contribution of various components of the model. Experiment 2 compares the performance of normal and frontally lesioned models to data from several studies using frontally intact and frontally lesioned individuals, as well as normal, healthy individuals under conditions of divided attention. Experiment 3 compares the model's performance on the recall of blocked and unblocked categorized lists of words to data from Stuss et al. (1994) for individuals with control and frontal lobe lesions. Overall, our model captures a number of aspects of human performance on free recall tasks: an increase in total words recalled and in semantic clustering scores across trials, superiority on blocked lists of related items compared to unblocked lists of related items, and similar patterns of performance across trials in the normal and frontally lesioned models, with poorer overall performance of the lesioned models on all measures. The model also has a number of shortcomings, in light of which we suggest extensions to the model that would enable more sophisticated forms of strategic control.

Global and regional brain mean diffusivity changes in patients with heart failure.

PubMed

Woo, Mary A; Palomares, Jose A; Macey, Paul M; Fonarow, Gregg C; Harper, Ronald M; Kumar, Rajesh

2015-04-01

Heart failure (HF) patients show gray and white matter changes in multiple brain sites, including autonomic and motor coordination areas. It is unclear whether the changes represent acute or chronic tissue pathology, a distinction necessary for understanding pathological processes that can be resolved with diffusion tensor imaging (DTI)-based mean diffusivity (MD) procedures. We collected four DTI series from 16 HF (age 55.1 ± 7.8 years, 12 male) and 26 control (49.7 ± 10.8 years, 17 male) subjects with a 3.0-Tesla magnetic resonance imaging scanner. MD maps were realigned, averaged, normalized, and smoothed. Global and regional MD values from autonomic and motor coordination sites were calculated by using normalized MD maps and brain masks; group MD values and whole-brain smoothed MD maps were compared by analysis of covariance (covariates; age and gender). Global brain MD (HF vs. controls, units × 10(-6) mm(2) /sec, 1103.8 ± 76.6 vs. 1035.9 ± 69.4, P = 0.038) and regional autonomic and motor control site values (left insula, 1,085.4 ± 95.7 vs. 975.7 ± 65.4, P = 0.001; right insula, 1,050.2 ± 100.6 vs. 965.7 ± 58.4, P = 0.004; left hypothalamus, 1,419.6 ± 165.2 vs. 1,234.9 ± 136.3, P = 0.002; right hypothalamus, 1,446.5 ± 178.8 vs. 1,273.3 ± 136.9, P = 0.004; left cerebellar cortex, 889.1 ± 81.9 vs. 796.6 ± 46.8, P < 0.001; right cerebellar cortex, 797.8 ± 50.8 vs. 750.3 ± 27.5, P = 0.001; cerebellar deep nuclei, 1,236.1 ± 193.8 vs. 1,071.7 ± 107.1, P = 0.002) were significantly higher in HF vs. control subjects, indicating chronic tissue changes. Whole-brain comparisons showed increased MD values in HF subjects, including limbic, basal-ganglia, thalamic, solitary tract nucleus, frontal, and cerebellar regions. Brain injury occurs in autonomic and motor control areas, which may contribute to deficient function in HF patients. The chronic tissue changes likely result from processes that develop over a prolonged period. © 2014 Wiley Periodicals, Inc.

The neuropathological study of myelin oligodendrocyte glycoprotein in the temporal lobe of schizophrenia patients.

PubMed

Marui, Tomoyasu; Torii, Youta; Iritani, Shuji; Sekiguchi, Hirotaka; Habuchi, Chikako; Fujishiro, Hiroshige; Oshima, Kenichi; Niizato, Kazuhiro; Hayashida, Shotaro; Masaki, Katsuhisa; Kira, Junichi; Ozaki, Norio

2018-03-22

Recent studies based on the neuroimaging analysis, genomic analysis and transcriptome analysis of the postmortem brain suggest that the pathogenesis of schizophrenia is related to myelin-oligodendrocyte abnormalities. However, no serious neuropathological investigation of this protein in the schizophrenic brain has yet been performed. In this study, to confirm the change in neuropathological findings due to the pathogenesis of this disease, we observed the expression of myelin-oligodendrocyte directly in the brain tissue of schizophrenia patients. Myelin oligodendrocyte glycoprotein (MOG) was evaluated in the cortex of the superior temporal gyrus (STG) and the hippocampus in 10 schizophrenic and nine age- and sex-matched normal control postmortem brains. The expression of MOG was significantly lower in the middle layer of the neocortex of the STG and stratum lucidum of CA3 in the hippocampus in the long-term schizophrenic brains (patients with ≥30 years of illness duration) than in the age-matched controls. Furthermore, the thickness of MOG-positive fibre-like structures was significantly lower in both regions of the long-term schizophrenic brains than in the age-matched controls. These findings suggest that a long duration of illness has a marked effect on the expression of MOG in these regions, and that myelin-oligodendrocyte abnormalities in these regions may be related to the progressive pathophysiology of schizophrenia.

Altered brain structural connectivity in post-traumatic stress disorder: a diffusion tensor imaging tractography study.

PubMed

Long, Zhiliang; Duan, Xujun; Xie, Bing; Du, Handan; Li, Rong; Xu, Qiang; Wei, Luqing; Zhang, Shao-xiang; Wu, Yi; Gao, Qing; Chen, Huafu

2013-09-25

Post-traumatic stress disorder (PTSD) is characterized by dysfunction of several discrete brain regions such as medial prefrontal gyrus with hypoactivation and amygdala with hyperactivation. However, alterations of large-scale whole brain topological organization of structural networks remain unclear. Seventeen patients with PTSD in motor vehicle accident survivors and 15 normal controls were enrolled in our study. Large-scale structural connectivity network (SCN) was constructed using diffusion tensor tractography, followed by thresholding the mean factional anisotropy matrix of 90 brain regions. Graph theory analysis was then employed to investigate their aberrant topological properties. Both patient and control group showed small-world topology in their SCNs. However, patients with PTSD exhibited abnormal global properties characterized by significantly decreased characteristic shortest path length and normalized characteristic shortest path length. Furthermore, the patient group showed enhanced nodal centralities predominately in salience network including bilateral anterior cingulate and pallidum, and hippocampus/parahippocamus gyrus, and decreased nodal centralities mainly in medial orbital part of superior frontal gyrus. The main limitation of this study is the small sample of PTSD patients, which may lead to decrease the statistic power. Consequently, this study should be considered an exploratory analysis. These results are consistent with the notion that PTSD can be understood by investigating the dysfunction of large-scale, spatially distributed neural networks, and also provide structural evidences for further exploration of neurocircuitry models in PTSD. © 2013 Elsevier B.V. All rights reserved.

The characteristic and changes of the event-related potentials (ERP) and brain topographic maps before and after treatment with rTMS in subjective tinnitus patients.

PubMed

Yang, Haidi; Xiong, Hao; Yu, Rongjun; Wang, Changming; Zheng, Yiqing; Zhang, Xueyuan

2013-01-01

To compare the event-related potentials (ERPs) and brain topographic maps characteristic and change in normal controls and subjective tinnitus patients before and after repetitive transcranial magnetic stimulation (rTMS) treatment. The ERPs and brain topographic maps elicited by target stimulus were compared before and after 1-week treatment with rTMS in 20 subjective tinnitus patients and 16 healthy controls. Before rTMS, target stimulus elicited a larger N1 component than the standard stimuli (repeating sounds)in control group but not in tinnitus patients. Instead, the tinnitus group pre-treatment exhibited larger amplitude of N1 in response to standard stimuli than to deviant stimuli. Furthermore tinnitus patients had smaller mismatch negativity (MMN) and late discriminative negativity (LDN)component at Fz compared with the control group. After rTMS treatment, tinnitus patients showed increased N1 response to deviant stimuli and larger MMN and LDN compared with pre-treatment. The topographic maps for the tinnitus group before rTMS -treatment demonstrated global asymmetry between the left and right cerebral hemispheres with more negative activities in left side and more positive activities in right side. In contrast, the brain topographic maps for patients after rTMS-treatment and controls seem roughly symmetrical. The ERP amplitudes and brain topographic maps in post-treatment patient group showed no significant difference with those in controls. The characterical changes in ERP and brain topographic maps in tinnitus patients maybe related with the electrophysiological mechanism of tinnitus induction and development. It can be used as an objective biomarker for the evaluation of auditory central in subjective tinnitus patients. These findings support the notion that rTMS treatment in tinnitus patients may exert a beneficial effect.

Semiautomated volumetry of the cerebrum, cerebellum-brain stem, and temporal lobe on brain magnetic resonance images.

PubMed

Hayashi, Norio; Sanada, Shigeru; Suzuki, Masayuki; Matsuura, Yukihiro; Kawahara, Kazuhiro; Tsujii, Hideo; Yamamoto, Tomoyuki; Matsui, Osamu

2008-02-01

The aim of this study was to develop an automated method of segmenting the cerebrum, cerebellum-brain stem, and temporal lobe simultaneously on magnetic resonance (MR) images. We obtained T1-weighted MR images from 10 normal subjects and 19 patients with brain atrophy. To perform automated volumetry from MR images, we performed the following three steps: (1) segmentation of the brain region; (2) separation between the cerebrum and the cerebellum-brain stem; and (3) segmentation of the temporal lobe. Evaluation was based on the correctly recognized region (CRR) (i.e., the region recognized by both the automated and manual methods). The mean CRRs of the normal and atrophic brains were 98.2% and 97.9% for the cerebrum, 87.9% and 88.5% for the cerebellum-brain stem, and 76.9% and 85.8% for the temporal lobe, respectively. We introduce an automated volumetric method for the cerebrum, cerebellum-brain stem, and temporal lobe on brain MR images. Our method can be applied to not only the normal brain but also the atrophic brain.

FGF signaling is required for brain left-right asymmetry and brain midline formation.

PubMed

Neugebauer, Judith M; Yost, H Joseph

2014-02-01

Early disruption of FGF signaling alters left-right (LR) asymmetry throughout the embryo. Here we uncover a role for FGF signaling that specifically disrupts brain asymmetry, independent of normal lateral plate mesoderm (LPM) asymmetry. When FGF signaling is inhibited during mid-somitogenesis, asymmetrically expressed LPM markers southpaw and lefty2 are not affected. However, asymmetrically expressed brain markers lefty1 and cyclops become bilateral. We show that FGF signaling controls expression of six3b and six7, two transcription factors required for repression of asymmetric lefty1 in the brain. We found that Z0-1, atypical PKC (aPKC) and β-catenin protein distribution revealed a midline structure in the forebrain that is dependent on a balance of FGF signaling. Ectopic activation of FGF signaling leads to overexpression of six3b, loss of organized midline adherins junctions and bilateral loss of lefty1 expression. Reducing FGF signaling leads to a reduction in six3b and six7 expression, an increase in cell boundary formation in the brain midline, and bilateral expression of lefty1. Together, these results suggest a novel role for FGF signaling in the brain to control LR asymmetry, six transcription factor expressions, and a midline barrier structure. Copyright © 2013 Elsevier Inc. All rights reserved.

Genetic Causes of Microcephaly and Lessons for Neuronal Development

PubMed Central

Gilmore, Edward C.; Walsh, Christopher A.

2012-01-01

The study of human developmental microcephaly is providing important insights into brain development. It has become clear that developmental microcephalies are associated with abnormalities in cellular production, and that the pathophysiology of microcephaly provides remarkable insights into how the brain generates the proper number of neurons that determine brain size. Most of the genetic causes of ‘primary’ developmental microcephaly (i.e., not associated with other syndromic features) are associated with centrosomal abnormalities. In addition to other functions, centrosomal proteins control the mitotic spindle, which is essential for normal cell proliferation during mitosis. However, the brain is often uniquely affected when microcephaly genes are mutated implying special centrosomal related functions in neuronal production. Although models explaining how this could occur have some compelling data, they are not without controversy. Interestingly, some of the microcephaly genes show evidence that they were targets of evolutionary selection in primates and human ancestors, suggesting potential evolutionary roles in controlling neuronal number and brain volume across species. Mutations in DNA repair pathway genes also lead to microcephaly. Double stranded DNA breaks appear to be a prominent type of damage that needs to be repaired during brain development, yet why defects in DNA repair affect the brain preferentially and if DNA repair relates to centrosome function, are not clearly understood. PMID:24014418

FGF Signaling is Required for Brain Left-Right Asymmetry and Brain Midline Formation

PubMed Central

Neugebauer, Judith M.; Yost, H. Joseph

2014-01-01

Early disruption of FGF signaling alters left-right (LR) asymmetry throughout the embryo. Here we uncover a role for FGF signaling that specifically disrupts brain asymmetry, independent of normal lateral plate mesoderm (LPM) asymmetry. When FGF signaling is inhibited during mid-somitogenesis, asymmetrically expressed LPM markers southpaw and lefty2 are not affected. However, asymmetrically expressed brain markers lefty1 and cyclops become bilateral. We show that FGF signaling controls expression of six3b and six7, two transcription factors required for repression of asymmetric lefty1 in the brain. We found that Z0-1, atypical PKC (aPKC) and β-catenin protein distribution revealed a midline structure in the forebrain that is dependent on a balance of FGF signaling. Ectopic activation of FGF signaling leads to overexpression of six3b, loss of organized midline adherins junctions and bilateral loss of lefty1 expression. Reducing FGF signaling leads to a reduction in six3b and six7 expression, an increase in cell boundary formation in the brain midline, and bilateral expression of lefty1. Together, these results suggest a novel role for FGF signaling in the brain to control LR asymmetry, six transcription factor expression, and a midline barrier structure. PMID:24333178

Combined Supplementation of Choline and Docosahexaenoic Acid during Pregnancy Enhances Neurodevelopment of Fetal Hippocampus.

PubMed

Thomas Rajarethnem, Huban; Megur Ramakrishna Bhat, Kumar; Jc, Malsawmzuali; Kumar Gopalkrishnan, Siva; Mugundhu Gopalram, Ramesh Babu; Rai, Kiranmai Sesappa

2017-01-01

Choline is an essential nutrient for humans which plays an important role in structural integrity and signaling functions. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid, highly enriched in cell membranes of the brain. Dietary intake of choline or DHA alone by pregnant mothers directly affects fetal brain development and function. But no studies show the efficacy of combined supplementation of choline and DHA on fetal neurodevelopment. The aim of the present study was to analyze fetal neurodevelopment on combined supplementation of pregnant dams with choline and DHA. Pregnant dams were divided into five groups: normal control [NC], saline control [SC], choline [C], DHA, and C + DHA. Saline, choline, and DHA were given as supplements to appropriate groups of dams. NC dams were undisturbed during entire gestation. On postnatal day (PND) 40, brains were processed for Cresyl staining. Pups from choline or DHA supplemented group showed significant ( p < 0.05) increase in number of neurons in hippocampus when compared to the same in NC and SC groups. Moreover, pups from C + DHA supplemented group showed significantly higher number of neurons ( p < 0.001) in hippocampus when compared to the same in NC and SC groups. Thus combined supplementation of choline and DHA during normal pregnancy enhances fetal hippocampal neurodevelopment better than supplementation of choline or DHA alone.

Individual Patient Diagnosis of AD and FTD via High-Dimensional Pattern Classification of MRI

PubMed Central

Davatzikos, C.; Resnick, S. M.; Wu, X.; Parmpi, P.; Clark, C. M.

2008-01-01

The purpose of this study is to determine the diagnostic accuracy of MRI-based high-dimensional pattern classification in differentiating between patients with Alzheimer’s Disease (AD), Frontotemporal Dementia (FTD), and healthy controls, on an individual patient basis. MRI scans of 37 patients with AD and 37 age-matched cognitively normal elderly individuals, as well as 12 patients with FTD and 12 age-matched cognitively normal elderly individuals, were analyzed using voxel-based analysis and high-dimensional pattern classification. Diagnostic sensitivity and specificity of spatial patterns of regional brain atrophy found to be characteristic of AD and FTD were determined via cross-validation and via split-sample methods. Complex spatial patterns of relatively reduced brain volumes were identified, including temporal, orbitofrontal, parietal and cingulate regions, which were predominantly characteristic of either AD or FTD. These patterns provided 100% diagnostic accuracy, when used to separate AD or FTD from healthy controls. The ability to correctly distinguish AD from FTD averaged 84.3%. All estimates of diagnostic accuracy were determined via cross-validation. In conclusion, AD- and FTD-specific patterns of brain atrophy can be detected with high accuracy using high-dimensional pattern classification of MRI scans obtained in a typical clinical setting. PMID:18474436

A Special Extract of Bacopa monnieri (CDRI-08) Restores Learning and Memory by Upregulating Expression of the NMDA Receptor Subunit GluN2B in the Brain of Scopolamine-Induced Amnesic Mice

PubMed Central

Rai, Rakesh; Singh, Hemant K.; Prasad, S.

2015-01-01

In the present communication, we have investigated effects of the CDRI-08, a well characterized extract of Bacopa monnieri, on expression of the GluN2B subunit of NMDAR in various brain regions of the scopolamine-induced amnesic mice. Our behavioral data reveal that scopolamine-treated amnesic mice exhibit significant decline in the spatial memory compared to the normal control mice. Our RT-PCR and immunoblotting data revealed that the scopolamine treatment resulted in a significant downregulation of the NMDAR GluN2B subunit expression in prefrontal cortex and hippocampus. Our enzyme assay data revealed that scopolamine caused a significant increase in the acetylcholinesterase activity in both the brain regions. Further, oral administration of the CDRI-08 to scopolamine-treated amnesic mice restored the spatial memory which was found to be associated with significant upregulation of the GluN2B subunit expression and decline in the acetylcholinesterase activity in prefrontal cortex as well as hippocampus towards their levels in the normal control mice. Our study provides the evidence for the mechanism underlying role of the Bacopa monnieri extract (CDRI-08) in restoring spatial memory in amnesic mice, which may have therapeutic implications. PMID:26413117

Methylmercury-cholinesterase interactions in rats.

PubMed Central

Hastings, F L; Lucier, G W; Klein, R

1975-01-01

The interaction of methylmercury hydroxide (MMH) and cholinesterases was studied in male and female rats. MMH administered subcutaneously in doses of 10 mg/kg for 2 days reduced the level of plasma cholinesterase (ButChE) by 68% in females and 47% in males while brain acetylcholinesterase (AChE) was unaffected. Normal females had higher but more variable ButChE levels than normal males. In a time-course experiment, a single dose of MMH (10 mg/kg) reduced ButChE levels when mercury levels reached 22 mug/ml in the blood. A 10% reduction in brain AChE was observed at 72 hours; however, mercury reached a concentration of only 2.0 mug/g in brain tissue. The determination of the Michaelis constant Km and maximum velocity value Vmax for butyrylcholine and ButChE in control and MMH-treated (1 mg/kg) animals indicated that MMH reduced Vmax only. Since no loss in ButChE activity occurred when MMH and control plasma were incubated in vitro, MMH is not a direct inhibitor of ButChE. Because only the inactive monomeric form of ButChE contains free sulfhydryl groups, it is postulated that MMH combines covalently with the sulfur, preventing formation of active enzyme. By analogy, it is believed this is also the case with AChE. PMID:1227853

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.

Combining Segmented Grey and White Matter Images Improves Voxel-based Morphometry for the Case of Dilated Lateral Ventricles.

PubMed

Goto, Masami; Abe, Osamu; Aoki, Shigeki; Kamagata, Koji; Hori, Masaaki; Miyati, Tosiaki; Gomi, Tsutomu; Takeda, Tohoru

2018-01-18

To evaluate the error in segmented tissue images and to show the usefulness of the brain image in voxel-based morphometry (VBM) using Statistical Parametric Mapping (SPM) 12 software and 3D T 1 -weighted magnetic resonance images (3D-T 1 WIs) processed to simulate idiopathic normal pressure hydrocephalus (iNPH). VBM analysis was performed on sagittal 3D-T 1 WIs obtained in 22 healthy volunteers using a 1.5T MR scanner. Regions of interest for the lateral ventricles of all subjects were carefully outlined on the original 3D-T 1 WIs, and two types of simulated 3D-T 1 WI were also prepared (non-dilated 3D-T 1 WI as normal control and dilated 3D-T 1 WI to simulate iNPH). All simulated 3D-T 1 WIs were segmented into gray matter, white matter, and cerebrospinal fluid images, and normalized to standard space. A brain image was made by adding the gray and white matter images. After smoothing with a 6-mm isotropic Gaussian kernel, group comparisons (dilated vs non-dilated) were made for gray and white matter, cerebrospinal fluid, and brain images using a paired t-test. In evaluation of tissue volume, estimation error was larger using gray or white matter images than using the brain image, and estimation errors in gray and white matter volume change were found for the brain surface. To our knowledge, this is the first VBM study to show the possibility that VBM of gray and white matter volume on the brain surface may be more affected by individual differences in the level of dilation of the lateral ventricles than by individual differences in gray and white matter volumes. We recommend that VBM evaluation in patients with iNPH should be performed using the brain image rather than the gray and white matter images.

Long-term valproic acid exposure increases the number of neocortical neurons in the developing rat brain. A possible new animal model of autism.

PubMed

Sabers, Anne; Bertelsen, Freja C B; Scheel-Krüger, Jørgen; Nyengaard, Jens R; Møller, Arne

2014-09-19

The aim of this study was to test the hypothesis that long-term fetal valproic acid (VPA) exposure at doses relevant to the human clinic interferes with normal brain development. Pregnant rats were given intraperitoneal injections of VPA (20mg/kg or 100mg/kg) continuously during the last 9-12 days of pregnancy and during the lactation period until sacrifice on the 23rd postnatal day. Total number of neocortical neurons was estimated using the optical fractionator and frontal cortical thicknesses were sampled in VPA exposed pups compared with an unexposed control group. We found that pups exposed to 20mg/kg and 100mg/kg doses of VPA had statistically significant higher total number of neurons in neocortex by 15.8% and 12.3%, respectively (p<0.05) compared to controls amounting to 15.5×10(6) neocortical neurons (p<0.01). There was no statistical difference between the two VPA groups. Pups exposed to100mg/kg, but not to 20mg/kg VPA displayed a significant (p<0.05) broader (7.5%) of frontal cortical thickness compared to controls. Our results support the hypothesis that fetal exposure of VPA may interfere with normal brain development by disturbing neocortical organization, resulting in overgrowth of frontal lobes and increased neuronal cell numbers. The results indirectly suggest that prenatal VPA may contribute as a causative factor in the brain developmental disturbances equivalent to those seen in human autism spectrum disorders. We therefore suggest that this version of the VPA model may provide a translational model of autism. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Brain basis of self: self-organization and lessons from dreaming

PubMed Central

Kahn, David

2013-01-01

Through dreaming, a different facet of the self is created as a result of a self-organizing process in the brain. Self-organization in biological systems often happens as an answer to an environmental change for which the existing system cannot cope; self-organization creates a system that can cope in the newly changed environment. In dreaming, self-organization serves the function of organizing disparate memories into a dream since the dreamer herself is not able to control how individual memories become weaved into a dream. The self-organized dream provides, thereby, a wide repertoire of experiences; this expanded repertoire of experience results in an expansion of the self beyond that obtainable when awake. Since expression of the self is associated with activity in specific areas of the brain, the article also discusses the brain basis of the self by reviewing studies of brain injured patients, discussing brain imaging studies in normal brain functioning when focused, when daydreaming and when asleep and dreaming. PMID:23882232

Neuroimaging Studies Illustrate the Commonalities Between Ageing and Brain Diseases.

PubMed

Cole, James H

2018-07-01

The lack of specificity in neuroimaging studies of neurological and psychiatric diseases suggests that these different diseases have more in common than is generally considered. Potentially, features that are secondary effects of different pathological processes may share common neurobiological underpinnings. Intriguingly, many of these mechanisms are also observed in studies of normal (i.e., non-pathological) brain ageing. Different brain diseases may be causing premature or accelerated ageing to the brain, an idea that is supported by a line of "brain ageing" research that combines neuroimaging data with machine learning analysis. In reviewing this field, I conclude that such observations could have important implications, suggesting that we should shift experimental paradigm: away from characterizing the average case-control brain differences resulting from a disease toward methods that place individuals in their age-appropriate context. This will also lead naturally to clinical applications, whereby neuroimaging can contribute to a personalized-medicine approach to improve brain health. © 2018 WILEY Periodicals, Inc.

Neural markers of social and monetary rewards in children with Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder.

PubMed

Gonzalez-Gadea, Maria Luz; Sigman, Mariano; Rattazzi, Alexia; Lavin, Claudio; Rivera-Rei, Alvaro; Marino, Julian; Manes, Facundo; Ibanez, Agustin

2016-07-28

Recent theories of decision making propose a shared value-related brain mechanism for encoding monetary and social rewards. We tested this model in children with Attention-Deficit/Hyperactivity Disorder (ADHD), children with Autism Spectrum Disorder (ASD) and control children. We monitored participants' brain dynamics using high density-electroencephalography while they played a monetary and social reward tasks. Control children exhibited a feedback Error-Related Negativity (fERN) modulation and Anterior Cingulate Cortex (ACC) source activation during both tasks. Remarkably, although cooperation resulted in greater losses for the participants, the betrayal options generated greater fERN responses. ADHD subjects exhibited an absence of fERN modulation and reduced ACC activation during both tasks. ASD subjects exhibited normal fERN modulation during monetary choices and inverted fERN/ACC responses in social options than did controls. These results suggest that in neurotypicals, monetary losses and observed disloyal social decisions induced similar activity in the brain value system. In ADHD children, difficulties in reward processing affected early brain signatures of monetary and social decisions. Conversely, ASD children showed intact neural markers of value-related monetary mechanisms, but no brain modulation by prosociality in the social task. These results offer insight into the typical and atypical developments of neural correlates of monetary and social reward processing.

Brain Responses to High-Protein Diets12

PubMed Central

Journel, Marion; Chaumontet, Catherine; Darcel, Nicolas; Fromentin, Gilles; Tomé, Daniel

2012-01-01

Proteins are suspected to have a greater satiating effect than the other 2 macronutrients. After protein consumption, peptide hormones released from the gastrointestinal tract (mainly anorexigenic gut peptides such as cholecystokinin, glucagon peptide 1, and peptide YY) communicate information about the energy status to the brain. These hormones and vagal afferents control food intake by acting on brain regions involved in energy homeostasis such as the brainstem and the hypothalamus. In fact, a high-protein diet leads to greater activation than a normal-protein diet in the nucleus tractus solitarius and in the arcuate nucleus. More specifically, neural mechanisms triggered particularly by leucine consumption involve 2 cellular energy sensors: the mammalian target of rapamycin and AMP-activated protein kinase. In addition, reward and motivation aspects of eating behavior, controlled mainly by neurons present in limbic regions, play an important role in the reduced hedonic response of a high-protein diet. This review examines how metabolic signals emanating from the gastrointestinal tract after protein ingestion target the brain to control feeding, energy expenditure, and hormones. Understanding the functional roles of brain areas involved in the satiating effect of proteins and their interactions will demonstrate how homeostasis and reward are integrated with the signals from peripheral organs after protein consumption. PMID:22585905

Inter-subject FDG PET Brain Networks Exhibit Multi-scale Community Structure with Different Normalization Techniques.

PubMed

Sperry, Megan M; Kartha, Sonia; Granquist, Eric J; Winkelstein, Beth A

2018-07-01

Inter-subject networks are used to model correlations between brain regions and are particularly useful for metabolic imaging techniques, like 18F-2-deoxy-2-(18F)fluoro-D-glucose (FDG) positron emission tomography (PET). Since FDG PET typically produces a single image, correlations cannot be calculated over time. Little focus has been placed on the basic properties of inter-subject networks and if they are affected by group size and image normalization. FDG PET images were acquired from rats (n = 18), normalized by whole brain, visual cortex, or cerebellar FDG uptake, and used to construct correlation matrices. Group size effects on network stability were investigated by systematically adding rats and evaluating local network connectivity (node strength and clustering coefficient). Modularity and community structure were also evaluated in the differently normalized networks to assess meso-scale network relationships. Local network properties are stable regardless of normalization region for groups of at least 10. Whole brain-normalized networks are more modular than visual cortex- or cerebellum-normalized network (p < 0.00001); however, community structure is similar at network resolutions where modularity differs most between brain and randomized networks. Hierarchical analysis reveals consistent modules at different scales and clustering of spatially-proximate brain regions. Findings suggest inter-subject FDG PET networks are stable for reasonable group sizes and exhibit multi-scale modularity.

Altered Effective Connectivity of Hippocampus-Dependent Episodic Memory Network in mTBI Survivors

PubMed Central

2016-01-01

Traumatic brain injuries (TBIs) are generally recognized to affect episodic memory. However, less is known regarding how external force altered the way functionally connected brain structures of the episodic memory system interact. To address this issue, we adopted an effective connectivity based analysis, namely, multivariate Granger causality approach, to explore causal interactions within the brain network of interest. Results presented that TBI induced increased bilateral and decreased ipsilateral effective connectivity in the episodic memory network in comparison with that of normal controls. Moreover, the left anterior superior temporal gyrus (aSTG, the concept forming hub), left hippocampus (the personal experience binding hub), and left parahippocampal gyrus (the contextual association hub) were no longer network hubs in TBI survivors, who compensated for hippocampal deficits by relying more on the right hippocampus (underlying perceptual memory) and the right medial frontal gyrus (MeFG) in the anterior prefrontal cortex (PFC). We postulated that the overrecruitment of the right anterior PFC caused dysfunction of the strategic component of episodic memory, which caused deteriorating episodic memory in mTBI survivors. Our findings also suggested that the pattern of brain network changes in TBI survivors presented similar functional consequences to normal aging. PMID:28074162

A paradigm of undernourishing and neonatal rehabilitation in the newborn rat.

PubMed

Perez-Torrero, Esther; Torrerob, Carmen; Collado, Paloma; Salas, Manuel

2003-04-01

Perinatal undernutrition as a deficiency of nutrient availability, affects body and brain developmental processes and promotes recurrent health problems. Thus, altered mother-litter bonds and deficient environmental interactions may interfere with the brain pluripotential capabilities of the newborn. To gather information concerning the mechanisms underlying perinatal undernutrition we designed a paradigm of undernutrition and neonatal rehabilitation in the rat. An underfed group came from pregnant Wistar rats fed with 50% of the diet from G6 to G12 and with 60% from G13 until G21. After birth, pups were daily undernourished during 12 h daily by rotating a pair of lactating well-nourished dams which had one of their nipples subcutaneously ligated. The rehabilitated animals were undernourished pups neonatally fed by a pair of normally lactating dams. Controls received plenty of food during the pre- and neonatal periods. Pups were sacrificed at 12, 20 and 30 days of age. Perinatal underfeeding significantly reduced body and brain weights and neuronal morphometric parameters. Normal neonatal feeding in the newborn ameliorated the damages associated to food deprivation. The current undernourishing paradigm may be helpful to assess brain development alterations, as well as to study the compensatory mechanisms associated to salutary epigenetic influences.

EEG based topography analysis in string recognition task

NASA Astrophysics Data System (ADS)

Ma, Xiaofei; Huang, Xiaolin; Shen, Yuxiaotong; Qin, Zike; Ge, Yun; Chen, Ying; Ning, Xinbao

2017-03-01

Vision perception and recognition is a complex process, during which different parts of brain are involved depending on the specific modality of the vision target, e.g. face, character, or word. In this study, brain activities in string recognition task compared with idle control state are analyzed through topographies based on multiple measurements, i.e. sample entropy, symbolic sample entropy and normalized rhythm power, extracted from simultaneously collected scalp EEG. Our analyses show that, for most subjects, both symbolic sample entropy and normalized gamma power in string recognition task are significantly higher than those in idle state, especially at locations of P4, O2, T6 and C4. It implies that these regions are highly involved in string recognition task. Since symbolic sample entropy measures complexity, from the perspective of new information generation, and normalized rhythm power reveals the power distributions in frequency domain, complementary information about the underlying dynamics can be provided through the two types of indices.

Glycoblotting method allows for rapid and efficient glycome profiling of human Alzheimer's disease brain, serum and cerebrospinal fluid towards potential biomarker discovery.

PubMed

Gizaw, Solomon T; Ohashi, Tetsu; Tanaka, Masakazu; Hinou, Hiroshi; Nishimura, Shin-Ichiro

2016-08-01

Understanding of the significance of posttranslational glycosylation in Alzheimer's disease (AD) is of growing importance for the investigation of the pathogenesis of AD as well as discovery research of the disease-specific serum biomarkers. We designed a standard protocol for the glycoblotting combined with MALDI-TOFMS to perform rapid and quantitative profiling of the glycan parts of glycoproteins (N-glycans) and glycosphingolipids (GSLs) using human AD's post-mortem samples such as brain tissues (dissected cerebral cortices such as frontal, parietal, occipital, and temporal domains), serum and cerebrospinal fluid (CSF). The structural profiles of the major N-glycans released from glycoproteins and the total expression levels of the glycans were found to be mostly similar between the brain tissues of the AD patients and those of the normal control group. In contrast, the expression levels of the serum and CSF protein N-glycans such as bisect-type and multiply branched glycoforms were increased significantly in AD patient group. In addition, the levels of some gangliosides such as GM1, GM2 and GM3 appeared to alter in the AD patient brain and serum samples when compared with the normal control groups. Alteration of the expression levels of major N- and GSL-glycans in human brain tissues, serum and CSF of AD patients can be monitored quantitatively by means of the glycoblotting-based standard protocols. The changes in the expression levels of the glycans derived from the human post-mortem samples uncovered by the standardized glycoblotting method provides potential serum biomarkers in central nervous system disorders and can contribute to the insight into the molecular mechanisms in the pathogenesis of neurodegenerative diseases and future drug discovery. Most importantly, the present preliminary trials using human post-mortem samples of AD patients suggest that large-scale serum glycomics cohort by means of various-types of human AD patients as well as the normal control sera can facilitate the discovery research of highly sensitive and reliable serum biomarkers for an early diagnosis of AD. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. Copyright © 2016 Elsevier B.V. All rights reserved.

Developmental dyslexia in Chinese and English populations: dissociating the effect of dyslexia from language differences

PubMed Central

Hu, Wei; Lee, Hwee Ling; Zhang, Qiang; Liu, Tao; Geng, Li Bo; Seghier, Mohamed L.; Shakeshaft, Clare; Twomey, Tae; Green, David W.; Yang, Yi Ming

2010-01-01

Previous neuroimaging studies have suggested that developmental dyslexia has a different neural basis in Chinese and English populations because of known differences in the processing demands of the Chinese and English writing systems. Here, using functional magnetic resonance imaging, we provide the first direct statistically based investigation into how the effect of dyslexia on brain activation is influenced by the Chinese and English writing systems. Brain activation for semantic decisions on written words was compared in English dyslexics, Chinese dyslexics, English normal readers and Chinese normal readers, while controlling for all other experimental parameters. By investigating the effects of dyslexia and language in one study, we show common activation in Chinese and English dyslexics despite different activation in Chinese versus English normal readers. The effect of dyslexia in both languages was observed as less than normal activation in the left angular gyrus and in left middle frontal, posterior temporal and occipitotemporal regions. Differences in Chinese and English normal reading were observed as increased activation for Chinese relative to English in the left inferior frontal sulcus; and increased activation for English relative to Chinese in the left posterior superior temporal sulcus. These cultural differences were not observed in dyslexics who activated both left inferior frontal sulcus and left posterior superior temporal sulcus, consistent with the use of culturally independent strategies when reading is less efficient. By dissociating the effect of dyslexia from differences in Chinese and English normal reading, our results reconcile brain activation results with a substantial body of behavioural studies showing commonalities in the cognitive manifestation of dyslexia in Chinese and English populations. They also demonstrate the influence of cognitive ability and learning environment on a common neural system for reading. PMID:20488886

Developmental dyslexia in Chinese and English populations: dissociating the effect of dyslexia from language differences.

PubMed

Hu, Wei; Lee, Hwee Ling; Zhang, Qiang; Liu, Tao; Geng, Li Bo; Seghier, Mohamed L; Shakeshaft, Clare; Twomey, Tae; Green, David W; Yang, Yi Ming; Price, Cathy J

2010-06-01

Previous neuroimaging studies have suggested that developmental dyslexia has a different neural basis in Chinese and English populations because of known differences in the processing demands of the Chinese and English writing systems. Here, using functional magnetic resonance imaging, we provide the first direct statistically based investigation into how the effect of dyslexia on brain activation is influenced by the Chinese and English writing systems. Brain activation for semantic decisions on written words was compared in English dyslexics, Chinese dyslexics, English normal readers and Chinese normal readers, while controlling for all other experimental parameters. By investigating the effects of dyslexia and language in one study, we show common activation in Chinese and English dyslexics despite different activation in Chinese versus English normal readers. The effect of dyslexia in both languages was observed as less than normal activation in the left angular gyrus and in left middle frontal, posterior temporal and occipitotemporal regions. Differences in Chinese and English normal reading were observed as increased activation for Chinese relative to English in the left inferior frontal sulcus; and increased activation for English relative to Chinese in the left posterior superior temporal sulcus. These cultural differences were not observed in dyslexics who activated both left inferior frontal sulcus and left posterior superior temporal sulcus, consistent with the use of culturally independent strategies when reading is less efficient. By dissociating the effect of dyslexia from differences in Chinese and English normal reading, our results reconcile brain activation results with a substantial body of behavioural studies showing commonalities in the cognitive manifestation of dyslexia in Chinese and English populations. They also demonstrate the influence of cognitive ability and learning environment on a common neural system for reading.

A One-Hour Sleep Restriction Impacts Brain Processing in Young Children Across Tasks: Evidence From Event-related Potentials

PubMed Central

Molfese, Dennis L.; Ivanenko, Anna; Key, Alexandra Fonaryova; Roman, Adrienne; Molfese, Victoria J.; O'Brien, Louise M.; Gozal, David; Kota, Srinivas; Hudac, Caitlin M.

2014-01-01

The effect of mild sleep restriction on cognitive functioning in young children is unclear, yet sleep loss may impact children's abilities to attend to tasks with high processing demands. In a preliminary investigation, six children (6.6 - 8.3 years of age) with normal sleep patterns performed three tasks: attention (“Oddball”), speech perception (conconant-vowel syllables) and executive function (Directional Stroop). Event-related potentials (ERP) responses were recorded before (Control) and following one-week of 1-hour per day of sleep restriction. Brain activity across all tasks following Sleep Restriction differed from activity during Control Sleep, indicating that minor sleep restriction impacts children's neurocognitive functioning. PMID:23862635

Demeclocycline as a contrast agent for detecting brain neoplasms using confocal microscopy

NASA Astrophysics Data System (ADS)

Wirth, Dennis; Smith, Thomas W.; Moser, Richard; Yaroslavsky, Anna N.

2015-04-01

Complete resection of brain tumors improves life expectancy and quality. Thus, there is a strong need for high-resolution detection and microscopically controlled removal of brain neoplasms. The goal of this study was to test demeclocycline as a contrast enhancer for the intraoperative detection of brain tumors. We have imaged benign and cancerous brain tumors using multimodal confocal microscopy. The tumors investigated included pituitary adenoma, meningiomas, glioblastomas, and metastatic brain cancers. Freshly excised brain tissues were stained in 0.75 mg ml-1 aqueous solution of demeclocyline. Reflectance images were acquired at 402 nm. Fluorescence signals were excited at 402 nm and registered between 500 and 540 nm. After imaging, histological sections were processed from the imaged specimens and compared to the optical images. Fluorescence images highlighted normal and cancerous brain cells, while reflectance images emphasized the morphology of connective tissue. The optical and histological images were in accordance with each other for all types of tumors investigated. Demeclocyline shows promise as a contrast agent for intraoperative detection of brain tumors.

Cumulative Brain Injury from Motor Vehicle-Induced Whole-Body Vibration and Prevention by Human Apolipoprotein A-I Molecule Mimetic (4F) Peptide (an Apo A-I Mimetic).

PubMed

Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; Yan, Yuhui; LoGiudice, John; Sanger, James R; Matloub, Hani S; Pritchard, Kirkwood A; Jaradeh, Safwan S; Havlik, Robert

2015-12-01

Insidious cumulative brain injury from motor vehicle-induced whole-body vibration (MV-WBV) has not yet been studied. The objective of the present study is to validate whether whole-body vibration for long periods causes cumulative brain injury and impairment of the cerebral function. We also explored a preventive method for MV-WBV injury. A study simulating whole-body vibration was conducted in 72 male Sprague-Dawley rats divided into 9 groups (N = 8): (1) 2-week normal control; (2) 2-week sham control (in the tube without vibration); (3) 2-week vibration (exposed to whole-body vibration at 30 Hz and .5 G acceleration for 4 hours/day, 5 days/week for 2 weeks; vibration parameters in the present study are similar to the most common driving conditions); (4) 4-week sham control; (5) 4-week vibration; (6) 4-week vibration with human apolipoprotein A-I molecule mimetic (4F)-preconditioning; (7) 8-week sham control; (8) 8-week vibration; and (9) 8-week 4F-preconditioning group. All the rats were evaluated by behavioral, physiological, and histological studies of the brain. Brain injury from vibration is a cumulative process starting with cerebral vasoconstriction, squeezing of the endothelial cells, increased free radicals, decreased nitric oxide, insufficient blood supply to the brain, and repeated reperfusion injury to brain neurons. In the 8-week vibration group, which indicated chronic brain edema, shrunken neuron numbers increased and whole neurons atrophied, which strongly correlated with neural functional impairment. There was no prominent brain neuronal injury in the 4F groups. The present study demonstrated cumulative brain injury from MV-WBV and validated the preventive effects of 4F preconditioning. Copyright © 2015 National Stroke Association. All rights reserved.

Daily supplementation with mushroom (Agaricus bisporus) improves balance and working memory in aged rats

USDA-ARS?s Scientific Manuscript database

Animals and humans show decrements in motor control, cognition, and brain function during normal aging, partly due to the long-term effects of oxidative stress and inflammation. Recent studies have identified a number of fruits and vegetables, whose phytochemical make-up contains potent antioxidant ...

Altered blood-brain barrier permeability in rats with prehepatic portal hypertension turns to normal when portal pressure is lowered

PubMed Central

Eizayaga, Francisco; Scorticati, Camila; Prestifilippo, Juan P; Romay, Salvador; Fernandez, Maria A; Castro, José L; Lemberg, Abraham; Perazzo, Juan C

2006-01-01

AIM: To study the blood-brain barrier integrity in prehepatic portal hypertensive rats induced by partial portal vein ligation, at 14 and 40 d after ligation when portal pressure is spontaneously normalized. METHODS: Adult male Wistar rats were divided into four groups: Group I: Sham14d , sham operated; Group II: PH14d , portal vein stenosis; (both groups were used 14 days after surgery); Group III: Sham40d, Sham operated and Group IV: PH40d Portal vein stenosis (Groups II and IV used 40 d after surgery). Plasma ammonia, plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined. Trypan and Evans blue dyes, systemically injected, were investigated in hippocampus to study blood-brain barrier integrity. Portal pressure was periodically recorded. RESULTS: Forty days after stricture, portal pressure was normalized, plasma ammonia was moderately high, and both dyes were absent in central nervous system parenchyma. All other parameters were reestablished. When portal pressure was normalized and ammonia level was lowered, but not normal, the altered integrity of blood-brain barrier becomes reestablished. CONCLUSION: The impairment of blood-brain barrier and subsequent normalization could be a mechanism involved in hepatic encephalopathy reversibility. Hemodynamic changes and ammonia could trigger blood-brain barrier alterations and its reestablishment. PMID:16552803

Resonance Raman imaging for detecting and monitoring molecular pathological changes in human brain tumors related to Warburg effect

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; Zhu, Ke; Zhang, Chunyuan; Yang, Yang; Yu, Xinguang; Hu, Hailong; Cheng, Gangge; Wu, Binlin; Shi, Lingyan; Alfano, Robert R.

2018-02-01

The goal of the research is to determine the prognostic molecular pathological changes in components and composition, for human brain glioma gradings in comparison with normal tissues in three-dimensional Raman imaging profiles by visible Resonance Raman (VRR) imaging. VRR images from twenty-five specimens including three healthy tissues, one normal control, and twenty-one glioma tissues of grades II, II-III and III-IV with histology examination were measured and investigated using WITec300R confocal micro Raman imaging system with laser excitation of 532nm. Two-dimensional RR spectral mappings performed in 20μm x 20μm generated 400 images which integrated the intensity of the specific biochemical bonds as the third dimension. The three-dimension (3D) map demonstrated the spatial distributions of three selected sets of RR spectra of molecular biomarkers, and revealed significant differences in the spectra between normal and glioma tissues of different grades due to the composition changes in key molimageecules. These RR molecular spectral fingerprints have displayed: a clear enhancement of RR vibrational modes at 1129-1131cm-1 and 2934cm-1 which are supposed to be arising from lipoproteins; evident decreased RR vibrational modes at 1442cm-1 and 2854cm-1 which are from saturated fatty acids bonds in all-grades of glioma brain tissues compared with normal tissues; and the enhanced RR spectral modes of 1129 cm-1 and 2938cm-1 which suggest contribution from lactate. These findings may provide a novel proof for anaerobic glycolysis metabolic process in brain glioma cancer tissues that has been explained by Warburg effects.

Rethinking schizophrenia in the context of normal neurodevelopment

PubMed Central

Catts, Vibeke S.; Fung, Samantha J.; Long, Leonora E.; Joshi, Dipesh; Vercammen, Ans; Allen, Katherine M.; Fillman, Stu G.; Rothmond, Debora A.; Sinclair, Duncan; Tiwari, Yash; Tsai, Shan-Yuan; Weickert, Thomas W.; Shannon Weickert, Cynthia

2013-01-01

The schizophrenia brain is differentiated from the normal brain by subtle changes, with significant overlap in measures between normal and disease states. For the past 25 years, schizophrenia has increasingly been considered a neurodevelopmental disorder. This frame of reference challenges biological researchers to consider how pathological changes identified in adult brain tissue can be accounted for by aberrant developmental processes occurring during fetal, childhood, or adolescent periods. To place schizophrenia neuropathology in a neurodevelopmental context requires solid, scrutinized evidence of changes occurring during normal development of the human brain, particularly in the cortex; however, too often data on normative developmental change are selectively referenced. This paper focuses on the development of the prefrontal cortex and charts major molecular, cellular, and behavioral events on a similar time line. We first consider the time at which human cognitive abilities such as selective attention, working memory, and inhibitory control mature, emphasizing that attainment of full adult potential is a process requiring decades. We review the timing of neurogenesis, neuronal migration, white matter changes (myelination), and synapse development. We consider how molecular changes in neurotransmitter signaling pathways are altered throughout life and how they may be concomitant with cellular and cognitive changes. We end with a consideration of how the response to drugs of abuse changes with age. We conclude that the concepts around the timing of cortical neuronal migration, interneuron maturation, and synaptic regression in humans may need revision and include greater emphasis on the protracted and dynamic changes occurring in adolescence. Updating our current understanding of post-natal neurodevelopment should aid researchers in interpreting gray matter changes and derailed neurodevelopmental processes that could underlie emergence of psychosis. PMID:23720610

Contribution of four lifelong factors of cognitive reserve on late cognition in normal aging and Parkinson's disease.

PubMed

Rouillard, Maud; Audiffren, Michel; Albinet, Cédric; Ali Bahri, Mohamed; Garraux, Gaëtan; Collette, Fabienne

2017-03-01

Cognitive reserve (CR) was proposed to explain how individual differences in brain function help to cope with the effects of normal aging and neurodegenerative diseases. Education, professional solicitations, and engagement in leisure and physical activities across the lifetime are considered as major determinants of this reserve. Using multiple linear regression analyses, we tested separately in healthy elderly and Parkinson's disease (PD) populations to what extent cognitive performance in several domains was explained by (a) any of these four environmental lifespan variables; (b) demographic and clinical variables (age, gender, depression score, and, for the PD group, duration of disease and dopaminergic drugs). We also tested for an interaction, if any, between these lifespan variables and brain pathology indexed by global atrophy measured from high-resolution anatomical magnetic resonance imaging. Age was negatively associated with cognitive performance in the PD group. In healthy elderly participants, we observed significant positive associations between cognitive performance and (a) education, (b) leisure activities, and (c) professional solicitation (decisional latitude). Furthermore, participants with greater brain atrophy benefited more from CR. In PD patients, education and professional solicitations contributed to cognitive performance but to a lesser extent than in controls. CR factors modulated the relationship between cognition and brain atrophy only in patients with a slight or moderate brain atrophy. Education is the CR factor that contributed the most to late cognitive functioning in both groups, closely followed by leisure activity in normal aging and professional solicitations in PD. Our results also provide evidence suggesting that the effects of CR does not express similarly in normal aging and PD. From a broader perspective, these results seem to indicate that CR factors the most consistently practiced across lifespan (education and professional solicitation) are those that are the more strongly associated to late cognitive efficiency.

Effect of experimental diabetes on the levels of aromatic and branched-chain amino acids in rat blood and brain.

PubMed

Crandall, E A; Fernstrom, J D

1983-03-01

Male rats treated 3 wk earlier with streptozotocin showed abnormally high blood levels of leucine, isoleucine, and valine throughout the 24-h period. Serum phenylalanine levels were slightly increased, while those of tryptophan and tyrosine were occasionally reduced. In brain, the level of each branched-chain amino acid was significantly increased above normal at all times. The brain concentration of each aromatic amino acid was always below normal. These changes were restored almost to normal by exogenous insulin therapy. Since the ingestion of protein is normally a major factor influencing blood amino acid levels, the effect of ingesting single, protein-containing meals on the blood and brain levels of these amino acids was also studied. After an overnight fast, the ingestion of a protein-containing meal by diabetic rats increased substantially both blood and brain levels of each branched-chain amino acid. No such increases occurred in normal rats. Ingestion of this meal produced only small changes in the brain and blood levels of the aromatic amino acids in both diabetic and normal rats. The changes in the brain level of each large neutral amino acid in some cases paralleled those in its blood level. More often, they paralleled the changes in the blood ratio of each amino acid to the sum of the other aromatic and branched-chain amino acids. This ratio is often a good predictor of the competitive transport of these amino acids into brain (Fernstrom and Faller, 1978). The observed changes in the brain levels of these amino acids in diabetes may influence the rates at which they are consumed in metabolic pathways within this organ.

Cortical venous disease severity in MELAS syndrome correlates with brain lesion development.

PubMed

Whitehead, M T; Wien, M; Lee, B; Bass, N; Gropman, A

2017-08-01

MELAS syndrome is a mitochondrial disorder typified by recurrent stroke-like episodes, seizures, and progressive brain injury. Abnormal mitochondria have been found in arterial walls implicating a vasculogenic etiology. We have observed abnormal cortical vein T2/FLAIR signal in MELAS patients, potentially representing wall thickening and sluggish flow. We sought to examine the relationship of hyperintense veins and brain lesions in MELAS. Imaging databases at two children's hospitals were searched for brain MRIs from MELAS patients. Artifact, sedated exams, and lack of 2D-T2/FLAIR sequences were exclusion criteria. Each exam was assigned a venous score based on number of T2/FLAIR hyperintense veins: 1 = <10, 2 = 10 to 20, 3 = >20. Cumulative brain lesions and venous score in MELAS and aged-matched normal exams were compared by Mann-Whitney test. A total of 106 exams from 14 unique MELAS patients (mean 16 ± 3 years) and 30 exams from normal aged-matched patients (mean 15 ± 3 years) were evaluated. Median venous score between MELAS and control patients significantly differed (3 versus 1; p < 0.001). In the MELAS group, venous score correlated with presence (median = 3) or absence (median = 1) of cumulative brain lesions. In all 8 MELAS patients who developed lesions, venous hyperintensity was present prior to, during, and after lesion onset. Venous score did not correlate with brain lesion acuity. Abnormal venous signal correlates with cumulative brain lesion severity in MELAS syndrome. Cortical venous stenosis, congestion, and venous ischemia may be mechanisms of brain injury. Identification of cortical venous pathology may aid in diagnosis and could be predictive of lesion development.

Quantitative Folding Pattern Analysis of Early Primary Sulci in Human Fetuses with Brain Abnormalities.

PubMed

Im, K; Guimaraes, A; Kim, Y; Cottrill, E; Gagoski, B; Rollins, C; Ortinau, C; Yang, E; Grant, P E

2017-07-01

Aberrant gyral folding is a key feature in the diagnosis of many cerebral malformations. However, in fetal life, it is particularly challenging to confidently diagnose aberrant folding because of the rapid spatiotemporal changes of gyral development. Currently, there is no resource to measure how an individual fetal brain compares with normal spatiotemporal variations. In this study, we assessed the potential for automatic analysis of early sulcal patterns to detect individual fetal brains with cerebral abnormalities. Triplane MR images were aligned to create a motion-corrected volume for each individual fetal brain, and cortical plate surfaces were extracted. Sulcal basins were automatically identified on the cortical plate surface and compared with a combined set generated from 9 normal fetal brain templates. Sulcal pattern similarities to the templates were quantified by using multivariate geometric features and intersulcal relationships for 14 normal fetal brains and 5 fetal brains that were proved to be abnormal on postnatal MR imaging. Results were compared with the gyrification index. Significantly reduced sulcal pattern similarities to normal templates were found in all abnormal individual fetuses compared with normal fetuses (mean similarity [normal, abnormal], left: 0.818, 0.752; P < .001; right: 0.810, 0.753; P < .01). Altered location and depth patterns of sulcal basins were the primary distinguishing features. The gyrification index was not significantly different between the normal and abnormal groups. Automated analysis of interrelated patterning of early primary sulci could outperform the traditional gyrification index and has the potential to quantitatively detect individual fetuses with emerging abnormal sulcal patterns. © 2017 by American Journal of Neuroradiology.

Brain Entropy Mapping Using fMRI

PubMed Central

Wang, Ze; Li, Yin; Childress, Anna Rose; Detre, John A.

2014-01-01

Entropy is an important trait for life as well as the human brain. Characterizing brain entropy (BEN) may provide an informative tool to assess brain states and brain functions. Yet little is known about the distribution and regional organization of BEN in normal brain. The purpose of this study was to examine the whole brain entropy patterns using a large cohort of normal subjects. A series of experiments were first performed to validate an approximate entropy measure regarding its sensitivity, specificity, and reliability using synthetic data and fMRI data. Resting state fMRI data from a large cohort of normal subjects (n = 1049) from multi-sites were then used to derive a 3-dimensional BEN map, showing a sharp low-high entropy contrast between the neocortex and the rest of brain. The spatial heterogeneity of resting BEN was further studied using a data-driven clustering method, and the entire brain was found to be organized into 7 hierarchical regional BEN networks that are consistent with known structural and functional brain parcellations. These findings suggest BEN mapping as a physiologically and functionally meaningful measure for studying brain functions. PMID:24657999

Comparison of WBRT alone, SRS alone, and their combination in the treatment of one or more brain metastases: Review and meta-analysis.

PubMed

Khan, Muhammad; Lin, Jie; Liao, Guixiang; Li, Rong; Wang, Baiyao; Xie, Guozhu; Zheng, Jieling; Yuan, Yawei

2017-07-01

Whole brain radiotherapy has been a standard treatment of brain metastases. Stereotactic radiosurgery provides more focal and aggressive radiation and normal tissue sparing but worse local and distant control. This meta-analysis was performed to assess and compare the effectiveness of whole brain radiotherapy alone, stereotactic radiosurgery alone, and their combination in the treatment of brain metastases based on randomized controlled trial studies. Electronic databases (PubMed, MEDLINE, Embase, and Cochrane Library) were searched to identify randomized controlled trial studies that compared treatment outcome of whole brain radiotherapy and stereotactic radiosurgery. This meta-analysis was performed using the Review Manager (RevMan) software (version 5.2) that is provided by the Cochrane Collaboration. The data used were hazard ratios with 95% confidence intervals calculated for time-to-event data extracted from survival curves and local tumor control rate curves. Odds ratio with 95% confidence intervals were calculated for dichotomous data, while mean differences with 95% confidence intervals were calculated for continuous data. Fixed-effects or random-effects models were adopted according to heterogeneity. Five studies (n = 763) were included in this meta-analysis meeting the inclusion criteria. All the included studies were randomized controlled trials. The sample size ranged from 27 to 331. In total 202 (26%) patients with whole brain radiotherapy alone, 196 (26%) patients receiving stereotactic radiosurgery alone, and 365 (48%) patients were in whole brain radiotherapy plus stereotactic radiosurgery group. No significant survival benefit was observed for any treatment approach; hazard ratio was 1.19 (95% confidence interval: 0.96-1.43, p = 0.12) based on three randomized controlled trials for whole brain radiotherapy only compared to whole brain radiotherapy plus stereotactic radiosurgery and hazard ratio was 1.03 (95% confidence interval: 0.82-1.29, p = 0.81) for stereotactic radiosurgery only compared to combined approach. Local control was best achieved when whole brain radiotherapy was combined with stereotactic radiosurgery. Hazard ratio 2.05 (95% confidence interval: 1.36-3.09, p = 0.0006) and hazard ratio 1.84 (95% confidence interval: 1.26-2.70, p = 0.002) were obtained from comparing whole brain radiotherapy only and stereotactic radiosurgery only to whole brain radiotherapy + stereotactic radiosurgery, respectively. No difference in adverse events for treatment difference; odds ratio 1.16 (95% confidence interval: 0.77-1.76, p = 0.48) and odds ratio 0.92 (95% confidence interval: 0.59-1.42, p = 71) for whole brain radiotherapy + stereotactic radiosurgery versus whole brain radiotherapy only and whole brain radiotherapy + stereotactic radiosurgery versus stereotactic radiosurgery only, respectively. Adding stereotactic radiosurgery to whole brain radiotherapy provides better local control as compared to whole brain radiotherapy only and stereotactic radiosurgery only with no difference in radiation related toxicities.

Amelioration of Acute Sequelae of Blast Induced Mild Traumatic Brain Injury by N-Acetyl Cysteine: A Double-Blind, Placebo Controlled Study

DTIC Science & Technology

2013-01-23

turning of the subjects head by the investigator [17]), an abnormal Romberg /tandem Rom- berg test (excessive swaying or falling while attempting to stand...of ,22. Criteria for resolution of balance dysfunction were no subjective dizziness, normal head thrust and Romberg tests , and a normal DGI...Agrawal Y, Carey JP, Hoffman HJ, Sklare DA, Schubert MC (2011) The modified Romberg Balance Test : normative data in U.S. adults. Otol Neurotol 32: 309–311

Spatial working memory in heavy cannabis users: a functional magnetic resonance imaging study.

PubMed

Kanayama, Gen; Rogowska, Jadwiga; Pope, Harrison G; Gruber, Staci A; Yurgelun-Todd, Deborah A

2004-11-01

Many neuropsychological studies have documented deficits in working memory among recent heavy cannabis users. However, little is known about the effects of cannabis on brain activity. We assessed brain function among recent heavy cannabis users while they performed a working memory task. Functional magnetic resonance imaging was used to examine brain activity in 12 long-term heavy cannabis users, 6-36 h after last use, and in 10 control subjects while they performed a spatial working memory task. Regional brain activation was analyzed and compared using statistical parametric mapping techniques. Compared with controls, cannabis users exhibited increased activation of brain regions typically used for spatial working memory tasks (such as prefrontal cortex and anterior cingulate). Users also recruited additional regions not typically used for spatial working memory (such as regions in the basal ganglia). These findings remained essentially unchanged when re-analyzed using subjects' ages as a covariate. Brain activation showed little or no significant correlation with subjects' years of education, verbal IQ, lifetime episodes of cannabis use, or urinary cannabinoid levels at the time of scanning. Recent cannabis users displayed greater and more widespread brain activation than normal subjects when attempting to perform a spatial working memory task. This observation suggests that recent cannabis users may experience subtle neurophysiological deficits, and that they compensate for these deficits by "working harder"-calling upon additional brain regions to meet the demands of the task.

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

Evaluation and diagnosis of brain death by functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Pan, Boan; Zhong, Fulin; Huang, Xiaobo; Pan, Lingai; Lu, Sen; Li, Ting

2017-02-01

Brain death, the irreversible and permanent loss of the brain and brainstem functions, is hard to be judged precisely for some clinical reasons. The traditional diagnostic methods are time consuming, expensive and some are even dangerous. Functional near infrared spectroscopy (FNIRS), using the good scattering properties of major component of blood to NIR, is capable of noninvasive monitoring cerebral hemodynamic responses. Here, we attempt to use portable FNIRS under patients' natural state for brain death diagnosis. Ten brain death patients and seven normal subjects participated in FNIRS measurements. All of them were provided different fractional concentration of inspired oxygen (FIO2) in different time periods. We found that the concentration variation of deoxyhemoglobin concentration (Δ[Hb]) presents the trend of decrease in the both brain death patients and normal subjects with the raise of the FIO2, however, the data in the normal subjects is more significant. And the concentration variation of oxyhemoglobins concentration (Δ[HbO2]) emerges the opposite trends. Thus Δ[HbO2]/Δ[Hb] in brain death patients is significantly higher than normal subjects, and emerges the rising trend as time went on. The findings indicated the potential of FNIRS-measured hemodynamic index in diagnosing brain death.

Diffuse traumatic axonal injury in mice induces complex behavioural alterations that are normalized by neutralization of interleukin-1β.

PubMed

Ekmark-Lewén, Sara; Flygt, Johanna; Fridgeirsdottir, Gudrun A; Kiwanuka, Olivia; Hånell, Anders; Meyerson, Bengt J; Mir, Anis K; Gram, Hermann; Lewén, Anders; Clausen, Fredrik; Hillered, Lars; Marklund, Niklas

2016-04-01

Widespread traumatic axonal injury (TAI) results in brain network dysfunction, which commonly leads to persisting cognitive and behavioural impairments following traumatic brain injury (TBI). TBI induces a complex neuroinflammatory response, frequently located at sites of axonal pathology. The role of the pro-inflammatory cytokine interleukin (IL)-1β has not been established in TAI. An IL-1β-neutralizing or a control antibody was administered intraperitoneally at 30 min following central fluid percussion injury (cFPI), a mouse model of widespread TAI. Mice subjected to moderate cFPI (n = 41) were compared with sham-injured controls (n = 20) and untreated, naive mice (n = 9). The anti-IL-1β antibody reached the target brain regions in adequate therapeutic concentrations (up to ~30 μg/brain tissue) at 24 h post-injury in both cFPI (n = 5) and sham-injured (n = 3) mice, with lower concentrations at 72 h post-injury (up to ~18 μg/g brain tissue in three cFPI mice). Functional outcome was analysed with the multivariate concentric square field (MCSF) test at 2 and 9 days post-injury, and the Morris water maze (MWM) at 14-21 days post-injury. Following TAI, the IL-1β-neutralizing antibody resulted in an improved behavioural outcome, including normalized behavioural profiles in the MCSF test. The performance in the MWM probe (memory) trial was improved, although not in the learning trials. The IL-1β-neutralizing treatment did not influence cerebral ventricle size or the number of microglia/macrophages. These findings support the hypothesis that IL-1β is an important contributor to the processes causing complex cognitive and behavioural disturbances following TAI. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Functional brain mapping of actual car-driving using [18F]FDG-PET.

PubMed

Jeong, Myeonggi; Tashiro, Manabu; Singh, Laxsmi N; Yamaguchi, Keiichiro; Horikawa, Etsuo; Miyake, Masayasu; Watanuki, Shouichi; Iwata, Ren; Fukuda, Hiroshi; Takahashi, Yasuo; Itoh, Masatoshi

2006-11-01

This study aims at identifying the brain activation during actual car-driving on the road, and at comparing the results to those of previous studies on simulated car-driving. Thirty normal volunteers, aged 20 to 56 years, were divided into three subgroups, active driving, passive driving and control groups, for examination by positron emission tomography (PET) and [18F]2-deoxy-2-fluoro-D-glucose (FDG). The active driving subjects (n = 10) drove for 30 minutes on quiet normal roads with a few traffic signals. The passive driving subjects (n = 10) participated as passengers on the front seat. The control subjects (n = 10) remained seated in a lit room with their eyes open. Voxel-based t-statistics were applied using SPM2 to search brain activation among the subgroups mentioned above. Significant brain activation was detected during active driving in the primary and secondary visual cortices, primary sensorimotor areas, premotor area, parietal association area, cingulate gyrus, the parahippocampal gyrus as well as in thalamus and cerebellum. The passive driving manifested a similar-looking activation pattern, lacking activations in the premotor area, cingulate and parahippocampal gyri and thalamus. Direct comparison of the active and passive driving conditions revealed activation in the cerebellum. The result of actual driving looked similar to that of simulated driving, suggesting that visual perception and visuomotor coordination were the main brain functions while driving. In terms of attention and autonomic arousal, however, it seems there was a significant difference between simulated and actual driving possibly due to risk of accidents. Autonomic and emotional aspects of driving should be studied using an actual driving study-design.

Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance

PubMed Central

Castellano, Christian-Alexandre; Baillargeon, Jean-Patrice; Nugent, Scott; Tremblay, Sébastien; Fortier, Mélanie; Imbeault, Hélène; Duval, Julie; Cunnane, Stephen C.

2015-01-01

Objective To investigate whether cerebral metabolic rate of glucose (CMRglu) is altered in normal weight young women with polycystic ovary syndrome (PCOS) who exhibit mild insulin resistance. Materials and methods Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR). A battery of cognitive tests was administered to evaluate working memory, attention and executive function. Results The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035) compared to the Controls. The PCOS group had 9–14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018). A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05). Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group. Conclusions The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer’s disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted. PMID:26650926

Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance.

PubMed

Castellano, Christian-Alexandre; Baillargeon, Jean-Patrice; Nugent, Scott; Tremblay, Sébastien; Fortier, Mélanie; Imbeault, Hélène; Duval, Julie; Cunnane, Stephen C

2015-01-01

To investigate whether cerebral metabolic rate of glucose (CMRglu) is altered in normal weight young women with polycystic ovary syndrome (PCOS) who exhibit mild insulin resistance. Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR). A battery of cognitive tests was administered to evaluate working memory, attention and executive function. The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035) compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018). A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05). Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group. The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

Network-Level Analysis of Cortical Thickness of the Epileptic Brain

PubMed Central

Raj, A; Mueller, S.G; Young, K; Laxer, K.D.; Weiner, M

2010-01-01

Temporal lobe epilepsy (TLE) characterized by an epileptogenic focus in the medial temporal lobe is the most common form of focal epilepsy. However, the seizures are not confined to the temporal lobe but can spread to other, anatomically connected brain regions where they can cause similar structural abnormalities as observed in the focus. The aim of this study was to derive whole brain networks from volumetric data and obtain network-centric measures which can capture cortical thinning characteristic for TLE and can be used for classifying a given MRI into TLE or normal, and to obtain additional summary statistics which relate to the extent and spread of the disease. T1 weighted whole brain images were acquired on a 4T magnet in 13 patients with TLE with mesial temporal lobe sclerosis (TLE-MTS), 14 patients with TLE with normal MRI (TLE-no) and 30 controls. Mean cortical thickness and curvature measurements were obtained using the Freesurfer software. These values were used to derive a graph, or network, for each subject. The nodes of the graph are brain regions, and edges represent disease progression paths. We show how to obtain summary statistics like mean, median and variance defined for these networks and to perform exploratory analyses like correlation and classification. Our results indicate that the proposed network approach can improve accuracy of classifying subjects into 2 groups (control and TLE), from 78% for non-network classifiers to 93% using the proposed approach. We also obtain network “peakiness” values using statistical measures like entropy and complexity - this appears to be a good characterizer of the disease, and may have utility in surgical planning. PMID:20553893

MR elastography of hydrocephalus

NASA Astrophysics Data System (ADS)

Pattison, Adam J.; Lollis, S. Scott; Perrinez, Phillip R.; Weaver, John B.; Paulsen, Keith D.

2009-02-01

Hydrocephalus occurs due to a blockage in the transmission of cerebrospinal fluid (CSF) in either the ventricles or subarachnoid space. Characteristics of this condition include increased intracranial pressure, which can result in neurologic deterioration [1]. Magnetic resonance elastography (MRE) is an imaging technique that estimates the mechanical properties of tissue in vivo. While some investigations of brain tissue have been performed using MRE [2,3,4,5], the effects due to changes in interstitial pressure and fluid content on the mechanical properties of the brain remain unknown. The purpose of this work is to assess the potential of MRE to differentiate between the reconstructed properties of normal and hydrocephalic brains. MRE data was acquired in 18 female feline subjects, 12 of which received kaolin injections resulting in an acute form of hydrocephalus. In each animal, four MRE scans were performed during the process including one pre-injection and three post-injection scans. The elastic parameters were obtained using a subzone-based reconstruction algorithm that solves Navier's equations for linearly elastic materials [6]. The remaining cats were used as controls, injected with saline instead of kaolin. To determine the state of hydrocephalus, ventricular volume was estimated from segmenting anatomical images. The mean ventricular volume of hydrocephalic cats significantly increased (P <~ 0.0001) between the first and second scans. The mean volume was not observed to increase (P >~ 0.5) for the control cats. Also, there was an observable increase in the recorded elastic shear modulus of brain tissue in the normal and hydrocephalic acquisitions. Results suggest that MRE is able to detect changes in the mechanical properties of brain tissue resulting from kaolin-induced hydrocephalus, indicating the need for further study.

Identification of the boundary between normal brain tissue and ischemia region using two-photon excitation fluorescence microscopy

NASA Astrophysics Data System (ADS)

Du, Huiping; Wang, Shu; Wang, Xingfu; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

2016-10-01

Ischemic stroke is one of the common neurological diseases, and it is becoming the leading causes of death and permanent disability around the world. Early and accurate identification of the potentially salvageable boundary region of ischemia brain tissues may enable selection of the most appropriate candidates for early stroke therapies. In this work, TPEF microscopy was used to image the microstructures of normal brain tissues, ischemia regions and the boundary region between normal and ischemia brain tissues. The ischemia brain tissues from Sprague-Dawley (SD) rats were subjected to 6 hours of middle cerebral artery occlusion (MCAO). Our study demonstrates that TPEF microscopy has the ability to not only reveal the morphological changes of the neurons but also identify the boundary between normal brain tissue and ischemia region, which correspond well to the hematoxylin and eosin (H and E) stained images. With the development of miniaturized TPEF microscope imaging devices, TPEF microscopy can be developed into an effectively diagnostic and monitoring tool for cerebral ischemia.

Brain cancer probed by native fluorescence and stokes shift spectroscopy

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; He, Yong; Pu, Yang; Li, Qingbo; Wang, Wei; Alfano, Robert R.

2012-12-01

Optical biopsy spectroscopy was applied to diagnosis human brain cancer in vitro. The spectra of native fluorescence, Stokes shift and excitation spectra were obtained from malignant meningioma, benign, normal meningeal tissues and acoustic neuroma benign tissues. The wide excitation wavelength ranges were used to establish the criterion for distinguishing brain diseases. The alteration of fluorescence spectra between normal and abnormal brain tissues were identified by the characteristic fluorophores under the excitation with UV to visible wavelength range. It was found that the ratios of the peak intensities and peak position in both spectra of fluorescence and Stokes shift may be used to diagnose human brain meninges diseases. The preliminary analysis of fluorescence spectral data from cancer and normal meningeal tissues by basic biochemical component analysis model (BBCA) and Bayes classification model based on statistical methods revealed the changes of components, and classified the difference between cancer and normal human brain meningeal tissues in a predictions accuracy rate is 0.93 in comparison with histopathology and immunohistochemistry reports (gold standard).

Glycolysis and the pentose phosphate pathway after human traumatic brain injury: microdialysis studies using 1,2-13C2 glucose

PubMed Central

Jalloh, Ibrahim; Carpenter, Keri L H; Grice, Peter; Howe, Duncan J; Mason, Andrew; Gallagher, Clare N; Helmy, Adel; Murphy, Michael P; Menon, David K; Carpenter, T Adrian; Pickard, John D; Hutchinson, Peter J

2015-01-01

Increased ‘anaerobic' glucose metabolism is observed after traumatic brain injury (TBI) attributed to increased glycolysis. An alternative route is the pentose phosphate pathway (PPP), which generates putatively protective and reparative molecules. To compare pathways we employed microdialysis to perfuse 1,2-13C2 glucose into the brains of 15 TBI patients and macroscopically normal brain in six patients undergoing surgery for benign tumors, and to simultaneously collect products for nuclear magnetic resonance (NMR) analysis. 13C enrichment for glycolytic 2,3-13C2 lactate was the median 5.4% (interquartile range (IQR) 4.6–7.5%) in TBI brain and 4.2% (2.4–4.4%) in ‘normal' brain (P<0.01). The ratio of PPP-derived 3-13C lactate to glycolytic 2,3-13C2 lactate was median 4.9% (3.6–8.2%) in TBI brain and 6.7% (6.3–8.9%) in ‘normal' brain. An inverse relationship was seen for PPP-glycolytic lactate ratio versus PbtO2 (r=−0.5, P=0.04) in TBI brain. Thus, glycolytic lactate production was significantly greater in TBI than ‘normal' brain. Several TBI patients exhibited PPP–lactate elevation above the ‘normal' range. There was proportionally greater PPP-derived lactate production with decreasing PbtO2. The study raises questions about the roles of the PPP and glycolysis after TBI, and whether they can be manipulated to achieve a better outcome. This study is the first direct comparison of glycolysis and PPP in human brain. PMID:25335801

Antidepressants normalize the default mode network in patients with dysthymia.

PubMed

Posner, Jonathan; Hellerstein, David J; Gat, Inbal; Mechling, Anna; Klahr, Kristin; Wang, Zhishun; McGrath, Patrick J; Stewart, Jonathan W; Peterson, Bradley S

2013-04-01

The default mode network (DMN) is a collection of brain regions that reliably deactivate during goal-directed behaviors and is more active during a baseline, or so-called resting, condition. Coherence of neural activity, or functional connectivity, within the brain's DMN is increased in major depressive disorder relative to healthy control (HC) subjects; however, whether similar abnormalities are present in persons with dysthymic disorder (DD) is unknown. Moreover, the effect of antidepressant medications on DMN connectivity in patients with DD is also unknown. To use resting-state functional-connectivity magnetic resonance imaging (MRI) to study (1) the functional connectivity of the DMN in subjects with DD vs HC participants and (2) the effects of antidepressant therapy on DMN connectivity. After collecting baseline MRI scans from subjects with DD and HC participants, we enrolled the participants with DD into a 10-week prospective, double-blind, placebo-controlled trial of duloxetine and collected MRI scans again at the conclusion of the study. Enrollment occurred between 2007 and 2011. University research institute. Volunteer sample of 41 subjects with DD and 25 HC participants aged 18 to 53 years. Control subjects were group matched to patients with DD by age and sex. We used resting-state functional-connectivity MRI to measure the functional connectivity of the brain's DMN in persons with DD compared with HC subjects, and we examined the effects of treatment with duloxetine vs placebo on DMN connectivity. Of the 41 subjects with DD, 32 completed the clinical trial and MRI scans, along with the 25 HC participants. At baseline, we found that the coherence of neural activity within the brain's DMN was greater in persons with DD compared with HC subjects. Following a 10-week clinical trial, we found that treatment with duloxetine, but not placebo, normalized DMN connectivity. The baseline imaging findings are consistent with those found in patients with major depressive disorder and suggest that increased connectivity within the DMN may be important in the pathophysiology of both acute and chronic manifestations of depressive illness. The normalization of DMN connectivity following antidepressant treatment suggests an important causal pathway through which antidepressants may reduce depression.

Do acute phase markers explain body temperature and brain temperature after ischemic stroke?

PubMed Central

Whiteley, William N.; Thomas, Ralph; Lowe, Gordon; Rumley, Ann; Karaszewski, Bartosz; Armitage, Paul; Marshall, Ian; Lymer, Katherine; Dennis, Martin

2012-01-01

Objective: Both brain and body temperature rise after stroke but the cause of each is uncertain. We investigated the relationship between circulating markers of inflammation with brain and body temperature after stroke. Methods: We recruited patients with acute ischemic stroke and measured brain temperature at hospital admission and 5 days after stroke with multivoxel magnetic resonance spectroscopic imaging in normal brain and the acute ischemic lesion (defined by diffusion-weighted imaging [DWI]). We measured body temperature with digital aural thermometers 4-hourly and drew blood daily to measure interleukin-6, C-reactive protein, and fibrinogen, for 5 days after stroke. Results: In 44 stroke patients, the mean temperature in DWI-ischemic brain soon after admission was 38.4°C (95% confidence interval [CI] 38.2–38.6), in DWI-normal brain was 37.7°C (95% CI 37.6–37.7), and mean body temperature was 36.6°C (95% CI 36.3–37.0). Higher mean levels of interleukin-6, C-reactive protein, and fibrinogen were associated with higher temperature in DWI-normal brain at admission and 5 days, and higher overall mean body temperature, but only with higher temperature in DWI-ischemic brain on admission. Conclusions: Systemic inflammation after stroke is associated with elevated temperature in normal brain and the body but not with later ischemic brain temperature. Elevated brain temperature is a potential mechanism for the poorer outcome observed in stroke patients with higher levels of circulating inflammatory markers. PMID:22744672

Error-related processing following severe traumatic brain injury: An event-related functional magnetic resonance imaging (fMRI) study

PubMed Central

Sozda, Christopher N.; Larson, Michael J.; Kaufman, David A.S.; Schmalfuss, Ilona M.; Perlstein, William M.

2011-01-01

Continuous monitoring of one’s performance is invaluable for guiding behavior towards successful goal attainment by identifying deficits and strategically adjusting responses when performance is inadequate. In the present study, we exploited the advantages of event-related functional magnetic resonance imaging (fMRI) to examine brain activity associated with error-related processing after severe traumatic brain injury (sTBI). fMRI and behavioral data were acquired while 10 sTBI participants and 12 neurologically-healthy controls performed a task-switching cued-Stroop task. fMRI data were analyzed using a random-effects whole-brain voxel-wise general linear model and planned linear contrasts. Behaviorally, sTBI patients showed greater error-rate interference than neurologically-normal controls. fMRI data revealed that, compared to controls, sTBI patients showed greater magnitude error-related activation in the anterior cingulate cortex (ACC) and an increase in the overall spatial extent of error-related activation across cortical and subcortical regions. Implications for future research and potential limitations in conducting fMRI research in neurologically-impaired populations are discussed, as well as some potential benefits of employing multimodal imaging (e.g., fMRI and event-related potentials) of cognitive control processes in TBI. PMID:21756946

Error-related processing following severe traumatic brain injury: an event-related functional magnetic resonance imaging (fMRI) study.

PubMed

Sozda, Christopher N; Larson, Michael J; Kaufman, David A S; Schmalfuss, Ilona M; Perlstein, William M

2011-10-01

Continuous monitoring of one's performance is invaluable for guiding behavior towards successful goal attainment by identifying deficits and strategically adjusting responses when performance is inadequate. In the present study, we exploited the advantages of event-related functional magnetic resonance imaging (fMRI) to examine brain activity associated with error-related processing after severe traumatic brain injury (sTBI). fMRI and behavioral data were acquired while 10 sTBI participants and 12 neurologically-healthy controls performed a task-switching cued-Stroop task. fMRI data were analyzed using a random-effects whole-brain voxel-wise general linear model and planned linear contrasts. Behaviorally, sTBI patients showed greater error-rate interference than neurologically-normal controls. fMRI data revealed that, compared to controls, sTBI patients showed greater magnitude error-related activation in the anterior cingulate cortex (ACC) and an increase in the overall spatial extent of error-related activation across cortical and subcortical regions. Implications for future research and potential limitations in conducting fMRI research in neurologically-impaired populations are discussed, as well as some potential benefits of employing multimodal imaging (e.g., fMRI and event-related potentials) of cognitive control processes in TBI. Copyright © 2011 Elsevier B.V. All rights reserved.

Reduced prefrontal and increased subcortical brain functioning assessed using positron emission tomography in predatory and affective murderers.

PubMed

Raine, A; Meloy, J R; Bihrle, S; Stoddard, J; LaCasse, L; Buchsbaum, M S

1998-01-01

There appear to be no brain imaging studies investigating which brain mechanisms subserve affective, impulsive violence versus planned, predatory violence. It was hypothesized that affectively violent offenders would have lower prefrontal activity, higher subcortical activity, and reduced prefrontal/subcortical ratios relative to controls, while predatory violent offenders would show relatively normal brain functioning. Glucose metabolism was assessed using positron emission tomography in 41 comparisons, 15 predatory murderers, and nine affective murderers in left and right hemisphere prefrontal (medial and lateral) and subcortical (amygdala, midbrain, hippocampus, and thalamus) regions. Affective murderers relative to comparisons had lower left and right prefrontal functioning, higher right hemisphere subcortical functioning, and lower right hemisphere prefrontal/subcortical ratios. In contrast, predatory murderers had prefrontal functioning that was more equivalent to comparisons, while also having excessively high right subcortical activity. Results support the hypothesis that emotional, unplanned impulsive murderers are less able to regulate and control aggressive impulses generated from subcortical structures due to deficient prefrontal regulation. It is hypothesized that excessive subcortical activity predisposes to aggressive behaviour, but that while predatory murderers have sufficiently good prefrontal functioning to regulate these aggressive impulses, the affective murderers lack such prefrontal control over emotion regulation.

Control effects of stimulus paradigms on characteristic firings of parkinsonism

NASA Astrophysics Data System (ADS)

Zhang, Honghui; Wang, Qingyun; Chen, Guanrong

2014-09-01

Experimental studies have shown that neuron population located in the basal ganglia of parkinsonian primates can exhibit characteristic firings with certain firing rates differing from normal brain activities. Motivated by recent experimental findings, we investigate the effects of various stimulation paradigms on the firing rates of parkinsonism based on the proposed dynamical models. Our results show that the closed-loop deep brain stimulation is superior in ameliorating the firing behaviors of the parkinsonism, and other control strategies have similar effects according to the observation of electrophysiological experiments. In addition, in conformity to physiological experiments, we found that there exists optimal delay of input in the closed-loop GPtrain|M1 paradigm, where more normal behaviors can be obtained. More interestingly, we observed that W-shaped curves of the firing rates always appear as stimulus delay varies. We furthermore verify the robustness of the obtained results by studying three pallidal discharge rates of the parkinsonism based on the conductance-based model, as well as the integrate-and-fire-or-burst model. Finally, we show that short-term plasticity can improve the firing rates and optimize the control effects on parkinsonism. Our conclusions may give more theoretical insight into Parkinson's disease studies.

Resting State Brain Entropy Alterations in Relapsing Remitting Multiple Sclerosis.

PubMed

Zhou, Fuqing; Zhuang, Ying; Gong, Honghan; Zhan, Jie; Grossman, Murray; Wang, Ze

2016-01-01

Brain entropy (BEN) mapping provides a novel approach to characterize brain temporal dynamics, a key feature of human brain. Using resting state functional magnetic resonance imaging (rsfMRI), reliable and spatially distributed BEN patterns have been identified in normal brain, suggesting a potential use in clinical populations since temporal brain dynamics and entropy may be altered in disease conditions. The purpose of this study was to characterize BEN in multiple sclerosis (MS), a neurodegenerative disease that affects millions of people. Since currently there is no cure for MS, developing treatment or medication that can slow down its progression represents a high research priority, for which validating a brain marker sensitive to disease and the related functional impairments is essential. Because MS can start long time before any measurable symptoms and structural deficits, assessing the dynamic brain activity and correspondingly BEN may provide a critical way to study MS and its progression. Because BEN is new to MS, we aimed to assess BEN alterations in the relapsing-remitting MS (RRMS) patients using a patient versus control design, to examine the correlation of BEN to clinical measurements, and to check the correlation of BEN to structural brain measures which have been more often used in MS studies. As compared to controls, RRMS patients showed increased BEN in motor areas, executive control area, spatial coordinating area, and memory system. Increased BEN was related to greater disease severity as measured by the expanded disability status scale (EDSS) and greater tissue damage as indicated by the mean diffusivity. Patients also showed decreased BEN in other places, which was associated with less disability or fatigue, indicating a disease-related BEN re-distribution. Our results suggest BEN as a novel and useful tool for characterizing RRMS.

[Expression of aquaporin-4 during brain edema in rats with thioacetamide-induced acute encephalopathy].

PubMed

Wang, Li-Qing; Zhu, Sheng-Mei; Zhou, Heng-Jun; Pan, Cai-Fei

2011-09-27

To investigate the expression of aquaporin-4 (AQP4) during brain edema in rats with thioacetamide-induced acute liver failure and encephalopathy. The rat model of acute hepatic failure and encephalopathy was induced by intraperitoneal injection of thioacetamide (TAA) at a 24-hour interval for 2 consecutive days. Thirty-two SD rats were randomly divided into the model group (n = 24) and the control group (normal saline, n = 8). And then the model group was further divided into 3 subgroups by the timepoint of decapitation: 24 h (n = 8), 48 h (n = 8) and 60 h (n = 8). Then we observed their clinical symptoms and stages of HE, indices of liver function and ammonia, liver histology and brain water content. The expression of AQP4 protein in brain tissues was measured with Western blot and the expression of AQP4mRNA with RT-PCR (reverse transcription-polymerase chain reaction). Typical clinical manifestations of hepatic encephalopathy occurred in all TAA-administrated rats. The model rats showed the higher indices of ALT (alanine aminotransferase), AST (aspartate aminotransferase), TBIL (total bilirubin) and ammonia than the control rats (P < 0.05). The brain water content was significantly elevated in TAA-administrated rats compared with the control (P < 0.05). The expressions of AQP4 protein and mRNA in brain tissues significantly increased in TAA-administrated rats (P < 0.05). In addition, the expressions of AQP4 protein and mRNA were positively correlated with brain water content (r = 0.536, P < 0.01; r = 0.566, P = 0.01). The high expression of AQP4 in rats with TAA-induced acute liver failure and encephalopathy plays a significant role during brain edema. AQP4 is one of the molecular mechanisms for the occurrence of brain edema in hepatic encephalopathy.

Prevalence and spectrum of in utero structural brain abnormalities in fetuses with complex congenital heart disease.

PubMed

Brossard-Racine, M; du Plessis, A J; Vezina, G; Robertson, R; Bulas, D; Evangelou, I E; Donofrio, M; Freeman, D; Limperopoulos, C

2014-08-01

Brain injury is a major complication in neonates with complex congenital heart disease. Preliminary evidence suggests that fetuses with congenital heart disease are at greater risk for brain abnormalities. However, the nature and frequency of these brain abnormalities detected by conventional fetal MR imaging has not been examined prospectively. Our primary objective was to determine the prevalence and spectrum of brain abnormalities detected on conventional clinical MR imaging in fetuses with complex congenital heart disease and, second, to compare the congenital heart disease cohort with a control group of fetuses from healthy pregnancies. We prospectively recruited pregnant women with a confirmed fetal congenital heart disease diagnosis and healthy volunteers with normal fetal echocardiogram findings who underwent a fetal MR imaging between 18 and 39 weeks gestational age. A total of 338 fetuses (194 controls; 144 with congenital heart disease) were studied at a mean gestational age of 30.61 ± 4.67 weeks. Brain abnormalities were present in 23% of the congenital heart disease group compared with 1.5% in the control group (P < .001). The most common abnormalities in the congenital heart disease group were mild unilateral ventriculomegaly in 12/33 (36.4%) and increased extra-axial spaces in 10/33 (30.3%). Subgroup analyses comparing the type and frequency of brain abnormalities based on cardiac physiology did not reveal significant associations, suggesting that the brain abnormalities were not limited to those with the most severe congenital heart disease. This is the first large prospective study reporting conventional MR imaging findings in fetuses with congenital heart disease. Our results suggest that brain abnormalities are prevalent but relatively mild antenatally in fetuses with congenital heart disease. The long-term predictive value of these findings awaits further study. © 2014 by American Journal of Neuroradiology.

Neural Development Under Conditions of Spaceflight

NASA Technical Reports Server (NTRS)

Kosik, Kenneth S.; Steward, Oswald; Temple, Meredith D.; Denslow, Maria J.

2003-01-01

One of the key tasks the developing brain must learn is how to navigate within the environment. This skill depends on the brain's ability to establish memories of places and things in the environment so that it can form cognitive maps. Earth's gravity defines the plane of orientation of the spatial environment in which animals navigate, and cognitive maps are based on this plane of orientation. Given that experience during early development plays a key role in the development of other aspects of brain function, experience in a gravitational environment is likely to be essential for the proper organization of brain regions mediating learning and memory of spatial information. Since the hippocampus is the brain region responsible for cognitive mapping abilities, this study evaluated the development of hippocampal structure and function in rats that spent part of their early development in microgravity. Litters of male and female Sprague-Dawley rats were launched into space aboard the Space Shuttle Columbia on either postnatal day eight (P8) or 14 (P14) and remained in space for 16 days. Upon return to Earth, the rats were tested for their ability to remember spatial information and navigate using a variety of tests (the Morris water maze, a modified radial arm maze, and an open field apparatus). These rats were then tested physiologically to determine whether they exhibited normal synaptic plasticity in the hippocampus. In a separate group of rats (flight and controls), the hippocampus was analyzed using anatomical, molecular biological, and biochemical techniques immediately postlanding. There were remarkably few differences between the flight groups and their Earth-bound controls in either the navigation and spatial memory tasks or activity-induced synaptic plasticity. Microscopic and immunocytochemical analyses of the brain also did not reveal differences between flight animals and ground-based controls. These data suggest that, within the developmental window studied, microgravity has minimal long-term impact on cognitive mapping function and cellular substrates important for this function. Any differences due to development in microgravity were transient and returned to normal soon after return to Earth.

The Royal Road to Time: How Understanding of the Evolution of Time in the Brain Addresses Memory, Dreaming, Flow, and Other Psychological Phenomena.

PubMed

Hancock, Peter A

2015-01-01

It has been claimed that dreams are the royal road to the unconscious mind. The present work argues that dreams and associated brain states such as memory, attention, flow, and perhaps even consciousness itself arise from diverse conflicts over control of time in the brain. Dreams are the brain's offline efforts to distill projections of the future, while memory represents the vestiges of the past successes and survived failures of those and other conscious projections. Memory thus acts to inform and improve the prediction of possible future states through the use of conscious prospects (planning) and unconscious prospective memory (dreams). When successful, these prospects result in states of flow for conscious planning and déjà vu for its unconscious comparator. In consequence, and contrary to normal expectation, memory is overwhelmingly oriented to deal with the future. Consciousness is the comparable process operating in the present moment. Thus past, present, and future are homeomorphic with the parts of memory (episodic and autobiographical) that recall a personal past, consciousness, and the differing dimensions of prospective memory to plan for future circumstances, respectively. Dreaming (i.e., unconscious prospective memory), has the luxury to run multiple "what if" simulations of many possible futures, essentially offline. I explicate these propositions and their relations to allied constructs such as déjà vu and flow. More generally, I propose that what appear to us as a range of normal psychological experiences are actually manifestations of an ongoing pathological battle for control within the brain. The landscape of this conflict is time. I suggest that there are at least 3 general systems bidding for this control, and in the process of evolution, each system has individually conferred a sequentially increasing survival advantage, but only at the expense of a still incomplete functional integration. Through juxtaposition of these respective brain systems, I endeavor to resolve some fundamental paradoxes and conundrums expressed in the basic psychological and behavioral processes of sleep, consciousness, and memory. The implication of this conceptual framework for the overall conception of time is then briefly adumbrated.

The autistic brain in the context of normal neurodevelopment.

PubMed

Ziats, Mark N; Edmonson, Catherine; Rennert, Owen M

2015-01-01

The etiology of autism spectrum disorders (ASDs) is complex and largely unclear. Among various lines of inquiry, many have suggested convergence onto disruptions in both neural circuitry and immune regulation/glial cell function pathways. However, the interpretation of the relationship between these two putative mechanisms has largely focused on the role of exogenous factors and insults, such as maternal infection, in activating immune pathways that in turn result in neural network abnormalities. Yet, given recent insights into our understanding of human neurodevelopment, and in particular the critical role of glia and the immune system in normal brain development, it is important to consider these putative pathological processes in their appropriate normal neurodevelopmental context. In this review, we explore the hypothesis that the autistic brain cellular phenotype likely represents intrinsic abnormalities of glial/immune processes constitutively operant in normal brain development that result in the observed neural network dysfunction. We review recent studies demonstrating the intercalated role of neural circuit development, the immune system, and glial cells in the normal developing brain, and integrate them with studies demonstrating pathological alterations in these processes in autism. By discussing known abnormalities in the autistic brain in the context of normal brain development, we explore the hypothesis that the glial/immune component of ASD may instead be related to intrinsic exaggerated/abnormal constitutive neurodevelopmental processes such as network pruning. Moreover, this hypothesis may be relevant to other neurodevelopmental disorders that share genetic, pathologic, and clinical features with autism.

Oligodendroglial response to ionizing radiation: Dose and dose-rate response

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

Levy, R.P.

1991-12-01

An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute {gamma}-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DICmore » 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain.« less

Oligodendroglial response to ionizing radiation: Dose and dose-rate response

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

Levy, Richard P.

1991-12-01

An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute γ-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DICmore » 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain.« less

Traumatic axonal injury: the prognostic value of lesion load in corpus callosum, brain stem, and thalamus in different magnetic resonance imaging sequences.

PubMed

Moen, Kent G; Brezova, Veronika; Skandsen, Toril; Håberg, Asta K; Folvik, Mari; Vik, Anne

2014-09-01

The aim of this study was to explore the prognostic value of visible traumatic axonal injury (TAI) loads in different MRI sequences from the early phase after adjusting for established prognostic factors. Likewise, we sought to explore the prognostic role of early apparent diffusion coefficient (ADC) values in normal-appearing corpus callosum. In this prospective study, 128 patients (mean age, 33.9 years; range, 11-69) with moderate (n = 64) and severe traumatic brain injury (TBI) were examined with MRI at a median of 8 days (range, 0-28) postinjury. TAI lesions in fluid-attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), and T2*-weighted gradient echo (T2*GRE) sequences were counted and FLAIR lesion volumes estimated. In patients and 47 healthy controls, mean ADC values were computed in 10 regions of interests in the normal-appearing corpus callosum. Outcome measure was the Glasgow Outcome Scale-Extended (GOS-E) at 12 months. In patients with severe TBI, number of DWI lesions and volume of FLAIR lesions in the corpus callosum, brain stem, and thalamus predicted outcome in analyses with adjustment for age, Glasgow Coma Scale score, and pupillary dilation (odds ratio, 1.3-6.9; p = <0.001-0.017). The addition of Rotterdam CT score and DWI lesions in the corpus callosum yielded the highest R2 (0.24), compared to all other MRI variables, including brain stem lesions. For patients with moderate TBI only the number of cortical contusions (p = 0.089) and Rotterdam CT score (p = 0.065) tended to predict outcome. Numbers of T2*GRE lesions did not affect outcome. Mean ADC values in the normal-appearing corpus callosum did not differ from controls. In conclusion, the loads of visible TAI lesions in the corpus callosum, brain stem, and thalamus in DWI and FLAIR were independent prognostic factors in patients with severe TBI. DWI lesions in the corpus callosum were the most important predictive MRI variable. Interestingly, number of cortical contusions in MRI and CT findings seemed more important for patients with moderate TBI.

Childhood and adolescent obesity and long-term cognitive consequences during aging.

PubMed

Wang, Jun; Freire, Daniel; Knable, Lindsay; Zhao, Wei; Gong, Bing; Mazzola, Paolo; Ho, Lap; Levine, Samara; Pasinetti, Giulio M

2015-04-01

The prevalence of childhood/adolescent obesity and insulin resistance has reached an epidemic level. Obesity's immediate clinical impacts have been extensively studied; however, current clinical evidence underscores the long-term implications. The current study explored the impacts of brief childhood/adolescent obesity and insulin resistance on cognitive function in later life. To mimic childhood/adolescent obesity and insulin resistance, we exposed 9-week-old C57BL/6J mice to a high-fat diet for 15 weeks, after which the mice exhibited diet-induced obesity and insulin resistance. We then put these mice back on a normal low-fat diet, after which the mice exhibited normal body weight and glucose tolerance. However, a spatial memory test in the forms of the Morris water maze (MWM) and contextual fear conditioning at 85 weeks of age showed that these mice had severe deficits in learning and long-term memory consolidation. Mechanistic investigations identified increased expression of histone deacetylases 5, accompanied by reduced expression of brain-derived neurotrophic factor, in the brains 61 weeks after the mice had been off the high-fat diet. Electrophysiology studies showed that hippocampal slices isolated from these mice are more susceptible to synaptic impairments compared with slices isolated from the control mice. We demonstrated that a 15-week occurrence of obesity and insulin resistance during childhood/adolescence induces irreversible epigenetic modifications in the brain that persist following restoration of normal metabolic homeostasis, leading to brain synaptic dysfunction during aging. Our study provides experimental evidence that limited early-life exposure to obesity and insulin resistance may have long-term deleterious consequences in the brain, contributing to the onset/progression of cognitive dysfunction during aging. © 2014 Wiley Periodicals, Inc.

CYP46A1 inhibition, brain cholesterol accumulation and neurodegeneration pave the way for Alzheimer's disease.

PubMed

Djelti, Fathia; Braudeau, Jerome; Hudry, Eloise; Dhenain, Marc; Varin, Jennifer; Bièche, Ivan; Marquer, Catherine; Chali, Farah; Ayciriex, Sophie; Auzeil, Nicolas; Alves, Sandro; Langui, Dominique; Potier, Marie-Claude; Laprevote, Olivier; Vidaud, Michel; Duyckaerts, Charles; Miles, Richard; Aubourg, Patrick; Cartier, Nathalie

2015-08-01

Abnormalities in neuronal cholesterol homeostasis have been suspected or observed in several neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and Huntington's disease. However, it has not been demonstrated whether an increased abundance of cholesterol in neurons in vivo contributes to neurodegeneration. To address this issue, we used RNA interference methodology to inhibit the expression of cholesterol 24-hydroxylase, encoded by the Cyp46a1 gene, in the hippocampus of normal mice. Cholesterol 24-hydroxylase controls cholesterol efflux from the brain and thereby plays a major role in regulating brain cholesterol homeostasis. We used an adeno-associated virus vector encoding short hairpin RNA directed against the mouse Cyp46a1 mRNA to decrease the expression of the Cyp46a1 gene in hippocampal neurons of normal mice. This increased the cholesterol concentration in neurons, followed by cognitive deficits and hippocampal atrophy due to apoptotic neuronal death. Prior to neuronal death, the recruitment of the amyloid protein precursor to lipid rafts was enhanced leading to the production of β-C-terminal fragment and amyloid-β peptides. Abnormal phosphorylation of tau and endoplasmic reticulum stress were also observed. In the APP23 mouse model of Alzheimer's disease, the abundance of amyloid-β peptides increased following inhibition of Cyp46a1 expression, and neuronal death was more widespread than in normal mice. Altogether, these results suggest that increased amounts of neuronal cholesterol within the brain may contribute to inducing and/or aggravating Alzheimer's disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Pregnant serum induces neuroinflammation and seizure activity via TNFα.

PubMed

Cipolla, Marilyn J; Pusic, Aya D; Grinberg, Yelena Y; Chapman, Abbie C; Poynter, Matthew E; Kraig, Richard P

2012-04-01

Preeclampsia is a hypertensive disorder of pregnancy that affects many organs including the brain. Neurological complications occur during preeclampsia, the most serious of which is seizure known as eclampsia. Although preeclampsia can precede the eclamptic seizure, it often occurs during normal pregnancy, suggesting that processes associated with normal pregnancy can promote neuronal excitability. Here we investigated whether circulating inflammatory mediators that are elevated late in gestation when seizure also occurs are hyperexcitable to neuronal tissue. Evoked field potentials were measured in hippocampal slices in which control horse serum that slices are normally grown in, was replaced with serum from nonpregnant or late-pregnant Wistar rats for 48 h. We found that serum from pregnant, but not nonpregnant rats, caused hyperexcitability to hippocampal neurons and seizure activity that was abrogated by inhibition of tumor necrosis factor alpha (TNFα) signaling. Additionally, application of TNFα mimicked this increased excitability. Pregnant serum also caused morphological changes in microglia characteristic of activation, and increased TNFα mRNA expression that was not seen with exposure to nonpregnant serum. However, TNFα protein was not found to be elevated in pregnant serum itself, suggesting that other circulating factors during pregnancy caused activation of hippocampal slice cells to produce a TNFα-mediated increase in neuronal excitability. Lastly, although pregnant serum caused neuroinflammation and hyperexcitability of hippocampal slices, it did not increase blood-brain barrier permeability, nor were pregnant rats from which the serum was taken undergoing seizure. Thus, the BBB has an important role in protecting the brain from circulating neuroinflammatory mediators that are hyperexcitable to the brain during pregnancy. These studies provide novel insight into the underlying cause of eclampsia without elevated blood pressure and the protective role of the BBB that prevents exposure of the brain to hyperexcitable factors. Copyright © 2012 Elsevier Inc. All rights reserved.

Time-resolved fluorescence spectroscopy of human brain tumors

NASA Astrophysics Data System (ADS)

Marcu, Laura; Thompson, Reid C.; Garde, Smita; Sedrak, Mark; Black, Keith L.; Yong, William H.

2002-05-01

Fluorescence spectroscopy of the endogenous emission of brain tumors has been researched as a potentially important method for the intraoperative localization of brain tumor margins. In this study, we investigate the use of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) for demarcation of primary brain tumors by studying the time-resolved spectra of gliomas of different histologic grades. Time-resolved fluorescence (3 ns, 337 nm excitation) from excised human brain tumor show differences between the time-resolved emission of malignant glioma and normal brain tissue (gray and white matter). Our findings suggest that brain tumors can be differentiated from normal brain tissue based upon unique time-resolved fluorescence signature.

Normal brain tissue volumes after long-term recovery in anorexia and bulimia nervosa.

PubMed

Wagner, Angela; Greer, Phil; Bailer, Ursula F; Frank, Guido K; Henry, Shannan E; Putnam, Karen; Meltzer, Carolyn C; Ziolko, Scott K; Hoge, Jessica; McConaha, Claire; Kaye, Walter H

2006-02-01

Individuals who are ill with anorexia (AN) and bulimia nervosa (BN) often have increased cerebrospinal fluid (CSF) volumes and decreased total gray and white matter volumes. It is unclear whether such disturbances persist after recovery from an eating disorder. Magnetic resonance imaging was performed on 40 women who were long-term recovered (>1 year no binging, purging, or restricting behaviors, normal weight, and menstrual cycles, not on medication) from restricting or binge/purging type AN or BN and 31 healthy control women (CW). Voxel-based morphometry (VBM) was used for data analysis. Recovered AN and BN subgroups were similar to CW in terms of cerebrospinal fluid (CSF) volume as well as total or regional gray or white matter volume. These findings suggest that structural brain abnormalities are reversible in individuals with eating disorders after long-term recovery.

Brain-computer interface signal processing at the Wadsworth Center: mu and sensorimotor beta rhythms.

PubMed

McFarland, Dennis J; Krusienski, Dean J; Wolpaw, Jonathan R

2006-01-01

The Wadsworth brain-computer interface (BCI), based on mu and beta sensorimotor rhythms, uses one- and two-dimensional cursor movement tasks and relies on user training. This is a real-time closed-loop system. Signal processing consists of channel selection, spatial filtering, and spectral analysis. Feature translation uses a regression approach and normalization. Adaptation occurs at several points in this process on the basis of different criteria and methods. It can use either feedforward (e.g., estimating the signal mean for normalization) or feedback control (e.g., estimating feature weights for the prediction equation). We view this process as the interaction between a dynamic user and a dynamic system that coadapt over time. Understanding the dynamics of this interaction and optimizing its performance represent a major challenge for BCI research.

Restoration of Normal Cerebral Oxygen Consumption with Rapamycin Treatment in a Rat Model of Autism-Tuberous Sclerosis.

PubMed

Chi, Oak Z; Wu, Chang-Chih; Liu, Xia; Rah, Kang H; Jacinto, Estela; Weiss, Harvey R

2015-09-01

Tuberous sclerosis (TSC) is associated with autism spectrum disorders and has been linked to metabolic dysfunction and unrestrained signaling of the mammalian target of rapamycin (mTOR). Inhibition of mTOR by rapamycin can mitigate some of the phenotypic abnormalities associated with TSC and autism, but whether this is due to the mTOR-related function in energy metabolism remains to be elucidated. In young Eker rats, an animal model of TSC and autism, which harbors a germ line heterozygous Tsc2 mutation, we previously reported that cerebral oxygen consumption was pronouncedly elevated. Young (4 weeks) male control Long-Evans and Eker rats were divided into control and rapamycin-treated (20 mg/kg once daily for 2 days) animals. Cerebral regional blood flow ((14)C-iodoantipyrine) and O2 consumption (cryomicrospectrophotometry) were determined in isoflurane-anesthetized rats. We found significantly increased basal O2 consumption in the cortex (8.7 ± 1.5 ml O2/min/100 g Eker vs. 2.7 ± 0.2 control), hippocampus, pons and cerebellum. Regional cerebral blood flow and cerebral O2 extractions were also elevated in all brain regions. Rapamycin had no significant effect on O2 consumption in any brain region of the control rats, but significantly reduced consumption in the cortex (4.1 ± 0.3) and all other examined regions of the Eker rats. Phosphorylation of mTOR and S6K1 was similar in the two groups and equally reduced by rapamycin. Thus, a rapamycin-sensitive, mTOR-dependent but S6K1-independent, signal led to enhanced oxidative metabolism in the Eker brain. We found decreased Akt phosphorylation in Eker but not Long-Evans rat brains, suggesting that this may be related to the increased cerebral O2 consumption in the Eker rat. Our findings suggest that rapamycin targeting of Akt to restore normal cerebral metabolism could have therapeutic potential in tuberous sclerosis and autism.

[Effect of perinatal recurrent infection on the brain development in immature mice].

PubMed

Song, Li-Li; Huang, Zhi-Heng; Pei, Yi-Ling; Chen, Chao

2014-12-01

To study the effects of perinatal recurrent infection on the brain development in immature mice. Six pregnant C57BL6 mice were randomly assigned to three groups: intrauterine infection, perinatal recurrent infection and control. The intrauterine infection group was intraperitoneally injected with LPS (0.5 mg/kg) on the 18th day of pregnancy. The perinatal recurrent infection group was injected with LPS (0.5 mg/kg) on the 18th day of pregnancy and their offsprings were intraperitoneally injected with the same dose of LPS daily from postnatal day 3 to 12. The control group was administered with normal saline at the same time points as the recurrent infection group. The short-time neurobehaviors were assessed on postnatal day 13. The mice were then sacrificed to measure brain weights and neuropathological changes using cresyl violet staining. Western blot was used to evaluate the expression of TNF-α, Caspase-3 and myelin basic protein (MBP). The brain weights of the recurrent infection group were significantly lower than the control and intrauterine infection groups (P<0.05) and the recurrent infection group displayed significant neuropathological changes. Perinatal recurrent infection resulted in increased expression levels of TNF-α and Caspase-3, and decreased expression level of MBP compared with the intrauterine infection and control groups (P<0.01). The neurobehavior test showed that the recurrent infection group used longer time in gait reflex, right reflex and geotaxis reflex compared with the control and intrauterine infection groups on postnatal day 13 (P<0.05). Perinatal recurrent infection may exacerbate inflammatory response and cell death in the immature brain, which may be one of the important factors for perinatal brain injury.

Brain-region–specific alterations of the trajectories of neuronal volume growth throughout the lifespan in autism

PubMed Central

2014-01-01

Several morphometric studies have revealed smaller than normal neurons in the neocortex of autistic subjects. To test the hypothesis that abnormal neuronal growth is a marker of an autism-associated global encephalopathy, neuronal volumes were estimated in 16 brain regions, including various subcortical structures, Ammon’s horn, archicortex, cerebellum, and brainstem in 14 brains from individuals with autism 4 to 60 years of age and 14 age-matched control brains. This stereological study showed a significantly smaller volume of neuronal soma in 14 of 16 regions in the 4- to 8-year-old autistic brains than in the controls. Arbitrary classification revealed a very severe neuronal volume deficit in 14.3% of significantly altered structures, severe in 50%, moderate in 21.4%, and mild in 14.3% structures. This pattern suggests desynchronized neuronal growth in the interacting neuronal networks involved in the autistic phenotype. The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old. Neuronal volumes in 75% of the structures examined in the older adults with autism are comparable to neuronal volume in age-matched controls. This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions. However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits. PMID:24612906

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

Epilepsy, regulation of brain energy metabolism and neurotransmission.

PubMed

Cloix, Jean-François; Hévor, Tobias

2009-01-01

Seizures are the result of a sudden and temporary synchronization of neuronal activity, the reason for which is not clearly understood. Astrocytes participate in the control of neurotransmitter storage and neurotransmission efficacy. They provide fuel to neurons, which need a high level of energy to sustain normal and pathological neuronal activities, such as during epilepsy. Various genetic or induced animal models have been developed and used to study epileptogenic mechanisms. Methionine sulfoximine induces both seizures and the accumulation of brain glycogen, which might be considered as a putative energy store to neurons in various animals. Animals subjected to methionine sulfoximine develop seizures similar to the most striking form of human epilepsy, with a long pre-convulsive period of several hours, a long convulsive period during up to 48 hours and a post convulsive period during which they recover normal behavior. The accumulation of brain glycogen has been demonstrated in both the cortex and cerebellum as early as the pre-convulsive period, indicating that this accumulation is not a consequence of seizures. The accumulation results from an activation of gluconeogenesis specifically localized to astrocytes, both in vivo and in vitro. Both seizures and brain glycogen accumulation vary when using different inbred strains of mice. C57BL/6J is the most "resistant" strain to methionine sulfoximine, while CBA/J is the most "sensitive" one. The present review describes the data obtained on methionine sulfoximine dependent seizures and brain glycogen in the light of neurotransmission, highlighting the relevance of brain glycogen content in epilepsies.

Chronic production of angiotensin IV in the brain leads to hypertension that is reversible with an angiotensin II AT1 receptor antagonist.

PubMed

Lochard, Nadheige; Thibault, Gaétan; Silversides, David W; Touyz, Rhian M; Reudelhuber, Timothy L

2004-06-11

Angiotensin IV (Ang IV) is a metabolite of the potent vasoconstrictor angiotensin II (Ang II). Because specific binding sites for this peptide have been reported in numerous tissues including the brain, it has been suggested that a specific Ang IV receptor (AT4) might exist. Bolus injection of Ang IV in brain ventricles has been implicated in learning, memory, and localized vasodilatation. However, the functions of Ang IV in a physiological context are still unknown. In this study, we generated a transgenic (TG) mouse model that chronically releases Ang IV peptide specifically in the brain. TG mice were found to be hypertensive by the tail-cuff method as compared with control littermates. Treatment with the angiotensin-converting enzyme inhibitor captopril had no effect on blood pressure, but surprisingly treatment with the Ang II AT1 receptor antagonist candesartan normalized the blood pressure despite the fact that the levels of Ang IV in the brains of TG mice were only 4-fold elevated over the normal endogenous level of Ang peptides. Calcium mobilization assays performed on cultured CHO cells chronically transfected with the AT1 receptor confirm that low-dose Ang IV can mobilize calcium via the AT1 receptor only in the presence of Ang II, consistent with an allosteric mechanism. These results suggest that chronic elevation of Ang IV in the brain can induce hypertension that can be treated with angiotensin II AT1 receptor antagonists.

Linking brain imaging and genomics in the study of Alzheimer's disease and aging.

PubMed

Reiman, Eric M

2007-02-01

My colleagues and I have been using positron emission tomography (PET) and magnetic resonance imaging (MRI) to detect and track the brain changes associated with Alzheimer's disease (AD) and normal brain aging in cognitively normal persons with two copies, one copy, and no copies of the apolipoprotein E (APOE) epsilon4 allele, a common AD susceptibility gene. In this review article, I consider how brain imaging techniques could be used to evaluate putative AD prevention therapies in cognitively normal APOE epsilon4 carriers and putative age-modifying therapies in cognitively normal APOE epsilon4 noncarriers, how they could help investigate the individual and aggregate effects of putative AD risk modifiers, and how they could help guide the investigation of a molecular mechanism associated with AD vulnerability and normal neurological aging. I suggest how high-resolution genome-wide genetic and transcriptomic studies could further help in the scientific understanding of AD, aging, and other common and genetically complex phenotypes, such as variation in normal human memory performance, and in the discovery and evaluation of promising treatments for these phenotypes. Finally, I illustrate the push-pull relationship between brain imaging, genomics research, and other neuroscientific research in the study of AD and aging.

Functional brain networks in Alzheimer's disease: EEG analysis based on limited penetrable visibility graph and phase space method

NASA Astrophysics Data System (ADS)

Wang, Jiang; Yang, Chen; Wang, Ruofan; Yu, Haitao; Cao, Yibin; Liu, Jing

2016-10-01

In this paper, EEG series are applied to construct functional connections with the correlation between different regions in order to investigate the nonlinear characteristic and the cognitive function of the brain with Alzheimer's disease (AD). First, limited penetrable visibility graph (LPVG) and phase space method map single EEG series into networks, and investigate the underlying chaotic system dynamics of AD brain. Topological properties of the networks are extracted, such as average path length and clustering coefficient. It is found that the network topology of AD in several local brain regions are different from that of the control group with no statistically significant difference existing all over the brain. Furthermore, in order to detect the abnormality of AD brain as a whole, functional connections among different brain regions are reconstructed based on similarity of clustering coefficient sequence (CCSS) of EEG series in the four frequency bands (delta, theta, alpha, and beta), which exhibit obvious small-world properties. Graph analysis demonstrates that for both methodologies, the functional connections between regions of AD brain decrease, particularly in the alpha frequency band. AD causes the graph index complexity of the functional network decreased, the small-world properties weakened, and the vulnerability increased. The obtained results show that the brain functional network constructed by LPVG and phase space method might be more effective to distinguish AD from the normal control than the analysis of single series, which is helpful for revealing the underlying pathological mechanism of the disease.

Analysis of Resting-State fMRI Topological Graph Theory Properties in Methamphetamine Drug Users Applying Box-Counting Fractal Dimension.

PubMed

Siyah Mansoory, Meysam; Oghabian, Mohammad Ali; Jafari, Amir Homayoun; Shahbabaie, Alireza

2017-01-01

Graph theoretical analysis of functional Magnetic Resonance Imaging (fMRI) data has provided new measures of mapping human brain in vivo. Of all methods to measure the functional connectivity between regions, Linear Correlation (LC) calculation of activity time series of the brain regions as a linear measure is considered the most ubiquitous one. The strength of the dependence obligatory for graph construction and analysis is consistently underestimated by LC, because not all the bivariate distributions, but only the marginals are Gaussian. In a number of studies, Mutual Information (MI) has been employed, as a similarity measure between each two time series of the brain regions, a pure nonlinear measure. Owing to the complex fractal organization of the brain indicating self-similarity, more information on the brain can be revealed by fMRI Fractal Dimension (FD) analysis. In the present paper, Box-Counting Fractal Dimension (BCFD) is introduced for graph theoretical analysis of fMRI data in 17 methamphetamine drug users and 18 normal controls. Then, BCFD performance was evaluated compared to those of LC and MI methods. Moreover, the global topological graph properties of the brain networks inclusive of global efficiency, clustering coefficient and characteristic path length in addict subjects were investigated too. Compared to normal subjects by using statistical tests (P<0.05), topological graph properties were postulated to be disrupted significantly during the resting-state fMRI. Based on the results, analyzing the graph topological properties (representing the brain networks) based on BCFD is a more reliable method than LC and MI.

Reactions to Media Violence: It’s in the Brain of the Beholder

PubMed Central

Alia-Klein, Nelly; Wang, Gene-Jack; Preston-Campbell, Rebecca N.; Moeller, Scott J.; Parvaz, Muhammad A.; Zhu, Wei; Jayne, Millard C.; Wong, Chris; Tomasi, Dardo; Goldstein, Rita Z.; Fowler, Joanna S.; Volkow, Nora D.

2014-01-01

Media portraying violence is part of daily exposures. The extent to which violent media exposure impacts brain and behavior has been debated. Yet there is not enough experimental data to inform this debate. We hypothesize that reaction to violent media is critically dependent on personality/trait differences between viewers, where those with the propensity for physical assault will respond to the media differently than controls. The source of the variability, we further hypothesize, is reflected in autonomic response and brain functioning that differentiate those with aggression tendencies from others. To test this hypothesis we pre-selected a group of aggressive individuals and non-aggressive controls from the normal healthy population; we documented brain, blood-pressure, and behavioral responses during resting baseline and while the groups were watching media violence and emotional media that did not portray violence. Positron Emission Tomography was used with [18F]fluoro-deoxyglucose (FDG) to image brain metabolic activity, a marker of brain function, during rest and during film viewing while blood-pressure and mood ratings were intermittently collected. Results pointed to robust resting baseline differences between groups. Aggressive individuals had lower relative glucose metabolism in the medial orbitofrontal cortex correlating with poor self-control and greater glucose metabolism in other regions of the default-mode network (DMN) where precuneus correlated with negative emotionality. These brain results were similar while watching the violent media, during which aggressive viewers reported being more Inspired and Determined and less Upset and Nervous, and also showed a progressive decline in systolic blood-pressure compared to controls. Furthermore, the blood-pressure and brain activation in orbitofrontal cortex and precuneus were differentially coupled between the groups. These results demonstrate that individual differences in trait aggression strongly couple with brain, behavioral, and autonomic reactivity to media violence which should factor into debates about the impact of media violence on the public. PMID:25208327

Reactions to media violence: it's in the brain of the beholder.

PubMed

Alia-Klein, Nelly; Wang, Gene-Jack; Preston-Campbell, Rebecca N; Moeller, Scott J; Parvaz, Muhammad A; Zhu, Wei; Jayne, Millard C; Wong, Chris; Tomasi, Dardo; Goldstein, Rita Z; Fowler, Joanna S; Volkow, Nora D

2014-01-01

Media portraying violence is part of daily exposures. The extent to which violent media exposure impacts brain and behavior has been debated. Yet there is not enough experimental data to inform this debate. We hypothesize that reaction to violent media is critically dependent on personality/trait differences between viewers, where those with the propensity for physical assault will respond to the media differently than controls. The source of the variability, we further hypothesize, is reflected in autonomic response and brain functioning that differentiate those with aggression tendencies from others. To test this hypothesis we pre-selected a group of aggressive individuals and non-aggressive controls from the normal healthy population; we documented brain, blood-pressure, and behavioral responses during resting baseline and while the groups were watching media violence and emotional media that did not portray violence. Positron Emission Tomography was used with [18F]fluoro-deoxyglucose (FDG) to image brain metabolic activity, a marker of brain function, during rest and during film viewing while blood-pressure and mood ratings were intermittently collected. Results pointed to robust resting baseline differences between groups. Aggressive individuals had lower relative glucose metabolism in the medial orbitofrontal cortex correlating with poor self-control and greater glucose metabolism in other regions of the default-mode network (DMN) where precuneus correlated with negative emotionality. These brain results were similar while watching the violent media, during which aggressive viewers reported being more Inspired and Determined and less Upset and Nervous, and also showed a progressive decline in systolic blood-pressure compared to controls. Furthermore, the blood-pressure and brain activation in orbitofrontal cortex and precuneus were differentially coupled between the groups. These results demonstrate that individual differences in trait aggression strongly couple with brain, behavioral, and autonomic reactivity to media violence which should factor into debates about the impact of media violence on the public.

Abnormal functional connectivity of EEG gamma band in patients with depression during emotional face processing.

PubMed

Li, Yingjie; Cao, Dan; Wei, Ling; Tang, Yingying; Wang, Jijun

2015-11-01

This paper evaluates the large-scale structure of functional brain networks using graph theoretical concepts and investigates the difference in brain functional networks between patients with depression and healthy controls while they were processing emotional stimuli. Electroencephalography (EEG) activities were recorded from 16 patients with depression and 14 healthy controls when they performed a spatial search task for facial expressions. Correlations between all possible pairs of 59 electrodes were determined by coherence, and the coherence matrices were calculated in delta, theta, alpha, beta, and gamma bands (low gamma: 30-50Hz and high gamma: 50-80Hz, respectively). Graph theoretical analysis was applied to these matrices by using two indexes: the clustering coefficient and the characteristic path length. The global EEG coherence of patients with depression was significantly higher than that of healthy controls in both gamma bands, especially in the high gamma band. The global coherence in both gamma bands from healthy controls appeared higher in negative conditions than in positive conditions. All the brain networks were found to hold a regular and ordered topology during emotion processing. However, the brain network of patients with depression appeared randomized compared with the normal one. The abnormal network topology of patients with depression was detected in both the prefrontal and occipital regions. The negative bias from healthy controls occurred in both gamma bands during emotion processing, while it disappeared in patients with depression. The proposed work studied abnormally increased connectivity of brain functional networks in patients with depression. By combing the clustering coefficient and the characteristic path length, we found that the brain networks of patients with depression and healthy controls had regular networks during emotion processing. Yet the brain networks of the depressed group presented randomization trends. Moreover, negative bias was detected in the healthy controls during emotion processing, while it was not detected in patients with depression, which might be related to the types of negative stimuli used in this study. The brain networks from both patients with depression and healthy controls were found to hold a regular and ordered topology. Yet the brain networks of patients with depression had randomization trends. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Brain control and information transfer.

PubMed

Tehovnik, Edward J; Chen, Lewis L

2015-12-01

In this review, we examine the importance of having a body as essential for the brain to transfer information about the outside world to generate appropriate motor responses. We discuss the context-dependent conditioning of the motor control neural circuits and its dependence on the completion of feedback loops, which is in close agreement with the insights of Hebb and colleagues, who have stressed that for learning to occur the body must be intact and able to interact with the outside world. Finally, we apply information theory to data from published studies to evaluate the robustness of the neuronal signals obtained by bypassing the body (as used for brain-machine interfaces) versus via the body to move in the world. We show that recording from a group of neurons that bypasses the body exhibits a vastly degraded level of transfer of information as compared to that of an entire brain using the body to engage in the normal execution of behaviour. We conclude that body sensations provide more than just feedback for movements; they sustain the necessary transfer of information as animals explore their environment, thereby creating associations through learning. This work has implications for the development of brain-machine interfaces used to move external devices.

Potential for intensity-modulated radiation therapy to permit dose escalation for canine nasal cancer.

PubMed

Vaudaux, Catherine; Schneider, Uwe; Kaser-Hotz, Barbara

2007-01-01

We evaluated the impact of inverse planned intensity-modulated radiation therapy (IMRT) on the dose-volume histograms (DVHs) and on the normal tissue complication probabilities (NTCPs) of brain and eyes in dogs with nasal tumors. Nine dogs with large, caudally located nasal tumors were planned using conventional techniques and inverse planned IMRT for a total prescribed dose of 52.5 Gy in 3.5 Gy fractions. The equivalent uniform dose for brain and eyes was calculated to estimate the normal tissue complication probability (NTCP) of these organs. The NTCP values as well as the DVHs were used to compare the treatment plans. The dose distribution in IMRT plans was more conformal than in conventional plans. The average dose delivered to one-third of the brain was 10 Gy lower with the IMRT plan compared with conventional planning. The mean partial brain volume receiving 43.6 Gy or more was reduced by 25.6% with IMRT. As a consequence, the NTCPs were also significantly lower in the IMRT plans. The mean NTCP of brain was two times lower and at least one eye could be saved in all patients planed with IMRT. Another possibility with IMRT is dose escalation in the target to improve tumor control while keeping the NTCPs at the same level as for conventional planning. Veterinary

Cerebral Gluconeogenesis and Diseases.

PubMed

Yip, James; Geng, Xiaokun; Shen, Jiamei; Ding, Yuchuan

2016-01-01

The gluconeogenesis pathway, which has been known to normally present in the liver, kidney, intestine, or muscle, has four irreversible steps catalyzed by the enzymes: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, and glucose 6-phosphatase. Studies have also demonstrated evidence that gluconeogenesis exists in brain astrocytes but no convincing data have yet been found in neurons. Astrocytes exhibit significant 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 activity, a key mechanism for regulating glycolysis and gluconeogenesis. Astrocytes are unique in that they use glycolysis to produce lactate, which is then shuttled into neurons and used as gluconeogenic precursors for reduction. This gluconeogenesis pathway found in astrocytes is becoming more recognized as an important alternative glucose source for neurons, specifically in ischemic stroke and brain tumor. Further studies are needed to discover how the gluconeogenesis pathway is controlled in the brain, which may lead to the development of therapeutic targets to control energy levels and cellular survival in ischemic stroke patients, or inhibit gluconeogenesis in brain tumors to promote malignant cell death and tumor regression. While there are extensive studies on the mechanisms of cerebral glycolysis in ischemic stroke and brain tumors, studies on cerebral gluconeogenesis are limited. Here, we review studies done to date regarding gluconeogenesis to evaluate whether this metabolic pathway is beneficial or detrimental to the brain under these pathological conditions.

Near infrared spectroscopy based brain-computer interface

NASA Astrophysics Data System (ADS)

Ranganatha, Sitaram; Hoshi, Yoko; Guan, Cuntai

2005-04-01

A brain-computer interface (BCI) provides users with an alternative output channel other than the normal output path of the brain. BCI is being given much attention recently as an alternate mode of communication and control for the disabled, such as patients suffering from Amyotrophic Lateral Sclerosis (ALS) or "locked-in". BCI may also find applications in military, education and entertainment. Most of the existing BCI systems which rely on the brain's electrical activity use scalp EEG signals. The scalp EEG is an inherently noisy and non-linear signal. The signal is detrimentally affected by various artifacts such as the EOG, EMG, ECG and so forth. EEG is cumbersome to use in practice, because of the need for applying conductive gel, and the need for the subject to be immobile. There is an urgent need for a more accessible interface that uses a more direct measure of cognitive function to control an output device. The optical response of Near Infrared Spectroscopy (NIRS) denoting brain activation can be used as an alternative to electrical signals, with the intention of developing a more practical and user-friendly BCI. In this paper, a new method of brain-computer interface (BCI) based on NIRS is proposed. Preliminary results of our experiments towards developing this system are reported.

Reduced Brain GABA in Primary Insomnia: Preliminary Data from 4T Proton Magnetic Resonance Spectroscopy (1H-MRS)

PubMed Central

Winkelman, John W.; Buxton, Orfeu M.; Jensen, J. Eric; Benson, Kathleen L.; O'Connor, Shawn P.; Wang, Wei; Renshaw, Perry F.

2008-01-01

Study Objectives: Both basic and clinical data suggest a potential significant role for GABA in the etiology and maintenance of primary insomnia (PI). Proton magnetic resonance spectroscopy (1H-MRS) can non-invasively determine GABA levels in human brain. Our objective was to assess GABA levels in unmedicated individuals with PI, using 1H-MRS. Design and Setting: Matched-groups, cross-sectional study conducted at two university-based hospitals. Participants: Sixteen non-medicated individuals (8 women) with PI (mean age = 37.3 +/− 8.1) and 16 (7 women) well-screened normal sleepers (mean age = 37.6 +/− 4.5). Methods and Measurements: PI was established with an unstructured clinical interview, a Structured Clinical Interview for DSM-IV (SCID), sleep diary, actigraphy and polysomnography (PSG). 1H-MRS data were collected on a Varian 4 Tesla magnetic resonance imaging/spectroscopy scanner. Global brain GABA levels were averaged from samples in the basal ganglia, thalamus, and temporal, parietal, and occipital white-matter and cortex. Results: Average brain GABA levels were nearly 30% lower in patients with PI (.18 +/− .06) compared to controls (.25 +/− .11). GABA levels were negatively correlated with wake after sleep onset (WASO) on two independent PSGs (r = −0.71, p = 0.0024 and −0.70, p = 0.0048). Conclusions: Our preliminary finding of a global reduction in GABA in non-medicated individuals with PI is the first demonstration of a neurochemical difference in the brains of those with PI compared to normal sleeping controls. 1H-MRS is a valuable tool to assess GABA in vivo, and may provide a means to shed further light on the neurobiology of insomnia. Citation: Winkelman JW; Buxton OM; Jensen JE; Benson KL; O'Connor SP; Wang W; Renshaw PF. Reduced brain GABA in primary insomnia: preliminary data from 4T proton magnetic resonance spectroscopy (1H-MRS). SLEEP 2008;31(11):1499–1506. PMID:19014069

Methylation, expression, and mutation analysis of the cell cycle control genes in human brain tumors.

PubMed

Yin, Dong; Xie, Dong; Hofmann, Wolf-Karsten; Miller, Carl W; Black, Keith L; Koeffler, H Phillip

2002-11-28

Methylation status of the p15(INK4B), p16(INK4A), p14(ARF) and retinoblastoma (RB) genes was studied using methylation specific polymerase chain reaction (MSP) in 85 human brain tumors of various subtypes and four normal brain samples. These genes play an important role in the control of the cell cycle. Twenty-four out of 85 cases (28%) had at least one of these genes methylated. The frequency of p14(ARF) methylation was 15 out of 85 (18%) cases, and the expression of p14(ARF) in methylated gliomas was significantly lower than in unmethylated gliomas. The incidence of methylation of p15(INK4B), p16(INK4A) and RB gene was 4%, 7%, and 4%, respectively. Samples with p14(ARF) methylation did not have p16(INK4A) methylation even though both genes physically overlap. None of the target genes was methylated in the normal brain samples. In addition, the p53 gene was mutated in 19 out of 85 (22%) samples as determined by single strand conformation polymorphism (SSCP) analysis and DNA sequencing. Thirty out of 85 (35%) brain tumors had either a p53 mutation or methylation of p14(ARF). Also, the p14(ARF) expression in p53 wild-type gliomas was lower than levels in p53 mutated gliomas. This finding is consistent with wild-type p53 being able to autoregulate its levels by down-regulating expression of p14(ARF). In summary, inactivation of the apoptosis pathway that included the p14(ARF) and p53 genes by hypermethylation and mutation, respectively, occurred frequently in human brain tumors. Down-regulation of p14(ARF) in gliomas was associated with hypermethylation of its promoter and the presence of a wild-type p53 in these samples.

Effects of microbeam radiation therapy on normal and tumoral blood vessels.

PubMed

Bouchet, Audrey; Serduc, Raphäel; Laissue, Jean Albert; Djonov, Valentin

2015-09-01

Microbeam radiation therapy (MRT) is a new form of preclinical radiotherapy using quasi-parallel arrays of synchrotron X-ray microbeams. While the deposition of several hundred Grays in the microbeam paths, the normal brain tissues presents a high tolerance which is accompanied by the permanence of apparently normal vessels. Conversely, the efficiency of MRT on tumor growth control is thought to be related to a preferential damaging of tumor blood vessels. The high resistance of the healthy vascular network was demonstrated in different animal models by in vivo biphoton microscopy, magnetic resonance imaging, and histological studies. While a transient increase in permeability was shown, the structure of the vessels remained intact. The use of a chick chorioallantoic membrane at different stages of development showed that the damages induced by microbeams depend on vessel maturation. In vivo and ultrastructural observations showed negligible effects of microbeams on the mature vasculature at late stages of development; nevertheless a complete destruction of the immature capillary plexus was found in the microbeam paths. The use of MRT in rodent models revealed a preferential effect on tumor vessels. Although no major modification was observed in the vasculature of normal brain tissue, tumors showed a denudation of capillaries accompanied by transient increased permeability followed by reduced tumor perfusion and finally, a decrease in number of tumor vessels. Thus, MRT is a very promising treatment strategy with pronounced tumor control effects most likely based on the anti-vascular effects of MRT. Copyright © 2015. Published by Elsevier Ltd.

Sibutramine promotes amygdala activity under fasting conditions in obese women.

PubMed

Oltmanns, Kerstin M; Heldmann, Marcus; Daul, Susanne; Klose, Silke; Rotte, Michael; Schäfer, Michael; Heinze, Hans-Jochen; Münte, Thomas F; Lehnert, Hendrik

2012-06-01

Sibutramine, a centrally-acting selective monoamine reuptake inhibitor, has been used as an appetite suppressant drug in obesity. To gain insight into the central nervous actions of sibutramine, brain responses to pictures of food items after sibutramine vs placebo application were assessed by functional magnetic resonance imaging (fMRI) in obese women. In a randomized double-blind crossover design, 10 healthy obese women (BMI 31.8-39.9 kg/m(2)) received 15 mg/d of sibutramine vs placebo for 14 d. Obese participants, and a group of 10 age-matched normal weight controls, viewed pictures of food items and control objects in hungry and satiated states while lying in the MR scanner. The paradigm followed a block design. In obese participants, fMRI measurements were conducted prior and after two weeks of daily sibutramine or placebo administration, whereas control participants were scanned only at one point in time. Upon food item presentation, obese participants showed increased brain activity in areas related to emotional and reward processing, perceptual processing, and cognitive control as compared to normal weight controls. Sibutramine exerted a divergent satiety-dependent effect on amygdala activity in obese participants, increasing activity in the hungry state while decreasing it under conditions of satiation. Our results demonstrate a modulatory influence of sibutramine on amygdala activity in obese women which may underlie the appetite suppressant effects of the drug.

Occult White Matter Damage Contributes to Intellectual Disability in Tuberous Sclerosis Complex

ERIC Educational Resources Information Center

Yu, Chunshui; Lin, Fuchun; Zhao, Li; Ye, Jing; Qin, Wen

2009-01-01

Whether patients with tuberous sclerosis complex (TSC) have brain normal-appearing white matter (NAWM) damage and whether such damage contributes to their intellectual disability were examined in 15 TSC patients and 15 gender- and age-matched healthy controls using diffusion tensor imaging (DTI). Histogram and region of interest (ROI) analyses of…

Hypothermic and antipyretic effects of ACTH (1-24) and alpha-melanotropin in guinea-pigs

NASA Technical Reports Server (NTRS)

Kandasamy, S. B.; Williams, B. A.

1984-01-01

Intracerebroventricular administration of adrenocorticotropin (ACTH 1-24) and alpha-melanotropin (alpha-MSH), peptides which occur naturally in brain induced dose-related hypothermia in guinea-pigs at room temperature (21 C) and also produced greater hypothermia at low (10 C) ambient temperature. However, when the experiments were repeated in a warm (30 C) environment, no effect on body temperature was observed. These results indicate that the peptides did not reduce the central set-point of temperature control. The hypothermia induced by ACTH and alpha-MSH was not mediated via histamine H1- or H2-receptors and serotonin since the H1-receptor antagonist, mepyramine, the H2-receptor antagonist, cimetidine, and the serotonin antagonist, methysergide, had no antagonistic effects. The peptides were antipyretic since they reduced pyrogen-induced-fever and hyperthermia due to prostaglandin E2, norepinephrine and dibutyryl cAMP, at a dose which did not affect normal body temperature. The powerful central effects of these peptides on normal body temperature, fever and hyperthermia, together with their presence of the brain regions important to temperature control, suggest that they participate in thermoregulation.

Antisocial and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin-releasing factor.

PubMed

Turner, Laura H; Lim, Chen E; Heinrichs, Stephen C

2007-02-01

Social interaction phenotyping is an unexplored niche in animal modeling of epilepsy despite the sensitivity of affiliative behaviors to emotionality and stress, which are known seizure triggers. Thus, the present studies examined the social phenotype of seizure-susceptible El and nonsusceptible ddY strains both in untreated animals and following preexposure to a handling stressor. The second aim of the present studies was to evaluate the dependence of sociability in El mice on the proconvulsive, stress neuropeptide corticotropin-releasing factor (CRF) using CRF-SAP, a conjugate of CRF and the toxin saporin, which selectively reduced CRF peptide levels in the basolateral amygdala of El mice. El mice exhibited lower social investigation times than ddY counterparts, whereas central administration of CRF-SAP normalized social investigation times relative to ddY controls. Moreover, handling-induced seizures in El mice were reduced by 50% following treatment with CRF-SAP relative to saporin alone-injected El controls. The results of this study suggest that tonically activated CRF systems in the El mouse brain suppress affiliative behavior and facilitate evoked seizures.

Localized N20 Component of Somatosensory Evoked Magnetic Fields in Frontoparietal Brain Tumor Patients Using Noise-Normalized Approaches.

PubMed

Elaina, Nor Safira; Malik, Aamir Saeed; Shams, Wafaa Khazaal; Badruddin, Nasreen; Abdullah, Jafri Malin; Reza, Mohammad Faruque

2018-06-01

To localize sensorimotor cortical activation in 10 patients with frontoparietal tumors using quantitative magnetoencephalography (MEG) with noise-normalized approaches. Somatosensory evoked magnetic fields (SEFs) were elicited in 10 patients with somatosensory tumors and in 10 control participants using electrical stimulation of the median nerve via the right and left wrists. We localized the N20m component of the SEFs using dynamic statistical parametric mapping (dSPM) and standardized low-resolution brain electromagnetic tomography (sLORETA) combined with 3D magnetic resonance imaging (MRI). The obtained coordinates were compared between groups. Finally, we statistically evaluated the N20m parameters across hemispheres using non-parametric statistical tests. The N20m sources were accurately localized to Brodmann area 3b in all members of the control group and in seven of the patients; however, the sources were shifted in three patients relative to locations outside the primary somatosensory cortex (SI). Compared with the affected (tumor) hemispheres in the patient group, N20m amplitudes and the strengths of the current sources were significantly lower in the unaffected hemispheres and in both hemispheres of the control group. These results were consistent for both dSPM and sLORETA approaches. Tumors in the sensorimotor cortex lead to cortical functional reorganization and an increase in N20m amplitude and current-source strengths. Noise-normalized approaches for MEG analysis that are integrated with MRI show accurate and reliable localization of sensorimotor function.

Cognitive performance in multiple sclerosis: the contribution of intellectual enrichment and brain MRI measures.

PubMed

Santangelo, Gabriella; Bisecco, Alvino; Trojano, Luigi; Sacco, Rosaria; Siciliano, Mattia; d'Ambrosio, Alessandro; Della Corte, Marida; Lavorgna, Luigi; Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2018-05-26

Cognitive reserve (CR) is a construct that originates from the observation of poor correspondence between brain damage and clinical symptoms. The aim of the study was to investigate the association between cognitive reserve (CR), brain reserve (BR) and cognitive functions and to evaluate whether CR might attenuate/moderate the negative impact of brain atrophy and lesion load on cognitive functions in multiple sclerosis (MS). To achieve these aims, ninety-eight relapsing-remitting MS patients underwent the brief repeatable battery of neuropsychological tests and Stroop test (ST). CR was assessed by vocabulary-based estimate of lifetime intellectual enrichment. All patients underwent a 3T MRI to assess T2-lesion load and atrophy measures, including normalized gray matter and white matter (nWMV) volumes. The BR was evaluated by maximal lifetime brain volume expressed by intracranial volume (ICV). Hierarchical regressions were used to investigate whether higher BR and/or CR is related to better cognitive performances after controlling for potentially confounding factors. The ICV was not associated with any cognitive tests. Intellectual enrichment was positively associated with performance on tests assessing memory, attention and information processing speed, verbal fluency and inhibitory control. Significant relationship between nWMV and ST was moderated by intellectual enrichment. In conclusion, the findings suggested that CR seems to mitigate cognitive dysfunction in MS patients and can reduce the negative impact of brain atrophy on inhibitory control, relevant for integrity of instrumental activities of daily living.

Dietary triglycerides act on mesolimbic structures to regulate the rewarding and motivational aspects of feeding

PubMed Central

Cansell, Céline; Castel, Julien; Denis, Raphaël G. P.; Rouch, Claude; Delbes, Anne-Sophie; Martinez, Sarah; Mestivier, Denis; Finan, Brian; Maldonado-Aviles, Jaime G.; Rijnsburger, Merel; Tschöp, Matthias H.; DiLeone, Ralph J.; Eckel, Robert H.; la Fleur, Susanne E.; Magnan, Christophe; Hnasko, Thomas S.; Luquet, Serge

2014-01-01

Circulating triglycerides (TG) normally increase after a meal but are altered in pathophysiological conditions such as obesity. Although TG metabolism in the brain remains poorly understood, several brain structures express enzymes that process TG-enriched particles, including mesolimbic structures. For this reason, and because consumption of high fat diet alters dopamine signaling, we tested the hypothesis that TG might directly target mesolimbic reward circuits to control reward-seeking behaviors. We found that the delivery of small amounts of TG to the brain through the carotid artery rapidly reduced both spontaneous and amphetamine-induced locomotion, abolished preference for palatable food, and reduced the motivation to engage in food-seeking behavior. Conversely, targeted disruption of the TG-hydrolyzing enzyme lipoprotein lipase specifically in the nucleus accumbens increased palatable food preference and food seeking behavior. Finally, prolonged TG perfusion resulted in a return to normal palatable food preference despite continued locomotor suppression, suggesting that adaptive mechanisms occur. These findings reveal new mechanisms by which dietary fat may alter mesolimbic circuit function and reward seeking. PMID:24732670

Brain-targeted stem cell gene therapy corrects mucopolysaccharidosis type II via multiple mechanisms.

PubMed

Gleitz, Hélène Fe; Liao, Ai Yin; Cook, James R; Rowlston, Samuel F; Forte, Gabriella Ma; D'Souza, Zelpha; O'Leary, Claire; Holley, Rebecca J; Bigger, Brian W

2018-06-08

The pediatric lysosomal storage disorder mucopolysaccharidosis type II is caused by mutations in IDS, resulting in accumulation of heparan and dermatan sulfate, causing severe neurodegeneration, skeletal disease, and cardiorespiratory disease. Most patients manifest with cognitive symptoms, which cannot be treated with enzyme replacement therapy, as native IDS does not cross the blood-brain barrier. We tested a brain-targeted hematopoietic stem cell gene therapy approach using lentiviral IDS fused to ApoEII (IDS.ApoEII) compared to a lentivirus expressing normal IDS or a normal bone marrow transplant. In mucopolysaccharidosis II mice, all treatments corrected peripheral disease, but only IDS.ApoEII mediated complete normalization of brain pathology and behavior, providing significantly enhanced correction compared to IDS. A normal bone marrow transplant achieved no brain correction. Whilst corrected macrophages traffic to the brain, secreting IDS/IDS.ApoEII enzyme for cross-correction, IDS.ApoEII was additionally more active in plasma and was taken up and transcytosed across brain endothelia significantly better than IDS via both heparan sulfate/ApoE-dependent receptors and mannose-6-phosphate receptors. Brain-targeted hematopoietic stem cell gene therapy provides a promising therapy for MPS II patients. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis.

PubMed

Barro, Christian; Benkert, Pascal; Disanto, Giulio; Tsagkas, Charidimos; Amann, Michael; Naegelin, Yvonne; Leppert, David; Gobbi, Claudio; Granziera, Cristina; Yaldizli, Özgür; Michalak, Zuzanna; Wuerfel, Jens; Kappos, Ludwig; Parmar, Katrin; Kuhle, Jens

2018-05-30

Neuro-axonal injury is a key factor in the development of permanent disability in multiple sclerosis. Neurofilament light chain in peripheral blood has recently emerged as a biofluid marker reflecting neuro-axonal damage in this disease. We aimed at comparing serum neurofilament light chain levels in multiple sclerosis and healthy controls, to determine their association with measures of disease activity and their ability to predict future clinical worsening as well as brain and spinal cord volume loss. Neurofilament light chain was measured by single molecule array assay in 2183 serum samples collected as part of an ongoing cohort study from 259 patients with multiple sclerosis (189 relapsing and 70 progressive) and 259 healthy control subjects. Clinical assessment, serum sampling and MRI were done annually; median follow-up time was 6.5 years. Brain volumes were quantified by structural image evaluation using normalization of atrophy, and structural image evaluation using normalization of atrophy, cross-sectional, cervical spinal cord volumes using spinal cord image analyser (cordial). Results were analysed using ordinary linear regression models and generalized estimating equation modelling. Serum neurofilament light chain was higher in patients with a clinically isolated syndrome or relapsing remitting multiple sclerosis as well as in patients with secondary or primary progressive multiple sclerosis than in healthy controls (age adjusted P < 0.001 for both). Serum neurofilament light chain above the 90th percentile of healthy controls values was an independent predictor of Expanded Disability Status Scale worsening in the subsequent year (P < 0.001). The probability of Expanded Disability Status Scale worsening gradually increased by higher serum neurofilament light chain percentile category. Contrast enhancing and new/enlarging lesions were independently associated with increased serum neurofilament light chain (17.8% and 4.9% increase per lesion respectively; P < 0.001). The higher the serum neurofilament light chain percentile level, the more pronounced was future brain and cervical spinal volume loss: serum neurofilament light chain above the 97.5th percentile was associated with an additional average loss in brain volume of 1.5% (P < 0.001) and spinal cord volume of 2.5% over 5 years (P = 0.009). Serum neurofilament light chain correlated with concurrent and future clinical and MRI measures of disease activity and severity. High serum neurofilament light chain levels were associated with both brain and spinal cord volume loss. Neurofilament light chain levels are a real-time, easy to measure marker of neuro-axonal injury that is conceptually more comprehensive than brain MRI.

Obesity and neuroinflammatory phenotype in mice lacking endothelial megalin.

PubMed

Bartolome, Fernando; Antequera, Desiree; Tavares, Eva; Pascual, Consuelo; Maldonado, Rosario; Camins, Antoni; Carro, Eva

2017-01-31

The multiligand receptor megalin controls the brain uptake of a number of ligands, including insulin and leptin. Despite the role of megalin in the transport of these metabolically relevant hormones, the role of megalin at the blood-brain-barrier (BBB) has not yet been explored in the context of metabolic regulation. Here we investigate the role of brain endothelial megalin in energy metabolism and leptin signaling using an endothelial cell-specific megalin deficient (EMD) mouse model. We found megalin is important to protect mice from developing obesity and metabolic syndrome when mice are fed a normal chow diet. EMD mice developed neuroinflammation, by triggering several pro-inflammatory cytokines, displayed reduced neurogenesis and mitochondrial deregulation. These results implicate brain endothelial megalin expression in obesity-related metabolic changes through the leptin signaling pathway proposing a potential link between obesity and neurodegeneration.

Accelerated Changes in Cortical Thickness Measurements with Age in Military Service Members with Traumatic Brain Injury.

PubMed

Savjani, Ricky R; Taylor, Brian A; Acion, Laura; Wilde, Elisabeth A; Jorge, Ricardo E

2017-11-15

Finding objective and quantifiable imaging markers of mild traumatic brain injury (TBI) has proven challenging, especially in the military population. Changes in cortical thickness after injury have been reported in animals and in humans, but it is unclear how these alterations manifest in the chronic phase, and it is difficult to characterize accurately with imaging. We used cortical thickness measures derived from Advanced Normalization Tools (ANTs) to predict a continuous demographic variable: age. We trained four different regression models (linear regression, support vector regression, Gaussian process regression, and random forests) to predict age from healthy control brains from publicly available datasets (n = 762). We then used these models to predict brain age in military Service Members with TBI (n = 92) and military Service Members without TBI (n = 34). Our results show that all four models overpredicted age in Service Members with TBI, and the predicted age difference was significantly greater compared with military controls. These data extend previous civilian findings and show that cortical thickness measures may reveal an association of accelerated changes over time with military TBI.

Multimodal imaging of the self-regulating developing brain.

PubMed

Fjell, Anders M; Walhovd, Kristine Beate; Brown, Timothy T; Kuperman, Joshua M; Chung, Yoonho; Hagler, Donald J; Venkatraman, Vijay; Roddey, J Cooper; Erhart, Matthew; McCabe, Connor; Akshoomoff, Natacha; Amaral, David G; Bloss, Cinnamon S; Libiger, Ondrej; Darst, Burcu F; Schork, Nicholas J; Casey, B J; Chang, Linda; Ernst, Thomas M; Gruen, Jeffrey R; Kaufmann, Walter E; Kenet, Tal; Frazier, Jean; Murray, Sarah S; Sowell, Elizabeth R; van Zijl, Peter; Mostofsky, Stewart; Jernigan, Terry L; Dale, Anders M

2012-11-27

Self-regulation refers to the ability to control behavior, cognition, and emotions, and self-regulation failure is related to a range of neuropsychiatric problems. It is poorly understood how structural maturation of the brain brings about the gradual improvement in self-regulation during childhood. In a large-scale multicenter effort, 735 children (4-21 y) underwent structural MRI for quantification of cortical thickness and surface area and diffusion tensor imaging for quantification of the quality of major fiber connections. Brain development was related to a standardized measure of cognitive control (the flanker task from the National Institutes of Health Toolbox), a critical component of self-regulation. Ability to inhibit responses and impose cognitive control increased rapidly during preteen years. Surface area of the anterior cingulate cortex accounted for a significant proportion of the variance in cognitive performance. This finding is intriguing, because characteristics of the anterior cingulum are shown to be related to impulse, attention, and executive problems in neurodevelopmental disorders, indicating a neural foundation for self-regulation abilities along a continuum from normality to pathology. The relationship was strongest in the younger children. Properties of large-fiber connections added to the picture by explaining additional variance in cognitive control. Although cognitive control was related to surface area of the anterior cingulate independently of basic processes of mental speed, the relationship between white matter quality and cognitive control could be fully accounted for by speed. The results underscore the need for integration of different aspects of brain maturation to understand the foundations of cognitive development.

Attentional control activation relates to working memory in attention-deficit/hyperactivity disorder.

PubMed

Burgess, Gregory C; Depue, Brendan E; Ruzic, Luka; Willcutt, Erik G; Du, Yiping P; Banich, Marie T

2010-04-01

Attentional control difficulties in individuals with attention-deficit/hyperactivity disorder (ADHD) might reflect poor working memory (WM) ability, especially because WM ability and attentional control rely on similar brain regions. The current study examined whether WM ability might explain group differences in brain activation between adults with ADHD and normal control subjects during attentional demand. Participants were 20 adults with ADHD combined subtype with no comorbid psychiatric or learning disorders and 23 control subjects similar in age, IQ, and gender. The WM measures were obtained from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-Revised. Brain activation was assessed with functional magnetic resonance imaging (fMRI) while performing a Color-Word Stroop task. Group differences in WM ability explained a portion of the activation in left dorsolateral prefrontal cortex (DLPFC), which has been related to the creation and maintenance of an attentional set for task-relevant information. In addition, greater WM ability predicted increased activation of brain regions related to stimulus-driven attention and response selection processes in the ADHD group but not in the control group. The inability to maintain an appropriate task set in young adults with combined type ADHD, associated with decreased activity in left DLPFC, might in part be due to poor WM ability. Furthermore, in individuals with ADHD, higher WM ability might relate to increased recruitment of stimulus-driven attention and response selection processes, perhaps as a compensatory strategy. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Correlation between standardized assessment of concussion scores and small-world brain network in mild traumatic brain injury.

PubMed

Yan, Yan; Song, Jian; Xu, Guozheng; Yao, Shun; Cao, Chenglong; Li, Chang; Peng, Guibao; Du, Hao

2017-10-01

This study investigated the characteristics of the small-world brain network architecture of patients with mild traumatic brain injury (MTBI), and a correlation between brain functional connectivity network properties in the resting-state fMRI and Standardized Assessment of Concussion (SAC) parameters. The neurological conditions of 22 MTBI patients and 17 normal control individuals were evaluated according to the SAC. Resting-state fMRI was performed in all subjects 3 and 7days after injury respectively. After preprocessing the fMRI data, cortex functional regions were marked using AAL90 and Dosenbach160 templates. The small-world network parameters and areas under the integral curves were computed in the range of sparsity from 0.01 to 0.5. Independent-sample t-tests were used to compare these parameters between the MTBI and control group. Significantly different parameters were investigated for correlations with SAC scores; those that correlated were chosen for further curve fitting. The clustering coefficient, the communication efficiency across in local networks, and the strength of connectivity were all higher in MTBI patients relative to control individuals. Parameters in 160 brain regions of the MTBI group significantly correlated with total SAC score and score for attention; the network parameters may be a quadratic function of attention scores of SAC and a cubic function of SAC scores. MTBI patients were characterized by elevated communication efficiency across global brain regions, and in local networks, and strength of mean connectivity. These features may be associated with brain function compensation. The network parameters significantly correlated with SAC total and attention scores. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of History of Brain Disease or Brain Trauma on Psychopathological Abnormality in Young Male in Korea : Analysis of Multiphasic Personal Inventory Test

PubMed Central

Paik, Ho Kyu; Oh, Chang-Hyun; Choi, Kang; Kim, Chul-Eung; Yoon, Seung Hwan

2011-01-01

Objective The purpose of this study is to confirm whether brain disease or brain trauma actually affect psychopathology in young male group in Korea. Methods The authors manually reviewed the result of Korean military multiphasic personal inventory (KMPI) in the examination of conscription in Korea from January 2008 to May 2010. There were total 237 young males in this review. Normal volunteers group (n=150) was composed of those who do not have history of brain disease or brain trauma. Brain disease group (n=33) was consisted of those with history of brain disease. Brain trauma group (n=54) was consisted of those with history of brain trauma. The results of KMPI in each group were compared. Results Abnormal results of KMPI were found in both brain disease and trauma groups. In the brain disease group, higher tendencies of faking bad response, anxiety, depression, somatization, personality disorder, schizophrenic and paranoid psychopathy was observed and compared to the normal volunteers group. In the brain trauma group, higher tendencies of faking-good, depression, somatization and personality disorder was observed and compared to the normal volunteers group. Conclusion Young male with history of brain disease or brain trauma may have higher tendencies to have abnormal results of multiphasic personal inventory test compared to young male without history of brain disease or brain trauma, suggesting that damaged brain may cause psychopathology in young male group in Korea. PMID:22053230

Efficacy of a modern neuroscience approach versus usual care evidence-based physiotherapy on pain, disability and brain characteristics in chronic spinal pain patients: protocol of a randomized clinical trial

PubMed Central

2014-01-01

Background Among the multiple conservative modalities, physiotherapy is a commonly utilized treatment modality in managing chronic non-specific spinal pain. Despite the scientific progresses with regard to pain and motor control neuroscience, treatment of chronic spinal pain (CSP) often tends to stick to a peripheral biomechanical model, without targeting brain mechanisms. With a view to enhance clinical efficacy of existing physiotherapeutic treatments for CSP, the development of clinical strategies targeted at ‘training the brain’ is to be pursued. Promising proof-of-principle results have been reported for the effectiveness of a modern neuroscience approach to CSP when compared to usual care, but confirmation is required in a larger, multi-center trial with appropriate evidence-based control intervention and long-term follow-up. The aim of this study is to assess the effectiveness of a modern neuroscience approach, compared to usual care evidence-based physiotherapy, for reducing pain and improving functioning in patients with CSP. A secondary objective entails examining the effectiveness of the modern neuroscience approach versus usual care physiotherapy for normalizing brain gray matter in patients with CSP. Methods/Design The study is a multi-center, triple-blind, two-arm (1:1) randomized clinical trial with 1-year follow-up. 120 CSP patients will be randomly allocated to either the experimental (receiving pain neuroscience education followed by cognition-targeted motor control training) or the control group (receiving usual care physiotherapy), each comprising of 3 months treatment. The main outcome measures are pain (including symptoms and indices of central sensitization) and self-reported disability. Secondary outcome measures include brain gray matter structure, motor control, muscle properties, and psychosocial correlates. Clinical assessment and brain imaging will be performed at baseline, post-treatment and at 1-year follow-up. Web-based questionnaires will be completed at baseline, after the first 3 treatment sessions, post-treatment, and at 6 and 12-months follow-up. Discussion Findings may provide empirical evidence on: (1) the effectiveness of a modern neuroscience approach to CSP for reducing pain and improving functioning, (2) the effectiveness of a modern neuroscience approach for normalizing brain gray matter in CSP patients, and (3) factors associated with therapy success. Hence, this trial might contribute towards refining guidelines for good clinical practice and might be used as a basis for health authorities’ recommendations. Trial registration ClinicalTrials.gov Identifier: NCT02098005. PMID:24885889

Neural markers of social and monetary rewards in children with Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

PubMed Central

Gonzalez-Gadea, Maria Luz; Sigman, Mariano; Rattazzi, Alexia; Lavin, Claudio; Rivera-Rei, Alvaro; Marino, Julian; Manes, Facundo; Ibanez, Agustin

2016-01-01

Recent theories of decision making propose a shared value-related brain mechanism for encoding monetary and social rewards. We tested this model in children with Attention-Deficit/Hyperactivity Disorder (ADHD), children with Autism Spectrum Disorder (ASD) and control children. We monitored participants’ brain dynamics using high density-electroencephalography while they played a monetary and social reward tasks. Control children exhibited a feedback Error-Related Negativity (fERN) modulation and Anterior Cingulate Cortex (ACC) source activation during both tasks. Remarkably, although cooperation resulted in greater losses for the participants, the betrayal options generated greater fERN responses. ADHD subjects exhibited an absence of fERN modulation and reduced ACC activation during both tasks. ASD subjects exhibited normal fERN modulation during monetary choices and inverted fERN/ACC responses in social options than did controls. These results suggest that in neurotypicals, monetary losses and observed disloyal social decisions induced similar activity in the brain value system. In ADHD children, difficulties in reward processing affected early brain signatures of monetary and social decisions. Conversely, ASD children showed intact neural markers of value-related monetary mechanisms, but no brain modulation by prosociality in the social task. These results offer insight into the typical and atypical developments of neural correlates of monetary and social reward processing. PMID:27464551

[Research of anti-aging mechanism of ginsenoside Rg1 on brain].

PubMed

Li, Cheng-peng; Zhang, Meng-si; Liu, Jun; Geng, Shan; Li, Jing; Zhu, Jia-hong; Zhang, Yan-yan; Jia, Yan-yan; Wang, Lu; Wang, Shun-he; Wang, Ya-ping

2014-11-01

Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus. Rats of Rg1 brain aging group had their spatial learning and memory capacities enhanced, SA-beta-Gal positive granules in section of brain tissue decreased, the activity of antioxidant enzyme SOD and the contents of GSH increased in hippocampus, the level of IL-1 and IL-6 in hippocampus decreased, the length contraction of telomere suppressed while the change of telomerase activity increased in hippocampus. Compared with that of normal group, the spatial learning and memory capacities were enhanced in Rg1 normal group, SA-beta-Gal positive granules in section of brain tissue decreased in Rg1 normal group, the level of IL-1 and IL-6 in hippocampus decreased in Rg1 normal group. The results indicated that improvement of antioxidant ability, regulating the level of proinflammatory cytokines and regulation of telomerase system may be the underlying anti-aging mechanism of Ginsenoside Rg1.

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.

Post-stroke acquired amusia: A comparison between right- and left-brain hemispheric damages.

PubMed

Jafari, Zahra; Esmaili, Mahdiye; Delbari, Ahmad; Mehrpour, Masoud; Mohajerani, Majid H

2017-01-01

Although extensive research has been published about the emotional consequences of stroke, most studies have focused on emotional words, speech prosody, voices, or facial expressions. The emotional processing of musical excerpts following stroke has been relatively unexplored. The present study was conducted to investigate the effects of chronic stroke on the recognition of basic emotions in music. Seventy persons, including 25 normal controls (NC), 25 persons with right brain damage (RBD) from stroke, and 20 persons with left brain damage (LBD) from stroke between the ages of 31-71 years were studied. The Musical Emotional Bursts (MEB) test, which consists of a set of short musical pieces expressing basic emotional states (happiness, sadness, and fear) and neutrality, was used to test musical emotional perception. Both stroke groups were significantly poorer than normal controls for the MEB total score and its subtests (p < 0.001). The RBD group was significantly less able than the LBD group to recognize sadness (p = 0.047) and neutrality (p = 0.015). Negative correlations were found between age and MEB scores for all groups, particularly the NC and RBD groups. Our findings indicated that stroke affecting the auditory cerebrum can cause acquired amusia with greater severity in RBD than LBD. These results supported the "valence hypothesis" of right hemisphere dominance in processing negative emotions.

Higher fasting plasma glucose is associated with smaller striatal volume and poorer fine motor skills in a longitudinal cohort.

PubMed

Zhang, Tianqi; Shaw, Marnie E; Walsh, Erin I; Sachdev, Perminder S; Anstey, Kaarin J; Cherbuin, Nicolas

2018-06-07

Previous studies have demonstrated associations between higher blood glucose and brain atrophy and functional deficits, however, little is known about the association between blood glucose, striatal volume and striatal function despite sensori-motor deficits being reported in diabetes. This study investigated the relationship between blood glucose levels, striatal volume and fine motor skills in a longitudinal cohort of cognitively healthy individuals living in the community with normal or impaired fasting glucose or type 2 diabetes. Participants were 271 cognitively healthy individuals (mean age 63 years at inclusion) with normal fasting glucose levels (<5.6 mmol/L) (n=173), impaired fasting glucose (5.6-6.9 mmol/L) (n=57), or with type 2 diabetes (≥7.0 mmol/L) (n=41). Fasting glucose, Purdue Pegboard scores as measurement of fine motor skills, and brain scans were collected at wave 1, 2 and 4, over a total follow-up of twelve years. Striatal volumes were measured using FreeSurfer after controlling for age, sex and intracranial volume. Results showed that type 2 diabetes was associated with smaller right putamen volume and lower Purdue Pegboard scores after controlling for age, sex and intracranial volume. These findings add to the evidence suggesting that higher blood glucose levels, especially type 2 diabetes, may impair brain structure and function. Copyright © 2018. Published by Elsevier B.V.

SU-E-T-587: Optimal Volumetric Modulated Arc Radiotherapy Treatment Planning Technique for Multiple Brain Metastases with Increasing Number of Arcs

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

Keeling, V; Hossain, S; Hildebrand, K

Purpose: To show improvements in dose conformity and normal brain tissue sparing using an optimal planning technique (OPT) against clinically acceptable planning technique (CAP) in the treatment of multiple brain metastases. Methods: A standardized international benchmark case with12 intracranial tumors was planned using two different VMAT optimization methods. Plans were split into four groups with 3, 6, 9, and 12 targets each planned with 3, 5, and 7 arcs using Eclipse TPS. The beam geometries were 1 full coplanar and half non-coplanar arcs. A prescription dose of 20Gy was used for all targets. The following optimization criteria was used (OPTmore » vs. CAP): (No upper limit vs.108% upper limit for target volume), (priority 140–150 vs. 75–85 for normal-brain-tissue), and (selection of automatic sparing Normal-Tissue-Objective (NTO) vs. Manual NTO). Both had priority 50 to critical structures such as brainstem and optic-chiasm, and both had an NTO priority 150. Normal-brain-tissue doses along with Paddick Conformity Index (PCI) were evaluated. Results: In all cases PCI was higher for OPT plans. The average PCI (OPT,CAP) for all targets was (0.81,0.64), (0.81,0.63), (0.79,0.57), and (0.72,0.55) for 3, 6, 9, and 12 target plans respectively. The percent decrease in normal brain tissue volume (OPT/CAP*100) achieved by OPT plans was (reported as follows: V4, V8, V12, V16, V20) (184, 343, 350, 294, 371%), (192, 417, 380, 299, 360%), and (235, 390, 299, 281, 502%) for the 3, 5, 7 arc 12 target plans, respectively. The maximum brainstem dose decreased for the OPT plan by 4.93, 4.89, and 5.30 Gy for 3, 5, 7 arc 12 target plans, respectively. Conclusion: Substantial increases in PCI, critical structure sparing, and decreases in normal brain tissue dose were achieved by eliminating upper limits from optimization, using automatic sparing of normal tissue function with high priority, and a high priority to normal brain tissue.« less

Compression Stiffening of Brain and its Effect on Mechanosensing by Glioma Cells

NASA Astrophysics Data System (ADS)

Pogoda, Katarzyna

The stiffness of tissues, often characterized by their time-dependent elastic properties, is tightly controlled under normal condition and central nervous system tissue is among the softest tissues. Changes in tissue and organ stiffness occur in some physiological conditions and are frequently symptoms of diseases such as fibrosis, cardiovascular disease and many forms of cancer. Primary cells isolated from various tissues often respond to changes in the mechanical properties of their substrates, and the range of stiffness over which these responses occur appear to be limited to the tissue elastic modulus from which they are derived. Our goal was to test the hypotheses that the stiffness of tumors derived from CNS tissue differs from that of normal brain, and that transformed cells derived from such tumors exhibit mechanical responses that differ from those of normal glial cells. Unlike breast and some other cancers where the stroma and the tumor itself is substantially stiffer than the surrounding normal tissue, our data suggest that gliomas can arise without a gross change in the macroscopic tissue stiffness when measured at low strains without compression. However, both normal brain and glioma samples stiffen with compression, but not in elongation and increased shear strains. On the other hand, different classes of immortalized cells derived from human glioblastoma show substantially different responses to the stiffness of substrates in vitrowhen grown on soft polyacrylamide and hyaluronic acid gels. This outcome supports the hypothesis that compression stiffening, which might occur with increased vascularization and interstitial pressure gradients that are characteristic of tumors, effectively stiffens the environment of glioma cells, and that in situ, the elastic resistance these cells sense might be sufficient to trigger the same responses that are activated in vitro by increased substrate stiffness.

Effects of levothyroxine on learning and memory deficits in a rat model of Alzheimer's disease: the role of BDNF and oxidative stress.

PubMed

Bavarsad, Kowsar; Hadjzadeh, Mousa-Al-Reza; Hosseini, Mahmoud; Pakdel, Roghayeh; Beheshti, Farimah; Bafadam, Soleyman; Ashaari, Zeinab

2018-06-21

The effect of levothyroxine (L-T4) on the learning and memory impairment induced by streptozotocin (STZ) and brain tissue oxidative damage in rats was evaluated. An animal model of the Alzheimer's disease (AD) was established by intracerebroventricular injection of STZ (3 mg/kg) in male Wistar rats (250 ± 50 g). After that, the rats were treated for 3 weeks with L-T4 (10, 100 μg/kg) or normal saline. Passive avoidance (PA) learning and spatial memory were evaluated using shuttle box and Morris water maze (MWM), respectively. Finally, the rats were euthanized, their blood samples were collected for further thyroxine assessment and their brains were removed after decapitation in order to measure the oxidative stress parameters and brain-derived neurotrophic factor (BDNF). In the MWM, latency (s) increased in the AD rats compared with the normal control group while it decreased in the 10 μg/kg L-T4 injected AD rats compared with the AD group. In the PA, the latency for entering the dark compartment was lower in the AD group than in the normal control group and it decreased in the 10 μg/kg L-T4 injected AD rats. The low dose of L-T4 (10 μg/kg) reduced malondialdehyde concentration but increased thiols concentration, superoxide dismutase, catalase activities and BDNF level in hippocampal tissues of the AD rats. Injection of L-T4 (10 μg/kg) alleviated memory deficits and also improved factors of oxidative stress and BDNF level in the STZ-induced AD rats.

Introducing Euro-Glo, a rare earth metal chelate with numerous applications for the fluorescent localization of myelin and amyloid plaques in brain tissue sections.

PubMed

Schmued, Larry; Raymick, James

2017-03-01

The vast majority of fluorochromes are organic in nature and none of the few existing chelates have been applied as histological tracers for localizing brain anatomy and pathology. In this study we have developed and characterized a Europium chelate with the ability to fluorescently label normal and pathological myelin in control and toxicant-exposed rats, as well as the amyloid plaques in aged AD/Tg mice. This study demonstrates how Euro-Glo can be used for the detailed labeling of both normal myelination in the control rat as well as myelin pathology in the kainic acid exposed rat. In addition, this study demonstrates how E-G will label the shell of amyloid plaques in an AD/Tg mouse model of Alzheimer's disease a red color, while the plaque core appears blue in color. The observed E-G staining pattern is compared with that of well characterized tracers specific for the localization of myelin (Black-Gold II), degenerating neurons (Fluoro-Jade C), A-beta aggregates (Amylo-Glo) and glycolipids (PAS). This study represents the first time a rare earth metal (REM) chelate has been used as a histochemical tracer in the brain. This novel tracer, Euro-Glo (E-G), exhibits numerous advantages over conventional organic fluorophores including high intensity emission, high resistance to fading, compatibility with multiple labeling protocols, high Stoke's shift value and an absence of bleed-through of the signal through other filters. Euro-Glo represents the first fluorescent metal chelate to be used as a histochemical tracer, specifically to localize normal and pathological myelin as well as amyloid plaques. Copyright © 2016. Published by Elsevier B.V.

Human serum albumin nanoparticles modified with apolipoprotein A-I cross the blood-brain barrier and enter the rodent brain.

PubMed

Zensi, Anja; Begley, David; Pontikis, Charles; Legros, Celine; Mihoreanu, Larisa; Büchel, Claudia; Kreuter, Jörg

2010-12-01

Nanoparticles made of human serum albumin (HSA) and modified with apolipoproteins have previously been shown to transport drugs, which normally do not enter the brain, across the blood-brain barrier (BBB). However the precise mechanism by which nanoparticles with different apolipoproteins on their surface can target to the brain, as yet, has not been totally elucidated. In the present study, HSA nanoparticles with covalently bound apolipoprotein A-I (Apo A-I) as a targetor for brain capillary endothelial cells were injected intravenously into SV 129 mice and Wistar rats. The rodents were sacrificed after 15 or 30 min, and their brains were examined by transmission electron microscopy. Apo A-I nanoparticles could be found inside the endothelial cells of brain capillaries as well as within parenchymal brain tissue of both, mice and rats, whereas control particles without Apo A-I on their surface did not cross the BBB during our experiments. The maintenance of tight junction integrity and barrier function during treatment with nanoparticles was demonstrated by perfusion with a fixative containing lanthanum nitrate as an electron dense marker for the permeability of tight junctions.

A Coordinated Action of Blood-Borne and Brain Insulin-Like Growth Factor I in the Response to Traumatic Brain Injury.

PubMed

Santi, A; Genis, L; Torres Aleman, I

2018-06-01

In response to injury, the brain produces different neuroprotective molecules, such as insulin-like growth factor I (IGF-I). However, IGF-I is also taken up by the brain from the circulation in response to physiological stimuli. Herein, we analyzed in mice the relative contribution of circulating and locally produced IGF-I to increased brain IGF-I levels after insult. Traumatic brain injury (TBI) induced by a controlled impact resulted in increased IGF-I levels in the vicinity of the lesion, but mice with low serum IGF-I showed significantly lower increases. Indeed, in normal mice, peripheral IGF-I accumulated at the lesion site after injury, and at the same time serum IGF-I levels decreased. Collectively, these data suggest that serum IGF-I enter into the brain after TBI and contributes to increased brain IGF-I levels at the injury site. This connection between central and circulating IGF-I provides an amenable route for treatment, as subcutaneous administration of IGF-I to TBI mice led to functional recovery. These latter results add further support to the use of systemic IGF-I or its mimetics for treatment of brain injuries.

CHOLESTEROL-RELATED GENETIC RISK SCORES ARE ASSOCIATED WITH HYPOMETABOLISM IN ALZHEIMER’S-AFFECTED BRAIN REGIONS

PubMed Central

Reiman, Eric M.; Chen, Kewei; Caselli, Richard J.; Alexander, Gene E.; Bandy, Daniel; Adamson, Jennifer L.; Lee, Wendy; Cannon, Ashley; Stephan, Elizabeth A.; Stephan, Dietrich A.; Papassotiropoulos, Andreas

2008-01-01

We recently implicated a cluster of nine single nucleotide polymorphisms from seven cholesterol-related genes in the risk of Alzheimer’s disease (AD) in a European cohort, and we proposed calculating an aggregate cholesterol-related genetic score (CREGS) to characterize a person’s risk. In a separate study, we found that apolipoprotein E (APOE) ε4 gene dose, an established AD risk factor, was correlated with fluorodeoxyglucose (FDG) positron emission tomography (PET) measurements of hypometabolism in AD-affected brain regions in a cognitively normal American cohort, and we proposed using PET as a presymptomatic endophenotype to help assess putative modifiers of AD risk. Thus, the objective in the present study is to determine whether CREGS is related to PET measurements of hypometabolism in AD-affected brain regions. DNA and PET data from 141 cognitively normal late middle-aged APOE ε4 homozygotes, heterozygotes and non-carriers were analyzed to evaluate the relationship between CREGS and regional PET measurements. Cholesterol-related genetic risk scores were associated with hypometabolism in AD-affected brain regions, even when controlling for the effects of APOE ε4 gene dose. The results support the role of cholesterol-related genes in the predisposition to AD, and support the value of neuroimaging in the presymptomatic assessment of putative modifiers of AD risk. PMID:18280754

Progressive brain atrophy in patients with chronic neuropsychiatric symptoms after mild traumatic brain injury: a preliminary study.

PubMed

Ross, David E; Ochs, Alfred L; Seabaugh, Jan M; Demark, Michael F; Shrader, Carole R; Marwitz, Jennifer H; Havranek, Michael D

2012-01-01

NeuroQuant® is a recently developed, FDA-approved software program for measuring brain MRI volume in clinical settings. The aims of this study were as follows: (1) to examine the test-retest reliability of NeuroQuant®; (2) to test the hypothesis that patients with mild traumatic brain injury (TBI) would have abnormally rapid progressive brain atrophy; and (3) to test the hypothesis that progressive brain atrophy in patients with mild TBI would be associated with vocational outcome. Sixteen patients with mild TBI were compared to 20 normal controls. Vocational outcome was assessed with the Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS). NeuroQuant® showed high test-re-test reliability. Patients had abnormally rapid progressive atrophy in several brain regions and the rate of atrophy was associated with inability to return to work. NeuroQuant®, is a reliable and valid method for assessing the anatomic effects of TBI. Progression of atrophy may continue for years after injury, even in patients with mild TBI.

Brain-Computer Interfaces in Medicine

PubMed Central

Shih, Jerry J.; Krusienski, Dean J.; Wolpaw, Jonathan R.

2012-01-01

Brain-computer interfaces (BCIs) acquire brain signals, analyze them, and translate them into commands that are relayed to output devices that carry out desired actions. BCIs do not use normal neuromuscular output pathways. The main goal of BCI is to replace or restore useful function to people disabled by neuromuscular disorders such as amyotrophic lateral sclerosis, cerebral palsy, stroke, or spinal cord injury. From initial demonstrations of electroencephalography-based spelling and single-neuron-based device control, researchers have gone on to use electroencephalographic, intracortical, electrocorticographic, and other brain signals for increasingly complex control of cursors, robotic arms, prostheses, wheelchairs, and other devices. Brain-computer interfaces may also prove useful for rehabilitation after stroke and for other disorders. In the future, they might augment the performance of surgeons or other medical professionals. Brain-computer interface technology is the focus of a rapidly growing research and development enterprise that is greatly exciting scientists, engineers, clinicians, and the public in general. Its future achievements will depend on advances in 3 crucial areas. Brain-computer interfaces need signal-acquisition hardware that is convenient, portable, safe, and able to function in all environments. Brain-computer interface systems need to be validated in long-term studies of real-world use by people with severe disabilities, and effective and viable models for their widespread dissemination must be implemented. Finally, the day-to-day and moment-to-moment reliability of BCI performance must be improved so that it approaches the reliability of natural muscle-based function. PMID:22325364

The influence of sex chromosome aneuploidy on brain asymmetry.

PubMed

Rezaie, Roozbeh; Daly, Eileen M; Cutter, William J; Murphy, Declan G M; Robertson, Dene M W; DeLisi, Lynn E; Mackay, Clare E; Barrick, Thomas R; Crow, Timothy J; Roberts, Neil

2009-01-05

The cognitive deficits present in individuals with sex chromosome aneuploidies suggest that hemispheric differentiation of function is determined by an X-Y homologous gene [Crow (1993); Lancet 342:594-598]. In particular, females with Turner's syndrome (TS) who have only one X-chromosome exhibit deficits of spatial ability whereas males with Klinefelter's syndrome (KS) who possess a supernumerary X-chromosome are delayed in acquiring words. Since spatial and verbal abilities are generally associated with right and left hemispheric function, such deficits may relate to anomalies of cerebral asymmetry. We therefore applied a novel image analysis technique to investigate the relationship between sex chromosome dosage and structural brain asymmetry. Specifically, we tested Crow's prediction that the magnitude of the brain torque (i.e., a combination of rightward frontal and leftward occipital asymmetry) would, as a function of sex chromosome dosage, be respectively decreased in TS women and increased in KS men, relative to genotypically normal controls. We found that brain torque was not significantly different in TS women and KS men, in comparison to controls. However, TS women exhibited significantly increased leftward brain asymmetry, restricted to the posterior of the brain and focused on the superior temporal and parietal-occipital association cortex, while KS men showed a trend for decreased brain asymmetry throughout the frontal lobes. The findings suggest that the number of sex chromosomes influences the development of brain asymmetry not simply to modify the torque but in a complex pattern along the antero-posterior axis. 2008 Wiley-Liss, Inc.

Near infrared Raman spectra of human brain lipids

NASA Astrophysics Data System (ADS)

Krafft, Christoph; Neudert, Lars; Simat, Thomas; Salzer, Reiner

2005-05-01

Human brain tissue, in particular white matter, contains high lipid content. These brain lipids can be divided into three principal classes: neutral lipids including the steroid cholesterol, phospholipids and sphingolipids. Major lipids in normal human brain tissue are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, sphingomyelin, galactocerebrosides, gangliosides, sulfatides and cholesterol. Minor lipids are cholesterolester and triacylglycerides. During transformation from normal brain tissue to tumors, composition and concentration of lipids change in a specific way. Therefore, analysis of lipids might be used as a diagnostic parameter to distinguish normal tissue from tumors and to determine the tumor type and tumor grade. Raman spectroscopy has been suggested as an analytical tool to detect these changes even under intra-operative conditions. We recorded Raman spectra of the 12 major and minor brain lipids with 785 nm excitation in order to identify their spectral fingerprints for qualitative and quantitative analyses.

Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer’s Disease

PubMed Central

Cunnane, Stephen C.; Courchesne-Loyer, Alexandre; Vandenberghe, Camille; St-Pierre, Valérie; Fortier, Mélanie; Hennebelle, Marie; Croteau, Etienne; Bocti, Christian; Fulop, Tamas; Castellano, Christian-Alexandre

2016-01-01

We propose that brain energy deficit is an important pre-symptomatic feature of Alzheimer’s disease (AD) that requires closer attention in the development of AD therapeutics. Our rationale is fourfold: (i) Glucose uptake is lower in the frontal cortex of people >65 years-old despite cognitive scores that are normal for age. (ii) The regional deficit in brain glucose uptake is present in adults <40 years-old who have genetic or lifestyle risk factors for AD but in whom cognitive decline has not yet started. Examples include young adult carriers of presenilin-1 or apolipoprotein E4, and young adults with mild insulin resistance or with a maternal family history of AD. (iii) Regional brain glucose uptake is impaired in AD and mild cognitive impairment (MCI), but brain uptake of ketones (beta-hydroxybutyrate and acetoacetate), remains the same in AD and MCI as in cognitively healthy age-matched controls. These observations point to a brain fuel deficit which appears to be specific to glucose, precedes cognitive decline associated with AD, and becomes more severe as MCI progresses toward AD. Since glucose is the brain’s main fuel, we suggest that gradual brain glucose exhaustion is contributing significantly to the onset or progression of AD. (iv) Interventions that raise ketone availability to the brain improve cognitive outcomes in both MCI and AD as well as in acute experimental hypoglycemia. Ketones are the brain’s main alternative fuel to glucose and brain ketone uptake is still normal in MCI and in early AD, which would help explain why ketogenic interventions improve some cognitive outcomes in MCI and AD. We suggest that the brain energy deficit needs to be overcome in order to successfully develop more effective therapeutics for AD. At present, oral ketogenic supplements are the most promising means of achieving this goal. PMID:27458340

Evaluation of [11C]TAZA for amyloid β plaque imaging in postmortem human Alzheimer's disease brain region and whole body distribution in rodent PET/CT.

PubMed

Pan, Min-Liang; Mukherjee, Meenakshi T; Patel, Himika H; Patel, Bhavin; Constantinescu, Cristian C; Mirbolooki, M Reza; Liang, Christopher; Mukherjee, Jogeshwar

2016-04-01

Alzheimer's disease (AD) is a neurodegenerative disease characterized by Aβ plaques in the brain. The aim of this study was to evaluate the effectiveness of a novel radiotracer, 4-[(11) C]methylamino-4'-N,N-dimethylaminoazobenzene ([(11)C]TAZA), for binding to Aβ plaques in postmortem human brain (AD and normal control (NC)). Radiosyntheses of [(11)C]TAZA, related [(11)C]Dalene ((11)C-methylamino-4'-dimethylaminostyrylbenzene), and reference [(11)C]PIB were carried out using [(11)C]methyltriflate prepared from [(11) C]CO(2) and purified using HPLC. In vitro binding affinities were carried out in human AD brain homogenate with Aβ plaques labeled with [(3) H]PIB. In vitro autoradiography studies with the three radiotracers were performed on hippocampus of AD and NC brains. PET/CT studies were carried out in normal rats to study brain and whole body distribution. The three radiotracers were produced in high radiochemical yields (>40%) and had specific activities >37 GBq/μmol. TAZA had an affinity, K(i) = 0.84 nM and was five times more potent than PIB. [(11)C]TAZA bound specifically to Aβ plaques present in AD brains with gray matter to white matter ratios >20. [(11)C]TAZA was displaced by PIB (>90%), suggesting similar binding site for [(11)C]TAZA and [(11)C]PIB. [(11)C]TAZA exhibited slow kinetics of uptake in the rat brain and whole body images showed uptake in interscapular brown adipose tissue (IBAT). Binding in brain and IBAT were affected by preinjection of atomoxetine, a norepinephrine transporter blocker. [(11)C]TAZA exhibited high binding to Aβ plaques in human AD hippocampus. Rat brain kinetics was slow and peripheral binding to IBAT needs to be further evaluated. © 2016 Wiley Periodicals, Inc.

Nonlocal Intracranial Cavity Extraction

PubMed Central

Manjón, José V.; Eskildsen, Simon F.; Coupé, Pierrick; Romero, José E.; Collins, D. Louis; Robles, Montserrat

2014-01-01

Automatic and accurate methods to estimate normalized regional brain volumes from MRI data are valuable tools which may help to obtain an objective diagnosis and followup of many neurological diseases. To estimate such regional brain volumes, the intracranial cavity volume (ICV) is often used for normalization. However, the high variability of brain shape and size due to normal intersubject variability, normal changes occurring over the lifespan, and abnormal changes due to disease makes the ICV estimation problem challenging. In this paper, we present a new approach to perform ICV extraction based on the use of a library of prelabeled brain images to capture the large variability of brain shapes. To this end, an improved nonlocal label fusion scheme based on BEaST technique is proposed to increase the accuracy of the ICV estimation. The proposed method is compared with recent state-of-the-art methods and the results demonstrate an improved performance both in terms of accuracy and reproducibility while maintaining a reduced computational burden. PMID:25328511

Puppets, robots, critics, and actors within a taxonomy of attention for developmental disorders

PubMed Central

DENNIS, MAUREEN; SINOPOLI, KATIA J.; FLETCHER, JACK M.; SCHACHAR, RUSSELL

2008-01-01

This review proposes a new taxonomy of automatic and controlled attention. The taxonomy distinguishes among the role of the attendee (puppet and robot, critic and actor), the attention process (stimulus orienting vs. response control), and the attention operation (activation vs. inhibition vs. adjustment), and identifies cognitive phenotypes by which attention is overtly expressed. We apply the taxonomy to four childhood attention disorders: attention deficit hyperactivity disorder, spina bifida meningomyelocele, traumatic brain injury, and acute lymphoblastic leukemia. Variations in attention are related to specific brain regions that support normal attention processes when intact, and produce disordered attention when impaired. The taxonomy explains group differences in behavioral inattention, hyperactivity, and impulsiveness, as well as medication response. We also discuss issues relevant to theories of the cognitive and neural architecture of attention: functional dissociations within and between automatic and controlled attention; the relative importance of type of brain damage and developmental timing to attention profile; cognitive-energetic models of attention and white matter damage; temporal processing deficits, attention deficits and cerebellar damage; and the issue of cognitive phenotypes as candidate endophenotypes. PMID:18764966

Neurocognitive functions and brain atrophy after proven neuroborreliosis: a case-control study.

PubMed

Schmidt, Holger; Djukic, Marija; Jung, Klaus; Holzgraefe, Manfred; Dechent, Peter; von Steinbüchel, Nicole; Blocher, Joachim; Eiffert, Helmut; Schmidt-Samoa, Carsten

2015-08-19

Patients often report neurocognitive difficulties after neuroborreliosis (NB). The frequency and extent of cognitive problems in European patients have been studied incompletely. Sixty patients received a neurological and neuropsychological work-up 6 months or longer after treatment for proven NB. Quality of life, psychiatric symptom load, and brain atrophy were measured. All results were compared with a group of 30 healthy control persons adapted for age, gender and education being serologically negative for Borrelia burgdorferi senso latu. A cognitive sum score and a global sum score including cognitive, psychological results and quality of life data was calculated for both groups. Patients after NB showed a lower (i.e. more impaired) score on the Scripps Neurological rating scale (SNRS), but the observed neurological deficits were generally mild (mean ± SD: 97.1 ± 4.7 vs. 99.1 ± 2.4, p = 0.02). The mean neuropsychological domain results of the NB group were all within the normal range. However, a lower performance was found for the frontal executive function z-values (mean ± SD -0.29 ± 0.60 vs. 0.09 ± 0.60; p = 0.0059) of NB patients. Comparing the global sum score (mean ± SD 11.3 ± 4.2 NB vs. 14.3 ± 2.9 control , p = 0.001) and the cognitive sum score of the NB group with those of the control group (mean ± SD -0.15 ± 0.42 NB vs. 0.08 ± 0.31 control , p = 0.0079), both differences were statistically different. The frequencies of impaired global sum scores and those of the pathological cognitive sum scores (p = 0.07) did not differ statistically. No significant differences were found for health-related quality of life (hrQoL), sleep, psychiatric symptom load, or brain atrophy. The mean cognitive functions of patients after proven NB were in the normal range. However, we were able to demonstrate a lower performance for the domain of frontal executive functions, for the mean cognitive sum score and the global sum score as a sign of subtle but measurable sequelae of neuroborreliosis. Brain atrophy is not a common consequence of neuroborreliosis.

Successful deep brain stimulation of the nucleus accumbens in severe alcohol dependence is associated with changed performance monitoring.

PubMed

Kuhn, Jens; Gründler, Theo O J; Bauer, Robert; Huff, Wolfgang; Fischer, Adrian G; Lenartz, Doris; Maarouf, Mohammad; Bührle, Christian; Klosterkötter, Joachim; Ullsperger, Markus; Sturm, Volker

2011-10-01

Following recent advances in neuromodulation therapy for mental disorders, we treated one patient with severe alcohol addiction with deep brain stimulation (DBS) of the nucleus accumbens (NAc). Before and one year following the surgery, we assessed the effects of DBS within the NAc on the addiction as well as on psychometric scores and electrophysiological measures of cognitive control. In our patient, DBS achieved normalization of addictive behavior and craving. An electrophysiological marker of error processing (the error-related negativity) linked to anterior mid-cingulate cortex (aMCC) functioning was altered through DBS, an effect that could be reversed by periods without stimulation. Thus, this case supports the hypothesis that DBS of the NAc could have a positive effect on addiction trough a normalization of craving associated with aMCC dysfunction. © 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

Simulations of exercise and brain effects of acute exposure to carbon monoxide in normal and vascular-diseased persons.

EPA Science Inventory

At some level, carboxyhemoglobin (RbCO) due to inhalation of carbon monoxide (CO) reduces maximum exercise duration in normal and ischemic heart patients. At high RbCO levels in normal subjects, brain function is also affected and behavioral performance is impaired. These are fin...

Normalization of Reverse Transcription Quantitative PCR Data During Ageing in Distinct Cerebral Structures.

PubMed

Bruckert, G; Vivien, D; Docagne, F; Roussel, B D

2016-04-01

Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) has become a routine method in many laboratories. Normalization of data from experimental conditions is critical for data processing and is usually achieved by the use of a single reference gene. Nevertheless, as pointed by the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, several reference genes should be used for reliable normalization. Ageing is a physiological process that results in a decline of many expressed genes. Reliable normalization of RT-qPCR data becomes crucial when studying ageing. Here, we propose a RT-qPCR study from four mouse brain regions (cortex, hippocampus, striatum and cerebellum) at different ages (from 8 weeks to 22 months) in which we studied the expression of nine commonly used reference genes. With the use of two different algorithms, we found that all brain structures need at least two genes for a good normalization step. We propose specific pairs of gene for efficient data normalization in the four brain regions studied. These results underline the importance of reliable reference genes for specific brain regions in ageing.

Effects of boron on growth and physiology in mallard ducklings

USGS Publications Warehouse

Hoffman, D.J.; Camardese, M.B.; LeCaptain, L.J.; Pendleton, G.W.

1990-01-01

High concentrations of boron (B) have been associated with irrigation drainwater and aquatic plants consumed by waterfowl. Day-old mallard (Anas platyrhynchos) ducklings received an untreated diet (controls) or diets containing 100, 400 or 1,600 ppm B as boric acid. Survival, growth and food consumption were measured for 10 weeks. At termination, blood and tissue samples were collected for biochemical assays and histological examination. The highest dietary concentration of B caused 10% mortality, decreased overall growth and the rate of growth (sexes combined), whereas lower concentrations of B altered growth only in females. Food consumption water lower during the first 3 weeks in the 1,600-ppm group and during the second week in all B-treated groups compared to controls. Hematocrit and hemaglobin were lower and plasma calcium concentration higher in the 1,600-ppm group compared to controls. Plasma triglyceride concentration was elevated in all B-treated groups. Brain B concentration increased to 25 times that of controls in the 1,600-ppm group. Brain ATP decreased with increasing dietary B. Brain acetylcholinesterase activity and total ATPase activity (in males) were elevated and protein concentration lowered in the 1,600-ppm group. Boron accumulated less in the liver than in the brain but resulted in an initial elevation of hepatic glutathione. These findings, in combination with altered duckling behavior, suggest that concentrations of B occurring in aquatic plants could adversely affect normal duckling development.

Effects of cathodal trans-spinal direct current stimulation on lower urinary tract function in normal and spinal cord injury mice with overactive bladder

NASA Astrophysics Data System (ADS)

Ahmed, Zaghloul

2017-10-01

Objective. Lower urinary tract (LUT) dysfunction is a monumental problem affecting quality of life following neurotrauma, such as spinal cord injury (SCI). Proper function of the bladder and its associated structures depends on coordinated activity of the neuronal circuitry in the spinal cord and brain. Disconnection between the spinal and brain centers controlling the LUT causes fundamental changes in the mechanisms involved in the micturition and storage reflexes. We investigated the effects of cathodal trans-spinal direct current stimulation (c-tsDCS) of the lumbosacral spine on bladder and external urinary sphincter (EUS) functions. Approach. We used cystometry and electromyography (EMG), in mice with and without SCI. Main results. c-tsDCS caused initiation of the micturition reflex in urethane-anesthetized normal mice with depressed micturition reflexes. This effect was associated with normalized EUS-EMG activity. Moreover, in urethane-anesthetized normal mice with expressed micturition reflexes, c-tsDCS increased the firing frequency, amplitude, and duration of EUS-EMG activity. These effects were associated with increased maximum intravesical pressure (P max) and intercontraction interval (ICI). In conscious normal animals, c-tsDCS caused significant increases in P max, ICI, threshold pressure (P thres), baseline pressure (P base), and number and amplitude of non-voiding contractions (NVCnumb and P im, respectively). In conscious mice with severe contusive SCI and overactive bladder, c-tsDCS increased P max, ICI, and P thres, but decreased P base, NVCnumb, and P im. c-tsDCS reduced the detrusor-overactivity/cystometry ratio, which is a measure of bladder overactivity associated with renal deterioration. Significance. These results indicate that c-tsDCS induces robust modulation of the lumbosacral spinal-cord circuitry that controls the LUT.

Betting on DBS: Effects of Subthalamic Nucleus Deep Brain Stimulation on Risk-Taking and Decision-Making in Patients with Parkinson’s Disease

PubMed Central

Brandt, Jason; Rogerson, Mark; Al-Joudi, Haya; Reckess, Gila; Shpritz, Barnett; Umeh, Chizoba C.; Aljehani, Noha; Mills, Kelly; Mari, Zoltan

2014-01-01

Objective Concerns persist that deep brain stimulation (DBS) for Parkinson’s disease (PD) increases impulsivity and/or induces excessive reward-seeking. We report here the performance of PD patients with implanted subthalamic nucleus electrodes, with stimulation on and off, on three laboratory tasks of risk-taking and decision-making. They are compared to PD patients maintained on medication and normal control subjects. Methods and Results In the Game of Dice Task, a test of “risky” decision-making, PD patients with or without DBS made highest-risk bets more often, and ended up with less money, than normal controls. There was a trend for DBS stimulation to ameliorate this effect. Deal or No-Deal is an “ambiguous” decision-making task that assessed preference for risk (holding on to one’s briefcase) over a “sure thing” (accepting the banker’s offer). Here, DBS patients were more conservative with stimulation on than off. They accepted smaller offers from the banker and won less money in the DBS-on condition. Overall, the two PD groups won less money than healthy participants. The Framing Paradigm assessed willingness to gamble on a fixed (unambiguous) prize depending on whether the reward was “framed” as a loss or a gain. Nonsurgical PD patients tended to be more risk-averse than normal subjects, whereas DBS patients were more willing to gamble for gains as well as losses both on and off stimulation. Conclusions On “risky” decision-making tasks, DBS patients were more risk-taking than normal, but stimulation may temper this tendency. In contrast, in an “ambiguous risk” situation, DBS patients were more risk-averse (conservative) than normal, and this tendency was greatest with stimulation. PMID:25486385

Neuroanatomical Diversity of Corpus Callosum and Brain Volume in Autism: Meta-analysis, Analysis of the Autism Brain Imaging Data Exchange Project, and Simulation.

PubMed

Lefebvre, Aline; Beggiato, Anita; Bourgeron, Thomas; Toro, Roberto

2015-07-15

Patients with autism have been often reported to have a smaller corpus callosum (CC) than control subjects. We conducted a meta-analysis of the literature, analyzed the CC in 694 subjects of the Autism Brain Imaging Data Exchange project, and performed computer simulations to study the effect of different analysis strategies. Our meta-analysis suggested a group difference in CC size; however, the studies were heavily underpowered (20% power to detect Cohen's d = .3). In contrast, we did not observe significant differences in the Autism Brain Imaging Data Exchange cohort, despite having achieved 99% power. However, we observed that CC scaled nonlinearly with brain volume (BV): large brains had a proportionally smaller CC. Our simulations showed that because of this nonlinearity, CC normalization could not control for eventual BV differences, but using BV as a covariate in a linear model would. We also observed a weaker correlation of IQ and BV in cases compared with control subjects. Our simulations showed that matching populations by IQ could then induce artifactual BV differences. The lack of statistical power in the previous literature prevents us from establishing the reality of the claims of a smaller CC in autism, and our own analyses did not find any. However, the nonlinear relationship between CC and BV and the different correlation between BV and IQ in cases and control subjects may induce artifactual differences. Overall, our results highlight the necessity for open data sharing to provide a more solid ground for the discovery of neuroimaging biomarkers within the context of the wide human neuroanatomical diversity. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Notch signaling and ageing.

PubMed

Polychronidou, Eleftheria; Vlachakis, Dimitrios; Vlamos, Panayiotis; Baumann, Marc; Kossida, Sophia

2015-01-01

Notch signaling is a master controller of the neural stem cell and neural development maintaining a significant role in the normal brain function. Notch genes are involved in embryogenesis, nervous system, and cardiovascular and endocrine function. On the other side, there are studies representing the involvement of Notch mutations in sporadic Alzheimer disease, other neurodegenerative diseases such as Down syndrome, Pick's and Prion's disease, and CADASIL. This manuscript attempts to present a holistic view of the positive or negative contribution of Notch signaling in the adult brain, and at the same time to present and promote the promising research fields of study.

Glymphatic MRI in idiopathic normal pressure hydrocephalus.

PubMed

Ringstad, Geir; Vatnehol, Svein Are Sirirud; Eide, Per Kristian

2017-10-01

The glymphatic system has in previous studies been shown as fundamental to clearance of waste metabolites from the brain interstitial space, and is proposed to be instrumental in normal ageing and brain pathology such as Alzheimer's disease and brain trauma. Assessment of glymphatic function using magnetic resonance imaging with intrathecal contrast agent as a cerebrospinal fluid tracer has so far been limited to rodents. We aimed to image cerebrospinal fluid flow characteristics and glymphatic function in humans, and applied the methodology in a prospective study of 15 idiopathic normal pressure hydrocephalus patients (mean age 71.3 ± 8.1 years, three female and 12 male) and eight reference subjects (mean age 41.1 + 13.0 years, six female and two male) with suspected cerebrospinal fluid leakage (seven) and intracranial cyst (one). The imaging protocol included T1-weighted magnetic resonance imaging with equal sequence parameters before and at multiple time points through 24 h after intrathecal injection of the contrast agent gadobutrol at the lumbar level. All study subjects were kept in the supine position between examinations during the first day. Gadobutrol enhancement was measured at all imaging time points from regions of interest placed at predefined locations in brain parenchyma, the subarachnoid and intraventricular space, and inside the sagittal sinus. Parameters demonstrating gadobutrol enhancement and clearance in different locations were compared between idiopathic normal pressure hydrocephalus and reference subjects. A characteristic flow pattern in idiopathic normal hydrocephalus was ventricular reflux of gadobutrol from the subarachnoid space followed by transependymal gadobutrol migration. At the brain surfaces, gadobutrol propagated antegradely along large leptomeningeal arteries in all study subjects, and preceded glymphatic enhancement in adjacent brain tissue, indicating a pivotal role of intracranial pulsations for glymphatic function. In idiopathic normal pressure hydrocephalus, we found delayed enhancement (P < 0.05) and decreased clearance of gadobutrol (P < 0.05) at the Sylvian fissure. Parenchymal (glymphatic) enhancement peaked overnight in both study groups, possibly indicating a crucial role of sleep, and was larger in normal pressure hydrocephalus patients (P < 0.05 at inferior frontal gyrus). We interpret decreased gadobutrol clearance from the subarachnoid space, along with persisting enhancement in brain parenchyma, as signs of reduced glymphatic clearance in idiopathic normal hydrocephalus, and hypothesize that reduced glymphatic function is instrumental for dementia in this disease. The study shows promise for glymphatic magnetic resonance imaging as a method to assess human brain metabolic function and renders a potential for contrast enhanced brain extravascular space imaging. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Approaches to transport therapeutic drugs across the blood-brain barrier to treat brain diseases.

PubMed

Gabathuler, Reinhard

2010-01-01

The central nervous system is protected by barriers which control the entry of compounds into the brain, thereby regulating brain homeostasis. The blood-brain barrier, formed by the endothelial cells of the brain capillaries, restricts access to brain cells of blood-borne compounds and facilitates nutrients essential for normal metabolism to reach brain cells. This very tight regulation of the brain homeostasis results in the inability of some small and large therapeutic compounds to cross the blood-brain barrier (BBB). Therefore, various strategies are being developed to enhance the amount and concentration of therapeutic compounds in the brain. In this review, we will address the different approaches used to increase the transport of therapeutics from blood into the brain parenchyma. We will mainly concentrate on the physiologic approach which takes advantage of specific receptors already expressed on the capillary endothelial cells forming the BBB and necessary for the survival of brain cells. Among all the approaches used for increasing brain delivery of therapeutics, the most accepted method is the use of the physiological approach which takes advantage of the transcytosis capacity of specific receptors expressed at the BBB. The low density lipoprotein receptor related protein (LRP) is the most adapted for such use with the engineered peptide compound (EPiC) platform incorporating the Angiopep peptide in new therapeutics the most advanced with promising data in the clinic.

Conjunctival microcirculatory blood flow is altered but not abolished in brain dead patients: a prospective observational study.

PubMed

Tamosuitis, Tomas; Pranskunas, Andrius; Balciuniene, Neringa; Pilvinis, Vidas; Boerma, E Christiaan

2016-07-11

The conjunctival microcirculation has potential as a window to cerebral perfusion due to related blood supply, close anatomical proximity and easy accessibility for microcirculatory imaging technique, such as sidestream dark field (SDF) imaging. Our study aims to evaluate conjunctival and sublingual microcirculation in brain dead patients and to compare it with healthy volunteers in two diametrically opposed conditions: full stop versus normal arterial blood supply to the brain. In a prospective observational study we analyzed conjunctival and sublingual microcirculation using SDF imaging in brain dead patients after reaching systemic hemodynamic targets to optimize perfusion of donor organs, and in healthy volunteers. All brain death diagnoses were confirmed by cerebral angiography. Microcirculatory images were obtained and analyzed using standardized published recommendations. Study registered at ClinicalTrials.gov, number NCT02483273. Eleven brain dead patients and eleven apparently healthy controls were enrolled in the study. Microvascular flow index (MFI) of small vessels was significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (2.7 [2.4-2.9] vs. 3.0 [2.9-3.0], p = 0.01) and in sublingual mucosa (2.8 [2.6-2.9] vs. 3.0 [2.9-3.0], p = 0.02). Total vessel density (TVD) and perfused vessel density (PVD) of small vessels were significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (10.2 [6.6-14.8] vs. 18.0 [18.0-25.4] mm/mm(2), p = 0.001 and 5.0 [3.5-7.3] vs. 10.9 [10.9-13.5] 1/mm, p = 0.001), but not in sublingual mucosa. In comparison to healthy controls brain dead patients had a significant reduction in conjunctival microvascular blood flow and density. However, the presence of conjunctival flow in case general cerebral flow is completely absent makes it impossible to use the conjunctival microcirculation as a substitute for brain flow, and further research should focus on the link between the ocular microcirculation, intracranial pressure and alternative ocular circulation.

Disrupted topological properties of brain white matter networks in left temporal lobe epilepsy: a diffusion tensor imaging study.

PubMed

Xu, Y; Qiu, S; Wang, J; Liu, Z; Zhang, R; Li, S; Cheng, L; Liu, Z; Wang, W; Huang, R

2014-10-24

Mesial temporal lobe epilepsy (mTLE) is the most common drug-refractory focal epilepsy in adults. Although previous functional and morphological studies have revealed abnormalities in the brain networks of mTLE, the topological organization of the brain white matter (WM) networks in mTLE patients is still ambiguous. In this study, we constructed brain WM networks for 14 left mTLE patients and 22 age- and gender-matched normal controls using diffusion tensor tractography and estimated the alterations of network properties in the mTLE brain networks using graph theoretical analysis. We found that networks for both the mTLE patients and the controls exhibited prominent small-world properties, suggesting a balanced topology of integration and segregation. However, the brain WM networks of mTLE patients showed a significant increased characteristic path length but significant decreased global efficiency, which indicate a disruption in the organization of the brain WM networks in mTLE patients. Moreover, we found significant between-group differences in the nodal properties in several brain regions, such as the left superior temporal gyrus, left hippocampus, the right occipital and right temporal cortices. The robustness analysis showed that the results were likely to be consistent for the networks constructed with different definitions of node and edge weight. Taken together, our findings may suggest an adverse effect of epileptic seizures on the organization of large-scale brain WM networks in mTLE patients. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Function Lateralization via Measuring Coherence Laterality

PubMed Central

Wang, Ze; Mechanic-Hamilton, Dawn; Pluta, John; Glynn, Simon; Detre, John A.

2009-01-01

A data-driven approach for lateralization of brain function based on the spatial coherence difference of functional MRI (fMRI) data in homologous regions-of-interest (ROI) in each hemisphere is proposed. The utility of using coherence laterality (CL) to determine function laterality was assessed first by examining motor laterality using normal subjects’ data acquired both at rest and with a simple unilateral motor task and subsequently by examining mesial temporal lobe memory laterality in normal subjects and patients with temporal lobe epilepsy. The motor task was used to demonstrate that CL within motor ROI correctly lateralized functional stimulation. In patients with unilateral epilepsy studied during a scene-encoding task, CL in a hippocampus-parahippocampus-fusiform (HPF) ROI was concordant with lateralization based on task activation, and the CL index (CLI) significantly differentiated the right side group to the left side group. By contrast, normal controls showed a symmetric HPF CLI distribution. Additionally, similar memory laterality prediction results were still observed using CL in epilepsy patients with unilateral seizures after the memory encoding effect was removed from the data, suggesting the potential for lateralization of pathological brain function based on resting fMRI data. A better lateralization was further achieved via a combination of the proposed approach and the standard activation based approach, demonstrating that assessment of spatial coherence changes provides a complementary approach to quantifying task-correlated activity for lateralizing brain function. PMID:19345736

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

Optical pathology of human brain metastasis of lung cancer using combined resonance Raman and spatial frequency spectroscopies

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; Pu, Yang; Cheng, Gangge; Zhou, Lixin; Chen, Jun; Zhu, Ke; Alfano, Robert R.

2016-03-01

Raman spectroscopy has become widely used for diagnostic purpose of breast, lung and brain cancers. This report introduced a new approach based on spatial frequency spectra analysis of the underlying tissue structure at different stages of brain tumor. Combined spatial frequency spectroscopy (SFS), Resonance Raman (RR) spectroscopic method is used to discriminate human brain metastasis of lung cancer from normal tissues for the first time. A total number of thirty-one label-free micrographic images of normal and metastatic brain cancer tissues obtained from a confocal micro- Raman spectroscopic system synchronously with examined RR spectra of the corresponding samples were collected from the identical site of tissue. The difference of the randomness of tissue structures between the micrograph images of metastatic brain tumor tissues and normal tissues can be recognized by analyzing spatial frequency. By fitting the distribution of the spatial frequency spectra of human brain tissues as a Gaussian function, the standard deviation, σ, can be obtained, which was used to generate a criterion to differentiate human brain cancerous tissues from the normal ones using Support Vector Machine (SVM) classifier. This SFS-SVM analysis on micrograph images presents good results with sensitivity (85%), specificity (75%) in comparison with gold standard reports of pathology and immunology. The dual-modal advantages of SFS combined with RR spectroscopy method may open a new way in the neuropathology applications.

Positron Spectroscopy Investigation of Normal Brain Section and Brain Section with Glioma Derived from a Rat Glioma Model

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

Yang, SH.; Ballmann, C.; Quarles, C. A.

2009-03-10

The application of positron annihilation lifetime spectroscopy (PALS) and Doppler broadening spectroscopy (DBS) to the study of animal or human tissue has only recently been reported [G. Liu, et al. phys. stat. sol. (C) 4, Nos. 10, 3912-3915 (2007)]. We have initiated a study of normal brain section and brain section with glioma derived from a rat glioma model. For the rat glioma model, 200,000 C6 cells were implanted in the basal ganglion of adult Sprague Dawley rats. The rats were sacrificed at 21 days after implantation. The brains were harvested, sliced into 2 mm thick coronal sections, and fixedmore » in 4% formalin. PALS lifetime runs were made with the samples soaked in formalin, and there was not significant evaporation of formalin during the runs. The lifetime spectra were analyzed into two lifetime components. While early results suggested a small decrease in ortho-Positronium (o-Ps) pickoff lifetime between the normal brain section and brain section with glioma, further runs with additional samples have showed no statistically significant difference between the normal and tumor tissue for this type of tumor. The o-Ps lifetime in formalin alone was lower than either the normal tissue or glioma sample. So annihilation in the formalin absorbed in the samples would lower the o-Ps lifetime and this may have masked any difference due to the glioma itself. DBS was also used to investigate the difference in positronium formation between tumor and normal tissue. Tissue samples are heterogeneous and this needs to be carefully considered if PALS and DBS are to become useful tools in distinguishing tissue samples.« less

Potential application of a handheld confocal endomicroscope imaging system using a variety of fluorophores in experimental gliomas and normal brain.

PubMed

Martirosyan, Nikolay L; Georges, Joseph; Eschbacher, Jennifer M; Cavalcanti, Daniel D; Elhadi, Ali M; Abdelwahab, Mohammed G; Scheck, Adrienne C; Nakaji, Peter; Spetzler, Robert F; Preul, Mark C

2014-02-01

The authors sought to assess the feasibility of a handheld visible-wavelength confocal endomicroscope imaging system (Optiscan 5.1, Optiscan Pty., Ltd.) using a variety of rapid-acting fluorophores to provide histological information on gliomas, tumor margins, and normal brain in animal models. Mice (n = 25) implanted with GL261 cells were used to image fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA), acridine orange (AO), acriflavine (AF), and cresyl violet (CV). A U251 glioma xenograft model in rats (n = 5) was used to image sulforhodamine 101 (SR101). A swine (n = 3) model with AO was used to identify confocal features of normal brain. Images of normal brain, obvious tumor, and peritumoral zones were collected using the handheld confocal endomicroscope. Histological samples were acquired through biopsies from matched imaging areas. Samples were visualized with a benchtop confocal microscope. Histopathological features in corresponding confocal images and photomicrographs of H & E-stained tissues were reviewed. Fluorescence induced by FNa, 5-ALA, AO, AF, CV, and SR101 and detected with the confocal endomicroscope allowed interpretation of histological features. Confocal endomicroscopy revealed satellite tumor cells within peritumoral tissue, a definitive tumor border, and striking fluorescent cellular and subcellular structures. Fluorescence in various tumor regions correlated with standard histology and known tissue architecture. Characteristic features of different areas of normal brain were identified as well. Confocal endomicroscopy provided rapid histological information precisely related to the site of microscopic imaging with imaging characteristics of cells related to the unique labeling features of the fluorophores. Although experimental with further clinical trial validation required, these data suggest that intraoperative confocal imaging can help to distinguish normal brain from tumor and tumor margin and may have application in improving intraoperative decisions during resection of brain tumors.

Deep brain stimulation effects in dystonia: time course of electrophysiological changes in early treatment.

PubMed

Ruge, Diane; Tisch, Stephen; Hariz, Marwan I; Zrinzo, Ludvic; Bhatia, Kailash P; Quinn, Niall P; Jahanshahi, Marjan; Limousin, Patricia; Rothwell, John C

2011-08-15

Deep brain stimulation to the internal globus pallidus is an effective treatment for primary dystonia. The optimal clinical effect often occurs only weeks to months after starting stimulation. To better understand the underlying electrophysiological changes in this period, we assessed longitudinally 2 pathophysiological markers of dystonia in patients prior to and in the early treatment period (1, 3, 6 months) after deep brain stimulation surgery. Transcranial magnetic stimulation was used to track changes in short-latency intracortical inhibition, a measure of excitability of GABA(A) -ergic corticocortical connections and long-term potentiation-like synaptic plasticity (as a response to paired associative stimulation). Deep brain stimulation remained on for the duration of the study. Prior to surgery, inhibition was reduced and plasticity increased in patients compared with healthy controls. Following surgery and commencement of deep brain stimulation, short-latency intracortical inhibition increased toward normal levels over the following months with the same monotonic time course as the patients' clinical benefit. In contrast, synaptic plasticity changed rapidly, following a nonmonotonic time course: it was absent early (1 month) after surgery, and then over the following months increased toward levels observed in healthy individuals. We postulate that before surgery preexisting high levels of plasticity form strong memories of dystonic movement patterns. When deep brain stimulation is turned on, it disrupts abnormal basal ganglia signals, resulting in the absent response to paired associative stimulation at 1 month. Clinical benefit is delayed because engrams of abnormal movement persist and take time to normalize. Our observations suggest that plasticity may be a driver of long-term therapeutic effects of deep brain stimulation in dystonia. Copyright © 2011 Movement Disorder Society.

Conditional N-WASP knockout in mouse brain implicates actin cytoskeleton regulation in hydrocephalus pathology.

PubMed

Jain, Neeraj; Lim, Lee Wei; Tan, Wei Ting; George, Bhawana; Makeyev, Eugene; Thanabalu, Thirumaran

2014-04-01

Cerebrospinal fluid (CSF) is produced by the choroid plexus and moved by multi-ciliated ependymal cells through the ventricular system of the vertebrate brain. Defects in the ependymal layer functionality are a common cause of hydrocephalus. N-WASP (Neural-Wiskott Aldrich Syndrome Protein) is a brain-enriched regulator of actin cytoskeleton and N-WASP knockout caused embryonic lethality in mice with neural tube and cardiac abnormalities. To shed light on the role of N-WASP in mouse brain development, we generated N-WASP conditional knockout mouse model N-WASP(fl/fl); Nestin-Cre (NKO-Nes). NKO-Nes mice were born with Mendelian ratios but exhibited reduced growth characteristics compared to their littermates containing functional N-WASP alleles. Importantly, all NKO-Nes mice developed cranial deformities due to excessive CSF accumulation and did not survive past weaning. Coronal brain sections of these animals revealed dilated lateral ventricles, defects in ciliogenesis, loss of ependymal layer integrity, reduced thickness of cerebral cortex and aqueductal stenosis. Immunostaining for N-cadherin suggests that ependymal integrity in NKO-Nes mice is lost as compared to normal morphology in the wild-type controls. Moreover, scanning electron microscopy and immunofluorescence analyses of coronal brain sections with anti-acetylated tubulin antibodies revealed the absence of cilia in ventricular walls of NKO-Nes mice indicative of ciliogenesis defects. N-WASP deficiency does not lead to altered expression of N-WASP regulatory proteins, Fyn and Cdc42, which have been previously implicated in hydrocephalus pathology. Taken together, our results suggest that N-WASP plays a critical role in normal brain development and implicate actin cytoskeleton regulation as a vulnerable axis frequently deregulated in hydrocephalus. Copyright © 2014 Elsevier Inc. All rights reserved.

Neural Correlates of Communication Skill and Symptom Severity in Autism: A Voxel-Based Morphometry Study

ERIC Educational Resources Information Center

Parks, Lauren K.; Hill, Dina E.; Thoma, Robert J.; Euler, Matthew J.; Lewine, Jeffrey D.; Yeo, Ronald A.

2009-01-01

Although many studies have compared the brains of normal controls and individuals with autism, especially older, higher-functioning individuals with autism, little is known of the neural correlates of the vast clinical heterogeneity characteristic of the disorder. In this study, we used voxel-based morphometry (VBM) to examine gray matter…

Diurnal changes in postural control in normal children: Computerized static and dynamic assessments.

PubMed

Bourelle, Sophie; Taiar, Redha; Berge, Benoit; Gautheron, Vincent; Cottalorda, Jerome

2014-01-01

Mild traumatic brain injury (mTBI) causes postural control deficits and accordingly comparison of aberrant postural control against normal postural control may help diagnose mTBI. However, in the current literature, little is known regarding the normal pattern of postural control in young children. This study was therefore conducted as an effort to fill this knowledge gap. Eight normal school-aged children participated. Posture assessment was conducted before (7-8 a.m. in the morning) and after (4-7 p.m. in the afternoon) school on regular school days using the Balance Master® evaluation system composed of 3 static tests and 2 dynamic balance tests. A significant difference in the weight-bearing squats was detected between morning hours and afternoon hours (P < 0.05). By end of afternoon, the body weight was borne mainly on the left side with the knee fully extended and at various degrees of knee flexion. A significantly better directional control of the lateral rhythmic weight shifts was observed at the end of the afternoon than at morning hours (P < 0.05). In summary, most of our findings are inconsistent with results from previous studies in adults, suggesting age-related differences in posture control in humans. On a regular school day, the capacity of postural control and laterality or medio-lateral balance in children varies between morning and afternoon hours. We suggest that posturographic assessment in children, either in normal (e.g., physical education and sports training) or in abnormal conditions (e.g., mTBI-associated balance disorders), be better performed late in the afternoon.

Subgroup of ADNI Normal Controls Characterized by Atrophy and Cognitive Decline Associated With Vascular Damage

PubMed Central

Nettiksimmons, Jasmine; Beckett, Laurel; Schwarz, Christopher; Carmichael, Owen; Fletcher, Evan; DeCarli, Charles

2013-01-01

Previous work examining Alzheimer’s Disease Neuroimaging Initiative (ADNI) normal controls using cluster analysis identified a subgroup characterized by substantial brain atrophy and white matter hyperintensities (WMH). We hypothesized that these effects could be related to vascular damage. Fifty-three individuals in the suspected vascular cluster (Normal 2) were compared with 31 individuals from the cluster characterized as healthy/typical (Normal 1) on a variety of outcomes, including magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers, vascular risk factors and outcomes, cognitive trajectory, and medications for vascular conditions. Normal 2 was significantly older but did not differ on ApoE4+ prevalence. Normal 2 differed significantly from Normal 1 on all MRI measures but not on Amyloid-Beta1-42 or total tau protein. Normal 2 had significantly higher body mass index (BMI), Hachinksi score, and creatinine levels, and took significantly more medications for vascular conditions. Normal 2 had marginally significantly higher triglycerides and blood glucose. Normal 2 had a worse cognitive trajectory on the Rey’s Auditory Verbal Learning Test (RAVLT) 30-min delay test and the Functional Activity Questionnaire (FAQ). Cerebral atrophy associated with multiple vascular risks is common among cognitively normal individuals, forming a distinct subgroup with significantly increased cognitive decline. Further studies are needed to determine the clinical impact of these findings. PMID:23527743

Do we need gadolinium-based contrast medium for brain magnetic resonance imaging in children?

PubMed

Dünger, Dennis; Krause, Matthias; Gräfe, Daniel; Merkenschlager, Andreas; Roth, Christian; Sorge, Ina

2018-06-01

Brain imaging is the most common examination in pediatric magnetic resonance imaging (MRI), often combined with the use of a gadolinium-based contrast medium. The application of gadolinium-based contrast medium poses some risk. There is limited evidence of the benefits of contrast medium in pediatric brain imaging. To assess the diagnostic gain of contrast-enhanced sequences in brain MRI when the unenhanced sequences are normal. We retrospectively assessed 6,683 brain MR examinations using contrast medium in children younger than 16 years in the pediatric radiology department of the University Hospital Leipzig to determine whether contrast-enhanced sequences delivered additional, clinically relevant information to pre-contrast sequences. All examinations were executed using a 1.5-T or a 3-T system. In 8 of 3,003 (95% confidence interval 0.12-0.52%) unenhanced normal brain examinations, a relevant additional finding was detected when contrast medium was administered. Contrast enhancement led to a change in diagnosis in only one of these cases. Children with a normal pre-contrast brain MRI rarely benefit from contrast medium application. Comparing these results to the risks and disadvantages of a routine gadolinium application, there is substantiated numerical evidence for avoiding routine administration of gadolinium in a pre-contrast normal MRI examination.

Brain Morphology and Cerebrovascular Risk in Mild Cognitive Impairment and Dementia: SCOBHI-P study

PubMed Central

He, Jing; Iosif, Ana-Maria; Lee, Dong Young; Martinez, Oliver; Ding, Ding; Carmichael, Owen; Mortimer, James A.; Zhao, Qianhua; Chu, Shugang; Guo, Qihao; Galasko, Douglas; Salmon, David; Dai, Qi; Wu, Yougui; Petersen, Ron; Hong, Zhen; Borenstein, Amy R.; DeCarli, Charles

2010-01-01

Objective To investigate associations between MRI brain morphology, cerebrovascular risk (VR), clinical diagnosis and cognition among elders living in urban Shanghai. Design Cross-sectional study. Setting Memory Disorders Clinic and community normal control (NC) subject recruitment. Participants Ninety-six older subjects, 32 with normal cognition, 30 with amnestic MCI (aMCI) and 34 with dementia. Main outcome measures Each subject received medical history, neurological/physical exams, neuropsychological evaluations, brain MRI and apolipoprotein E-ε4 (APOE -ε4) genotype test. MRI volumes were assessed using a semi-automatic method. Results Brain volume (BV) was significantly smaller in the demented compared with NC (p < 0.001) or aMCI (p = 0.043). Hippocampal volume (HV) was lower, and white matter hyperintensity volume (WMH) was higher, in aMCI (HV: p = 0.028; WMH: p = 0.041) and dementia (HV: p < 0.001; WMH: p = 0.002) compared with NC. APOE -ε4 presence was significantly associated with reduced HV (p = 0.02). Systolic blood pressure was positively associated with VR score (p = 0.037); diastolic blood pressure (p = 0.021) and VR score (p = 0.036) were both positively associated with WMH. WMH (p = 0.029) and VR (p = 0.031) were both higher among the demented than NC. Conclusion MRI brain morphology changes were significantly associated clinical diagnosis, in addition, blood pressure was highly associated with VR score and WMH. These results suggest that MRI is a valuable measure of brain injury in a Chinese cohort and can serve to assess the effects of various degenerative and cerebrovascular pathologies. PMID:20937951

Source Space Estimation of Oscillatory Power and Brain Connectivity in Tinnitus

PubMed Central

Zobay, Oliver; Palmer, Alan R.; Hall, Deborah A.; Sereda, Magdalena; Adjamian, Peyman

2015-01-01

Tinnitus is the perception of an internally generated sound that is postulated to emerge as a result of structural and functional changes in the brain. However, the precise pathophysiology of tinnitus remains unknown. Llinas’ thalamocortical dysrhythmia model suggests that neural deafferentation due to hearing loss causes a dysregulation of coherent activity between thalamus and auditory cortex. This leads to a pathological coupling of theta and gamma oscillatory activity in the resting state, localised to the auditory cortex where normally alpha oscillations should occur. Numerous studies also suggest that tinnitus perception relies on the interplay between auditory and non-auditory brain areas. According to the Global Brain Model, a network of global fronto—parietal—cingulate areas is important in the generation and maintenance of the conscious perception of tinnitus. Thus, the distress experienced by many individuals with tinnitus is related to the top—down influence of this global network on auditory areas. In this magnetoencephalographic study, we compare resting-state oscillatory activity of tinnitus participants and normal-hearing controls to examine effects on spectral power as well as functional and effective connectivity. The analysis is based on beamformer source projection and an atlas-based region-of-interest approach. We find increased functional connectivity within the auditory cortices in the alpha band. A significant increase is also found for the effective connectivity from a global brain network to the auditory cortices in the alpha and beta bands. We do not find evidence of effects on spectral power. Overall, our results provide only limited support for the thalamocortical dysrhythmia and Global Brain models of tinnitus. PMID:25799178

Structural brain abnormalities in adolescent anorexia nervosa before and after weight recovery and associated hormonal changes.

PubMed

Mainz, Verena; Schulte-Rüther, Martin; Fink, Gereon R; Herpertz-Dahlmann, Beate; Konrad, Kerstin

2012-01-01

The neurobiological mechanisms of structural brain abnormalities in patients with anorexia nervosa (AN) remain poorly understood. In particular, little is known about the changes in and the recovery of gray matter (GM) volumes after weight gain and the relation to hormonal normalization in adolescent patients with AN. Nineteen female patients aged 12 to 17 years were assessed using magnetic resonance imaging at the time of admission to the hospital (T1) and after weight recovery (T2). Patients were compared with typically developing girls matched for age and intelligence quotient. Structural brain images were analyzed using a voxel-based morphometric approach. Circulating levels of cortisol and gonadotropins were assessed in blood samples. Compared with controls, patients with AN showed reduced GM in several brain regions along the cortical midline, reaching from the occipital cortex to the medial frontal areas. These GM reductions were mostly reversible at T1. Patients showed a GM increase from T1 to T2 along the cortical midline and in the occipital, temporal, parietal, and frontal lobes. GM increases at T2 correlated inversely with cortisol levels at T1 and positively with weight gain at T2. The strongest associations between regional GM increase and weight gain were found in the cerebellum. In addition, increases in GM volumes at T2 in the thalamus, hippocampus, and amygdala were associated with increases in follicle-stimulating hormone. Our data suggest that brain alterations in adolescents with acute AN are mostly reversible at T1 and that GM recovery in specific brain regions is associated with weight and hormonal normalization.

Permeability of the blood-brain barrier predicts conversion from optic neuritis to multiple sclerosis.

PubMed

Cramer, Stig P; Modvig, Signe; Simonsen, Helle J; Frederiksen, Jette L; Larsson, Henrik B W

2015-09-01

Optic neuritis is an acute inflammatory condition that is highly associated with multiple sclerosis. Currently, the best predictor of future development of multiple sclerosis is the number of T2 lesions visualized by magnetic resonance imaging. Previous research has found abnormalities in the permeability of the blood-brain barrier in normal-appearing white matter of patients with multiple sclerosis and here, for the first time, we present a study on the capability of blood-brain barrier permeability in predicting conversion from optic neuritis to multiple sclerosis and a direct comparison with cerebrospinal fluid markers of inflammation, cellular trafficking and blood-brain barrier breakdown. To this end, we applied dynamic contrast-enhanced magnetic resonance imaging at 3 T to measure blood-brain barrier permeability in 39 patients with monosymptomatic optic neuritis, all referred for imaging as part of the diagnostic work-up at time of diagnosis. Eighteen healthy controls were included for comparison. Patients had magnetic resonance imaging and lumbar puncture performed within 4 weeks of onset of optic neuritis. Information on multiple sclerosis conversion was acquired from hospital records 2 years after optic neuritis onset. Logistic regression analysis showed that baseline permeability in normal-appearing white matter significantly improved prediction of multiple sclerosis conversion (according to the 2010 revised McDonald diagnostic criteria) within 2 years compared to T2 lesion count alone. There was no correlation between permeability and T2 lesion count. An increase in permeability in normal-appearing white matter of 0.1 ml/100 g/min increased the risk of multiple sclerosis 8.5 times whereas having more than nine T2 lesions increased the risk 52.6 times. Receiver operating characteristic curve analysis of permeability in normal-appearing white matter gave a cut-off of 0.13 ml/100 g/min, which predicted conversion to multiple sclerosis with a sensitivity of 88% and specificity of 72%. We found a significant correlation between permeability and the leucocyte count in cerebrospinal fluid as well as levels of CXCL10 and MMP9 in the cerebrospinal fluid. These findings suggest that blood-brain barrier permeability, as measured by magnetic resonance imaging, may provide novel pathological information as a marker of neuroinflammation related to multiple sclerosis, to some extent reflecting cellular permeability of the blood-brain barrier, whereas T2 lesion count may more reflect the length of the subclinical pre-relapse phase.See Naismith and Cross (doi:10.1093/brain/awv196) for a scientific commentary on this article. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Neurocognitive sparing of desktop microbeam irradiation.

PubMed

Bazyar, Soha; Inscoe, Christina R; Benefield, Thad; Zhang, Lei; Lu, Jianping; Zhou, Otto; Lee, Yueh Z

2017-08-11

Normal tissue toxicity is the dose-limiting side effect of radiotherapy. Spatial fractionation irradiation techniques, like microbeam radiotherapy (MRT), have shown promising results in sparing the normal brain tissue. Most MRT studies have been conducted at synchrotron facilities. With the aim to make this promising treatment more available, we have built the first desktop image-guided MRT device based on carbon nanotube x-ray technology. In the current study, our purpose was to evaluate the effects of MRT on the rodent normal brain tissue using our device and compare it with the effect of the integrated equivalent homogenous dose. Twenty-four, 8-week-old male C57BL/6 J mice were randomly assigned to three groups: MRT, broad-beam (BB) and sham. The hippocampal region was irradiated with two parallel microbeams in the MRT group (beam width = 300 μm, center-to-center = 900 μm, 160 kVp). The BB group received the equivalent integral dose in the same area of their brain. Rotarod, marble burying and open-field activity tests were done pre- and every month post-irradiation up until 8 months to evaluate the cognitive changes and potential irradiation side effects on normal brain tissue. The open-field activity test was substituted by Barnes maze test at 8th month. A multilevel model, random coefficients approach was used to evaluate the longitudinal and temporal differences among treatment groups. We found significant differences between BB group as compared to the microbeam-treated and sham mice in the number of buried marble and duration of the locomotion around the open-field arena than shams. Barnes maze revealed that BB mice had a lower capacity for spatial learning than MRT and shams. Mice in the BB group tend to gain weight at the slower pace than shams. No meaningful differences were found between MRT and sham up until 8-month follow-up using our measurements. Applying MRT with our newly developed prototype compact CNT-based image-guided MRT system utilizing the current irradiation protocol can better preserve the integrity of normal brain tissue. Consequently, it enables applying higher irradiation dose that promises better tumor control. Further studies are required to evaluate the full extent effects of this novel modality.

Brain-derived neurotrophic factor (BDNF) in children with ASD and their parents: a 3-year follow-up.

PubMed

Francis, K; Dougali, A; Sideri, K; Kroupis, C; Vasdekis, V; Dima, K; Douzenis, A

2018-05-01

Several lines of evidence point to a probable relationship between brain-derived neurotrophic factor (BDNF) and autism spectrum disorder (ASD), but studies have yielded inconsistent findings on the BDNF serum level in ASD. The study aimed to assess those levels in children with ASD and their families. BDNF serum levels were measured in 45 ASD children without intellectual disability (ID) and allergies, age 30-42 months and age-matched normal controls. BDNF serum levels in the parents of the ASD subjects were compared to normal controls. BDNF serum levels in the ASD subjects were followed up for 3 years and correlated with adaptive functioning changes. BDNF serum levels were measured to be lower in children with ASD and independent of all the major baseline characteristics of the subjects. Having a child with ASD raises the BDNF levels in parents comparing to controls. Prospectively, no correlation between the change of BDNF variables in time and the change of the Vineland scores was found. Our results contradict those from recent published meta-analyses with the age, the presence of ID and allergies being possible contributing factors. The parents' data indeed point to a role of BDNF in the pathophysiology of ASD. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Speech-induced striatal dopamine release is left lateralized and coupled to functional striatal circuits in healthy humans: A combined PET, fMRI and DTI study

PubMed Central

Simonyan, Kristina; Herscovitch, Peter; Horwitz, Barry

2013-01-01

Considerable progress has been recently made in understanding the brain mechanisms underlying speech and language control. However, the neurochemical underpinnings of normal speech production remain largely unknown. We investigated the extent of striatal endogenous dopamine release and its influences on the organization of functional striatal speech networks during production of meaningful English sentences using a combination of positron emission tomography (PET) with the dopamine D2/D3 receptor radioligand [11C]raclopride and functional MRI (fMRI). In addition, we used diffusion tensor tractography (DTI) to examine the extent of dopaminergic modulatory influences on striatal structural network organization. We found that, during sentence production, endogenous dopamine was released in the ventromedial portion of the dorsal striatum, in its both associative and sensorimotor functional divisions. In the associative striatum, speech-induced dopamine release established a significant relationship with neural activity and influenced the left-hemispheric lateralization of striatal functional networks. In contrast, there were no significant effects of endogenous dopamine release on the lateralization of striatal structural networks. Our data provide the first evidence for endogenous dopamine release in the dorsal striatum during normal speaking and point to the possible mechanisms behind the modulatory influences of dopamine on the organization of functional brain circuits controlling normal human speech. PMID:23277111