Measuring brain connectivity: diffusion tensor imaging validates resting state temporal correlations.

PubMed

Skudlarski, Pawel; Jagannathan, Kanchana; Calhoun, Vince D; Hampson, Michelle; Skudlarska, Beata A; Pearlson, Godfrey

2008-11-15

Diffusion tensor imaging (DTI) and resting state temporal correlations (RSTC) are two leading techniques for investigating the connectivity of the human brain. They have been widely used to investigate the strength of anatomical and functional connections between distant brain regions in healthy subjects, and in clinical populations. Though they are both based on magnetic resonance imaging (MRI) they have not yet been compared directly. In this work both techniques were employed to create global connectivity matrices covering the whole brain gray matter. This allowed for direct comparisons between functional connectivity measured by RSTC with anatomical connectivity quantified using DTI tractography. We found that connectivity matrices obtained using both techniques showed significant agreement. Connectivity maps created for a priori defined anatomical regions showed significant correlation, and furthermore agreement was especially high in regions showing strong overall connectivity, such as those belonging to the default mode network. Direct comparison between functional RSTC and anatomical DTI connectivity, presented here for the first time, links two powerful approaches for investigating brain connectivity and shows their strong agreement. It provides a crucial multi-modal validation for resting state correlations as representing neuronal connectivity. The combination of both techniques presented here allows for further combining them to provide richer representation of brain connectivity both in the healthy brain and in clinical conditions.

Degree connectivity in body dysmorphic disorder and relationships with obsessive and compulsive symptoms.

PubMed

Beucke, Jan C; Sepulcre, Jorge; Buhlmann, Ulrike; Kathmann, Norbert; Moody, Teena; Feusner, Jamie D

2016-10-01

Individuals with body dysmorphic disorder (BDD) and obsessive-compulsive disorder (OCD) are categorized within the same major diagnostic group and both show regional brain hyperactivity in the orbitofrontal cortex (OFC) and the basal ganglia during symptom provocation. While recent studies revealed that degree connectivity of these areas is abnormally high in OCD and positively correlates with symptom severity, no study has investigated degree connectivity in BDD. We used functional magnetic resonance imaging (fMRI) to compare the local and distant degree of functional connectivity in all brain areas between 28 unmedicated BDD participants and 28 demographically matched healthy controls during a face-processing task. Correlational analyses tested for associations between degree connectivity and symptom severity assessed by the BDD version of the Yale-Brown obsessive-compulsive scale (BDD-Y-BOCS). Reduced local amygdalar connectivity was found in participants with BDD. No differences in distant connectivity were found. BDD-Y-BOCS scores significantly correlated with the local connectivity of the posterior-lateral OFC, and distant connectivity of the posterior-lateral and post-central OFC, respectively. These findings represent preliminary evidence that individuals with BDD exhibit brain-behavioral associations related to obsessive thoughts and compulsive behaviors that are highly similar to correlations previously found in OCD, further underscoring their related pathophysiology. This relationship could be further elucidated through investigation of resting-state functional connectivity in BDD, ideally in direct comparison with OCD and other obsessive-compulsive and related disorders. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Development of brain-wide connectivity architecture in awake rats.

PubMed

Ma, Zilu; Ma, Yuncong; Zhang, Nanyin

2018-08-01

Childhood and adolescence are both critical developmental periods, evidenced by complex neurophysiological changes the brain undergoes and high occurrence rates of neuropsychiatric disorders during these periods. Despite substantial progress in elucidating the developmental trajectories of individual neural circuits, our knowledge of developmental changes of whole-brain connectivity architecture in animals is sparse. To fill this gap, here we longitudinally acquired rsfMRI data in awake rats during five developmental stages from juvenile to adulthood. We found that the maturation timelines of brain circuits were heterogeneous and system specific. Functional connectivity (FC) tended to decrease in subcortical circuits, but increase in cortical circuits during development. In addition, the developing brain exhibited hemispheric functional specialization, evidenced by reduced inter-hemispheric FC between homotopic regions, and lower similarity of region-to-region FC patterns between the two hemispheres. Finally, we showed that whole-brain network development was characterized by reduced clustering (i.e. local communication) but increased integration (distant communication). Taken together, the present study has systematically characterized the development of brain-wide connectivity architecture from juvenile to adulthood in awake rats. It also serves as a critical reference point for understanding circuit- and network-level changes in animal models of brain development-related disorders. Furthermore, FC data during brain development in awake rodents contain high translational value and can shed light onto comparative neuroanatomy. Copyright © 2018 Elsevier Inc. All rights reserved.

Modeling Brain Dynamics in Brain Tumor Patients Using the Virtual Brain.

PubMed

Aerts, Hannelore; Schirner, Michael; Jeurissen, Ben; Van Roost, Dirk; Achten, Eric; Ritter, Petra; Marinazzo, Daniele

2018-01-01

Presurgical planning for brain tumor resection aims at delineating eloquent tissue in the vicinity of the lesion to spare during surgery. To this end, noninvasive neuroimaging techniques such as functional MRI and diffusion-weighted imaging fiber tracking are currently employed. However, taking into account this information is often still insufficient, as the complex nonlinear dynamics of the brain impede straightforward prediction of functional outcome after surgical intervention. Large-scale brain network modeling carries the potential to bridge this gap by integrating neuroimaging data with biophysically based models to predict collective brain dynamics. As a first step in this direction, an appropriate computational model has to be selected, after which suitable model parameter values have to be determined. To this end, we simulated large-scale brain dynamics in 25 human brain tumor patients and 11 human control participants using The Virtual Brain, an open-source neuroinformatics platform. Local and global model parameters of the Reduced Wong-Wang model were individually optimized and compared between brain tumor patients and control subjects. In addition, the relationship between model parameters and structural network topology and cognitive performance was assessed. Results showed (1) significantly improved prediction accuracy of individual functional connectivity when using individually optimized model parameters; (2) local model parameters that can differentiate between regions directly affected by a tumor, regions distant from a tumor, and regions in a healthy brain; and (3) interesting associations between individually optimized model parameters and structural network topology and cognitive performance.

Connecting long distance: semantic distance in analogical reasoning modulates frontopolar cortex activity.

PubMed

Green, Adam E; Kraemer, David J M; Fugelsang, Jonathan A; Gray, Jeremy R; Dunbar, Kevin N

2010-01-01

Solving problems often requires seeing new connections between concepts or events that seemed unrelated at first. Innovative solutions of this kind depend on analogical reasoning, a relational reasoning process that involves mapping similarities between concepts. Brain-based evidence has implicated the frontal pole of the brain as important for analogical mapping. Separately, cognitive research has identified semantic distance as a key characteristic of the kind of analogical mapping that can support innovation (i.e., identifying similarities across greater semantic distance reveals connections that support more innovative solutions and models). However, the neural substrates of semantically distant analogical mapping are not well understood. Here, we used functional magnetic resonance imaging (fMRI) to measure brain activity during an analogical reasoning task, in which we parametrically varied the semantic distance between the items in the analogies. Semantic distance was derived quantitatively from latent semantic analysis. Across 23 participants, activity in an a priori region of interest (ROI) in left frontopolar cortex covaried parametrically with increasing semantic distance, even after removing effects of task difficulty. This ROI was centered on a functional peak that we previously associated with analogical mapping. To our knowledge, these data represent a first empirical characterization of how the brain mediates semantically distant analogical mapping.

Increased transfer of 45Ca into brain and cerebrospinal fluid from plasma during chronic hypocalcemia in rats.

PubMed

Murphy, V A; Rapoport, S I

1988-06-28

Recent studies have shown regulation of central nervous system [Ca] after chronic hypo- and hypercalcemia. To investigate the mechanism of this regulation, 3-week-old rats were fed diets for 8 weeks that contained low or normal levels of Ca. Plasma [Ca] was 40% less in rats fed the low Ca diet than in animals fed normal diet. Unidirectional transfer coefficients for Ca (KCa) and Cl (KCl) into cerebrospinal fluid (CSF) and brain were determined from the 10 min uptake of intravenously injected 45Ca and 36Cl in awake animals. KCa for CSF was 68% greater in low-Ca rats than in normal rats. Likewise, the values of KCa for brain regions with areas adjacent to the ventricles like the hippocampus and pons-medulla were 50% higher than in normal animals. On the other hand, KCas for parietal cortex, a brain region distant from the choroid plexus and not expected to be influenced by Ca entry into CSF, were similar between the groups. Comparison of the regional ratios of KCa/KCl revealed that a selective increase of Ca transport occurred into CSF and all brain regions except the parietal cortex in Ca-deficient rats. The results suggest that Ca homeostasis of CSF and brain [Ca] during chronic hypocalcemia is due to increased transfer of Ca from blood to brain, and that the regulation occurs via the CSF, possibly at the choroid plexus, but not via the cerebral capillaries.

EEG functional connectivity, axon delays and white matter disease.

PubMed

Nunez, Paul L; Srinivasan, Ramesh; Fields, R Douglas

2015-01-01

Both structural and functional brain connectivities are closely linked to white matter disease. We discuss several such links of potential interest to neurologists, neurosurgeons, radiologists, and non-clinical neuroscientists. Treatment of brains as genuine complex systems suggests major emphasis on the multi-scale nature of brain connectivity and dynamic behavior. Cross-scale interactions of local, regional, and global networks are apparently responsible for much of EEG's oscillatory behaviors. Finite axon propagation speed, often assumed to be infinite in local network models, is central to our conceptual framework. Myelin controls axon speed, and the synchrony of impulse traffic between distant cortical regions appears to be critical for optimal mental performance and learning. Several experiments suggest that axon conduction speed is plastic, thereby altering the regional and global white matter connections that facilitate binding of remote local networks. Combined EEG and high resolution EEG can provide distinct multi-scale estimates of functional connectivity in both healthy and diseased brains with measures like frequency and phase spectra, covariance, and coherence. White matter disease may profoundly disrupt normal EEG coherence patterns, but currently these kinds of studies are rare in scientific labs and essentially missing from clinical environments. Copyright © 2014 International Federation of Clinical Neurophysiology. All rights reserved.

Convergent Differential Regulation of Parvalbumin in the Brains of Vocal Learners

PubMed Central

Hara, Erina; Rivas, Miriam V.; Ward, James M.; Okanoya, Kazuo; Jarvis, Erich D.

2012-01-01

Spoken language and learned song are complex communication behaviors found in only a few species, including humans and three groups of distantly related birds – songbirds, parrots, and hummingbirds. Despite their large phylogenetic distances, these vocal learners show convergent behaviors and associated brain pathways for vocal communication. However, it is not clear whether this behavioral and anatomical convergence is associated with molecular convergence. Here we used oligo microarrays to screen for genes differentially regulated in brain nuclei necessary for producing learned vocalizations relative to adjacent brain areas that control other behaviors in avian vocal learners versus vocal non-learners. A top candidate gene in our screen was a calcium-binding protein, parvalbumin (PV). In situ hybridization verification revealed that PV was expressed significantly higher throughout the song motor pathway, including brainstem vocal motor neurons relative to the surrounding brain regions of all distantly related avian vocal learners. This differential expression was specific to PV and vocal learners, as it was not found in avian vocal non-learners nor for control genes in learners and non-learners. Similar to the vocal learning birds, higher PV up-regulation was found in the brainstem tongue motor neurons used for speech production in humans relative to a non-human primate, macaques. These results suggest repeated convergent evolution of differential PV up-regulation in the brains of vocal learners separated by more than 65–300 million years from a common ancestor and that the specialized behaviors of learned song and speech may require extra calcium buffering and signaling. PMID:22238614

Atypical Distant Metastasis of Breast Malignant Phyllodes Tumors: A Case Report and Literature Review.

PubMed

de Foucher, Tiphaine; Roussel, Hélène; Hivelin, Mikael; Rossi, Léa; Cornou, Caroline; Bats, Anne-Sophie; Deloménie, Myriam; Lécuru, Fabrice; Ngô, Charlotte

2017-01-01

Malignant phyllodes tumors (MPT) are rare breast neoplasms. Preoperative diagnosis is often challenging due to the unspecific clinical, radiological, and histological characteristics of the tumor. Dissemination pathways are local with chest wall invasion, regional with lymph nodes metastasis, and distant, hematogenous, mostly to the lungs, bones, and brain. Distant metastasis (DM) can be synchronous or appear months to years after the diagnosis and initial management. The current report describes the case of a 57-year-old woman presenting with a giant/neglected MPT of the breast, with no DM at initial staging, treated by radical modified mastectomy. Motor disorders due to medullar compression by a paravertebral mass appeared at short follow-up, also treated surgically. The patient died from several DM of rapid evolution. To our knowledge, this is the only case described of MPT with metastases to soft tissue causing medullar compression. We present a literature review on unusual metastatic localizations of MPT.

A nomogram for predicting distant brain failure in patients treated with gamma knife stereotactic radiosurgery without whole brain radiotherapy

PubMed Central

Ayala-Peacock, Diandra N.; Peiffer, Ann M.; Lucas, John T.; Isom, Scott; Kuremsky, J. Griff; Urbanic, James J.; Bourland, J. Daniel; Laxton, Adrian W.; Tatter, Stephen B.; Shaw, Edward G.; Chan, Michael D.

2014-01-01

Background We review our single institution experience to determine predictive factors for early and delayed distant brain failure (DBF) after radiosurgery without whole brain radiotherapy (WBRT) for brain metastases. Materials and methods Between January 2000 and December 2010, a total of 464 patients were treated with Gamma Knife stereotactic radiosurgery (SRS) without WBRT for primary management of newly diagnosed brain metastases. Histology, systemic disease, RPA class, and number of metastases were evaluated as possible predictors of DBF rate. DBF rates were determined by serial MRI. Kaplan–Meier method was used to estimate rate of DBF. Multivariate analysis was performed using Cox Proportional Hazard regression. Results Median number of lesions treated was 1 (range 1–13). Median time to DBF was 4.9 months. Twenty-seven percent of patients ultimately required WBRT with median time to WBRT of 5.6 months. Progressive systemic disease (χ2= 16.748, P < .001), number of metastases at SRS (χ2 = 27.216, P < .001), discovery of new metastases at time of SRS (χ2 = 9.197, P < .01), and histology (χ2 = 12.819, P < .07) were factors that predicted for earlier time to distant failure. High risk histologic subtypes (melanoma, her2 negative breast, χ2 = 11.020, P < .001) and low risk subtypes (her2 + breast, χ2 = 11.343, P < .001) were identified. Progressive systemic disease (χ2 = 9.549, P < .01), number of brain metastases (χ2 = 16.953, P < .001), minimum SRS dose (χ2 = 21.609, P < .001), and widespread metastatic disease (χ2 = 29.396, P < .001) were predictive of shorter time to WBRT. Conclusion Systemic disease, number of metastases, and histology are factors that predict distant failure rate after primary radiosurgical management of brain metastases. PMID:24558022

Abnormal Vestibulo-Ocular Reflexes in Autism: A Potential Endophenotype

DTIC Science & Technology

2014-08-01

among. Saccades and smooth pursuit are complex sensorimotor behaviors that involve several spatially distant brain regions and long- fiber tracts between...time, at a rate of 100 Hz. Visual stimuli were presented as a red laser -light, generated by NKI Pursuit Tracker® laser . The Pursuit Tracker® laser ...the testing equipment by projecting a laser stimulus onto the cylindrical screen and providing a fixed target at + 10º in both the horizontal and

Atrophy of spared gray matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke.

PubMed

Gauthier, Lynne V; Taub, Edward; Mark, Victor W; Barghi, Ameen; Uswatte, Gitendra

2012-02-01

Although the motor deficit after stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to constraint-induced movement therapy in patients with chronic stroke may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Voxel-based morphometry analysis was performed on MRI scans from 80 patients with chronic stroke to investigate whether variations in gray matter density were correlated with extent of residual motor impairment or with constraint-induced movement therapy-induced motor recovery. Decreased gray matter density in noninfarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced gray matter density in multiple remote brain regions predicted a lesser extent of motor improvement from constraint-induced movement therapy. Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke.

Atrophy of spared grey matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke

PubMed Central

Gauthier, Lynne V.; Taub, Edward; Mark, Victor W.; Barghi, Ameen; Uswatte, Gitendra

2011-01-01

Background and Purpose Although the motor deficit following stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to Constraint-Induced Movement therapy (CI therapy) in chronic stroke patients may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Methods Voxel-based morphometry (VBM) analysis was performed on MRI scans from 80 chronic stroke patients to investigate whether variations in grey matter density were correlated with extent of residual motor impairment or with CI therapy-induced motor recovery. Results Decreased grey matter density in non-infarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced grey matter density in multiple remote brain regions predicted a lesser extent of motor improvement from CI therapy. Conclusions Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke. PMID:22096036

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

PubMed Central

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

2015-01-01

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

Distant influences of amygdala lesion on visual cortical activation during emotional face processing.

PubMed

Vuilleumier, Patrik; Richardson, Mark P; Armony, Jorge L; Driver, Jon; Dolan, Raymond J

2004-11-01

Emotional visual stimuli evoke enhanced responses in the visual cortex. To test whether this reflects modulatory influences from the amygdala on sensory processing, we used event-related functional magnetic resonance imaging (fMRI) in human patients with medial temporal lobe sclerosis. Twenty-six patients with lesions in the amygdala, the hippocampus or both, plus 13 matched healthy controls, were shown pictures of fearful or neutral faces in task-releant or task-irrelevant positions on the display. All subjects showed increased fusiform cortex activation when the faces were in task-relevant positions. Both healthy individuals and those with hippocampal damage showed increased activation in the fusiform and occipital cortex when they were shown fearful faces, but this was not the case for individuals with damage to the amygdala, even though visual areas were structurally intact. The distant influence of the amygdala was also evidenced by the parametric relationship between amygdala damage and the level of emotional activation in the fusiform cortex. Our data show that combining the fMRI and lesion approaches can help reveal the source of functional modulatory influences between distant but interconnected brain regions.

Sensory system plasticity in a visually specialized, nocturnal spider.

PubMed

Stafstrom, Jay A; Michalik, Peter; Hebets, Eileen A

2017-04-21

The interplay between an animal's environmental niche and its behavior can influence the evolutionary form and function of its sensory systems. While intraspecific variation in sensory systems has been documented across distant taxa, fewer studies have investigated how changes in behavior might relate to plasticity in sensory systems across developmental time. To investigate the relationships among behavior, peripheral sensory structures, and central processing regions in the brain, we take advantage of a dramatic within-species shift of behavior in a nocturnal, net-casting spider (Deinopis spinosa), where males cease visually-mediated foraging upon maturation. We compared eye diameters and brain region volumes across sex and life stage, the latter through micro-computed X-ray tomography. We show that mature males possess altered peripheral visual morphology when compared to their juvenile counterparts, as well as juvenile and mature females. Matching peripheral sensory structure modifications, we uncovered differences in relative investment in both lower-order and higher-order processing regions in the brain responsible for visual processing. Our study provides evidence for sensory system plasticity when individuals dramatically change behavior across life stages, uncovering new avenues of inquiry focusing on altered reliance of specific sensory information when entering a new behavioral niche.

Mapping the Information Trace in Local Field Potentials by a Computational Method of Two-Dimensional Time-Shifting Synchronization Likelihood Based on Graphic Processing Unit Acceleration.

PubMed

Zhao, Zi-Fang; Li, Xue-Zhu; Wan, You

2017-12-01

The local field potential (LFP) is a signal reflecting the electrical activity of neurons surrounding the electrode tip. Synchronization between LFP signals provides important details about how neural networks are organized. Synchronization between two distant brain regions is hard to detect using linear synchronization algorithms like correlation and coherence. Synchronization likelihood (SL) is a non-linear synchronization-detecting algorithm widely used in studies of neural signals from two distant brain areas. One drawback of non-linear algorithms is the heavy computational burden. In the present study, we proposed a graphic processing unit (GPU)-accelerated implementation of an SL algorithm with optional 2-dimensional time-shifting. We tested the algorithm with both artificial data and raw LFP data. The results showed that this method revealed detailed information from original data with the synchronization values of two temporal axes, delay time and onset time, and thus can be used to reconstruct the temporal structure of a neural network. Our results suggest that this GPU-accelerated method can be extended to other algorithms for processing time-series signals (like EEG and fMRI) using similar recording techniques.

Phase 3 Trials of Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for 1 to 4 Brain Metastases: Individual Patient Data Meta-Analysis

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

Sahgal, Arjun, E-mail: arjun.sahgal@sunnybrook.ca; Aoyama, Hidefumi; Kocher, Martin

Purpose: To perform an individual patient data (IPD) meta-analysis of randomized controlled trials evaluating stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy (WBRT) for patients presenting with 1 to 4 brain metastases. Method and Materials: Three trials were identified through a literature search, and IPD were obtained. Outcomes of interest were survival, local failure, and distant brain failure. The treatment effect was estimated after adjustments for age, recursive partitioning analysis (RPA) score, number of brain metastases, and treatment arm. Results: A total of 364 of the pooled 389 patients met eligibility criteria, of whom 51% were treated with SRSmore » alone and 49% were treated with SRS plus WBRT. For survival, age was a significant effect modifier (P=.04) favoring SRS alone in patients ≤50 years of age, and no significant differences were observed in older patients. Hazard ratios (HRs) for patients 35, 40, 45, and 50 years of age were 0.46 (95% confidence interval [CI] = 0.24-0.90), 0.52 (95% CI = 0.29-0.92), 0.58 (95% CI = 0.35-0.95), and 0.64 (95% CI = 0.42-0.99), respectively. Patients with a single metastasis had significantly better survival than those who had 2 to 4 metastases. For distant brain failure, age was a significant effect modifier (P=.043), with similar rates in the 2 arms for patients ≤50 of age; otherwise, the risk was reduced with WBRT for patients >50 years of age. Patients with a single metastasis also had a significantly lower risk of distant brain failure than patients who had 2 to 4 metastases. Local control significantly favored additional WBRT in all age groups. Conclusions: For patients ≤50 years of age, SRS alone favored survival, in addition, the initial omission of WBRT did not impact distant brain relapse rates. SRS alone may be the preferred treatment for this age group.« less

Epicenters of dynamic connectivity in the adaptation of the ventral visual system.

PubMed

Prčkovska, Vesna; Huijbers, Willem; Schultz, Aaron; Ortiz-Teran, Laura; Peña-Gomez, Cleofe; Villoslada, Pablo; Johnson, Keith; Sperling, Reisa; Sepulcre, Jorge

2017-04-01

Neuronal responses adapt to familiar and repeated sensory stimuli. Enhanced synchrony across wide brain systems has been postulated as a potential mechanism for this adaptation phenomenon. Here, we used recently developed graph theory methods to investigate hidden connectivity features of dynamic synchrony changes during a visual repetition paradigm. Particularly, we focused on strength connectivity changes occurring at local and distant brain neighborhoods. We found that connectivity reorganization in visual modal cortex-such as local suppressed connectivity in primary visual areas and distant suppressed connectivity in fusiform areas-is accompanied by enhanced local and distant connectivity in higher cognitive processing areas in multimodal and association cortex. Moreover, we found a shift of the dynamic functional connections from primary-visual-fusiform to primary-multimodal/association cortex. These findings suggest that repetition-suppression is made possible by reorganization of functional connectivity that enables communication between low- and high-order areas. Hum Brain Mapp 38:1965-1976, 2017. © 2017 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

NMDA receptor antagonist-enhanced high frequency oscillations: are they generated broadly or regionally specific?

PubMed

Olszewski, Maciej; Dolowa, Wioleta; Matulewicz, Pawel; Kasicki, Stefan; Hunt, Mark J

2013-12-01

Systemic administration of NMDA receptor antagonists, used to model schizophrenia, increase the power of high-frequency oscillations (130-180Hz, HFO) in a variety of neuroanatomical and functionally distinct brain regions. However, it is unclear whether HFO are independently and locally generated or instead spread from a distant source. To address this issue, we used local infusion of tetrodotoxin (TTX) to distinct brain areas to determine how accurately HFO recorded after injection of NMDAR antagonists reflect the activity actually generated at the electrode tip. Changes in power were evaluated in local field potentials (LFPs) recorded from the nucleus accumbens (NAc), prefrontal cortex and caudate and in electrocorticograms (ECoGs) from visual and frontal areas. HFO recorded in frontal and visual cortices (ECoGs) or in the prefrontal cortex, caudate (LFPs) co-varied in power and frequency with observed changes in the NAc. TTX infusion to the NAc immediately and profoundly reduced the power of accumbal HFO which correlated with changes in HFO recorded in distant cortical sites. In contrast, TTX infusion to the prefrontal cortex did not change HFO power recorded locally, although gamma power was reduced. A very similar result was found after TTX infusion to the caudate. These findings raise the possibility that the NAc is an important neural generator. Our data also support existing studies challenging the idea that high frequencies recorded in LFPs are necessarily generated at the recording site. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Rodent Zic Genes in Neural Network Wiring.

PubMed

Herrera, Eloísa

2018-01-01

The formation of the nervous system is a multistep process that yields a mature brain. Failure in any of the steps of this process may cause brain malfunction. In the early stages of embryonic development, neural progenitors quickly proliferate and then, at a specific moment, differentiate into neurons or glia. Once they become postmitotic neurons, they migrate to their final destinations and begin to extend their axons to connect with other neurons, sometimes located in quite distant regions, to establish different neural circuits. During the last decade, it has become evident that Zic genes, in addition to playing important roles in early development (e.g., gastrulation and neural tube closure), are involved in different processes of late brain development, such as neuronal migration, axon guidance, and refinement of axon terminals. ZIC proteins are therefore essential for the proper wiring and connectivity of the brain. In this chapter, we review our current knowledge of the role of Zic genes in the late stages of neural circuit formation.

Apollo’s gift: new aspects of neurologic music therapy

PubMed Central

Altenmüller, Eckart; Schlaug, Gottfried

2015-01-01

Music listening and music making activities are powerful tools to engage multisensory and motor networks, induce changes within these networks, and foster links between distant, but functionally related brain regions with continued and life-long musical practice. These multimodal effects of music together with music’s ability to tap into the emotion and reward system in the brain can be used to facilitate and enhance therapeutic approaches geared toward rehabilitating and restoring neurological dysfunctions and impairments of an acquired or congenital brain disorder. In this article, we review plastic changes in functional networks and structural components of the brain in response to short- and long-term music listening and music making activities. The specific influence of music on the developing brain is emphasized and possible transfer effects on emotional and cognitive processes are discussed. Furthermore, we present data on the potential of using musical tools and activities to support and facilitate neurorehabilitation. We will focus on interventions such as melodic intonation therapy and music-supported motor rehabilitation to showcase the effects of neurologic music therapies and discuss their underlying neural mechanisms. PMID:25725918

Apollo's gift: new aspects of neurologic music therapy.

PubMed

Altenmüller, Eckart; Schlaug, Gottfried

2015-01-01

Music listening and music making activities are powerful tools to engage multisensory and motor networks, induce changes within these networks, and foster links between distant, but functionally related brain regions with continued and life-long musical practice. These multimodal effects of music together with music's ability to tap into the emotion and reward system in the brain can be used to facilitate and enhance therapeutic approaches geared toward rehabilitating and restoring neurological dysfunctions and impairments of an acquired or congenital brain disorder. In this article, we review plastic changes in functional networks and structural components of the brain in response to short- and long-term music listening and music making activities. The specific influence of music on the developing brain is emphasized and possible transfer effects on emotional and cognitive processes are discussed. Furthermore, we present data on the potential of using musical tools and activities to support and facilitate neurorehabilitation. We will focus on interventions such as melodic intonation therapy and music-supported motor rehabilitation to showcase the effects of neurologic music therapies and discuss their underlying neural mechanisms. © 2015 Elsevier B.V. All rights reserved.

Altered local spontaneous activity in frontal lobe epilepsy: a resting-state functional magnetic resonance imaging study.

PubMed

Dong, Li; Li, Hechun; He, Zhongqiong; Jiang, Sisi; Klugah-Brown, Benjamin; Chen, Lin; Wang, Pu; Tan, Song; Luo, Cheng; Yao, Dezhong

2016-11-01

The purpose of this study was to investigate the local spatiotemporal consistency of spontaneous brain activity in patients with frontal lobe epilepsy (FLE). Eyes closed resting-state functional magnetic resonance imaging (fMRI) data were collected from 19 FLE patients and 19 age- and gender-matched healthy controls. A novel measure, named FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was used to assess the spatiotemporal consistency of local spontaneous activity (emphasizing both local temporal homogeneity and regional stability of brain activity states). Then, two-sample t test was performed to detect the FOCA differences between two groups. Partial correlations between the FOCA values and durations of epilepsy were further analyzed. Compared with controls, FLE patients demonstrated increased FOCA in distant brain regions including the frontal and parietal cortices, as well as the basal ganglia. The decreased FOCA was located in the temporal cortex, posterior default model regions, and cerebellum. In addition, the FOCA measure was linked to the duration of epilepsy in basal ganglia. Our study suggested that alterations of local spontaneous activity in frontoparietal cortex and basal ganglia was associated with the pathophysiology of FLE; and the abnormality in frontal and default model regions might account for the potential cognitive impairment in FLE. We also presumed that the FOCA measure had potential to provide important insights into understanding epilepsy such as FLE.

Pseudotyped Lentiviral Vectors for Retrograde Gene Delivery into Target Brain Regions

PubMed Central

Kobayashi, Kenta; Inoue, Ken-ichi; Tanabe, Soshi; Kato, Shigeki; Takada, Masahiko; Kobayashi, Kazuto

2017-01-01

Gene transfer through retrograde axonal transport of viral vectors offers a substantial advantage for analyzing roles of specific neuronal pathways or cell types forming complex neural networks. This genetic approach may also be useful in gene therapy trials by enabling delivery of transgenes into a target brain region distant from the injection site of the vectors. Pseudotyping of a lentiviral vector based on human immunodeficiency virus type 1 (HIV-1) with various fusion envelope glycoproteins composed of different combinations of rabies virus glycoprotein (RV-G) and vesicular stomatitis virus glycoprotein (VSV-G) enhances the efficiency of retrograde gene transfer in both rodent and nonhuman primate brains. The most recently developed lentiviral vector is a pseudotype with fusion glycoprotein type E (FuG-E), which demonstrates highly efficient retrograde gene transfer in the brain. The FuG-E–pseudotyped vector permits powerful experimental strategies for more precisely investigating the mechanisms underlying various brain functions. It also contributes to the development of new gene therapy approaches for neurodegenerative disorders, such as Parkinson’s disease, by delivering genes required for survival and protection into specific neuronal populations. In this review article, we report the properties of the FuG-E–pseudotyped vector, and we describe the application of the vector to neural circuit analysis and the potential use of the FuG-E vector in gene therapy for Parkinson’s disease. PMID:28824385

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.

Metastatic patterns and metastatic sites in mucosal melanoma: a retrospective study.

PubMed

Grözinger, Gerd; Mann, Steven; Mehra, Tarun; Klumpp, Bernhard; Grosse, Ulrich; Nikolaou, Konstantin; Garbe, Claus; Clasen, Stephan

2016-06-01

Melanomas arising from mucosa are rare and associated with a poor prognosis. This study aims to provide an analysis of metastatic pathways, time intervals, factors influencing metastatic spread and organs for distant metastases. A total of 116 patients with mucosal melanomas of different sites were included. The mean follow-up interval was 47 ± 52 months. Patients were assigned to two different metastatic pathways, either presenting loco-regional lymph node metastases as first spread or direct distant metastases. The distribution of distant metastases was assessed. Twenty-six patients presented with a pre-existing metastatic spread and were not assigned to pathways. Of the included patients, 44 developed metastases after treatment of the primary tumour; 25 patients directly developed distant metastases; 16 patients developed regional lymph node metastases prior to distant metastases. Location of the primary tumour in the upper airway or GI tract and advanced T stage were significant risk factors of direct distant metastases. Distant metastases are mainly located in the lung, the liver and non-regional lymph nodes. Mucosal melanomas show a high rate of direct distant metastases rather than regional lymph node metastases. Thus the follow-up should always include a whole-body cross-sectional imaging in high-risk tumours. • Mucosal melanomas show a high rate of direct distant metastases. • T stage and primary location are predictors for direct distant metastases. • Distant metastases were mainly found in lung, liver and lymph nodes. • Follow-up of a high-risk mucosal melanoma should include whole-body imaging.

Intraoperative monitoring of brain tissue oxygenation during arteriovenous malformation resection.

PubMed

Arikan, Fuat; Vilalta, Jordi; Noguer, Montserrat; Olive, Montserrat; Vidal-Jorge, Marian; Sahuquillo, Juan

2014-10-01

In normal perfusion pressure breakthrough (NPPB) it is assumed that following arteriovenous malformation (AVM) resection, vasoparalysis persists in the margins of the lesion and that a sudden increase in cerebral blood flow (CBF) after AVM exclusion leads to brain swelling and postsurgical complications. However, the pathophysiology NPPB remains controversial.The aim of our study was to investigate the oxygenation status in tissue surrounding AVMs and in the distant brain using intraoperative monitoring of cerebral partial pressure of oxygen (PtiO(2)) to achieve a better understanding of NPPB pathophysiology. Patients with supratentorial AVMs were monitored intraoperatively using 2 polarographic Clark-type electrodes. To establish reference values, we also studied PtiO(2) in a group of patients who underwent surgery to treat incidental aneurysms. Twenty-two patients with supratentorial AVMs and 16 patients with incidentally found aneurysms were included. Hypoxic pattern was defined as PtiO(2)≤15 mm Hg and/or PtiO(2)/PaO(2) ratio ≤0.10. Tissue hypoxia was detected in 63.6% of the catheters placed in the perinidal area and in 43.8% of catheters placed in a distant area. AVM excision significantly improved oxygenation both around the AVM and in the distant area. The PtiO(2)/PaO(2) ratio is a better indicator than absolute PtiO(2) in detecting tissue hypoxia in mechanically ventilated patients. Intraoperative monitoring showed tissue hypoxia in the margins of AVMs and in the distant ipsilateral brain as the most common finding. Surgical removal of AVMs induces a significant improvement in the oxygenation status in both areas.

Individual brain structure and modelling predict seizure propagation

PubMed Central

Proix, Timothée; Bartolomei, Fabrice; Guye, Maxime; Jirsa, Viktor K.

2017-01-01

Abstract See Lytton (doi:10.1093/awx018) for a scientific commentary on this article. Neural network oscillations are a fundamental mechanism for cognition, perception and consciousness. Consequently, perturbations of network activity play an important role in the pathophysiology of brain disorders. When structural information from non-invasive brain imaging is merged with mathematical modelling, then generative brain network models constitute personalized in silico platforms for the exploration of causal mechanisms of brain function and clinical hypothesis testing. We here demonstrate with the example of drug-resistant epilepsy that patient-specific virtual brain models derived from diffusion magnetic resonance imaging have sufficient predictive power to improve diagnosis and surgery outcome. In partial epilepsy, seizures originate in a local network, the so-called epileptogenic zone, before recruiting other close or distant brain regions. We create personalized large-scale brain networks for 15 patients and simulate the individual seizure propagation patterns. Model validation is performed against the presurgical stereotactic electroencephalography data and the standard-of-care clinical evaluation. We demonstrate that the individual brain models account for the patient seizure propagation patterns, explain the variability in postsurgical success, but do not reliably augment with the use of patient-specific connectivity. Our results show that connectome-based brain network models have the capacity to explain changes in the organization of brain activity as observed in some brain disorders, thus opening up avenues towards discovery of novel clinical interventions. PMID:28364550

Muscle metastasis from non-small cell lung cancer: two cases and literature review.

PubMed

Tezcan, Y; Koc, M

2014-08-01

Non-small cell lung cancers (NSCLC) is the most commonly observed group among lung cancers. Adenocancers are histopathologically more common. Males are more affected than females, an effect which is directly related to smoking. They generally cause distant haematogenous and lymphatic metastasis. Distant haematogenous metastases are often seen in contralateral lung, brain, bone, adrenals, and liver. Muscle metastases from NSCLC are quite rare and male cases are more frequently affected compared to female cases. NSCLC cases with muscle metastasis are at the same time accompanied by distant organ metastases such as bone, brain, and liver. All treatment approaches are considered to be palliative in these cases, which are symptomatologically quite severe. In the present study, we presented the rarely observed cases of two male patients with muscle metastasis from NSCLC together with the related literature.

Survival was Significantly Better with Surgical/Medical/Radiation Co-interventions in a Single-Institution Practice Audit of Frameless Stereotactic Radiosurgery.

PubMed

Taggar, Amandeep; MacKenzie, Joanna; Li, Haocheng; Lau, Harold; Lim, Gerald; Nordal, Robert; Hudson, Alana; Khan, Rao; Spencer, David; Voroney, Jon-Paul

2016-05-17

To audit outcomes after introducing frameless stereotactic radiosurgery (SRS) for brain metastases, including co-interventions: neurosurgery, systemic therapy, and whole brain radiotherapy (WBRT). We report median overall survival (MS), local failure, and distant brain failure. We hypothesized patients treated with SRS would have clinically meaningful improved MS compared with historic institutional values. We further hypothesized that patients treated with co-interventions would have clinically meaningful improved MS compared with patients treated with SRS alone. One hundred twenty patients (N = 120) with limited intracranial disease underwent 130 frameless SRS sessions from April 2010 to May 2013. Median follow-up was 11 months. MS was measured from brain metastases diagnosis, local failure, and distant brain failure from the time of first SRS. Practice pattern during the first year of the study favored upfront WBRT (79%) over SRS (21%) while upfront SRS (45%) was almost as common as upfront WBRT (55%) in the last year of the study. MS was 18 months; 37% received SRS alone as initial radiotherapy (MS 12 months); 63% received WBRT prior to SRS (MS 19 months); 50% received systemic therapy post-SRS (MS 21 months); and 26% had tumor resection then SRS to the surgical cavity (MS 42 months). Local failure occurred in 10% of lesions and radio-necrosis occurred in 4%. Differences in distant brain failure among patients treated with upfront SRS (40% rate), WBRT followed by SRS (33% rate) or systemic therapy post-SRS (37% rate) were not statistically significant. Frameless SRS effectively treats surgical cavities, persistent tumors post-WBRT, and can be used as an upfront treatment of brain metastases. Surgery, systemic therapy, and WBRT are associated with longer MS. Patients can live for years while receiving multiple therapies. Systemic therapy for patients with brain metastases is increasingly common, palliative care occurs earlier and improves survival, and WBRT use is not routine. Modern series sometimes produce unexpectedly good results. Classification and treatment protocols are evolving. This practice audit is note-worthy for (i) high median overall survival, (ii) systemic therapy after radiosurgery for patients with tumors treated by radiosurgery, (iii) distant brain failure not significantly related to WBRT, and (iv) neurosurgery, systemic therapy, and WBRT are independently associated with improved MS.

Resolvin D1 Halts Remote Neuroinflammation and Improves Functional Recovery after Focal Brain Damage Via ALX/FPR2 Receptor-Regulated MicroRNAs.

PubMed

Bisicchia, Elisa; Sasso, Valeria; Catanzaro, Giuseppina; Leuti, Alessandro; Besharat, Zein Mersini; Chiacchiarini, Martina; Molinari, Marco; Ferretti, Elisabetta; Viscomi, Maria Teresa; Chiurchiù, Valerio

2018-01-22

Remote damage is a secondary phenomenon that usually occurs after a primary brain damage in regions that are distant, yet functionally connected, and that is critical for determining the outcomes of several CNS pathologies, including traumatic brain and spinal cord injuries. The understanding of remote damage-associated mechanisms has been mostly achieved in several models of focal brain injury such as the hemicerebellectomy (HCb) experimental paradigm, which helped to identify the involvement of many key players, such as inflammation, oxidative stress, apoptosis and autophagy. Currently, few interventions have been shown to successfully limit the progression of secondary damage events and there is still an unmet need for new therapeutic options. Given the emergence of the novel concept of resolution of inflammation, mediated by the newly identified ω3-derived specialized pro-resolving lipid mediators, such as resolvins, we reported a reduced ability of HCb-injured animals to produce resolvin D1 (RvD1) and an increased expression of its target receptor ALX/FPR2 in remote brain regions. The in vivo administration of RvD1 promoted functional recovery and neuroprotection by reducing the activation of Iba-1+ microglia and GFAP+ astrocytes as well as by impairing inflammatory-induced neuronal cell death in remote regions. These effects were counteracted by intracerebroventricular neutralization of ALX/FPR2, whose activation by RvD1 also down-regulated miR-146b- and miR-219a-1-dependent inflammatory markers. In conclusion, we propose that innovative therapies based on RvD1-ALX/FPR2 axis could be exploited to curtail remote damage and enable neuroprotective effects after acute focal brain damage.

A microinjection technique for targeting regions of embryonic and neonatal mouse brain in vivo

PubMed Central

Davidson, Steve; Truong, Hai; Nakagawa, Yasushi; Giesler, Glenn J

2009-01-01

A simple pressure injection technique was developed to deliver substances into specific regions of the embryonic and neonatal mouse brain in vivo. The retrograde tracers Fluorogold and cholera toxin B subunit were used to test the validity of the technique. Injected animals survived the duration of transport (24–48 hrs) and then were sacrificed and perfused with fixative. Small injections (≤ 50 nL) were contained within targeted structures of the perinatal brain and labeled distant cells of origin in several model neural pathways. Traced neural pathways in the perinatal mouse were further examined with immunohistochemical methods to test the feasibility of double labeling experiments during development. Several experimental situations in which this technique would be useful are discussed, for example, to label projection neurons in slice or culture preparations of mouse embryos and neonates. The administration of pharmacological or genetic vectors directly into specific neural targets during development should also be feasible. An examination of the form of neural pathways during early stages of life may lead to insights regarding the functional changes that occur during critical periods of development and provide an anatomic basis for some neurodevelopmental disorders. PMID:19840780

Long-term effects of musical training and functional plasticity in salience system.

PubMed

Luo, Cheng; Tu, Shipeng; Peng, Yueheng; Gao, Shan; Li, Jianfu; Dong, Li; Li, Gujing; Lai, Yongxiu; Li, Hong; Yao, Dezhong

2014-01-01

Musicians undergoing long-term musical training show improved emotional and cognitive function, which suggests the presence of neuroplasticity. The structural and functional impacts of the human brain have been observed in musicians. In this study, we used data-driven functional connectivity analysis to map local and distant functional connectivity in resting-state functional magnetic resonance imaging data from 28 professional musicians and 28 nonmusicians. Compared with nonmusicians, musicians exhibited significantly greater local functional connectivity density in 10 regions, including the bilateral dorsal anterior cingulate cortex, anterior insula, and anterior temporoparietal junction. A distant functional connectivity analysis demonstrated that most of these regions were included in salience system, which is associated with high-level cognitive control and fundamental attentional process. Additionally, musicians had significantly greater functional integration in this system, especially for connections to the left insula. Increased functional connectivity between the left insula and right temporoparietal junction may be a response to long-term musical training. Our findings indicate that the improvement of salience network is involved in musical training. The salience system may represent a new avenue for exploration regarding the underlying foundations of enhanced higher-level cognitive processes in musicians.

Transcranial magnetic stimulation-induced global propagation of transient phase resetting associated with directional information flow.

PubMed

Kawasaki, Masahiro; Uno, Yutaka; Mori, Jumpei; Kobata, Kenji; Kitajo, Keiichi

2014-01-01

Electroencephalogram (EEG) phase synchronization analyses can reveal large-scale communication between distant brain areas. However, it is not possible to identify the directional information flow between distant areas using conventional phase synchronization analyses. In the present study, we applied transcranial magnetic stimulation (TMS) to the occipital area in subjects who were resting with their eyes closed, and analyzed the spatial propagation of transient TMS-induced phase resetting by using the transfer entropy (TE), to quantify the causal and directional flow of information. The time-frequency EEG analysis indicated that the theta (5 Hz) phase locking factor (PLF) reached its highest value at the distant area (the motor area in this study), with a time lag that followed the peak of the transient PLF enhancements of the TMS-targeted area at the TMS onset. Phase-preservation index (PPI) analyses demonstrated significant phase resetting at the TMS-targeted area and distant area. Moreover, the TE from the TMS-targeted area to the distant area increased clearly during the delay that followed TMS onset. Interestingly, the time lags were almost coincident between the PLF and TE results (152 vs. 165 ms), which provides strong evidence that the emergence of the delayed PLF reflects the causal information flow. Such tendencies were observed only in the higher-intensity TMS condition, and not in the lower-intensity or sham TMS conditions. Thus, TMS may manipulate large-scale causal relationships between brain areas in an intensity-dependent manner. We demonstrated that single-pulse TMS modulated global phase dynamics and directional information flow among synchronized brain networks. Therefore, our results suggest that single-pulse TMS can manipulate both incoming and outgoing information in the TMS-targeted area associated with functional changes.

The effect of distant metastases sites on survival in de novo stage-IV breast cancer: A SEER database analysis.

PubMed

Wu, San-Gang; Li, Hui; Tang, Li-Ying; Sun, Jia-Yuan; Zhang, Wen-Wen; Li, Feng-Yan; Chen, Yong-Xiong; He, Zhen-Yu

2017-06-01

To investigate the effect of distant metastases sites on survival in patients with de novo stage-IV breast cancer. From 2010 to 2013, patients with a diagnosis of de novo stage-IV breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on breast cancer-specific survival and overall survival. A total of 7575 patients were identified. The most common metastatic sites were bone, followed by lung, liver, and brain. Patients with hormone receptor+/human epidermal growth factor receptor 2- and hormone receptor+/human epidermal growth factor receptor 2+ status were more prone to bone metastases. Lung and brain metastases were common in hormone receptor-/human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2- subtypes, and patients with hormone receptor+/ human epidermal growth factor receptor 2+ and hormone receptor-/human epidermal growth factor receptor 2+ subtypes were more prone to liver metastases. Patients with liver and brain metastases had unfavorable prognosis for breast cancer-specific survival and overall survival, whereas bone and lung metastases had no effect on patient survival in multivariate analyses. The hormone receptor-/human epidermal growth factor receptor 2- subtype conferred a significantly poorer outcome in terms of breast cancer-specific survival and overall survival. hormone receptor+/human epidermal growth factor receptor 2+ disease was associated with the best prognosis in terms of breast cancer-specific survival and overall survival. Patients with liver and brain metastases were more likely to experience poor prognosis for breast cancer-specific survival and overall survival by various breast cancer subtypes. Distant metastases sites have differential impact on clinical outcomes in stage-IV breast cancer. Follow-up screening for brain and liver metastases might be effective in improving breast cancer-specific survival and overall survival.

Individual brain structure and modelling predict seizure propagation.

PubMed

Proix, Timothée; Bartolomei, Fabrice; Guye, Maxime; Jirsa, Viktor K

2017-03-01

See Lytton (doi:10.1093/awx018) for a scientific commentary on this article.Neural network oscillations are a fundamental mechanism for cognition, perception and consciousness. Consequently, perturbations of network activity play an important role in the pathophysiology of brain disorders. When structural information from non-invasive brain imaging is merged with mathematical modelling, then generative brain network models constitute personalized in silico platforms for the exploration of causal mechanisms of brain function and clinical hypothesis testing. We here demonstrate with the example of drug-resistant epilepsy that patient-specific virtual brain models derived from diffusion magnetic resonance imaging have sufficient predictive power to improve diagnosis and surgery outcome. In partial epilepsy, seizures originate in a local network, the so-called epileptogenic zone, before recruiting other close or distant brain regions. We create personalized large-scale brain networks for 15 patients and simulate the individual seizure propagation patterns. Model validation is performed against the presurgical stereotactic electroencephalography data and the standard-of-care clinical evaluation. We demonstrate that the individual brain models account for the patient seizure propagation patterns, explain the variability in postsurgical success, but do not reliably augment with the use of patient-specific connectivity. Our results show that connectome-based brain network models have the capacity to explain changes in the organization of brain activity as observed in some brain disorders, thus opening up avenues towards discovery of novel clinical interventions. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

LOCAL CORTICAL ACTIVITY OF DISTANT BRAIN AREAS CAN PHASE-LOCK TO THE OLFACTORY BULB'S RESPIRATORY RHYTHM IN THE FREELY BEHAVING RAT.

PubMed

Rojas-Líbano, Daniel; Wimmer Del Solar, Jonathan; Aguilar-Rivera, Marcelo; Montefusco-Siegmund, Rodrigo; Maldonado, Pedro Esteban

2018-05-16

An important unresolved question about neural processing is the mechanism by which distant brain areas coordinate their activities and relate their local processing to global neural events. A potential candidate for the local-global integration are slow rhythms such as respiration. In this article, we asked if there are modulations of local cortical processing which are phase-locked to (peripheral) sensory-motor exploratory rhythms. We studied rats on an elevated platform where they would spontaneously display exploratory and rest behaviors. Concurrent with behavior, we monitored whisking through EMG and the respiratory rhythm from the olfactory bulb (OB) local field potential (LFP). We also recorded LFPs from dorsal hippocampus, primary motor cortex, primary somatosensory cortex and primary visual cortex. We defined exploration as simultaneous whisking and sniffing above 5 Hz and found that this activity peaked at about 8 Hz. We considered rest as the absence of whisking and sniffing, and in this case, respiration occurred at about 3 Hz. We found a consistent shift across all areas toward these rhythm peaks accompanying behavioral changes. We also found, across areas, that LFP gamma (70-100 Hz) amplitude could phase-lock to the animal's OB respiratory rhythm, a finding indicative of respiration-locked changes in local processing. In a subset of animals, we also recorded the hippocampal theta activity and found that occurred at frequencies overlapped with respiration but was not spectrally coherent with it, suggesting a different oscillator. Our results are consistent with the notion of respiration as a binder or integrator of activity between brain regions.

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

PubMed

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

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

Structural covariance of neostriatal and limbic regions in patients with obsessive-compulsive disorder.

PubMed

Subirà, Marta; Cano, Marta; de Wit, Stella J; Alonso, Pino; Cardoner, Narcís; Hoexter, Marcelo Q; Kwon, Jun Soo; Nakamae, Takashi; Lochner, Christine; Sato, João R; Jung, Wi Hoon; Narumoto, Jin; Stein, Dan J; Pujol, Jesus; Mataix-Cols, David; Veltman, Dick J; Menchón, José M; van den Heuvel, Odile A; Soriano-Mas, Carles

2016-03-01

Frontostriatal and frontoamygdalar connectivity alterations in patients with obsessive-compulsive disorder (OCD) have been typically described in functional neuroimaging studies. However, structural covariance, or volumetric correlations across distant brain regions, also provides network-level information. Altered structural covariance has been described in patients with different psychiatric disorders, including OCD, but to our knowledge, alterations within frontostriatal and frontoamygdalar circuits have not been explored. We performed a mega-analysis pooling structural MRI scans from the Obsessive-compulsive Brain Imaging Consortium and assessed whole-brain voxel-wise structural covariance of 4 striatal regions (dorsal and ventral caudate nucleus, and dorsal-caudal and ventral-rostral putamen) and 2 amygdalar nuclei (basolateral and centromedial-superficial). Images were preprocessed with the standard pipeline of voxel-based morphometry studies using Statistical Parametric Mapping software. Our analyses involved 329 patients with OCD and 316 healthy controls. Patients showed increased structural covariance between the left ventral-rostral putamen and the left inferior frontal gyrus/frontal operculum region. This finding had a significant interaction with age; the association held only in the subgroup of older participants. Patients with OCD also showed increased structural covariance between the right centromedial-superficial amygdala and the ventromedial prefrontal cortex. This was a cross-sectional study. Because this is a multisite data set analysis, participant recruitment and image acquisition were performed in different centres. Most patients were taking medication, and treatment protocols differed across centres. Our results provide evidence for structural network-level alterations in patients with OCD involving 2 frontosubcortical circuits of relevance for the disorder and indicate that structural covariance contributes to fully characterizing brain alterations in patients with psychiatric disorders.

Genetic influences on functional connectivity associated with feedback processing and prediction error: Phase coupling of theta-band oscillations in twins.

PubMed

Demiral, Şükrü Barış; Golosheykin, Simon; Anokhin, Andrey P

2017-05-01

Detection and evaluation of the mismatch between the intended and actually obtained result of an action (reward prediction error) is an integral component of adaptive self-regulation of behavior. Extensive human and animal research has shown that evaluation of action outcome is supported by a distributed network of brain regions in which the anterior cingulate cortex (ACC) plays a central role, and the integration of distant brain regions into a unified feedback-processing network is enabled by long-range phase synchronization of cortical oscillations in the theta band. Neural correlates of feedback processing are associated with individual differences in normal and abnormal behavior, however, little is known about the role of genetic factors in the cerebral mechanisms of feedback processing. Here we examined genetic influences on functional cortical connectivity related to prediction error in young adult twins (age 18, n=399) using event-related EEG phase coherence analysis in a monetary gambling task. To identify prediction error-specific connectivity pattern, we compared responses to loss and gain feedback. Monetary loss produced a significant increase of theta-band synchronization between the frontal midline region and widespread areas of the scalp, particularly parietal areas, whereas gain resulted in increased synchrony primarily within the posterior regions. Genetic analyses showed significant heritability of frontoparietal theta phase synchronization (24 to 46%), suggesting that individual differences in large-scale network dynamics are under substantial genetic control. We conclude that theta-band synchronization of brain oscillations related to negative feedback reflects genetically transmitted differences in the neural mechanisms of feedback processing. To our knowledge, this is the first evidence for genetic influences on task-related functional brain connectivity assessed using direct real-time measures of neuronal synchronization. Copyright © 2016 Elsevier B.V. All rights reserved.

Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model

PubMed Central

Tagge, Chad A; Fisher, Andrew M; Minaeva, Olga V; Gaudreau-Balderrama, Amanda; Moncaster, Juliet A; Zhang, Xiao-Lei; Wojnarowicz, Mark W; Casey, Noel; Lu, Haiyan; Kokiko-Cochran, Olga N; Saman, Sudad; Ericsson, Maria; Onos, Kristen D; Veksler, Ronel; Senatorov, Vladimir V; Kondo, Asami; Zhou, Xiao Z; Miry, Omid; Vose, Linnea R; Gopaul, Katisha R; Upreti, Chirag; Nowinski, Christopher J; Cantu, Robert C; Alvarez, Victor E; Hildebrandt, Audrey M; Franz, Erich S; Konrad, Janusz; Hamilton, James A; Hua, Ning; Tripodis, Yorghos; Anderson, Andrew T; Howell, Gareth R; Kaufer, Daniela; Hall, Garth F; Lu, Kun P; Ransohoff, Richard M; Cleveland, Robin O; Kowall, Neil W; Stein, Thor D; Lamb, Bruce T; Huber, Bertrand R; Moss, William C; Friedman, Alon; Stanton, Patric K; McKee, Ann C; Goldstein, Lee E

2018-01-01

Abstract The mechanisms underpinning concussion, traumatic brain injury, and chronic traumatic encephalopathy, and the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in the acute-subacute period after mild closed-head impact injury and found astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral closed-head impact injury that uses momentum transfer to induce traumatic head acceleration. Unanaesthetized mice subjected to unilateral impact exhibited abrupt onset, transient course, and rapid resolution of a concussion-like syndrome characterized by altered arousal, contralateral hemiparesis, truncal ataxia, locomotor and balance impairments, and neurobehavioural deficits. Experimental impact injury was associated with axonopathy, blood–brain barrier disruption, astrocytosis, microgliosis (with activation of triggering receptor expressed on myeloid cells, TREM2), monocyte infiltration, and phosphorylated tauopathy in cerebral cortex ipsilateral and subjacent to impact. Phosphorylated tauopathy was detected in ipsilateral axons by 24 h, bilateral axons and soma by 2 weeks, and distant cortex bilaterally at 5.5 months post-injury. Impact pathologies co-localized with serum albumin extravasation in the brain that was diagnostically detectable in living mice by dynamic contrast-enhanced MRI. These pathologies were also accompanied by early, persistent, and bilateral impairment in axonal conduction velocity in the hippocampus and defective long-term potentiation of synaptic neurotransmission in the medial prefrontal cortex, brain regions distant from acute brain injury. Surprisingly, acute neurobehavioural deficits at the time of injury did not correlate with blood–brain barrier disruption, microgliosis, neuroinflammation, phosphorylated tauopathy, or electrophysiological dysfunction. Furthermore, concussion-like deficits were observed after impact injury, but not after blast exposure under experimental conditions matched for head kinematics. Computational modelling showed that impact injury generated focal point loading on the head and seven-fold greater peak shear stress in the brain compared to blast exposure. Moreover, intracerebral shear stress peaked before onset of gross head motion. By comparison, blast induced distributed force loading on the head and diffuse, lower magnitude shear stress in the brain. We conclude that force loading mechanics at the time of injury shape acute neurobehavioural responses, structural brain damage, and neuropathological sequelae triggered by neurotrauma. These results indicate that closed-head impact injuries, independent of concussive signs, can induce traumatic brain injury as well as early pathologies and functional sequelae associated with chronic traumatic encephalopathy. These results also shed light on the origins of concussion and relationship to traumatic brain injury and its aftermath. PMID:29360998

Dysfunctional whole brain networks in mild cognitive impairment patients: an fMRI study

NASA Astrophysics Data System (ADS)

Liu, Zhenyu; Bai, Lijun; Dai, Ruwei; Zhong, Chongguang; Xue, Ting; You, Youbo; Tian, Jie

2012-03-01

Mild cognitive impairment (MCI) was recognized as the prodromal stage of Alzheimer's disease (AD). Recent researches have shown that cognitive and memory decline in AD patients is coupled with losses of small-world attributes. However, few studies pay attention to the characteristics of the whole brain networks in MCI patients. In the present study, we investigated the topological properties of the whole brain networks utilizing graph theoretical approaches in 16 MCI patients, compared with 18 age-matched healthy subjects as a control. Both MCI patients and normal controls showed small-world architectures, with large clustering coefficients and short characteristic path lengths. We detected significantly longer characteristic path length in MCI patients compared with normal controls at the low sparsity. The longer characteristic path lengths in MCI indicated disrupted information processing among distant brain regions. Compared with normal controls, MCI patients showed decreased nodal centrality in the brain areas of the angular gyrus, heschl gyrus, hippocampus and superior parietal gyrus, while increased nodal centrality in the calcarine, inferior occipital gyrus and superior frontal gyrus. These changes in nodal centrality suggested a widespread rewiring in MCI patients, which may be an integrated reflection of reorganization of the brain networks accompanied with the cognitive decline. Our findings may be helpful for further understanding the pathological mechanisms of MCI.

Amygdala Damage Affects Event-Related Potentials for Fearful Faces at Specific Time Windows

PubMed Central

Rotshtein, Pia; Richardson, Mark P; Winston, Joel S; Kiebel, Stefan J; Vuilleumier, Patrik; Eimer, Martin; Driver, Jon; Dolan, Raymond J

2010-01-01

The amygdala is known to influence processing of threat-related stimuli in distant brain regions, including visual cortex. The time-course of these distant influences is unknown, although this information is important for resolving debates over likely pathways mediating an apparent rapidity in emotional processing. To address this, we recorded event-related potentials (ERPs) to seen fearful face expressions, in preoperative patients with medial temporal lobe epilepsy who had varying degrees of amygdala pathology, plus healthy volunteers. We found that amygdala damage diminished ERPs for fearful versus neutral faces within the P1 time-range, ∼100–150 ms, and for a later component at ∼500–600 ms. Individual severity of amygdala damage determined the magnitude of both these effects, consistent with a causal amygdala role. By contrast, amygdala damage did not affect explicit perception of fearful expressions nor a distinct emotional ERP effect at 150–250 ms. These results demonstrate two distinct time-points at which the amygdala influences fear processing. The data also demonstrate that while not all aspects of expression processing are disrupted by amygdala damage, there is a crucial impact on an early P1 component. These findings are consistent with the existence of multiple processing stages or routes for fearful faces that vary in their dependence on amygdala function. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc. PMID:20017134

Adaptation measures to drought in Mongolian rangeland: The long-distant movement of people and livestock

NASA Astrophysics Data System (ADS)

Kakinuma, K.; Kanae, S.

2015-12-01

Coping with droughts are one of the most important issues in arid and semi-arid regions. Mongolia, where are located in central Asia, are concerned the increase of droughts in the future (IPCC 2014). Mongolia has long history of livestock grazing. Herders have developed the mobile grazing systems to use spatiotemporal variable vegetation. Especially, they often take a rapid and long-distant movement to avoid drought condition ("otor" in Mongolia). The movement is a main adaptation measure to droughts for herders, and it would be applicable to other regions where will be increase the frequency of droughts in the future. However there are few knowledge about processes and actual conditions of the long-distant movement of herders and livestock across Mongolia. Therefore our objective is to discuss the long-distance movement as adaptation measures to droughts. Mongolia has a climatic gradient along the latitude; rainfall variability in southern regions are higher than that in northern regions. Previous theoretical studies predicted that rainfall variability affect the grazing strategies. Based on them, we established two hypotheses about the relationship between climatic variability and the form of long distant movement. (1) The long-distance movement likely occur in southern regions because the frequency of drought are higher in southern regions than in northern regions (2) Cooperation among herders, such as acceptance of livestock that from other prefectures, are likely occur in southern regions while exclusive management are likely occur in northern regions. We interviewed to local herders, decision makers about the long-distant movement, and investigated the number of livestock that across the border of prefectures in recent year across Mongolia. We will discuss long-distant movements as an adaptation measure to drought thorough these results.

Regional lymph node metastases are a strong risk factor for venous thromboembolism: results from the Vienna Cancer and Thrombosis Study

PubMed Central

Dickmann, Boris; Ahlbrecht, Jonas; Ay, Cihan; Dunkler, Daniela; Thaler, Johannes; Scheithauer, Werner; Quehenberger, Peter; Zielinski, Christoph; Pabinger, Ingrid

2013-01-01

Advanced cancer is a risk factor for venous thromboembolism. However, lymph node metastases are usually not considered an established risk factor. In the framework of the prospective, observational Vienna Cancer and Thrombosis Study we investigated the association between local (N0), regional (N1–3), and distant (M1) cancer stages and the occurrence of venous thromboembolism. Furthermore, we were specifically interested in the relationship between stage and biomarkers that have been reported to be associated with venous thromboembolism. We followed 832 patients with solid tumors for a median of 527 days. The study end-point was symptomatic venous thromboembolism. At study inclusion, 241 patients had local, 138 regional, and 453 distant stage cancer. The cumulative probability of venous thromboembolism after 6 months in patients with local, regional and distant stage cancer was 2.1%, 6.5% and 6.0%, respectively (P=0.002). Compared to patients with local stage disease, patients with regional and distant stage disease had a significantly higher risk of venous thromboembolism in multivariable Cox-regression analysis including age, newly diagnosed cancer (versus progression of disease), surgery, radiotherapy, and chemotherapy (regional: HR=3.7, 95% CI: 1.5–9.6; distant: HR=5.4, 95% CI: 2.3–12.9). Furthermore, patients with regional or distant stage disease had significantly higher levels of D-dimer, factor VIII, and platelets, and lower hemoglobin levels than those with local stage disease. These results demonstrate an increased risk of venous thromboembolism in patients with regional disease. Elevated levels of predictive biomarkers in patients with regional disease underpin the results and are in line with the activation of the hemostatic system in the early phase of metastatic dissemination. PMID:23585523

Neuroanatomy and neuropathology associated with Korsakoff's syndrome.

PubMed

Kril, Jillian J; Harper, Clive G

2012-06-01

Although the neuropathology of Korsakoff's syndrome (KS) was first described well over a century ago and the characteristic brain pathology does not pose a diagnostic challenge to pathologists, there is still controversy over the neuroanatomical substrate of the distinctive memory impairment in these patients. Cohort studies of KS suggest a central role for the mammillary bodies and mediodorsal thalamus, and quantitative studies suggest additional damage to the anterior thalamus is required. Rare cases of KS caused by pathologies other than those of nutritional origin provide support for the role of the anterior thalamus and mammillary bodies. Taken together the evidence to date shows that damage to the thalamus and hypothalamus is required, in particular the anterior thalamic nucleus and the medial mammillary nucleus of the hypothalamus. As these nuclei form part of wider memory circuits, damage to the inter-connecting white matter tracts can also result in a similar deficit as direct damage to the nuclei. Although these nuclei and their connections appear to be the primary site of damage, input from other brain regions within the circuits, such as the frontal cortex and hippocampus, or more distant regions, including the cerebellum and amygdala, may have a modulatory role on memory function. Further studies to confirm the precise site(s) and extend of brain damage necessary for the memory impairment of KS are required.

Potential Novel Mechanism for Axenfeld-Rieger Syndrome: Deletion of a Distant Region Containing Regulatory Elements of PITX2

PubMed Central

Volkmann, Bethany A.; Zinkevich, Natalya S.; Mustonen, Aki; Schilter, Kala F.; Bosenko, Dmitry V.; Reis, Linda M.; Broeckel, Ulrich; Link, Brian A.

2011-01-01

Purpose. Mutations in PITX2 are associated with Axenfeld-Rieger syndrome (ARS), which involves ocular, dental, and umbilical abnormalities. Identification of cis-regulatory elements of PITX2 is important to better understand the mechanisms of disease. Methods. Conserved noncoding elements surrounding PITX2/pitx2 were identified and examined through transgenic analysis in zebrafish; expression pattern was studied by in situ hybridization. Patient samples were screened for deletion/duplication of the PITX2 upstream region using arrays and probes. Results. Zebrafish pitx2 demonstrates conserved expression during ocular and craniofacial development. Thirteen conserved noncoding sequences positioned within a gene desert as far as 1.1 Mb upstream of the human PITX2 gene were identified; 11 have enhancer activities consistent with pitx2 expression. Ten elements mediated expression in the developing brain, four regions were active during eye formation, and two sequences were associated with craniofacial expression. One region, CE4, located approximately 111 kb upstream of PITX2, directed a complex pattern including expression in the developing eye and craniofacial region, the classic sites affected in ARS. Screening of ARS patients identified an approximately 7600-kb deletion that began 106 to 108 kb upstream of the PITX2 gene, leaving PITX2 intact while removing regulatory elements CE4 to CE13. Conclusions. These data suggest the presence of a complex distant regulatory matrix within the gene desert located upstream of PITX2 with an essential role in its activity and provides a possible mechanism for the previous reports of ARS in patients with balanced translocations involving the 4q25 region upstream of PITX2 and the current patient with an upstream deletion. PMID:20881290

High-Throughput Mapping of Single-Neuron Projections by Sequencing of Barcoded RNA.

PubMed

Kebschull, Justus M; Garcia da Silva, Pedro; Reid, Ashlan P; Peikon, Ian D; Albeanu, Dinu F; Zador, Anthony M

2016-09-07

Neurons transmit information to distant brain regions via long-range axonal projections. In the mouse, area-to-area connections have only been systematically mapped using bulk labeling techniques, which obscure the diverse projections of intermingled single neurons. Here we describe MAPseq (Multiplexed Analysis of Projections by Sequencing), a technique that can map the projections of thousands or even millions of single neurons by labeling large sets of neurons with random RNA sequences ("barcodes"). Axons are filled with barcode mRNA, each putative projection area is dissected, and the barcode mRNA is extracted and sequenced. Applying MAPseq to the locus coeruleus (LC), we find that individual LC neurons have preferred cortical targets. By recasting neuroanatomy, which is traditionally viewed as a problem of microscopy, as a problem of sequencing, MAPseq harnesses advances in sequencing technology to permit high-throughput interrogation of brain circuits. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis and Exchange of Multimedia Laboratory Data Using the Brain Database

PubMed Central

Wertheim, Steven L.

1990-01-01

Two principal goals of the Brain Database are: 1) to support laboratory data collection and analysis of multimedia information about the nervous system and 2) to support exchange of these data among researchers and clinicians who may be physically distant. This has been achieved by an implementation of experimental and clinical records within a relational database. An Image Series Editor has been created that provides a graphical interface to these data for the purposes of annotation, quantification and other analyses. Cooperating laboratories each maintain their own copies of the Brain Database to which they may add private data. Although the data in a given experimental or patient record will be distributed among many tables and external image files, the user can treat each record as a unit that can be extracted from the local database and sent to a distant colleague.

Optical monitoring of shock wave-induced spreading depolarization and concomitant hypoxemia in rat brain

NASA Astrophysics Data System (ADS)

Okuda, Wataru; Kawauchi, Satoko; Ashida, Hiroshi; Sato, Shunichi; Nishidate, Izumi

2014-03-01

Blast-induced traumatic brain injury is a growing concern, but its underlying pathophysiology and mechanism are still unknown. Thus, study using an animal model is needed. We have been proposing the use of a laser-induced shock wave (LISW), whose energy is highly controllable and reproducible, to mimic blast-related injury. We previously observed the occurrence of spreading depolarization (SD) and prolonged hypoxemia in the rat brain exposed to an LISW. However, the relationship between these two events is unclear. In this study, we investigated the spatiotemporal characteristics of hypoxemia and SD to examine their correlation, for which multichannel fiber measurement and multispectral imaging of the diffuse reflectance were performed for the rat brain exposed to an LISW. We also quantified tissue oxygen saturation (StO2) in the hypoxemic phase, which is associated with possible neuronal cell death, based on an inverse Monte Carlo simulation. Fiber measurement showed that the region of hypoxemia was expanding from the site of LISW application to the distant region over the brain; the speed of expansion was similar to that of the propagation speed of SD. Simulation showed that oxygen saturation was decreased by ~40%. Multispectral imaging showed that after LISW application, a vasodilatation occurred for ~1 min, which was followed by a long-lasting vasoconstriction. In the phase of vasoconstriction, StO2 declined all over the field of view. These results indicate a strong correlation between SD and hypoxemia; the estimated StO2 seems to be low enough to induce neuronal cell death.

Functional Brain Connectivity as a New Feature for P300 Speller.

PubMed

Kabbara, Aya; Khalil, Mohamad; El-Falou, Wassim; Eid, Hassan; Hassan, Mahmoud

2016-01-01

The brain is a large-scale complex network often referred to as the "connectome". Cognitive functions and information processing are mainly based on the interactions between distant brain regions. However, most of the 'feature extraction' methods used in the context of Brain Computer Interface (BCI) ignored the possible functional relationships between different signals recorded from distinct brain areas. In this paper, the functional connectivity quantified by the phase locking value (PLV) was introduced to characterize the evoked responses (ERPs) obtained in the case of target and non-targets visual stimuli. We also tested the possibility of using the functional connectivity in the context of 'P300 speller'. The proposed approach was compared to the well-known methods proposed in the state of the art of "P300 Speller", mainly the peak picking, the area, time/frequency based features, the xDAWN spatial filtering and the stepwise linear discriminant analysis (SWLDA). The electroencephalographic (EEG) signals recorded from ten subjects were analyzed offline. The results indicated that phase synchrony offers relevant information for the classification in a P300 speller. High synchronization between the brain regions was clearly observed during target trials, although no significant synchronization was detected for a non-target trial. The results showed also that phase synchrony provides higher performance than some existing methods for letter classification in a P300 speller principally when large number of trials is available. Finally, we tested the possible combination of both approaches (classical features and phase synchrony). Our findings showed an overall improvement of the performance of the P300-speller when using Peak picking, the area and frequency based features. Similar performances were obtained compared to xDAWN and SWLDA when using large number of trials.

Influence of anodal transcranial direct current stimulation (tDCS) over the right angular gyrus on brain activity during rest.

PubMed

Clemens, Benjamin; Jung, Stefanie; Mingoia, Gianluca; Weyer, David; Domahs, Frank; Willmes, Klaus

2014-01-01

Although numerous studies examined resting-state networks (RSN) in the human brain, so far little is known about how activity within RSN might be modulated by non-invasive brain stimulation applied over parietal cortex. Investigating changes in RSN in response to parietal cortex stimulation might tell us more about how non-invasive techniques such as transcranial direct current stimulation (tDCS) modulate intrinsic brain activity, and further elaborate our understanding of how the resting brain responds to external stimulation. Here we examined how activity within the canonical RSN changed in response to anodal tDCS applied over the right angular gyrus (AG). We hypothesized that changes in resting-state activity can be induced by a single tDCS session and detected with functional magnetic resonance imaging (fMRI). Significant differences between two fMRI sessions (pre-tDCS and post-tDCS) were found in several RSN, including the cerebellar, medial visual, sensorimotor, right frontoparietal, and executive control RSN as well as the default mode and the task positive network. The present results revealed decreased and increased RSN activity following tDCS. Decreased RSN activity following tDCS was found in bilateral primary and secondary visual areas, and in the right putamen. Increased RSN activity following tDCS was widely distributed across the brain, covering thalamic, frontal, parietal and occipital regions. From these exploratory results we conclude that a single session of anodal tDCS over the right AG is sufficient to induce large-scale changes in resting-state activity. These changes were localized in sensory and cognitive areas, covering regions close to and distant from the stimulation site.

Influence of Anodal Transcranial Direct Current Stimulation (tDCS) over the Right Angular Gyrus on Brain Activity during Rest

PubMed Central

Clemens, Benjamin; Jung, Stefanie; Mingoia, Gianluca; Weyer, David; Domahs, Frank; Willmes, Klaus

2014-01-01

Although numerous studies examined resting-state networks (RSN) in the human brain, so far little is known about how activity within RSN might be modulated by non-invasive brain stimulation applied over parietal cortex. Investigating changes in RSN in response to parietal cortex stimulation might tell us more about how non-invasive techniques such as transcranial direct current stimulation (tDCS) modulate intrinsic brain activity, and further elaborate our understanding of how the resting brain responds to external stimulation. Here we examined how activity within the canonical RSN changed in response to anodal tDCS applied over the right angular gyrus (AG). We hypothesized that changes in resting-state activity can be induced by a single tDCS session and detected with functional magnetic resonance imaging (fMRI). Significant differences between two fMRI sessions (pre-tDCS and post-tDCS) were found in several RSN, including the cerebellar, medial visual, sensorimotor, right frontoparietal, and executive control RSN as well as the default mode and the task positive network. The present results revealed decreased and increased RSN activity following tDCS. Decreased RSN activity following tDCS was found in bilateral primary and secondary visual areas, and in the right putamen. Increased RSN activity following tDCS was widely distributed across the brain, covering thalamic, frontal, parietal and occipital regions. From these exploratory results we conclude that a single session of anodal tDCS over the right AG is sufficient to induce large-scale changes in resting-state activity. These changes were localized in sensory and cognitive areas, covering regions close to and distant from the stimulation site. PMID:24760013

Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model.

PubMed

Tagge, Chad A; Fisher, Andrew M; Minaeva, Olga V; Gaudreau-Balderrama, Amanda; Moncaster, Juliet A; Zhang, Xiao-Lei; Wojnarowicz, Mark W; Casey, Noel; Lu, Haiyan; Kokiko-Cochran, Olga N; Saman, Sudad; Ericsson, Maria; Onos, Kristen D; Veksler, Ronel; Senatorov, Vladimir V; Kondo, Asami; Zhou, Xiao Z; Miry, Omid; Vose, Linnea R; Gopaul, Katisha R; Upreti, Chirag; Nowinski, Christopher J; Cantu, Robert C; Alvarez, Victor E; Hildebrandt, Audrey M; Franz, Erich S; Konrad, Janusz; Hamilton, James A; Hua, Ning; Tripodis, Yorghos; Anderson, Andrew T; Howell, Gareth R; Kaufer, Daniela; Hall, Garth F; Lu, Kun P; Ransohoff, Richard M; Cleveland, Robin O; Kowall, Neil W; Stein, Thor D; Lamb, Bruce T; Huber, Bertrand R; Moss, William C; Friedman, Alon; Stanton, Patric K; McKee, Ann C; Goldstein, Lee E

2018-02-01

The mechanisms underpinning concussion, traumatic brain injury, and chronic traumatic encephalopathy, and the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in the acute-subacute period after mild closed-head impact injury and found astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral closed-head impact injury that uses momentum transfer to induce traumatic head acceleration. Unanaesthetized mice subjected to unilateral impact exhibited abrupt onset, transient course, and rapid resolution of a concussion-like syndrome characterized by altered arousal, contralateral hemiparesis, truncal ataxia, locomotor and balance impairments, and neurobehavioural deficits. Experimental impact injury was associated with axonopathy, blood-brain barrier disruption, astrocytosis, microgliosis (with activation of triggering receptor expressed on myeloid cells, TREM2), monocyte infiltration, and phosphorylated tauopathy in cerebral cortex ipsilateral and subjacent to impact. Phosphorylated tauopathy was detected in ipsilateral axons by 24 h, bilateral axons and soma by 2 weeks, and distant cortex bilaterally at 5.5 months post-injury. Impact pathologies co-localized with serum albumin extravasation in the brain that was diagnostically detectable in living mice by dynamic contrast-enhanced MRI. These pathologies were also accompanied by early, persistent, and bilateral impairment in axonal conduction velocity in the hippocampus and defective long-term potentiation of synaptic neurotransmission in the medial prefrontal cortex, brain regions distant from acute brain injury. Surprisingly, acute neurobehavioural deficits at the time of injury did not correlate with blood-brain barrier disruption, microgliosis, neuroinflammation, phosphorylated tauopathy, or electrophysiological dysfunction. Furthermore, concussion-like deficits were observed after impact injury, but not after blast exposure under experimental conditions matched for head kinematics. Computational modelling showed that impact injury generated focal point loading on the head and seven-fold greater peak shear stress in the brain compared to blast exposure. Moreover, intracerebral shear stress peaked before onset of gross head motion. By comparison, blast induced distributed force loading on the head and diffuse, lower magnitude shear stress in the brain. We conclude that force loading mechanics at the time of injury shape acute neurobehavioural responses, structural brain damage, and neuropathological sequelae triggered by neurotrauma. These results indicate that closed-head impact injuries, independent of concussive signs, can induce traumatic brain injury as well as early pathologies and functional sequelae associated with chronic traumatic encephalopathy. These results also shed light on the origins of concussion and relationship to traumatic brain injury and its aftermath.awx350media15713427811001. © The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain.

Pressure wave injuries to the nervous system caused by high-energy missile extremity impact: Part II. Distant effects on the central nervous system--a light and electron microscopic study on pigs.

PubMed

Suneson, A; Hansson, H A; Seeman, T

1990-03-01

The aim of the present study was to investigate if distant effects could be detected within the central nervous system after impact of a high-energy missile in the left thigh of young pigs. Pressure transducers implanted in various parts of the body of the animal, including the brain, recorded a short-lasting burst of oscillating pressure waves with high frequencies and large amplitudes, traversing the body tissue with a velocity of about that of sound in water (1,460 m/s). The distance between the point of impact and the brain and cervical spinal cord is in the range of 0.5 m. Macroscopic examination revealed that there was no gross brain tissue disruption or visible blood-brain barrier dysfunction. Light microscopic examination demonstrated myelin invaginations in the largest axons and shrinkage of axoplasm. Electron microscopic examination revealed a reduction in the number of microtubules, especially in the larger axons in the brainstem. Disintegration of Nissl substance, i.e., chromatolysis, was noticed after 48 hr in many Purkinje nerve cells in the cerebellum, concomitantly with the appearance of an increased frequency of association between lamellar bodies and mitochondria. Changes could also be observed in the cervical spinal cord and, at reduced frequency and extent, in the optic nerve and in other parts of the brain. These effects were evident within a few minutes after the trauma and persisted even 48 hr after the extremity injury. It is concluded that distant effects, likely to be caused by the oscillating high-frequency pressure waves, appear in the central nervous system after a high-energy missile extremity impact.

The role of whole brain radiation therapy in the management of melanoma brain metastases

PubMed Central

2014-01-01

Background Brain metastases are common in patients with melanoma, and optimal management is not well defined. As melanoma has traditionally been thought of as “radioresistant,” the role of whole brain radiation therapy (WBRT) in particular is unclear. We conducted this retrospective study to identify prognostic factors for patients treated with stereotactic radiosurgery (SRS) for melanoma brain metastases and to investigate the role of additional up-front treatment with whole brain radiation therapy (WBRT). Methods We reviewed records of 147 patients who received SRS as part of initial management of their melanoma brain metastases from January 2000 through June 2010. Overall survival (OS) and time to distant intracranial progression were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results WBRT was employed with SRS in 27% of patients and as salvage in an additional 22%. Age at SRS > 60 years (hazard ratio [HR] 0.64, p = 0.05), multiple brain metastases (HR 1.90, p = 0.008), and omission of up-front WBRT (HR 2.24, p = 0.005) were associated with distant intracranial progression on multivariate analysis. Extensive extracranial metastases (HR 1.86, p = 0.0006), Karnofsky Performance Status (KPS) ≤ 80% (HR 1.58, p = 0.01), and multiple brain metastases (HR 1.40, p = 0.06) were associated with worse OS on univariate analysis. Extensive extracranial metastases (HR 1.78, p = 0.001) and KPS (HR 1.52, p = 0.02) remained significantly associated with OS on multivariate analysis. In patients with absent or stable extracranial disease, multiple brain metastases were associated with worse OS (multivariate HR 5.89, p = 0.004), and there was a trend toward an association with worse OS when up-front WBRT was omitted (multivariate HR 2.56, p = 0.08). Conclusions Multiple brain metastases and omission of up-front WBRT (particularly in combination) are associated with distant intracranial progression. Improvement in intracranial disease control may be especially important in the subset of patients with absent or stable extracranial disease, where the competing risk of death from extracranial disease is low. These results are hypothesis generating and require confirmation from ongoing randomized trials. PMID:24954062

A Bayesian network meta-analysis of whole brain radiotherapy and stereotactic radiotherapy for brain metastasis.

PubMed

Yuan, Xi; Liu, Wen-Jie; Li, Bing; Shen, Ze-Tian; Shen, Jun-Shu; Zhu, Xi-Xu

2017-08-01

This study was conducted to compare the effects of whole brain radiotherapy (WBRT) and stereotactic radiotherapy (SRS) in treatment of brain metastasis.A systematical retrieval in PubMed and Embase databases was performed for relative literatures on the effects of WBRT and SRS in treatment of brain metastasis. A Bayesian network meta-analysis was performed by using the ADDIS software. The effect sizes included odds ratio (OR) and 95% confidence interval (CI). A random effects model was used for the pooled analysis for all the outcome measures, including 1-year distant control rate, 1-year local control rate, 1-year survival rate, and complication. The consistency was tested by using node-splitting analysis and inconsistency standard deviation. The convergence was estimated according to the Brooks-Gelman-Rubin method.A total of 12 literatures were included in this meta-analysis. WBRT + SRS showed higher 1-year distant control rate than SRS. WBRT + SRS was better for the 1-year local control rate than WBRT. SRS and WBRT + SRS had higher 1-year survival rate than the WBRT. In addition, there was no difference in complication among the three therapies.Comprehensively, WBRT + SRS might be the choice of treatment for brain metastasis.

Two Anatomically and Computationally Distinct Learning Signals Predict Changes to Stimulus-Outcome Associations in Hippocampus.

PubMed

Boorman, Erie D; Rajendran, Vani G; O'Reilly, Jill X; Behrens, Tim E

2016-03-16

Complex cognitive processes require sophisticated local processing but also interactions between distant brain regions. It is therefore critical to be able to study distant interactions between local computations and the neural representations they act on. Here we report two anatomically and computationally distinct learning signals in lateral orbitofrontal cortex (lOFC) and the dopaminergic ventral midbrain (VM) that predict trial-by-trial changes to a basic internal model in hippocampus. To measure local computations during learning and their interaction with neural representations, we coupled computational fMRI with trial-by-trial fMRI suppression. We find that suppression in a medial temporal lobe network changes trial-by-trial in proportion to stimulus-outcome associations. During interleaved choice trials, we identify learning signals that relate to outcome type in lOFC and to reward value in VM. These intervening choice feedback signals predicted the subsequent change to hippocampal suppression, suggesting a convergence of signals that update the flexible representation of stimulus-outcome associations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Expression of Histone Deacetylases in Cellular Compartments of the Mouse Brain and the Effects of Ischemia

PubMed Central

Bachleda, Amelia; Morrison, Richard S.; Murphy, Sean P.

2011-01-01

Drugs that inhibit specific histone deacetylase (HDAC) activities have enormous potential in preventing the consequences of acute injury to the nervous system and in allaying neurodegeneration. However, very little is known about the expression pattern of the HDACs in the central nervous system (CNS). Identifying the cell types that express HDACs in the CNS is important for determining therapeutic targets for HDAC inhibitors and evaluating potential side effects. We characterized the cellular expression of HDACs 1–3, and HDACs 4 and 6, in the adult mouse brain in the cingulate cortex, parietal cortex, dentate gyrus, and CA1 regions of the hippocampus and subcortical white matter. Expression of class I HDACs showed a cell-and region-specific pattern. Transient focal ischemia induced by temporary middle cerebral artery occlusion, or global ischemia induced by in vitro oxygen–glucose deprivation, altered the extent of HDAC expression in a region- and cell-specific manner. The pan-HDAC inhibitor, SAHA, reduced ischemia-induced alterations in HDACs. The results suggest that in addition to promoting epigenetic changes in transcriptional activity in the nucleus of neurons and glia, HDACs may also have non-transcriptional actions in axons and the distant processes of glial cells and may significantly modulate the response to injury in a cell- and region-specific manner. PMID:21966324

Outcomes of surgery followed by local brain radiotherapy compared with surgery followed by whole brain radiotherapy for single brain metastasis.

PubMed

Igaki, Hiroshi; Harada, Ken; Umezawa, Rei; Miyakita, Yasuji; Ohno, Makoto; Takahashi, Masamichi; Sumi, Minako; Inaba, Koji; Murakami, Naoya; Ito, Yoshinori; Narita, Yoshitaka; Itami, Jun

2017-07-31

To determine the clinical efficacy of surgery followed by local brain radiotherapy (LBRT) for patients with a single brain metastasis, by comparing the results with those of postoperative whole brain radiotherapy (WBRT). We performed a retrospective analysis to compare the survival rate, recurrence-free rates, and causes of death for single brain metastasis patients who underwent surgery followed by LBRT or WBRT in the 2010-2015 period. After their surgery, 22 and 32 patients were treated by LBRT and WBRT, respectively. The median survival times for these LBRT and WBRT groups were 18.3 months and 19.2 months, respectively (p = 0.356). The local recurrence-free rates were 81.2% at 1 year and 81.2% at 2 years after LBRT, and 63.8% at 1 year and 58.9% at 2 years after WBRT (p = 0.589). The distant brain recurrence-free rates were 42.5% at 1 year and 25.5% at 2 years after LBRT, and 69.8% at 1 year and 52.4% at 2 years after WBRT (p = 0.044). Distant brain recurrences were observed significantly more frequently in the LBRT group, but the rates of salvage treatment application and survival were not significantly different between the LBRT and WBRT groups. The probability of neurologic death was not significantly higher in the LBRT group compared with the WBRT group. Surgery followed by LBRT for single brain metastasis is not inferior to postoperative WBRT, because survival and the necessity of salvage treatment after LBRT were equivalent to those after WBRT.

Primary Generators of Visually Evoked Field Potentials Recorded in the Macaque Auditory Cortex.

PubMed

Kajikawa, Yoshinao; Smiley, John F; Schroeder, Charles E

2017-10-18

Prior studies have reported "local" field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be "contaminated" by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such "far-field" activity, in addition to, or in absence of, local synaptic responses. SIGNIFICANCE STATEMENT Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is problematic as the default assumption is that FPs originate from local activity, and thus are termed "local" (LFP). We examine this general problem in the context of previously reported face-evoked FPs in macaque auditory cortex. Our findings suggest that face-FPs are indeed generated in the underlying inferotemporal cortex and volume-conducted to the auditory cortex. The note of caution raised by these findings is of particular importance for studies that seek to assign FP/LFP recordings to specific cortical layers. Copyright © 2017 the authors 0270-6474/17/3710139-15$15.00/0.

Primary Generators of Visually Evoked Field Potentials Recorded in the Macaque Auditory Cortex

PubMed Central

Smiley, John F.; Schroeder, Charles E.

2017-01-01

Prior studies have reported “local” field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be “contaminated” by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such “far-field” activity, in addition to, or in absence of, local synaptic responses. SIGNIFICANCE STATEMENT Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is problematic as the default assumption is that FPs originate from local activity, and thus are termed “local” (LFP). We examine this general problem in the context of previously reported face-evoked FPs in macaque auditory cortex. Our findings suggest that face-FPs are indeed generated in the underlying inferotemporal cortex and volume-conducted to the auditory cortex. The note of caution raised by these findings is of particular importance for studies that seek to assign FP/LFP recordings to specific cortical layers. PMID:28924008

Individual differences in transcranial electrical stimulation current density

PubMed Central

Russell, Michael J; Goodman, Theodore; Pierson, Ronald; Shepherd, Shane; Wang, Qiang; Groshong, Bennett; Wiley, David F

2013-01-01

Transcranial electrical stimulation (TCES) is effective in treating many conditions, but it has not been possible to accurately forecast current density within the complex anatomy of a given subject's head. We sought to predict and verify TCES current densities and determine the variability of these current distributions in patient-specific models based on magnetic resonance imaging (MRI) data. Two experiments were performed. The first experiment estimated conductivity from MRIs and compared the current density results against actual measurements from the scalp surface of 3 subjects. In the second experiment, virtual electrodes were placed on the scalps of 18 subjects to model simulated current densities with 2 mA of virtually applied stimulation. This procedure was repeated for 4 electrode locations. Current densities were then calculated for 75 brain regions. Comparison of modeled and measured external current in experiment 1 yielded a correlation of r = .93. In experiment 2, modeled individual differences were greatest near the electrodes (ten-fold differences were common), but simulated current was found in all regions of the brain. Sites that were distant from the electrodes (e.g. hypothalamus) typically showed two-fold individual differences. MRI-based modeling can effectively predict current densities in individual brains. Significant variation occurs between subjects with the same applied electrode configuration. Individualized MRI-based modeling should be considered in place of the 10-20 system when accurate TCES is needed. PMID:24285948

Review of the genus Signoretia (Hemiptera: Cicadellidae: Signoretiinae) of the Oriental region with description of nine new species.

PubMed

Viraktamath, C A

2016-11-17

Species of Signoretia Stål from the Oriental region are reviewed and types of five species described by Baker, two species described by Distant and one species described by Schmidt are illustrated. A checklist of 20 species of the genus from the Oriental region including 9 new species is given. The new species described and illustrated are Signoretia dulitensis sp. nov. (Malaysia: Mt Dulit), S. lunglei sp. nov. (India: Mizoram), S. mishmiensis sp. nov. (Myanmar: Mishmi Hills), S. quoinensis sp. nov. (Malaysia: Quoin Hill), S. rubra sp. nov. (Thailand: Chiang Mai), S. sahyadrica sp. nov. (India: Kerala), S. similaris sp. nov. (Vietnam: Fyan), S. sinuata sp. nov. (India: West Bengal) and S. takiyae sp. nov. (India: Andaman Is.). Both S. aureola Distant and S. maculata Baker are redescribed and illustrated. Lectotypes are designated for S. greeni Distant and S. aureola Distant.

A meta-analysis of neuroimaging studies on divergent thinking using activation likelihood estimation.

PubMed

Wu, Xin; Yang, Wenjing; Tong, Dandan; Sun, Jiangzhou; Chen, Qunlin; Wei, Dongtao; Zhang, Qinglin; Zhang, Meng; Qiu, Jiang

2015-07-01

In this study, an activation likelihood estimation (ALE) meta-analysis was used to conduct a quantitative investigation of neuroimaging studies on divergent thinking. Based on the ALE results, the functional magnetic resonance imaging (fMRI) studies showed that distributed brain regions were more active under divergent thinking tasks (DTTs) than those under control tasks, but a large portion of the brain regions were deactivated. The ALE results indicated that the brain networks of the creative idea generation in DTTs may be composed of the lateral prefrontal cortex, posterior parietal cortex [such as the inferior parietal lobule (BA 40) and precuneus (BA 7)], anterior cingulate cortex (ACC) (BA 32), and several regions in the temporal cortex [such as the left middle temporal gyrus (BA 39), and left fusiform gyrus (BA 37)]. The left dorsolateral prefrontal cortex (BA 46) was related to selecting the loosely and remotely associated concepts and organizing them into creative ideas, whereas the ACC (BA 32) was related to observing and forming distant semantic associations in performing DTTs. The posterior parietal cortex may be involved in the semantic information related to the retrieval and buffering of the formed creative ideas, and several regions in the temporal cortex may be related to the stored long-term memory. In addition, the ALE results of the structural studies showed that divergent thinking was related to the dopaminergic system (e.g., left caudate and claustrum). Based on the ALE results, both fMRI and structural MRI studies could uncover the neural basis of divergent thinking from different aspects (e.g., specific cognitive processing and stable individual difference of cognitive capability). © 2015 Wiley Periodicals, Inc.

Detection of resting state functional connectivity using partial correlation analysis: A study using multi-distance and whole-head probe near-infrared spectroscopy.

PubMed

Sakakibara, Eisuke; Homae, Fumitaka; Kawasaki, Shingo; Nishimura, Yukika; Takizawa, Ryu; Koike, Shinsuke; Kinoshita, Akihide; Sakurada, Hanako; Yamagishi, Mika; Nishimura, Fumichika; Yoshikawa, Akane; Inai, Aya; Nishioka, Masaki; Eriguchi, Yosuke; Matsuoka, Jun; Satomura, Yoshihiro; Okada, Naohiro; Kakiuchi, Chihiro; Araki, Tsuyoshi; Kan, Chiemi; Umeda, Maki; Shimazu, Akihito; Uga, Minako; Dan, Ippeita; Hashimoto, Hideki; Kawakami, Norito; Kasai, Kiyoto

2016-11-15

Multichannel near-infrared spectroscopy (NIRS) is a functional neuroimaging modality that enables easy-to-use and noninvasive measurement of changes in blood oxygenation levels. We developed a clinically-applicable method for estimating resting state functional connectivity (RSFC) with NIRS using a partial correlation analysis to reduce the influence of extraneural components. Using a multi-distance probe arrangement NIRS, we measured resting state brain activity for 8min in 17 healthy participants. Independent component analysis was used to extract shallow and deep signals from the original NIRS data. Pearson's correlation calculated from original signals was significantly higher than that calculated from deep signals, while partial correlation calculated from original signals was comparable to that calculated from deep (cerebral-tissue) signals alone. To further test the validity of our method, we also measured 8min of resting state brain activity using a whole-head NIRS arrangement consisting of 17 cortical regions in 80 healthy participants. Significant RSFC between neighboring, interhemispheric homologous, and some distant ipsilateral brain region pairs was revealed. Additionally, females exhibited higher RSFC between interhemispheric occipital region-pairs, in addition to higher connectivity between some ipsilateral pairs in the left hemisphere, when compared to males. The combined results of the two component experiments indicate that partial correlation analysis is effective in reducing the influence of extracerebral signals, and that NIRS is able to detect well-described resting state networks and sex-related differences in RSFC. Copyright © 2016 Elsevier Inc. All rights reserved.

Altered neural activity and emotions following right middle cerebral artery stroke.

PubMed

Paradiso, Sergio; Anderson, Beth M; Boles Ponto, Laura L; Tranel, Daniel; Robinson, Robert G

2011-01-01

Stroke of the right MCA is common. Such strokes often have consequences for emotional experience, but these can be subtle. In such cases diagnosis is difficult because emotional awareness (limiting reporting of emotional changes) may be affected. The present study sought to clarify the mechanisms of altered emotion experience after right MCA stroke. It was predicted that after right MCA stroke the anterior cingulate cortex (ACC), a brain region concerned with emotional awareness, would show reduced neural activity. Brain activity during presentation of emotional stimuli was measured in 6 patients with stable stroke, and in 12 age- and sex-matched nonlesion comparisons using positron emission tomography and the [(15)O]H(2)O autoradiographic method. MCA stroke was associated with weaker pleasant experience and decreased activity ipsilaterally in the ACC. Other regions involved in emotional processing including thalamus, dorsal and medial prefrontal cortex showed reduced activity ipsilaterally. Dorsal and medial prefrontal cortex, association visual cortex and cerebellum showed reduced activity contralaterally. Experience from unpleasant stimuli was unaltered and was associated with decreased activity only in the left midbrain. Right MCA stroke may reduce experience of pleasant emotions by altering brain activity in limbic and paralimbic regions distant from the area of direct damage, in addition to changes due to direct tissue damage to insula and basal ganglia. The knowledge acquired in this study begins to explain the mechanisms underlying emotional changes following right MCA stroke. Recognizing these changes may improve diagnoses, management and rehabilitation of right MCA stroke victims. Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Modeling the impact of COPD on the brain.

PubMed

Borson, Soo; Scanlan, James; Friedman, Seth; Zuhr, Elizabeth; Fields, Julie; Aylward, Elizabeth; Mahurin, Rodney; Richards, Todd; Anzai, Yoshimi; Yukawa, Michi; Yeh, Shingshing

2008-01-01

Previous studies have shown that COPD adversely affects distant organs and body systems, including the brain. This pilot study aims to model the relationships between respiratory insufficiency and domains related to brain function, including low mood, subtly impaired cognition, systemic inflammation, and brain structural and neurochemical abnormalities. Nine healthy controls were compared with 18 age- and education-matched medically stable-COPD patients, half of whom were oxygen-dependent. Measures included depression, anxiety, cognition, health status, spirometry, oximetry at rest and during 6-minute walk, and resting plasma cytokines and soluble receptors, brain MRI, and MR spectroscopy in regions relevant to mood and cognition. ANOVA was used to compare controls with patients and with COPD subgroups (oxygen users [n = 9] and nonusers [n = 9]), and only variables showing group differences at p < or = 0.05 were included in multiple regressions controlling for age, gender, and education to develop the final model. Controls and COPD patients differed significantly in global cognition and memory, mood, and soluble TNFR1 levels but not brain structural or neurochemical measures. Multiple regressions identified pathways linking disease severity with impaired performance on sensitive cognitive processing measures, mediated through oxygen dependence, and with systemic inflammation (TNFR1), related through poor 6-minute walk performance. Oxygen desaturation with activity was related to indicators of brain tissue damage (increased frontal choline, which in turn was associated with subcortical white matter attenuation). This empirically derived model provides a conceptual framework for future studies of clinical interventions to protect the brain in patients with COPD, such as earlier oxygen supplementation for patients with desaturation during everyday activities.

Modeling the impact of COPD on the brain

PubMed Central

Borson, Soo; Scanlan, James; Friedman, Seth; Zuhr, Elizabeth; Fields, Julie; Aylward, Elizabeth; Mahurin, Rodney; Richards, Todd; Anzai, Yoshimi; Yukawa, Michi; Yeh, Shingshing

2008-01-01

Previous studies have shown that COPD adversely affects distant organs and body systems, including the brain. This pilot study aims to model the relationships between respiratory insufficiency and domains related to brain function, including low mood, subtly impaired cognition, systemic inflammation, and brain structural and neurochemical abnormalities. Nine healthy controls were compared with 18 age- and education-matched medically stable COPD patients, half of whom were oxygen-dependent. Measures included depression, anxiety, cognition, health status, spirometry, oximetry at rest and during 6-minute walk, and resting plasma cytokines and soluble receptors, brain MRI, and MR spectroscopy in regions relevant to mood and cognition. ANOVA was used to compare controls with patients and with COPD subgroups (oxygen users [n = 9] and nonusers [n = 9]), and only variables showing group differences at p ≤ 0.05 were included in multiple regressions controlling for age, gender, and education to develop the final model. Controls and COPD patients differed significantly in global cognition and memory, mood, and soluble TNFR1 levels but not brain structural or neurochemical measures. Multiple regressions identified pathways linking disease severity with impaired performance on sensitive cognitive processing measures, mediated through oxygen dependence, and with systemic inflammation (TNFR1), related through poor 6-minute walk performance. Oxygen desaturation with activity was related to indicators of brain tissue damage (increased frontal choline, which in turn was associated with subcortical white matter attenuation). This empirically derived model provides a conceptual framework for future studies of clinical interventions to protect the brain in patients with COPD, such as earlier oxygen supplementation for patients with desaturation during everyday activities. PMID:18990971

Tracking thoughts: Exploring the neural architecture of mental time travel during mind-wandering.

PubMed

Karapanagiotidis, Theodoros; Bernhardt, Boris C; Jefferies, Elizabeth; Smallwood, Jonathan

2017-02-15

The capacity to imagine situations that have already happened or fictitious events that may take place in the future is known as mental time travel (MTT). Studies have shown that MTT is an important aspect of spontaneous thought, yet we lack a clear understanding of how the neurocognitive architecture of the brain constrains this element of human cognition. Previous functional magnetic resonance imaging (MRI) studies have shown that MTT involves the coordination between multiple regions that include mesiotemporal structures such as the hippocampus, as well as prefrontal and parietal regions commonly associated with the default mode network (DMN). The current study used a multimodal neuroimaging approach to identify the structural and functional brain organisation that underlies individual differences in the capacity to spontaneously engage in MTT. Using regionally unconstrained diffusion tractography analysis, we found increased diffusion anisotropy in right lateralised temporo-limbic, corticospinal, inferior fronto-occipital tracts in participants who reported greater MTT. Probabilistic connectivity mapping revealed a significantly higher connection probability of the right hippocampus with these tracts. Resting-state functional MRI connectivity analysis using the right hippocampus as a seed region revealed greater functional coupling to the anterior regions of the DMN with increasing levels of MTT. These findings demonstrate that the interactions between the hippocampus and regions of the cortex underlie the capacity to engage in MTT, and support contemporary theoretical accounts that suggest that the integration of the hippocampus with the DMN provides the neurocognitive landscape that allows us to imagine distant times and places. Copyright © 2016 Elsevier Inc. All rights reserved.

Patient-specific connectivity pattern of epileptic network in frontal lobe epilepsy

PubMed Central

Luo, Cheng; An, Dongmei; Yao, Dezhong; Gotman, Jean

2014-01-01

There is evidence that focal epilepsy may involve the dysfunction of a brain network in addition to the focal region. To delineate the characteristics of this epileptic network, we collected EEG/fMRI data from 23 patients with frontal lobe epilepsy. For each patient, EEG/fMRI analysis was first performed to determine the BOLD response to epileptic spikes. The maximum activation cluster in the frontal lobe was then chosen as the seed to identify the epileptic network in fMRI data. Functional connectivity analysis seeded at the same region was also performed in 63 healthy control subjects. Nine features were used to evaluate the differences of epileptic network patterns in three connection levels between patients and controls. Compared with control subjects, patients showed overall more functional connections between the epileptogenic region and the rest of the brain and higher laterality. However, the significantly increased connections were located in the neighborhood of the seed, but the connections between the seed and remote regions actually decreased. Comparing fMRI runs with interictal epileptic discharges (IEDs) and without IEDs, the patient-specific connectivity pattern was not changed significantly. These findings regarding patient-specific connectivity patterns of epileptic networks in FLE reflect local high connectivity and connections with distant regions differing from those of healthy controls. Moreover, the difference between the two groups in most features was observed in the strictest of the three connection levels. The abnormally high connectivity might reflect a predominant attribute of the epileptic network, which may facilitate propagation of epileptic activity among regions in the network. PMID:24936418

Monitoring vigabatrin in head injury patients by cerebral microdialysis: obtaining pharmacokinetic measurements in a neurocritical care setting

PubMed Central

Shannon, Richard J; Timofeev, Ivan; Nortje, Jürgens; Hutchinson, Peter J; Carpenter, Keri L H

2014-01-01

Aims The aims were to determine blood–brain barrier penetration and brain extracellular pharmacokinetics for the anticonvulsant vigabatrin (VGB; γ-vinyl-γ-aminobutyric acid) in brain extracellular fluid and plasma from severe traumatic brain injury (TBI) patients, and to measure the response of γ-aminobutyric acid (GABA) concentration in brain extracellular fluid. Methods Severe TBI patients (n = 10) received VGB (0.5 g enterally, every 12 h). Each patient had a cerebral microdialysis catheter; two patients had a second catheter in a different region of the brain. Plasma samples were collected 0.5 h before and 2, 4 and 11.5 h after the first VGB dose. Cerebral microdialysis commenced before the first VGB dose and continued through at least three doses of VGB. Controls were seven severe TBI patients with microdialysis, without VGB. Results After the first VGB dose, the maximum concentration of VGB (Cmax) was 31.7 (26.9–42.6) μmol l−1 (median and interquartile range for eight patients) in plasma and 2.41 (2.03–5.94) μmol l−1 in brain microdialysates (nine patients, 11 catheters), without significant plasma–brain correlation. After three doses, median Cmax in microdialysates increased to 5.22 (4.24–7.14) μmol l−1 (eight patients, 10 catheters). Microdialysate VGB concentrations were higher close to focal lesions than in distant sites. Microdialysate GABA concentrations increased modestly in some of the patients after VGB administration. Conclusions Vigabatrin, given enterally to severe TBI patients, crosses the blood–brain barrier into the brain extracellular fluid, where it accumulates with multiple dosing. Pharmacokinetics suggest delayed uptake from the blood. PMID:24802902

Theta coupling between V4 and prefrontal cortex predicts visual short-term memory performance.

PubMed

Liebe, Stefanie; Hoerzer, Gregor M; Logothetis, Nikos K; Rainer, Gregor

2012-01-29

Short-term memory requires communication between multiple brain regions that collectively mediate the encoding and maintenance of sensory information. It has been suggested that oscillatory synchronization underlies intercortical communication. Yet, whether and how distant cortical areas cooperate during visual memory remains elusive. We examined neural interactions between visual area V4 and the lateral prefrontal cortex using simultaneous local field potential (LFP) recordings and single-unit activity (SUA) in monkeys performing a visual short-term memory task. During the memory period, we observed enhanced between-area phase synchronization in theta frequencies (3-9 Hz) of LFPs together with elevated phase locking of SUA to theta oscillations across regions. In addition, we found that the strength of intercortical locking was predictive of the animals' behavioral performance. This suggests that theta-band synchronization coordinates action potential communication between V4 and prefrontal cortex that may contribute to the maintenance of visual short-term memories.

Altered Connectivity and Action Model Formation in Autism Is Autism

PubMed Central

Mostofsky, Stewart H.; Ewen, Joshua B.

2014-01-01

Internal action models refer to sensory-motor programs that form the brain basis for a wide range of skilled behavior and for understanding others’ actions. Development of these action models, particularly those reliant on visual cues from the external world, depends on connectivity between distant brain regions. Studies of children with autism reveal anomalous patterns of motor learning and impaired execution of skilled motor gestures. These findings robustly correlate with measures of social and communicative function, suggesting that anomalous action model formation may contribute to impaired development of social and communicative (as well as motor) capacity in autism. Examination of the pattern of behavioral findings, as well as convergent data from neuroimaging techniques, further suggests that autism-associated action model formation may be related to abnormalities in neural connectivity, particularly decreased function of long-range connections. This line of study can lead to important advances in understanding the neural basis of autism and, more critically, can be used to guide effective therapies targeted at improving social, communicative, and motor function. PMID:21467306

Hippocampal-prefrontal theta-gamma coupling during performance of a spatial working memory task.

PubMed

Tamura, Makoto; Spellman, Timothy J; Rosen, Andrew M; Gogos, Joseph A; Gordon, Joshua A

2017-12-19

Cross-frequency coupling supports the organization of brain rhythms and is present during a range of cognitive functions. However, little is known about whether and how long-range cross-frequency coupling across distant brain regions subserves working memory. Here we report that theta-slow gamma coupling between the hippocampus and medial prefrontal cortex (mPFC) is augmented in a genetic mouse model of cognitive dysfunction. This increased cross-frequency coupling is observed specifically when the mice successfully perform a spatial working memory task. In wild-type mice, increasing task difficulty by introducing a long delay or by optogenetically interfering with encoding, also increases theta-gamma coupling during correct trials. Finally, epochs of high hippocampal theta-prefrontal slow gamma coupling are associated with increased synchronization of neurons within the mPFC. These findings suggest that enhancement of theta-slow gamma coupling reflects a compensatory mechanism to maintain spatial working memory performance in the setting of increased difficulty.

Three or More Courses of Stereotactic Radiosurgery for Patients with Multiply Recurrent Brain Metastases.

PubMed

Kotecha, Rupesh; Damico, Nicholas; Miller, Jacob A; Suh, John H; Murphy, Erin S; Reddy, Chandana A; Barnett, Gene H; Vogelbaum, Michael A; Angelov, Lilyana; Mohammadi, Alireza M; Chao, Samuel T

2017-06-01

Although patients with brain metastasis are treated with primary stereotactic radiosurgery (SRS), the use of salvage therapies and their consequence remains understudied. To study the intracranial recurrence patterns and salvage therapies for patients who underwent multiple SRS courses. A retrospective review was performed of 59 patients with brain metastases who underwent ≥3 SRS courses for new lesions. Cox regression analyzed factors predictive for overall survival. The median age at diagnosis was 52 years. Over time, patients underwent a median of 3 courses of SRS (range: 3-8) to a total of 765 different brain metastases. The 6-month risk of distant intracranial recurrence after the first SRS treatment was 64% (95% confidence interval: 52%-77%). Overall survival was 40% (95% confidence interval: 28%-53%) at 24 months. Only 24 patients (41%) had a decline in their Karnofsky Performance Status ≤70 at last office visit. Quality of life was preserved among 77% of patients at 12 months, with 45% experiencing clinically significant improvement during clinical follow-up. Radiation necrosis developed in 10 patients (17%). On multivariate analysis, gender (males, Hazard Ratio [HR]: 2.0, P < .05), Karnofsky Performance Status ≤80 (HR 3.2, P < .001), extracranial metastases (HR: 3.6, P < .001), and a distant intracranial recurrence ≤3 months from initial to repeat SRS (HR: 3.8, P < .001) were associated with a poorer survival. In selected patients, performing ≥3 SRS courses controls intracranial disease. Patients may need salvage SRS for distant intracranial relapse, but focal retreatments are associated with modest toxicity, do not appear to negatively affect a patient's performance status, and help preserve quality of life. Copyright © 2017 by the Congress of Neurological Surgeons

How do probiotics and prebiotics function at distant sites?

PubMed

Reid, G; Abrahamsson, T; Bailey, M; Bindels, L B; Bubnov, R; Ganguli, K; Martoni, C; O'Neill, C; Savignac, H M; Stanton, C; Ship, N; Surette, M; Tuohy, K; van Hemert, S

2017-08-24

The realisation that microbes regarded as beneficial to the host can impart effects at sites distant from their habitat, has raised many possibilities for treatment of diseases. The objective of a workshop hosted in Turku, Finland, by the International Scientific Association for Probiotics and Prebiotics, was to assess the evidence for these effects and the extent to which early life microbiome programming influences how the gut microbiota communicates with distant sites. In addition, we examined how probiotics and prebiotics might affect the skin, airways, heart, brain and metabolism. The growing levels of scientific and clinical evidence showing how microbes influence the physiology of many body sites, leads us to call for more funding to advance a potentially exciting avenue for novel therapies for many chronic diseases.

Shining light on neurons--elucidation of neuronal functions by photostimulation.

PubMed

Eder, Matthias; Zieglgänsberger, Walter; Dodt, Hans-Ulrich

2004-01-01

Many neuronal functions can be elucidated by techniques that allow for a precise stimulation of defined regions of a neuron and its afferents. Photolytic release of neurotransmitters from 'caged' derivates in the vicinity of visualized neurons in living brain slices meets this request. This technique allows the study of the subcellular distribution and properties of functional native neurotransmitter receptors. These are prerequisites for a detailed analysis of the expression and spatial specificity of synaptic plasticity. Photostimulation can further be used to fast map the synaptic connectivity between nearby and, more importantly, distant cells in a neuronal network. Here we give a personal review of some of the technical aspects of photostimulation and recent findings, which illustrate the advantages of this technique.

Scanning fast and slow: current limitations of 3 Tesla functional MRI and future potential

NASA Astrophysics Data System (ADS)

Boubela, Roland N.; Kalcher, Klaudius; Nasel, Christian; Moser, Ewald

2014-02-01

Functional MRI at 3T has become a workhorse for the neurosciences, e.g., neurology, psychology, and psychiatry, enabling non-invasive investigation of brain function and connectivity. However, BOLD-based fMRI is a rather indirect measure of brain function, confounded by fluctuation related signals, e.g. head or brain motion, brain pulsation, blood flow, intermixed with susceptibility differences close or distant to the region of neuronal activity. Even though a plethora of preprocessing strategies have been published to address these confounds, their efficiency is still under discussion. In particular, physiological signal fluctuations closely related to brain supply may mask BOLD signal changes related to "true" neuronal activation. Here we explore recent technical and methodological advancements aimed at disentangling the various components, employing fast multiband vs. standard EPI, in combination with fast temporal ICA.Our preliminary results indicate that fast (TR< 0.5s) scanning may help to identify and eliminate physiologic components, increasing tSNR and functional contrast. In addition, biological variability can be studied and task performance better correlated to other measures. This should increase specificity and reliability in fMRI studies. Furthermore, physiological signal changes during scanning may then be recognized as a source of information rather than a nuisance. As we are currently still undersampling the complexity of the brain, even at a rather coarse macroscopic level, we should be very cautious in the interpretation of neuroscientific findings, in particular when comparing different groups (e.g., age, sex, medication, pathology, etc.). From a technical point of view our goal should be to sample brain activity at layer specific resolution with low TR, covering as much of the brain as possible without violating SAR limits. We hope to stimulate discussion towards a better understanding and a more quantitative use of fMRI.

Novel Risk Stratification Score for Predicting Early Distant Brain Failure and Salvage Whole Brain Radiotherapy after Stereotactic Radiosurgery for Brain Metastases

PubMed Central

Press, Robert H.; Prabhu, Roshan S.; Nickleach, Dana C.; Liu, Yuan; Shu, Hui-Kuo G.; Kandula, Shravan; Patel, Kirtesh R.; Curran, Walter J.; Crocker, Ian

2015-01-01

Background The purpose of this study was to evaluate predictors of early distant brain failure (DBF) and salvage whole brain radiotherapy (WBRT) after treatment with stereotactic radiosurgery (SRS) for brain metastases and create a clinically relevant risk score in order to stratify patients’ risk of these events. Methods We reviewed records of 270 patients with brain metastases treated with SRS between 2003-2012. Pre-treatment patient and tumor characteristics were analyzed by univariate and multivariable analyses. Cumulative incidence (CI) of first DBF and salvage WBRT were calculated. Significant factors were used to create a score for stratifying early (6-month) DBF risk. Results No prior WBRT, total lesion volume <1.3 cm3, primary breast cancer or malignant melanoma histology, and multiple metastases (≥2) were found to be significant predictors for early DBF. Each factor was ascribed one point due to similar hazard ratios. Scores of 0-1, 2, and 3-4 were considered low, intermediate, and high risk, respectively. This correlated with 6-month CI of DBF of 16.6%, 28.8%, and 54.4%, respectively (p<0.001). For patients without prior WBRT, the 6-month CI of salvage WBRT by 6-months was 2%, 17.7%, and 25.7%, respectively (p<0.001). Conclusion Early DBF after SRS requiring salvage WBRT remains a significant clinical problem. Patient stratification for early DBF can better inform the decision for initial treatment strategy for brain metastases. The provided risk score may help predict for early DBF and subsequent salvage WBRT if initial SRS is used. External validation is needed prior to clinical implementation. PMID:26242475

Multidose Stereotactic Radiosurgery (9 Gy × 3) of the Postoperative Resection Cavity for Treatment of Large Brain Metastases

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

Minniti, Giuseppe, E-mail: gminniti@ospedalesantandrea.it; Department of Neurological Sciences, Scientific Institute IRCCS Neuromed, Pozzilli; Esposito, Vincenzo

2013-07-15

Purpose: To evaluate the clinical outcomes with linear accelerator-based multidose stereotactic radiosurgery (SRS) to large postoperative resection cavities in patients with large brain metastases. Methods and Materials: Between March 2005 to May 2012, 101 patients with a single brain metastasis were treated with surgery and multidose SRS (9 Gy × 3) for large resection cavities (>3 cm). The target volume was the resection cavity with the inclusion of a 2-mm margin. The median cavity volume was 17.5 cm{sup 3} (range, 12.6-35.7 cm{sup 3}). The primary endpoint was local control. Secondary endpoints were survival and distant failure rates, cause of death,more » performance measurements, and toxicity of treatment. Results: With a median follow-up of 16 months (range, 6-44 months), the 1-year and 2-year actuarial survival rates were 69% and 34%, respectively. The 1-year and 2-year local control rates were 93% and 84%, with respective incidences of new distant brain metastases of 50% and 66%. Local control was similar for radiosensitive (non-small cell lung cancer and breast cancer) and radioresistant (melanoma and renal cell cancer) brain metastases. On multivariate Cox analysis stable extracranial disease, breast cancer histology, and Karnofsky performance status >70 were associated with significant survival benefit. Brain radionecrosis occurred in 9 patients (9%), being symptomatic in 5 patients (5%). Conclusions: Adjuvant multidose SRS to resection cavity represents an effective treatment option that achieves excellent local control and defers the use of whole-brain radiation therapy in selected patients with large brain metastases.« less

Racial differences in breast cancer stage at diagnosis in the mammography era.

PubMed

Chatterjee, Neal A; He, Yulei; Keating, Nancy L

2013-01-01

We assessed racial differences in breast cancer mortality by stage at diagnosis, since mammography became available. We calculated adjusted odds of distant (versus local or regional) tumors for 143,249 White and 13,571 Black women aged 50 to 69 years, diagnosed with breast cancer between 1982 and 2007 and living in a Surveillance, Epidemiology, and End Results region. We compared linear trends in stage at diagnosis before and after 1998. Distant-stage cancer was diagnosed in 5.8% of White and 10.2% of Black participants. The Black-White disparity in distant tumors narrowed until 1998 (1998 adjusted difference = 0.65%), before increasing. Between 1982 and 1997, the proportion of distant tumors decreased for Blacks (adjusted odds ratio [AOR]/y = 0.973; 95% confidence interval [CI] = 0.960, 0.987) and Whites (AOR/y = 0.978; 95% CI = 0.973, 0.983), with no racial differences (P = .47). From 1998 to 2007, the odds of distant versus local or regional tumors increased for Blacks (AOR/y = 1.036; 95% CI = 1.013, 1.060) and Whites (AOR/y = 1.011; 95% CI = 1.002, 1.021); the rate of increase was greater for Blacks than Whites (P = .04). In the mammography era, racial disparities remain in stage at diagnosis.

Double streams of protons in the distant geomagnetic tail

NASA Technical Reports Server (NTRS)

Villante, U.; Lazarus, A. J.

1975-01-01

Two intermingled streams of protons have been observed in the distant geomagnetic tail. The number densities of the two streams are comparable, and their velocity difference tends to lie along the field direction. The lower-velocity stream is probably composed of magnetosheath protons which have diffused through the boundary of the distant tail. The higher-velocity stream appears to originate in the field reversal region.

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

PubMed

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

2016-01-01

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

Hot Ion Flows in the Distant Magnetotail: ARTEMIS Observations From Lunar Orbit to ˜-200 RE

NASA Astrophysics Data System (ADS)

Artemyev, A. V.; Angelopoulos, V.; Runov, A.; Vasko, I. Y.

2017-10-01

Plasma energization in Earth's magnetotail is supported by acceleration processes in (and around) magnetic reconnection regions. Hot plasma flows and strong electromagnetic waves, generated by magnetic energy release during reconnection, transport energy necessary for current system intensification and particle acceleration in the inner magnetosphere. Earth's magnetotail configuration includes two main reconnection regions (X lines): the near-Earth X line, which has been well studied by several multispacecraft missions, and the distant X line, which has been much less investigated. In this paper, we utilize the unique data set gathered by two ARTEMIS spacecraft in 2010 at radial distances between lunar orbit and ˜200 RE (Earth radii). We identify an X line at around ˜80 RE and collect statistics on hot plasma flows observed around and beyond this distance. Ion spectra within these flows are well fitted by a power law with the exponential tail starting above an energy ɛ0˜ 2-5 keV. Assuming that these spectra are originated at the distant X line, we examine the characteristics of the acceleration at the distant tail reconnection region.

Action verbs are processed differently in metaphorical and literal sentences depending on the semantic match of visual primes

PubMed Central

Troyer, Melissa; Curley, Lauren B.; Miller, Luke E.; Saygin, Ayse P.; Bergen, Benjamin K.

2014-01-01

Language comprehension requires rapid and flexible access to information stored in long-term memory, likely influenced by activation of rich world knowledge and by brain systems that support the processing of sensorimotor content. We hypothesized that while literal language about biological motion might rely on neurocognitive representations of biological motion specific to the details of the actions described, metaphors rely on more generic representations of motion. In a priming and self-paced reading paradigm, participants saw video clips or images of (a) an intact point-light walker or (b) a scrambled control and read sentences containing literal or metaphoric uses of biological motion verbs either closely or distantly related to the depicted action (walking). We predicted that reading times for literal and metaphorical sentences would show differential sensitivity to the match between the verb and the visual prime. In Experiment 1, we observed interactions between the prime type (walker or scrambled video) and the verb type (close or distant match) for both literal and metaphorical sentences, but with strikingly different patterns. We found no difference in the verb region of literal sentences for Close-Match verbs after walker or scrambled motion primes, but Distant-Match verbs were read more quickly following walker primes. For metaphorical sentences, the results were roughly reversed, with Distant-Match verbs being read more slowly following a walker compared to scrambled motion. In Experiment 2, we observed a similar pattern following still image primes, though critical interactions emerged later in the sentence. We interpret these findings as evidence for shared recruitment of cognitive and neural mechanisms for processing visual and verbal biological motion information. Metaphoric language using biological motion verbs may recruit neurocognitive mechanisms similar to those used in processing literal language but be represented in a less-specific way. PMID:25538604

Dynamical Signatures of Structural Connectivity Damage to a Model of the Brain Posed at Criticality.

PubMed

Haimovici, Ariel; Balenzuela, Pablo; Tagliazucchi, Enzo

2016-12-01

Synchronization of brain activity fluctuations is believed to represent communication between spatially distant neural processes. These interareal functional interactions develop in the background of a complex network of axonal connections linking cortical and subcortical neurons, termed the human "structural connectome." Theoretical considerations and experimental evidence support the view that the human brain can be modeled as a system operating at a critical point between ordered (subcritical) and disordered (supercritical) phases. Here, we explore the hypothesis that pathologies resulting from brain injury of different etiologies are related to this model of a critical brain. For this purpose, we investigate how damage to the integrity of the structural connectome impacts on the signatures of critical dynamics. Adopting a hybrid modeling approach combining an empirical weighted network of human structural connections with a conceptual model of critical dynamics, we show that lesions located at highly transited connections progressively displace the model toward the subcritical regime. The topological properties of the nodes and links are of less importance when considered independently of their weight in the network. We observe that damage to midline hubs such as the middle and posterior cingulate cortex is most crucial for the disruption of criticality in the model. However, a similar effect can be achieved by targeting less transited nodes and links whose connection weights add up to an equivalent amount. This implies that brain pathology does not necessarily arise due to insult targeted at well-connected areas and that intersubject variability could obscure lesions located at nonhub regions. Finally, we discuss the predictions of our model in the context of clinical studies of traumatic brain injury and neurodegenerative disorders.

Stereotactic radiotherapy following surgery for brain metastasis: Predictive factors for local control and radionecrosis.

PubMed

Doré, M; Martin, S; Delpon, G; Clément, K; Campion, L; Thillays, F

2017-02-01

To evaluate local control and adverse effects after postoperative hypofractionated stereotactic radiosurgery in patients with brain metastasis. We reviewed patients who had hypofractionated stereotactic radiosurgery (7.7Gy×3 prescribed to the 70% isodose line, with 2mm planning target volume margin) following resection from March 2008 to January 2014. The primary endpoint was local failure defined as recurrence within the surgical cavity. Secondary endpoints were distant failure rates and the occurrence of radionecrosis. Out of 95 patients, 39.2% had metastatic lesions from a non-small cell lung cancer primary tumour. The median Graded Prognostic Assessment score was 3 (48% of patients). One-year local control rates were 84%. Factors associated with improved local control were no cavity enhancement on pre-radiation MRI (P<0.00001), planning target volume less than 12cm 3 (P=0.005), Graded Prognostic Assessment score 2 or above (P=0.009). One-year distant cerebral control rates were 56%. Thirty-three percent of patients received whole brain radiation therapy. Histologically proven radionecrosis of brain tissue occurred in 7.2% of cases. The size of the preoperative lesion and the volume of healthy brain tissue receiving 21Gy (V 21 ) were both predictive of the incidence of radionecrosis (P=0.010 and 0.036, respectively). Adjuvant hypofractionated stereotactic radiosurgery to the postoperative cavity in patients with brain metastases results in excellent local control in selected patients, helps delay the use of whole brain radiation, and is associated with a relatively low risk of radionecrosis. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Coordination of gene expression of arachidonic and docosahexaenoic acid cascade enzymes during human brain development and aging.

PubMed

Ryan, Veronica H; Primiani, Christopher T; Rao, Jagadeesh S; Ahn, Kwangmi; Rapoport, Stanley I; Blanchard, Helene

2014-01-01

The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA) participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades. AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging. The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism. Expression patterns were split into Development (0 to 20 years) and Aging (21 to 78 years) intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2), cyclooxygenases (COX)-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA) and PTGS2 (COX-2) genes at 1q25, highly inter-correlated genes were at distant chromosomal loci. Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.

An unusual subcutaneous breast cancer metastasis in a 86-year-old woman.

PubMed

Metere, A; Di Cosimo, C; Chiesa, C; Esposito, A; Giacomelli, L; Redler, A

2012-04-01

The most common metastasis site of breast cancer are the local and distant lymph nodes, bone, lungs, liver and brain. We report a 86-year-old woman with an unusual abdominal subcutaneous metastasis of breast cancer. The patient was diagnosed with invasive lobular breast cancer and had been treated six months earlier with modified radical mastectomy. Later she presented a painless mass on the middle upper abdominal wall. She was subsequently admitted to the hospital to perform a whole body CT scan, confirming the presence of the abdominal mass in epigastric region, causing a partial compression of the stomach. Histopathological studies confirmed that the abdominal mass was a rare subcutaneous metastatic lesion of breast origin. The patient underwent a surgical intervention to remove the metastasis and she recovered fully.

Monitoring vigabatrin in head injury patients by cerebral microdialysis: obtaining pharmacokinetic measurements in a neurocritical care setting.

PubMed

Shannon, Richard J; Timofeev, Ivan; Nortje, Jürgens; Hutchinson, Peter J; Carpenter, Keri L H

2014-11-01

The aims were to determine blood-brain barrier penetration and brain extracellular pharmacokinetics for the anticonvulsant vigabatrin (VGB; γ-vinyl-γ-aminobutyric acid) in brain extracellular fluid and plasma from severe traumatic brain injury (TBI) patients, and to measure the response of γ-aminobutyric acid (GABA) concentration in brain extracellular fluid. Severe TBI patients (n = 10) received VGB (0.5 g enterally, every 12 h). Each patient had a cerebral microdialysis catheter; two patients had a second catheter in a different region of the brain. Plasma samples were collected 0.5 h before and 2, 4 and 11.5 h after the first VGB dose. Cerebral microdialysis commenced before the first VGB dose and continued through at least three doses of VGB. Controls were seven severe TBI patients with microdialysis, without VGB. After the first VGB dose, the maximum concentration of VGB (Cmax ) was 31.7 (26.9-42.6) μmol l(-1) (median and interquartile range for eight patients) in plasma and 2.41 (2.03-5.94) μmol l(-1) in brain microdialysates (nine patients, 11 catheters), without significant plasma-brain correlation. After three doses, median Cmax in microdialysates increased to 5.22 (4.24-7.14) μmol l(-1) (eight patients, 10 catheters). Microdialysate VGB concentrations were higher close to focal lesions than in distant sites. Microdialysate GABA concentrations increased modestly in some of the patients after VGB administration. Vigabatrin, given enterally to severe TBI patients, crosses the blood-brain barrier into the brain extracellular fluid, where it accumulates with multiple dosing. Pharmacokinetics suggest delayed uptake from the blood. © 2014 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.

Detecting Large-Scale Brain Networks Using EEG: Impact of Electrode Density, Head Modeling and Source Localization

PubMed Central

Liu, Quanying; Ganzetti, Marco; Wenderoth, Nicole; Mantini, Dante

2018-01-01

Resting state networks (RSNs) in the human brain were recently detected using high-density electroencephalography (hdEEG). This was done by using an advanced analysis workflow to estimate neural signals in the cortex and to assess functional connectivity (FC) between distant cortical regions. FC analyses were conducted either using temporal (tICA) or spatial independent component analysis (sICA). Notably, EEG-RSNs obtained with sICA were very similar to RSNs retrieved with sICA from functional magnetic resonance imaging data. It still remains to be clarified, however, what technological aspects of hdEEG acquisition and analysis primarily influence this correspondence. Here we examined to what extent the detection of EEG-RSN maps by sICA depends on the electrode density, the accuracy of the head model, and the source localization algorithm employed. Our analyses revealed that the collection of EEG data using a high-density montage is crucial for RSN detection by sICA, but also the use of appropriate methods for head modeling and source localization have a substantial effect on RSN reconstruction. Overall, our results confirm the potential of hdEEG for mapping the functional architecture of the human brain, and highlight at the same time the interplay between acquisition technology and innovative solutions in data analysis. PMID:29551969

Dynamic connectivity states estimated from resting fMRI Identify differences among Schizophrenia, bipolar disorder, and healthy control subjects.

PubMed

Rashid, Barnaly; Damaraju, Eswar; Pearlson, Godfrey D; Calhoun, Vince D

2014-01-01

Schizophrenia (SZ) and bipolar disorder (BP) share significant overlap in clinical symptoms, brain characteristics, and risk genes, and both are associated with dysconnectivity among large-scale brain networks. Resting state functional magnetic resonance imaging (rsfMRI) data facilitates studying macroscopic connectivity among distant brain regions. Standard approaches to identifying such connectivity include seed-based correlation and data-driven clustering methods such as independent component analysis (ICA) but typically focus on average connectivity. In this study, we utilize ICA on rsfMRI data to obtain intrinsic connectivity networks (ICNs) in cohorts of healthy controls (HCs) and age matched SZ and BP patients. Subsequently, we investigated difference in functional network connectivity, defined as pairwise correlations among the timecourses of ICNs, between HCs and patients. We quantified differences in both static (average) and dynamic (windowed) connectivity during the entire scan duration. Disease-specific differences were identified in connectivity within different dynamic states. Notably, results suggest that patients make fewer transitions to some states (states 1, 2, and 4) compared to HCs, with most such differences confined to a single state. SZ patients showed more differences from healthy subjects than did bipolars, including both hyper and hypo connectivity in one common connectivity state (dynamic state 3). Also group differences between SZ and bipolar patients were identified in patterns (states) of connectivity involving the frontal (dynamic state 1) and frontal-parietal regions (dynamic state 3). Our results provide new information about these illnesses and strongly suggest that state-based analyses are critical to avoid averaging together important factors that can help distinguish these clinical groups.

Autobiographical Planning and the Brain: Activation and Its Modulation by Qualitative Features.

PubMed

Spreng, R Nathan; Gerlach, Kathy D; Turner, Gary R; Schacter, Daniel L

2015-11-01

To engage in purposeful behavior, it is important to make plans, which organize subsequent actions. Most studies of planning involve "look-ahead" puzzle tasks that are unrelated to personal goals. We developed a task to assess autobiographical planning, which involves the formulation of personal plans in response to real-world goals, and examined autobiographical planning in 63 adults during fMRI scanning. Autobiographical planning was found to engage the default network, including medial-temporal lobe and midline structures, and executive control regions in lateral pFC and parietal cortex and caudate. To examine how specific qualitative features of autobiographical plans modulate neural activity, we performed parametric modulation analyses. Ratings of plan detail, novelty, temporal distance, ease of plan formulation, difficulty in goal completion, and confidence in goal accomplishment were used as covariates in six hierarchical linear regression models. This modeling procedure removed shared variance among the ratings, allowing us to determine the independent relationship between ratings of interest and trial-wise BOLD signal. We found that specific autobiographical planning, describing a detailed, achievable, and actionable planning process for attaining a clearly envisioned future, recruited both default and frontoparietal brain regions. In contrast, abstract autobiographical planning, plans that were constructed from more generalized semantic or affective representations of a less tangible and distant future, involved interactions among default, sensory perceptual, and limbic brain structures. Specific qualities of autobiographical plans are important predictors of default and frontoparietal control network engagement during plan formation and reflect the contribution of mnemonic and executive control processes to autobiographical planning.

Neural mechanisms of dissonance: an fMRI investigation of choice justification.

PubMed

Kitayama, Shinobu; Chua, Hannah Faye; Tompson, Steven; Han, Shihui

2013-04-01

Cognitive dissonance theory proposes that difficult choice produces negatively arousing cognitive conflict (called dissonance), which motivates the chooser to justify her decision by increasing her preference for the chosen option while decreasing her preference for the rejected option. At present, however, neural mechanisms of dissonance are poorly understood. To address this gap of knowledge, we scanned 24 young Americans as they made 60 choices between pairs of popular music CDs. As predicted, choices between CDs that were close (vs. distant) in attractiveness (referred to as difficult vs. easy choices) resulted in activations of the dorsal anterior cingulate cortex (dACC), a brain region associated with cognitive conflict, and the left anterior insula (left aINS), a region often linked with aversive emotional arousal. Importantly, a separate analysis showed that choice-justifying attitude change was predicted by the in-choice signal intensity of the posterior cingulate cortex (PCC), a region that is linked to self-processing. The three regions identified (dACC, left aINS, and PCC) were correlated, within-subjects, across choices. The results were interpreted to support the hypothesis that cognitive dissonance plays a key role in producing attitudes that justify the choice. Copyright © 2012 Elsevier Inc. All rights reserved.

Incidence and sites of distant metastases from head and neck cancer.

PubMed

Ferlito, A; Shaha, A R; Silver, C E; Rinaldo, A; Mondin, V

2001-01-01

The incidence of distant metastases in head and neck squamous cell carcinoma (SCC) is relatively small in comparison to other malignancies. Distant metastases adversely impact survival and may significantly affect treatment planning. The incidence of distant metastases is influenced by location of the primary tumor, initial T and N stage of the neoplasm, and the presence or absence of regional control above the clavicle. Patients with advanced nodal disease have a high incidence of distant metastases, particularly in the presence of jugular vein invasion or extensive soft tissue disease in the neck. Primary tumors of advanced T stages in the hypopharynx, oropharynx and oral cavity are associated with the highest incidence of distant metastases. Pulmonary metastases are the most frequent in SCC, accounting for 66% of distant metastases. It may be difficult to distinguish pulmonary metastasis from a new primary tumor, particularly if solitary. Other metastatic sites include bone (22%), liver (10%), skin, mediastinum and bone marrow. An important question remains as to how intensely pre- and postoperative screening for distant metastases should be performed. Preoperative chest X-ray is warranted in all cases. If the primary tumor and nodal status place the patient at high risk for pulmonary metastasis, then preoperative computed tomography scan of the chest should be done. Screening for distant metastases at other sites is usually not indicated in SCC of the upper aerodigestive tract. Postoperatively, annual X-rays of the chest are usually sufficient, but in high-risk situations a chest X-ray performed every 3-6 months may be beneficial. Certain histologic types of primary tumor have greater or lesser propensity to metastasize distantly, and have a different natural history. Adenoid cystic carcinoma metastasizes frequently, even in the absence of extensive local or regional disease. Basaloid squamous cell carcinoma and neuroendocrine carcinomas also metastasize widely. Extensive evaluation for distant metastases is justified for these tumors. Knowledge of the natural history of various neoplasms and the factors that contribute to distant metastases as well as good judgement are essential for cost-effective treatment planning and decision-making with regard to pre- and postoperative evaluation for distant metastases in cancer of the head and neck. Copyright 2001 S. Karger AG, Basel

Clinical correlates and prognostic value of different metastatic sites in patients with malignant melanoma of the skin: a SEER database analysis.

PubMed

Abdel-Rahman, Omar

2018-03-01

Population-based data on the clinical correlates and prognostic value of the pattern of metastases among patients with cutaneous melanoma are needed. Surveillance, Epidemiology and End Results (SEER) database (2010-2013) has been explored through SEER*Stat program. For each of six distant metastatic sites (bone, brain, liver, lung, distant lymph nodes, and skin/subcutaneous), relevant correlation with baseline characteristics were reported. Survival analysis has been conducted through Kaplan-Meier analysis, and multivariate analysis has been conducted through a Cox proportional hazard model. A total of 2691 patients with metastatic cutaneous melanoma were identified in the period from 2010 to 2013. Patients with isolated skin/subcutaneous metastases have the best overall and melanoma-specific survival (MSS) followed by patients with isolated distant lymph node metastases followed by patients with isolated lung metastases. Patients with isolated liver, bone, or brain metastases have the worst overall and MSS (p < .0001 for both end points). Multivariate analysis revealed that age more than 70 at diagnosis (p = .012); multiple sites of metastases (p <.0001), no surgery to the primary tumor (p <.0001), and no surgery to the metastatic disease (p < .0001) were associated with worse overall survival (OS). For MSS, nodal positivity (p = .038), multiple sites of metastases (p < .0001), no surgery to the primary tumor (p < .0001), and no surgery to the metastatic disease (p < .0001) were associated with worse survival. The prognosis of metastatic cutaneous melanoma patients differs considerably according to the site of distant metastases. Further prospective studies are required to evaluate the role of local treatment in the management of metastatic disease.

The role of stereotactic radiosurgery and whole brain radiation therapy as primary treatment in the treatment of patients with brain oligometastases — A systematic review

PubMed Central

Sheehan, Jason P.

2016-01-01

The management of patients presenting with a limited number of brain metastases (BM) (oligo-metastases, defined as less than 3 BM) has evolved from Whole-Brain Radiotherapy (WBRT) alone to more aggressive strategies adding surgical resection and Stereotactic Radiosurgery (SRS) to the armamentarium. In choosing treatment modalities, the relative importance of the patient’s age and clinical parameters, the number or volume of BM and the potential treatment related adverse-effects has been a matter of much debate. For patients with oligometastatic BM, local therapy using SRS in addition to WBRT was shown to improve time to neurologic deterioration, relapse rate and Overall Survival (OS). In patients who receive local therapy (SRS or surgery), adjuvant WBRT was shown to improve regional (brain) relapse rate. In the contemporary era, the beneficial effect of WBRT on lengthening the time of neurologic independence or OS when compared to no further treatment is unclear. One Meta-analysis pooling of information from several reports concluded that for younger patients (<50 years), SRS alone favored survival and that the initial omission of WBRT did not impact distant brain relapse rates. Other recent reports demonstrated on the contrary an OS benefit, more pronounced in good prognosis patients (diagnosis-specific Graded Prognostic Assessment 2.4–4.0) treated with SRS+WBRT compared to those who received SRS alone. As of today, there remains a role for both SRS and WBRT in the management of patients with oligo-metastatic BM but consensus about when to employ one or both is lacking. The exact patient selection criteria to benefit from either or both are still a matter of active research and heated debate. PMID:29296432

Intracranial control and radiographic changes with adjuvant radiation therapy for resected brain metastases: whole brain radiotherapy versus stereotactic radiosurgery alone.

PubMed

Patel, Kirtesh R; Prabhu, Roshan S; Kandula, Shravan; Oliver, Daniel E; Kim, Sungjin; Hadjipanayis, Constantinos; Olson, Jeffery J; Oyesiku, Nelson; Curran, Walter J; Khan, Mohammad K; Shu, Hui-Kuo; Crocker, Ian

2014-12-01

The aim of this study was to compare outcomes of postoperative whole brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) alone in patients with resected brain metastases (BM). We reviewed records of patients who underwent surgical resection of BM followed by WBRT or SRS alone between 2003 and 2013. Local control (LC) of the treated resected cavity, distant brain control (DBC), leptomeningeal disease (LMD), overall survival (OS), and radiographic leukoencephalopathy rates were estimated by the Kaplan-Meier method. One-hundred thirty-two patients underwent surgical resection for 141 intracranial metastases: 36 (27 %) patients received adjuvant WBRT and 96 (73 %) received SRS alone to the resection cavity. One-year OS (56 vs. 55 %, p = 0.64) and LC (83 vs. 74 %, p = 0.31) were similar between patients receiving WBRT and SRS. After controlling for number of BM, WBRT was associated with higher 1-year DBC compared with SRS (70 vs. 48 %, p = 0.03); single metastasis and WBRT were the only significant predictors for reduced distant brain recurrence in multi-variate analysis. Freedom from LMD was higher with WBRT at 18 months (87 vs. 69 %, p = 0.045), while incidence of radiographic leukoencephalopathy was higher with WBRT at 12 months (47 vs. 7 %, p = 0.001). One-year freedom from WBRT in the SRS alone group was 86 %. Compared with WBRT for patients with resected BM, SRS alone demonstrated similar LC, higher rates of LMD and inferior DBC, after controlling for the number of BM. However, OS was similar between groups. The results of ongoing clinical trials are needed to confirm these findings.

Coordination of Gene Expression of Arachidonic and Docosahexaenoic Acid Cascade Enzymes during Human Brain Development and Aging

PubMed Central

Ryan, Veronica H.; Primiani, Christopher T.; Rao, Jagadeesh S.; Ahn, Kwangmi; Rapoport, Stanley I.; Blanchard, Helene

2014-01-01

Background The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA) participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades. Hypothesis AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging. Methods The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism. Results Expression patterns were split into Development (0 to 20 years) and Aging (21 to 78 years) intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2), cyclooxygenases (COX)-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA) and PTGS2 (COX-2) genes at 1q25, highly inter-correlated genes were at distant chromosomal loci. Conclusions Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease. PMID:24963629

Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS

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

Shultz, David B.; Modlin, Leslie A.; Jayachandran, Priya

Purpose: To report the outcomes of repeat stereotactic radiosurgery (SRS), deferring whole-brain radiation therapy (WBRT), for distant intracranial recurrences and identify factors associated with prolonged overall survival (OS). Patients and Methods: We retrospectively identified 652 metastases in 95 patients treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox regression analyzed factors predictive for OS. Results: Patients had a median of 2 metastases (range, 1-14) treated per course, with a median of 2 courses (range, 2-14) of SRS per patient. With a median follow-up after first SRS of 15 months (range, 3-98 months), the median OS from the timemore » of the first and second course of SRS was 18 (95% confidence interval [CI] 15-24) and 11 months (95% CI 6-17), respectively. On multivariate analysis, histology, graded prognostic assessment score, aggregate tumor volume (but not number of metastases), and performance status correlated with OS. The 1-year cumulative incidence, with death as a competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75 deaths were from neurologic causes. Nineteen patients (20%) eventually received WBRT. Adverse radiation events developed in 2% of SRS sites. Conclusion: Multiple courses of SRS, deferring WBRT, for distant brain metastases after initial SRS, seem to be a safe and effective approach. The graded prognostic assessment score, updated at each course, and aggregate tumor volume may help select patients in whom the deferral of WBRT might be most beneficial.« less

Emerging role of brain metastases in the prognosis of breast cancer patients.

PubMed

Hambrecht, Amanda; Jandial, Rahul; Neman, Josh

2011-08-10

Cancer starts with one rogue cell. Through mutations and genomic alterations, the cell acquires specific and stem cell-like characteristics necessary for invasion of a distant organ and ultimately metastasis. Metastatic brain cancer is a particularly formidable disease because of its poor prognosis and the highly resistant nature of the tumor to chemotherapy. Although several types of primary tumors have a tendency to metastasize to the brain, the incidence of brain metastases has increased dramatically in some subsets of breast cancer patients. Several conventional treatments are available, but success is limited and often short-lived. Given that no standard treatment options exist, there is a significant need to investigate the biology of these clinically recalcitrant tumors.

Emerging role of brain metastases in the prognosis of breast cancer patients

PubMed Central

Hambrecht, Amanda; Jandial, Rahul; Neman, Josh

2011-01-01

Cancer starts with one rogue cell. Through mutations and genomic alterations, the cell acquires specific and stem cell-like characteristics necessary for invasion of a distant organ and ultimately metastasis. Metastatic brain cancer is a particularly formidable disease because of its poor prognosis and the highly resistant nature of the tumor to chemotherapy. Although several types of primary tumors have a tendency to metastasize to the brain, the incidence of brain metastases has increased dramatically in some subsets of breast cancer patients. Several conventional treatments are available, but success is limited and often short-lived. Given that no standard treatment options exist, there is a significant need to investigate the biology of these clinically recalcitrant tumors. PMID:24367178

Scanning fast and slow: current limitations of 3 Tesla functional MRI and future potential

PubMed Central

Boubela, Roland N.; Kalcher, Klaudius; Nasel, Christian; Moser, Ewald

2017-01-01

Functional MRI at 3T has become a workhorse for the neurosciences, e.g., neurology, psychology, and psychiatry, enabling non-invasive investigation of brain function and connectivity. However, BOLD-based fMRI is a rather indirect measure of brain function, confounded by physiology related signals, e.g., head or brain motion, brain pulsation, blood flow, intermixed with susceptibility differences close or distant to the region of neuronal activity. Even though a plethora of preprocessing strategies have been published to address these confounds, their efficiency is still under discussion. In particular, physiological signal fluctuations closely related to brain supply may mask BOLD signal changes related to “true” neuronal activation. Here we explore recent technical and methodological advancements aimed at disentangling the various components, employing fast multiband vs. standard EPI, in combination with fast temporal ICA. Our preliminary results indicate that fast (TR <0.5 s) scanning may help to identify and eliminate physiologic components, increasing tSNR and functional contrast. In addition, biological variability can be studied and task performance better correlated to other measures. This should increase specificity and reliability in fMRI studies. Furthermore, physiological signal changes during scanning may then be recognized as a source of information rather than a nuisance. As we are currently still undersampling the complexity of the brain, even at a rather coarse macroscopic level, we should be very cautious in the interpretation of neuroscientific findings, in particular when comparing different groups (e.g., age, sex, medication, pathology, etc.). From a technical point of view our goal should be to sample brain activity at layer specific resolution with low TR, covering as much of the brain as possible without violating SAR limits. We hope to stimulate discussion toward a better understanding and a more quantitative use of fMRI. PMID:28164083

Distant and Regional Atmospheric Circulation Influences Governing Integrated Water Vapor Transport and the Occurrence of Extreme Precipitation Events

NASA Astrophysics Data System (ADS)

Bosart, L. F.; Papin, P. P.; Bentley, A. M.

2017-12-01

This presentation will show how the evolution of the large-scale and regional-scale atmospheric circulation contributes to the occurrence of extreme precipitation events (EPEs). An EPE requires that tropospheric moisture flux convergence (MFC) and the associated removal of hydrometeors be balanced by moisture replenishment via integrated (water) vapor transport (IVT) to continuously replenish condensed moisture. Moisture source regions may be distant or regional. Distant moisture sources may require the interaction of lower- and upper-level jet streams with a pre-existing mobile atmospheric disturbance to produce sufficient lift to condense moisture. Pre-existing regional moisture sources may require frontal lifting the presence of MFC to condense moisture. In cases of long-range IVT, such as moisture from a western North Pacific typhoon being drawn poleward along an atmospheric river (AR) toward the west coast of North America, moisture may be transported 1000s of kilometers along a low-level jet before a combination of dynamic and orographic lift results in an EPE. Alternatively, in the case of a typical summer warm and humid air mass over the continental United States, unused moisture may exist for several days in this air mass before sufficient MFC associated with a thermally direct mesoscale frontal circulation can concentrate and condense the moisture. In this case, there may be no long-range IVT via ARs. Instead, the atmospheric circulations may evolve to produce sustained MFC associated with mesoscale frontal circulations, especially in the presence of complex terrain, to produce an EPE. During this presentation, examples of EPEs associated with long-range IVT and distant MFC versus EPEs associated with regional MFC and mesoscale frontal circulations will be illustrated.

Role of the neural niche in brain metastatic cancer

PubMed Central

Termini, John; Neman, Josh; Jandial, Rahul

2014-01-01

Metastasis is the relenteless pursuit of cancer to escape its primary site and colonize distant organs. This malignant evolutionary process is biologically heterogeneous, yet one unifying element is the critical role of the microenvironment for arriving metastatic cells. Historically brain metastases were rarely investigated since patients with advanced cancer were considered terminal. Fortunately, advances in molecular therapies have led to patients living longer with metastatic cancer. However, one site remains recalcitrant to our treatment efforts – the brain. The central nervous system is the most complex biological system, which poses unique obstacles but also harbors opportunities for discovery. Much of what we know about the brain microenvironment comes from neuroscience. We suggest that the interrelated cellular responses in traumatic brain injury may guide us towards new perspectives in understanding brain metastases. In this view, brain metastases may be conceptualized as progressive oncologic injury to the nervous system. This review discusses our evolving understanding of the bidirectional interactions between the brain milieu and metastatic cancer. PMID:25035392

Role of the neural niche in brain metastatic cancer.

PubMed

Termini, John; Neman, Josh; Jandial, Rahul

2014-08-01

Metastasis is the relentless pursuit of cancer to escape its primary site and colonize distant organs. This malignant evolutionary process is biologically heterogeneous, yet one unifying element is the critical role of the microenvironment for arriving metastatic cells. Historically, brain metastases were rarely investigated because patients with advanced cancer were considered terminal. Fortunately, advances in molecular therapies have led to patients living longer with metastatic cancer. However, one site remains recalcitrant to our treatment efforts, the brain. The central nervous system is the most complex biologic system, which poses unique obstacles but also harbors opportunities for discovery. Much of what we know about the brain microenvironment comes from neuroscience. We suggest that the interrelated cellular responses in traumatic brain injury may guide us toward new perspectives in understanding brain metastases. In this view, brain metastases may be conceptualized as progressive oncologic injury to the nervous system. This review discusses our evolving understanding of bidirectional interactions between the brain milieu and metastatic cancer. ©2014 American Association for Cancer Research.

Large Sex Differences in Chicken Behavior and Brain Gene Expression Coincide with Few Differences in Promoter DNA-Methylation

PubMed Central

Nätt, Daniel; Agnvall, Beatrix; Jensen, Per

2014-01-01

While behavioral sex differences have repeatedly been reported across taxa, the underlying epigenetic mechanisms in the brain are mostly lacking. Birds have previously shown to have only limited dosage compensation, leading to high sex bias of Z-chromosome gene expression. In chickens, a male hyper-methylated region (MHM) on the Z-chromosome has been associated with a local type of dosage compensation, but a more detailed characterization of the avian methylome is limiting our interpretations. Here we report an analysis of genome wide sex differences in promoter DNA-methylation and gene expression in the brain of three weeks old chickens, and associated sex differences in behavior of Red Junglefowl (ancestor of domestic chickens). Combining DNA-methylation tiling arrays with gene expression microarrays we show that a specific locus of the MHM region, together with the promoter for the zinc finger RNA binding protein (ZFR) gene on chromosome 1, is strongly associated with sex dimorphism in gene expression. Except for this, we found few differences in promoter DNA-methylation, even though hundreds of genes were robustly differentially expressed across distantly related breeds. Several of the differentially expressed genes are known to affect behavior, and as suggested from their functional annotation, we found that female Red Junglefowl are more explorative and fearful in a range of tests performed throughout their lives. This paper identifies new sites and, with increased resolution, confirms known sites where DNA-methylation seems to affect sexually dimorphic gene expression, but the general lack of this association is noticeable and strengthens the view that birds do not have dosage compensation. PMID:24782041

Functional Brain Networks Develop from a “Local to Distributed” Organization

PubMed Central

Power, Jonathan D.; Dosenbach, Nico U. F.; Church, Jessica A.; Miezin, Francis M.; Schlaggar, Bradley L.; Petersen, Steven E.

2009-01-01

The mature human brain is organized into a collection of specialized functional networks that flexibly interact to support various cognitive functions. Studies of development often attempt to identify the organizing principles that guide the maturation of these functional networks. In this report, we combine resting state functional connectivity MRI (rs-fcMRI), graph analysis, community detection, and spring-embedding visualization techniques to analyze four separate networks defined in earlier studies. As we have previously reported, we find, across development, a trend toward ‘segregation’ (a general decrease in correlation strength) between regions close in anatomical space and ‘integration’ (an increased correlation strength) between selected regions distant in space. The generalization of these earlier trends across multiple networks suggests that this is a general developmental principle for changes in functional connectivity that would extend to large-scale graph theoretic analyses of large-scale brain networks. Communities in children are predominantly arranged by anatomical proximity, while communities in adults predominantly reflect functional relationships, as defined from adult fMRI studies. In sum, over development, the organization of multiple functional networks shifts from a local anatomical emphasis in children to a more “distributed” architecture in young adults. We argue that this “local to distributed” developmental characterization has important implications for understanding the development of neural systems underlying cognition. Further, graph metrics (e.g., clustering coefficients and average path lengths) are similar in child and adult graphs, with both showing “small-world”-like properties, while community detection by modularity optimization reveals stable communities within the graphs that are clearly different between young children and young adults. These observations suggest that early school age children and adults both have relatively efficient systems that may solve similar information processing problems in divergent ways. PMID:19412534

Functional brain networks develop from a "local to distributed" organization.

PubMed

Fair, Damien A; Cohen, Alexander L; Power, Jonathan D; Dosenbach, Nico U F; Church, Jessica A; Miezin, Francis M; Schlaggar, Bradley L; Petersen, Steven E

2009-05-01

The mature human brain is organized into a collection of specialized functional networks that flexibly interact to support various cognitive functions. Studies of development often attempt to identify the organizing principles that guide the maturation of these functional networks. In this report, we combine resting state functional connectivity MRI (rs-fcMRI), graph analysis, community detection, and spring-embedding visualization techniques to analyze four separate networks defined in earlier studies. As we have previously reported, we find, across development, a trend toward 'segregation' (a general decrease in correlation strength) between regions close in anatomical space and 'integration' (an increased correlation strength) between selected regions distant in space. The generalization of these earlier trends across multiple networks suggests that this is a general developmental principle for changes in functional connectivity that would extend to large-scale graph theoretic analyses of large-scale brain networks. Communities in children are predominantly arranged by anatomical proximity, while communities in adults predominantly reflect functional relationships, as defined from adult fMRI studies. In sum, over development, the organization of multiple functional networks shifts from a local anatomical emphasis in children to a more "distributed" architecture in young adults. We argue that this "local to distributed" developmental characterization has important implications for understanding the development of neural systems underlying cognition. Further, graph metrics (e.g., clustering coefficients and average path lengths) are similar in child and adult graphs, with both showing "small-world"-like properties, while community detection by modularity optimization reveals stable communities within the graphs that are clearly different between young children and young adults. These observations suggest that early school age children and adults both have relatively efficient systems that may solve similar information processing problems in divergent ways.

The anatomy of the bill tip of kiwi and associated somatosensory regions of the brain: comparisons with shorebirds.

PubMed

Cunningham, Susan J; Corfield, Jeremy R; Iwaniuk, Andrew N; Castro, Isabel; Alley, Maurice R; Birkhead, Tim R; Parsons, Stuart

2013-01-01

Three families of probe-foraging birds, Scolopacidae (sandpipers and snipes), Apterygidae (kiwi), and Threskiornithidae (ibises, including spoonbills) have independently evolved long, narrow bills containing clusters of vibration-sensitive mechanoreceptors (Herbst corpuscles) within pits in the bill-tip. These 'bill-tip organs' allow birds to detect buried or submerged prey via substrate-borne vibrations and/or interstitial pressure gradients. Shorebirds, kiwi and ibises are only distantly related, with the phylogenetic divide between kiwi and the other two taxa being particularly deep. We compared the bill-tip structure and associated somatosensory regions in the brains of kiwi and shorebirds to understand the degree of convergence of these systems between the two taxa. For comparison, we also included data from other taxa including waterfowl (Anatidae) and parrots (Psittaculidae and Cacatuidae), non-apterygid ratites, and other probe-foraging and non probe-foraging birds including non-scolopacid shorebirds (Charadriidae, Haematopodidae, Recurvirostridae and Sternidae). We show that the bill-tip organ structure was broadly similar between the Apterygidae and Scolopacidae, however some inter-specific variation was found in the number, shape and orientation of sensory pits between the two groups. Kiwi, scolopacid shorebirds, waterfowl and parrots all shared hypertrophy or near-hypertrophy of the principal sensory trigeminal nucleus. Hypertrophy of the nucleus basorostralis, however, occurred only in waterfowl, kiwi, three of the scolopacid species examined and a species of oystercatcher (Charadriiformes: Haematopodidae). Hypertrophy of the principal sensory trigeminal nucleus in kiwi, Scolopacidae, and other tactile specialists appears to have co-evolved alongside bill-tip specializations, whereas hypertrophy of nucleus basorostralis may be influenced to a greater extent by other sensory inputs. We suggest that similarities between kiwi and scolopacid bill-tip organs and associated somatosensory brain regions are likely a result of similar ecological selective pressures, with inter-specific variations reflecting finer-scale niche differentiation.

Visible rodent brain-wide networks at single-neuron resolution

PubMed Central

Yuan, Jing; Gong, Hui; Li, Anan; Li, Xiangning; Chen, Shangbin; Zeng, Shaoqun; Luo, Qingming

2015-01-01

There are some unsolvable fundamental questions, such as cell type classification, neural circuit tracing and neurovascular coupling, though great progresses are being made in neuroscience. Because of the structural features of neurons and neural circuits, the solution of these questions needs us to break through the current technology of neuroanatomy for acquiring the exactly fine morphology of neuron and vessels and tracing long-distant circuit at axonal resolution in the whole brain of mammals. Combined with fast-developing labeling techniques, efficient whole-brain optical imaging technology emerging at the right moment presents a huge potential in the structure and function research of specific-function neuron and neural circuit. In this review, we summarize brain-wide optical tomography techniques, review the progress on visible brain neuronal/vascular networks benefit from these novel techniques, and prospect the future technical development. PMID:26074784

Remote acute demyelination after focal proton radiation therapy for optic nerve meningioma.

PubMed

Redjal, Navid; Agarwalla, Pankaj K; Dietrich, Jorg; Dinevski, Nikolaj; Stemmer-Rachamimov, Anat; Nahed, Brian V; Loeffler, Jay S

2015-08-01

We present a unique patient with delayed onset, acute demyelination that occurred distant to the effective field of radiation after proton beam radiotherapy for an optic nerve sheath meningioma. The use of stereotactic radiotherapy as an effective treatment modality for some brain tumors is increasing, given technological advances which allow for improved targeting precision. Proton beam radiotherapy improves the precision further by reducing unnecessary radiation to surrounding tissues. A 42-year-old woman was diagnosed with an optic nerve sheath meningioma after initially presenting with vision loss. After biopsy of the lesion to establish diagnosis, the patient underwent stereotactic proton beam radiotherapy to a small area localized to the tumor. Subsequently, the patient developed a large enhancing mass-like lesion with edema in a region outside of the effective radiation field in the ipsilateral frontal lobe. Given imaging features suggestive of possible primary malignant brain tumor, biopsy of this new lesion was performed and revealed an acute demyelinating process. This patient illustrates the importance of considering delayed onset acute demyelination in the differential diagnosis of enhancing lesions in patients previously treated with radiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Limits on soft X-ray flux from distant emission regions

NASA Technical Reports Server (NTRS)

Burrows, D. N.; Mccammon, D.; Sanders, W. T.; Kraushaar, W. L.

1984-01-01

The all-sky soft X-ray data of McCammon et al. and the new N sub H survey (Stark et al. was used to place limits on the amount of the soft X-ray diffuse background that can originate beyond the neutral gas of the galactic disk. The X-ray data for two regions of the sky near the galactic poles are shown to be uncorrelated with 21 cm column densities. Most of the observed x-ray flux must therefore originate on the near side of the most distant neutral gas. The results from these regions are consistent with X-ray emission from a locally isotropic, unabsorbed source, but require large variations in the emission of the local region over large angular scales.

The impact of histology on recurrence patterns in esophageal cancer treated with definitive chemoradiotherapy.

PubMed

Xi, Mian; Xu, Cai; Liao, Zhongxing; Hofstetter, Wayne L; Blum Murphy, Mariela; Maru, Dipen M; Bhutani, Manoop S; Lee, Jeffrey H; Weston, Brian; Komaki, Ritsuko; Lin, Steven H

2017-08-01

To assess the impact of histology on recurrence patterns and survival outcomes in patients with esophageal cancer (EC) treated with definitive chemoradiotherapy (CRT). We analyzed 590 consecutive EC patients who received definitive CRT from 1998 to 2014, including 182 patients (30.8%) with squamous cell carcinoma (SCC) and 408 (69.2%) with adenocarcinoma. Recurrence pattern and timing, survival, and potential prognostic factors were compared. After a median follow-up time of 58.0months, the SCC group demonstrated a comparable locoregional recurrence rate (42.9% vs. 38.0%, P=0.264) but a significantly lower distant failure rate (27.5% vs. 48.0%, P<0.001) than adenocarcinoma group. No significant difference was found in overall survival or locoregional failure-free survival between groups, whereas the SCC group was associated with significantly more favorable recurrence-free survival (P=0.009) and distant metastasis-free survival (P<0.001). The adenocarcinoma group had higher hematogenous metastasis rates of bone, brain, and liver, whereas the SCC group had a marginally higher regional recurrence rate. Among patients who received salvage surgery after locoregional recurrence, no significant difference in survival was found between groups (P=0.12). The patterns and sites of recurrence, survival outcomes, and prognostic factors were significantly different between esophageal SCC and adenocarcinoma. Copyright © 2017 Elsevier B.V. All rights reserved.

Increased dopamine receptor expression and anti-depressant response following deep brain stimulation of the medial forebrain bundle.

PubMed

Dandekar, Manoj P; Luse, Dustin; Hoffmann, Carson; Cotton, Patrick; Peery, Travis; Ruiz, Christian; Hussey, Caroline; Giridharan, Vijayasree V; Soares, Jair C; Quevedo, Joao; Fenoy, Albert J

2017-08-01

Among several potential neuroanatomical targets pursued for deep brain stimulation (DBS) for treating those with treatment-resistant depression (TRD), the superolateral-branch of the medial forebrain bundle (MFB) is emerging as a privileged location. We investigated the antidepressant-like phenotypic and chemical changes associated with reward-processing dopaminergic systems in rat brains after MFB-DBS. Male Wistar rats were divided into three groups: sham-operated, DBS-Off, and DBS-On. For DBS, a concentric bipolar electrode was stereotactically implanted into the right MFB. Exploratory activity and depression-like behavior were evaluated using the open-field and forced-swimming test (FST), respectively. MFB-DBS effects on the dopaminergic system were evaluated using immunoblotting for tyrosine hydroxylase (TH), dopamine transporter (DAT), and dopamine receptors (D1-D5), and high-performance liquid chromatography for quantifying dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in brain homogenates of prefrontal cortex (PFC), hippocampus, amygdala, and nucleus accumbens (NAc). Animals receiving MFB-DBS showed a significant increase in swimming time without alterations in locomotor activity, relative to the DBS-Off (p<0.039) and sham-operated groups (p<0.014), indicating an antidepressant-like response. MFB-DBS led to a striking increase in protein levels of dopamine D2 receptors and DAT in the PFC and hippocampus, respectively. However, we did not observe appreciable differences in the expression of other dopamine receptors, TH, or in the concentrations of dopamine, DOPAC, and HVA in PFC, hippocampus, amygdala, and NAc. This study was not performed on an animal model of TRD. MFB-DBS rescues the depression-like phenotypes and selectively activates expression of dopamine receptors in brain regions distant from the target area of stimulation. Copyright © 2017. Published by Elsevier B.V.

Hypofractionated Dose-Painting Intensity Modulated Radiation Therapy With Chemotherapy for Nasopharyngeal Carcinoma: A Prospective Trial

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

Bakst, Richard L.; Lee, Nancy; Pfister, David G.

2011-05-01

Purpose: To evaluate the feasibility of dose-painting intensity-modulated radiation therapy (DP-IMRT) with a hypofractionated regimen to treat nasopharyngeal carcinoma (NPC) with concomitant toxicity reduction. Methods and Materials: From October 2002 through April 2007, 25 newly diagnosed NPC patients were enrolled in a prospective trial. DP-IMRT was prescribed to deliver 70.2 Gy using 2.34-Gy fractions to the gross tumor volume for the primary and nodal sites while simultaneously delivering 54 Gy in 1.8-Gy fractions to regions at risk of microscopic disease. Patients received concurrent and adjuvant platin-based chemotherapy similar to the Intergroup 0099 trial. Results: Patient and disease characteristics are asmore » follows: median age, 46; 44% Asian; 68% male; 76% World Health Organization III; 20% T1, 52% T2, 16% T3, 12% T4; 20% N0, 36% N1, 36% N2, 8% N3. With median follow-up of 33 months, 3-year local control was 91%, regional control was 91%, freedom from distant metastases was 91%, and overall survival was 89%. The average mean dose to each cochlea was 43 Gy. With median audiogram follow-up of 14 months, only one patient had clinically significant (Grade 3) hearing loss. Twelve percent of patients developed temporal lobe necrosis; one patient required surgical resection. Conclusions: Preliminary findings using a hypofractionated DP-IMRT regimen demonstrated that local control, freedom from distant metastases, and overall survival compared favorably with other series of IMRT and chemotherapy. The highly conformal boost to the tumor bed resulted low rates of severe ototoxicity (Grade 3-4). However, the incidence of in-field brain radiation necrosis indicates that 2.34 Gy per fraction is not safe in this setting.« less

Clinico-pathology of lung cancer in a regional cancer center in Northeastern India.

PubMed

Mandal, Sanjeet Kumar; Singh, Thaudem Tomcha; Sharma, Takhenchangbam Dhaneshor; Amrithalingam, Venkatesan

2013-01-01

Globally, there have been important changes in trends amongst gender, histology and smoking patterns of lung cancer cases. This retrospective study was conducted on 466 patients with lung cancer who were registered in Regional Cancer Center, Regional Institute of Medical Sciences, Manipur from January 2008 to December 2012. Most were more than 60 years of age (67.8%) with a male: female ratio of 1.09:1. Some 78.8% of patients were chronic smokers with male smoker to female smoker ratio of 1.43:1. Consumption of alcohol was found in 29.4%, both smoking and alcohol in 27.5%, betel nut chewing in 37.9% and tobacco chewing in 25.3%. A history of tuberculosis was present in 16.3% of patients. The most frequent symptom was coughing (36.6%) and most common radiological presentation was a mass lesion (70%). Most of the patients had primary lung cancer in the right lung (60.3%). The most common histological subtype was squamous cell carcinoma (49.1%), also in the 40-60 year age group (45.9%), more than 60 year age group (51.6%), males (58.1%) and females (41.8%). As many as 91.9% of squamous cell carcinoma patients had a history of smoking. About 32.5% of patients had distant metastasis at presentation with brain (23.8%) and positive malignant cells in pleural effusions (23.1%) as common sites. The majority of patients were in stage III (34.4%), stage IV (32.5%) and stage II (30.2%). Our analysis suggests that the gender gap has been narrowed such that about half of the patients diagnosed with lung cancer are women in this part of India. This alarming rise in female incidence is mainly attributed to an increased smoking pattern. Squamous cell carcinoma still remains the commonest histological subtype. Most of the patients were elderly aged and presented at locally or distantly advanced stages.

Patterns of failure after involved field radiotherapy for locally advanced esophageal squamous cell carcinoma.

PubMed

Li, Duo-Jie; Li, Hong-Wei; He, Bin; Wang, Geng-Ming; Cai, Han-Fei; Duan, Shi-Miao; Liu, Jing-Jing; Zhang, Ya-Jun; Cui, Zhen; Jiang, Hao

2016-01-01

To retrospectively analyze the patterns of failure and the treatment effects of involved-field irradiation (IFI) on patients treated with locally advanced esophageal squamous cell carcinoma (ESCC) and to determine whether IFI is practicable in these patients. A total of 79 patients with locally advanced ESCC underwent three dimensional conformal (3D)CRT) or intensity modulated radiotherapy (IMRT) using IFI or elective nodal irradiation (ENI) according to the target volume. The patterns of failure were defined as local/regional, in-field, out)of)field regional lymph node (LN) and distant failure. With a median follow)up of 32.0 months, failures were observed in 66 (83.6%) patients. The cumulative incidence of local/regional failure (55.8 vs 52.8%) and in)field regional lymph node failure (25.6 vs 19.4%) showed no statistically significant difference between the IFI and the ENI group (p=0.526 and 0.215, respectively). Out)of)field nodal relapse rate of only 7.0% was seen in the IFI group. Three)year survival rates for the ENI and IFI group were 22.2 and 18.6%, respectively (p=0.240), and 3)year distant metastasis rates were 27.8 and 32.6%, respectively (p=0.180). The lung V10, V20, V30 and mean lung dose of the ENI group were greater than those of the IFI group, while the mean lung dose and V10 had statistically significant difference. The patterns of failure and survival rates in the IFI group were similar as in the ENI group; the regional recurrence and distant metastasis are the main cause of treatment failure. IFI is feasible for locally advanced ESCC. Further investigation is needed to increase local control and decrease distant metastasis in these patients.

Stress Can Be a Good Thing for Blood Formation.

PubMed

Speck, Nancy A

2016-09-01

Like politics, most developmental signals are local. However, in this issue of Cell Stem Cell, Kwan et al. (2016) and colleagues describe how a stress-induced signal that originates in the zebrafish brain promotes the formation of blood at a distant site, the dorsal aorta. Copyright © 2016 Elsevier Inc. All rights reserved.

Regional traumatic limb hypothermia attenuates distant hepatic and renal injury following blast limb trauma in rats.

PubMed

Zhao, Hongzhi; Ning, Jiaolin; Duan, Jiaxiang; Gu, Jianteng; Yi, Bin; Lu, Kaizhi; Mo, Liwen; Lai, Xinan; Hennah, Lindsay; Ma, Daqing

2014-09-01

Blast limb injury was reported to result in distant organ injury including the lungs, which can be attenuated with transient regional hypothermia (RH) to the injured limb. We aimed to further study hepatic and renal injuries following blast limb trauma and also to evaluate the protective effects of regional traumatic limb hypothermia on such injuries in rats. Blast limb trauma (BLT) was created using chartaceous electricity detonators in anesthetized male Sprague-Dawley rats. The BLT rats were randomly allocated to undergo regional traumatic limb hypothermic treatment (RH) for 30 minutes, 60 minutes, or 6 hours immediately after the onset of blast or without RH (n = 8 per group). The severity of hepatic and renal injury was assessed through histologic examination and water content (wet/dry weight) in all animals 6 hours later. The level of plasma tumor necrosis factor α (TNF-α), interleukin 6, hydrogen sulfide (H2S), and myeloperoxidase (MPO) together with hepatic and renal MPO, malondialdehyde (MDA), superoxide dismutase, and total antioxidant capacity were measured 6 hours after the blast injury. Following BLT, hepatic injury was evidenced by histopathologic changes, increased water content, as well as plasma alanine aminotransferase and aspartate aminotransferase. Renal histopathologic but not functional changes were also found. RH treatment for all durations attenuated this distant renal injury, but only RH treatment for 60 minutes and 6 hours attenuated distant hepatic injury following BLT. RH treatment for all durations decreased plasma TNF-α and interleukin 6, reduced liver and kidney MPO activity and kidney MDA, and elevated superoxide dismutase and total antioxidant capacity in both liver and kidneys. RH treatment for 60 minutes is the most effective duration to reduce hepatic MPO activity, plasma TNF-α, and kidney MDA. This study indicates that BLT-induced distant renal and hepatic injury could be attenuated by RH treatment through reduction of cytokine release and inhibition of neutrophil accumulation and oxidative stress.

Propagation of Aß pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies.

PubMed

Eisele, Yvonne S; Duyckaerts, Charles

2016-01-01

In brains of patients with Alzheimer's disease (AD), Aβ peptides accumulate in parenchyma and, almost invariably, also in the vascular walls. Although Aβ aggregation is, by definition, present in AD, its impact is only incompletely understood. It occurs in a stereotypical spatiotemporal distribution within neuronal networks in the course of the disease. This suggests a role for synaptic connections in propagating Aβ pathology, and possibly of axonal transport in an antero- or retrograde way-although, there is also evidence for passive, extracellular diffusion. Striking, in AD, is the conjunction of tau and Aβ pathology. Tau pathology in the cell body of neurons precedes Aβ deposition in their synaptic endings in several circuits such as the entorhino-dentate, cortico-striatal or subiculo-mammillary connections. However, genetic evidence suggests that Aβ accumulation is the first step in AD pathogenesis. To model the complexity and consequences of Aβ aggregation in vivo, various transgenic (tg) rodents have been generated. In rodents tg for the human Aβ precursor protein, focal injections of preformed Aβ aggregates can induce Aβ deposits in the vicinity of the injection site, and over time in more distant regions of the brain. This suggests that Aβ shares with α-synuclein, tau and other proteins the property to misfold and aggregate homotypic molecules. We propose to group those proteins under the term "propagons". Propagons may lack the infectivity of prions. We review findings from neuropathological examinations of human brains in different stages of AD and from studies in rodent models of Aβ aggregation and discuss putative mechanisms underlying the initiation and spread of Aβ pathology.

Spatial distribution and cellular composition of adult brain proliferative zones in the teleost, Gymnotus omarorum

PubMed Central

Olivera-Pasilio, Valentina; Peterson, Daniel A.; Castelló, María E.

2014-01-01

Proliferation of stem/progenitor cells during development provides for the generation of mature cell types in the CNS. While adult brain proliferation is highly restricted in the mammals, it is widespread in teleosts. The extent of adult neural proliferation in the weakly electric fish, Gymnotus omarorum has not yet been described. To address this, we used double thymidine analog pulse-chase labeling of proliferating cells to identify brain proliferation zones, characterize their cellular composition, and analyze the fate of newborn cells in adult G. omarorum. Short thymidine analog chase periods revealed the ubiquitous distribution of adult brain proliferation, similar to other teleosts, particularly Apteronotus leptorhynchus. Proliferating cells were abundant at the ventricular-subventricular lining of the ventricular-cisternal system, adjacent to the telencephalic subpallium, the diencephalic preoptic region and hypothalamus, and the mesencephalic tectum opticum and torus semicircularis. Extraventricular proliferation zones, located distant from the ventricular-cisternal system surface, were found in all divisions of the rombencephalic cerebellum. We also report a new adult proliferation zone at the caudal-lateral border of the electrosensory lateral line lobe. All proliferation zones showed a heterogeneous cellular composition. The use of short (24 h) and long (30 day) chase periods revealed abundant fast cycling cells (potentially intermediate amplifiers), sparse slow cycling (potentially stem) cells, cells that appear to have entered a quiescent state, and cells that might correspond to migrating newborn neural cells. Their abundance and migration distance differed among proliferation zones: greater numbers and longer range and/or pace of migrating cells were associated with subpallial and cerebellar proliferation zones. PMID:25249943

Signal propagation along the axon.

PubMed

Rama, Sylvain; Zbili, Mickaël; Debanne, Dominique

2018-03-08

Axons link distant brain regions and are usually considered as simple transmission cables in which reliable propagation occurs once an action potential has been generated. Safe propagation of action potentials relies on specific ion channel expression at strategic points of the axon such as nodes of Ranvier or axonal branch points. However, while action potentials are generally considered as the quantum of neuronal information, their signaling is not entirely digital. In fact, both their shape and their conduction speed have been shown to be modulated by activity, leading to regulations of synaptic latency and synaptic strength. We report here newly identified mechanisms of (1) safe spike propagation along the axon, (2) compartmentalization of action potential shape in the axon, (3) analog modulation of spike-evoked synaptic transmission and (4) alteration in conduction time after persistent regulation of axon morphology in central neurons. We discuss the contribution of these regulations in information processing. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evolution and development of brain networks: from Caenorhabditis elegans to Homo sapiens.

PubMed

Kaiser, Marcus; Varier, Sreedevi

2011-01-01

Neural networks show a progressive increase in complexity during the time course of evolution. From diffuse nerve nets in Cnidaria to modular, hierarchical systems in macaque and humans, there is a gradual shift from simple processes involving a limited amount of tasks and modalities to complex functional and behavioral processing integrating different kinds of information from highly specialized tissue. However, studies in a range of species suggest that fundamental similarities, in spatial and topological features as well as in developmental mechanisms for network formation, are retained across evolution. 'Small-world' topology and highly connected regions (hubs) are prevalent across the evolutionary scale, ensuring efficient processing and resilience to internal (e.g. lesions) and external (e.g. environment) changes. Furthermore, in most species, even the establishment of hubs, long-range connections linking distant components, and a modular organization, relies on similar mechanisms. In conclusion, evolutionary divergence leads to greater complexity while following essential developmental constraints.

Role of inhibitory control in modulating focal seizure spread.

PubMed

Liou, Jyun-You; Ma, Hongtao; Wenzel, Michael; Zhao, Mingrui; Baird-Daniel, Eliza; Smith, Elliot H; Daniel, Andy; Emerson, Ronald; Yuste, Rafael; Schwartz, Theodore H; Schevon, Catherine A

2018-05-10

Focal seizure propagation is classically thought to be spatially contiguous. However, distribution of seizures through a large-scale epileptic network has been theorized. Here, we used a multielectrode array, wide field calcium imaging, and two-photon calcium imaging to study focal seizure propagation pathways in an acute rodent neocortical 4-aminopyridine model. Although ictal neuronal bursts did not propagate beyond a 2-3-mm region, they were associated with hemisphere-wide field potential fluctuations and parvalbumin-positive interneuron activity outside the seizure focus. While bicuculline surface application enhanced contiguous seizure propagation, focal bicuculline microinjection at sites distant to the 4-aminopyridine focus resulted in epileptic network formation with maximal activity at the two foci. Our study suggests that both classical and epileptic network propagation can arise from localized inhibition defects, and that the network appearance can arise in the context of normal brain structure without requirement for pathological connectivity changes between sites.

Zic-Proteins Are Repressors of Dopaminergic Forebrain Fate in Mice and C. elegans.

PubMed

Tiveron, Marie-Catherine; Beclin, Christophe; Murgan, Sabrina; Wild, Stefan; Angelova, Alexandra; Marc, Julie; Coré, Nathalie; de Chevigny, Antoine; Herrera, Eloisa; Bosio, Andreas; Bertrand, Vincent; Cremer, Harold

2017-11-01

In the postnatal forebrain regionalized neural stem cells along the ventricular walls produce olfactory bulb (OB) interneurons with varying neurotransmitter phenotypes and positions. To understand the molecular basis of this region-specific variability we analyzed gene expression in the postnatal dorsal and lateral lineages in mice of both sexes from stem cells to neurons. We show that both lineages maintain transcription factor signatures of their embryonic site of origin, the pallium and subpallium. However, additional factors, including Zic1 and Zic2, are postnatally expressed in the dorsal stem cell compartment and maintained in the lineage that generates calretinin-positive GABAergic neurons for the OB. Functionally, we show that Zic1 and Zic2 induce the generation of calretinin-positive neurons while suppressing dopaminergic fate in the postnatal dorsal lineage. We investigated the evolutionary conservation of the dopaminergic repressor function of Zic proteins and show that it is already present in C. elegans SIGNIFICANCE STATEMENT The vertebrate brain generates thousands of different neuron types. In this work we investigate the molecular mechanisms underlying this variability. Using a genomics approach we identify the transcription factor signatures of defined neural stem cells and neuron populations. Based thereon we show that two related transcription factors, Zic1 and Zic2, are essential to control the balance between two defined neuron types in the postnatal brain. We show that this mechanism is conserved in evolutionary very distant species. Copyright © 2017 the authors 0270-6474/17/3710611-13$15.00/0.

Brain Metastasis Velocity: A Novel Prognostic Metric Predictive of Overall Survival and Freedom From Whole-Brain Radiation Therapy After Distant Brain Failure Following Upfront Radiosurgery Alone

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

Farris, Michael, E-mail: mfarris@wakehealth.edu; McTyre, Emory R.; Cramer, Christina K.

Purpose: Prior statistical models attempted to identify risk factors for time to distant brain failure (DBF) or time to salvage whole-brain radiation therapy (WBRT) to predict the benefit of early WBRT versus stereotactic radiosurgery (SRS) alone. We introduce a novel clinical metric, brain metastasis velocity (BMV), for predicting clinical outcomes after initial DBF following upfront SRS alone. Methods and Materials: BMV was defined as the cumulative number of new brain metastases that developed over time since first SRS in years. Patients were classified by BMV into low-, intermediate-, and high-risk groups, consisting of <4, 4 to 13, and >13 newmore » metastases per year, respectively. Histology, number of metastases at the time of first SRS, and systemic disease status were assessed for effect on BMV. Results: Of 737 patients treated at our institution with upfront SRS without WBRT, 286 had ≥1 DBF event. A lower BMV predicted for improved overall survival (OS) following initial DBF (log-rank P<.0001). Median OS for the low, intermediate, and high BMV groups was 12.4 months (95% confidence interval [CI], 10.4-16.9 months), 8.2 months (95% CI, 5.0-9.7 months), and 4.3 months (95% CI, 2.6-6.7 months), respectively. Multivariate analysis showed that BMV remained the dominant predictor of OS, with a hazard ratio of 2.75 for the high BMV group (95% CI, 1.94-3.89; P<.0001) and a hazard ratio of 1.65 for the intermediate BMV group (95% CI, 1.18-2.30; P<.004). A lower BMV was associated with decreased rates of salvage WBRT (P=.02) and neurologic death (P=.008). Factors predictive for a higher BMV included ≥2 initial brain metastases (P=.004) and melanoma histology (P=.008). Conclusions: BMV is a novel metric associated with OS, neurologic death, and need for salvage WBRT after initial DBF following upfront SRS alone.« less

External Validity of a Risk Stratification Score Predicting Early Distant Brain Failure and Salvage Whole Brain Radiation Therapy After Stereotactic Radiosurgery for Brain Metastases.

PubMed

Press, Robert H; Boselli, Danielle M; Symanowski, James T; Lankford, Scott P; McCammon, Robert J; Moeller, Benjamin J; Heinzerling, John H; Fasola, Carolina E; Burri, Stuart H; Patel, Kirtesh R; Asher, Anthony L; Sumrall, Ashley L; Curran, Walter J; Shu, Hui-Kuo G; Crocker, Ian R; Prabhu, Roshan S

2017-07-01

A scoring system using pretreatment factors was recently published for predicting the risk of early (≤6 months) distant brain failure (DBF) and salvage whole brain radiation therapy (WBRT) after stereotactic radiosurgery (SRS) alone. Four risk factors were identified: (1) lack of prior WBRT; (2) melanoma or breast histologic features; (3) multiple brain metastases; and (4) total volume of brain metastases <1.3 cm 3 , with each factor assigned 1 point. The purpose of this study was to assess the validity of this scoring system and its appropriateness for clinical use in an independent external patient population. We reviewed the records of 247 patients with 388 brain metastases treated with SRS between 2010 at 2013 at Levine Cancer Institute. The Press (Emory) risk score was calculated and applied to the validation cohort population, and subsequent risk groups were analyzed using cumulative incidence. The low-risk (LR) group had a significantly lower risk of early DBF than did the high-risk (HR) group (22.6% vs 44%, P=.004), but there was no difference between the HR and intermediate-risk (IR) groups (41.2% vs 44%, P=.79). Total lesion volume <1.3 cm 3  (P=.004), malignant melanoma (P=.007), and multiple metastases (P<.001) were validated as predictors for early DBF. Prior WBRT and breast cancer histologic features did not retain prognostic significance. Risk stratification for risk of early salvage WBRT were similar, with a trend toward an increased risk for HR compared with LR (P=.09) but no difference between IR and HR (P=.53). The 3-level Emory risk score was shown to not be externally valid, but the model was able to stratify between 2 levels (LR and not-LR [combined IR and HR]) for early (≤6 months) DBF. These results reinforce the importance of validating predictive models in independent cohorts. Further refinement of this scoring system with molecular information and in additional contemporary patient populations is warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

Low rates of loco-regional recurrence following extended lymph node dissection for gastric cancer.

PubMed

Muratore, A; Zimmitti, G; Lo Tesoriere, R; Mellano, A; Massucco, P; Capussotti, L

2009-06-01

The study by MacDonald et al. [Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725-30] has reported low loco-regional recurrence rates (19%) after gastric cancer resection and adjuvant radiotherapy. However, the lymph node dissection was often "inadequate". The aim of this retrospective study is to analyse if an extended lymph node dissection (D2) without adjuvant radiotherapy may achieve comparable loco-regional recurrence rates. A prospective database of 200 patients who underwent a curative resection for gastric carcinoma from January 2000 to December 2006 was analysed. D2 lymph node dissection was standard. Recurrences were categorized as loco-regional, peritoneal, or distant. No patients received neoadjuvant or adjuvant radiotherapy. The in-hospital mortality rate was 1% (2 patients). The mean number of dissected lymph nodes was 25.9. Overall and disease-free survival at 5years were 60.7% and 61.2% respectively. During the follow-up, 60 patients (30%) have recurred at 76 sites: 38 (50%) distant metastases, 25 (32.9%) peritoneal metastases, and 13 (17.1%) loco-regional recurrences. The loco-regional recurrence was isolated in 6 patients and associated with peritoneal or distant metastases in 7 patients. The mean time to the first recurrence was 18.9 (95% confidence interval: 15.0-21.9) months. Extended lymph node dissection is safe and warrants low loco-regional recurrence rates.

Characterization of Streptococcus constellatus strains recovered from a brain abscess and periodontal pockets in an immunocompromised patient.

PubMed

Marques da Silva, Rafael; Caugant, Dominique A; Josefsen, Roger; Tronstad, Leif; Olsen, Ingar

2004-12-01

There have been a number of reports of brain abscesses suggesting an odontogenic etiology. However, no efforts have been made to compare brain abscess isolates with isolates from the oral cavity using highly discriminative methods. We report a brain abscess caused by Streptococcus constellatus in an immunocompromised patient where oral infection (periodontitis) was suspected to be implicated. The brain abscess and oral isolates were compared by means of one phenotypic and three genetic (restriction fragment length polymorphism [RFLP], ribotyping, and random amplified polymorphic DNA [RAPD]) fingerprinting techniques. The phenotypic method and RFLP showed identical profiles between brain and periodontal isolates, while ribotyping and RAPD showed very close similarity, with only one band difference in one of the three ribotypes and in one of the three polymorphic RAPD. Gene transfer by genetic recombinational events in the periodontal pocket might have been responsible for the emergence of a strain variant of S. constellatus that had the potential to cause an abscess at a distant site (brain). The importance of odontogenic sources as potential foci of infection for brain abscesses is discussed.

Machine-learning in grading of gliomas based on multi-parametric magnetic resonance imaging at 3T.

PubMed

Citak-Er, Fusun; Firat, Zeynep; Kovanlikaya, Ilhami; Ture, Ugur; Ozturk-Isik, Esin

2018-06-15

The objective of this study was to assess the contribution of multi-parametric (mp) magnetic resonance imaging (MRI) quantitative features in the machine learning-based grading of gliomas with a multi-region-of-interests approach. Forty-three patients who were newly diagnosed as having a glioma were included in this study. The patients were scanned prior to any therapy using a standard brain tumor magnetic resonance (MR) imaging protocol that included T1 and T2-weighted, diffusion-weighted, diffusion tensor, MR perfusion and MR spectroscopic imaging. Three different regions-of-interest were drawn for each subject to encompass tumor, immediate tumor periphery, and distant peritumoral edema/normal. The normalized mp-MRI features were used to build machine-learning models for differentiating low-grade gliomas (WHO grades I and II) from high grades (WHO grades III and IV). In order to assess the contribution of regional mp-MRI quantitative features to the classification models, a support vector machine-based recursive feature elimination method was applied prior to classification. A machine-learning model based on support vector machine algorithm with linear kernel achieved an accuracy of 93.0%, a specificity of 86.7%, and a sensitivity of 96.4% for the grading of gliomas using ten-fold cross validation based on the proposed subset of the mp-MRI features. In this study, machine-learning based on multiregional and multi-parametric MRI data has proven to be an important tool in grading glial tumors accurately even in this limited patient population. Future studies are needed to investigate the use of machine learning algorithms for brain tumor classification in a larger patient cohort. Copyright © 2018. Published by Elsevier Ltd.

Finding Distant Galactic HII Regions

NASA Astrophysics Data System (ADS)

Anderson, L. D.; Armentrout, W. P.; Johnstone, B. M.; Bania, T. M.; Balser, Dana S.; Wenger, Trey V.; Cunningham, V.

2015-12-01

The WISE Catalog of Galactic H ii Regions contains ˜2000 H ii region candidates lacking ionized gas spectroscopic observations. All candidates have the characteristic H ii region mid-infrared morphology of WISE 12 μ {{m}} emission surrounding 22 μ {{m}} emission, and additionally have detected radio continuum emission. We here report Green Bank Telescope hydrogen radio recombination line and radio continuum detections in the X-band (9 GHz; 3 cm) of 302 WISE H ii region candidates (out of 324 targets observed) in the zone 225^\\circ ≥slant {\\ell }≥slant -20^\\circ , | {\\text{}}b| ≤slant 6^\\circ . Here we extend the sky coverage of our H ii region Discovery Survey, which now contains nearly 800 H ii regions distributed across the entire northern sky. We provide LSR velocities for the 302 detections and kinematic distances for 131 of these. Of the 302 new detections, 5 have ({\\ell },{\\text{}}b,v) coordinates consistent with the Outer Scutum-Centaurus Arm (OSC), the most distant molecular spiral arm of the Milky Way. Due to the Galactic warp, these nebulae are found at Galactic latitudes >1° in the first Galactic quadrant, and therefore were missed in previous surveys of the Galactic plane. One additional region has a longitude and velocity consistent with the OSC but lies at a negative Galactic latitude (G039.183-01.422 -54.9 {km} {{{s}}}-1). With Heliocentric distances >22 kpc and Galactocentric distances >16 kpc, the OSC H ii regions are the most distant known in the Galaxy. We detect an additional three H ii regions near {\\ell }≃ 150^\\circ whose LSR velocities place them at Galactocentric radii >19 kpc. If their distances are correct, these nebulae may represent the limit to Galactic massive star formation.

Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis.

PubMed

McDonald, Oliver G; Li, Xin; Saunders, Tyler; Tryggvadottir, Rakel; Mentch, Samantha J; Warmoes, Marc O; Word, Anna E; Carrer, Alessandro; Salz, Tal H; Natsume, Sonoko; Stauffer, Kimberly M; Makohon-Moore, Alvin; Zhong, Yi; Wu, Hao; Wellen, Kathryn E; Locasale, Jason W; Iacobuzio-Donahue, Christine A; Feinberg, Andrew P

2017-03-01

During the progression of pancreatic ductal adenocarcinoma (PDAC), heterogeneous subclonal populations emerge that drive primary tumor growth, regional spread, distant metastasis, and patient death. However, the genetics of metastases largely reflects that of the primary tumor in untreated patients, and PDAC driver mutations are shared by all subclones. This raises the possibility that an epigenetic process might operate during metastasis. Here we report large-scale reprogramming of chromatin modifications during the natural evolution of distant metastasis. Changes were targeted to thousands of large chromatin domains across the genome that collectively specified malignant traits, including euchromatin and large organized chromatin histone H3 lysine 9 (H3K9)-modified (LOCK) heterochromatin. Remarkably, distant metastases co-evolved a dependence on the oxidative branch of the pentose phosphate pathway (oxPPP), and oxPPP inhibition selectively reversed reprogrammed chromatin, malignant gene expression programs, and tumorigenesis. These findings suggest a model whereby linked metabolic-epigenetic programs are selected for enhanced tumorigenic fitness during the evolution of distant metastasis.

Pattern of distant extrahepatic metastases in primary liver cancer: a SEER based study.

PubMed

Wu, Wenrui; He, Xingkang; Andayani, Dewi; Yang, Liya; Ye, Jianzhong; Li, Yating; Chen, Yanfei; Li, Lanjuan

2017-01-01

Background and Aims : Primary liver cancer remains still the common cause of cancer-related deaths globally and the prognosis for patients with extrahepatic metastasis is poor. The aim of our study was to assess extrahepatic metastatic pattern of different histological subtypes and evaluate prognostic effects of extrahepatic metastasis in patients with advanced disease. Methods: Based on the Surveillance, Epidemiology and End Results (SEER) database, eligible patients diagnosed with primary liver cancer was identified between 2010 to 2012. We adopted Chi-square test to compared metastasis distribution among different histological types. We compared survival difference of patients with different extrahepatic metastasises by Kaplan-Meier analysis. Cox proportional hazard models were performed to identify other prognostic factors of overall survival. Results: We finally identified 8677 patients who were diagnosed with primary liver cancer from 2010 to 2012 and 1775 patients were in distant metastasis stages. Intrahepatic cholangiocarcinoma was more invasive and had a higher percentage of metastasis compared with hepatocellular carcinoma. Lung was the most common metastasis and brain was the least common site for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Extrahepatic metastasis could consider as an independent prognostic factor for patients with liver cancer. Patients with brain metastasis had the worst prognosis, compared with other metastasis in overall survival (OS) and cancer-specific survival (CSS) analysis. Conclusions: Different histological subtypes of liver cancer had different metastasis patterns. There were profound differences in risk of mortality among distant extrahepatic metastatic sites. Results from our studies would provide some information for follow-up strategies and future studies.

Nodal Lymphangiogenesis and Metastasis

PubMed Central

Hirakawa, Satoshi; Detmar, Michael; Kerjaschki, Dontscho; Nagamatsu, Shogo; Matsuo, Keitaro; Tanemura, Atsushi; Kamata, Nobuyuki; Higashikawa, Koichiro; Okazaki, Hidenori; Kameda, Kenji; Nishida-Fukuda, Hisayo; Mori, Hideki; Hanakawa, Yasushi; Sayama, Koji; Shirakata, Yuji; Tohyama, Mikiko; Tokumaru, Sho; Katayama, Ichiro; Hashimoto, Koji

2009-01-01

Nodal lymphangiogenesis promotes distant lymph node (LN) metastasis in experimental cancer models. However, the role of nodal lymphangiogenesis in distant metastasis and in the overall survival of cancer patients remains unknown. Therefore, we investigated mechanisms that might facilitate regional and distant LN metastasis in extramammary Paget’s disease (EMPD). We retrospectively analyzed the impact of tumor-induced lymphatic vessel activation on the survival of 116 patients, the largest cohort with EMPD studied to date. Nodal lymphangiogenesis was significantly increased in metastatic, compared with tumor-free, LNs (P = 0.022). Increased lymphatic invasion within regional LNs was significantly associated with distant metastasis in LN (P = 0.047) and organs (P = 0.003). Thus, invasion within regional LNs is a powerful indicator of systemic tumor spread and reduced patient survival in EMPD (P = 0.0004). Lymphatic vessels associated with tumors expressed stromal cell-derived factor-1 (SDF-1), whereas CXCR4 was expressed on invasive Paget cells undergoing epithelial-mesenchymal transition (EMT)-like process. A431 cells overexpressing Snail expressed increased levels of CXCR4 in the presence of transforming growth factor-β1. Haptotactic migration assays confirmed that Snail-induced EMT-like process promotes tumor cell motility via the CXCR4-SDF-1 axis. Sinusoidal lymphatic endothelial cells and macrophages expressed SDF-1 in subcapsular sinuses of lymph nodes before Paget cell arrival. Our findings reveal that EMT-related features likely promote lymphatic metastasis of EMPD by activating the CXCR4-SDF-1 axis. PMID:19815713

Thunderstorms observed by radio astronomy Explorer 1 over regions of low man made noise

NASA Technical Reports Server (NTRS)

Caruso, J. A.; Herman, J. R.

1974-01-01

Radio Astronomy Explorer (RAE) I observations of thunderstorms over regions of low man-made noise levels are analyzed to assess the satellite's capability for noise source differentiation. The investigation of storms over Australia indicates that RAE can resolve noise generation due to thunderstorms from the general noise background over areas of low man-made noise activity. Noise temperatures observed by RAE over stormy regions are on the average 10DB higher than noise temperatures over the same regions in the absence of thunderstorms. In order to determine the extent of noise contamination due to distant transmitters comprehensive three dimensional computer ray tracings were generated. The results indicate that generally, distant transmitters contribute negligibly to the total noise power, being 30DB or more below contributions arriving from an area immediately below the satellite.

Management of Mediastinal Relapse after Treatment with Stereotactic Body Radiotherapy or Accelerated Hypofractionated Radiotherapy for Stage I/II Non–Small-Cell Lung Cancer

PubMed Central

Kilburn, Jeremy M.; Lester, Scott C.; Lucas, John T.; Soike, Michael H.; Blackstock, A. William; Kearns, William T.; Hinson, William H.; Miller, Antonius A.; Petty, William J.; Munley, Michael T.; Urbanic, James J.

2014-01-01

Purpose/Objective(s) Regional failures occur in up to 15% of patients treated with stereotactic body radiotherapy (SBRT) for stage I/II lung cancer. This report focuses on the management of the unique scenario of isolated regional failures. Methods Patients treated initially with SBRT or accelerated hypo-fractionated radiotherapy were screened for curative intent treatment of isolated mediastinal failures (IMFs). Local control, regional control, progression-free survival, and distant control were estimated from the date of salvage treatment using the Kaplan–Meier method. Results Among 160 patients treated from 2002 to 2012, 12 suffered IMF and were amenable to salvage treatment. The median interval between treatments was 16 months (2–57 mo). Median salvage dose was 66 Gy (60–70 Gy). With a median follow-up of 10 months, the median overall survival was 15 months (95% confidence interval, 5.8–37 mo). When estimated from original treatment, the median overall survival was 38 months (95% confidence interval, 17–71 mo). No subsequent regional failures occurred. Distant failure was the predominant mode of relapse following salvage for IMF with a 2-year distant control rate of 38%. At the time of this analysis, three patients have died without recurrence while four are alive and no evidence of disease. High-grade toxicity was uncommon. Conclusions To our knowledge, this is first analysis of salvage mediastinal radiation after SBRT or accelerated hypofractionated radiotherapy in lung cancer. Outcomes appear similar to stage III disease at presentation. Distant failures were common, suggesting a role for concurrent or sequential chemotherapy. A standard full course of external beam radiotherapy is advisable in this unique clinical scenario. PMID:24736084

Spatiotemporal relations of primary sensorimotor and secondary motor activation patterns mapped by NIR imaging

PubMed Central

Khan, Bilal; Chand, Pankaj; Alexandrakis, George

2011-01-01

Functional near infrared (fNIR) imaging was used to identify spatiotemporal relations between spatially distinct cortical regions activated during various hand and arm motion protocols. Imaging was performed over a field of view (FOV, 12 x 8.4 cm) including the secondary motor, primary sensorimotor, and the posterior parietal cortices over a single brain hemisphere. This is a more extended FOV than typically used in current fNIR studies. Three subjects performed four motor tasks that induced activation over this extended FOV. The tasks included card flipping (pronation and supination) that, to our knowledge, has not been performed in previous functional magnetic resonance imaging (fMRI) or fNIR studies. An earlier rise and a longer duration of the hemodynamic activation response were found in tasks requiring increased physical or mental effort. Additionally, analysis of activation images by cluster component analysis (CCA) demonstrated that cortical regions can be grouped into clusters, which can be adjacent or distant from each other, that have similar temporal activation patterns depending on whether the performed motor task is guided by visual or tactile feedback. These analyses highlight the future potential of fNIR imaging to tackle clinically relevant questions regarding the spatiotemporal relations between different sensorimotor cortex regions, e.g. ones involved in the rehabilitation response to motor impairments. PMID:22162826

Cognitive control during audiovisual working memory engages frontotemporal theta-band interactions.

PubMed

Daume, Jonathan; Graetz, Sebastian; Gruber, Thomas; Engel, Andreas K; Friese, Uwe

2017-10-03

Working memory (WM) maintenance of sensory information has been associated with enhanced cross-frequency coupling between the phase of low frequencies and the amplitude of high frequencies, particularly in medial temporal lobe (MTL) regions. It has been suggested that these WM maintenance processes are controlled by areas of the prefrontal cortex (PFC) via frontotemporal phase synchronisation in low frequency bands. Here, we investigated whether enhanced cognitive control during audiovisual WM as compared to visual WM alone is associated with increased low-frequency phase synchronisation between sensory areas maintaining WM content and areas from PFC. Using magnetoencephalography, we recorded neural oscillatory activity from healthy human participants engaged in an audiovisual delayed-match-to-sample task. We observed that regions from MTL, which showed enhanced theta-beta phase-amplitude coupling (PAC) during the WM delay window, exhibited stronger phase synchronisation within the theta-band (4-7 Hz) to areas from lateral PFC during audiovisual WM as compared to visual WM alone. Moreover, MTL areas also showed enhanced phase synchronisation to temporooccipital areas in the beta-band (20-32 Hz). Our results provide further evidence that a combination of long-range phase synchronisation and local PAC might constitute a mechanism for neuronal communication between distant brain regions and across frequencies during WM maintenance.

The role of tropical cyclones in precipitation over the tropical and subtropical North America

NASA Astrophysics Data System (ADS)

Dominguez, Christian; Magaña, Victor

2018-03-01

Tropical cyclones (TCs) are essential elements of the hydrological cycle in tropical and subtropical regions. In the present study, the contribution of TCs to seasonal precipitation around the tropical and subtropical North America is examined. When TC activity over the tropical eastern Pacific (TEP) or the Intra Americas Seas (IAS) is below (above-normal), regional precipitation may be below (above-normal). However, it is not only the number of TCs what may change seasonal precipitation, but the trajectory of the systems. TCs induce intense precipitation over continental regions if they are close enough to shorelines, for instance, if the TC center is located, on average, less than 500 km-distant from the coast. However, if TCs are more remote than this threshold distance, the chances of rain over continental regions decrease, particularly in arid and semi-arid regions. In addition, a distant TC may induce subsidence or produce moisture divergence that inhibits, at least for a few days, convective activity farther away than the threshold distance. An analysis of interannual variability in the TCs that produce precipitation over the tropical and subtropical North America shows that some regions in northern Mexico, which mostly depend on this effect to undergo wet years, may experience seasonal negative anomalies in precipitation if TCs trajectories are remote. Therefore, TCs (activity and trajectories) are important modulators of climate variability on various time scales, either by producing intense rainfall or by inhibiting convection at distant regions from their trajectory. The impact of such variations on water availability in northern Mexico may be relevant, since water availability in dams recovers under the effects of TC rainfall. Seasonal precipitation forecasts or climate change scenarios for these regions should take into account the effect of TCs, if regional adaptation strategies are implemented.

Assessing the clinical outcome of Vim radiosurgery with voxel-based morphometry: visual areas are linked with tremor arrest!

PubMed

Tuleasca, Constantin; Witjas, Tatiana; Najdenovska, Elena; Verger, Antoine; Girard, Nadine; Champoudry, Jerome; Thiran, Jean-Philippe; Van de Ville, Dimitri; Cuadra, Meritxell Bach; Levivier, Marc; Guedj, Eric; Régis, Jean

2017-11-01

Radiosurgery (RS) is an alternative to open standard stereotactic procedures (deep-brain stimulation or radiofrequency thalamotomy) for drug-resistant essential tremor (ET), aiming at the same target (ventro-intermediate nucleus, Vim). We investigated the Vim RS outcome using voxel-based morphometry by evaluating the interaction between clinical response and time. Thirty-eight patients with right-sided ET benefited from left unilateral Vim RS. Targeting was performed using 130 Gy and a single 4-mm collimator. Neurological and neuroimaging assessment was completed at baseline and 1 year. Clinical responders were considered those with at least 50% improvement in tremor score on the treated hand (TSTH). Interaction between clinical response and time showed the left temporal pole and occipital cortex (Brodmann area 19, including V4, V5 and the parahippocampal place area) as statistically significant. A decrease in gray matter density (GMD) 1 year after Vim RS correlated with higher TSTH improvement (Spearman = 0.01) for both anatomical areas. Higher baseline GMD within the left temporal pole correlated with better TSTH improvement (Spearman = 0.004). Statistically significant structural changes in the relationship to clinical response after Vim RS are present in remote areas, advocating a distant neurobiological effect. The former regions are mainly involved in locomotor monitoring toward the local and distant environment, suggesting the recruiting requirement in targeting of the specific visuomotor networks.

Stellar Population and Star Formation History of the Distant Galactic H II Regions NGC 2282 and Sh2-149

NASA Astrophysics Data System (ADS)

Dutta, S.; Mondal, S.; Jose, J.; Das, R. K.

2017-06-01

We present here the recent results on two distant Galactic H II regions, namely NGC 2282 and Sh2-149, obtained with multiwavelength observations. Our optical spectroscopic analysis of the bright sources have been used to identify the massive members, and to derive the fundamental parameters such as age and distance of these regions. Using IR color-color criteria and Hα-emission properties, we have identified and classified the candidate young stellar objects (YSOs) in these regions. The 12CO(1-0) continuum maps along with the K-band extinction maps, and spatial distribution of YSOs are used to investigate the structure and morphology of the molecular cloud associated with these H II regions. Overall analysis of these regions suggests that the star formation occurs at the locations of the denser gas, and we also find possible evidences of the induced star formation due to the feedback from massive stars to its surrounding molecular medium.

Nucleosome-free DNA regions differentially affect distant communication in chromatin

PubMed Central

Nizovtseva, Ekaterina V.; Clauvelin, Nicolas; Todolli, Stefjord; Kulaeva, Olga I.; Wengrzynek, Scott

2017-01-01

Abstract Communication between distantly spaced genomic regions is one of the key features of gene regulation in eukaryotes. Chromatin per se can stimulate efficient enhancer-promoter communication (EPC); however, the role of chromatin structure and dynamics in this process remains poorly understood. Here we show that nucleosome spacing and the presence of nucleosome-free DNA regions can modulate chromatin structure/dynamics and, in turn, affect the rate of EPC in vitro and in silico. Increasing the length of internucleosomal linker DNA from 25 to 60 bp results in more efficient EPC. The presence of longer nucleosome-free DNA regions can positively or negatively affect the rate of EPC, depending upon the length and location of the DNA region within the chromatin fiber. Thus the presence of histone-free DNA regions can differentially affect the efficiency of EPC, suggesting that gene regulation over a distance could be modulated by changes in the length of internucleosomal DNA spacers. PMID:27940560

Brain Metastases in Newly Diagnosed Breast Cancer: A Population-Based Study.

PubMed

Martin, Allison M; Cagney, Daniel N; Catalano, Paul J; Warren, Laura E; Bellon, Jennifer R; Punglia, Rinaa S; Claus, Elizabeth B; Lee, Eudocia Q; Wen, Patrick Y; Haas-Kogan, Daphne A; Alexander, Brian M; Lin, Nancy U; Aizer, Ayal A

2017-08-01

Population-based estimates of the incidence and prognosis of brain metastases at diagnosis of breast cancer are lacking. To characterize the incidence proportions and median survivals of patients with breast cancer and brain metastases at the time of cancer diagnosis. Patients with breast cancer and brain metastases at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. Data were stratified by subtype, age, sex, and race. Multivariable logistic and Cox regression were performed to identify predictors of the presence of brain metastases at diagnosis and factors associated with all-cause mortality, respectively. For incidence, we identified a population-based sample of 238 726 adult patients diagnosed as having invasive breast cancer between 2010 and 2013 for whom the presence or absence of brain metastases at diagnosis was known. Patients diagnosed at autopsy or with an unknown follow-up were excluded from the survival analysis, leaving 231 684 patients in this cohort. Incidence proportion and median survival of patients with brain metastases and newly diagnosed breast cancer. We identified 968 patients with brain metastases at the time of diagnosis of breast cancer, representing 0.41% of the entire cohort and 7.56% of the subset with metastatic disease to any site. A total of 57 were 18 to 40 years old, 423 were 41 to 60 years old, 425 were 61-80 years old, and 63 were older than 80 years. Ten were male and 958 were female. Incidence proportions were highest among patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive (1.1% among entire cohort, 11.5% among patients with metastatic disease to any distant site) and triple-negative (0.7% among entire cohort, 11.4% among patients with metastatic disease to any distant site) subtypes. Median survival among the entire cohort with brain metastases was 10.0 months. Patients with HR-positive HER2-positive subtype displayed the longest median survival (21.0 months); patients with triple-negative subtype had the shortest median survival (6.0 months). The findings of this study provides population-based estimates of the incidence and prognosis for patients with brain metastases at time of diagnosis of breast cancer. The findings lend support to consideration of screening imaging of the brain for patients with HER2-positive or triple-negative subtypes and extracranial metastases.

A comparison of brain gene expression levels in domesticated and wild animals.

PubMed

Albert, Frank W; Somel, Mehmet; Carneiro, Miguel; Aximu-Petri, Ayinuer; Halbwax, Michel; Thalmann, Olaf; Blanco-Aguiar, Jose A; Plyusnina, Irina Z; Trut, Lyudmila; Villafuerte, Rafael; Ferrand, Nuno; Kaiser, Sylvia; Jensen, Per; Pääbo, Svante

2012-09-01

Domestication has led to similar changes in morphology and behavior in several animal species, raising the question whether similarities between different domestication events also exist at the molecular level. We used mRNA sequencing to analyze genome-wide gene expression patterns in brain frontal cortex in three pairs of domesticated and wild species (dogs and wolves, pigs and wild boars, and domesticated and wild rabbits). We compared the expression differences with those between domesticated guinea pigs and a distant wild relative (Cavia aperea) as well as between two lines of rats selected for tameness or aggression towards humans. There were few gene expression differences between domesticated and wild dogs, pigs, and rabbits (30-75 genes (less than 1%) of expressed genes were differentially expressed), while guinea pigs and C. aperea differed more strongly. Almost no overlap was found between the genes with differential expression in the different domestication events. In addition, joint analyses of all domesticated and wild samples provided only suggestive evidence for the existence of a small group of genes that changed their expression in a similar fashion in different domesticated species. The most extreme of these shared expression changes include up-regulation in domesticates of SOX6 and PROM1, two modulators of brain development. There was almost no overlap between gene expression in domesticated animals and the tame and aggressive rats. However, two of the genes with the strongest expression differences between the rats (DLL3 and DHDH) were located in a genomic region associated with tameness and aggression, suggesting a role in influencing tameness. In summary, the majority of brain gene expression changes in domesticated animals are specific to the given domestication event, suggesting that the causative variants of behavioral domestication traits may likewise be different.

Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease.

PubMed

Ferrer, Isidro; Garcia-Esparcia, Paula; Carmona, Margarita; Carro, Eva; Aronica, Eleonora; Kovacs, Gabor G; Grison, Alice; Gustincich, Stefano

2016-01-01

Olfactory receptors (ORs) and down-stream functional signaling molecules adenylyl cyclase 3 (AC3), olfactory G protein α subunit (Gαolf), OR transporters receptor transporter proteins 1 and 2 (RTP1 and RTP2), receptor expression enhancing protein 1 (REEP1), and UDP-glucuronosyltransferases (UGTs) are expressed in neurons of the human and murine central nervous system (CNS). In vitro studies have shown that these receptors react to external stimuli and therefore are equipped to be functional. However, ORs are not directly related to the detection of odors. Several molecules delivered from the blood, cerebrospinal fluid, neighboring local neurons and glial cells, distant cells through the extracellular space, and the cells' own self-regulating internal homeostasis can be postulated as possible ligands. Moreover, a single neuron outside the olfactory epithelium expresses more than one receptor, and the mechanism of transcriptional regulation may be different in olfactory epithelia and brain neurons. OR gene expression is altered in several neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 with disease-, region- and subtype-specific patterns. Altered gene expression is also observed in the prefrontal cortex in schizophrenia with a major but not total influence of chlorpromazine treatment. Preliminary parallel observations have also shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are also abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain.

Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease

PubMed Central

Ferrer, Isidro; Garcia-Esparcia, Paula; Carmona, Margarita; Carro, Eva; Aronica, Eleonora; Kovacs, Gabor G.; Grison, Alice; Gustincich, Stefano

2016-01-01

Olfactory receptors (ORs) and down-stream functional signaling molecules adenylyl cyclase 3 (AC3), olfactory G protein α subunit (Gαolf), OR transporters receptor transporter proteins 1 and 2 (RTP1 and RTP2), receptor expression enhancing protein 1 (REEP1), and UDP-glucuronosyltransferases (UGTs) are expressed in neurons of the human and murine central nervous system (CNS). In vitro studies have shown that these receptors react to external stimuli and therefore are equipped to be functional. However, ORs are not directly related to the detection of odors. Several molecules delivered from the blood, cerebrospinal fluid, neighboring local neurons and glial cells, distant cells through the extracellular space, and the cells’ own self-regulating internal homeostasis can be postulated as possible ligands. Moreover, a single neuron outside the olfactory epithelium expresses more than one receptor, and the mechanism of transcriptional regulation may be different in olfactory epithelia and brain neurons. OR gene expression is altered in several neurodegenerative diseases including Parkinson’s disease (PD), Alzheimer’s disease (AD), progressive supranuclear palsy (PSP) and sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 with disease-, region- and subtype-specific patterns. Altered gene expression is also observed in the prefrontal cortex in schizophrenia with a major but not total influence of chlorpromazine treatment. Preliminary parallel observations have also shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are also abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain. PMID:27458372

A Comparison of Brain Gene Expression Levels in Domesticated and Wild Animals

PubMed Central

Albert, Frank W.; Somel, Mehmet; Carneiro, Miguel; Aximu-Petri, Ayinuer; Halbwax, Michel; Thalmann, Olaf; Blanco-Aguiar, Jose A.; Trut, Lyudmila; Villafuerte, Rafael; Ferrand, Nuno; Kaiser, Sylvia; Jensen, Per; Pääbo, Svante

2012-01-01

Domestication has led to similar changes in morphology and behavior in several animal species, raising the question whether similarities between different domestication events also exist at the molecular level. We used mRNA sequencing to analyze genome-wide gene expression patterns in brain frontal cortex in three pairs of domesticated and wild species (dogs and wolves, pigs and wild boars, and domesticated and wild rabbits). We compared the expression differences with those between domesticated guinea pigs and a distant wild relative (Cavia aperea) as well as between two lines of rats selected for tameness or aggression towards humans. There were few gene expression differences between domesticated and wild dogs, pigs, and rabbits (30–75 genes (less than 1%) of expressed genes were differentially expressed), while guinea pigs and C. aperea differed more strongly. Almost no overlap was found between the genes with differential expression in the different domestication events. In addition, joint analyses of all domesticated and wild samples provided only suggestive evidence for the existence of a small group of genes that changed their expression in a similar fashion in different domesticated species. The most extreme of these shared expression changes include up-regulation in domesticates of SOX6 and PROM1, two modulators of brain development. There was almost no overlap between gene expression in domesticated animals and the tame and aggressive rats. However, two of the genes with the strongest expression differences between the rats (DLL3 and DHDH) were located in a genomic region associated with tameness and aggression, suggesting a role in influencing tameness. In summary, the majority of brain gene expression changes in domesticated animals are specific to the given domestication event, suggesting that the causative variants of behavioral domestication traits may likewise be different. PMID:23028369

External validity of two nomograms for predicting distant brain failure after radiosurgery for brain metastases in a bi-institutional independent patient cohort.

PubMed

Prabhu, Roshan S; Press, Robert H; Boselli, Danielle M; Miller, Katherine R; Lankford, Scott P; McCammon, Robert J; Moeller, Benjamin J; Heinzerling, John H; Fasola, Carolina E; Patel, Kirtesh R; Asher, Anthony L; Sumrall, Ashley L; Curran, Walter J; Shu, Hui-Kuo G; Burri, Stuart H

2018-03-01

Patients treated with stereotactic radiosurgery (SRS) for brain metastases (BM) are at increased risk of distant brain failure (DBF). Two nomograms have been recently published to predict individualized risk of DBF after SRS. The goal of this study was to assess the external validity of these nomograms in an independent patient cohort. The records of consecutive patients with BM treated with SRS at Levine Cancer Institute and Emory University between 2005 and 2013 were reviewed. Three validation cohorts were generated based on the specific nomogram or recursive partitioning analysis (RPA) entry criteria: Wake Forest nomogram (n = 281), Canadian nomogram (n = 282), and Canadian RPA (n = 303) validation cohorts. Freedom from DBF at 1-year in the Wake Forest study was 30% compared with 50% in the validation cohort. The validation c-index for both the 6-month and 9-month freedom from DBF Wake Forest nomograms was 0.55, indicating poor discrimination ability, and the goodness-of-fit test for both nomograms was highly significant (p < 0.001), indicating poor calibration. The 1-year actuarial DBF in the Canadian nomogram study was 43.9% compared with 50.9% in the validation cohort. The validation c-index for the Canadian 1-year DBF nomogram was 0.56, and the goodness-of-fit test was also highly significant (p < 0.001). The validation accuracy and c-index of the Canadian RPA classification was 53% and 0.61, respectively. The Wake Forest and Canadian nomograms for predicting risk of DBF after SRS were found to have limited predictive ability in an independent bi-institutional validation cohort. These results reinforce the importance of validating predictive models in independent patient cohorts.

Resurrection of the genera Crophius Stal and Mayana Distant from synonymy under Anomaloptera Amyot and Serville, description of a new genus, and key to the New World Oxycarenid genera (Hemiptera: Heteroptera: Oxycarenidae)

USDA-ARS?s Scientific Manuscript database

The largely New World genus Crophius Stal, revised status, and Mayana Distant, revised status, are resurrected from synonymy with the genus Anomaloptera Amyot and Serville, which is restricted to contain only the type species, A. helianthemi Amyot and Serville, from the western Mediterranean Region....

Expression patterns of Xenopus FGF receptor-like 1/nou-darake in early Xenopus development resemble those of planarian nou-darake and Xenopus FGF8.

PubMed

Hayashi, Shuichi; Itoh, Mari; Taira, Sumiko; Agata, Kiyokazu; Taira, Masanori

2004-08-01

Fibroblast growth factors (FGFs) mediate many cell-to-cell signaling events during early development. Nou-darake (ndk), a gene encoding an FGF receptor (FGFR)-like molecule, was found to be highly and specifically expressed in the head region of the planarian Dugesia japonica, and its functional analyses provided strong molecular evidence for the existence of a brain-inducing circuit based on the FGF signaling pathway. To analyze the role of ndk during vertebrate development, we isolated the Xenopus ortholog of ndk, the vertebrate FGFR-like 1 gene (XFGFRL1). Expression of XFGFRL1/Xndk was first detected in the anterior region at the late gastrula stage and dramatically increased at the early neurula stage in an overall anterior mesendodermal region, including the prechordal plate, paraxial mesoderm, anterior endoderm, and archenteron roof. This anterior expression pattern resembles that of ndk in planarians, suggesting that the expression of FGFRL1/ndk is conserved in evolution between these two distantly diverged organisms. During the tail bud stages, XFGFRL1/Xndk expression was detected in multiple regions, including the forebrain, eyes, midbrain-hindbrain boundary, otic vesicles, visceral arches, and somites. In many of these regions, XFGFRL1/Xndk was coexpressed with XFGF8, indicating that XFGFRL1/Xndk is a member of the XFGF8 synexpression group, which includes sprouty, sef, and isthmin. Copyright 2004 Wiley-Liss, Inc.

Evolution of brain region volumes during artificial selection for relative brain size.

PubMed

Kotrschal, Alexander; Zeng, Hong-Li; van der Bijl, Wouter; Öhman-Mägi, Caroline; Kotrschal, Kurt; Pelckmans, Kristiaan; Kolm, Niclas

2017-12-01

The vertebrate brain shows an extremely conserved layout across taxa. Still, the relative sizes of separate brain regions vary markedly between species. One interesting pattern is that larger brains seem associated with increased relative sizes only of certain brain regions, for instance telencephalon and cerebellum. Till now, the evolutionary association between separate brain regions and overall brain size is based on comparative evidence and remains experimentally untested. Here, we test the evolutionary response of brain regions to directional selection on brain size in guppies (Poecilia reticulata) selected for large and small relative brain size. In these animals, artificial selection led to a fast response in relative brain size, while body size remained unchanged. We use microcomputer tomography to investigate how the volumes of 11 main brain regions respond to selection for larger versus smaller brains. We found no differences in relative brain region volumes between large- and small-brained animals and only minor sex-specific variation. Also, selection did not change allometric scaling between brain and brain region sizes. Our results suggest that brain regions respond similarly to strong directional selection on relative brain size, which indicates that brain anatomy variation in contemporary species most likely stem from direct selection on key regions. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Photodynamic therapy stimulates anti-tumor immune response in mouse models: the role of regulatory Tcells, anti-tumor antibodies, and immune attacks on brain metastases

NASA Astrophysics Data System (ADS)

Vatansever, Fatma; Kawakubo, Masayoshi; Chung, Hoon; Hamblin, Michael R.

2013-02-01

We have previously shown that photodynamic therapy mediated by a vascular regimen of benzoporphyrin derivative and 690nm light is capable of inducing a robust immune response in the mouse CT26.CL25 tumor model that contains a tumor-rejection antigen, beta-galactosidase (β-gal). For the first time we show that PDT can stimulate the production of serum IgG antibodies against the β-gal antigen. It is known that a common cause of death from cancer, particularly lung cancer, is brain metastases; especially the inoperable ones that do not respond to traditional cytotoxic therapies either. We asked whether PDT of a primary tumor could stimulate immune response that could attack the distant brain metastases. We have developed a mouse model of generating brain metastases by injecting CT26.CL25 tumor cells into the brain as well as injecting the same cancer cells under the skin at the same time. When the subcutaneous tumor was treated with PDT, we observed a survival advantage compared to mice that had untreated brain metastases alone.

[Lymph node and distant metastases of thyroid gland cancer. Metastases in the thyroid glands].

PubMed

Schmid, K W

2015-11-01

The different biological features of the various major entities of thyroid cancer, e.g. papillary, follicular, poorly differentiated, anaplastic and medullary, depend to a large extent on their different metastatic spread. Papillary thyroid cancer (PTC) has a propensity for cervical lymphatic spread that occurs in 20-50 % of patients whereas distant metastasis occurs in < 5 % of cases. Cervical lymphadenopathy may be the first symptom particularly of (micro) PTC. In contrast follicular thyroid cancer (FTC) has a marked propensity for vascular but not lymphatic invasion and 10-20 % of FTC develop distant metastases. At the time of diagnosis approximately one third of medullary thyroid cancer (MTC) cases show lymph node metastases, in 10-15 % distant metastases and 25 % develop metastases during the course of the disease. Poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC) spread via both lymphatic and vascular invasion. Thus distant metastases are relatively uncommon in DTC and when they occur, long-term stable disease is the typical clinical course. The major sites of distant metastases are the lungs and bone. Metastases to the brain, breasts, liver, kidneys, muscle and skin are relatively rare or even rare. The thyroid gland itself can be a site of metastases from a variety of other tumors. In autopsy series of patients with disseminated cancer disease, metastases to the thyroid gland were found in up to 10 % of cases. Metastases from other primary tumors to the thyroid gland have been reported in 1.4-3 % of patients who have surgery for suspected cancer of the thyroid gland. The most common primary cancers that metastasize to the thyroid gland are renal cell (48.1 %), colorectal (10.4 %), lung (8.3 %) and breast cancer (7.8 %) and surprisingly often sarcomas (4.0 %).

Prognostic value of site-specific metastases in pancreatic adenocarcinoma: A Surveillance Epidemiology and End Results database analysis.

PubMed

Oweira, Hani; Petrausch, Ulf; Helbling, Daniel; Schmidt, Jan; Mannhart, Meinrad; Mehrabi, Arianeb; Schöb, Othmar; Giryes, Anwar; Decker, Michael; Abdel-Rahman, Omar

2017-03-14

To evaluate the prognostic value of site-specific metastases among patients with metastatic pancreatic carcinoma registered within the Surveillance, Epidemiology and End Results (SEER) database. SEER database (2010-2013) has been queried through SEER*Stat program to determine the presentation, treatment outcomes and prognostic outcomes of metastatic pancreatic adenocarcinoma according to the site of metastasis. In this study, metastatic pancreatic adenocarcinoma patients were classified according to the site of metastases (liver, lung, bone, brain and distant lymph nodes). We utilized chi-square test to compare the clinicopathological characteristics among different sites of metastases. We used Kaplan-Meier analysis and log-rank testing for survival comparisons. We employed Cox proportional model to perform multivariate analyses of the patient population; and accordingly hazard ratios with corresponding 95%CI were generated. Statistical significance was considered if a two-tailed P value < 0.05 was achieved. A total of 13233 patients with stage IV pancreatic cancer and known sites of distant metastases were identified in the period from 2010-2013 and they were included into the current analysis. Patients with isolated distant nodal involvement or lung metastases have better overall and pancreatic cancer-specific survival compared to patients with isolated liver metastases (for overall survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001) (for pancreatic cancer-specific survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001). Multivariate analysis revealed that age < 65 years, white race, being married, female gender; surgery to the primary tumor and surgery to the metastatic disease were associated with better overall survival and pancreatic cancer-specific survival. Pancreatic adenocarcinoma patients with isolated liver metastases have worse outcomes compared to patients with isolated lung or distant nodal metastases. Further research is needed to identify the highly selected subset of patients who may benefit from local treatment of the primary tumor and/or metastatic disease.

In-vivo animation of midazolam-induced electrocorticographic changes in humans.

PubMed

Nishida, Masaaki; Sood, Sandeep; Asano, Eishi

2009-12-15

Previous human studies have demonstrated that midazolam-induced signal changes on scalp EEG recording include widespread augmentation of sigma-oscillations and that the amplitude of such oscillations is correlated to the severity of midazolam-induced amnesia. Still unanswered questions include whether midazolam-induced sigma-augmentation also involves the medial temporal region, which plays a role in memory encoding. Taking advantage of rare and unique opportunities to monitor neuronal activities using intracranial electrocorticography (ECoG) recording, we determined how intravenous administration of midazolam elicited spectral frequency changes in the human cerebral cortex, including the medial temporal region. We studied three children with focal epilepsy who underwent subdural electrode placement and extraoperative ECoG recording for subsequent resection of the seizure focus; an intravenous bolus of midazolam was given to abort an ongoing simple partial seizure or to provide sedation prior to induction of general anesthesia. 'Midazolam-induced ECoG frequency alteration' in sites distant from the seizure focus was sequentially animated on their individual three-dimensional MR images. The common ECoG changes induced by midazolam included gradual augmentation of sigma-oscillations (12-16 Hz) in the widespread non-epileptic regions, including the medial temporal region. The spatial and temporal alteration of ECoG spectral frequency pattern can be appreciated via animation movies. Midazolam-induced sigma-augmentation was observed in the medial temporal region in our relatively small cohort of human subjects. In-vivo animation of ECoG spectral measures provided a unique situation to study the effect of midazolam on neuronal processing in the deep brain regions.

In-vivo animation of midazolam-induced electrocorticographic changes in humans

PubMed Central

Nishida, Masaaki; Sood, Sandeep; Asano, Eishi

2009-01-01

Previous human studies have demonstrated that midazolam-induced signal changes on scalp EEG recording include widespread augmentation of sigma-oscillations and that the amplitude of such oscillations is correlated to the severity of midazolam-induced amnesia. Still unanswered questions include whether midazolam-induced sigma-augmentation also involves the medial temporal region, which plays a role in memory encoding. Taking advantage of rare and unique opportunities to monitor neuronal activities using intracranial electrocorticography (ECoG) recording, we determined how intravenous administration of midazolam induced spectral frequency changes in the human cerebral cortex, including the medial temporal region. We studied three children with focal epilepsy who underwent subdural electrode placement and extraoperative ECoG recording for subsequent resection of the seizure focus; an intravenous bolus of midazolam was given to abort an ongoing simple-partial seizure or to provide sedation prior to induction of general anesthesia. ‘Midazolam-induced ECoG frequency alteration’ in sites distant from the seizure focus was sequentially animated on their individual three-dimensional MR images. The common ECoG changes induced by midazolam included gradual augmentation of sigma-oscillations (12-16 Hz) in the widespread non-epileptic regions, including the medial temporal region. The spatial and temporal alteration of ECoG spectral frequency pattern can be appreciated via animation movies. Midazolam-induced sigma-augmentation was observed in the medial temporal region in our relatively small cohort of human subjects. In-vivo animation of ECoG spectral measures provided a unique situation to study the effect of midazolam on neuronal processing in the deep brain regions. PMID:19733366

Investigation of phase synchronization of interictal EEG in right temporal lobe epilepsy

NASA Astrophysics Data System (ADS)

Yu, Haitao; Cai, Lihui; Wu, Xinyu; Song, Zhenxi; Wang, Jiang; Xia, Zijie; Liu, Jing; Cao, Yibin

2018-02-01

Epilepsy is commonly associated with abnormally synchronous activity of neurons located in epileptogenic zones. In this study, we investigated the synchronization characteristic of right temporal lobe epilepsy (RTLE). Multichannel electroencephalography (EEG) data were recorded from the RTLE patients during interictal period and normal controls. Power spectral density was first used to analyze the EEG power for two groups of subjects. It was found that the power of epileptics is increased in the whole brain compared with that of the control. We calculated phase lag index (PLI) to measure the phase synchronization between each pair of EEG signals. A higher degree of synchronization was observed in the epileptics especially between distant channels. In particular, the regional synchronization degree was negatively correlated with power spectral density and the correlation was weaker for epileptics. Moreover, the synchronization degree decayed with the increase of relative distance of channels for both the epilepsy and control, but the dependence was weakened in the former. The obtained results may provide new insights into the generation mechanism of epilepsy.

Correspondence between large-scale ictal and interictal epileptic networks revealed by single photon emission computed tomography (SPECT) and electroencephalography (EEG)-functional magnetic resonance imaging (fMRI).

PubMed

Tousseyn, Simon; Dupont, Patrick; Goffin, Karolien; Sunaert, Stefan; Van Paesschen, Wim

2015-03-01

Epilepsy is increasingly recognized as a network disorder, but the spatial relationship between ictal and interictal networks is still largely unexplored. In this work, we compared hemodynamic changes related to seizures and interictal spikes on a whole brain scale. Twenty-eight patients with refractory focal epilepsy (14 temporal and 14 extratemporal lobe) underwent both subtraction ictal single photon emission computed tomography (SPECT) coregistered to magnetic resonance imaging (MRI) (SISCOM) and spike-related electroencephalography (EEG-functional MRI (fMRI). SISCOM visualized relative perfusion changes during seizures, whereas EEG-fMRI mapped blood oxygen level-dependent (BOLD) changes related to spikes. Similarity between statistical maps of both modalities was analyzed per patient using the following two measures: (1) correlation between unthresholded statistical maps (Pearson's correlation coefficient) and (2) overlap between thresholded images (Dice coefficient). Overlap was evaluated at a regional level, for hyperperfusions and activations and for hypoperfusions and deactivations separately, using different thresholds. Nonparametric permutation tests were applied to assess statistical significance (p ≤ 0.05). We found significant and positive correlations between hemodynamic changes related to seizures and spikes in 27 (96%) of 28 cases (median correlation coefficient 0.29 [range -0.12 to 0.62]). In 20 (71%) of 28 cases, spatial overlap between hyperperfusion on SISCOM and activation on EEG-fMRI was significantly larger than expected by chance. Congruent changes were not restricted to the territory of the presumed epileptogenic zone, but could be seen at distant sites (e.g., cerebellum and basal ganglia). Overlap between ictal hypoperfusion and interictal deactivation was statistically significant in 22 (79%) of 28 patients. Despite the high rate of congruence, discrepancies were observed for both modalities. We conclude that hemodynamic changes related to seizures and spikes varied spatially with the same sign and within a common network. Overlap was present in regions nearby and distant from discharge origin. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

An fMRI study of differences in brain activity among elite, expert, and novice archers at the moment of optimal aiming.

PubMed

Kim, Woojong; Chang, Yongmin; Kim, Jingu; Seo, Jeehye; Ryu, Kwangmin; Lee, Eunkyung; Woo, Minjung; Janelle, Christopher M

2014-12-01

We investigated brain activity in elite, expert, and novice archers during a simulated archery aiming task to determine whether neural correlates of performance differ by skill level. Success in shooting sports depends on complex mental routines just before the shot, when the brain prepares to execute the movement. During functional magnetic resonance imaging, 40 elite, expert, or novice archers aimed at a simulated 70-meter-distant target and pushed a button when they mentally released the bowstring. At the moment of optimal aiming, the elite and expert archers relied primarily on a dorsal pathway, with greatest activity in the occipital lobe, temporoparietal lobe, and dorsolateral pre-motor cortex. The elites showed activity in the supplementary motor area, temporoparietal area, and cerebellar dentate, while the experts showed activity only in the superior frontal area. The novices showed concurrent activity in not only the dorsolateral pre-motor cortex but also the ventral pathways linked to the ventrolateral pre-motor cortex. The novices exhibited broad activity in the superior frontal area, inferior frontal area, ventral prefrontal cortex, primary motor cortex, superior parietal lobule, and primary somatosensory cortex. The more localized neural activity of elite and expert archers than novices permits greater efficiency in the complex processes subserved by these regions. The elite group's high activity in the cerebellar dentate indicates that the cerebellum is involved in automating simultaneous movements by integrating the sensorimotor memory enabled by greater expertise in self-paced aiming tasks. A companion article comments on and generalizes our findings.

Voxel-Wise Comparisons of the Morphology of Diffusion Tensors Across Groups of Experimental Subjects

PubMed Central

Bansal, Ravi; Staib, Lawrence H.; Plessen, Kerstin J.; Xu, Dongrong; Royal, Jason; Peterson, Bradley S.

2007-01-01

Water molecules in the brain diffuse preferentially along the fiber tracts within white matter, which form the anatomical connections across spatially distant brain regions. A diffusion tensor (DT) is a probabilistic ellipsoid composed of 3 orthogonal vectors, each having a direction and an associated scalar magnitude, that represent the probability of water molecules diffusing in each of those directions. The 3D morphologies of DTs can be compared across groups of subjects to reveal disruptions in structural organization and neuroanatomical connectivity of the brains of persons with various neuropsychiatric illnesses. Comparisons of tensor morphology across groups have typically been performed on scalar measures of diffusivity, such as Fractional Anisotropy (FA), rather than directly on the complex 3D morphologies of DTs. Scalar measures, however, are related in nonlinear ways to the eigenvalues and eigenvectors that create the 3D morphologies of DTs. We present a mathematical framework that permits the direct comparison across groups of mean eigenvalues and eigenvectors of individual DTs. We show that group-mean eigenvalues and eigenvectors are multivariate Gaussian distributed, and we use the Delta method to compute their approximate covariance matrices. Our results show that the theoretically computed Mean Tensor (MT) eigenvectors and eigenvalues match well with their respective true values. Furthermore, a comparison of synthetically generated groups of DTs highlights the limitations of using FA to detect group differences. Finally, analyses of in vivo DT data using our method reveal significant between-group differences in diffusivity along fiber tracts within white matter, whereas analyses based on FA values failed to detect some of these differences. PMID:18006284

Libraries Without Walls 4: The Delivery of Library Services to Distant Users. Proceedings of an International Conference Organized by the Centre for Research in Library and Information Management (CERLIM), Manchester Metropolitan University (Manchester, England, September 14-18, 2001).

ERIC Educational Resources Information Center

Brophy, Peter, Ed.; Fisher, Shelagh, Ed.; Clarke, Zoe, Ed.

This proceedings of the fourth Libraries Without Walls Conference addresses key strategic issues arising from international, regional, and cross-sectoral approaches to the provision of library services to distant users. The following papers are included: Theme 1: Libraries and Virtual Learning Environments: "Introduction" (Peter Brophy,…

[Neural mechanism underlying autistic savant and acquired savant syndrome].

PubMed

Takahata, Keisuke; Kato, Motoichiro

2008-07-01

It is well known that the cases with savant syndrome, demonstrate outstanding mental capability despite coexisting severe mental disabilities. In many cases, savant skills are characterized by its domain-specificity, enhanced memory capability, and excessive focus on low-level perceptual processing. In addition, impaired integrative cognitive processing such as social cognition or executive function, restricted interest, and compulsive repetition of the same act are observed in savant individuals. All these are significantly relevant to the behavioral characteristics observed in individuals with autistic spectrum disorders (ASD). A neurocognitive model of savant syndrome should explain these cognitive features and the juxtaposition of outstanding talents with cognitive disabilities. In recent neuropsychological studies, Miller (1998) reported clinical cases of "acquired savant," i.e., patients who improved or newly acquired an artistic savant-like skill in the early stage of frontotemporal dementia (FTD). Although the relationship between an autistic savant and acquired savant remains to be elucidated, the advent of neuroimaging study of ASD and the clarification of FTD patients with savant-like skills may clarify the shared neural mechanisms of both types of talent. In this review, we classified current cognitive models of savant syndrome into the following 3 categories. (1) A hypermnesic model that suggests that savant skills develop from existing or dormant cognitive functions such as memory. However, recent findings obtained through neuropsychological examinations imply that savant individuals solve problems using a strategy that is fairly different from a non-autistic one. (2) A paradoxical functional facilitation model (Kapur, 1996) that offers possible explanations about how pathological states in the brain lead to development of prodigious skills. This model emphasizes the role of reciprocal inhibitory interaction among adjacent or distant cortical regions, especially that of the prefrontal cortex and the posterior regions of the brain. (3) Autistic models, including those based on weak central coherence theory (Frith, 1989), that focus on how savant skills emerge from an autistic brain. Based on recent neuroimaging studies of ASD, Just et al. (2004) suggested the underconnectivity theory, which emphasizes the disruption of long-range connectivity and the relative intact or even more enhanced local connectivity in the autistic brain. All the models listed above have certain advantages and shortcomings. At the end of this review, we propose another integrative model of savant syndrome. In this model, we predict an altered balance of local/global connectivity patterns that contribute to an altered functional segregation/integration ratio. In particular, we emphasize the crucial role played by the disruption of global connectivity in a parallel distributed cortical network, which might result in impairment in integrated cognitive processing, such as impairment in executive function and social cognition. On the other hand, the reduced inter-regional collaboration could lead to a disinhibitory enhancement of neural activity and connectivity in local cortical regions. In addition, enhanced connectivity in the local brain regions is partly due to the abnormal organization of the cortical network as a result of developmental and pathological states. This enhanced local connectivity results in the specialization and facilitation of low-level cognitive processing. The disruption of connectivity between the prefrontal cortex and other regions is considered to be a particularly important factor because the prefrontal region shows the most influential inhibitory control on other cortical areas. We propose that these neural mechanisms as the underlying causes for the emergence of savant ability in ASD and FTD patients.

Identification of a distant cis-regulatory element controlling pharyngeal arch-specific expression of zebrafish gdf6a/radar

PubMed Central

Reed, Nykolaus P.; Mortlock, Douglas P.

2011-01-01

Skeletal formation is an essential and intricately regulated part of vertebrate development. Humans and mice deficient in Growth and Differentiation Factor 6 (Gdf6) have numerous skeletal abnormalities including joint fusions and cartilage reductions. The expression of Gdf6 is dynamic and in part regulated by distant evolutionarily conserved cis-regulatory elements. radar/gdf6a is a zebrafish ortholog of Gdf6 and has an essential role in embryonic patterning. Here we show that radar is transcribed in the cells surrounding and between the developing cartilages of the ventral pharyngeal arches, similar to mouse Gdf6. A 312 bp evolutionarily conserved region (ECR5), 122 kilobases downstream, drives expression in a pharyngeal arch-specific manner similar to endogenous radar/gdf6a. Deletion analysis identified a 78 bp region within ECR5 that is essential for transgene activity. This work illustrates that radar is regulated in the pharyngeal arches by a distant conserved element and suggests radar has similar functions in skeletal development in fish and mammals. PMID:20201106

Algorithms for Adaptation in Aerial Surveillance

DTIC Science & Technology

2002-03-01

In the brain small local structures can involve inhibition whereas more distant functional areas are less likely to have inhibition. This appeals to...and 2. retains a more conventional programming model [than the PDP approach]. The former is achieved by appealing to well understood ideas from...1980s. The statistical techniques used in our implementation of these ideas (GRAVA) are appealing to us for three reasons: 91 5.2. PRIOR WORK 1. GRAVA

Electrocortical correlations between pairs of isolated people: A reanalysis

PubMed Central

Radin, Dean

2017-01-01

A previously reported experiment collected electrocortical data recorded simultaneously in pairs of people separated by distance. Reanalysis of those data confirmed the presence of a time-synchronous, statistically significant correlation in brain electrical activity of these distant “sender-receiver” pairs. Given the sensory shielding employed in the original experiment to avoid mundane explanations for such a correlation, this outcome is suggestive of an anomalous intersubjective connection. PMID:28713556

Distant Metastasis Risk Stratification for Patients Undergoing Curative Resection Followed by Adjuvant Chemoradiation for Extrahepatic Bile Duct Cancer

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

Kim, Kyubo; Chie, Eui Kyu, E-mail: ekchie93@snu.ac.kr; Jang, Jin-Young

2012-09-01

Purpose: To analyze the prognostic factors predicting distant metastasis in patients undergoing adjuvant chemoradiation for extrahepatic bile duct (EHBD) cancer. Methods and Materials: Between January 1995 and August 2006, 166 patients with EHBD cancer underwent resection with curative intent, followed by adjuvant chemoradiation. There were 120 males and 46 females, and median age was 61 years (range, 34-86). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes (median dose, 40 Gy; range, 34-56 Gy). A total of 157 patients also received fluoropyrimidine chemotherapy as a radiosensitizer, and fluoropyrimidine-based maintenance chemotherapy was administered to 127 patients. Median follow-up durationmore » was 29 months. Results: The treatment failed for 97 patients, and the major pattern of failure was distant metastasis (76 patients, 78.4%). The 5-year distant metastasis-free survival rate was 49.4%. The most common site of distant failure was the liver (n = 36). On multivariate analysis, hilar tumor, tumor size {>=}2 cm, involved lymph node, and poorly differentiated tumor were associated with inferior distant metastasis-free survival (p = 0.0348, 0.0754, 0.0009, and 0.0078, respectively), whereas T stage was not (p = 0.8081). When patients were divided into four groups based on these risk factors, the 5-year distant metastasis-free survival rates for patients with 0, 1, 2, and 3 risk factors were 86.4%, 59.9%, 32.5%, and 0%, respectively (p < 0.0001). Conclusion: Despite maintenance chemotherapy, distant metastasis was the major pattern of failure in patients undergoing adjuvant chemoradiation for EHBD cancer after resection with curative intent. Intensified chemotherapy is warranted to improve the treatment outcome, especially in those with multiple risk factors.« less

Local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsy.

PubMed

Neubauer, Florian B; Sederberg, Audrey; MacLean, Jason N

2014-01-01

During the generalization of epileptic seizures, pathological activity in one brain area recruits distant brain structures into joint synchronous discharges. However, it remains unknown whether specific changes in local circuit activity are related to the aberrant recruitment of anatomically distant structures into epileptiform discharges. Further, it is not known whether aberrant areas recruit or entrain healthy ones into pathological activity. Here we study the dynamics of local circuit activity during the spread of epileptiform discharges in the zero-magnesium in vitro model of epilepsy. We employ high-speed multi-photon imaging in combination with dual whole-cell recordings in acute thalamocortical (TC) slices of the juvenile mouse to characterize the generalization of epileptic activity between neocortex and thalamus. We find that, although both structures are exposed to zero-magnesium, the initial onset of focal epileptiform discharge occurs in cortex. This suggests that local recurrent connectivity that is particularly prevalent in cortex is important for the initiation of seizure activity. Subsequent recruitment of thalamus into joint, generalized discharges is coincident with an increase in the coherence of local cortical circuit activity that itself does not depend on thalamus. Finally, the intensity of population discharges is positively correlated between both brain areas. This suggests that during and after seizure generalization not only the timing but also the amplitude of epileptiform discharges in thalamus is entrained by cortex. Together these results suggest a central role of neocortical activity for the onset and the structure of pathological recruitment of thalamus into joint synchronous epileptiform discharges.

Local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsy

PubMed Central

Neubauer, Florian B.; Sederberg, Audrey; MacLean, Jason N.

2014-01-01

During the generalization of epileptic seizures, pathological activity in one brain area recruits distant brain structures into joint synchronous discharges. However, it remains unknown whether specific changes in local circuit activity are related to the aberrant recruitment of anatomically distant structures into epileptiform discharges. Further, it is not known whether aberrant areas recruit or entrain healthy ones into pathological activity. Here we study the dynamics of local circuit activity during the spread of epileptiform discharges in the zero-magnesium in vitro model of epilepsy. We employ high-speed multi-photon imaging in combination with dual whole-cell recordings in acute thalamocortical (TC) slices of the juvenile mouse to characterize the generalization of epileptic activity between neocortex and thalamus. We find that, although both structures are exposed to zero-magnesium, the initial onset of focal epileptiform discharge occurs in cortex. This suggests that local recurrent connectivity that is particularly prevalent in cortex is important for the initiation of seizure activity. Subsequent recruitment of thalamus into joint, generalized discharges is coincident with an increase in the coherence of local cortical circuit activity that itself does not depend on thalamus. Finally, the intensity of population discharges is positively correlated between both brain areas. This suggests that during and after seizure generalization not only the timing but also the amplitude of epileptiform discharges in thalamus is entrained by cortex. Together these results suggest a central role of neocortical activity for the onset and the structure of pathological recruitment of thalamus into joint synchronous epileptiform discharges. PMID:25232306

Neurophysiology of space travel: energetic solar particles cause cell type-specific plasticity of neurotransmission.

PubMed

Lee, Sang-Hun; Dudok, Barna; Parihar, Vipan K; Jung, Kwang-Mook; Zöldi, Miklós; Kang, Young-Jin; Maroso, Mattia; Alexander, Allyson L; Nelson, Gregory A; Piomelli, Daniele; Katona, István; Limoli, Charles L; Soltesz, Ivan

2017-07-01

In the not too distant future, humankind will embark on one of its greatest adventures, the travel to distant planets. However, deep space travel is associated with an inevitable exposure to radiation fields. Space-relevant doses of protons elicit persistent disruptions in cognition and neuronal structure. However, whether space-relevant irradiation alters neurotransmission is unknown. Within the hippocampus, a brain region crucial for cognition, perisomatic inhibitory control of pyramidal cells (PCs) is supplied by two distinct cell types, the cannabinoid type 1 receptor (CB 1 )-expressing basket cells (CB 1 BCs) and parvalbumin (PV)-expressing interneurons (PVINs). Mice subjected to low-dose proton irradiation were analyzed using electrophysiological, biochemical and imaging techniques months after exposure. In irradiated mice, GABA release from CB 1 BCs onto PCs was dramatically increased. This effect was abolished by CB 1 blockade, indicating that irradiation decreased CB 1 -dependent tonic inhibition of GABA release. These alterations in GABA release were accompanied by decreased levels of the major CB 1 ligand 2-arachidonoylglycerol. In contrast, GABA release from PVINs was unchanged, and the excitatory connectivity from PCs to the interneurons also underwent cell type-specific alterations. These results demonstrate that energetic charged particles at space-relevant low doses elicit surprisingly selective long-term plasticity of synaptic microcircuits in the hippocampus. The magnitude and persistent nature of these alterations in synaptic function are consistent with the observed perturbations in cognitive performance after irradiation, while the high specificity of these changes indicates that it may be possible to develop targeted therapeutic interventions to decrease the risk of adverse events during interplanetary travel.

Early versus late distant metastasis and adjuvant chemotherapy alone versus both radiotherapy and chemotherapy in molecular apocrine breast cancer

PubMed Central

Liu, Xiaozhen; Yang, Yang; Feng, Xiaolong; Shen, Honghong; Liu, Jian; Liu, Xia; Niu, Yun

2016-01-01

As a new subtype of breast cancer, molecular apocrine breast cancer (MABC) is estrogen receptor (ER) and progesterone receptor (PR) negative expression, but androgen receptor (AR) positive expression. The prognostic significance and clinical biological behavior of MABC have remained unclear up to now. This study aimed to analysis the distant metastasis behavior and response to adjuvant radiotherapy and chemotherapy of MABC subgroup. The report showed that there were significant differences between early and late distant metastasizing tumors with respect to Ki67, epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) expressions by a retrospective analysis consisting of 410 invasive breast cancer patients, which included 205 MABC and 205 nonMABC cases. MABC subgroup metastasized earlier than nonMABC subgroup, and MABC showed a tendency for a higher metastasis rate in lung, liver and brain, but lower in bone. HER2-positive or VEGF-positive tumors were more inclined to develop bone metastasis within MABC subgroup. The survival rate was superior for patients undergone both adjuvant radiotherapy and chemotherapy than those undergone chemotherapy alone in nonMABC subgroup, but there was no significant difference in MABC subgroup. Our data suggested that MABC subgroup seemed to develop distant metastasis earlier than nonMABC subgroup, and patients with MABC indicated poor prognosis. This study might also provide a foundation for helping patients receive reasonable treatments according to molecular subtype. PMID:27340922

Early versus late distant metastasis and adjuvant chemotherapy alone versus both radiotherapy and chemotherapy in molecular apocrine breast cancer.

PubMed

Liu, Xiaozhen; Yang, Yang; Feng, Xiaolong; Shen, Honghong; Liu, Jian; Liu, Xia; Niu, Yun

2016-08-02

As a new subtype of breast cancer, molecular apocrine breast cancer (MABC) is estrogen receptor (ER) and progesterone receptor (PR) negative expression, but androgen receptor (AR) positive expression. The prognostic significance and clinical biological behavior of MABC have remained unclear up to now. This study aimed to analysis the distant metastasis behavior and response to adjuvant radiotherapy and chemotherapy of MABC subgroup. The report showed that there were significant differences between early and late distant metastasizing tumors with respect to Ki67, epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor (VEGF) expressions by a retrospective analysis consisting of 410 invasive breast cancer patients, which included 205 MABC and 205 nonMABC cases. MABC subgroup metastasized earlier than nonMABC subgroup, and MABC showed a tendency for a higher metastasis rate in lung, liver and brain, but lower in bone. HER2-positive or VEGF-positive tumors were more inclined to develop bone metastasis within MABC subgroup. The survival rate was superior for patients undergone both adjuvant radiotherapy and chemotherapy than those undergone chemotherapy alone in nonMABC subgroup, but there was no significant difference in MABC subgroup. Our data suggested that MABC subgroup seemed to develop distant metastasis earlier than nonMABC subgroup, and patients with MABC indicated poor prognosis. This study might also provide a foundation for helping patients receive reasonable treatments according to molecular subtype.

Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center.

PubMed

Suki, Dima; Khoury Abdulla, Rami; Ding, Minming; Khatua, Soumen; Sawaya, Raymond

2014-10-01

Metastasis to the brain is frequent in adult cancer patients but rare among children. Advances in primary tumor treatment and the associated prolonged survival are said to have increased the frequency of brain metastasis in children. The authors present a series of cases of brain metastases in children diagnosed with a solid primary cancer, evaluate brain metastasis trends, and describe tumor type, patterns of occurrence, and prognosis. Patients with brain metastases whose primary cancer was diagnosed during childhood were identified in the 1990-2012 Tumor Registry at The University of Texas M.D. Anderson Cancer Center. A review of their hospital records provided demographic data, history, and clinical data, including primary cancer sites, number and location of brain metastases, sites of extracranial metastases, treatments, and outcomes. Fifty-four pediatric patients (1.4%) had a brain metastasis from a solid primary tumor. Sarcomas were the most common (54%), followed by melanoma (15%). The patients' median ages at diagnosis of the primary cancer and the brain metastasis were 11.37 years and 15.03 years, respectively. The primary cancer was localized at diagnosis in 48% of patients and disseminated regionally in only 14%. The primary tumor and brain metastasis presented synchronously in 15% of patients, and other extracranial metastases were present when the primary cancer was diagnosed. The remaining patients were diagnosed with brain metastasis after initiation of primary cancer treatment, with a median presentation interval of 17 months after primary cancer diagnosis (range 2-77 months). At the time of diagnosis, the brain metastasis was the first site of systemic metastasis in only 4 (8%) of the 51 patients for whom data were available. Up to 70% of patients had lung metastases when brain metastases were found. Symptoms led to the brain metastasis diagnosis in 65% of cases. Brain metastases were single in 60% of cases and multiple in 35%; 6% had only leptomeningeal disease. The median Kaplan-Meier estimates of survival after diagnoses of primary cancer and brain metastasis were 29 months (95% CI 24-34 months) and 9 months (95% CI 6-11 months), respectively. Untreated patients survived for a median of 0.9 months after brain metastasis diagnosis (95% CI 0.3-1.5 months). Those receiving treatment survived for a median of 8 months after initiation of therapy (95% CI 6-11 months). The results of this study challenge the current notion of an increased incidence of brain metastases among children with a solid primary cancer. The earlier diagnosis of the primary cancer, prior to its dissemination to distant sites (especially the brain), and initiation of presumably more effective treatments may support such an observation. However, although the actual number of cases may not be increasing, the prognosis after the diagnosis of a brain metastasis remains poor regardless of the management strategy.

Uterine cervical cancer with brain metastasis as the initial site of presentation.

PubMed

Sato, Yumi; Tanaka, Kei; Kobayashi, Yoichi; Shibuya, Hiromi; Nishigaya, Yoshiko; Momomura, Mai; Matsumoto, Hironori; Iwashita, Mitsutoshi

2015-07-01

Brain metastasis from uterine cervical cancer is rare, with an incidence of 0.5%, and usually occurs late in the course of the disease. We report a case of uterine cervical cancer with brain metastasis as the initial site of presentation. A 50-year-old woman with headache, vertigo, amnesia and loss of appetite was admitted for persistent vomiting. Contrast enhanced computed tomography showed a solitary right frontal cerebral lesion with ring enhancement and uterine cervical tumor. She was diagnosed with uterine cervical squamous cell carcinoma with parametrium invasion and no other distant affected organs were detected. The cerebral lesion was surgically removed and pathologically proved to be metastasis of uterine cervical squamous cell carcinoma. The patient underwent concurrent chemoradiotherapy, followed by cerebral radiation therapy, but multiple metastases to the liver and lung developed and the patient died 7 months after diagnosis of brain metastasis. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

Outbreaks of Neuroinvasive Astrovirus Associated with Encephalomyelitis, Weakness, and Paralysis among Weaned Pigs, Hungary

PubMed Central

Boros, Ákos; Albert, Mihály; Pankovics, Péter; Bíró, Hunor; Pesavento, Patricia A.; Phan, Tung Gia; Delwart, Eric

2017-01-01

A large, highly prolific swine farm in Hungary had a 2-year history of neurologic disease among newly weaned (25- to 35-day-old) pigs, with clinical signs of posterior paraplegia and a high mortality rate. Affected pigs that were necropsied had encephalomyelitis and neural necrosis. Porcine astrovirus type 3 was identified by reverse transcription PCR and in situ hybridization in brain and spinal cord samples in 6 animals from this farm. Among tissues tested by quantitative RT-PCR, the highest viral loads were detected in brain stem and spinal cord. Similar porcine astrovirus type 3 was also detected in archived brain and spinal cord samples from another 2 geographically distant farms. Viral RNA was predominantly restricted to neurons, particularly in the brain stem, cerebellum (Purkinje cells), and cervical spinal cord. Astrovirus was generally undetectable in feces but present in respiratory samples, indicating a possible respiratory infection. Astrovirus could cause common, neuroinvasive epidemic disease. PMID:29148391

Outbreaks of Neuroinvasive Astrovirus Associated with Encephalomyelitis, Weakness, and Paralysis among Weaned Pigs, Hungary.

PubMed

Boros, Ákos; Albert, Mihály; Pankovics, Péter; Bíró, Hunor; Pesavento, Patricia A; Phan, Tung Gia; Delwart, Eric; Reuter, Gábor

2017-12-01

A large, highly prolific swine farm in Hungary had a 2-year history of neurologic disease among newly weaned (25- to 35-day-old) pigs, with clinical signs of posterior paraplegia and a high mortality rate. Affected pigs that were necropsied had encephalomyelitis and neural necrosis. Porcine astrovirus type 3 was identified by reverse transcription PCR and in situ hybridization in brain and spinal cord samples in 6 animals from this farm. Among tissues tested by quantitative RT-PCR, the highest viral loads were detected in brain stem and spinal cord. Similar porcine astrovirus type 3 was also detected in archived brain and spinal cord samples from another 2 geographically distant farms. Viral RNA was predominantly restricted to neurons, particularly in the brain stem, cerebellum (Purkinje cells), and cervical spinal cord. Astrovirus was generally undetectable in feces but present in respiratory samples, indicating a possible respiratory infection. Astrovirus could cause common, neuroinvasive epidemic disease.

GBM skin metastasis: a case report and review of the literature

PubMed Central

Lewis, Gary D; Rivera, Andreana L; Tremont-Lukats, Ivo W; Ballester-Fuentes, Leomar Y; Zhang, Yi Jonathan; Teh, Bin S

2017-01-01

Glioblastoma (GBM) is the most common type of malignant tumor found in the brain, and acts very aggressively by quickly and diffusely infiltrating the surrounding brain parenchyma. Despite its aggressive nature, GBM is rarely found to spread extracranially and develop distant metastases. The most common sites of these rare metastases are the lungs, pleura and cervical lymph nodes. There are also a few case reports of skin metastasis. We present the clinical, imaging and pathologic features of a case of a GBM with metastasis to the soft tissue scar and skin near the original craniotomy site. In addition, we discuss the details of this case in the context of the previously reported literature. PMID:28718312

Characterization of Cerebral White Matter Properties Using Quantitative Magnetic Resonance Imaging Stains

PubMed Central

Hurley, Samuel A.; Samsonov, Alexey A.; Adluru, Nagesh; Hosseinbor, Ameer Pasha; Mossahebi, Pouria; Tromp, Do P.M.; Zakszewski, Elizabeth; Field, Aaron S.

2011-01-01

Abstract The image contrast in magnetic resonance imaging (MRI) is highly sensitive to several mechanisms that are modulated by the properties of the tissue environment. The degree and type of contrast weighting may be viewed as image filters that accentuate specific tissue properties. Maps of quantitative measures of these mechanisms, akin to microstructural/environmental-specific tissue stains, may be generated to characterize the MRI and physiological properties of biological tissues. In this article, three quantitative MRI (qMRI) methods for characterizing white matter (WM) microstructural properties are reviewed. All of these measures measure complementary aspects of how water interacts with the tissue environment. Diffusion MRI, including diffusion tensor imaging, characterizes the diffusion of water in the tissues and is sensitive to the microstructural density, spacing, and orientational organization of tissue membranes, including myelin. Magnetization transfer imaging characterizes the amount and degree of magnetization exchange between free water and macromolecules like proteins found in the myelin bilayers. Relaxometry measures the MRI relaxation constants T1 and T2, which in WM have a component associated with the water trapped in the myelin bilayers. The conduction of signals between distant brain regions occurs primarily through myelinated WM tracts; thus, these methods are potential indicators of pathology and structural connectivity in the brain. This article provides an overview of the qMRI stain mechanisms, acquisition and analysis strategies, and applications for these qMRI stains. PMID:22432902

Sexually Monomorphic Maps and Dimorphic Responses in Rat Genital Cortex.

PubMed

Lenschow, Constanze; Copley, Sean; Gardiner, Jayne M; Talbot, Zoe N; Vitenzon, Ariel; Brecht, Michael

2016-01-11

Mammalian external genitals show sexual dimorphism [1, 2] and can change size and shape upon sexual arousal. Genitals feature prominently in the oldest pieces of figural art [3] and phallic depictions of penises informed psychoanalytic thought about sexuality [4, 5]. Despite this longstanding interest, the neural representations of genitals are still poorly understood [6]. In somatosensory cortex specifically, many studies did not detect any cortical representation of genitals [7-9]. Studies in humans debate whether genitals are represented displaced below the foot of the cortical body map [10-12] or whether they are represented somatotopically [13-15]. We wondered what a high-resolution mapping of genital representations might tell us about the sexual differentiation of the mammalian brain. We identified genital responses in rat somatosensory cortex in a region previously assigned as arm/leg cortex. Genital responses were more common in males than in females. Despite such response dimorphism, we observed a stunning anatomical monomorphism of cortical penis and clitoris input maps revealed by cytochrome-oxidase-staining of cortical layer 4. Genital representations were somatotopic and bilaterally symmetric, and their relative size increased markedly during puberty. Size, shape, and erect posture give the cortical penis representation a phallic appearance pointing to a role in sexually aroused states. Cortical genital neurons showed unusual multi-body-part responses and sexually dimorphic receptive fields. Specifically, genital neurons were co-activated by distant body regions, which are touched during mounting in the respective sex. Genital maps indicate a deep homology of penis and clitoris representations in line with a fundamentally bi-sexual layout [16] of the vertebrate brain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Natural world physical, brain operational, and mind phenomenal space-time

NASA Astrophysics Data System (ADS)

Fingelkurts, Andrew A.; Fingelkurts, Alexander A.; Neves, Carlos F. H.

2010-06-01

Concepts of space and time are widely developed in physics. However, there is a considerable lack of biologically plausible theoretical frameworks that can demonstrate how space and time dimensions are implemented in the activity of the most complex life-system - the brain with a mind. Brain activity is organized both temporally and spatially, thus representing space-time in the brain. Critical analysis of recent research on the space-time organization of the brain's activity pointed to the existence of so-called operational space-time in the brain. This space-time is limited to the execution of brain operations of differing complexity. During each such brain operation a particular short-term spatio-temporal pattern of integrated activity of different brain areas emerges within related operational space-time. At the same time, to have a fully functional human brain one needs to have a subjective mental experience. Current research on the subjective mental experience offers detailed analysis of space-time organization of the mind. According to this research, subjective mental experience (subjective virtual world) has definitive spatial and temporal properties similar to many physical phenomena. Based on systematic review of the propositions and tenets of brain and mind space-time descriptions, our aim in this review essay is to explore the relations between the two. To be precise, we would like to discuss the hypothesis that via the brain operational space-time the mind subjective space-time is connected to otherwise distant physical space-time reality.

Unmasking local activity within local field potentials (LFPs) by removing distal electrical signals using independent component analysis.

PubMed

Whitmore, Nathan W; Lin, Shih-Chieh

2016-05-15

Local field potentials (LFPs) are commonly thought to reflect the aggregate dynamics in local neural circuits around recording electrodes. However, we show that when LFPs are recorded in awake behaving animals against a distal reference on the skull as commonly practiced, LFPs are significantly contaminated by non-local and non-neural sources arising from the reference electrode and from movement-related noise. In a data set with simultaneously recorded LFPs and electroencephalograms (EEGs) across multiple brain regions while rats perform an auditory oddball task, we used independent component analysis (ICA) to identify signals arising from electrical reference and from volume-conducted noise based on their distributed spatial pattern across multiple electrodes and distinct power spectral features. These sources of distal electrical signals collectively accounted for 23-77% of total variance in unprocessed LFPs, as well as most of the gamma oscillation responses to the target stimulus in EEGs. Gamma oscillation power was concentrated in volume-conducted noise and was tightly coupled with the onset of licking behavior, suggesting a likely origin of muscle activity associated with body movement or orofacial movement. The removal of distal signal contamination also selectively reduced correlations of LFP/EEG signals between distant brain regions but not within the same region. Finally, the removal of contamination from distal electrical signals preserved an event-related potential (ERP) response to auditory stimuli in the frontal cortex and also increased the coupling between the frontal ERP amplitude and neuronal activity in the basal forebrain, supporting the conclusion that removing distal electrical signals unmasked local activity within LFPs. Together, these results highlight the significant contamination of LFPs by distal electrical signals and caution against the straightforward interpretation of unprocessed LFPs. Our results provide a principled approach to identify and remove such contamination to unmask local LFPs. Published by Elsevier Inc.

Unmasking local activity within local field potentials (LFPs) by removing distal electrical signals using independent component analysis

PubMed Central

Whitmore, Nathan W.; Lin, Shih-Chieh

2016-01-01

Local field potentials (LFPs) are commonly thought to reflect the aggregate dynamics in local neural circuits around recording electrodes. However, we show that when LFPs are recorded in awake behaving animals against a distal reference on the skull as commonly practiced, LFPs are significantly contaminated by non-local and non-neural sources arising from the reference electrode and from movement-related noise. In a data set with simultaneously recorded LFPs and electroencephalograms (EEGs) across multiple brain regions while rats perform an auditory oddball task, we used independent component analysis (ICA) to identify signals arising from electrical reference and from volume-conducted noise based on their distributed spatial pattern across multiple electrodes and distinct power spectral features. These sources of distal electrical signals collectively accounted for 23–77% of total variance in unprocessed LFPs, as well as most of the gamma oscillation responses to the target stimulus in EEGs. Gamma oscillation power was concentrated in volume-conducted noise and was tightly coupled with the onset of licking behavior, suggesting a likely origin of muscle activity associated with body movement or orofacial movement. The removal of distal signal contamination also selectively reduced correlations of LFP/EEG signals between distant brain regions but not within the same region. Finally, the removal of contamination from distal electrical signals preserved an event-related potential (ERP) response to auditory stimuli in the frontal cortex and also increased the coupling between the frontal ERP amplitude and neuronal activity in the basal forebrain, supporting the conclusion that removing distal electrical signals unmasked local activity within LFPs. Together, these results highlight the significant contamination of LFPs by distal electrical signals and caution against the straightforward interpretation of unprocessed LFPs. Our results provide a principled approach to identify and remove such contamination to unmask local LFPs. PMID:26899209

A High-Resolution Enhancer Atlas of the Developing Telencephalon

PubMed Central

Visel, Axel; Taher, Leila; Girgis, Hani; May, Dalit; Golonzhka, Olga; Hoch, Renee; McKinsey, Gabriel L.; Pattabiraman, Kartik; Silberberg, Shanni N.; Blow, Matthew J.; Hansen, David V.; Nord, Alex S.; Akiyama, Jennifer A.; Holt, Amy; Hosseini, Roya; Phouanenavong, Sengthavy; Plajzer-Frick, Ingrid; Shoukry, Malak; Afzal, Veena; Kaplan, Tommy; Kriegstein, Arnold R.; Rubin, Edward M.; Ovcharenko, Ivan; Pennacchio, Len A.; Rubenstein, John L. R.

2013-01-01

Summary The mammalian telencephalon plays critical roles in cognition, motor function, and emotion. While many of the genes required for its development have been identified, the distant-acting regulatory sequences orchestrating their in vivo expression are mostly unknown. Here we describe a digital atlas of in vivo enhancers active in subregions of the developing telencephalon. We identified over 4,600 candidate embryonic forebrain enhancers and studied the in vivo activity of 329 of these sequences in transgenic mouse embryos. We generated serial sets of histological brain sections for 145 reproducible forebrain enhancers, resulting in a publicly accessible web-based data collection comprising over 32,000 sections. We also used epigenomic analysis of human and mouse cortex tissue to directly compare the genome-wide enhancer architecture in these species. These data provide a primary resource for investigating gene regulatory mechanisms of telencephalon development and enable studies of the role of distant-acting enhancers in neurodevelopmental disorders. PMID:23375746

Beaming into the News: A System for and Case Study of Tele-Immersive Journalism.

PubMed

Kishore, Sameer; Navarro, Xavi; Dominguez, Eva; de la Pena, Nonny; Slater, Mel

2016-05-25

We show how a combination of virtual reality and robotics can be used to beam a physical representation of a person to a distant location, and describe an application of this system in the context of journalism. Full body motion capture data of a person is streamed and mapped in real time, onto the limbs of a humanoid robot present at the remote location. A pair of cameras in the robot's 'eyes' stream stereoscopic video back to the HMD worn by the visitor, and a two-way audio connection allows the visitor to talk to people in the remote destination. By fusing the multisensory data of the visitor with the robot, the visitor's 'consciousness' is transformed to the robot's body. This system was used by a journalist to interview a neuroscientist and a chef 900 miles distant, about food for the brain, resulting in an article published in the popular press.

Beaming into the News: A System for and Case Study of Tele-Immersive Journalism.

PubMed

Kishore, Sameer; Navarro, Xavi; Dominguez, Eva; De La Pena, Nonny; Slater, Mel

2018-03-01

We show how a combination of virtual reality and robotics can be used to beam a physical representation of a person to a distant location, and describe an application of this system in the context of journalism. Full body motion capture data of a person is streamed and mapped in real time, onto the limbs of a humanoid robot present at the remote location. A pair of cameras in the robots eyes stream stereoscopic video back to the HMD worn by the visitor, and a two-way audio connection allows the visitor to talk to people in the remote destination. By fusing the multisensory data of the visitor with the robot, the visitors consciousness is transformed to the robots body. This system was used by a journalist to interview a neuroscientist and a chef 900 miles distant, about food for the brain, resulting in an article published in the popular press.

Proton MRS of the peritumoral brain.

PubMed

Chernov, Mikhail F; Kubo, Osami; Hayashi, Motohiro; Izawa, Masahiro; Maruyama, Takashi; Usukura, Masao; Ono, Yuko; Hori, Tomokatsu; Takakura, Kintomo

2005-02-15

Long-echo (TR: 2000 ms, TE: 136 ms) proton MRS of the cerebral tissue in the vicinity to intracranial lesion was done in 15 patients, mainly with parenchymal brain tumors. Significant decrease of N-acetylaspartate (NAA) (P<0.001) and more frequent presence of lactate (P<0.01) comparing with distant normal white matter were found in the perilesional brain tissue. The level of NAA in the perilesional brain tissue had negative associations with presence of lactate in the lesion (P<0.05), excess of lactate in the lesion compared to perilesional brain (P<0.01), grade of the perilesional edema (P<0.01) and patient's age (P<0.05). Multivariate analysis disclosed that identification of lactate in the lesion is associated with lower relative NAA content in the perilesional brain tissue, independently on the presence or absence of any other factor, including brain edema (P<0.001). In patients with lobar lesions who had at least one epileptic seizure during course of their disease the relative NAA content in the perilesional brain was significantly lower, comparing with those who were seizure-free (P<0.05). Therefore, lactate diffused from the tumor, or other metabolites secreted by lactate-producing neoplasm, should be considered as important contributors to the neuronal dysfunction in the surrounding brain. Decrease of NAA in the vicinity to intracranial lesions may reflect neuronal alteration responsible for associated epilepsy.

The role of high-frequency oscillatory activity in reward processing and learning.

PubMed

Marco-Pallarés, Josep; Münte, Thomas F; Rodríguez-Fornells, Antoni

2015-02-01

Oscillatory activity has been proposed as a key mechanism in the integration of brain activity of distant structures. Particularly, high frequency brain oscillatory activity in the beta and gamma range has received increasing interest in the domains of attention and memory. In addition, a number of recent studies have revealed an increase of beta-gamma activity (20-35 Hz) after unexpected or relevant positive reward outcomes. In the present manuscript we review the literature on this phenomenon and we propose that this activity is a brain signature elicited by unexpected positive outcomes in order to transmit a fast motivational value signal to the reward network. In addition, we hypothesize that beta-gamma oscillatory activity indexes the interaction between attentional and emotional systems, and that it directly reflects the appearance of unexpected positive rewards in learning-related contexts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Multiple distant origins for green sea turtles aggregating off Gorgona Island in the Colombian eastern Pacific.

PubMed

Amorocho, Diego F; Abreu-Grobois, F Alberto; Dutton, Peter H; Reina, Richard D

2012-01-01

Mitochondrial DNA analyses have been useful for resolving maternal lineages and migratory behavior to foraging grounds (FG) in sea turtles. However, little is known about source rookeries and haplotype composition of foraging green turtle aggregations in the southeastern Pacific. We used mitochondrial DNA control region sequences to identify the haplotype composition of 55 green turtles, Chelonia mydas, captured in foraging grounds of Gorgona National Park in the Colombian Pacific. Amplified fragments of the control region (457 bp) revealed the presence of seven haplotypes, with haplotype (h) and nucleotide (π) diversities of h = 0.300±0.080 and π = 0.009±0.005 respectively. The most common haplotype was CMP4 observed in 83% of individuals, followed by CMP22 (5%). The genetic composition of the Gorgona foraging population primarily comprised haplotypes that have been found at eastern Pacific rookeries including Mexico and the Galapagos, as well as haplotypes of unknown stock origin that likely originated from more distant western Pacific rookeries. Mixed stock analysis suggests that the Gorgona FG population is comprised mostly of animals from the Galapagos rookery (80%). Lagrangian drifter data showed that movement of turtles along the eastern Pacific coast and eastward from distant western and central Pacific sites was possible through passive drift. Our results highlight the importance of this protected area for conservation management of green turtles recruited from distant sites along the eastern Pacific Ocean.

Multiple Distant Origins for Green Sea Turtles Aggregating off Gorgona Island in the Colombian Eastern Pacific

PubMed Central

Amorocho, Diego F.; Abreu-Grobois, F. Alberto; Dutton, Peter H.; Reina, Richard D.

2012-01-01

Mitochondrial DNA analyses have been useful for resolving maternal lineages and migratory behavior to foraging grounds (FG) in sea turtles. However, little is known about source rookeries and haplotype composition of foraging green turtle aggregations in the southeastern Pacific. We used mitochondrial DNA control region sequences to identify the haplotype composition of 55 green turtles, Chelonia mydas, captured in foraging grounds of Gorgona National Park in the Colombian Pacific. Amplified fragments of the control region (457 bp) revealed the presence of seven haplotypes, with haplotype (h) and nucleotide (π) diversities of h = 0.300±0.080 and π = 0.009±0.005 respectively. The most common haplotype was CMP4 observed in 83% of individuals, followed by CMP22 (5%). The genetic composition of the Gorgona foraging population primarily comprised haplotypes that have been found at eastern Pacific rookeries including Mexico and the Galapagos, as well as haplotypes of unknown stock origin that likely originated from more distant western Pacific rookeries. Mixed stock analysis suggests that the Gorgona FG population is comprised mostly of animals from the Galapagos rookery (80%). Lagrangian drifter data showed that movement of turtles along the eastern Pacific coast and eastward from distant western and central Pacific sites was possible through passive drift. Our results highlight the importance of this protected area for conservation management of green turtles recruited from distant sites along the eastern Pacific Ocean. PMID:22319635

Metastases from distant primary tumours on the head and neck: clinical manifestation and diagnostics of 91 cases.

PubMed

Baum, Sven Holger; Mohr, Christopher

2018-06-01

The aim of this study was to evaluate which primary tumours metastasize on the head and neck region, identify the kind of clinical manifestation, the types of diagnostics that should be performed, and prove that the therapy appears possible and useful. As many as 91 patients with a distant metastasis on the head and neck were enrolled in this retrospective clinical study from January 2004 to September 2016. All the patients were evaluated for clinical symptoms, primary tumour, localization, diagnostics, and surgical procedure. A total of 31 patients had asymptomatic swelling, 27 patients had symptomatic swelling, and nine experienced isolated pain without swelling. Most other symptoms were organ-specific. The most frequent localizations were the orbit (44 metastases), mandible (19), neck region (9), and skin (7). The most common primary tumours were breast carcinoma (44), bronchial carcinoma (12), and renal carcinoma (9). A biopsy was performed on 38 patients, a partial resection was done on 28 patients, extirpation on six patients, and a radical resection on 19 patients. Distant metastases on the head and neck are rare and, therefore, pose a challenge for the oncologist and other involved disciplines. Most distant metastases occur within the first five years. Late metastases, especially in breast carcinoma, are still possible after 20 years. A surgical examination should be carried out if the findings are not clear due to multiple differential diagnoses. In particular, surgical options under palliative aspects should be examined.

Overall survival and the response to radiotherapy among molecular subtypes of breast cancer brain metastases treated with targeted therapies.

PubMed

Miller, Jacob A; Kotecha, Rupesh; Ahluwalia, Manmeet S; Mohammadi, Alireza M; Chao, Samuel T; Barnett, Gene H; Murphy, Erin S; Vogelbaum, Michael A; Angelov, Lilyana; Peereboom, David M; Suh, John H

2017-06-15

The current study was conducted to investigate survival and the response to radiotherapy among patients with molecular subtypes of breast cancer brain metastases treated with or without targeted therapies. Patients diagnosed with breast cancer brain metastases at a single tertiary care institution were included. The primary outcome was overall survival, whereas secondary outcomes included the cumulative incidences of distant intracranial failure, local failure, and radiation necrosis. Competing risks regression was used to model secondary outcomes. Within the study period, 547 patients presented with 3224 brain metastases and met inclusion criteria. Among patients with human epidermal growth factor receptor 2 (HER2)-amplified disease, 80% received HER2 antibodies and 38% received HER2/epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The median survival was significantly shorter in the basal cohort (8.4 months), and progressively increased in the luminal A (12.3 months), HER2-positive (15.4 months), and luminal B (18.8 months) cohorts (P<.001). Among patients with HER2-amplified disease, the median survival was extended with the use of both HER2 antibodies (17.9 months vs 15.1 months; P = .04) and TKIs (21.1 months vs 15.4 months; P = .03). The 12-month cumulative incidences of local failure among molecular subtypes were 6.0% in the luminal A cohort, 10.3% in the luminal B cohort, 15.4% in the HER2-positive cohort, and 9.9% in the basal cohort (P = .01). Concurrent HER2/epidermal growth factor receptor TKIs with stereotactic radiosurgery significantly decreased the 12-month cumulative incidence of local failure from 15.1% to 5.7% (P<.001). Molecular subtypes appear to be prognostic for survival and predictive of the response to radiotherapy. TKIs were found to improve survival and local control, and may decrease the rate of distant failure. To preserve neurocognition, these results support a paradigm of upfront radiosurgery and HER2-directed therapy in the HER2-amplified population, reserving whole-brain radiotherapy for salvage. Cancer 2017;123:2283-2293. © 2017 American Cancer Society. © 2017 American Cancer Society.

Amygdala atrophy affects emotion-related activity in face-responsive regions in frontotemporal degeneration.

PubMed

De Winter, François-Laurent; Van den Stock, Jan; de Gelder, Beatrice; Peeters, Ronald; Jastorff, Jan; Sunaert, Stefan; Vanduffel, Wim; Vandenberghe, Rik; Vandenbulcke, Mathieu

2016-09-01

In the healthy brain, modulatory influences from the amygdala commonly explain enhanced activation in face-responsive areas by emotional facial expressions relative to neutral expressions. In the behavioral variant frontotemporal dementia (bvFTD) facial emotion recognition is impaired and has been associated with atrophy of the amygdala. By combining structural and functional MRI in 19 patients with bvFTD and 20 controls we investigated the neural effects of emotion in face-responsive cortex and its relationship with amygdalar gray matter (GM) volume in neurodegeneration. Voxel-based morphometry revealed decreased GM volume in anterior medio-temporal regions including amygdala in patients compared to controls. During fMRI, we presented dynamic facial expressions (fear and chewing) and their spatiotemporally scrambled versions. We found enhanced activation for fearful compared to neutral faces in ventral temporal cortex and superior temporal sulcus in controls, but not in patients. In the bvFTD group left amygdalar GM volume correlated positively with emotion-related activity in left fusiform face area (FFA). This correlation was amygdala-specific and driven by GM in superficial and basolateral (BLA) subnuclei, consistent with reported amygdalar-cortical networks. The data suggests that anterior medio-temporal atrophy in bvFTD affects emotion processing in distant posterior areas. Copyright © 2016 Elsevier Ltd. All rights reserved.

Remote Triggering in the Koyna-Warna Reservoir-Induced Seismic Zone, Western India

NASA Astrophysics Data System (ADS)

Bansal, Abhey Ram; Rao, N. Purnachandra; Peng, Zhigang; Shashidhar, D.; Meng, Xiaofeng

2018-03-01

Dynamic triggering following large distant earthquakes has been observed in many regions globally. In this study, we present evidence for remote dynamic triggering in the Koyna-Warna region of Western India, which is known to be a premier site of reservoir-induced seismicity. Using data from a closely spaced broadband network of 11 stations operated in the region since 2005, we conduct a systematic search for dynamic triggering following 20 large distant earthquakes with dynamic stresses of at least 1 kPa in the region. We find that the only positive cases of dynamic triggering occurred during 11 April 2012, Mw8.6 Indian Ocean earthquake and its largest aftershock of Mw8.2. In the first case, microearthquakes started to occur in the first few cycles of the Love waves, and the largest event of magnitude 3.3 occurred during the first few cycles of the Rayleigh waves. The increase of microseismicity lasted for up to five days, including a magnitude 4.8 event occurred approximately three days later. Our results suggest that the Koyna-Warna region is stress sensitive and susceptible for remote dynamic triggering, although the apparent triggering threshold appears to be slightly higher than other regions.

Contributions of regional and intercontinental transport to surface ozone in the Tokyo area

NASA Astrophysics Data System (ADS)

Yoshitomi, M.; Wild, O.; Akimoto, H.

2011-08-01

Japan lies downwind of the Asian continent and for much of the year air quality is directly influenced by emissions of ozone precursors over these heavily-populated and rapidly-industrializing regions. This study examines the extent to which oxidant transport from regional and distant anthropogenic sources influences air quality in Japan in springtime, when these contributions are largest. We find that European and North American contributions to surface ozone over Japan in spring are persistent, averaging 3.5±1.1 ppb and 2.8±0.5 ppb respectively, and are greatest in cold continental outflow conditions following the passage of cold fronts. Contributions from China are larger, 4.0±2.8 ppb, and more variable, as expected for a closer source region, and are generally highest near cold fronts preceding the influence of more distant sources. The stratosphere provides a varying but ever-present background of ozone of about 11.2±2.5 ppb during spring. Local sources over Japan and Korea have a relatively small impact on mean ozone, 2.4±7.6 ppb, but this masks a strong diurnal signal, and local sources clearly dominate during episodes of high daytime ozone. By examining the meteorological mechanisms that favour transport from different source regions, we demonstrate that while maximum foreign influence generally does not occur at the same time as the greatest buildup of oxidants from local sources, it retains a significant influence under these conditions. It is thus clear that while meteorological boundaries provide some protection from foreign influence during oxidant outbreaks in Tokyo, these distant sources still make a substantial contribution to exceedance of the Japanese ozone air quality standard in springtime.

Contributions of regional and intercontinental transport to surface ozone in Tokyo

NASA Astrophysics Data System (ADS)

Yoshitomi, M.; Wild, O.; Akimoto, H.

2011-04-01

Japan lies downwind of the Asian continent and for much of the year air quality is directly influenced by emissions of ozone precursors over these heavily-populated and rapidly-industrializing regions. This study examines the extent to which oxidant transport from regional and distant anthropogenic sources influences air quality in Japan in springtime, when these contributions are largest. We find that European and North American contributions to surface ozone over Japan in spring are persistent, averaging 3.5±1.1 ppb and 2.8±0.5 ppb respectively, and are greatest in cold continental outflow conditions following the passage of cold fronts. Contributions from China are larger, 4.0±2.8 ppb, and more variable, as expected for a closer source region, and are generally highest near cold fronts preceding the influence of more distant sources. The stratosphere provides a varying but ever-present background of ozone of about 11.2±2.5 ppb during spring. Local sources over Japan and Korea have a relatively small impact on mean ozone, 2.4±7.6 ppb, but this masks a strong diurnal signal, and local sources clearly dominate during episodes of high daytime ozone. By examining the meteorological mechanisms that favour transport from different source regions, we demonstrate that while maximum foreign influence generally does not occur at the same time as the greatest buildup of oxidants from local sources, it retains a significant influence under these conditions. It is thus clear that while meteorological boundaries provide some protection from foreign influence during oxidant outbreaks in Tokyo, these distant sources still make a substantial contribution to exceedance of the Japanese ozone air quality standard in springtime.

Optogenetic approaches to characterize the long-range synaptic pathways from the hypothalamus to brain stem autonomic nuclei

PubMed Central

Piñol, Ramón A.; Bateman, Ryan; Mendelowitz, David

2012-01-01

Recent advances in optogenetic methods demonstrate the feasibility of selective photoactivation at the soma of neurons that express channelrhodopsin-2 (ChR2), but a comprehensive evaluation of different methods to selectively evoke transmitter release from distant synapses using optogenetic approaches is needed. Here we compared different lentiviral vectors, with sub-population-specific and strong promoters, and transgenic methods to express and photostimulate ChR2 in the long-range projections of paraventricular nucleus of the hypothalamus (PVN) neurons to brain stem cardiac vagal neurons (CVNs). Using PVN subpopulation-specific promoters for vasopressin and oxytocin, we were able to depolarize the soma of these neurons upon photostimulation, but these promoters were not strong enough to drive sufficient expression for optogenetic stimulation and synaptic release from the distal axons. However, utilizing the synapsin promoter photostimulation of distal PVN axons successfully evoked glutamatergic excitatory post-synaptic currents in CVNs. Employing the Cre/loxP system, using the Sim-1 Cre-driver mouse line, we found that the Rosa-CAG-LSL-ChR2-EYFP Cre-responder mice expressed higher levels of ChR2 than the Rosa-CAG-LSL-ChR2-tdTomato line in the PVN, judged by photo-evoked currents at the soma. However, neither was able to drive sufficient expression to observe and photostimulate the long-range projections to brainstem autonomic regions. We conclude that a viral vector approach with a strong promoter is required for successful optogenetic stimulation of distal axons to evoke transmitter release in pre-autonomic PVN neurons. This approach can be very useful to study important hypothalamus-brainstem connections, and can be easily modified to selectively activate other long-range projections within the brain. PMID:22890236

Cortico-cortical and motor evoked potentials to single and paired-pulse stimuli: An exploratory transcranial magnetic and intracranial electric brain stimulation study.

PubMed

Boulogne, Sébastien; Andre-Obadia, Nathalie; Kimiskidis, Vasilios K; Ryvlin, Philippe; Rheims, Sylvain

2016-11-01

Paired-pulse (PP) paradigms are commonly employed to assess in vivo cortical excitability using transcranial magnetic stimulation (TMS) to stimulate the primary motor cortex and modulate the induced motor evoked potential (MEP). Single-pulse cortical direct electrical stimulation (DES) during intracerebral EEG monitoring allows the investigation of brain connectivity by eliciting cortico-cortical evoked potentials (CCEPs). However, PP paradigm using intracerebral DES has rarely been reported and has never been previously compared with TMS. The work was intended (i) to verify that the well-established modulations of MEPs following PP TMS remain similar using DES in the motor cortex, and (ii) to evaluate if a similar pattern could be observed in distant cortico-cortical connections through modulations of CCEP. Three patients undergoing intracerebral EEG monitoring with electrodes implanted in the central region were studied. Single-pulse DES (1-3 mA, 1 ms, 0.2 Hz) and PP DES using six interstimulus intervals (5, 15, 30, 50, 100, and 200 ms) in the motor cortex with concomitant recording of CCEPs and MEPs in contralateral muscles were performed. Finally, a navigated PP TMS session targeted the intracranial stimulation site to record TMS-induced MEPs in two patients. MEP modulations elicited by PP intracerebral DES proved similar among the three patients and to those obtained by PP TMS. CCEP modulations elicited by PP intracerebral DES usually showed a pattern comparable to that of MEP, although a different pattern could be observed occasionally. PP intracerebral DES seems to involve excitatory and inhibitory mechanisms similar to PP TMS and allows the recording of intracortical inhibition and facilitation modulation on cortico-cortical connections. Hum Brain Mapp 37:3767-3778, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Advanced fiber tracking in early acquired brain injury causing cerebral palsy.

PubMed

Lennartsson, F; Holmström, L; Eliasson, A-C; Flodmark, O; Forssberg, H; Tournier, J-D; Vollmer, B

2015-01-01

Diffusion-weighted MR imaging and fiber tractography can be used to investigate alterations in white matter tracts in patients with early acquired brain lesions and cerebral palsy. Most existing studies have used diffusion tensor tractography, which is limited in areas of complex fiber structures or pathologic processes. We explored a combined normalization and probabilistic fiber-tracking method for more realistic fiber tractography in this patient group. This cross-sectional study included 17 children with unilateral cerebral palsy and 24 typically developing controls. DWI data were collected at 1.5T (45 directions, b=1000 s/mm(2)). Regions of interest were defined on a study-specific fractional anisotropy template and mapped onto subjects for fiber tracking. Probabilistic fiber tracking of the corticospinal tract and thalamic projections to the somatosensory cortex was performed by using constrained spherical deconvolution. Tracts were qualitatively assessed, and DTI parameters were extracted close to and distant from lesions and compared between groups. The corticospinal tract and thalamic projections to the somatosensory cortex were realistically reconstructed in both groups. Structural changes to tracts were seen in the cerebral palsy group and included splits, dislocations, compaction of the tracts, or failure to delineate the tract and were associated with underlying pathology seen on conventional MR imaging. Comparisons of DTI parameters indicated primary and secondary neurodegeneration along the corticospinal tract. Corticospinal tract and thalamic projections to the somatosensory cortex showed dissimilarities in both structural changes and DTI parameters. Our proposed method offers a sensitive means to explore alterations in WM tracts to further understand pathophysiologic changes following early acquired brain injury. © 2015 by American Journal of Neuroradiology.

Differential induction and spread of tau pathology in young PS19 tau transgenic mice following intracerebral injections of pathological tau from Alzheimer’s disease or corticobasal degeneration brains

PubMed Central

Boluda, Susana; Iba, Michiyo; Zhang, Bin; Raible, Kevin M.; Lee, Virginia M-Y.; Trojanowski, John Q.

2015-01-01

Filamentous tau pathologies are hallmark lesions of several neurodegenerative tauopathies including Alzheimer’s disease (AD) and corticobasal degeneration (CBD) which show cell type-specific and topographically distinct tau inclusions. Growing evidence supports templated transmission of tauopathies through functionally interconnected neuroanatomical pathways suggesting that different self-propagating strains of pathological tau could account for the diverse manifestations of neurodegenerative tauopathies. Here, we describe the rapid and distinct cell type-specific spread of pathological tau following intracerebral injections of CBD or AD brain extracts enriched in pathological tau (designated CBD-Tau and AD-Tau, respectively) in young human mutant P301S tau transgenic (Tg) mice (line PS19) ~6–9 months before they show onset of mutant tau transgene-induced tau pathology. At 1 month post-injection of CBD-Tau, tau inclusions developed predominantly in oligodendrocytes of the fimbria and white matter near the injection sites with infrequent intraneuronal tau aggregates. In contrast, injections of AD-Tau in young PS19 mice induced tau pathology predominantly in neuronal perikarya with little or no oligodendrocyte involvement 1 month post-injection. With longer post-injection survival intervals of up to 6 months, CBD-Tau- and AD-Tau-induced tau pathology spread to different brain regions distant from the injection sites while maintaining the cell type-specific pattern noted above. Finally, CA3 neuron loss was detected 3 months post-injection of AD-Tau but not CBD-Tau. Thus, AD-Tau and CBD-Tau represent specific pathological tau strains that spread differentially and may underlie distinct clinical and pathological features of these two tauopathies. Hence, these strains could become targets to develop disease-modifying therapies for CBD and AD. PMID:25534024

Afferent projections to the mammillary complex of the rat, with special reference to those from surrounding hypothalamic regions

NASA Technical Reports Server (NTRS)

Gonzalo-Ruiz, A.; Alonso, A.; Sanz, J. M.; Llinas, R. R.

1992-01-01

To better understand the functional organization of the mammillary nuclei, we investigated the afferents to this nuclear complex in the rat with iontophoretically injected wheat germ agglutinin conjugated to horseradish peroxidase. Particular attention was paid to tracing local hypothalamic afferents to these nuclei. Injections into the medial mammillary nucleus (MMN) revealed strong projections from the subicular region, and weaker projections from the prefrontal cortex, medial septum, and the nucleus of the diagonal band of Broca. Other descending subcortical projections to the MMN arise from the anterior and the lateral hypothalamic area, the medial preoptic area, and the bed nucleus of the stria terminalis. Ascending afferents to the MMN were found to originate in the raphe and various tegmental nuclei. Following all injections into the MMN, labelled neurons were found in nuclei surrounding the mammillary body. The lateral and posterior subdivisions of the tuberomammillary nucleus projected mainly to the pars medianus and pars medialis of the MMN. The dorsal and ventral premammillary nuclei projected to the pars lateralis of the MMN. The supramammillary nucleus at rostral level had a small projection to the pars medialis and lateralis of the MMN. However, the most obvious projection from this nucleus was to the pars posterior of the MMN, chiefly from the lateral part of the caudal supramammillary nucleus. Injections into the lateral mammillary nucleus revealed inputs from the presubiculum, parasubiculum, septal region, dorsal tegmental nucleus, dorsal raphe nucleus, and periaqueductal gray. In addition, the lateral mammillary nucleus was found to receive a moderate projection from the medial part of the supramammillary nucleus and stronger projections from the lateral part of the caudal supramammillary nucleus. A very light projection was also seen from the lateral and posterior subdivisions of the tuberomammillary nucleus. These findings add to our knowledge of the extensive and complex connectivity of the mammillary nuclei. In particular, the local connections we have demonstrated with the supramammillary and tuberomammillary nuclei indicate the existence of significant local circuits as well as circuits involving more distant brain regions such as the septal nuclei, subiculum, prefrontal cortex, and brain stem tegmentum.

Distance biases in the estimation of the physical properties of Hi-GAL compact sources - I. Clump properties and the identification of high-mass star-forming candidates

NASA Astrophysics Data System (ADS)

Baldeschi, Adriano; Elia, D.; Molinari, S.; Pezzuto, S.; Schisano, E.; Gatti, M.; Serra, A.; Merello, M.; Benedettini, M.; Di Giorgio, A. M.; Liu, J. S.

2017-04-01

The degradation of spatial resolution in star-forming regions, observed at large distances (d ≳ 1 kpc) with Herschel, can lead to estimates of the physical parameters of the detected compact sources (clumps), which do not necessarily mirror the properties of the original population of cores. This paper aims at quantifying the bias introduced in the estimation of these parameters by the distance effect. To do so, we consider Herschel maps of nearby star-forming regions taken from the Herschel Gould Belt survey, and simulate the effect of increased distance to understand what amount of information is lost when a distant star-forming region is observed with Herschel resolution. In the maps displaced to different distances we extract compact sources, and we derive their physical parameters as if they were original Herschel infrared Galactic Plane Survey maps of the extracted source samples. In this way, we are able to discuss how the main physical properties change with distance. In particular, we discuss the ability of clumps to form massive stars: we estimate the fraction of distant sources that are classified as high-mass stars-forming objects due to their position in the mass versus radius diagram, that are only 'false positives'. We also give a threshold for high-mass star formation M>1282 (r/ [pc])^{1.42} M_{⊙}. In conclusion, this paper provides the astronomer dealing with Herschel maps of distant star-forming regions with a set of prescriptions to partially recover the character of the core population in unresolved clumps.

Relationship between the Geotail spacecraft potential and the magnetospheric electron number density including the distant tail regions

NASA Astrophysics Data System (ADS)

Ishisaka, K.; Okada, T.; Tsuruda, K.; Hayakawa, H.; Mukai, T.; Matsumoto, H.

2001-04-01

The spacecraft potential has been used to derive the electron number density surrounding the spacecraft in the magnetosphere and solar wind. We have investigated the correlation between the spacecraft potential of the Geotail spacecraft and the electron number density derived from the plasma waves in the solar wind and almost all the regions of the magnetosphere, except for the high-density plasmasphere, and obtained an empirical formula to show their relation. The new formula is effective in the range of spacecraft potential from a few volts up to 90 V, corresponding to the electron number density from 0.001 to 50 cm-3. We compared the electron number density obtained by the empirical formula with the density obtained by the plasma wave and plasma particle measurements. On occasions the density determined by plasma wave measurements in the lobe region is different from that calculated by the empirical formula. Using the difference in the densities measured by two methods, we discuss whether or not the lower cutoff frequency of the plasma waves, such as continuum radiation, indicates the local electron density near the spacecraft. Then we applied the new relation to the spacecraft potential measured by the Geotail spacecraft during the period from October 1993 to December 1995, and obtained the electron spatial distribution in the solar wind and magnetosphere, including the distant tail region. Higher electron number density is clearly observed on the dawnside than on the duskside of the magnetosphere in the distant tail beyond 100RE.

Does Travel Distance Affect Readmission Rates after Cardiac Surgery?

PubMed

Juo, Yen-Yi; Woods, Alexis; Ou, Ryan; Ramos, Gianna; Shemin, Richard; Benharash, Peyman

2017-10-01

With emphasis on value-based health care, empiric models are used to estimate expected readmission rates for individual institutions. The aim of this study was to determine the relationship between distance traveled to seek surgical care and likelihood of readmission in adult patients undergoing cardiac operations at a single medical center. All adults undergoing major cardiac surgeries from 2008 to 2015 were included. Patients were stratified by travel distance into regional and distant travel groups. Multivariable logistic regression models were developed to assess the impact of distance traveled on odds of readmission. Of the 4232 patients analyzed, 29 per cent were in the regional group and 71 per cent in the distant. Baseline characteristics between the two groups were comparable except mean age (62 vs 61 years, P < 0.01) and Caucasian race (59 vs 73%, P < 0.01). Distant travel was associated with a significantly longer hospital length of stay (11.8 vs 10.5 days, P < 0.01) and lower risk of readmission (9.5 vs 13.4%, P < 0.01). Odds of readmission was inversely associated with logarithm of distance traveled (odds ratio 0.75). Travel distance in patients undergoing major cardiac surgeries was inversely associated with odds of readmission.

Embracing the comparative approach: how robust phylogenies and broader developmental sampling impacts the understanding of nervous system evolution.

PubMed

Hejnol, Andreas; Lowe, Christopher J

2015-12-19

Molecular biology has provided a rich dataset to develop hypotheses of nervous system evolution. The startling patterning similarities between distantly related animals during the development of their central nervous system (CNS) have resulted in the hypothesis that a CNS with a single centralized medullary cord and a partitioned brain is homologous across bilaterians. However, the ability to precisely reconstruct ancestral neural architectures from molecular genetic information requires that these gene networks specifically map with particular neural anatomies. A growing body of literature representing the development of a wider range of metazoan neural architectures demonstrates that patterning gene network complexity is maintained in animals with more modest levels of neural complexity. Furthermore, a robust phylogenetic framework that provides the basis for testing the congruence of these homology hypotheses has been lacking since the advent of the field of 'evo-devo'. Recent progress in molecular phylogenetics is refining the necessary framework to test previous homology statements that span large evolutionary distances. In this review, we describe recent advances in animal phylogeny and exemplify for two neural characters-the partitioned brain of arthropods and the ventral centralized nerve cords of annelids-a test for congruence using this framework. The sequential sister taxa at the base of Ecdysozoa and Spiralia comprise small, interstitial groups. This topology is not consistent with the hypothesis of homology of tripartitioned brain of arthropods and vertebrates as well as the ventral arthropod and rope-like ladder nervous system of annelids. There can be exquisite conservation of gene regulatory networks between distantly related groups with contrasting levels of nervous system centralization and complexity. Consequently, the utility of molecular characters to reconstruct ancestral neural organization in deep time is limited. © 2015 The Authors.

Embracing the comparative approach: how robust phylogenies and broader developmental sampling impacts the understanding of nervous system evolution

PubMed Central

Hejnol, Andreas; Lowe, Christopher J.

2015-01-01

Molecular biology has provided a rich dataset to develop hypotheses of nervous system evolution. The startling patterning similarities between distantly related animals during the development of their central nervous system (CNS) have resulted in the hypothesis that a CNS with a single centralized medullary cord and a partitioned brain is homologous across bilaterians. However, the ability to precisely reconstruct ancestral neural architectures from molecular genetic information requires that these gene networks specifically map with particular neural anatomies. A growing body of literature representing the development of a wider range of metazoan neural architectures demonstrates that patterning gene network complexity is maintained in animals with more modest levels of neural complexity. Furthermore, a robust phylogenetic framework that provides the basis for testing the congruence of these homology hypotheses has been lacking since the advent of the field of ‘evo-devo’. Recent progress in molecular phylogenetics is refining the necessary framework to test previous homology statements that span large evolutionary distances. In this review, we describe recent advances in animal phylogeny and exemplify for two neural characters—the partitioned brain of arthropods and the ventral centralized nerve cords of annelids—a test for congruence using this framework. The sequential sister taxa at the base of Ecdysozoa and Spiralia comprise small, interstitial groups. This topology is not consistent with the hypothesis of homology of tripartitioned brain of arthropods and vertebrates as well as the ventral arthropod and rope-like ladder nervous system of annelids. There can be exquisite conservation of gene regulatory networks between distantly related groups with contrasting levels of nervous system centralization and complexity. Consequently, the utility of molecular characters to reconstruct ancestral neural organization in deep time is limited. PMID:26554039

Human breast cancer metastases to the brain display GABAergic properties in the neural niche.

PubMed

Neman, Josh; Termini, John; Wilczynski, Sharon; Vaidehi, Nagarajan; Choy, Cecilia; Kowolik, Claudia M; Li, Hubert; Hambrecht, Amanda C; Roberts, Eugene; Jandial, Rahul

2014-01-21

Dispersion of tumors throughout the body is a neoplastic process responsible for the vast majority of deaths from cancer. Despite disseminating to distant organs as malignant scouts, most tumor cells fail to remain viable after their arrival. The physiologic microenvironment of the brain must become a tumor-favorable microenvironment for successful metastatic colonization by circulating breast cancer cells. Bidirectional interplay of breast cancer cells and native brain cells in metastasis is poorly understood and rarely studied. We had the rare opportunity to investigate uncommonly available specimens of matched fresh breast-to-brain metastases tissue and derived cells from patients undergoing neurosurgical resection. We hypothesized that, to metastasize, breast cancers may escape their normative genetic constraints by accommodating and coinhabiting the neural niche. This acquisition or expression of brain-like properties by breast cancer cells could be a malignant adaptation required for brain colonization. Indeed, we found breast-to-brain metastatic tissue and cells displayed a GABAergic phenotype similar to that of neuronal cells. The GABAA receptor, GABA transporter, GABA transaminase, parvalbumin, and reelin were all highly expressed in breast cancer metastases to the brain. Proliferative advantage was conferred by the ability of breast-to-brain metastases to take up and catabolize GABA into succinate with the resultant formation of NADH as a biosynthetic source through the GABA shunt. The results suggest that breast cancers exhibit neural characteristics when occupying the brain microenvironment and co-opt GABA as an oncometabolite.

Human breast cancer metastases to the brain display GABAergic properties in the neural niche

PubMed Central

Neman, Josh; Termini, John; Wilczynski, Sharon; Vaidehi, Nagarajan; Choy, Cecilia; Kowolik, Claudia M.; Li, Hubert; Hambrecht, Amanda C.; Roberts, Eugene; Jandial, Rahul

2014-01-01

Dispersion of tumors throughout the body is a neoplastic process responsible for the vast majority of deaths from cancer. Despite disseminating to distant organs as malignant scouts, most tumor cells fail to remain viable after their arrival. The physiologic microenvironment of the brain must become a tumor-favorable microenvironment for successful metastatic colonization by circulating breast cancer cells. Bidirectional interplay of breast cancer cells and native brain cells in metastasis is poorly understood and rarely studied. We had the rare opportunity to investigate uncommonly available specimens of matched fresh breast-to-brain metastases tissue and derived cells from patients undergoing neurosurgical resection. We hypothesized that, to metastasize, breast cancers may escape their normative genetic constraints by accommodating and coinhabiting the neural niche. This acquisition or expression of brain-like properties by breast cancer cells could be a malignant adaptation required for brain colonization. Indeed, we found breast-to-brain metastatic tissue and cells displayed a GABAergic phenotype similar to that of neuronal cells. The GABAA receptor, GABA transporter, GABA transaminase, parvalbumin, and reelin were all highly expressed in breast cancer metastases to the brain. Proliferative advantage was conferred by the ability of breast-to-brain metastases to take up and catabolize GABA into succinate with the resultant formation of NADH as a biosynthetic source through the GABA shunt. The results suggest that breast cancers exhibit neural characteristics when occupying the brain microenvironment and co-opt GABA as an oncometabolite. PMID:24395782

Unified theory of the exciplex formation/dissipation.

PubMed

Khokhlova, Svetlana S; Burshtein, Anatoly I

2010-11-04

The natural extension and reformulation of the unified theory (UT) proposed here makes it integro-differential and capable of describing the distant quenching of excitation by electron transfer, accompanied with contact but reversible exciplex formation. The numerical solution of the new UT equations allows specifying the kinetics of the fluorescence quenching and exciplex association/dissociation as well as those reactions' quantum yields. It was demonstrated that the distant electron transfer in either the normal or inverted Marcus regions screens the contact reaction of exciplex formation, especially at slow diffusion.

Environmental and Body Concentrations of Heavy Metals at Sites Near and Distant from Industrial Complexes in Ulsan, Korea.

PubMed

Sung, Joo Hyun; Oh, Inbo; Kim, Ahra; Lee, Jiho; Sim, Chang Sun; Yoo, Cheolin; Park, Sang Jin; Kim, Geun Bae; Kim, Yangho

2018-01-29

Industrial pollution may affect the heavy metal body burden of people living near industrial complexes. We determined the average concentrations of atmospheric heavy metals in areas close to and distant from industrial complexes in Korea, and the body concentrations of these heavy metals in residents living near and distant from these facilities. The atmospheric data of heavy metals (lead and cadmium) were from the Regional Air Monitoring Network in Ulsan. We recruited 1,148 participants, 872 who lived near an industrial complex ("exposed" group) and 276 who lived distant from industrial complexes ("non-exposed" group), and measured their concentrations of blood lead, urinary cadmium, and urinary total mercury. The results showed that atmospheric and human concentrations of heavy metals were higher in areas near industrial complexes. In addition, residents living near industrial complexes had higher individual and combined concentrations (cadmium + lead + mercury) of heavy metals. We conclude that residents living near industrial complexes are exposed to high concentrations of heavy metals, and should be carefully monitored. © 2018 The Korean Academy of Medical Sciences.

Environmental and Body Concentrations of Heavy Metals at Sites Near and Distant from Industrial Complexes in Ulsan, Korea

PubMed Central

2017-01-01

Background Industrial pollution may affect the heavy metal body burden of people living near industrial complexes. We determined the average concentrations of atmospheric heavy metals in areas close to and distant from industrial complexes in Korea, and the body concentrations of these heavy metals in residents living near and distant from these facilities. Methods The atmospheric data of heavy metals (lead and cadmium) were from the Regional Air Monitoring Network in Ulsan. We recruited 1,148 participants, 872 who lived near an industrial complex (“exposed” group) and 276 who lived distant from industrial complexes (“non-exposed” group), and measured their concentrations of blood lead, urinary cadmium, and urinary total mercury. Results The results showed that atmospheric and human concentrations of heavy metals were higher in areas near industrial complexes. In addition, residents living near industrial complexes had higher individual and combined concentrations (cadmium + lead + mercury) of heavy metals. Conclusion We conclude that residents living near industrial complexes are exposed to high concentrations of heavy metals, and should be carefully monitored. PMID:29349943

The detection of distant cooling flows and the formation of dark matter

NASA Technical Reports Server (NTRS)

Fabian, A. C.; Arnaud, K. A.; Nulsen, P. E. J.; Mushotzky, R. F.

1986-01-01

Cooling flows involving substantial mass inflow rates appear to be common in many nearby rich and poor clusters and in isolated galaxies. The extensive optical and ultraviolet filaments produced by the thermal instability of large flows are detectable out to redshifts greater than 1. It is proposed that this may explain the extended optical line emission reported in, and around, many distant radio galaxies, narrow-line quasars, and even nearby normal and active galaxies. An important diagnostic to distinguish cooling flows from other possible origins of emission line filaments is the presence of extensive regions at high thermal pressure. Other evidence for distant cooling flows and the resultant star formation is further discussed, together with the implications of cooling flow initial-mass functions for galaxy formation and the nature of 'dark' matter.

Transfer and capture into distant retrograde orbits

NASA Astrophysics Data System (ADS)

Scott, Christopher J.

This dissertation utilizes theory and techniques derived from the fields of dynamical systems theory, astrodyanamics, celestial mechanics, and fluid mechanics to analyze the phenomenon of satellite capture and interrelated spacecraft transfers in restricted three-body systems. The results extend current knowledge and understanding of capture dynamics in the context of astrodynamics and celestial mechanics. Manifold theory, fast Lyapunov indicator maps, and the classification of space structure facilitate an analysis of the transport of objects from the chaotic reaches of the solar system to the distant retrograde region in the sun-Jupiter system. Apart from past studies this dissertation considers the role of the complex lobe structure encompassing stable regions in the circular restricted three-body problem. These structures are shown to be responsible for the phenomenon of sticky orbits and the transport of objects among stable regions. Since permanent capture can only be achieved through a change in energy, fast Lyapunov indicator maps and other methods which reveal the structure of the conservative system are used to discern capture regions and identify the underpinnings of the dynamics. Fast Lyapunov indicator maps provide an accurate classification of orbits of permanent capture and escape, yet monopolize computational resources. In anticipation of a fully three-dimensional analysis in the dissipative system a new mapping parameter is introduced based on energy degradation and averaged velocity. Although the study specifically addresses the sun-Jupiter system, the qualitative results and devised techniques can be applied throughout the solar system and to capture about extrasolar planets. Extending the analysis beyond the exterior of the stable distant retrograde region fosters the construction of transfer orbits from low-Earth orbit to a stable periodic orbit at the center of the stable distant retrograde region. Key to this analysis is the predictability of collision orbits within the highly chaotic region commonly recognized as a saddle point on the energy manifold. The pragmatic techniques derived from this analysis solve a number of complications apparent in the literature. Notably a reliable methodology for the construction of an arbitrary number of transfer orbits circumvents the requirement of computing specialized periodic orbits or extensive numerical sampling of the phase space. The procedure provides a complete description of the design space accessing a wide range of distant retrograde orbits sizes, insertion points, and parking orbit altitudes in an automated manner. The transfers are studied in a similar fashion to periodic orbits unveiling the intimate relationship among design parameters and phase space structure. An arbitrary number of Earth return periodic orbits can be generated as a by-product. These orbits may be useful for spacecraft that must make a number of passes near the second primary without a reduction in energy. Further analysis of the lobe dynamics and a modification of the transfers to the center of the stable region yields sets of single impulse transfers to sticky distant retrograde orbits. It is shown that the evolution of the phase space structures with energy corresponds to the variation of capture time and target size. Capture phenomenon is related to the stability characteristics of the unstable periodic orbit and the geometry of the corresponding homoclinic tangle at various energies. Future spacecraft with little or no propulsive means may take advantage of these natural trajectories for operations in the region. Temporary capture along a sticky orbit may come before incremental stabilization of the spacecraft by way of a series of small impulsive or a low continuous thrust maneuvers. The requirements of small stabilization maneuver are calculated and compared to a direct transfer to the center of stable region. This mission design may be desirable as any failure in the classic set of maneuvers to the center of the stable region could result in the loss of the spacecraft. A simple low-thrust stabilization method is analyzed in a similar manner to nebular drag. It is shown that stabilization maneuvers initiated within the sticky region can be achieved via a simple control law. Moreover, the sticky region can be used as a staging point for both spiral-in and spiral-out maneuvers. For the spiral in maneuver this negates a large, initial maneuver required to reach the center of the stable region. It is shown that large lengths of orbits exist within the sticky regions which reliably lead to permanent capture. In the case of spiral-out the spacecraft is transported to a highly energetic yet stable orbit about the second primary. From here a small maneuver could allow the spacecraft to access other regions of the solar system.

Preablation 131-I scans with SPECT/CT in postoperative thyroid cancer patients: what is the impact on staging?

PubMed

Avram, Anca M; Fig, Lorraine M; Frey, Kirk A; Gross, Milton D; Wong, Ka Kit

2013-03-01

The utility of preablation radioiodine scans for the management of differentiated thyroid cancer remains controversial. To determine the contribution of preablation Iodine 131 (131-I) planar with single-photon emission computed tomography/computed tomography (SPECT/CT; diagnostic [Dx] scans) to differentiated thyroid cancer staging. Prospective sequential series at university clinic. Using American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging, seventh edition 320 patients post-total thyroidectomy were initially staged based on clinical and pathology data (pTN) and then restaged after imaging (TNM). The impact of Dx scans with SPECT/CT on N and M scores, and TNM stage, was assessed in younger, age <45 years, n = 138 (43%), and older, age ≥ 45 years, n = 182 (57%) patients, with subgroup analysis for T1a and T1b tumors. In younger patients Dx scans detected distant metastases in 5 of 138 patients (4%), and nodal metastases in 61 of 138 patients (44%), including unsuspected nodal metastases in 24 of 63 (38%) patients initially assigned pathologic (p) N0 or pNx. In older patients distant metastases were detected in 18 of 182 patients (10%), and nodal metastases in 51 of 182 patients (28%), including unsuspected nodal metastases in 26 of 108 (24%) patients initially assigned pN0 or pNx. Dx scans detected distant metastases in 2 of 49 (4%) T1a, and 3 of 67 (4.5%) T1b patients. Dx scans detected regional metastases in 35% of patients, and distant metastases in 8% of patients. Information acquired with Dx scans changed staging in 4% of younger, and 25% of older patients. Preablation scans with SPECT/CT contribute to staging of thyroid cancer. Identification of regional and distant metastases prior to radioiodine therapy has significant potential to alter patient management.

James Webb Space Telescope (JWST) and Star Formation

NASA Technical Reports Server (NTRS)

Greene, Thomas P.

2010-01-01

The 6.5-m aperture James Webb Space Telescope (JWST) will be a powerful tool for studying and advancing numerous areas of astrophysics. Its Fine Guidance Sensor, Near-Infrared Camera, Near-Infrared Spectrograph, and Mid-Infrared Instrument will be capable of making very sensitive, high angular resolution imaging and spectroscopic observations spanning 0.7 - 28 ?m wavelength. These capabilities are very well suited for probing the conditions of star formation in the distant and local Universe. Indeed, JWST has been designed to detect first light objects as well as to study the fine details of jets, disks, chemistry, envelopes, and the central cores of nearby protostars. We will be able to use its cameras, coronagraphs, and spectrographs (including multi-object and integral field capabilities) to study many aspects of star forming regions throughout the galaxy, the Local Group, and more distant regions. I will describe the basic JWST scientific capabilities and illustrate a few ways how they can be applied to star formation issues and conditions with a focus on Galactic regions.

Magnetospheric access of solar particles and the configuration of the distant geomagnetic field, volume 1. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Evans, L. C.

1972-01-01

The access of 1.2 to 40 MeV protons and 0.4 to 1.0 MeV electrons from interplanetary space to the polar cap regions was investigated with an experiment on board a low altitude, polar-orbiting satellite (0G0 4). A total of 333 quiet time observations of the electron polar cap boundary give a mapping of the boundary between open and closed geomagnetic field lines. Observations of events associated with co-rotating regions of enhanced proton flux in interplanetary space were used to establish the characteristics of the 1.2 to 40 MeV proton access windows. The results were compared to particle access predictions of the distant geomagnetic tail configurations. The role played by interplanetary anisotropies in the observation of persistent polar cap features is discussed. Special emphasis is given to the problem of nonadiabatic particle entry through regions where the magnetic field is changing direction.

Racial disparities in stage-specific colorectal cancer mortality rates from 1985 to 2008.

PubMed

Robbins, Anthony S; Siegel, Rebecca L; Jemal, Ahmedin

2012-02-01

Since the early 1980s, colorectal cancer (CRC) mortality rates for whites and blacks in the United States have been diverging as a result of earlier and larger reductions in death rates for whites. We examined whether this mortality pattern varies by stage at diagnosis. The Incidence-Based Mortality database of the Surveillance, Epidemiology, and End Results (SEER) Program was used to examine data from the nine original SEER regions. Our main outcome measures were changes in stage-specific mortality rates by race. From 1985 to 1987 to 2006 to 2008, CRC mortality rates decreased for each stage in both blacks and whites, but for every stage, the decreases were smaller for blacks, particularly for distant-stage disease. For localized stage, mortality rates decreased 30.3% in whites compared with 13.2% in blacks; for regional stage, declines were 48.5% in whites compared with 34.0% in blacks; and for distant stage, declines were 32.6% in whites compared with 4.6% in blacks. As a result, the black-white rate ratios increased from 1.17 (95% CI, 0.98 to 1.39) to 1.41 (95% CI, 1.21 to 1.63) for localized disease, from 1.03 (95% CI, 0.93 to 1.14) to 1.30 (95% CI, 1.17 to 1.44) for regional disease, and from 1.21 (95% CI, 1.10 to 1.34) to 1.72 (95% CI, 1.58 to 1.86) for distant-stage disease. In absolute terms, the disparity in distant-stage mortality rates accounted for approximately 60% of the overall black-white mortality disparity. The black-white disparities in CRC mortality increased for each stage of the disease, but the overall disparity in overall mortality was largely driven by trends for late-stage disease. Concerted efforts to prevent or detect CRC at earlier stages in blacks could improve the worsening black- white disparities.

Systemic siRNA Nanoparticle-Based Drugs Combined with Radiofrequency Ablation for Cancer Therapy

PubMed Central

Ahmed, Muneeb; Kumar, Gaurav; Navarro, Gemma; Wang, Yuanguo; Gourevitch, Svetlana; Moussa, Marwan H.; Rozenblum, Nir; Levchenko, Tatyana; Galun, Eithan; Torchilin, Vladimir P.; Goldberg, S. Nahum

2015-01-01

Purpose Radiofrequency thermal ablation (RFA) of hepatic and renal tumors can be accompanied by non-desired tumorigenesis in residual, untreated tumor. Here, we studied the use of micelle-encapsulated siRNA to suppress IL-6-mediated local and systemic secondary effects of RFA. Methods We compared standardized hepatic or renal RFA (laparotomy, 1 cm active tip at 70±2°C for 5 min) and sham procedures without and with administration of 150nm micelle-like nanoparticle (MNP) anti-IL6 siRNA (DOPE-PEI conjugates, single IP dose 15 min post-RFA, C57Bl mouse:3.5 ug/100ml, Fisher 344 rat: 20ug/200ul), RFA/scrambled siRNA, and RFA/empty MNPs. Outcome measures included: local periablational cellular infiltration (α-SMA+ stellate cells), regional hepatocyte proliferation, serum/tissue IL-6 and VEGF levels at 6-72hr, and distant tumor growth, tumor proliferation (Ki-67) and microvascular density (MVD, CD34) in subcutaneous R3230 and MATBIII breast adenocarcinoma models at 7 days. Results For liver RFA, adjuvant MNP anti-IL6 siRNA reduced RFA-induced increases in tissue IL-6 levels, α-SMA+ stellate cell infiltration, and regional hepatocyte proliferation to baseline (p<0.04, all comparisons). Moreover, adjuvant MNP anti-IL6- siRNA suppressed increased distant tumor growth and Ki-67 observed in R3230 and MATBIII tumors post hepatic RFA (p<0.01). Anti-IL6 siRNA also reduced RFA-induced elevation in VEGF and tumor MVD (p<0.01). Likewise, renal RFA-induced increases in serum IL-6 levels and distant R3230 tumor growth was suppressed with anti-IL6 siRNA (p<0.01). Conclusions Adjuvant nanoparticle-encapsulated siRNA against IL-6 can be used to modulate local and regional effects of hepatic RFA to block potential unwanted pro-oncogenic effects of hepatic or renal RFA on distant tumor. PMID:26154425

Stereotactic radiosurgery alone for multiple brain metastases? A review of clinical and technical issues

PubMed Central

Ruschin, Mark; Ma, Lijun; Verbakel, Wilko; Larson, David; Brown, Paul D.

2017-01-01

Abstract Over the past three decades several randomized trials have enabled evidence-based practice for patients presenting with limited brain metastases. These trials have focused on the role of surgery or stereotactic radiosurgery (SRS) with or without whole brain radiation therapy (WBRT). As a result, it is clear that local control should be optimized with surgery or SRS in patients with optimal prognostic factors presenting with up to 4 brain metastases. The routine use of adjuvant WBRT remains debatable, as although greater distant brain control rates are observed, there is no impact on survival, and modern outcomes suggest adverse effects from WBRT on patient cognition and quality of life. With dramatic technologic advances in radiation oncology facilitating the adoption of SRS into mainstream practice, the optimal management of patients with multiple brain metastases is now being put forward. Practice is evolving to SRS alone in these patients despite a lack of level 1 evidence to support a clinical departure from WBRT. The purpose of this review is to summarize the current state of the evidence for patients presenting with limited and multiple metastases, and to present an in-depth analysis of the technology and dosimetric issues specific to the treatment of multiple metastases. PMID:28380635

The Social Brain Is Not Enough: On the Importance of the Ecological Brain for the Origin of Language.

PubMed

Ferretti, Francesco

2016-01-01

In this paper, I assume that the study of the origin of language is strictly connected to the analysis of the traits that distinguish human language from animal communication. Usually, human language is said to be unique in the animal kingdom because it enables and/or requires intentionality or mindreading. By emphasizing the importance of mindreading, the social brain hypothesis has provided major insights within the origin of language debate. However, as studies on non-human primates have demonstrated that intentional forms of communication are already present in these species to a greater or lesser extent, I maintain that the social brain is a necessary but not a sufficient condition to explain the uniqueness of language. In this paper, I suggest that the distinctive feature of human communication resides in the ability to tell stories, and that the origin of language should be traced with respect to the capacity to produce discourses, rather than phrases or words. As narrative requires the ability to link events distant from one another in space and time, my proposal is that in order to explain the origin of language, we need to appeal to both the social brain and the ecological brain - that is, the cognitive devices which allow us to mentally travel in space and time.

Encoding of Spatio-Temporal Input Characteristics by a CA1 Pyramidal Neuron Model

PubMed Central

Pissadaki, Eleftheria Kyriaki; Sidiropoulou, Kyriaki; Reczko, Martin; Poirazi, Panayiota

2010-01-01

The in vivo activity of CA1 pyramidal neurons alternates between regular spiking and bursting, but how these changes affect information processing remains unclear. Using a detailed CA1 pyramidal neuron model, we investigate how timing and spatial arrangement variations in synaptic inputs to the distal and proximal dendritic layers influence the information content of model responses. We find that the temporal delay between activation of the two layers acts as a switch between excitability modes: short delays induce bursting while long delays decrease firing. For long delays, the average firing frequency of the model response discriminates spatially clustered from diffused inputs to the distal dendritic tree. For short delays, the onset latency and inter-spike-interval succession of model responses can accurately classify input signals as temporally close or distant and spatially clustered or diffused across different stimulation protocols. These findings suggest that a CA1 pyramidal neuron may be capable of encoding and transmitting presynaptic spatiotemporal information about the activity of the entorhinal cortex-hippocampal network to higher brain regions via the selective use of either a temporal or a rate code. PMID:21187899

Presumed choroidal metastasis of Merkel cell carcinoma

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

Small, K.W.; Rosenwasser, G.O.; Alexander, E. III

1990-05-01

Merkel cell carcinoma is a rare skin tumor of neural crest origin and is part of the amine precursor uptake and decarboxylase system. It typically occurs on the face of elderly people. Distant metastasis is almost uniformly fatal. Choroidal metastasis, to our knowledge, has not been described. We report a patient with Merkel cell carcinoma who had a synchronous solid choroidal tumor and a biopsy-proven brain metastasis. Our 56-year-old patient presented with a rapidly growing, violaceous preauricular skin tumor. Computed tomography of the head disclosed incidental brain and choroidal tumors. Light and electron microscopy of biopsy specimens of both themore » skin and the brain lesions showed Merkel cell carcinoma. Ophthalmoscopy, fluorescein angiography, and A and B echography revealed a solid choroidal mass. The brain and skin tumors responded well to irradiation. A radioactive episcleral plaque was applied subsequently to the choroidal tumor. All tumors regressed, and the patient was doing well 28 months later. To our knowledge this is the first case of presumed choroidal metastasis of Merkel cell carcinoma.« less

Brain size and visual environment predict species differences in paper wasp sensory processing brain regions (hymenoptera: vespidae, polistinae).

PubMed

O'Donnell, Sean; Clifford, Marie R; DeLeon, Sara; Papa, Christopher; Zahedi, Nazaneen; Bulova, Susan J

2013-01-01

The mosaic brain evolution hypothesis predicts that the relative volumes of functionally distinct brain regions will vary independently and correlate with species' ecology. Paper wasp species (Hymenoptera: Vespidae, Polistinae) differ in light exposure: they construct open versus enclosed nests and one genus (Apoica) is nocturnal. We asked whether light environments were related to species differences in the size of antennal and optic processing brain tissues. Paper wasp brains have anatomically distinct peripheral and central regions that process antennal and optic sensory inputs. We measured the volumes of 4 sensory processing brain regions in paper wasp species from 13 Neotropical genera including open and enclosed nesters, and diurnal and nocturnal species. Species differed in sensory region volumes, but there was no evidence for trade-offs among sensory modalities. All sensory region volumes correlated with brain size. However, peripheral optic processing investment increased with brain size at a higher rate than peripheral antennal processing investment. Our data suggest that mosaic and concerted (size-constrained) brain evolution are not exclusive alternatives. When brain regions increase with brain size at different rates, these distinct allometries can allow for differential investment among sensory modalities. As predicted by mosaic evolution, species ecology was associated with some aspects of brain region investment. Nest architecture variation was not associated with brain investment differences, but the nocturnal genus Apoica had the largest antennal:optic volume ratio in its peripheral sensory lobes. Investment in central processing tissues was not related to nocturnality, a pattern also noted in mammals. The plasticity of neural connections in central regions may accommodate evolutionary shifts in input from the periphery with relatively minor changes in volume. © 2013 S. Karger AG, Basel.

Review: mucosal melanoma of the head and neck.

PubMed

Gavriel, Haim; McArthur, Grant; Sizeland, Andrew; Henderson, Michael

2011-08-01

Head and neck mucosal melanoma (MM) is a rare and aggressive neoplasm, with high rates of local, regional, and distant failure. Owing to the small size of most reported series and their retrospective nature, and the lack of uniform comprehensive staging system, the effect of various treatment strategies on disease control and survival has been difficult to assess. The optimal management of head and neck MM is not well defined. Surgical treatment has being advocated as the primary treatment modality, with growing consideration for postoperative radiotherapy, as wide surgical resection in the head and neck region is often difficult. Radiotherapy is recently reported as a beneficial management modality, regardless of the fact that MM has been considered to be radioresistant. As significant morbidity is expected in high doses of radiotherapy to the head and neck region, new radiographic modalities with better precision are required. Furthermore, high-energy radiotherapy was suggested as a better therapy to mucosal MM due to the suggested biology of the tumor. The high rates of locoregional recurrence and distant metastasis also suggest that a systemic treatment is needed. Currently, there is no role for adjuvant systemic therapy for patients who have been successfully resected, but recent developments in the understanding of the biology of melanoma and, in particular, specific growth pathways holds promise for the future. We strongly recommend further evaluation of the role of chemotherapy and immunotherapy to decrease the rates of distant metastasis and improve survival.

Seismicity in 2010 and major earthquakes recorded and located in Costa Rica from 1983 until 2012, by the local OVSICORI-UNA seismic network

NASA Astrophysics Data System (ADS)

Ronnie, Q.; Segura, J.; Burgoa, B.; Jimenez, W.; McNally, K. C.

2013-05-01

This work is the result of the analysis of existing information in the earthquake database of the Observatorio Sismológico y Vulcanológico de Costa Rica, Universidad Nacional (OVSICORI-UNA), and seeks disclosure of basic seismological information recorded and processed in 2010. In this year there was a transition between the software used to record, store and locate earthquakes. During the first three months of 2010, we used Earthworm (http://folkworm.ceri.memphis.edu/ew-doc), SEISAN (Haskov y Ottemoller, 1999) and Hypocenter (Lienert y Haskov, 1995) to capture, store and locate the earthquakes, respectively; in April 2010, ANTELOPE (http://www.brtt.com/software.html) start to be used for recording and storing and GENLOC (Fan at al, 2006) and LOCSAT (Bratt and Bache 1988), to locate earthquakes. GENLOC was used for local events and LOCSAT for regional and distant earthquakes. The local earthquakes were located using the 1D velocity model of Quintero and Kissling (2001) and for regional and distant earthquakes IASPEI91 (Kennett and Engdahl, 1991) was used. All the events for 2010 and shown in this work were rechecked by the authors. We located 3903 earthquakes in and around Costa Rica and 746 regional and distant seismic events were recorded (see Figure 1). In this work we also give a summary of major earthquakes recorded and located by OVSICORI-UNA network between 1983 and 2012. Seismicity recorded by OVSICORI-UNA network in 2010

The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases

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

Mehta, Minesh P.; Tsao, May N.; Whelan, Timothy J.

2005-09-01

Purpose: To systematically review the evidence for the use of stereotactic radiosurgery in adult patients with brain metastases. Methods: Key clinical questions to be addressed in this evidence-based review were identified. Outcomes considered were overall survival, quality of life or symptom control, brain tumor control or response and toxicity. MEDLINE (1990-2004 June Week 2), CANCERLIT (1990-2003), CINAHL (1990-2004 June Week 2), EMBASE (1990-2004 Week 25), and the Cochrane library (2004 issue 2) databases were searched using OVID. In addition, the Physician Data Query clinical trials database, the proceedings of the American Society of Clinical Oncology (ASCO) (1997-2004), ASTRO (1997-2004), andmore » the European Society of Therapeutic Radiology and Oncology (ESTRO) (1997-2003) were searched. Data from the literature search were reviewed and tabulated. This process included an assessment of the level of evidence. Results: For patients with newly diagnosed brain metastases, managed with whole-brain radiotherapy alone vs. whole-brain radiotherapy and radiosurgery boost, there were three randomized controlled trials, zero prospective studies, and seven retrospective series (which satisfied inclusion criteria). For patients with up to three (<4 cm) newly diagnosed brain metastases (and in one study up to four brain metastases), radiosurgery boost with whole-brain radiotherapy significantly improves local brain control rates as compared with whole-brain radiotherapy alone (Level I-III evidence). In one large randomized trial, survival benefit with whole-brain radiotherapy was observed in patients with single brain metastasis. In this trial, an overall increased ability to taper down on steroid dose and an improvement in Karnofsky performance status was seen in patients who were treated with radiosurgery boost as compared with patients treated with whole-brain radiotherapy alone. However, Level I evidence regarding overall quality of life outcomes using a validated instrument has not been reported. All randomized trials showed improved local control with the addition of radiosurgery to whole-brain radiotherapy. For patients with multiple brain metastases, there is no overall survival benefit with the use of radiosurgery boost to whole-brain radiotherapy (Level I-III evidence). Radiosurgery boost is associated with a small risk of early or late toxicity. In patients treated with radiosurgery alone (withholding whole-brain radiotherapy) as initial treatment, there were 2 randomized trials, 2 prospective cohort studies, and 16 retrospective series. There is Level I to Level III evidence that the use of radiosurgery alone does not alter survival as compared to the use of whole-brain radiotherapy. However, there is Level I to Level III evidence that omission of whole-brain radiotherapy results in poorer intracranial disease control, both local and distant (defined as remaining brain, outside the radiosurgery field). Quality of life outcomes have not been adequately reported. Radiosurgery is associated with a small risk of early or late toxicity. Radiosurgery as salvage for patients with brain metastases was reported in zero randomized trials, one prospective study, and seven retrospective series. Conclusions: Based on Level I-III evidence, for selected patients with small (up to 4 cm) brain metastases (up to three in number and four in one randomized trial), the addition of radiosurgery boost to whole-brain radiotherapy improves brain control as compared with whole-brain radiotherapy alone. In patients with a single brain metastasis, radiosurgery boost with whole-brain radiotherapy improves survival. There is a small risk of toxicity associated with radiosurgery boost as compared with whole-brain radiotherapy alone. In selected patients treated with radiosurgery alone for newly diagnosed brain metastases, overall survival is not altered. However, local and distant brain control is significantly poorer with omission of upfront whole-brain radiotherapy (Level I-III evidence). Whether neurocognition or quality of life outcomes are different between initial radiosurgery alone vs. whole-brain radiotherapy (with or without radiosurgery boost) is unknown, because this has not been adequately tested. There was no statistically significant difference in overall toxicity between those treated with radiosurgery alone vs. whole-brain radiotherapy and radiosurgery boost based on an interim report from one randomized study. There is insufficient evidence as to the clinical benefit/risks radiosurgery used in the setting of recurrent or progressive brain metastases, although radiographic responses are well-documented.« less

The relationship between spatial configuration and functional connectivity of brain regions

PubMed Central

Woolrich, Mark W; Glasser, Matthew F; Robinson, Emma C; Beckmann, Christian F; Van Essen, David C

2018-01-01

Brain connectivity is often considered in terms of the communication between functionally distinct brain regions. Many studies have investigated the extent to which patterns of coupling strength between multiple neural populations relates to behaviour. For example, studies have used ‘functional connectivity fingerprints’ to characterise individuals' brain activity. Here, we investigate the extent to which the exact spatial arrangement of cortical regions interacts with measures of brain connectivity. We find that the shape and exact location of brain regions interact strongly with the modelling of brain connectivity, and present evidence that the spatial arrangement of functional regions is strongly predictive of non-imaging measures of behaviour and lifestyle. We believe that, in many cases, cross-subject variations in the spatial configuration of functional brain regions are being interpreted as changes in functional connectivity. Therefore, a better understanding of these effects is important when interpreting the relationship between functional imaging data and cognitive traits. PMID:29451491

Category representations in the brain are both discretely localized and widely distributed.

PubMed

Shehzad, Zarrar; McCarthy, Gregory

2018-06-01

Whether category information is discretely localized or represented widely in the brain remains a contentious issue. Initial functional MRI studies supported the localizationist perspective that category information is represented in discrete brain regions. More recent fMRI studies using machine learning pattern classification techniques provide evidence for widespread distributed representations. However, these latter studies have not typically accounted for shared information. Here, we find strong support for distributed representations when brain regions are considered separately. However, localized representations are revealed by using analytical methods that separate unique from shared information among brain regions. The distributed nature of shared information and the localized nature of unique information suggest that brain connectivity may encourage spreading of information but category-specific computations are carried out in distinct domain-specific regions. NEW & NOTEWORTHY Whether visual category information is localized in unique domain-specific brain regions or distributed in many domain-general brain regions is hotly contested. We resolve this debate by using multivariate analyses to parse functional MRI signals from different brain regions into unique and shared variance. Our findings support elements of both models and show information is initially localized and then shared among other regions leading to distributed representations being observed.

The Effects of Explosive Blast as Compared to Post-Traumatic Stress Disorder on Brain Function and Stucture

DTIC Science & Technology

2011-04-01

fractional anisotropymeasures of axonal tracts derived from diffusion tensor imaging ( DTI ). Nine soldiers who incurred a blast-related mTBI during...nauseous for 24 to 36 h, blurred vision, tingling in legs , poor coordination for 3 h. Yes, for unknown period None 5 Subject was a gunner in a Humvee...pairs of distant electrodes in all frequency bands. DTI acquisition and processing Diffusionweighted images were acquired on a 1.5T Philips Achieva

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

Cognitive and physical training for the elderly: evaluating outcome efficacy by means of neurophysiological synchronization.

PubMed

Frantzidis, Christos A; Ladas, Aristea-Kiriaki I; Vivas, Ana B; Tsolaki, Magda; Bamidis, Panagiotis D

2014-07-01

Recent neuroscientific research has demonstrated that both healthy and pathological aging induces alterations in the co-operative capacity of neuronal populations in the brain. Both compensatory and neurodegenerative mechanisms contribute to neurophysiological synchronization patterns, which provide a valuable marker for age-related cognitive decline. In this study, we propose that neuroplasticity-based training may facilitate coherent interaction of distant brain regions and consequently enhance cognitive performance in elderly people. If this is true, this would make neurophysiological synchronization a valid outcome measure to assess the efficacy of non-pharmacological interventions to prevent or delay age-related cognitive decline. The present study aims at providing an objective, synchronization-based tool to assess cognitive and/or physical interventions, adopting the notion of Relative Wavelet Entropy. This mathematical model employs a robust and parameter-free synchronization metric. By using data mining techniques, a distance value was computed for all participants so as to quantify the proximity of their individual profile to the mean group synchronization increase. In support of our hypothesis, results showed a significant increase in synchronization, for four electrode pairs, in the intervention group as compared to the active control group. It is concluded that the novel introduction of neurophysiological synchronization features could be used as a valid and reliable outcome measure; while the distance-based analysis could provide a reliable means of evaluating individual benefits. Copyright © 2014 Elsevier B.V. All rights reserved.

Synchronization of stochastic systems: from paddlefish electroreceptors to human epileptic glial cell cultures

NASA Astrophysics Data System (ADS)

Neiman, Alexander

2000-03-01

Synchronization is one of the fundamental nonlinear phenomena observed in nature. We have studied stochastic synchronization in the electrosensitive system of the paddlefish, Polyodon spathula and have also applied synchronization analysis to networks of glial cells cultured from brain tissue of patients with severe epilepsy. We also present theoretical and numerical models for stochastic synchronization. The electrosensitive system of the paddlefish consists of tens of thousands of electroreceptors located mainly on the "rostrum", which serves as an antenna to locate plankton. Each electroreceptor is a noisy oscillator with natural frequencies in the range of 30-90 Hz. We study synchronization in vivo due to 3-20 Hz external periodic electric fields, which correspond to natural signals produced by Daphnia, the usual prey of paddlefish. We find that for signals whose strengths are in the range that paddlefish customarily encounter in the wild, synchronization coding offers a plausible alternative to the more usual rate coding. We also have studied mutual synchronization between different electroreceptors. Although the spontaneous firing of distant electroreceptors is not synchronized, synchronization is observed when external periodic or even noisy electric fields are applied. We have applied the same analysis techniques to examine synchronization between groups of glial cells. In contrast to cultures of healthy astrocytes, which demonstrate calcium waves, the networks from epileptic tissue are characterized by spatially disordered hyper activity. Nevertheless, we have found that, in many cases, synchronized activity is a rather typical for tissue taken from the uncus region of the brain.

Conserved pattern of tangential neuronal migration during forebrain development.

PubMed

Métin, Christine; Alvarez, Chantal; Moudoux, David; Vitalis, Tania; Pieau, Claude; Molnár, Zoltán

2007-08-01

Origin, timing and direction of neuronal migration during brain development determine the distinct organization of adult structures. Changes in these processes might have driven the evolution of the forebrain in vertebrates. GABAergic neurons originate from the ganglionic eminence in mammals and migrate tangentially to the cortex. We are interested in differences and similarities in tangential migration patterns across corresponding telencephalic territories in mammals and reptiles. Using morphological criteria and expression patterns of Darpp-32, Tbr1, Nkx2.1 and Pax6 genes, we show in slice cultures of turtle embryos that early cohorts of tangentially migrating cells are released from the medial ganglionic eminence between stages 14 and 18. Additional populations migrate tangentially from the dorsal subpallium. Large cohorts of tangentially migrating neurons originate ventral to the dorsal ventricular ridge at stage 14 and from the lateral ganglionic eminence from stage 15. Release of GABAergic cells from these regions was investigated further in explant cultures. Tangential migration in turtle proceeds in a fashion similar to mammals. In chimeric slice culture and in ovo graft experiments, the tangentially migrating cells behaved according to the host environment - turtle cells responded to the available cues in mouse slices and mouse cells assumed characteristic migratory routes in turtle brains, indicating highly conserved embryonic signals between these distant species. Our study contributes to the evaluation of theories on the origin of the dorsal cortex and indicates that tangential migration is universal in mammals and sauropsids.

Temporal Plasticity Involved in Recovery from Manual Dexterity Deficit after Motor Cortex Lesion in Macaque Monkeys

PubMed Central

Higo, Noriyuki; Hayashi, Takuya; Nishimura, Yukio; Sugiyama, Yoko; Oishi, Takao; Tsukada, Hideo; Isa, Tadashi; Onoe, Hirotaka

2015-01-01

The question of how intensive motor training restores motor function after brain damage or stroke remains unresolved. Here we show that the ipsilesional ventral premotor cortex (PMv) and perilesional primary motor cortex (M1) of rhesus macaque monkeys are involved in the recovery of manual dexterity after a lesion of M1. A focal lesion of the hand digit area in M1 was made by means of ibotenic acid injection. This lesion initially caused flaccid paralysis in the contralateral hand but was followed by functional recovery of hand movements, including precision grip, during the course of daily postlesion motor training. Brain imaging of regional cerebral blood flow by means of H215O-positron emission tomography revealed enhanced activity of the PMv during the early postrecovery period and increased functional connectivity within M1 during the late postrecovery period. The causal role of these areas in motor recovery was confirmed by means of pharmacological inactivation by muscimol during the different recovery periods. These findings indicate that, in both the remaining primary motor and premotor cortical areas, time-dependent plastic changes in neural activity and connectivity are involved in functional recovery from the motor deficit caused by the M1 lesion. Therefore, it is likely that the PMv, an area distant from the core of the lesion, plays an important role during the early postrecovery period, whereas the perilesional M1 contributes to functional recovery especially during the late postrecovery period. PMID:25568105

Age-related macular degeneration changes the processing of visual scenes in the brain.

PubMed

Ramanoël, Stephen; Chokron, Sylvie; Hera, Ruxandra; Kauffmann, Louise; Chiquet, Christophe; Krainik, Alexandre; Peyrin, Carole

2018-01-01

In age-related macular degeneration (AMD), the processing of fine details in a visual scene, based on a high spatial frequency processing, is impaired, while the processing of global shapes, based on a low spatial frequency processing, is relatively well preserved. The present fMRI study aimed to investigate the residual abilities and functional brain changes of spatial frequency processing in visual scenes in AMD patients. AMD patients and normally sighted elderly participants performed a categorization task using large black and white photographs of scenes (indoors vs. outdoors) filtered in low and high spatial frequencies, and nonfiltered. The study also explored the effect of luminance contrast on the processing of high spatial frequencies. The contrast across scenes was either unmodified or equalized using a root-mean-square contrast normalization in order to increase contrast in high-pass filtered scenes. Performance was lower for high-pass filtered scenes than for low-pass and nonfiltered scenes, for both AMD patients and controls. The deficit for processing high spatial frequencies was more pronounced in AMD patients than in controls and was associated with lower activity for patients than controls not only in the occipital areas dedicated to central and peripheral visual fields but also in a distant cerebral region specialized for scene perception, the parahippocampal place area. Increasing the contrast improved the processing of high spatial frequency content and spurred activation of the occipital cortex for AMD patients. These findings may lead to new perspectives for rehabilitation procedures for AMD patients.

TIMING AND INTERSTELLAR SCATTERING OF 35 DISTANT PULSARS DISCOVERED IN THE PALFA SURVEY

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

Nice, D. J.; Altiere, E.; Farrington, D.

2013-07-20

We have made extensive observations of 35 distant slow (non-recycled) pulsars discovered in the ongoing Arecibo PALFA pulsar survey. Timing observations of these pulsars over several years at Arecibo Observatory and Jodrell Bank Observatory have yielded high-precision positions and measurements of rotation properties. Despite being a relatively distant population, these pulsars have properties that mirror those of the previously known pulsar population. Many of the sources exhibit timing noise, and one underwent a small glitch. We have used multifrequency data to measure the interstellar scattering properties of these pulsars. We find scattering to be higher than predicted along some linesmore » of sight, particularly in the Cygnus region. Finally, we present XMM-Newton and Chandra observations of the youngest and most energetic of the pulsars, J1856+0245, which has previously been associated with the GeV-TeV pulsar wind nebula HESS J1857+026.« less

Topological Organization of Functional Brain Networks in Healthy Children: Differences in Relation to Age, Sex, and Intelligence

PubMed Central

Wu, Kai; Taki, Yasuyuki; Sato, Kazunori; Hashizume, Hiroshi; Sassa, Yuko; Takeuchi, Hikaru; Thyreau, Benjamin; He, Yong; Evans, Alan C.; Li, Xiaobo; Kawashima, Ryuta; Fukuda, Hiroshi

2013-01-01

Recent studies have demonstrated developmental changes of functional brain networks derived from functional connectivity using graph theoretical analysis, which has been rapidly translated to studies of brain network organization. However, little is known about sex- and IQ-related differences in the topological organization of functional brain networks during development. In this study, resting-state fMRI (rs-fMRI) was used to map the functional brain networks in 51 healthy children. We then investigated the effects of age, sex, and IQ on economic small-world properties and regional nodal properties of the functional brain networks. At a global level of whole networks, we found significant age-related increases in the small-worldness and local efficiency, significant higher values of the global efficiency in boys compared with girls, and no significant IQ-related difference. Age-related increases in the regional nodal properties were found predominately in the frontal brain regions, whereas the parietal, temporal, and occipital brain regions showed age-related decreases. Significant sex-related differences in the regional nodal properties were found in various brain regions, primarily related to the default mode, language, and vision systems. Positive correlations between IQ and the regional nodal properties were found in several brain regions related to the attention system, whereas negative correlations were found in various brain regions primarily involved in the default mode, emotion, and language systems. Together, our findings of the network topology of the functional brain networks in healthy children and its relationship with age, sex, and IQ bring new insights into the understanding of brain maturation and cognitive development during childhood and adolescence. PMID:23390528

Topological organization of functional brain networks in healthy children: differences in relation to age, sex, and intelligence.

PubMed

Wu, Kai; Taki, Yasuyuki; Sato, Kazunori; Hashizume, Hiroshi; Sassa, Yuko; Takeuchi, Hikaru; Thyreau, Benjamin; He, Yong; Evans, Alan C; Li, Xiaobo; Kawashima, Ryuta; Fukuda, Hiroshi

2013-01-01

Recent studies have demonstrated developmental changes of functional brain networks derived from functional connectivity using graph theoretical analysis, which has been rapidly translated to studies of brain network organization. However, little is known about sex- and IQ-related differences in the topological organization of functional brain networks during development. In this study, resting-state fMRI (rs-fMRI) was used to map the functional brain networks in 51 healthy children. We then investigated the effects of age, sex, and IQ on economic small-world properties and regional nodal properties of the functional brain networks. At a global level of whole networks, we found significant age-related increases in the small-worldness and local efficiency, significant higher values of the global efficiency in boys compared with girls, and no significant IQ-related difference. Age-related increases in the regional nodal properties were found predominately in the frontal brain regions, whereas the parietal, temporal, and occipital brain regions showed age-related decreases. Significant sex-related differences in the regional nodal properties were found in various brain regions, primarily related to the default mode, language, and vision systems. Positive correlations between IQ and the regional nodal properties were found in several brain regions related to the attention system, whereas negative correlations were found in various brain regions primarily involved in the default mode, emotion, and language systems. Together, our findings of the network topology of the functional brain networks in healthy children and its relationship with age, sex, and IQ bring new insights into the understanding of brain maturation and cognitive development during childhood and adolescence.

Three-dimensional conformal radiation therapy for esophageal squamous cell carcinoma: is elective nodal irradiation necessary?

PubMed

Zhao, Kuai-le; Ma, Jin-bo; Liu, Guang; Wu, Kai-liang; Shi, Xue-hui; Jiang, Guo-liang

2010-02-01

To evaluate the local control, survival, and toxicity associated with three-dimensional conformal radiotherapy (3D-CRT) for squamous cell carcinoma (SCC) of the esophagus, to determine the appropriate target volumes, and to determine whether elective nodal irradiation is necessary in these patients. A prospective study of 3D-CRT was undertaken in patients with esophageal SCC without distant metastases. Patients received 68.4 Gy in 41 fractions over 44 days using late-course accelerated hyperfractionated 3D-CRT. Only the primary tumor and positive lymph nodes were irradiated. Isolated out-of-field regional nodal recurrence was defined as a recurrence in an initially uninvolved regional lymph node. All 53 patients who made up the study population tolerated the irradiation well. No acute or late Grade 4 or 5 toxicity was observed. The median survival time was 30 months (95% confidence interval, 17.7-41.8). The overall survival rate at 1, 2, and 3 years was 77%, 56%, and 41%, respectively. The local control rate at 1, 2, and 3 years was 83%, 74%, and 62%, respectively. Thirty-nine of the 53 patients (74%) showed treatment failure. Seventeen of the 39 (44%) developed an in-field recurrence, 18 (46%) distant metastasis with or without regional failure, and 3 (8%) an isolated out-of-field nodal recurrence only. One patient died of disease in an unknown location. In patients treated with 3D-CRT for esophageal SCC, the omission of elective nodal irradiation was not associated with a significant amount of failure in lymph node regions not included in the planning target volume. Local failure and distant metastases remained the predominant problems. Copyright 2010 Elsevier Inc. All rights reserved.

Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: Phase I study

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

McGarry, Ronald C.; Papiez, Lech; Williams, Mark

Purpose: A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer. Methods and Materials: All patients had non-small-cell lung carcinoma, Stage T1a or T1b N0, M0. Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total (3 x 8 Gy fractions) using 7-10 beams. Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods. Results: The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy),more » but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis. Local failure occurred in 4/19 T1 and 6/28 T2 patients. Nine local failures occurred at doses {<=}16 Gy and only 1 at higher doses. Local failures occurred between 3 and 31 months from treatment. Within the T1 group, 5 patients had distant or regional recurrence as an isolated event, whereas 3 patients had both distant and regional recurrence. Within the T2 group, 2 patients had solitary regional recurrences, and the 4 patients who failed distantly also failed regionally. Conclusions: Stereotactic body radiation therapy seems to be a safe, effective means of treating early-stage lung cancer in medically inoperable patients. Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors.« less

Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

PubMed

Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

2017-04-12

Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We found that social recognition memory is consolidated through CREB-meditated gene expression in the hippocampus, medial prefrontal cortex, anterior cingulate cortex (ACC), and amygdala. Importantly, network analyses based on c-fos expression suggest that functional connectivity of these four brain regions with other brain regions is increased with time spent in social investigation toward the generation of brain networks to consolidate social recognition memory. Furthermore, our findings suggest that hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. Copyright © 2017 the authors 0270-6474/17/374103-14$15.00/0.

Impact of Blood-Brain Barrier Integrity on Tumor Growth and Therapy Response in Brain Metastases.

PubMed

Osswald, Matthias; Blaes, Jonas; Liao, Yunxiang; Solecki, Gergely; Gömmel, Miriam; Berghoff, Anna S; Salphati, Laurent; Wallin, Jeffrey J; Phillips, Heidi S; Wick, Wolfgang; Winkler, Frank

2016-12-15

The role of blood-brain barrier (BBB) integrity for brain tumor biology and therapy is a matter of debate. We developed a new experimental approach using in vivo two-photon imaging of mouse brain metastases originating from a melanoma cell line to investigate the growth kinetics of individual tumor cells in response to systemic delivery of two PI3K/mTOR inhibitors over time, and to study the impact of microregional vascular permeability. The two drugs are closely related but differ regarding a minor chemical modification that greatly increases brain penetration of one drug. Both inhibitors demonstrated a comparable inhibition of downstream targets and melanoma growth in vitro In vivo, increased BBB permeability to sodium fluorescein was associated with accelerated growth of individual brain metastases. Melanoma metastases with permeable microvessels responded similarly to equivalent doses of both inhibitors. In contrast, metastases with an intact BBB showed an exclusive response to the brain-penetrating inhibitor. The latter was true for macro- and micrometastases, and even single dormant melanoma cells. Nuclear morphology changes and single-cell regression patterns implied that both inhibitors, if extravasated, target not only perivascular melanoma cells but also those distant to blood vessels. Our study provides the first direct evidence that nonpermeable brain micro- and macrometastases can effectively be targeted by a drug designed to cross the BBB. Small-molecule inhibitors with these optimized properties are promising agents in preventing or treating brain metastases in patients. Clin Cancer Res; 22(24); 6078-87. ©2016 AACRSee related commentary by Steeg et al., p. 5953. ©2016 American Association for Cancer Research.

[The Role of Supraclavicular lymph node dissection in Breast Cancer Patients with Synchronous Ipsilateral Supraclavicular Lymph Node Metastasis].

PubMed

Zhang, W; Qi, X M; Chen, A X; Zhang, P; Cao, X C; Xiao, C H

2017-05-23

Objective: In this study, we evaluated the effect of supraclavicular lymph node dissection in breast cancer patients who presented with ipsilateral supraclavicular lymph node metastasis (ISLM) without distant metastasis. Methods: A total of 90 patients with synchronous ISLM without distant metastasis between 2000 and 2009 were retrospectively analyzed. Patients were retrospectively divided into two groups, namely supraclavicular lymph node dissection group(34 patients) and non-dissection group(56 patients), according to whether they underwentsupraclavicular lymph node dissection or not.The Kaplan-Meier method was applied to analyze the locoregional relapse free survival (LRFS) and overall survival(OS). Results: Median follow-upwas 85 months(range, 6 to 11 months). Local recurrence in 32 cases, 47 cases of distant metastasis, of which 25 patients were accompanied by both locoregional relapse and distant metastasis. Of the 32 patients with locoregional relapse, 11 patients were in the lymph node dissection group and 21 patients in the control group. Of the 47 patients with distant metastases, 17 were treated with lymph node dissection, 30 in the control group. Thirty-two patients died in the whole group and 16 patients underwentlymph node dissection and 16 patients didn't. There was no significant difference between the rate of 5-year LRFS and 5-year OS ( P =0.359, P =0.246). For patients of ER negative, the 5-year loco-regional relapse free survival rates were 63.7% and 43.3% in supraclavicular lymph node dissection group and control group, respectively. The 5-year overall survival rates were 52.1% and 52.3%, respectively, and there were no statistically significant differences ( P =0.118, P =0.951). For patients of PR negative, the 5-yearloco-regional relapse free rates were 59.8% and 46.2%, respectively, and the 5-year overall survival rates were 50.6% and 43.2%, respectively, and there was no significant difference between the two groups ( P =0.317, P =0.973). The 5-year recurrence-free survival rates of human epidermal growth factor receptor 2 (HER2)-positive patients were 61.2% and 48.0%( P =0.634), respectively, and the 5-year overall survival rates were 37.2% and 65.4%( P =0.032). Forty-seven patients suffered distant metastases and the 5-year metastases free survival rates were 37.3% and 38.5% in supraclavicular lymph node dissection group and control group, respectively. Conclusion: Supraclavicular lymph node dissection maybe an effective approach to improve the loco-regional control for the patients with ISLM, especially for ER negative and PR negative subtypes, but it might has adverseeffects for the patients with negative HER2 status.

Direct imaging of neural currents using ultra-low field magnetic resonance techniques

DOEpatents

Volegov, Petr L [Los Alamos, NM; Matlashov, Andrei N [Los Alamos, NM; Mosher, John C [Los Alamos, NM; Espy, Michelle A [Los Alamos, NM; Kraus, Jr., Robert H.

2009-08-11

Using resonant interactions to directly and tomographically image neural activity in the human brain using magnetic resonance imaging (MRI) techniques at ultra-low field (ULF), the present inventors have established an approach that is sensitive to magnetic field distributions local to the spin population in cortex at the Larmor frequency of the measurement field. Because the Larmor frequency can be readily manipulated (through varying B.sub.m), one can also envision using ULF-DNI to image the frequency distribution of the local fields in cortex. Such information, taken together with simultaneous acquisition of MEG and ULF-NMR signals, enables non-invasive exploration of the correlation between local fields induced by neural activity in cortex and more `distant` measures of brain activity such as MEG and EEG.

Genomic connectivity networks based on the BrainSpan atlas of the developing human brain

NASA Astrophysics Data System (ADS)

Mahfouz, Ahmed; Ziats, Mark N.; Rennert, Owen M.; Lelieveldt, Boudewijn P. F.; Reinders, Marcel J. T.

2014-03-01

The human brain comprises systems of networks that span the molecular, cellular, anatomic and functional levels. Molecular studies of the developing brain have focused on elucidating networks among gene products that may drive cellular brain development by functioning together in biological pathways. On the other hand, studies of the brain connectome attempt to determine how anatomically distinct brain regions are connected to each other, either anatomically (diffusion tensor imaging) or functionally (functional MRI and EEG), and how they change over development. A global examination of the relationship between gene expression and connectivity in the developing human brain is necessary to understand how the genetic signature of different brain regions instructs connections to other regions. Furthermore, analyzing the development of connectivity networks based on the spatio-temporal dynamics of gene expression provides a new insight into the effect of neurodevelopmental disease genes on brain networks. In this work, we construct connectivity networks between brain regions based on the similarity of their gene expression signature, termed "Genomic Connectivity Networks" (GCNs). Genomic connectivity networks were constructed using data from the BrainSpan Transcriptional Atlas of the Developing Human Brain. Our goal was to understand how the genetic signatures of anatomically distinct brain regions relate to each other across development. We assessed the neurodevelopmental changes in connectivity patterns of brain regions when networks were constructed with genes implicated in the neurodevelopmental disorder autism (autism spectrum disorder; ASD). Using graph theory metrics to characterize the GCNs, we show that ASD-GCNs are relatively less connected later in development with the cerebellum showing a very distinct expression of ASD-associated genes compared to other brain regions.

Location of subventricular zone recurrence and its radiation dose predicts survival in patients with glioblastoma.

PubMed

Weinberg, Brent D; Boreta, Lauren; Braunstein, Steve; Cha, Soonmee

2018-07-01

Glioblastomas are aggressive brain tumors that frequently recur in the subventricular zone (SVZ) despite maximal treatment. The purpose of this study was to evaluate imaging patterns of subventricular progression and impact of recurrent subventricular tumor involvement and radiation dose to patient outcome. Retrospective review of 50 patients diagnosed with glioblastoma and treated with surgery, radiation, and concurrent temozolomide from January 2012 to June 2013 was performed. Tumors were classified based on location, size, and cortical and subventricular zone involvement. Survival was compared based on recurrence type, distance from the initial enhancing tumor (local ≤ 2 cm, distant > 2 cm), and the radiation dose at the recurrence site. Progression of enhancing subventricular tumor was common at both local (58%) and distant (42%) sites. Median survival was better after local SVZ recurrence than distant SVZ recurrence (8.7 vs. 4.3 months, p = 0.04). Radiation doses at local SVZ recurrence sites recurrence averaged 57.0 ± 4.0 Gy compared to 44.7 ± 6.7 Gy at distant SVZ recurrence sites (p = 0.008). Distant subventricular progression at a site receiving ≤ 45 Gy predicted worse subsequent survival (p = 0.05). Glioblastomas frequently recurred in the subventricular zone, and patient survival was worse when enhancing tumor occurred at sites that received lower radiation doses. This recurrent disease may represent disease undertreated at the time of diagnosis, and further study is needed to determine if improved treatment strategies, such as including the subventricular zone in radiation fields, could improve clinical outcomes.

Learning to cooperate is essential for progress in physics

NASA Astrophysics Data System (ADS)

Dickau, Jonathan J.

2012-06-01

At the 10th Frontiers of Fundamental Physics symposium, Gerard't Hooft stated that, for some of the advances we hope to see in Physics during the future, there must be a great deal of cooperation between physicists from different disciplines, as well as mathematicians, programmers, technologists, and others. This requires us to evolve a new mindset; however, as so much of our past progress has come out of a fiercely competitive process - especially since a critical review of our ideas about reality remains essential to making clear progress and checking our progress. We must also address the fact that some frameworks appear incompatible, as with relativity and quantum mechanics, whose unification remains distant despite years of attempts to find a quantum gravity theory. I explore the idea that playful exploration, using both left-brained and right-brained approaches to learning, allows us to resolve conflicting ideas by taking advantage of innate human developmental and learning strategies and brain structure. It may thus foster the kind of interdisciplinary cooperation we are hoping to see.

A high-resolution enhancer atlas of the developing telencephalon.

PubMed

Visel, Axel; Taher, Leila; Girgis, Hani; May, Dalit; Golonzhka, Olga; Hoch, Renee V; McKinsey, Gabriel L; Pattabiraman, Kartik; Silberberg, Shanni N; Blow, Matthew J; Hansen, David V; Nord, Alex S; Akiyama, Jennifer A; Holt, Amy; Hosseini, Roya; Phouanenavong, Sengthavy; Plajzer-Frick, Ingrid; Shoukry, Malak; Afzal, Veena; Kaplan, Tommy; Kriegstein, Arnold R; Rubin, Edward M; Ovcharenko, Ivan; Pennacchio, Len A; Rubenstein, John L R

2013-02-14

The mammalian telencephalon plays critical roles in cognition, motor function, and emotion. Though many of the genes required for its development have been identified, the distant-acting regulatory sequences orchestrating their in vivo expression are mostly unknown. Here, we describe a digital atlas of in vivo enhancers active in subregions of the developing telencephalon. We identified more than 4,600 candidate embryonic forebrain enhancers and studied the in vivo activity of 329 of these sequences in transgenic mouse embryos. We generated serial sets of histological brain sections for 145 reproducible forebrain enhancers, resulting in a publicly accessible web-based data collection comprising more than 32,000 sections. We also used epigenomic analysis of human and mouse cortex tissue to directly compare the genome-wide enhancer architecture in these species. These data provide a primary resource for investigating gene regulatory mechanisms of telencephalon development and enable studies of the role of distant-acting enhancers in neurodevelopmental disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Functional connectivity in the developing brain: A longitudinal study from 4 to 9 months of age

PubMed Central

Damaraju, E.; Caprihan, A.; Lowe, J.R.; Allen, E.A.; Calhoun, V.D.; Phillips, J.P.

2013-01-01

We characterize the development of intrinsic connectivity networks (ICNs) from 4 to 9 months of age with resting state magnetic resonance imaging performed on sleeping infants without sedative medication. Data is analyzed with independent component analysis (ICA). Using both low (30 components) and high (100 components) ICA model order decompositions, we find that the functional network connectivity (FNC) map is largely similar at both 4 and 9 months. However at 9 months the connectivity strength decreases within local networks and increases between more distant networks. The connectivity within the default-mode network, which contains both local and more distant nodes, also increases in strength with age. The low frequency power spectrum increases with age only in the posterior cingulate cortex and posterior default mode network. These findings are consistent with a general developmental pattern of increasing longer distance functional connectivity over the first year of life and raise questions regarding the developmental importance of the posterior cingulate at this age. PMID:23994454

Functional connectivity in the developing brain: a longitudinal study from 4 to 9months of age.

PubMed

Damaraju, E; Caprihan, A; Lowe, J R; Allen, E A; Calhoun, V D; Phillips, J P

2014-01-01

We characterize the development of intrinsic connectivity networks (ICNs) from 4 to 9months of age with resting state magnetic resonance imaging performed on sleeping infants without sedative medication. Data is analyzed with independent component analysis (ICA). Using both low (30 components) and high (100 components) ICA model order decompositions, we find that the functional network connectivity (FNC) map is largely similar at both 4 and 9months. However at 9months the connectivity strength decreases within local networks and increases between more distant networks. The connectivity within the default-mode network, which contains both local and more distant nodes, also increases in strength with age. The low frequency power spectrum increases with age only in the posterior cingulate cortex and posterior default mode network. These findings are consistent with a general developmental pattern of increasing longer distance functional connectivity over the first year of life and raise questions regarding the developmental importance of the posterior cingulate at this age. © 2013.

[Therapy of malignant melanoma at the stage of distant metastasis].

PubMed

Garbe, C; Eigentler, T K

2004-02-01

Treatment of melanoma in the stage of distant metastasis aims on palliation and achievement of durable tumor remission with prolongation of survival. As long as metastasis is confined to one organ system and is removable, surgery remains the treatment of first choice. In limited metastasis radiotherapy may likewise be indicated, particularly in bone and brain metastasis. More extensive metastasis should be treated by chemotherapy or chemoimmunotherapy. Monochemotherapy with dacarbazine, temozolomide, fotemustine and vindesine or its combinations with interferon-alpha are currently preferred. Polychemotherapy or its combinations with interferon-alpha and interleukin-2 are suitable to produce higher response rates but failed to prolong survival. As these treatments are associated with substantially higher toxicity they have been widely abandoned. Combined treatment with dacarbazine and interferon-alpha obtain tumor responses or stable disease in 40-50% and objective tumor remissions in 15-20% of patients. Effective cancer vaccination strategies and blockade of melanoma specific target molecules are currently developed as new treatment options.

Machine Learning Classification Combining Multiple Features of A Hyper-Network of fMRI Data in Alzheimer's Disease

PubMed Central

Guo, Hao; Zhang, Fan; Chen, Junjie; Xu, Yong; Xiang, Jie

2017-01-01

Exploring functional interactions among various brain regions is helpful for understanding the pathological underpinnings of neurological disorders. Brain networks provide an important representation of those functional interactions, and thus are widely applied in the diagnosis and classification of neurodegenerative diseases. Many mental disorders involve a sharp decline in cognitive ability as a major symptom, which can be caused by abnormal connectivity patterns among several brain regions. However, conventional functional connectivity networks are usually constructed based on pairwise correlations among different brain regions. This approach ignores higher-order relationships, and cannot effectively characterize the high-order interactions of many brain regions working together. Recent neuroscience research suggests that higher-order relationships between brain regions are important for brain network analysis. Hyper-networks have been proposed that can effectively represent the interactions among brain regions. However, this method extracts the local properties of brain regions as features, but ignores the global topology information, which affects the evaluation of network topology and reduces the performance of the classifier. This problem can be compensated by a subgraph feature-based method, but it is not sensitive to change in a single brain region. Considering that both of these feature extraction methods result in the loss of information, we propose a novel machine learning classification method that combines multiple features of a hyper-network based on functional magnetic resonance imaging in Alzheimer's disease. The method combines the brain region features and subgraph features, and then uses a multi-kernel SVM for classification. This retains not only the global topological information, but also the sensitivity to change in a single brain region. To certify the proposed method, 28 normal control subjects and 38 Alzheimer's disease patients were selected to participate in an experiment. The proposed method achieved satisfactory classification accuracy, with an average of 91.60%. The abnormal brain regions included the bilateral precuneus, right parahippocampal gyrus\\hippocampus, right posterior cingulate gyrus, and other regions that are known to be important in Alzheimer's disease. Machine learning classification combining multiple features of a hyper-network of functional magnetic resonance imaging data in Alzheimer's disease obtains better classification performance. PMID:29209156

Local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer.

PubMed

Kimoto, Takuya; Yamazaki, Hideya; Suzuki, Gen; Aibe, Norihiro; Masui, Koji; Tatekawa, Kotoha; Sasaki, Naomi; Fujiwara, Hitoshi; Shiozaki, Atsushi; Konishi, Hirotaka; Nakamura, Satoaki; Yamada, Kei

2017-09-01

Radiotherapy is an effective treatment for the postoperative loco-regional recurrence of esophageal cancer; however, the optimal treatment field remains controversial. This study aims to evaluate the outcome of local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer. We retrospectively investigated 35 patients treated for a postoperative loco-regional recurrence of esophageal cancer with local field radiotherapy between December 2008 and March 2016. The median irradiation dose was 60 Gy (range: 50-67.5 Gy). Thirty-one (88.6%) patients received concurrent chemotherapy. The median follow-up period was 18 months (range: 5-94 months). The 2-year overall survival was 55.7%, with a median survival time of 29.9 months. In the univariate analysis, the maximal diameter ≤20 mm (P = 0.0383), solitary lesion (P = 0.0352), and the complete remission after treatment (P = 0.00411) had a significantly better prognosis. A total of 27 of 35 patients (77.1%) had progressive disease (loco-regional failure [n = 9], distant metastasis [n = 7], and both loco-regional failure and distant metastasis [n = 11]). No patients had Grade 3 or greater mucositis. Local field radiotherapy is a considerable treatment option for postoperative loco-regional recurrence of esophageal cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip.

PubMed

Dauth, Stephanie; Maoz, Ben M; Sheehy, Sean P; Hemphill, Matthew A; Murty, Tara; Macedonia, Mary Kate; Greer, Angie M; Budnik, Bogdan; Parker, Kevin Kit

2017-03-01

Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: the scarcity of comparative data for cells originating from distinct brain regions and the lack of multiregional brain in vitro models. We demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro. In vivo, the brain is unique in its structural and functional organization, and the interactions and communication between different brain areas are essential components of proper brain function. This fact and the observation that neurons from different areas of the brain exhibit unique behaviors in vitro underline the importance of establishing multiregional brain in vitro models. Therefore, we here developed a multiregional brain-on-a-chip and observed a reduction of overall firing activity, as well as altered amounts of astrocytes and specific neuronal cell types compared with separately cultured neurons. Furthermore, this multiregional model was used to study the effects of phencyclidine, a drug known to induce schizophrenia-like symptoms in vivo, on individual brain areas separately while monitoring downstream effects on interconnected regions. Overall, this work provides a comparison of cells from different brain regions in vitro and introduces a multiregional brain-on-a-chip that enables the development of unique disease models incorporating essential in vivo features. NEW & NOTEWORTHY Due to the scarcity of comparative data for cells from different brain regions in vitro, we demonstrated that neurons isolated from distinct brain areas exhibit unique behaviors in vitro. Moreover, in vivo proper brain function is dependent on the connection and communication of several brain regions, underlining the importance of developing multiregional brain in vitro models. We introduced a novel brain-on-a-chip model, implementing essential in vivo features, such as different brain areas and their functional connections. Copyright © 2017 the American Physiological Society.

Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip

PubMed Central

Dauth, Stephanie; Maoz, Ben M.; Sheehy, Sean P.; Hemphill, Matthew A.; Murty, Tara; Macedonia, Mary Kate; Greer, Angie M.; Budnik, Bogdan

2017-01-01

Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: the scarcity of comparative data for cells originating from distinct brain regions and the lack of multiregional brain in vitro models. We demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro. In vivo, the brain is unique in its structural and functional organization, and the interactions and communication between different brain areas are essential components of proper brain function. This fact and the observation that neurons from different areas of the brain exhibit unique behaviors in vitro underline the importance of establishing multiregional brain in vitro models. Therefore, we here developed a multiregional brain-on-a-chip and observed a reduction of overall firing activity, as well as altered amounts of astrocytes and specific neuronal cell types compared with separately cultured neurons. Furthermore, this multiregional model was used to study the effects of phencyclidine, a drug known to induce schizophrenia-like symptoms in vivo, on individual brain areas separately while monitoring downstream effects on interconnected regions. Overall, this work provides a comparison of cells from different brain regions in vitro and introduces a multiregional brain-on-a-chip that enables the development of unique disease models incorporating essential in vivo features. NEW & NOTEWORTHY Due to the scarcity of comparative data for cells from different brain regions in vitro, we demonstrated that neurons isolated from distinct brain areas exhibit unique behaviors in vitro. Moreover, in vivo proper brain function is dependent on the connection and communication of several brain regions, underlining the importance of developing multiregional brain in vitro models. We introduced a novel brain-on-a-chip model, implementing essential in vivo features, such as different brain areas and their functional connections. PMID:28031399

Chandra X-Ray Observatory Image of the Distant Galaxy, 3C294

NASA Technical Reports Server (NTRS)

2000-01-01

This most distant x-ray cluster of galaxies yet has been found by astronomers using Chandra X-ray Observatory (CXO). Approximately 10 billion light-years from Earth, the cluster 3C294 is 40 percent farther than the next most distant x-ray galaxy cluster. The existence of such a faraway cluster is important for understanding how the universe evolved. CXO's image reveals an hourglass-shaped region of x-ray emissions centered on the previously known central radio source (seen in this image as the blue central object) that extends outward for 60,000 light- years. The vast clouds of hot gas that surround such galaxies in clusters are thought to be heated by collapse toward the center of the cluster. Until CXO, x-ray telescopes have not had the needed sensitivity to identify such distant clusters of galaxies. Galaxy clusters are the largest gravitationally bound structures in the universe. The intensity of the x-rays in this CXO image of 3C294 is shown as red for low energy x-rays, green for intermediate, and blue for the most energetic x-rays. (Photo credit: NASA/loA/A. Fabian et al)

The relationship between spatial configuration and functional connectivity of brain regions.

PubMed

Bijsterbosch, Janine Diane; Woolrich, Mark W; Glasser, Matthew F; Robinson, Emma C; Beckmann, Christian F; Van Essen, David C; Harrison, Samuel J; Smith, Stephen M

2018-02-16

Brain connectivity is often considered in terms of the communication between functionally distinct brain regions. Many studies have investigated the extent to which patterns of coupling strength between multiple neural populations relates to behaviour. For example, studies have used 'functional connectivity fingerprints' to characterise individuals' brain activity. Here, we investigate the extent to which the exact spatial arrangement of cortical regions interacts with measures of brain connectivity. We find that the shape and exact location of brain regions interact strongly with the modelling of brain connectivity, and present evidence that the spatial arrangement of functional regions is strongly predictive of non-imaging measures of behaviour and lifestyle. We believe that, in many cases, cross-subject variations in the spatial configuration of functional brain regions are being interpreted as changes in functional connectivity. Therefore, a better understanding of these effects is important when interpreting the relationship between functional imaging data and cognitive traits. © 2018, Bijsterbosch et al.

Aberrant Global and Regional Topological Organization of the Fractional Anisotropy-weighted Brain Structural Networks in Major Depressive Disorder

PubMed Central

Chen, Jian-Huai; Yao, Zhi-Jian; Qin, Jiao-Long; Yan, Rui; Hua, Ling-Ling; Lu, Qing

2016-01-01

Background: Most previous neuroimaging studies have focused on the structural and functional abnormalities of local brain regions in major depressive disorder (MDD). Moreover, the exactly topological organization of networks underlying MDD remains unclear. This study examined the aberrant global and regional topological patterns of the brain white matter networks in MDD patients. Methods: The diffusion tensor imaging data were obtained from 27 patients with MDD and 40 healthy controls. The brain fractional anisotropy-weighted structural networks were constructed, and the global network and regional nodal metrics of the networks were explored by the complex network theory. Results: Compared with the healthy controls, the brain structural network of MDD patients showed an intact small-world topology, but significantly abnormal global network topological organization and regional nodal characteristic of the network in MDD were found. Our findings also indicated that the brain structural networks in MDD patients become a less strongly integrated network with a reduced central role of some key brain regions. Conclusions: All these resulted in a less optimal topological organization of networks underlying MDD patients, including an impaired capability of local information processing, reduced centrality of some brain regions and limited capacity to integrate information across different regions. Thus, these global network and regional node-level aberrations might contribute to understanding the pathogenesis of MDD from the view of the brain network. PMID:26960371

A viscoelastic analysis of the P56 mouse brain under large-deformation dynamic indentation.

PubMed

MacManus, David B; Pierrat, Baptiste; Murphy, Jeremiah G; Gilchrist, Michael D

2017-01-15

The brain is a complex organ made up of many different functional and structural regions consisting of different types of cells such as neurons and glia, as well as complex anatomical geometries. It is hypothesized that the different regions of the brain exhibit significantly different mechanical properties which may be attributed to the diversity of cells within individual brain regions. The regional viscoelastic properties of P56 mouse brain tissue, up to 70μm displacement, are presented and discussed in the context of traumatic brain injury, particularly how the different regions of the brain respond to mechanical loads. Force-relaxation data obtained from micro-indentation measurements were fit to both linear and quasi-linear viscoelastic models to determine the time and frequency domain viscoelastic response of the pons, cortex, medulla oblongata, cerebellum, and thalamus. The damping ratio of each region was also determined. Each region was found to have a unique mechanical response to the applied displacement, with the pons and thalamus exhibiting the largest and smallest force-response, respectively. All brain regions appear to have an optimal frequency for the dissipation of energies which lies between 1 and 10Hz. We present the first mechanical characterization of the viscoelastic response for different regions of mouse brain. Force-relaxation tests are performed under large strain dynamic micro-indentation, and viscoelastic models are used subsequently, providing time-dependent mechanical properties of brain tissue under loading conditions comparable to what is experienced in TBI. The unique mechanical properties of different brain regions are highlighted, with substantial variations in the viscoelastic properties and damping ratio of each region. Cortex and pons were the stiffest regions, while the thalamus and medulla were most compliant. The cerebellum and thalamus had highest damping ratio values and those of the medulla were lowest. The reported material parameters can be implemented into finite element computer models of the mouse to investigate the effects of trauma on individual brain regions. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Communication of brain network core connections altered in behavioral variant frontotemporal dementia but possibly preserved in early-onset Alzheimer's disease

NASA Astrophysics Data System (ADS)

Daianu, Madelaine; Jahanshad, Neda; Mendez, Mario F.; Bartzokis, George; Jimenez, Elvira E.; Thompson, Paul M.

2015-03-01

Diffusion imaging and brain connectivity analyses can assess white matter deterioration in the brain, revealing the underlying patterns of how brain structure declines. Fiber tractography methods can infer neural pathways and connectivity patterns, yielding sensitive mathematical metrics of network integrity. Here, we analyzed 1.5-Tesla wholebrain diffusion-weighted images from 64 participants - 15 patients with behavioral variant frontotemporal dementia (bvFTD), 19 with early-onset Alzheimer's disease (EOAD), and 30 healthy elderly controls. Using whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We evaluated the brain's networks focusing on the most highly central and connected regions, also known as hubs, in each diagnostic group - specifically the "high-cost" structural backbone used in global and regional communication. The high-cost backbone of the brain, predicted by fiber density and minimally short pathways between brain regions, accounted for 81-92% of the overall brain communication metric in all diagnostic groups. Furthermore, we found that the set of pathways interconnecting high-cost and high-capacity regions of the brain's communication network are globally and regionally altered in bvFTD, compared to healthy participants; however, the overall organization of the high-cost and high-capacity networks were relatively preserved in EOAD participants, relative to controls. Disruption of the major central hubs that transfer information between brain regions may impair neural communication and functional integrity in characteristic ways typical of each subtype of dementia.

A squamous cell lung carcinoma with abscess-like distant metastasis.

PubMed

Dursunoğlu, Neşe; Başer, Sevin; Evyapan, Fatma; Kiter, Göksel; Ozkurt, Sibel; Polat, Bahattin; Karabulut, Nevzat

2007-01-01

This is a metastatic spread of squamous cell lung carcinoma to lungs, liver, lymph node, bone and subcutanous region as multiple abscess-like lesions. A fifty-five years old man admitted to the out-patient clinic with fever, cough, hemopthysis, night sweats, chest pain, abdominal pain and weight loss. In a short period of time abcess like lesions developed in his lungs, liver, lymph node, bone and subcutanous region. Though the clinical presentation is suggestive for an infectious condition, no success to antimicrobial treatment and negative results of microbiological studies have arised a need to further investigations. Histopathological studies of the abscess wall ultimately gave the definitive diagnosis as metastatic squamous cell carcinoma. We believe that case report is interesting because of the uncommon metastatic lesions masquerading the abscesses and also wide-spread multiple distant invasions of a squamous cell lung carcinoma in a short time period.

Patterns in hospitals' use of a regional poison information center.

PubMed Central

Chafee-Bahamon, C; Caplan, D L; Lovejoy, F H

1983-01-01

A statewide poison center undertook a study to identify types of hospitals which used its information services. Initial trends in calls from hospitals to the center over the center's first two years and percentages of hospitals' patient caseloads for which the center consulted were analyzed for 104 acute care hospitals by hospitals' location, size, and emergency room staffing. After the center's establishment as a regional resource, emergency room staff in urban teaching hospitals showed the greatest increase in calls within a year (88 per cent) and the highest consultation rates for poison patients seen (57 per cent). Private physician emergency room staff, and staff in distant and rural hospitals, showed lower or no increases in calls and lower consultation rates. Findings suggest that private physician emergency room staff and staff in distant and rural hospitals be considered for poison center outreach. Marketing of consultation services for non-pediatric overdoses is also indicated. PMID:6829822

Parotid adenoid cystic carcinoma: Retrospective single institute analysis.

PubMed

Mannelli, Giuditta; Cecconi, Lorenzo; Fasolati, Martina; Santoro, Roberto; Franchi, Alessandro; Gallo, Oreste

Adenoid cystic carcinoma (ACC) is a uncommon salivary malignant tumor. Our aim was to review our experience with parotid ACC, to identify clinical-pathological parameters predictive for outcome. We retrospectively reviewed 228 patients affected by parotid gland carcinomas surgically treated at our Institution. Forty-four ACC were included in this study. Multivariate analysis risk models were built to predict recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and disease free survival (DFS). Twenty-one patients (47.7%) died from ACC and 2.3% for other causes. The 41% presented local-regional recurrence, with a regional-RFP rate of 93%, and the 34% reported distant metastases (DM). The five and ten-year OS rates were 74% and 50%, respectively. Recurrences were mainly influenced by the presence of perineural invasion and nerve paralysis, whilst female gender and age<50 were predictors for good prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Kubicek, Gregory J., E-mail: kubicek-gregory@cooperhealth.edu; Turtz, Alan; Xue, Jinyu

Purpose: Patients with poor performance status (PS), usually defined as a Karnofsky Performance Status of 60 or less, were not eligible for randomized stereotactic radiosurgery (SRS) studies, and many guidelines suggest that whole-brain radiation therapy (WBRT) is the most appropriate treatment for poor PS patients. Methods and Materials: In this retrospective review of our SRS database, we identified 36 patients with PS of 60 or less treated with SRS for central nervous system (CNS) metastatic disease. PS, as defined by the Karnofsky Performance Status, was 60 (27 patients), 50 (8 patients), or 40 (1 patient). The median number of CNSmore » lesions treated was 3. Results: Median overall survival (OS) was 7.2 months (range, 0.73-25.6 months). Fifteen patients (41%) were alive at 6 months, and 6 patients (16.6%) were alive at 1 year. There was no difference in OS in patients who underwent previous WBRT. There were no local failures or cases of radiation toxicity. Distant CNS failures were seen in 9 patients (25%). Conclusions: Our patients with poor PS had reasonable median OS and relatively low distant CNS failure rates. Patients in this patient population may be ideal candidates for SRS compared with WBRT given the low incidence of distant failure over their remaining lives and the favorable logistics of single-fraction treatment for these patients with debility and their caregivers.« less

Galactic Teamwork Makes Distant Bubbles

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2016-03-01

During the period of reionization that followed the dark ages of our universe, hydrogen was transformed from a neutral state, which is opaque to radiation, to an ionized one, which is transparent to radiation. But what generated the initial ionizing radiation? The recent discovery of multiple distant galaxies offers evidence for how this process occurred.Two Distant GalaxiesWe believe reionization occurred somewhere between a redshift of z = 6 and 7, because Ly-emitting galaxies drop out at roughly this redshift. Beyond this distance, were generally unable to see the light from these galaxies, because the universe is no longer transparent to their emission. This is not always the case, however: if a bubble of ionized gas exists around a distant galaxy, the radiation can escape, allowing us to see the galaxy.This is true of two recently-discovered Ly-emitting galaxies, confirmed to be at a redshift of z~7 and located near one another in a region known as the Bremer Deep Field. The fact that were able to see the radiation from these galaxies means that they are in an ionized HII region presumably one of the earlier regions to have become reionized in the universe.But on their own, neither of these galaxies is capable of generating an ionized bubble large enough for their light to escape. So what ionized the region around them, and what does this mean for our understanding of how reionization occurred in the universe?A Little Help From FriendsLocation in different filters of the objects in the Hubble Bremer Deep Field catalog. The z~7 selection region is outlined by the grey box. BDF-521 and BDF-3299 were the two originally discovered galaxies; the remaining red markers indicate the additional six galaxies discovered in the same region. [Castellano et al. 2016]A team of scientists led by Marco Castellano (Rome Observatory, INAF) investigated the possibility that there are other, faint galaxies near these two that have helped to ionize the region. Performing a survey using deep field Hubble observations, Castellano and collaborators found an additional 6 galaxies in the same region as the first two, also at a redshift of z~7!The authors believe these galaxies provide a simple explanation of the ionized bubble: each of these faint, normal galaxies produced a small ionized bubble. The overlap of these many small bubbles provided the larger ionized region from which the light of the two originally discovered galaxies was able to escape.How normal is this clustering of galaxies found by Castellano and collaborators? The team demonstrates via cosmological modeling that the number density of galaxies in this region is a factor of 34 greater than would be expected at this distance in a random pointing of the same size.These results greatly support the theoretical prediction that the first ionization fronts in the universe were formed in regions with significant galaxy overdensities. The discovery of this deep-field collection of galaxies strongly suggests that reionization was driven by faint, normal star-forming galaxies in a clumpy process.CitationM. Castellano et al 2016 ApJ 818 L3. doi:10.3847/2041-8205/818/1/L3

Evaluation of Denoising Strategies to Address Motion-Correlated Artifacts in Resting-State Functional Magnetic Resonance Imaging Data from the Human Connectome Project

PubMed Central

Kandala, Sridhar; Nolan, Dan; Laumann, Timothy O.; Power, Jonathan D.; Adeyemo, Babatunde; Harms, Michael P.; Petersen, Steven E.; Barch, Deanna M.

2016-01-01

Abstract Like all resting-state functional connectivity data, the data from the Human Connectome Project (HCP) are adversely affected by structured noise artifacts arising from head motion and physiological processes. Functional connectivity estimates (Pearson's correlation coefficients) were inflated for high-motion time points and for high-motion participants. This inflation occurred across the brain, suggesting the presence of globally distributed artifacts. The degree of inflation was further increased for connections between nearby regions compared with distant regions, suggesting the presence of distance-dependent spatially specific artifacts. We evaluated several denoising methods: censoring high-motion time points, motion regression, the FMRIB independent component analysis-based X-noiseifier (FIX), and mean grayordinate time series regression (MGTR; as a proxy for global signal regression). The results suggest that FIX denoising reduced both types of artifacts, but left substantial global artifacts behind. MGTR significantly reduced global artifacts, but left substantial spatially specific artifacts behind. Censoring high-motion time points resulted in a small reduction of distance-dependent and global artifacts, eliminating neither type. All denoising strategies left differences between high- and low-motion participants, but only MGTR substantially reduced those differences. Ultimately, functional connectivity estimates from HCP data showed spatially specific and globally distributed artifacts, and the most effective approach to address both types of motion-correlated artifacts was a combination of FIX and MGTR. PMID:27571276

Transcranial current stimulation focality using disc and ring electrode configurations: FEM analysis

NASA Astrophysics Data System (ADS)

Datta, Abhishek; Elwassif, Maged; Battaglia, Fortunato; Bikson, Marom

2008-06-01

We calculated the electric fields induced in the brain during transcranial current stimulation (TCS) using a finite-element concentric spheres human head model. A range of disc electrode configurations were simulated: (1) distant-bipolar; (2) adjacent-bipolar; (3) tripolar; and three ring designs, (4) belt, (5) concentric ring, and (6) double concentric ring. We compared the focality of each configuration targeting cortical structures oriented normal to the surface ('surface-radial' and 'cross-section radial'), cortical structures oriented along the brain surface ('surface-tangential' and 'cross-section tangential') and non-oriented cortical surface structures ('surface-magnitude' and 'cross-section magnitude'). For surface-radial fields, we further considered the 'polarity' of modulation (e.g. superficial cortical neuron soma hyper/depolarizing). The distant-bipolar configuration, which is comparable with commonly used TCS protocols, resulted in diffuse (un-focal) modulation with bi-directional radial modulation under each electrode and tangential modulation between electrodes. Increasing the proximity of the two electrodes (adjacent-bipolar electrode configuration) increased focality, at the cost of more surface current. At similar electrode distances, the tripolar-electrodes configuration produced comparable peak focality, but reduced radial bi-directionality. The concentric-ring configuration resulted in the highest spatial focality and uni-directional radial modulation, at the expense of increased total surface current. Changing ring dimensions, or use of two concentric rings, allow titration of this balance. The concentric-ring design may thus provide an optimized configuration for targeted modulation of superficial cortical neurons.

The prognosis analysis of different metastasis pattern in patients with different breast cancer subtypes: a SEER based study.

PubMed

Wang, Haiyong; Zhang, Chenyue; Zhang, Jingze; Kong, Li; Zhu, Hui; Yu, Jinming

2017-04-18

Studies on prognosis of different metastasis patterns in patients with different breast cancer subtypes (BCS) are limited. Therefore, we identified 7862 breast cancer patients with distant metastasis from 2010 to 2013 using Surveillance, Epidemiology, wand End Results (SEER) population-based data. The results showed that bone was the most common metastatic site and brain was the least common metastatic site, and the patients with HR+/HER2- occupied the highest metastasis proportion, the lowest metastasis proportion were found in HR-/HER2+ patients. Univariate and multivariate logistic regression analysis were used to analyze the association, and it was found that there were significant differences of distant metastasis patterns in patients with different BCS(different P value). Importantly, univariate and multivariate Cox regression analysis were used to analyze the prognosis. It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subgroup (all, P > 0.05), and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS (all, P<0.01). Interestingly, for patients with two metastatic sites, those with bone and lung metastasis had best CSS in the HR+/HER2- (P<0.001) and HR+/HER2+ subgroups (P=0.009) However, for patients with three and four metastatic sites, there was no statistical difference in their CSS (all, P>0.05).

The prognosis analysis of different metastasis pattern in patients with different breast cancer subtypes: a SEER based study

PubMed Central

Wang, Haiyong; Zhang, Chenyue; Zhang, Jingze; Kong, Li; Zhu, Hui; Yu, Jinming

2017-01-01

Studies on prognosis of different metastasis patterns in patients with different breast cancer subtypes (BCS) are limited. Therefore, we identified 7862 breast cancer patients with distant metastasis from 2010 to 2013 using Surveillance, Epidemiology, wand End Results (SEER) population-based data. The results showed that bone was the most common metastatic site and brain was the least common metastatic site, and the patients with HR+/HER2− occupied the highest metastasis proportion, the lowest metastasis proportion were found in HR-/HER2+ patients. Univariate and multivariate logistic regression analysis were used to analyze the association, and it was found that there were significant differences of distant metastasis patterns in patients with different BCS(different P value). Importantly, univariate and multivariate Cox regression analysis were used to analyze the prognosis. It was proven that only bone metastasis was not a prognostic factor in the HR+/HER2-, HR+/HER2+ and HR-/HER2+ subgroup (all, P > 0.05), and patients with brain metastasis had the worst cancer specific survival (CSS) in all the subgroups of BCS (all, P<0.01). Interestingly, for patients with two metastatic sites, those with bone and lung metastasis had best CSS in the HR+/HER2- (P<0.001) and HR+/HER2+ subgroups (P=0.009) However, for patients with three and four metastatic sites, there was no statistical difference in their CSS (all, P>0.05). PMID:28038448

Efficacy, safety and outcome of frameless image-guided robotic radiosurgery for brain metastases after whole brain radiotherapy.

PubMed

Lohkamp, Laura-Nanna; Vajkoczy, Peter; Budach, Volker; Kufeld, Markus

2018-05-01

Estimating efficacy, safety and outcome of frameless image-guided robotic radiosurgery for the treatment of recurrent brain metastases after whole brain radiotherapy (WBRT). We performed a retrospective single-center analysis including patients with recurrent brain metastases after WBRT, who have been treated with single session radiosurgery, using the CyberKnife® Radiosurgery System (CKRS) (Accuray Inc., CA) between 2011 and 2016. The primary end point was local tumor control, whereas secondary end points were distant tumor control, treatment-related toxicity and overall survival. 36 patients with 140 recurrent brain metastases underwent 46 single session CKRS treatments. Twenty one patients had multiple brain metastases (58%). The mean interval between WBRT and CKRS accounted for 2 years (range 0.2-7 years). The median number of treated metastases per treatment session was five (range 1-12) with a tumor volume of 1.26 ccm (mean) and a median tumor dose of 18 Gy prescribed to the 70% isodose line. Two patients experienced local tumor recurrence within the 1st year after treatment and 13 patients (36%) developed novel brain metastases. Nine of these patients underwent additional one to three CKRS treatments. Eight patients (22.2%) showed treatment-related radiation reactions on MRI, three with clinical symptoms. Median overall survival was 19 months after CKRS. The actuarial 1-year local control rate was 94.2%. CKRS has proven to be locally effective and safe due to high local tumor control rates and low toxicity. Thus CKRS offers a reliable salvage treatment option for recurrent brain metastases after WBRT.

Novel Intrinsic Ignition Method Measuring Local-Global Integration Characterizes Wakefulness and Deep Sleep

PubMed Central

Tagliazucchi, Enzo; Sanjuán, Ana

2017-01-01

Abstract A precise definition of a brain state has proven elusive. Here, we introduce the novel local-global concept of intrinsic ignition characterizing the dynamical complexity of different brain states. Naturally occurring intrinsic ignition events reflect the capability of a given brain area to propagate neuronal activity to other regions, giving rise to different levels of integration. The ignitory capability of brain regions is computed by the elicited level of integration for each intrinsic ignition event in each brain region, averaged over all events. This intrinsic ignition method is shown to clearly distinguish human neuroimaging data of two fundamental brain states (wakefulness and deep sleep). Importantly, whole-brain computational modelling of this data shows that at the optimal working point is found where there is maximal variability of the intrinsic ignition across brain regions. Thus, combining whole brain models with intrinsic ignition can provide novel insights into underlying mechanisms of brain states. PMID:28966977

Novel Intrinsic Ignition Method Measuring Local-Global Integration Characterizes Wakefulness and Deep Sleep.

PubMed

Deco, Gustavo; Tagliazucchi, Enzo; Laufs, Helmut; Sanjuán, Ana; Kringelbach, Morten L

2017-01-01

A precise definition of a brain state has proven elusive. Here, we introduce the novel local-global concept of intrinsic ignition characterizing the dynamical complexity of different brain states. Naturally occurring intrinsic ignition events reflect the capability of a given brain area to propagate neuronal activity to other regions, giving rise to different levels of integration. The ignitory capability of brain regions is computed by the elicited level of integration for each intrinsic ignition event in each brain region, averaged over all events. This intrinsic ignition method is shown to clearly distinguish human neuroimaging data of two fundamental brain states (wakefulness and deep sleep). Importantly, whole-brain computational modelling of this data shows that at the optimal working point is found where there is maximal variability of the intrinsic ignition across brain regions. Thus, combining whole brain models with intrinsic ignition can provide novel insights into underlying mechanisms of brain states.

Patterns of failure and survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy in Saudi Arabia.

PubMed

Maklad, Ahmed Marzouk; Bayoumi, Yasser; Senosy Hassan, Mohamed Abdalazez; Elawadi, AbuSaleh A; AlHussain, Hussain; Elyamany, Ashraf; Aldhahri, Saleh F; Al-Qahtani, Khalid Hussain; AlQahtani, Mubarak; Tunio, Mutahir A

2016-01-01

We aimed to investigate the patterns of failure (locoregional and distant metastasis), associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT) combined with chemotherapy. From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66-70 Gy, 63 Gy to clinical target volume, and 50.4-56 Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. The median follow-up time was 52.2 months (range: 11-87 months). Epstein-Barr virus infection was positive in 63.2% of patients. Overall disease failure developed in 21 patients, of whom 85.8% belonged to stage III/IV disease. Among these, there were seven locoregional recurrences, three regional recurrences with distant metastases, and eleven distant metastases. The median interval from the date of diagnosis to failure was 26.5 months (range: 16-50 months). Six of ten (60%) locoregional recurrences were treated with reirradiation ± concurrent chemotherapy. The 5-year locoregional control, distant metastasis control, disease-free survival, and overall survival rates of whole cohort were 81.1%, 74.3%, 60.1%, and 73.4%, respectively. Cox regression analyses revealed that neoadjuvant chemotherapy, age, and Epstein-Barr virus were independent predictors for disease-free survival. Neoadjuvant chemotherapy followed by IMRT with or without chemotherapy improves the long-term survival of Saudi patients with nasopharyngeal carcinoma. Distant metastasis was the main pattern of treatment failure. Neoadjuvant chemotherapy, age, and Epstein-Barr virus status before IMRT were important independent prognostic factors.

Combining Cytotoxic and Immune-Mediated Gene Therapy to Treat Brain Tumors

PubMed Central

Curtin, James F.; King, Gwendalyn D.; Candolfi, Marianela; Greeno, Remy B.; Kroeger, Kurt M.; Lowenstein, Pedro R.; Castro, Maria G.

2006-01-01

Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implementation, e.g. conditional cytotoxic approaches, targeted delivery of toxins into the tumor mass, immune stimulatory strategies, and these will all be the focus of this review. Both conditional cytotoxicity and targeted toxin mediated tumor death, are aimed at eliminating an established tumor mass and preventing further growth. Tumors employ several defensive strategies that suppress and inhibit anti-tumor immune responses. A better understanding of the mechanisms involved in eliciting anti-tumor immune responses has identified promising targets for immunotherapy. Immunotherapy is designed to aid the immune system to recognize and destroy tumor cells in order to eliminate the tumor burden. Also, immune-therapeutic strategies have the added advantage that an activated immune system has the capability of recognizing tumor cells at distant sites from the primary tumor, therefore targeting metastasis distant from the primary tumor locale. Pre-clinical models and clinical trials have demonstrated that in spite of their location within the central nervous system (CNS), a tissue described as ‘immune privileged’, brain tumors can be effectively targeted by the activated immune system following various immunotherapeutic strategies. This review will highlight recent advances in brain tumor immunotherapy, with particular emphasis on advances made using gene therapy strategies, as well as reviewing other novel therapies that can be used in combination with immunotherapy. Another important aspect of implementing gene therapy in the clinical arena is to be able to image the targeting of the therapeutics to the tumors, treatment effectiveness and progression of disease. We have therefore reviewed the most exciting non-invasive, in vivo imaging techniques which can be used in combination with gene therapy to monitor therapeutic efficacy over time. PMID:16248789

Regional brain volumetry and brain function in severely brain-injured patients.

PubMed

Annen, Jitka; Frasso, Gianluca; Crone, Julia Sophia; Heine, Lizette; Di Perri, Carol; Martial, Charlotte; Cassol, Helena; Demertzi, Athena; Naccache, Lionel; Laureys, Steven

2018-04-01

The relationship between residual brain tissue in patients with disorders of consciousness (DOC) and the clinical condition is unclear. This observational study aimed to quantify gray (GM) and white matter (WM) atrophy in states of (altered) consciousness. Structural T1-weighted magnetic resonance images were processed for 102 severely brain-injured and 52 healthy subjects. Regional brain volume was quantified for 158 (sub)cortical regions using Freesurfer. The relationship between regional brain volume and clinical characteristics of patients with DOC and conscious brain-injured patients was assessed using a linear mixed-effects model. Classification of patients with unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) using regional volumetric information was performed and compared to classification using cerebral glucose uptake from fluorodeoxyglucose positron emission tomography. For validation, the T1-based classifier was tested on independent datasets. Patients were characterized by smaller regional brain volumes than healthy subjects. Atrophy occurred faster in UWS compared to MCS (GM) and conscious (GM and WM) patients. Classification was successful (misclassification with leave-one-out cross-validation between 2% and 13%) and generalized to the independent data set with an area under the receiver operator curve of 79% (95% confidence interval [CI; 67-91.5]) for GM and 70% (95% CI [55.6-85.4]) for WM. Brain volumetry at the single-subject level reveals that regions in the default mode network and subcortical gray matter regions, as well as white matter regions involved in long range connectivity, are most important to distinguish levels of consciousness. Our findings suggest that changes of brain structure provide information in addition to the assessment of functional neuroimaging and thus should be evaluated as well. Ann Neurol 2018;83:842-853. © 2018 American Neurological Association.

Brain region distribution and patterns of bioaccumulative perfluoroalkyl carboxylates and sulfonates in east greenland polar bears (Ursus maritimus).

PubMed

Greaves, Alana K; Letcher, Robert J; Sonne, Christian; Dietz, Rune

2013-03-01

The present study investigated the comparative accumulation of perfluoroalkyl acids (PFAAs) in eight brain regions of polar bears (Ursus maritimus, n = 19) collected in 2006 from Scoresby Sound, East Greenland. The PFAAs studied were perfluoroalkyl carboxylates (PFCAs, C(6) -C(15) chain lengths) and sulfonates (C(4) , C(6) , C(8) , and C(10) chain lengths) as well as selected precursors including perfluorooctane sulfonamide. On a wet-weight basis, blood-brain barrier transport of PFAAs occurred for all brain regions, although inner regions of the brain closer to incoming blood flow (pons/medulla, thalamus, and hypothalamus) contained consistently higher PFAA concentrations compared to outer brain regions (cerebellum, striatum, and frontal, occipital, and temporal cortices). For pons/medulla, thalamus, and hypothalamus, the most concentrated PFAAs were perfluorooctane sulfonate (PFOS), ranging from 47 to 58 ng/g wet weight, and perfluorotridecanoic acid, ranging from 43 to 49 ng/g wet weight. However, PFOS and the longer-chain PFCAs (C(10) -C(15) ) were significantly (p < 0.002) positively correlated with lipid content for all brain regions. Lipid-normalized PFOS and PFCA (C(10) -C(15) ) concentrations were not significantly (p > 0.05) different among brain regions. The burden of the sum of PFCAs, perfluoroalkyl sulfonates, and perfluorooctane sulfonamide in the brain (average mass, 392 g) was estimated to be 46 µg. The present study demonstrates that both PFCAs and perfluoroalkyl sulfonates cross the blood-brain barrier in polar bears and that wet-weight concentrations are brain region-specific. Copyright © 2012 SETAC.

Regulation of CYBB Gene Expression in Human Phagocytes by a Distant Upstream NF-κB Binding Site.

PubMed

Frazão, Josias B; Thain, Alison; Zhu, Zhiqing; Luengo, Marcos; Condino-Neto, Antonio; Newburger, Peter E

2015-09-01

The human CYBB gene encodes the gp91-phox component of the phagocyte oxidase enzyme complex, which is responsible for generating superoxide and other downstream reactive oxygen species essential to microbial killing. In the present study, we have identified by sequence analysis a putative NF-κB binding site in a DNase I hypersensitive site, termed HS-II, located in the distant 5' flanking region of the CYBB gene. Electrophoretic mobility assays showed binding of the sequence element by recombinant NF-κB protein p50 and by proteins in nuclear extract from the HL-60 myeloid leukemia cell line corresponding to p50 and to p50/p65 heterodimers. Chromatin immunoprecipitation demonstrated NF-κB binding to the site in intact HL-60 cells. Chromosome conformation capture (3C) assays demonstrated physical interaction between the NF-κB binding site and the CYBB promoter region. Inhibition of NF-κB activity by salicylate reduced CYBB expression in peripheral blood neutrophils and differentiated U937 monocytic leukemia cells. U937 cells transfected with a mutant inhibitor of κB "super-repressor" showed markedly diminished CYBB expression. Luciferase reporter analysis of the NF-κB site linked to the CYBB 5' flanking promoter region revealed enhanced expression, augmented by treatment with interferon-γ. These studies indicate a role for this distant, 15 kb upstream, binding site in NF-κB regulation of the CYBB gene, an essential component of phagocyte-mediated host defense. © 2015 Wiley Periodicals, Inc.

CD11c- and CD11b-expressing mouse leukocytes transport single Toxoplasma gondii tachyzoites to the brain

PubMed Central

Courret, Nathalie; Darche, Sylvie; Sonigo, Pierre; Milon, Geneviève; Buzoni-Gâtel, Dominique; Tardieux, Isabelle

2006-01-01

The protozoan parasite Toxoplasma gondii enters hosts through the intestinal mucosa and colonizes distant tissues such as the brain, where its progeny persists for a lifetime. We investigated the role of CD11c- and CD11b-expressing leukocytes in T gondii transport during the early step of parasitism from the mouse small intestine and during subsequent parasite localization in the brain. Following intragastric inoculation of cyst-containing parasites in mice, CD11c+ dendritic cells from the intestinal lamina propria, the Peyer patches, and the mesenteric lymph nodes were parasitized while in the blood, parasites were associated with the CD11c- CD11b+ monocytes. Using adoptive transfer experiments, we demonstrated that these parasitized cells triggered a parasitic process in the brain of naive recipient mice. Ex vivo analysis of parasitized leukocytes showed that single tachyzoites remained at the cell periphery, often surrounded by the host cell plasma membrane, but did not divide. Using either a dye that labels circulating leukocytes or an antibody known to prevent CD11b+ circulating leukocytes from leaving the microvascular bed lumen, and chimeric mice in which the hematopoietic cells expressed the green fluorescent protein, we established that T gondii zoites hijacked CD11b+ leukocytes to reach the brain extravascular space. PMID:16051744

Art, energy, and the brain.

PubMed

Pepperell, Robert

2018-01-01

Recent years have seen a growing interest among neuroscientists and vision scientists in art and aesthetics, exemplifying a more general trend toward interdisciplinary integration in the arts, humanities, and sciences. However, true art-science integration remains a distant prospect due to fundamental differences in outlook and approach between disciplines. I consider two great challenges for any project designed to explain the role of the brain in art appreciation. First, scientists and artists need to identify common ground, common questions, and a shared motivation for inquiry. Second, the neuroscience of art must transcend its current goal of correlating brain functions to behavior and begin to explain the connection between activity in the brain and the phenomenology of art appreciation. I propose that both challenges can be tackled using an energy-based approach. The concept of "energy" is clearly of central importance to the physical sciences, and to neuroscience in particular. Meanwhile, energy is a concept that artists and art historians have consistently referred to when trying to articulate how artworks are made and appreciated. I survey the role of energy in art, philosophical and psychological aesthetics, and neuroscience, and suggest how this approach could help to further integrate art and neuroscience, and explain how brain activity contributes to aesthetic experience. © 2018 Elsevier B.V. All rights reserved.

The Social Brain Is Not Enough: On the Importance of the Ecological Brain for the Origin of Language

PubMed Central

Ferretti, Francesco

2016-01-01

In this paper, I assume that the study of the origin of language is strictly connected to the analysis of the traits that distinguish human language from animal communication. Usually, human language is said to be unique in the animal kingdom because it enables and/or requires intentionality or mindreading. By emphasizing the importance of mindreading, the social brain hypothesis has provided major insights within the origin of language debate. However, as studies on non-human primates have demonstrated that intentional forms of communication are already present in these species to a greater or lesser extent, I maintain that the social brain is a necessary but not a sufficient condition to explain the uniqueness of language. In this paper, I suggest that the distinctive feature of human communication resides in the ability to tell stories, and that the origin of language should be traced with respect to the capacity to produce discourses, rather than phrases or words. As narrative requires the ability to link events distant from one another in space and time, my proposal is that in order to explain the origin of language, we need to appeal to both the social brain and the ecological brain – that is, the cognitive devices which allow us to mentally travel in space and time. PMID:27531987

Regional infant brain development: an MRI-based morphometric analysis in 3 to 13 month olds.

PubMed

Choe, Myong-Sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S; Benasich, April A; Grant, P Ellen

2013-09-01

Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants' whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders.

Regional Infant Brain Development: An MRI-Based Morphometric Analysis in 3 to 13 Month Olds

PubMed Central

Choe, Myong-sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S.; Benasich, April A.; Grant, P. Ellen

2013-01-01

Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants’ whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders. PMID:22772652

Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

PubMed

Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

2015-12-01

The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cultivar development and selection

USDA-ARS?s Scientific Manuscript database

Successful blackberry production and marketing depends on planting cultivars that are adapted to the region, efficiently produce high yields, and have the fruit quality the market, whether local or distant, demands. Blackberry breeding programs have developed cultivars that consumers like to eat and...

Distant Influence of Kuroshio Eddies on North Pacific Weather Patterns?

PubMed

Ma, Xiaohui; Chang, Ping; Saravanan, R; Montuoro, Raffaele; Hsieh, Jen-Shan; Wu, Dexing; Lin, Xiaopei; Wu, Lixin; Jing, Zhao

2015-12-04

High-resolution satellite measurements of surface winds and sea-surface temperature (SST) reveal strong coupling between meso-scale ocean eddies and near-surface atmospheric flow over eddy-rich oceanic regions, such as the Kuroshio and Gulf Stream, highlighting the importance of meso-scale oceanic features in forcing the atmospheric planetary boundary layer (PBL). Here, we present high-resolution regional climate modeling results, supported by observational analyses, demonstrating that meso-scale SST variability, largely confined in the Kuroshio-Oyashio confluence region (KOCR), can further exert a significant distant influence on winter rainfall variability along the U.S. Northern Pacific coast. The presence of meso-scale SST anomalies enhances the diabatic conversion of latent heat energy to transient eddy energy, intensifying winter cyclogenesis via moist baroclinic instability, which in turn leads to an equivalent barotropic downstream anticyclone anomaly with reduced rainfall. The finding points to the potential of improving forecasts of extratropical winter cyclones and storm systems and projections of their response to future climate change, which are known to have major social and economic impacts, by improving the representation of ocean eddy-atmosphere interaction in forecast and climate models.

Templated sequence insertion polymorphisms in the human genome

NASA Astrophysics Data System (ADS)

Onozawa, Masahiro; Aplan, Peter

2016-11-01

Templated Sequence Insertion Polymorphism (TSIP) is a recently described form of polymorphism recognized in the human genome, in which a sequence that is templated from a distant genomic region is inserted into the genome, seemingly at random. TSIPs can be grouped into two classes based on nucleotide sequence features at the insertion junctions; Class 1 TSIPs show features of insertions that are mediated via the LINE-1 ORF2 protein, including 1) target-site duplication (TSD), 2) polyadenylation 10-30 nucleotides downstream of a “cryptic” polyadenylation signal, and 3) preference for insertion at a 5’-TTTT/A-3’ sequence. In contrast, class 2 TSIPs show features consistent with repair of a DNA double-strand break via insertion of a DNA “patch” that is derived from a distant genomic region. Survey of a large number of normal human volunteers demonstrates that most individuals have 25-30 TSIPs, and that these TSIPs track with specific geographic regions. Similar to other forms of human polymorphism, we suspect that these TSIPs may be important for the generation of human diversity and genetic diseases.

Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains.

PubMed

Chen, Min; Yang, Weiwei; Li, Xin; Li, Xuran; Wang, Peng; Yue, Feng; Yang, Hui; Chan, Piu; Yu, Shun

2016-02-23

We previously reported that the levels of α-syn oligomers, which play pivotal pathogenic roles in age-related Parkinson's disease (PD) and dementia with Lewy bodies, increase heterogeneously in the aging brain. Here, we show that exogenous α-syn incubated with brain extracts from older cynomolgus monkeys and in Lewy body pathology (LBP)-susceptible brain regions (striatum and hippocampus) forms higher amounts of phosphorylated and oligomeric α-syn than that in extracts from younger monkeys and LBP-insusceptible brain regions (cerebellum and occipital cortex). The increased α-syn phosphorylation and oligomerization in the brain extracts from older monkeys and in LBP-susceptible brain regions were associated with higher levels of polo-like kinase 2 (PLK2), an enzyme promoting α-syn phosphorylation, and lower activity of protein phosphatase 2A (PP2A), an enzyme inhibiting α-syn phosphorylation, in these brain extracts. Further, the extent of the age- and brain-dependent increase in α-syn phosphorylation and oligomerization was reduced by inhibition of PLK2 and activation of PP2A. Inversely, phosphorylated α-syn oligomers reduced the activity of PP2A and showed potent cytotoxicity. In addition, the activity of GCase and the levels of ceramide, a product of GCase shown to activate PP2A, were lower in brain extracts from older monkeys and in LBP-susceptible brain regions. Our results suggest a role for altered intrinsic metabolic enzymes in age- and brain region-dependent α-syn oligomerization in aging brains.

The imprint of China’s first emperor on the distant realm of eastern Shandong

PubMed Central

Feinman, Gary M.; Nicholas, Linda M.; Hui, Fang

2010-01-01

Imperial expansion is recurrent in human history. For early empires, such as in ancient China, this process generally is known from texts that glorify and present the perspective of victors. The legacy of the Qin king, Shihuangdi, who first unified China in 221 BC, remains vital, but we have few details about the consequences of his distant conquests or how they changed the path of local histories. We integrate documentary accounts with the findings of a systematic regional survey of archaeological sites to provide a holistic context for this imperialistic episode and the changes that followed in coastal Shandong. PMID:20194758

Cerebral Perfusion Is Perturbed by Preterm Birth and Brain Injury.

PubMed

Mahdi, E S; Bouyssi-Kobar, M; Jacobs, M B; Murnick, J; Chang, T; Limperopoulos, C

2018-05-10

Early disturbances in systemic and cerebral hemodynamics are thought to mediate prematurity-related brain injury. However, the extent to which CBF is perturbed by preterm birth is unknown. Our aim was to compare global and regional CBF in preterm infants with and without brain injury on conventional MR imaging using arterial spin-labeling during the third trimester of ex utero life and to examine the relationship between clinical risk factors and CBF. We prospectively enrolled preterm infants younger than 32 weeks' gestational age and <1500 g and performed arterial spin-labeling MR imaging studies. Global and regional CBF in the cerebral cortex, thalami, pons, and cerebellum was quantified. Preterm infants were stratified into those with and without structural brain injury. We further categorized preterm infants by brain injury severity: moderate-severe and mild. We studied 78 preterm infants: 31 without brain injury and 47 with brain injury (29 with mild and 18 with moderate-severe injury). Global CBF showed a borderline significant increase with increasing gestational age at birth ( P = .05) and trended lower in preterm infants with brain injury ( P = .07). Similarly, regional CBF was significantly lower in the right thalamus and midpons ( P < .05) and trended lower in the midtemporal, left thalamus, and anterior vermis regions ( P < .1) in preterm infants with brain injury. Regional CBF in preterm infants with moderate-severe brain injury trended lower in the midpons, right cerebellar hemisphere, and dentate nuclei compared with mild brain injury ( P < .1). In addition, a significant, lower regional CBF was associated with ventilation, sepsis, and cesarean delivery ( P < .05). We report early disturbances in global and regional CBF in preterm infants following brain injury. Regional cerebral perfusion alterations were evident in the thalamus and pons, suggesting regional vulnerability of the developing cerebro-cerebellar circuitry. © 2018 by American Journal of Neuroradiology.

Control of brain development and homeostasis by local and systemic insulin signalling.

PubMed

Liu, J; Spéder, P; Brand, A H

2014-09-01

Insulin and insulin-like growth factors (IGFs) are important regulators of growth and metabolism. In both vertebrates and invertebrates, insulin/IGFs are made available to various organs, including the brain, through two routes: the circulating systemic insulin/IGFs act on distant organs via endocrine signalling, whereas insulin/IGF ligands released by local tissues act in a paracrine or autocrine fashion. Although the mechanisms governing the secretion and action of systemic insulin/IGF have been the focus of extensive investigation, the significance of locally derived insulin/IGF has only more recently come to the fore. Local insulin/IGF signalling is particularly important for the development and homeostasis of the central nervous system, which is insulated from the systemic environment by the blood-brain barrier. Local insulin/IGF signalling from glial cells, the blood-brain barrier and the cerebrospinal fluid has emerged as a potent regulator of neurogenesis. This review will address the main sources of local insulin/IGF and how they affect neurogenesis during development. In addition, we describe how local insulin/IGF signalling couples neural stem cell proliferation with systemic energy state in Drosophila and in mammals. © 2014 John Wiley & Sons Ltd.

The gut in trauma.

PubMed

Patel, Jayshil J; Rosenthal, Martin D; Miller, Keith R; Martindale, Robert G

2016-08-01

The purpose of this review is to describe established and emerging mechanisms of gut injury and dysfunction in trauma, describe emerging strategies to improve gut dysfunction, detail the effect of trauma on the gut microbiome, and describe the gut-brain connection in traumatic brain injury. Newer data suggest intraluminal contents, pancreatic enzymes, and hepatobiliary factors disrupt the intestinal mucosal layer. These mechanisms serve to perpetuate the inflammatory response leading to multiple organ dysfunction syndrome (MODS). To date, therapies to mitigate acute gut dysfunction have included enteral nutrition and immunonutrition; emerging therapies aimed to intestinal mucosal layer disruption, however, include protease inhibitors such as tranexamic acid, parenteral nutrition-supplemented bombesin, and hypothermia. Clinical trials to demonstrate benefit in humans are needed before widespread applications can be recommended. Despite resuscitation, gut dysfunction promotes distant organ injury. In addition, postresuscitation nosocomial and iatrogenic 'hits' exaggerate the immune response, contributing to MODS. This was a provocative concept, suggesting infectious and noninfectious causes of inflammation may trigger, heighten, and perpetuate an inflammatory response culminating in MODS and death. Emerging evidence suggests posttraumatic injury mechanisms, such as intestinal mucosal disruption and shifting of the gut microbiome to a pathobiome. In addition, traumatic brain injury activates the gut-brain axis and increases intestinal permeability.

Brain imaging in the study of Alzheimer's disease.

PubMed

Reiman, Eric M; Jagust, William J

2012-06-01

Over the last 20 years, there has been extraordinary progress in brain imaging research and its application to the study of Alzheimer's disease (AD). Brain imaging researchers have contributed to the scientific understanding, early detection and tracking of AD. They have set the stage for imaging techniques to play growing roles in the clinical setting, the evaluation of disease-modifying treatments, and the identification of demonstrably effective prevention therapies. They have developed ground-breaking methods, including positron emission tomography (PET) ligands to measure fibrillar amyloid-β (Aβ) deposition, new magnetic resonance imaging (MRI) pulse sequences, and powerful image analysis techniques, to help in these endeavors. Additional work is needed to develop even more powerful imaging methods, to further clarify the relationship and time course of Aβ and other disease processes in the predisposition to AD, to establish the role of brain imaging methods in the clinical setting, and to provide the scientific means and regulatory approval pathway needed to evaluate the range of promising disease-modifying and prevention therapies as quickly as possible. Twenty years from now, AD may not yet be a distant memory, but the best is yet to come. Copyright © 2011 Elsevier Inc. All rights reserved.

BRAIN IMAGING IN THE STUDY OF ALZHEIMER'S DISEASE

PubMed Central

Reiman, Eric M.; Jagust, William J.

2012-01-01

Over the last 20 years, there has been extraordinary progress in brain imaging research and its application to the study of Alzheimer's disease (AD). Brain imaging researchers have contributed to the scientific understanding, early detection and tracking of AD. They have set the stage for imaging techniques to play growing roles in the clinical setting, the evaluation of disease-modifying treatments, and the identification of demonstrably effective prevention therapies. They have developed ground-breaking methods, including positron emission tomography (PET) ligands to measure fibrillar amyloid-β (Aβ) deposition, new magnetic resonance imaging (MRI) pulse sequences, and powerful image analysis techniques, to help in these endeavors. Additional work is needed to develop even more powerful imaging methods, to further clarify the relationship and time course of Aβ and other disease processes in the predisposition to AD, to establish the role of brain imaging methods in the clinical setting, and to provide the scientific means and regulatory approval pathway needed to evaluate the range of promising disease-modifying and prevention therapies as quickly as possible. Twenty years from now, AD may not yet be a distant memory, but the best is yet to come. PMID:22173295

An Examination of Dynamic Gene Expression Changes in the Mouse Brain During Pregnancy and the Postpartum Period.

PubMed

Ray, Surjyendu; Tzeng, Ruei-Ying; DiCarlo, Lisa M; Bundy, Joseph L; Vied, Cynthia; Tyson, Gary; Nowakowski, Richard; Arbeitman, Michelle N

2015-11-23

The developmental transition to motherhood requires gene expression changes that alter the brain to drive the female to perform maternal behaviors. We broadly examined the global transcriptional response in the mouse maternal brain, by examining four brain regions: hypothalamus, hippocampus, neocortex, and cerebellum, in virgin females, two pregnancy time points, and three postpartum time points. We find that overall there are hundreds of differentially expressed genes, but each brain region and time point shows a unique molecular signature, with only 49 genes differentially expressed in all four regions. Interestingly, a set of "early-response genes" is repressed in all brain regions during pregnancy and postpartum stages. Several genes previously implicated in underlying postpartum depression change expression. This study serves as an atlas of gene expression changes in the maternal brain, with the results demonstrating that pregnancy, parturition, and postpartum maternal experience substantially impact diverse brain regions. Copyright © 2016 Ray et al.

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

Brain regions involved in observing and trying to interpret dog behaviour.

PubMed

Desmet, Charlotte; van der Wiel, Alko; Brass, Marcel

2017-01-01

Humans and dogs have interacted for millennia. As a result, humans (and especially dog owners) sometimes try to interpret dog behaviour. While there is extensive research on the brain regions that are involved in mentalizing about other peoples' behaviour, surprisingly little is known of whether we use these same brain regions to mentalize about animal behaviour. In this fMRI study we investigate whether brain regions involved in mentalizing about human behaviour are also engaged when observing dog behaviour. Here we show that these brain regions are more engaged when observing dog behaviour that is difficult to interpret compared to dog behaviour that is easy to interpret. Interestingly, these results were not only obtained when participants were instructed to infer reasons for the behaviour but also when they passively viewed the behaviour, indicating that these brain regions are activated by spontaneous mentalizing processes.

Brain regions involved in observing and trying to interpret dog behaviour

PubMed Central

Desmet, Charlotte; van der Wiel, Alko; Brass, Marcel

2017-01-01

Humans and dogs have interacted for millennia. As a result, humans (and especially dog owners) sometimes try to interpret dog behaviour. While there is extensive research on the brain regions that are involved in mentalizing about other peoples’ behaviour, surprisingly little is known of whether we use these same brain regions to mentalize about animal behaviour. In this fMRI study we investigate whether brain regions involved in mentalizing about human behaviour are also engaged when observing dog behaviour. Here we show that these brain regions are more engaged when observing dog behaviour that is difficult to interpret compared to dog behaviour that is easy to interpret. Interestingly, these results were not only obtained when participants were instructed to infer reasons for the behaviour but also when they passively viewed the behaviour, indicating that these brain regions are activated by spontaneous mentalizing processes. PMID:28931030

On Expression Patterns and Developmental Origin of Human Brain Regions.

PubMed

Kirsch, Lior; Chechik, Gal

2016-08-01

Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions.

On Expression Patterns and Developmental Origin of Human Brain Regions

PubMed Central

Kirsch, Lior; Chechik, Gal

2016-01-01

Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions. PMID:27564987

Microparticles shed from multidrug resistant breast cancer cells provide a parallel survival pathway through immune evasion.

PubMed

Jaiswal, Ritu; Johnson, Michael S; Pokharel, Deep; Krishnan, S Rajeev; Bebawy, Mary

2017-02-06

Breast cancer is the most frequently diagnosed cancer in women. Resident macrophages at distant sites provide a highly responsive and immunologically dynamic innate immune response against foreign infiltrates. Despite extensive characterization of the role of macrophages and other immune cells in malignant tissues, there is very little known about the mechanisms which facilitate metastatic breast cancer spread to distant sites of immunological integrity. The mechanisms by which a key healthy defense mechanism fails to protect distant sites from infiltration by metastatic cells in cancer patients remain undefined. Breast tumors, typical of many tumor types, shed membrane vesicles called microparticles (MPs), ranging in size from 0.1-1 μm in diameter. MPs serve as vectors in the intercellular transfer of functional proteins and nucleic acids and in drug sequestration. In addition, MPs are also emerging to be important players in the evasion of cancer cell immune surveillance. A comparative analysis of effects of MPs isolated from human breast cancer cells and non-malignant human brain endothelial cells were examined on THP-1 derived macrophages in vitro. MP-mediated effects on cell phenotype and functionality was assessed by cytokine analysis, cell chemotaxis and phagocytosis, immunolabelling, flow cytometry and confocal imaging. Student's t-test or a one-way analysis of variance (ANOVA) was used for comparison and statistical analysis. In this paper we report on the discovery of a new cellular basis for immune evasion, which is mediated by breast cancer derived MPs. MPs shed from multidrug resistant (MDR) cells were shown to selectively polarize macrophage cells to a functionally incapacitated state and facilitate their engulfment by foreign cells. We propose this mechanism may serve to physically disrupt the inherent immune response prior to cancer cell colonization whilst releasing mediators required for the recruitment of distant immune cells. These findings introduce a new paradigm in cancer cell biology with significant implications in understanding breast cancer colonization at distant sites. Most importantly, this is also the first demonstration that MPs serve as conduits in a parallel pathway supporting the cellular survival of MDR cancer cells through immune evasion.

Progranulin Gene Therapy Improves Lysosomal Dysfunction and Microglial Pathology Associated with Frontotemporal Dementia and Neuronal Ceroid Lipofuscinosis.

PubMed

Arrant, Andrew E; Onyilo, Vincent C; Unger, Daniel E; Roberson, Erik D

2018-02-28

Loss-of-function mutations in progranulin, a lysosomal glycoprotein, cause neurodegenerative disease. Progranulin haploinsufficiency causes frontotemporal dementia (FTD) and complete progranulin deficiency causes CLN11 neuronal ceroid lipofuscinosis (NCL). Progranulin replacement is a rational therapeutic strategy for these disorders, but there are critical unresolved mechanistic questions about a progranulin gene therapy approach, including its potential to reverse existing pathology. Here, we address these issues using an AAV vector (AAV- Grn ) to deliver progranulin in Grn -/- mice (both male and female), which model aspects of NCL and FTD pathology, developing lysosomal dysfunction, lipofuscinosis, and microgliosis. We first tested whether AAV- Grn could improve preexisting pathology. Even with treatment after onset of pathology, AAV- Grn reduced lipofuscinosis in several brain regions of Grn -/- mice. AAV- Grn also reduced microgliosis in brain regions distant from the injection site. AAV-expressed progranulin was only detected in neurons, not in microglia, indicating that the microglial activation in progranulin deficiency can be improved by targeting neurons and thus may be driven at least in part by neuronal dysfunction. Even areas with sparse transduction and almost undetectable progranulin showed improvement, indicating that low-level replacement may be sufficiently effective. The beneficial effects of AAV- Grn did not require progranulin binding to sortilin. Finally, we tested whether AAV- Grn improved lysosomal function. AAV-derived progranulin was delivered to the lysosome, ameliorated the accumulation of LAMP-1 in Grn -/- mice, and corrected abnormal cathepsin D activity. These data shed light on progranulin biology and support progranulin-boosting therapies for NCL and FTD due to GRN mutations. SIGNIFICANCE STATEMENT Heterozygous loss-of-function progranulin ( GRN ) mutations cause frontotemporal dementia (FTD) and homozygous mutations cause neuronal ceroid lipofuscinosis (NCL). Here, we address several mechanistic questions about the potential of progranulin gene therapy for these disorders. GRN mutation carriers with NCL or FTD exhibit lipofuscinosis and Grn -/- mouse models develop a similar pathology. AAV-mediated progranulin delivery reduced lipofuscinosis in Grn -/- mice even after the onset of pathology. AAV delivered progranulin only to neurons, not microglia, but improved microgliosis in several brain regions, indicating cross talk between neuronal and microglial pathology. Its beneficial effects were sortilin independent. AAV-derived progranulin was delivered to lysosomes and corrected lysosomal abnormalities. These data provide in vivo support for the efficacy of progranulin-boosting therapies for FTD and NCL. Copyright © 2018 the authors 0270-6474/18/382342-18$15.00/0.

Visual control of navigation in insects and its relevance for robotics.

PubMed

Srinivasan, Mandyam V

2011-08-01

Flying insects display remarkable agility, despite their diminutive eyes and brains. This review describes our growing understanding of how these creatures use visual information to stabilize flight, avoid collisions with objects, regulate flight speed, detect and intercept other flying insects such as mates or prey, navigate to a distant food source, and orchestrate flawless landings. It also outlines the ways in which these insights are now being used to develop novel, biologically inspired strategies for the guidance of autonomous, airborne vehicles. Copyright © 2011 Elsevier Ltd. All rights reserved.

Investigation of brain structure in the 1-month infant.

PubMed

Dean, Douglas C; Planalp, E M; Wooten, W; Schmidt, C K; Kecskemeti, S R; Frye, C; Schmidt, N L; Goldsmith, H H; Alexander, A L; Davidson, R J

2018-05-01

The developing brain undergoes systematic changes that occur at successive stages of maturation. Deviations from the typical neurodevelopmental trajectory are hypothesized to underlie many early childhood disorders; thus, characterizing the earliest patterns of normative brain development is essential. Recent neuroimaging research provides insight into brain structure during late childhood and adolescence; however, few studies have examined the infant brain, particularly in infants under 3 months of age. Using high-resolution structural MRI, we measured subcortical gray and white matter brain volumes in a cohort (N = 143) of 1-month infants and examined characteristics of these volumetric measures throughout this early period of neurodevelopment. We show that brain volumes undergo age-related changes during the first month of life, with the corresponding patterns of regional asymmetry and sexual dimorphism. Specifically, males have larger total brain volume and volumes differ by sex in regionally specific brain regions, after correcting for total brain volume. Consistent with findings from studies of later childhood and adolescence, subcortical regions appear more rightward asymmetric. Neither sex differences nor regional asymmetries changed with gestation-corrected age. Our results complement a growing body of work investigating the earliest neurobiological changes associated with development and suggest that asymmetry and sexual dimorphism are present at birth.

Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity.

PubMed

Banerjee, Soumyabrata; Poddar, Mrinal K

2015-03-01

Aging is a natural biological process associated with several neurological disorders along with the biochemical changes in brain. Aim of the present investigation is to study the effect of carnosine (0.5-2.5μg/kg/day, i.t. for 21 consecutive days) on aging-induced changes in brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) mitochondrial monoamine oxidase-A (MAO-A) activity with its kinetic parameters. The results of the present study are: (1) The brain regional mitochondrial MAO-A activity and their kinetic parameters (except in Km of pons-medulla) were significantly increased with the increase of age (4-24 months), (2) Aging-induced increase of brain regional MAO-A activity including its Vmax were attenuated with higher dosages of carnosine (1.0-2.5μg/kg/day) and restored toward the activity that observed in young, though its lower dosage (0.5μg/kg/day) were ineffective in these brain regional MAO-A activity, (3) Carnosine at higher dosage in young rats, unlike aged rats significantly inhibited all the brain regional MAO-A activity by reducing their only Vmax excepting cerebral cortex, where Km was also significantly enhanced. These results suggest that carnosine attenuated the aging-induced increase of brain regional MAO-A activity by attenuating its kinetic parameters and restored toward the results of MAO-A activity that observed in corresponding brain regions of young rats. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Regulated Extracellular Choline Acetyltransferase Activity— The Plausible Missing Link of the Distant Action of Acetylcholine in the Cholinergic Anti-Inflammatory Pathway

PubMed Central

Aeinehband, Shahin; Behbahani, Homira; Grandien, Alf; Nilsson, Bo; Ekdahl, Kristina N.; Lindblom, Rickard P. F.; Piehl, Fredrik; Darreh-Shori, Taher

2013-01-01

Acetylcholine (ACh), the classical neurotransmitter, also affects a variety of nonexcitable cells, such as endothelia, microglia, astrocytes and lymphocytes in both the nervous system and secondary lymphoid organs. Most of these cells are very distant from cholinergic synapses. The action of ACh on these distant cells is unlikely to occur through diffusion, given that ACh is very short-lived in the presence of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), two extremely efficient ACh-degrading enzymes abundantly present in extracellular fluids. In this study, we show compelling evidence for presence of a high concentration and activity of the ACh-synthesizing enzyme, choline-acetyltransferase (ChAT) in human cerebrospinal fluid (CSF) and plasma. We show that ChAT levels are physiologically balanced to the levels of its counteracting enzymes, AChE and BuChE in the human plasma and CSF. Equilibrium analyses show that soluble ChAT maintains a steady-state ACh level in the presence of physiological levels of fully active ACh-degrading enzymes. We show that ChAT is secreted by cultured human-brain astrocytes, and that activated spleen lymphocytes release ChAT itself rather than ACh. We further report differential CSF levels of ChAT in relation to Alzheimer’s disease risk genotypes, as well as in patients with multiple sclerosis, a chronic neuroinflammatory disease, compared to controls. Interestingly, soluble CSF ChAT levels show strong correlation with soluble complement factor levels, supporting a role in inflammatory regulation. This study provides a plausible explanation for the long-distance action of ACh through continuous renewal of ACh in extracellular fluids by the soluble ChAT and thereby maintenance of steady-state equilibrium between hydrolysis and synthesis of this ubiquitous cholinergic signal substance in the brain and peripheral compartments. These findings may have important implications for the role of cholinergic signaling in states of inflammation in general and in neurodegenerative disease, such as Alzheimer’s disease and multiple sclerosis in particular. PMID:23840379

Regional differences in brain glucose metabolism determined by imaging mass spectrometry.

PubMed

Kleinridders, André; Ferris, Heather A; Reyzer, Michelle L; Rath, Michaela; Soto, Marion; Manier, M Lisa; Spraggins, Jeffrey; Yang, Zhihong; Stanton, Robert C; Caprioli, Richard M; Kahn, C Ronald

2018-06-01

Glucose is the major energy substrate of the brain and crucial for normal brain function. In diabetes, the brain is subject to episodes of hypo- and hyperglycemia resulting in acute outcomes ranging from confusion to seizures, while chronic metabolic dysregulation puts patients at increased risk for depression and Alzheimer's disease. In the present study, we aimed to determine how glucose is metabolized in different regions of the brain using imaging mass spectrometry (IMS). To examine the relative abundance of glucose and other metabolites in the brain, mouse brain sections were subjected to imaging mass spectrometry at a resolution of 100 μm. This was correlated with immunohistochemistry, qPCR, western blotting and enzyme assays of dissected brain regions to determine the relative contributions of the glycolytic and pentose phosphate pathways to regional glucose metabolism. In brain, there are significant regional differences in glucose metabolism, with low levels of hexose bisphosphate (a glycolytic intermediate) and high levels of the pentose phosphate pathway (PPP) enzyme glucose-6-phosphate dehydrogenase (G6PD) and PPP metabolite hexose phosphate in thalamus compared to cortex. The ratio of ATP to ADP is significantly higher in white matter tracts, such as corpus callosum, compared to less myelinated areas. While the brain is able to maintain normal ratios of hexose phosphate, hexose bisphosphate, ATP, and ADP during fasting, fasting causes a large increase in cortical and hippocampal lactate. These data demonstrate the importance of direct measurement of metabolic intermediates to determine regional differences in brain glucose metabolism and illustrate the strength of imaging mass spectrometry for investigating the impact of changing metabolic states on brain function at a regional level with high resolution. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

Identification of a set of genes showing regionally enriched expression in the mouse brain

PubMed Central

D'Souza, Cletus A; Chopra, Vikramjit; Varhol, Richard; Xie, Yuan-Yun; Bohacec, Slavita; Zhao, Yongjun; Lee, Lisa LC; Bilenky, Mikhail; Portales-Casamar, Elodie; He, An; Wasserman, Wyeth W; Goldowitz, Daniel; Marra, Marco A; Holt, Robert A; Simpson, Elizabeth M; Jones, Steven JM

2008-01-01

Background The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters (< 4 kb) that drive gene expression in specific brain regions or cell-types of therapeutic interest. Our goal was to first identify genes displaying regionally enriched expression in the mouse brain so that promoters designed from orthologous human genes can then be tested to drive reporter expression in a similar pattern in the mouse brain. Results We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Conclusion Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression. PMID:18625066

Identification of a set of genes showing regionally enriched expression in the mouse brain.

PubMed

D'Souza, Cletus A; Chopra, Vikramjit; Varhol, Richard; Xie, Yuan-Yun; Bohacec, Slavita; Zhao, Yongjun; Lee, Lisa L C; Bilenky, Mikhail; Portales-Casamar, Elodie; He, An; Wasserman, Wyeth W; Goldowitz, Daniel; Marra, Marco A; Holt, Robert A; Simpson, Elizabeth M; Jones, Steven J M

2008-07-14

The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters (< 4 kb) that drive gene expression in specific brain regions or cell-types of therapeutic interest. Our goal was to first identify genes displaying regionally enriched expression in the mouse brain so that promoters designed from orthologous human genes can then be tested to drive reporter expression in a similar pattern in the mouse brain. We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression.

Synthesis and Demonstration of the Biological Relevance of sp3 -rich Scaffolds Distantly Related to Natural Product Frameworks.

PubMed

Foley, Daniel J; Craven, Philip G E; Collins, Patrick M; Doveston, Richard G; Aimon, Anthony; Talon, Romain; Churcher, Ian; von Delft, Frank; Marsden, Stephen P; Nelson, Adam

2017-10-26

The productive exploration of chemical space is an enduring challenge in chemical biology and medicinal chemistry. Natural products are biologically relevant, and their frameworks have facilitated chemical tool and drug discovery. A "top-down" synthetic approach is described that enabled a range of complex bridged intermediates to be converted with high step efficiency into 26 diverse sp 3 -rich scaffolds. The scaffolds have local natural product-like features, but are only distantly related to specific natural product frameworks. To assess biological relevance, a set of 52 fragments was prepared, and screened by high-throughput crystallography against three targets from two protein families (ATAD2, BRD1 and JMJD2D). In each case, 3D fragment hits were identified that would serve as distinctive starting points for ligand discovery. This demonstrates that frameworks that are distantly related to natural products can facilitate discovery of new biologically relevant regions within chemical space. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and Demonstration of the Biological Relevance of sp3‐rich Scaffolds Distantly Related to Natural Product Frameworks

PubMed Central

Foley, Daniel J.; Craven, Philip G. E.; Collins, Patrick M.; Doveston, Richard G.; Aimon, Anthony; Talon, Romain; Churcher, Ian; von Delft, Frank

2017-01-01

Abstract The productive exploration of chemical space is an enduring challenge in chemical biology and medicinal chemistry. Natural products are biologically relevant, and their frameworks have facilitated chemical tool and drug discovery. A “top‐down” synthetic approach is described that enabled a range of complex bridged intermediates to be converted with high step efficiency into 26 diverse sp3‐rich scaffolds. The scaffolds have local natural product‐like features, but are only distantly related to specific natural product frameworks. To assess biological relevance, a set of 52 fragments was prepared, and screened by high‐throughput crystallography against three targets from two protein families (ATAD2, BRD1 and JMJD2D). In each case, 3D fragment hits were identified that would serve as distinctive starting points for ligand discovery. This demonstrates that frameworks that are distantly related to natural products can facilitate discovery of new biologically relevant regions within chemical space. PMID:28983993

A detailed examination of a X-line region in the distant tail: ISEE-3 observations of jet flow and B(sub z) reversals and a pair of slow shocks

NASA Technical Reports Server (NTRS)

Ho, C. M.; Tsurutani, B. T.; Smith, E. J.; Feldman, W. C.

1994-01-01

We report an observation of Petschek-type magnetic reconnection at a distant neutral line (X = -230 R(sub e)) with a full set of signatures of the magnetic merging process. These features include a reversal of plasma flows from earthward to tailward, a pair of slow shocks and the magnetic field X-type line. These two slow shocks are shown to satisfy the shock criteria used by Feldman et al. (1987). The spacecraft first crosses a slow shock to enter the earthward flowing plasmasheet with velocity of about 440 km/s. The embedded magnetic field has a positive B(sub z) component. The spacecraft next enters a region of tailward plasma flow with speed approximately 670 km/s and an embedded negative B(sub z), indicating entry into the plasmasheet tailward of the X-line. These observed velocities are comparable to calculated velocities based on Rankine-Hugoniot conservation relationships. The spacecraft subsequently returns into the south tail lobe by crossing another slow shock. Coplanarity analyses shows that the two slow shocks have orientations consistent with that predicted by the Petschek reconnection model. We note that this event occurs during northward interplanetary magnetic fields. Thus, a magnetic stress built-up in the distant tail may be responsible for this reconnection process.

Down syndrome's brain dynamics: analysis of fractality in resting state.

PubMed

Hemmati, Sahel; Ahmadlou, Mehran; Gharib, Masoud; Vameghi, Roshanak; Sajedi, Firoozeh

2013-08-01

To the best knowledge of the authors there is no study on nonlinear brain dynamics of down syndrome (DS) patients, whereas brain is a highly complex and nonlinear system. In this study, fractal dimension of EEG, as a key characteristic of brain dynamics, showing irregularity and complexity of brain dynamics, was used for evaluation of the dynamical changes in the DS brain. The results showed higher fractality of the DS brain in almost all regions compared to the normal brain, which indicates less centrality and higher irregular or random functioning of the DS brain regions. Also, laterality analysis of the frontal lobe showed that the normal brain had a right frontal laterality of complexity whereas the DS brain had an inverse pattern (left frontal laterality). Furthermore, the high accuracy of 95.8 % obtained by enhanced probabilistic neural network classifier showed the potential of nonlinear dynamic analysis of the brain for diagnosis of DS patients. Moreover, the results showed that the higher EEG fractality in DS is associated with the higher fractality in the low frequencies (delta and theta), in broad regions of the brain, and the high frequencies (beta and gamma), majorly in the frontal regions.

Intelligence is associated with the modular structure of intrinsic brain networks.

PubMed

Hilger, Kirsten; Ekman, Matthias; Fiebach, Christian J; Basten, Ulrike

2017-11-22

General intelligence is a psychological construct that captures in a single metric the overall level of behavioural and cognitive performance in an individual. While previous research has attempted to localise intelligence in circumscribed brain regions, more recent work focuses on functional interactions between regions. However, even though brain networks are characterised by substantial modularity, it is unclear whether and how the brain's modular organisation is associated with general intelligence. Modelling subject-specific brain network graphs from functional MRI resting-state data (N = 309), we found that intelligence was not associated with global modularity features (e.g., number or size of modules) or the whole-brain proportions of different node types (e.g., connector hubs or provincial hubs). In contrast, we observed characteristic associations between intelligence and node-specific measures of within- and between-module connectivity, particularly in frontal and parietal brain regions that have previously been linked to intelligence. We propose that the connectivity profile of these regions may shape intelligence-relevant aspects of information processing. Our data demonstrate that not only region-specific differences in brain structure and function, but also the network-topological embedding of fronto-parietal as well as other cortical and subcortical brain regions is related to individual differences in higher cognitive abilities, i.e., intelligence.

Analyzing and Assessing Brain Structure with Graph Connectivity Measures

DTIC Science & Technology

2014-05-09

structural brain networks, i.e. determining which regions of the brain are physically connected. Meanwhile, functional MRI ( fMRI ) yields an image of...produced by fMRI is a map of which parts are of the brain are active and which are not at a given time. In creating functional networks, regions of...the brain which often activitate together, i.e., often show up on fMRI as deoxygenated regions together, are considered connected. DTI allows the

Understanding brain networks and brain organization

PubMed Central

Pessoa, Luiz

2014-01-01

What is the relationship between brain and behavior? The answer to this question necessitates characterizing the mapping between structure and function. The aim of this paper is to discuss broad issues surrounding the link between structure and function in the brain that will motivate a network perspective to understanding this question. As others in the past, I argue that a network perspective should supplant the common strategy of understanding the brain in terms of individual regions. Whereas this perspective is needed for a fuller characterization of the mind-brain, it should not be viewed as panacea. For one, the challenges posed by the many-to-many mapping between regions and functions is not dissolved by the network perspective. Although the problem is ameliorated, one should not anticipate a one-to-one mapping when the network approach is adopted. Furthermore, decomposition of the brain network in terms of meaningful clusters of regions, such as the ones generated by community-finding algorithms, does not by itself reveal “true” subnetworks. Given the hierarchical and multi-relational relationship between regions, multiple decompositions will offer different “slices” of a broader landscape of networks within the brain. Finally, I described how the function of brain regions can be characterized in a multidimensional manner via the idea of diversity profiles. The concept can also be used to describe the way different brain regions participate in networks. PMID:24819881

Brain Region-Specific Activity Patterns after Recent or Remote Memory Retrieval of Auditory Conditioned Fear

ERIC Educational Resources Information Center

Kwon, Jeong-Tae; Jhang, Jinho; Kim, Hyung-Su; Lee, Sujin; Han, Jin-Hee

2012-01-01

Memory is thought to be sparsely encoded throughout multiple brain regions forming unique memory trace. Although evidence has established that the amygdala is a key brain site for memory storage and retrieval of auditory conditioned fear memory, it remains elusive whether the auditory brain regions may be involved in fear memory storage or…

Structural connectivity asymmetry in the neonatal brain.

PubMed

Ratnarajah, Nagulan; Rifkin-Graboi, Anne; Fortier, Marielle V; Chong, Yap Seng; Kwek, Kenneth; Saw, Seang-Mei; Godfrey, Keith M; Gluckman, Peter D; Meaney, Michael J; Qiu, Anqi

2013-07-15

Asymmetry of the neonatal brain is not yet understood at the level of structural connectivity. We utilized DTI deterministic tractography and structural network analysis based on graph theory to determine the pattern of structural connectivity asymmetry in 124 normal neonates. We tracted white matter axonal pathways characterizing interregional connections among brain regions and inferred asymmetry in left and right anatomical network properties. Our findings revealed that in neonates, small-world characteristics were exhibited, but did not differ between the two hemispheres, suggesting that neighboring brain regions connect tightly with each other, and that one region is only a few paths away from any other region within each hemisphere. Moreover, the neonatal brain showed greater structural efficiency in the left hemisphere than that in the right. In neonates, brain regions involved in motor, language, and memory functions play crucial roles in efficient communication in the left hemisphere, while brain regions involved in emotional processes play crucial roles in efficient communication in the right hemisphere. These findings suggest that even at birth, the topology of each cerebral hemisphere is organized in an efficient and compact manner that maps onto asymmetric functional specializations seen in adults, implying lateralized brain functions in infancy. Copyright © 2013 Elsevier Inc. All rights reserved.

Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period

PubMed Central

Whiteus, Christina; Freitas, Catarina; Grutzendler, Jaime

2013-01-01

During the neonatal period, activity-dependent neural circuit remodeling coincides with growth and refinement of the cerebral microvasculature1,2. Whether neural activity also influences the patterning of the vascular bed is not known. Here we show in neonatal mice, that neither reduction of sensory input through whisker trimming nor moderately increased activity by environmental enrichment affected cortical microvascular development. Surprisingly however, chronic stimulation by repetitive sounds, whisker deflection, or motor activity led to a near arrest of angiogenesis in barrel, auditory, and motor cortices, respectively. Chemically-induced seizures also caused robust reductions in microvascular density. Altering neural activity in adult mice, however, did not affect the vasculature. Histological analysis and time-lapse in vivo two-photon microscopy revealed that hyperactivity did not lead to cell death or pruning of existing vessels but rather reduced endothelial proliferation and vessel sprouting. This anti-angiogenic effect was prevented by administration of the nitric oxide synthase (NOS) inhibitor L-NAME and in mice with neuronal and inducible NOS deficiency, suggesting that excessive nitric oxide released from hyperactive interneurons and glia inhibited vessel growth. Vascular deficits persisted long after cessation of hyperstimulation, providing evidence for a critical period after which proper microvascular patterning cannot be re-established. Reduced microvascular density diminished the ability of the brain to compensate for hypoxic challenges, leading to dendritic spine loss in regions distant from capillaries. Therefore, excessive sensorimotor stimulation and repetitive neural activation during early childhood may cause lifelong deficits in microvascular reserve, which could have important consequences on brain development, function, and pathology. PMID:24305053

Perturbed neural activity disrupts cerebral angiogenesis during a postnatal critical period.

PubMed

Whiteus, Christina; Freitas, Catarina; Grutzendler, Jaime

2014-01-16

During the neonatal period, activity-dependent neural-circuit remodelling coincides with growth and refinement of the cerebral microvasculature. Whether neural activity also influences the patterning of the vascular bed is not known. Here we show in neonatal mice, that neither reduction of sensory input through whisker trimming nor moderately increased activity by environmental enrichment affects cortical microvascular development. Unexpectedly, chronic stimulation by repetitive sounds, whisker deflection or motor activity led to a near arrest of angiogenesis in barrel, auditory and motor cortices, respectively. Chemically induced seizures also caused robust reductions in microvascular density. However, altering neural activity in adult mice did not affect the vasculature. Histological analysis and time-lapse in vivo two-photon microscopy revealed that hyperactivity did not lead to cell death or pruning of existing vessels but rather to reduced endothelial proliferation and vessel sprouting. This anti-angiogenic effect was prevented by administration of the nitric oxide synthase (NOS) inhibitor L-NAME and in mice with neuronal and inducible NOS deficiency, suggesting that excessive nitric oxide released from hyperactive interneurons and glia inhibited vessel growth. Vascular deficits persisted long after cessation of hyperstimulation, providing evidence for a critical period after which proper microvascular patterning cannot be re-established. Reduced microvascular density diminished the ability of the brain to compensate for hypoxic challenges, leading to dendritic spine loss in regions distant from capillaries. Therefore, excessive sensorimotor stimulation and repetitive neural activation during early childhood may cause lifelong deficits in microvascular reserve, which could have important consequences for brain development, function and pathology.

Increased risk of brain metastases in women with breast cancer and p16 expression in metastatic lymph-nodes.

PubMed

Furet, Elise; El Bouchtaoui, Morad; Feugeas, Jean-Paul; Miquel, Catherine; Leboeuf, Christophe; Beytout, Clémentine; Bertheau, Philippe; Le Rhun, Emilie; Bonneterre, Jacques; Janin, Anne; Bousquet, Guilhem

2017-06-06

Metastatic breast cancer is a leading cause of mortality in women, partly on account of brain metastases. However, the mechanisms by which cancer cells cross the blood-brain barrier remain undeciphered. Most molecular studies predicting metastatic risk have been performed on primary breast cancer samples. Here we studied metastatic lymph-nodes from patients with breast cancers to identify markers associated with the occurrence of brain metastases. Transcriptomic analyses identified CDKN2A/p16 as a gene potentially associated with brain metastases. Fifty-two patients with HER2-overexpressing or triple-negative breast carcinoma with lymph nodes and distant metastases were included in this study. Transcriptomic analyses were performed on laser-microdissected tumor cells from 28 metastatic lymph-nodes. Supervised analyses compared the transcriptomic profiles of women who developed brain metastases and those who did not. As a validation series, we studied metastatic lymph-nodes from 24 other patients.Immunohistochemistry investigations showed that p16 mean scores were significantly higher in patients with brain metastases than in patients without (7.4 vs. 1.7 respectively, p < 0.01). This result was confirmed on the validation series. Multivariate analyses showed that the p16 score was the only variable positively associated with the risk of brain metastases (p = 0.01).With the same threshold of 5 for p16 scores using a Cox model, overall survival was shorter in women with a p16 score over 5 in both series. The risk of brain metastases in women with HER2-overexpressing or triple-negative breast cancer could be better assessed by studying p16 protein expression on surgically removed axillary lymph-nodes.

Stereotactic Radiosurgery in the Management of Limited (1-4) Brain Metasteses: Systematic Review and International Stereotactic Radiosurgery Society Practice Guideline.

PubMed

Chao, Samuel T; De Salles, Antonio; Hayashi, Motohiro; Levivier, Marc; Ma, Lijun; Martinez, Roberto; Paddick, Ian; Régis, Jean; Ryu, Samuel; Slotman, Ben J; Sahgal, Arjun

2017-11-03

Guidelines regarding stereotactic radiosurgery (SRS) for brain metastases are missing recently published evidence. To conduct a systematic review and provide an objective summary of publications regarding SRS in managing patients with 1 to 4 brain metastases. Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted using PubMed and Medline up to November 2016. A separate search was conducted for SRS for larger brain metastases. Twenty-seven prospective studies, critical reviews, meta-analyses, and published consensus guidelines were reviewed. Four key points came from these studies. First, there is no detriment to survival by withholding whole brain radiation (WBRT) in the upfront management of brain metastases with SRS. Second, while SRS on its own provides a high rate of local control (LC), WBRT may provide further increase in LC. Next, WBRT does provide distant brain control with less need for salvage therapy. Finally, the addition of WBRT does affect neurocognitive function and quality of life more than SRS alone. For larger brain metastases, surgical resection should be considered, especially when factoring lower LC with single-session radiosurgery. There is emerging data showing good LC and/or decreased toxicity with multisession radiosurgery. A number of well-conducted prospective and meta-analyses studies demonstrate good LC, without compromising survival, using SRS alone for patients with a limited number of brain metastases. Some also demonstrated less impact on neurocognitive function with SRS alone. Practice guidelines were developed using these data with International Stereotactic Radiosurgery Society consensus. Copyright © 2017 by the Congress of Neurological Surgeons

Dynamic functional brain networks involved in simple visual discrimination learning.

PubMed

Fidalgo, Camino; Conejo, Nélida María; González-Pardo, Héctor; Arias, Jorge Luis

2014-10-01

Visual discrimination tasks have been widely used to evaluate many types of learning and memory processes. However, little is known about the brain regions involved at different stages of visual discrimination learning. We used cytochrome c oxidase histochemistry to evaluate changes in regional brain oxidative metabolism during visual discrimination learning in a water-T maze at different time points during training. As compared with control groups, the results of the present study reveal the gradual activation of cortical (prefrontal and temporal cortices) and subcortical brain regions (including the striatum and the hippocampus) associated to the mastery of a simple visual discrimination task. On the other hand, the brain regions involved and their functional interactions changed progressively over days of training. Regions associated with novelty, emotion, visuo-spatial orientation and motor aspects of the behavioral task seem to be relevant during the earlier phase of training, whereas a brain network comprising the prefrontal cortex was found along the whole learning process. This study highlights the relevance of functional interactions among brain regions to investigate learning and memory processes. Copyright © 2014 Elsevier Inc. All rights reserved.

Coherent activity between brain regions that code for value is linked to the malleability of human behavior

PubMed Central

Cooper, Nicole; Bassett, Danielle S.; Falk, Emily B.

2017-01-01

Brain activity in medial prefrontal cortex (MPFC) during exposure to persuasive messages can predict health behavior change. This brain-behavior relationship has been linked to areas of MPFC previously associated with self-related processing; however, the mechanism underlying this relationship is unclear. We explore two components of self-related processing – self-reflection and subjective valuation – and examine coherent activity between relevant networks of brain regions during exposure to health messages encouraging exercise and discouraging sedentary behaviors. We find that objectively logged reductions in sedentary behavior in the following month are linked to functional connectivity within brain regions associated with positive valuation, but not within regions associated with self-reflection on personality traits. Furthermore, functional connectivity between valuation regions contributes additional information compared to average brain activation within single brain regions. These data support an account in which MPFC integrates the value of messages to the self during persuasive health messaging and speak to broader questions of how humans make decisions about how to behave. PMID:28240271

Structural connectome topology relates to regional BOLD signal dynamics in the mouse brain

NASA Astrophysics Data System (ADS)

Sethi, Sarab S.; Zerbi, Valerio; Wenderoth, Nicole; Fornito, Alex; Fulcher, Ben D.

2017-04-01

Brain dynamics are thought to unfold on a network determined by the pattern of axonal connections linking pairs of neuronal elements; the so-called connectome. Prior work has indicated that structural brain connectivity constrains pairwise correlations of brain dynamics ("functional connectivity"), but it is not known whether inter-regional axonal connectivity is related to the intrinsic dynamics of individual brain areas. Here we investigate this relationship using a weighted, directed mesoscale mouse connectome from the Allen Mouse Brain Connectivity Atlas and resting state functional MRI (rs-fMRI) time-series data measured in 184 brain regions in eighteen anesthetized mice. For each brain region, we measured degree, betweenness, and clustering coefficient from weighted and unweighted, and directed and undirected versions of the connectome. We then characterized the univariate rs-fMRI dynamics in each brain region by computing 6930 time-series properties using the time-series analysis toolbox, hctsa. After correcting for regional volume variations, strong and robust correlations between structural connectivity properties and rs-fMRI dynamics were found only when edge weights were accounted for, and were associated with variations in the autocorrelation properties of the rs-fMRI signal. The strongest relationships were found for weighted in-degree, which was positively correlated to the autocorrelation of fMRI time series at time lag τ = 34 s (partial Spearman correlation ρ = 0.58 ), as well as a range of related measures such as relative high frequency power (f > 0.4 Hz: ρ = - 0.43 ). Our results indicate that the topology of inter-regional axonal connections of the mouse brain is closely related to intrinsic, spontaneous dynamics such that regions with a greater aggregate strength of incoming projections display longer timescales of activity fluctuations.

Age-and Brain Region-Specific Differences in Mitochondrial ...

EPA Pesticide Factsheets

Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cerebellum (CER), striatum (STR), hippocampus (HIP)] of four diverse age groups [1 Month (young), 4 Month (adult), 12 Month (middle-aged), 24 Month (old age)] to understand age-related differences in selected brain regions and their contribution to age-related chemical sensitivity. Mitochondrial bioenergetics parameters and enzyme activity were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State 111 respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12 and 24 Month age groups. Activities of mitochondrial pyruvate dehydrogenase complex (PDHC) and electron transport chain (ETC) complexes I, II, and IV enzymes were also age- and brain-region specific. In general changes associated with age were more pronounced, with

Brain state-dependent recruitment of high-frequency oscillations in the human hippocampus.

PubMed

Billeke, Pablo; Ossandon, Tomas; Stockle, Marcelo; Perrone-Bertolotti, Marcela; Kahane, Philippe; Lachaux, Jean-Philippe; Fuentealba, Pablo

2017-09-01

Ripples are high-frequency bouts of coordinated hippocampal activity believed to be crucial for information transfer and memory formation. We used intracortical macroelectrodes to record neural activity in the human hippocampus of awake subjects undergoing surgical treatment for refractory epilepsy and distinguished two populations of ripple episodes based on their frequency spectrum. The phase-coupling of one population, slow ripples (90-110 Hz), to cortical delta oscillations was differentially modulated by cognitive task; whereas the second population, fast ripples (130-170 Hz), was not seemingly correlated to local neural activity. Furthermore, as cognitive tasks changed, the ongoing coordination of neural activity associated to slow ripples progressively augmented along the parahippocampal axis. Thus, during resting states, slow ripples were coordinated in restricted hippocampal territories; whereas during active states, such as attentionally-demanding tasks, high frequency activity emerged across the hippocampus and parahippocampal cortex, that was synchronized with slow ripples, consistent with ripples supporting information transfer and coupling anatomically distant regions. Hence, our results provide further evidence of neural diversity in hippocampal high-frequency oscillations and their association to cognitive processing in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Expression of Tau Pathology-Related Proteins in Different Brain Regions: A Molecular Basis of Tau Pathogenesis.

PubMed

Hu, Wen; Wu, Feng; Zhang, Yanchong; Gong, Cheng-Xin; Iqbal, Khalid; Liu, Fei

2017-01-01

Microtubule-associated protein tau is hyperphosphorylated and aggregated in affected neurons in Alzheimer disease (AD) brains. The tau pathology starts from the entorhinal cortex (EC), spreads to the hippocampus and frontal and temporal cortices, and finally to all isocortex areas, but the cerebellum is spared from tau lesions. The molecular basis of differential vulnerability of different brain regions to tau pathology is not understood. In the present study, we analyzed brain regional expressions of tau and tau pathology-related proteins. We found that tau was hyperphosphorylated at multiple sites in the frontal cortex (FC), but not in the cerebellum, from AD brain. The level of tau expression in the cerebellum was about 1/4 of that seen in the frontal and temporal cortices in human brain. In the rat brain, the expression level of tau with three microtubule-binding repeats (3R-tau) was comparable in the hippocampus, EC, FC, parietal-temporal cortex (PTC), occipital-temporal cortex (OTC), striatum, thalamus, olfactory bulb (OB) and cerebellum. However, the expression level of 4R-tau was the highest in the EC and the lowest in the cerebellum. Tau phosphatases, kinases, microtubule-related proteins and other tau pathology-related proteins were also expressed in a region-specific manner in the rat brain. These results suggest that higher levels of tau and tau kinases in the EC and low levels of these proteins in the cerebellum may accounts for the vulnerability and resistance of these representative brain regions to the development of tau pathology, respectively. The present study provides the regional expression profiles of tau and tau pathology-related proteins in the brain, which may help understand the brain regional vulnerability to tau pathology in neurodegenerative tauopathies.

Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain

PubMed Central

Nayak, Prasunpriya; Chatterjee, Ajay K

2003-01-01

Background Alteration of glutamate and γ-aminobutyrate system have been reported to be associated with neurodegenerative disorders and have been postulated to be involved in aluminum-induced neurotoxicity as well. Aluminum, an well known and commonly exposed neurotoxin, was found to alter glutamate and γ-aminobutyrate levels as well as activities of associated enzymes with regional specificity. Protein malnutrition also reported to alter glutamate level and some of its metabolic enzymes. Thus the region-wise study of levels of brain glutamate and γ-aminobutyrate system in protein adequacy and inadequacy may be worthwhile to understand the mechanism of aluminum-induced neurotoxicity. Results Protein restriction does not have any significant impact on regional aluminum and γ-aminobutyrate contents of rat brain. Significant interaction of dietary protein restriction and aluminum intoxication to alter regional brain glutamate level was observed in the tested brain regions except cerebellum. Alteration in glutamate α-decarboxylase and γ-aminobutyrate transaminase activities were found to be significantly influenced by interaction of aluminum intoxication and dietary protein restriction in all the tested brain regions. In case of regional brain succinic semialdehyde content, this interaction was significant only in cerebrum and thalamic area. Conclusion The alterations of regional brain glutamate and γ-aminobutyrate levels by aluminum are region specific as well as dependent on dietary protein intake. The impact of aluminum exposure on the metabolism of these amino acid neurotransmitters are also influenced by dietary protein level. Thus, modification of dietary protein level or manipulation of the brain amino acid homeostasis by any other means may be an useful tool to find out a path to restrict amino acid neurotransmitter alterations in aluminum-associated neurodisorders. PMID:12657166

Medication Overuse Headache: Pathophysiological Insights from Structural and Functional Brain MRI Research.

PubMed

Schwedt, Todd J; Chong, Catherine D

2017-07-01

Research imaging of brain structure and function has helped to elucidate the pathophysiology of medication overuse headache (MOH). This is a narrative review of imaging research studies that have investigated brain structural and functional alterations associated with MOH. Studies included in this review have investigated abnormal structure and function of pain processing regions in people with MOH, functional patterns that might predispose individuals to development of MOH, similarity of brain functional patterns in patients with MOH to those found in people with addiction, brain structure that could predict headache improvement following discontinuation of the overused medication, and changes in brain structure and function after discontinuation of medication overuse. MOH is associated with atypical structure and function of brain regions responsible for pain processing as well as brain regions that are commonly implicated in addiction. Several studies have shown "normalization" of structure and function in pain processing regions following discontinuation of the overused medication and resolution of MOH. However, some of the abnormalities in regions also implicated in addiction tend to persist following discontinuation of the overused medication, suggesting that they are a brain trait that predisposes certain individuals to medication overuse and MOH. © 2017 American Headache Society.

Postnatal brain development of the pulse type, weakly electric gymnotid fish Gymnotus omarorum.

PubMed

Iribarne, Leticia; Castelló, María E

2014-01-01

Teleosts are a numerous and diverse group of fish showing great variation in body shape, ecological niches and behaviors, and a correspondent diversity in brain morphology, usually associated with their functional specialization. Weakly electric fish are a paradigmatic example of functional specialization, as these teleosts use self-generated electric fields to sense the nearby environment and communicate with conspecifics, enabling fish to better exploit particular ecological niches. We analyzed the development of the brain of the pulse type gymnotid Gymnotus omarorum, focusing on the brain regions involved directly or indirectly in electrosensory information processing. A morphometric analysis has been made of the whole brain and of brain regions of interest, based on volumetric data obtained from 3-D reconstructions to study the growth of the whole brain and the relative growth of brain regions, from late larvae to adulthood. In the smallest studied larvae some components of the electrosensory pathway appeared to be already organized and functional, as evidenced by tract-tracing and in vivo field potential recordings of electrosensory-evoked activity. From late larval to adult stages, rombencephalic brain regions (cerebellum and electrosensory lateral line lobe) showed a positive allometric growth, mesencephalic brain regions showed a negative allometric growth, and the telencephalon showed an isometric growth. In a first step towards elucidating the role of cell proliferation in the relative growth of the analyzed brain regions, we also studied the spatial distribution of proliferation zones by means of pulse type BrdU labeling revealed by immunohistochemistry. The brain of G. omarorum late larvae showed a widespread distribution of proliferating zones, most of which were located at the ventricular-cisternal lining. Interestingly, we also found extra ventricular-cisternal proliferation zones at in the rombencephalic cerebellum and electrosensory lateral line lobe. We discuss the role of extraventricular-cisternal proliferation in the relative growth of the latter brain regions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Trends in Imaging after Thyroid Cancer Diagnosis

PubMed Central

Banerjee, Mousumi; Muenz, Daniel G.; Worden, Francis P.; Haymart, Megan R.

2015-01-01

Background The largest growth in differentiated thyroid cancer (DTC) diagnosis is in low-risk cancers. Trends in imaging after DTC diagnosis are understudied. Hypothesizing a reduction in imaging utilization due to rising low-risk disease, we evaluated post-diagnosis imaging patterns over time and patient characteristics that are associated with likelihood of imaging. Methods Using the Surveillance Epidemiology and End Results-Medicare database, we identified patients diagnosed with localized, regional or distant DTC between 1991 and 2009. We reviewed Medicare claims for neck ultrasound, I-131 scan, or PET scan within 3 years post-diagnosis. Using regression analyses we evaluated trends of imaging utilization. Multivariable logistic regression was used to estimate the likelihood of imaging based on patient characteristics. Results 23,669 patients were included. Patients diagnosed during 2001-2009, compared to 1991-2000, were more likely to have localized disease (p<0.001) and tumors less than 1cm (p<0.001). Use of neck ultrasound and I-131 scan increased in patients with localized disease (p=<0.001 and p=0.003, respectively), regional disease (p<0.001 and p<0.001), and distant metastasis (p=0.001 and p=0.015). Patients diagnosed after 2000 were more likely to undergo neck ultrasound (OR 2.15, 95% CI 2.02-2.28) and I-131 scan (OR 1.44, 95% CI 1.35-1.54). PET scan use from 2005-2009, compared to 1996-2004, increased 32.4-fold (p=<0.001) in localized patients, 13.1-fold (p<0.001) in regional disease patients, and 33.4-fold (p<0.001) in patients with distant DTC. Conclusion Despite a rise in low-risk disease, the use of post-diagnosis imaging increased in all stages of disease. The largest growth was in use of PET scan after 2004. PMID:25565063

Identifying metastatic breast tumors using textural kinetic features of a contrast based habitat in DCE-MRI

NASA Astrophysics Data System (ADS)

Chaudhury, Baishali; Zhou, Mu; Goldgof, Dmitry B.; Hall, Lawrence O.; Gatenby, Robert A.; Gillies, Robert J.; Drukteinis, Jennifer S.

2015-03-01

The ability to identify aggressive tumors from indolent tumors using quantitative analysis on dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) would dramatically change the breast cancer treatment paradigm. With this prognostic information, patients with aggressive tumors that have the ability to spread to distant sites outside of the breast could be selected for more aggressive treatment and surveillance regimens. Conversely, patients with tumors that do not have the propensity to metastasize could be treated less aggressively, avoiding some of the morbidity associated with surgery, radiation and chemotherapy. We propose a computer aided detection framework to determine which breast cancers will metastasize to the loco-regional lymph nodes as well as which tumors will eventually go on to develop distant metastses using quantitative image analysis and radiomics. We defined a new contrast based tumor habitat and analyzed textural kinetic features from this habitat for classification purposes. The proposed tumor habitat, which we call combined-habitat, is derived from the intersection of two individual tumor sub-regions: one that exhibits rapid initial contrast uptake and the other that exhibits rapid delayed contrast washout. Hence the combined-habitat represents the tumor sub-region within which the pixels undergo both rapid initial uptake and rapid delayed washout. We analyzed a dataset of twenty-seven representative two dimensional (2D) images from volumetric DCE-MRI of breast tumors, for classification of tumors with no lymph nodes from tumors with positive number of axillary lymph nodes. For this classification an accuracy of 88.9% was achieved. Twenty of the twenty-seven patients were analyzed for classification of distant metastatic tumors from indolent cancers (tumors with no lymph nodes), for which the accuracy was 84.3%.

Nonthermal ablation with microbubble-enhanced focused ultrasound close to the optic tract without affecting nerve function.

PubMed

McDannold, Nathan; Zhang, Yong-Zhi; Power, Chanikarn; Jolesz, Ferenc; Vykhodtseva, Natalia

2013-11-01

Tumors at the skull base are challenging for both resection and radiosurgery given the presence of critical adjacent structures, such as cranial nerves, blood vessels, and brainstem. Magnetic resonance imaging-guided thermal ablation via laser or other methods has been evaluated as a minimally invasive alternative to these techniques in the brain. Focused ultrasound (FUS) offers a noninvasive method of thermal ablation; however, skull heating limits currently available technology to ablation at regions distant from the skull bone. Here, the authors evaluated a method that circumvents this problem by combining the FUS exposures with injected microbubble-based ultrasound contrast agent. These microbubbles concentrate the ultrasound-induced effects on the vasculature, enabling an ablation method that does not cause significant heating of the brain or skull. In 29 rats, a 525-kHz FUS transducer was used to ablate tissue structures at the skull base that were centered on or adjacent to the optic tract or chiasm. Low-intensity, low-duty-cycle ultrasound exposures (sonications) were applied for 5 minutes after intravenous injection of an ultrasound contrast agent (Definity, Lantheus Medical Imaging Inc.). Using histological analysis and visual evoked potential (VEP) measurements, the authors determined whether structural or functional damage was induced in the optic tract or chiasm. Overall, while the sonications produced a well-defined lesion in the gray matter targets, the adjacent tract and chiasm had comparatively little or no damage. No significant changes (p > 0.05) were found in the magnitude or latency of the VEP recordings, either immediately after sonication or at later times up to 4 weeks after sonication, and no delayed effects were evident in the histological features of the optic nerve and retina. This technique, which selectively targets the intravascular microbubbles, appears to be a promising method of noninvasively producing sharply demarcated lesions in deep brain structures while preserving function in adjacent nerves. Because of low vascularity--and thus a low microbubble concentration--some large white matter tracts appear to have some natural resistance to this type of ablation compared with gray matter. While future work is needed to develop methods of monitoring the procedure and establishing its safety at deep brain targets, the technique does appear to be a potential solution that allows FUS ablation of deep brain targets while sparing adjacent nerve structures.

Nonthermal ablation with microbubble-enhanced focused ultrasound close to the optic tract without affecting nerve function

PubMed Central

McDannold, Nathan; Zhang, Yong-Zhi; Power, Chanikarn; Jolesz, Ferenc; Vykhodtseva, Natalia

2014-01-01

Object Tumors at the skull base are challenging for both resection and radiosurgery given the presence of critical adjacent structures, such as cranial nerves, blood vessels, and brainstem. Magnetic resonance imaging–guided thermal ablation via laser or other methods has been evaluated as a minimally invasive alternative to these techniques in the brain. Focused ultrasound (FUS) offers a noninvasive method of thermal ablation; however, skull heating limits currently available technology to ablation at regions distant from the skull bone. Here, the authors evaluated a method that circumvents this problem by combining the FUS exposures with injected microbubble-based ultrasound contrast agent. These microbubbles concentrate the ultrasound-induced effects on the vasculature, enabling an ablation method that does not cause significant heating of the brain or skull. Methods In 29 rats, a 525-kHz FUS transducer was used to ablate tissue structures at the skull base that were centered on or adjacent to the optic tract or chiasm. Low-intensity, low-duty-cycle ultrasound exposures (sonications) were applied for 5 minutes after intravenous injection of an ultrasound contrast agent (Definity, Lantheus Medical Imaging Inc.). Using histological analysis and visual evoked potential (VEP) measurements, the authors determined whether structural or functional damage was induced in the optic tract or chiasm. Results Overall, while the sonications produced a well-defined lesion in the gray matter targets, the adjacent tract and chiasm had comparatively little or no damage. No significant changes (p > 0.05) were found in the magnitude or latency of the VEP recordings, either immediately after sonication or at later times up to 4 weeks after sonication, and no delayed effects were evident in the histological features of the optic nerve and retina. Conclusions This technique, which selectively targets the intravascular microbubbles, appears to be a promising method of noninvasively producing sharply demarcated lesions in deep brain structures while preserving function in adjacent nerves. Because of low vascularity—and thus a low microbubble concentration—some large white matter tracts appear to have some natural resistance to this type of ablation compared with gray matter. While future work is needed to develop methods of monitoring the procedure and establishing its safety at deep brain targets, the technique does appear to be a potential solution that allows FUS ablation of deep brain targets while sparing adjacent nerve structures. PMID:24010975

Bridging the San Francisco System: 21st Century Strategic Partnerships for the Asian Pacific

DTIC Science & Technology

2016-04-08

apparatuses characterized their newly obtained national sovereignty. Further, a union of these disparate and distant archipelagic states in a multilateral...the Nixon administration released the Guam Doctrine in 1969. Later known as the Nixon Doctrine , this policy aimed primarily at Asia, promoted...allies to the North, the archipelagic regional states also continue to offer the United States key regional defense positioning. Moreover, these

Statistical Analyses of Brain Surfaces Using Gaussian Random Fields on 2-D Manifolds

PubMed Central

Staib, Lawrence H.; Xu, Dongrong; Zhu, Hongtu; Peterson, Bradley S.

2008-01-01

Interest in the morphometric analysis of the brain and its subregions has recently intensified because growth or degeneration of the brain in health or illness affects not only the volume but also the shape of cortical and subcortical brain regions, and new image processing techniques permit detection of small and highly localized perturbations in shape or localized volume, with remarkable precision. An appropriate statistical representation of the shape of a brain region is essential, however, for detecting, localizing, and interpreting variability in its surface contour and for identifying differences in volume of the underlying tissue that produce that variability across individuals and groups of individuals. Our statistical representation of the shape of a brain region is defined by a reference region for that region and by a Gaussian random field (GRF) that is defined across the entire surface of the region. We first select a reference region from a set of segmented brain images of healthy individuals. The GRF is then estimated as the signed Euclidean distances between points on the surface of the reference region and the corresponding points on the corresponding region in images of brains that have been coregistered to the reference. Correspondences between points on these surfaces are defined through deformations of each region of a brain into the coordinate space of the reference region using the principles of fluid dynamics. The warped, coregistered region of each subject is then unwarped into its native space, simultaneously bringing into that space the map of corresponding points that was established when the surfaces of the subject and reference regions were tightly coregistered. The proposed statistical description of the shape of surface contours makes no assumptions, other than smoothness, about the shape of the region or its GRF. The description also allows for the detection and localization of statistically significant differences in the shapes of the surfaces across groups of subjects at both a fine and coarse scale. We demonstrate the effectiveness of these statistical methods by applying them to study differences in shape of the amygdala and hippocampus in a large sample of normal subjects and in subjects with attention deficit/hyperactivity disorder (ADHD). PMID:17243583

Advances in diagnosis and treatment of metastatic cervical cancer

PubMed Central

2016-01-01

Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases. PMID:27171673

Possible Quantum Absorber Effects in Cortical Synchronization

NASA Astrophysics Data System (ADS)

Kämpf, Uwe

The Wheeler-Feynman transactional "absorber" approach was proposed originally to account for anomalous resonance coupling between spatio-temporally distant measurement partners in entangled quantum states of so-called Einstein-Podolsky-Rosen paradoxes, e.g. of spatio-temporal non-locality, quantum teleportation, etc. Applied to quantum brain dynamics, however, this view provides an anticipative resonance coupling model for aspects of cortical synchronization and recurrent visual action control. It is proposed to consider the registered activation patterns of neuronal loops in so-called synfire chains not as a result of retarded brain communication processes, but rather as surface effects of a system of standing waves generated in the depth of visual processing. According to this view, they arise from a counterbalance between the actual input's delayed bottom-up data streams and top-down recurrent information-processing of advanced anticipative signals in a Wheeler-Feynman-type absorber mode. In the framework of a "time-loop" model, findings about mirror neurons in the brain cortex are suggested to be at least partially associated with temporal rather than spatial mirror functions of visual processing, similar to phase conjugate adaptive resonance-coupling in nonlinear optics.

Advances in diagnosis and treatment of metastatic cervical cancer.

PubMed

Li, Haoran; Wu, Xiaohua; Cheng, Xi

2016-07-01

Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases.

Brain metastasis from squamous cell carcinoma of the head and neck: a review of the literature in the genomic era.

PubMed

Barrett, Thomas F; Gill, Corey M; Miles, Brett A; Iloreta, Alfred M C; Bakst, Richard L; Fowkes, Mary; Brastianos, Priscilla K; Bederson, Joshua B; Shrivastava, Raj K

2018-06-01

Squamous cell carcinoma of the head and neck (HNSCC) affects nearly 500,000 individuals globally each year. With the rise of human papillomavirus (HPV) in the general population, clinicians are seeing a concomitant rise in HPV-related HNSCC. Notably, a hallmark of HPV-related HNSCC is a predilection for unique biological and clinical features, which portend a tendency for hematogenous metastasis to distant locations, such as the brain. Despite the classic belief that HNSCC is restricted to local spread via passive lymphatic drainage, brain metastases (BMs) are a rare complication that occurs in less than 1% of all HNSCC cases. Time between initial diagnosis of HNSCC and BM development can vary considerably. Some patients experience more than a decade of disease-free survival, whereas others present with definitive neurological symptoms that precede primary tumor detection. The authors systematically review the current literature on HNSCC BMs and discuss the current understanding of the effect of HPV status on the risk of developing BMs in the modern genomic era.

Design and Construction of a Multi-Organ Microfluidic Chip Mimicking the in vivo Microenvironment of Lung Cancer Metastasis.

PubMed

Xu, Zhiyun; Li, Encheng; Guo, Zhe; Yu, Ruofei; Hao, Hualong; Xu, Yitong; Sun, Zhao; Li, Xiancheng; Lyu, Jianxin; Wang, Qi

2016-10-05

Metastasis is a complex pathophysiological process. As the main cause of cancer mortality in humans it represents a serious challenge to both basic researchers and clinicians. Here we report the design and construction of a multi-organ microfluidic chip that closely mimics the in vivo microenvironment of lung cancer metastasis. This multi-organs-on-a-chip includes an upstream "lung" and three downstream "distant organs", with three polydimethylsiloxane (PDMS) layers and two thin PDMS microporous membranes bonded to form three parallel microchannels. Bronchial epithelial, lung cancer, microvascular endothelial, mononuclear, and fibroblast cells were grown separated by the biomembrane in upstream "lung", while astrocytes, osteocytes, and hepatocytes were grown in distant chambers, to mimic lung cancer cell metastasis to the brain, bone, and liver. After culture in this system, lung cancer cells formed a "tumor mass", showed epithelial-mesenchymal transition (with altered expression of E-cadherin, N-cadherin, Snail1, and Snail2) and invasive capacity. A549 cells co-cultured with astrocytes overexpressed CXCR4 protein, indicating damage of astrocytes after cancer cell metastasis to the brain. Osteocytes overexpressed RANKL protein indicates damage of osteocytes after cancer cell metastasis to the bone, and hepatocytes overexpressed AFP protein indicates damage to hepatocytes after cancer cell metastasis to the liver. Finally, in vivo imaging of cancer growth and metastasis in a nude mice model validated the performance of metastasis in the organs-on-chip system. This system provides a useful tool to mimic the in vivo microenvironment of cancer metastasis and to investigate cell-cell interactions during metastasis.

The developing dorsal ganglion of the salp Thalia democratica, and the nature of the ancestral chordate brain

PubMed Central

C.Lacalli, T.

1998-01-01

The development of the dorsal ganglion of the salp, Thalia democratica, is described from electron microscope reconstructions up to the stage of central neuropile formation. The central nervous system (CNS) rudiment is initially tubular with an open central canal. Early developmental events include: (i) the formation of a thick dorsal mantle of neuroblasts from which paired dorsal paraxial neuropiles arise; (ii) the differentiation of clusters of primary motor neurons along the ventral margin of the mantle; and (iii) the development from the latter of a series of peripheral nerves. The dorsal paraxial neuropiles ultimately connect to the large central neuropile, which develops later. Direct contact between neuroblasts and muscle appears to be involved in the development of some anterior nerves. The caudal nerves responsible for innervating more distant targets in the posterior part of the body develop without such contacts, which suggests that a different patterning mechanism may be employed in this part of the neuromuscular system. The results are compared with patterns of brain organization in other chordates. Because the salp CNS is symmetrical and generally less reduced than that of ascidian larvae, it is more easily compared with the CNS of amphioxus and vertebrates. The dorsal paraxial centres in the salp resemble the dorsolateral tectal centres in amphioxus in both position and organization; the central neuropile in salps likewise resembles the translumenal system in amphioxus. The neurons themselves are similar in that many of their neurites appear to be derived from the apical surface instead of the basal surface of the cell. Such neurons, with extensively developed apical neurites, may represent a new cell type that evolved in the earliest chordates in conjunction with the formation of translumenal or intralumenal integrative centres. In comparing the salp ganglion with vertebrates, we suggest that the main core of the ganglion is most like the mes-metencephalic region of the vertebrate brain, i.e. the zone occupied by the midbrain, isthmus, and anterior hindbrain. Counterparts of more anterior regions (forebrain) and posterior ones (segmented hindbrain) appear to be absent in salps, but are found in other tunicates, suggesting that evolution has acted quite differently on the main subdivisions of the CNS in different types of tunicates.

Automatic detection of the hippocampal region associated with Alzheimer's disease from microscopic images of mice brain

NASA Astrophysics Data System (ADS)

Albaidhani, Tahseen; Hawkes, Cheryl; Jassim, Sabah; Al-Assam, Hisham

2016-05-01

The hippocampus is the region of the brain that is primarily associated with memory and spatial navigation. It is one of the first brain regions to be damaged when a person suffers from Alzheimer's disease. Recent research in this field has focussed on the assessment of damage to different blood vessels within the hippocampal region from a high throughput brain microscopic images. The ultimate aim of our research is the creation of an automatic system to count and classify different blood vessels such as capillaries, veins, and arteries in the hippocampus region. This work should provide biologists with efficient and accurate tools in their investigation of the causes of Alzheimer's disease. Locating the boundary of the Region of Interest in the hippocampus from microscopic images of mice brain is the first essential stage towards developing such a system. This task benefits from the variation in colour channels and texture between the two sides of the hippocampus and the boundary region. Accordingly, the developed initial step of our research to locating the hippocampus edge uses a colour-based segmentation of the brain image followed by Hough transforms on the colour channel that isolate the hippocampus region. The output is then used to split the brain image into two sides of the detected section of the boundary: the inside region and the outside region. Experimental results on a sufficiently number of microscopic images demonstrate the effectiveness of the developed solution.

Thermodynamic laws apply to brain function.

PubMed

Salerian, Alen J

2010-02-01

Thermodynamic laws and complex system dynamics govern brain function. Thus, any change in brain homeostasis by an alteration in brain temperature, neurotransmission or content may cause region-specific brain dysfunction. This is the premise for the Salerian Theory of Brain built upon a new paradigm for neuropsychiatric disorders: the governing influence of neuroanatomy, neurophysiology, thermodynamic laws. The principles of region-specific brain function thermodynamics are reviewed. The clinical and supporting evidence including the paradoxical effects of various agents that alter brain homeostasis is demonstrated.

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

Brown, M. E.; Rhoden, A. R., E-mail: mbrown@caltech.edu, E-mail: Alyssa.Rhoden@jhuapl.edu

We present a medium resolution spectrum of Jupiter's irregular satellite Himalia covering the critical 3 μm spectral region. The spectrum shows no evidence for aqueously altered phyllosilicates, as had been suggested from the tentative detection of a 0.7 μm absorption, but instead shows a spectrum strikingly similar to the C/CF type asteroid 52 Europa. 52 Europa is the prototype of a class of asteroids generally situated in the outer asteroid belt between less distant asteroids which show evidence for aqueous alteration and more distant asteroids which show evidence for water ice. The spectral match between Himalia and this group of asteroids ismore » surprising and difficult to reconcile with models of the origin of the irregular satellites.« less

Highly divergent cyclo-like virus in a great roundleaf bat (Hipposideros armiger) in Vietnam.

PubMed

Kemenesi, Gábor; Kurucz, Kornélia; Zana, Brigitta; Tu, Vuong Tan; Görföl, Tamás; Estók, Péter; Földes, Fanni; Sztancsik, Katalin; Urbán, Péter; Fehér, Enikő; Jakab, Ferenc

2017-08-01

Members of the viral family Circoviridae are increasingly recognized worldwide. Bats seem to be natural reservoirs or dietary-related dispensers of these viruses. Here, we report a distantly related member of the genus Cyclovirus detected in the faeces of a great roundleaf bat (Hipposideros armiger). Interestingly, the novel virus lacks a Circoviridae-specific stem-loop structure, although a Geminiviridae-like nonamer sequence was detected in the large intergenic region. Based on these differences and its phylogenetic position, we propose that our new virus represents a distant and highly divergent member of the genus Cyclovirus. However it is lacking several characteristics of members of the genus, which raises a challenge in its taxonomic classification.

Age related rise in lactate and its correlation with lactate dehydrogenase (LDH) status in post-mitochondrial fractions isolated from different regions of brain in mice.

PubMed

Datta, Siddhartha; Chakrabarti, Nilkanta

2018-04-18

Rise in brain lactate is the hallmark of ageing. Separate studies report that ageing is associated with elevation of lactate level and alterations of lactate dehydrogenase (LDH)-A/B mRNA-expression-ratio in cerebral cortex and hippocampus. However, age related lactate rise in brain and its association with LDH status and their brain regional variations are still elusive. In the present study, level of lactate, LDH (A and B) activity and LDH-A expression were evaluated in post-mitochondrial fraction of tissues isolated from four different brain regions (cerebral cortex, hippocampus, substantia nigra and cerebellum) of young and aged mice. Lactate levels elevated in four brain regions with maximum rise in substantia nigra of aged mice. LDH-A protein expression and its activity decreased in cerebral cortex, hippocampus and substantia nigra without any changes of these parameters in cerebellum of aged mice. LDH-B activity decreased in hippocampus, substantia nigra and cerebellum whereas its activity remains unaltered in cerebral cortex of aged mice. Accordingly, the ratio of LDH-A/LDH-B-activity remains unaltered in hippocampus and substantia nigra, decreased in cerebral cortex and increased in cerebellum. Therefore, rise of lactate in three brain regions (cerebral cortex, hippocampus, substantia nigra) appeared to be not correlated with the alterations of its regulatory enzymes activities in these three brain regions, rather it supports the fact of involvement of other mechanisms, like lactate transport and/or aerobic/anaerobic metabolism as the possible cause(s) of lactate rise in these three brain regions. The increase in LDH-A/LDH-B-activity-ratio appeared to be positively correlated with elevated lactate level in cerebellum of aged mice. Overall, the present study indicates that the mechanism of rise in lactate in brain varies with brain regions where LDH status plays an important role during ageing. Copyright © 2018 Elsevier Ltd. All rights reserved.

Extensive cortical rewiring after brain injury.

PubMed

Dancause, Numa; Barbay, Scott; Frost, Shawn B; Plautz, Erik J; Chen, Daofen; Zoubina, Elena V; Stowe, Ann M; Nudo, Randolph J

2005-11-02

Previously, we showed that the ventral premotor cortex (PMv) underwent neurophysiological remodeling after injury to the primary motor cortex (M1). In the present study, we examined cortical connections of PMv after such lesions. The neuroanatomical tract tracer biotinylated dextran amine was injected into the PMv hand area at least 5 months after ischemic injury to the M1 hand area. Comparison of labeling patterns between experimental and control animals demonstrated extensive proliferation of novel PMv terminal fields and the appearance of retrogradely labeled cell bodies within area 1/2 of the primary somatosensory cortex after M1 injury. Furthermore, evidence was found for alterations in the trajectory of PMv intracortical axons near the site of the lesion. The results suggest that M1 injury results in axonal sprouting near the ischemic injury and the establishment of novel connections within a distant target. These results support the hypothesis that, after a cortical injury, such as occurs after stroke, cortical areas distant from the injury undergo major neuroanatomical reorganization. Our results reveal an extraordinary anatomical rewiring capacity in the adult CNS after injury that may potentially play a role in recovery.

Region-Specific Protein Abundance Changes in the Brain of MPTP-induced Parkinson’s Disease Mouse Model

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

Zhang, Xu; Zhou, Jianying; Chin, Mark H

2010-02-15

Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration in the nigrostriatal region of the brain; however, the neurodegeneration extends well beyond dopaminergic neurons. To gain a better understanding of the molecular changes relevant to PD, we applied two-dimensional LC-MS/MS to comparatively analyze the proteome changes in four brain regions (striatum, cerebellum, cortex, and the rest of brain) using a MPTP-induced PD mouse model with the objective to identify nigrostriatal-specific and other region-specific protein abundance changes. The combined analyses resulted in the identification of 4,895 non-redundant proteins with at least two unique peptides per protein. The relative abundance changes in eachmore » analyzed brain region were estimated based on the spectral count information. A total of 518 proteins were observed with significant MPTP-induced changes across different brain regions. 270 of these proteins were observed with specific changes occurring either only in the striatum and/or in the rest of the brain region that contains substantia nigra, suggesting that these proteins are associated with the underlying nigrostriatal pathways. Many of the proteins that exhibit significant abundance changes were associated with dopamine signaling, mitochondrial dysfunction, the ubiquitin system, calcium signaling, the oxidative stress response, and apoptosis. A set of proteins with either consistent change across all brain regions or with changes specific to the cortex and cerebellum regions were also detected. One of the interesting proteins is ubiquitin specific protease (USP9X), a deubiquination enzyme involved in the protection of proteins from degradation and promotion of the TGF-β pathway, which exhibited altered abundances in all brain regions. Western blot validation showed similar spatial changes, suggesting that USP9X is potentially associated with neurodegeneration. Together, this study for the first time presents an overall picture of proteome changes underlying both nigrostriatal pathways and other brain regions potentially involved in MPTP-induced neurodegeneration. The observed molecular changes provide a valuable reference resource for future hypothesis-driven functional studies of PD.« less

Review of the leafhopper genus Penthimia Germar (Hemiptera: Cicadellidae: Deltocephalinae) from the Indian subcontinent with description of seven new species.

PubMed

Shobharani, M; Viraktamath, C A; Webb, M D

2018-01-02

Species of the leafhopper genus Penthimia Germar known from the Indian subcontinent are reviewed based on the examination of type specimens. Seven new species of the genus, Penthimia curvata sp. nov. (Karnataka: Bandipur), P. meghalayensis sp. nov. (Meghalaya: Nangpoh), P. neoattenuata sp. nov. (India: Tamil Nadu), P. ribhoi sp. nov. (India: Meghalaya), P. sahyadrica sp. nov. (Karnataka: Dharmasthala, Agumbe; Kerala: Thekkady), P. spiculata sp. nov. (Karnataka: Nagarahole) and P. tumida sp. nov. (Tamil Nadu: Ootacamund; Kerala: Munnar) are described. The following nomenclatorial changes are proposed: Penthimia alba Zahniser, McKamey Dmitriev, 2012 (replacement name for P. thoracica Distant, 1918, nec Panzer, 1799), syn. nov. of P. quadrinotata Distant, 1918; Neodartus scutellatus Distant, 1908 syn. nov. of Penthimia ereba Distant 1908; P. nilgiriensis Distant, 1918 syn. nov. of P. montana Distant, 1918; P. scutellata (Distant) comb. nov. (from genus Neodartus); a lectotype is designated for P. maculosa Distant, stat. revived, thereby removing its synonymy with P. scapularis Distant. The following other lectotypes are designated: P. attenuata Distant, P. subniger Distant, P. scapularis Distant, P. distanti Baker, P. ereba Distant, N. scutellatus Distant, P. fraterna Distant, P. funebris Distant, P. juno Distant, P. maculosa Distant, P. montana Distant, P. noctua Distant, P. quadrinotata Distant, P. alba Zahniser, McKamey Dmitriev. Examination of types of Penthimia rufopunctata Motschulsky revealed that it belongs to Penthimia and hence it is transferred back to that genus from Neodartus, revised placement. The following species previously included in the genus Penthimia are transferred to the genera Tambila Distant and Vulturnus Kirkaldy: Tambila badia (Distant) comb. nov., T. majuscula (Distant) comb. nov., T. vittatifrons (Distant) comb. nov., T. variabilis (Distant) comb. nov. and Vulturnus flavocapitata (Distant) comb. nov. Three species are treated in a new Penthimia compacta Walker complex, i.e., Penthimia compacta Walker 1851, Penthimia subniger Distant 1908 and Penthimia scapularis Distant 1908. All taxa are described and a key to Penthimiini genera found in the subcontinent and also a key to species of Penthimia are included.

Regional brain injury on conventional and diffusion weighted MRI is associated with outcome after pediatric cardiac arrest.

PubMed

Fink, Ericka L; Panigrahy, A; Clark, R S B; Fitz, C R; Landsittel, D; Kochanek, P M; Zuccoli, G

2013-08-01

To assess regional brain injury on magnetic resonance imaging (MRI) after pediatric cardiac arrest (CA) and to associate regional injury with patient outcome and effects of hypothermia therapy for neuroprotection. We performed a retrospective chart review with prospective imaging analysis. Children between 1 week and 17 years of age who had a brain MRI in the first 2 weeks after CA without other acute brain injury between 2002 and 2008 were included. Brain MRI (1.5 T General Electric, Milwaukee, WI, USA) images were analyzed by 2 blinded neuroradiologists with adjudication; images were visually graded. Brain lobes, basal ganglia, thalamus, brain stem, and cerebellum were analyzed using T1, T2, and diffusion-weighted images (DWI). We examined 28 subjects with median age 1.9 years (IQR 0.4-13.0) and 19 (68 %) males. Increased intensity on T2 in the basal ganglia and restricted diffusion in the brain lobes were associated with unfavorable outcome (all P < 0.05). Therapeutic hypothermia had no effect on regional brain injury. Repeat brain MRI was infrequently performed but demonstrated evolution of lesions. Children with lesions in the basal ganglia on conventional MRI and brain lobes on DWI within the first 2 weeks after CA represent a group with increased risk of poor outcome. These findings may be important for developing neuroprotective strategies based on regional brain injury and for evaluating response to therapy in interventional clinical trials.

Brain temperature profiles during epidural cooling with the ChillerPad in a monkey model of traumatic brain injury.

PubMed

King, Christopher; Robinson, Timothy; Dixon, C Edward; Rao, Gutti R; Larnard, Donald; Nemoto, C Edwin M

2010-10-01

Therapeutic hypothermia remains a promising treatment for patients with severe traumatic brain injury (TBI). Multiple animal studies have suggested that hypothermia is neuroprotective after TBI, but clinical trials have been inconclusive. Systemic hypothermia, the method used in almost all major clinical trials, is limited by the time to target temperature, the depth of hypothermia, and complications, problems that may be solved by selective brain cooling. We evaluated the effects on brain temperature of a cooling device called the ChillerPad,™ which is applied to the dura in a non-human primate TBI model using controlled cortical impact (CCI). The cortical surface was rapidly cooled to approximately 15°C and maintained at that level for 24 h, followed by rewarming over about 10 h. Brain temperatures fell to 34-35°C at a depth of 15 mm at the cortical gray/white matter interface, and to 28-32°C at 10 mm deep. Intracranial pressure was mildly elevated (8-12 mm Hg) after cooling and rewarming, likely due to TBI. Other physiological variables were unchanged. Cooling was rapidly diminished at points distant from the cooling pad. The ChillerPad may be useful for highly localized cooling of the brain in circumstances in which a craniotomy is clinically indicated. However, because of the delay required by the craniotomy, other methods that are more readily available for inducing hypothermia may be used as a bridge between the time of injury to placement of the ChillerPad.

Evidence for hubs in human functional brain networks

PubMed Central

Power, Jonathan D; Schlaggar, Bradley L; Lessov-Schlaggar, Christina N; Petersen, Steven E

2013-01-01

Summary Hubs integrate and distribute information in powerful ways due to the number and positioning of their contacts in a network. Several resting state functional connectivity MRI reports have implicated regions of the default mode system as brain hubs; we demonstrate that previous degree-based approaches to hub identification may have identified portions of large brain systems rather than critical nodes of brain networks. We utilize two methods to identify hub-like brain regions: 1) finding network nodes that participate in multiple sub-networks of the brain, and 2) finding spatial locations where several systems are represented within a small volume. These methods converge on a distributed set of regions that differ from previous reports on hubs. This work identifies regions that support multiple systems, leading to spatially constrained predictions about brain function that may be tested in terms of lesions, evoked responses, and dynamic patterns of activity. PMID:23972601

Locality preserving non-negative basis learning with graph embedding.

PubMed

Ghanbari, Yasser; Herrington, John; Gur, Ruben C; Schultz, Robert T; Verma, Ragini

2013-01-01

The high dimensionality of connectivity networks necessitates the development of methods identifying the connectivity building blocks that not only characterize the patterns of brain pathology but also reveal representative population patterns. In this paper, we present a non-negative component analysis framework for learning localized and sparse sub-network patterns of connectivity matrices by decomposing them into two sets of discriminative and reconstructive bases. In order to obtain components that are designed towards extracting population differences, we exploit the geometry of the population by using a graphtheoretical scheme that imposes locality-preserving properties as well as maintaining the underlying distance between distant nodes in the original and the projected space. The effectiveness of the proposed framework is demonstrated by applying it to two clinical studies using connectivity matrices derived from DTI to study a population of subjects with ASD, as well as a developmental study of structural brain connectivity that extracts gender differences.

What can fish brains tell us about visual perception?

PubMed Central

Rosa Salva, Orsola; Sovrano, Valeria Anna; Vallortigara, Giorgio

2014-01-01

Fish are a complex taxonomic group, whose diversity and distance from other vertebrates well suits the comparative investigation of brain and behavior: in fish species we observe substantial differences with respect to the telencephalic organization of other vertebrates and an astonishing variety in the development and complexity of pallial structures. We will concentrate on the contribution of research on fish behavioral biology for the understanding of the evolution of the visual system. We shall review evidence concerning perceptual effects that reflect fundamental principles of the visual system functioning, highlighting the similarities and differences between distant fish groups and with other vertebrates. We will focus on perceptual effects reflecting some of the main tasks that the visual system must attain. In particular, we will deal with subjective contours and optical illusions, invariance effects, second order motion and biological motion and, finally, perceptual binding of object properties in a unified higher level representation. PMID:25324728

Long-term variability of importance of brain regions in evolving epileptic brain networks

NASA Astrophysics Data System (ADS)

Geier, Christian; Lehnertz, Klaus

2017-04-01

We investigate the temporal and spatial variability of the importance of brain regions in evolving epileptic brain networks. We construct these networks from multiday, multichannel electroencephalographic data recorded from 17 epilepsy patients and use centrality indices to assess the importance of brain regions. Time-resolved indications of highest importance fluctuate over time to a greater or lesser extent, however, with some periodic temporal structure that can mostly be attributed to phenomena unrelated to the disease. In contrast, relevant aspects of the epileptic process contribute only marginally. Indications of highest importance also exhibit pronounced alternations between various brain regions that are of relevance for studies aiming at an improved understanding of the epileptic process with graph-theoretical approaches. Nonetheless, these findings may guide new developments for individualized diagnosis, treatment, and control.

Cerebral Apolipoprotein-D Is Hypoglycosylated Compared to Peripheral Tissues and Is Variably Expressed in Mouse and Human Brain Regions.

PubMed

Li, Hongyun; Ruberu, Kalani; Karl, Tim; Garner, Brett

2016-01-01

Recent studies have shown that cerebral apoD levels increase with age and in Alzheimer's disease (AD). In addition, loss of cerebral apoD in the mouse increases sensitivity to lipid peroxidation and accelerates AD pathology. Very little data are available, however, regarding the expression of apoD protein levels in different brain regions. This is important as both brain lipid peroxidation and neurodegeneration occur in a region-specific manner. Here we addressed this using western blotting of seven different regions (olfactory bulb, hippocampus, frontal cortex, striatum, cerebellum, thalamus and brain stem) of the mouse brain. Our data indicate that compared to most brain regions, the hippocampus is deficient in apoD. In comparison to other major organs and tissues (liver, spleen, kidney, adrenal gland, heart and skeletal muscle), brain apoD was approximately 10-fold higher (corrected for total protein levels). Our analysis also revealed that brain apoD was present at a lower apparent molecular weight than tissue and plasma apoD. Utilising peptide N-glycosidase-F and neuraminidase to remove N-glycans and sialic acids, respectively, we found that N-glycan composition (but not sialylation alone) were responsible for this reduction in molecular weight. We extended the studies to an analysis of human brain regions (hippocampus, frontal cortex, temporal cortex and cerebellum) where we found that the hippocampus had the lowest levels of apoD. We also confirmed that human brain apoD was present at a lower molecular weight than in plasma. In conclusion, we demonstrate apoD protein levels are variable across different brain regions, that apoD levels are much higher in the brain compared to other tissues and organs, and that cerebral apoD has a lower molecular weight than peripheral apoD; a phenomenon that is due to the N-glycan content of the protein.

Determination of regional brain temperature using proton magnetic resonance spectroscopy to assess brain-body temperature differences in healthy human subjects.

PubMed

Childs, Charmaine; Hiltunen, Yrjö; Vidyasagar, Rishma; Kauppinen, Risto A

2007-01-01

Proton magnetic resonance spectroscopy ((1)H MRS) was used to determine brain temperature in healthy volunteers. Partially water-suppressed (1)H MRS data sets were acquired at 3T from four different gray matter (GM)/white matter (WM) volumes. Brain temperatures were determined from the chemical-shift difference between the CH(3) of N-acetyl aspartate (NAA) at 2.01 ppm and water. Brain temperatures in (1)H MRS voxels of 2 x 2 x 2 cm(3) showed no substantial heterogeneity. The volume-averaged temperature from single-voxel spectroscopy was compared with body temperatures obtained from the oral cavity, tympanum, and temporal artery regions. The mean brain parenchyma temperature was 0.5 degrees C cooler than readings obtained from three extra-brain sites (P < 0.01). (1)H MRS imaging (MRSI) data were acquired from a slice encompassing the single-voxel volumes to assess the ability of spectroscopic imaging to determine regional brain temperature within the imaging slice. Brain temperature away from the center of the brain determined by MRSI differed from that obtained by single-voxel MRS in the same brain region, possibly due to a poor line width (LW) in MRSI. The data are discussed in the light of proposed brain-body temperature gradients and the use of (1)H MRSI to monitor brain temperature in pathologies, such as brain trauma.

Intranasal Administration of PACAP: Uptake by Brain and Brain Region Targeting with Cyclodextrins

PubMed Central

Nonaka, Naoko; Farr, Susan A.; Nakamachi, Tomoya; Morley, John E.; Nakamura, Masanori; Shioda, Seiji; Banks, William A.

2012-01-01

Pituitary adenylate cyclase activating polypeptide (PACAP) is a potent neurotrophic and neuroprotectant that is transported across the blood-brain barrier in amounts sufficient to affect brain function. However, its short half-life in blood makes it difficult to administer peripherally. Here, we determined whether the radioactively labeled 38 amino acid form of PACAP can enter the brain after intranasal (i.n.) administration. Occipital cortex and striatum were the regions with the highest uptake, peaking at levels of about 2-4 percent of the injected dose per g of brain region. Inclusion of unlabeled PACAP greatly increased retention of I-PACAP by brain probably because of inhibition of the brain-to-blood efflux transporter for PACAP located at the blood-brain barrier. Sufficient amounts of PACAP could be delivered to the brain to affect function as shown by improvement of memory in aged SAMP8 mice, a model of Alzheimer’s disease. We found that each of three cyclodextrins when included in the i.n. injection produced a unique distribution pattern of I-PACAP among brain regions. As examples, β-cyclodextrin greatly increased uptake by the occipital cortex and hypothalamus, α-cyclodextrin increased uptake by the olfactory bulb and decreased uptake by the occipital cortex and striatum, and (2-hydropropyl)-β-cyclodextrin increased uptake by the thalamus and decreased uptake by the striatum. These results show that therapeutic amounts of PACAP can be delivered to the brain by intranasal administration and that cyclodextrins may be useful in the therapeutic targeting of peptides to specific brain regions. PMID:22687366

Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation

PubMed Central

Paulk, Angelique C.; Zhou, Yanqiong; Stratton, Peter; Liu, Li

2013-01-01

Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel “whole brain” readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior. PMID:23864378

Patterns of failure and survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy in Saudi Arabia

PubMed Central

Maklad, Ahmed Marzouk; Bayoumi, Yasser; Senosy Hassan, Mohamed Abdalazez; Elawadi, AbuSaleh A; AlHussain, Hussain; Elyamany, Ashraf; Aldhahri, Saleh F; Al-Qahtani, Khalid Hussain; AlQahtani, Mubarak; Tunio, Mutahir A

2016-01-01

Background We aimed to investigate the patterns of failure (locoregional and distant metastasis), associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT) combined with chemotherapy. Patients and methods From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66–70 Gy, 63 Gy to clinical target volume, and 50.4–56 Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. Results The median follow-up time was 52.2 months (range: 11–87 months). Epstein–Barr virus infection was positive in 63.2% of patients. Overall disease failure developed in 21 patients, of whom 85.8% belonged to stage III/IV disease. Among these, there were seven locoregional recurrences, three regional recurrences with distant metastases, and eleven distant metastases. The median interval from the date of diagnosis to failure was 26.5 months (range: 16–50 months). Six of ten (60%) locoregional recurrences were treated with reirradiation ± concurrent chemotherapy. The 5-year locoregional control, distant metastasis control, disease-free survival, and overall survival rates of whole cohort were 81.1%, 74.3%, 60.1%, and 73.4%, respectively. Cox regression analyses revealed that neoadjuvant chemotherapy, age, and Epstein–Barr virus were independent predictors for disease-free survival. Conclusion Neoadjuvant chemotherapy followed by IMRT with or without chemotherapy improves the long-term survival of Saudi patients with nasopharyngeal carcinoma. Distant metastasis was the main pattern of treatment failure. Neoadjuvant chemotherapy, age, and Epstein–Barr virus status before IMRT were important independent prognostic factors. PMID:27822060

Distant Influence of Kuroshio Eddies on North Pacific Weather Patterns?

PubMed Central

Ma, Xiaohui; Chang, Ping; Saravanan, R.; Montuoro, Raffaele; Hsieh, Jen-Shan; Wu, Dexing; Lin, Xiaopei; Wu, Lixin; Jing, Zhao

2015-01-01

High-resolution satellite measurements of surface winds and sea-surface temperature (SST) reveal strong coupling between meso-scale ocean eddies and near-surface atmospheric flow over eddy-rich oceanic regions, such as the Kuroshio and Gulf Stream, highlighting the importance of meso-scale oceanic features in forcing the atmospheric planetary boundary layer (PBL). Here, we present high-resolution regional climate modeling results, supported by observational analyses, demonstrating that meso-scale SST variability, largely confined in the Kuroshio-Oyashio confluence region (KOCR), can further exert a significant distant influence on winter rainfall variability along the U.S. Northern Pacific coast. The presence of meso-scale SST anomalies enhances the diabatic conversion of latent heat energy to transient eddy energy, intensifying winter cyclogenesis via moist baroclinic instability, which in turn leads to an equivalent barotropic downstream anticyclone anomaly with reduced rainfall. The finding points to the potential of improving forecasts of extratropical winter cyclones and storm systems and projections of their response to future climate change, which are known to have major social and economic impacts, by improving the representation of ocean eddy–atmosphere interaction in forecast and climate models. PMID:26635077

Cosmic Ray Transport in the Distant Heliosheath

NASA Technical Reports Server (NTRS)

Florinski, V.; Adams, James H.; Washimi, H.

2011-01-01

The character of energetic particle transport in the distant heliosheath and especially in the vicinity of the heliopause could be quite distinct from the other regions of the heliosphere. The magnetic field structure is dominated by a tightly wrapped oscillating heliospheric current sheet which is transported to higher latitudes by the nonradial heliosheath flows. Both Voyagers have, or are expected to enter a region dominated by the sectored field formed during the preceding solar maximum. As the plasma flow slows down on approach to the heliopause, the distance between the folds of the current sheet decreases to the point where it becomes comparable to the cyclotron radius of an energetic ion, such as a galactic cosmic ray. Then, a charged particle can effectively drift across a stack of magnetic sectors with a speed comparable with the particle s velocity. Cosmic rays should also be able to efficiently diffuse across the mean magnetic field if the distance between sector boundaries varies. The region of the heliopause could thus be much more permeable to cosmic rays than was previously thought. This new transport proposed mechanism could explain the very high intensities (approaching the model interstellar values) of galactic cosmic rays measured by Voyager 1 during 2010-2011.

Post-operative radiation therapy for advanced-stage oropharyngeal cancer.

PubMed

Hansen, Eric; Panwala, Kathryn; Holland, John

2002-11-01

Between 1985 and 1999, 43 patients with locally-advanced, resectable oropharyngeal cancer were treated with combined surgery and post-operative radiation therapy (RT) at Oregon Health and Science University. Five patients (12 per cent) had Stage III disease and 38 patients (88 per cent) had Stage IV disease. All patients had gross total resections of the primary tumour. Thirty-seven patients had neck dissections for regional disease. RT consisted of a mean tumour-bed dose of 63.0 Gy delivered in 1.8-2.0 Gy fractions over a mean of 49 days. At three- and five-years, the actuarial local control was 96 per cent and the actuarial local/regional control was 80 per cent. The three- and five-year actuarial rates of distant metastases were 41 per cent and 46 per cent, respectively. The actuarial overall survival at three- and five-years was 41 per cent and 34 per cent, respectively. The actuarial rates of progression-free survival were 49 per cent at three-years and 45 per cent at five years. Combined surgery and post-operative RT for advanced-stage oropharyngeal cancer results in excellent local/regional control. This particular group of patients experienced a high-rate of developing distant metastases.

Fused cerebral organoids model interactions between brain regions.

PubMed

Bagley, Joshua A; Reumann, Daniel; Bian, Shan; Lévi-Strauss, Julie; Knoblich, Juergen A

2017-07-01

Human brain development involves complex interactions between different regions, including long-distance neuronal migration or formation of major axonal tracts. Different brain regions can be cultured in vitro within 3D cerebral organoids, but the random arrangement of regional identities limits the reliable analysis of complex phenotypes. Here, we describe a coculture method combining brain regions of choice within one organoid tissue. By fusing organoids of dorsal and ventral forebrain identities, we generate a dorsal-ventral axis. Using fluorescent reporters, we demonstrate CXCR4-dependent GABAergic interneuron migration from ventral to dorsal forebrain and describe methodology for time-lapse imaging of human interneuron migration. Our results demonstrate that cerebral organoid fusion cultures can model complex interactions between different brain regions. Combined with reprogramming technology, fusions should offer researchers the possibility to analyze complex neurodevelopmental defects using cells from neurological disease patients and to test potential therapeutic compounds.

Elective Nodal Irradiation and Patterns of Failure in Head and Neck Cancer After Primary Radiation Therapy

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

Kjems, Julie; Gothelf, Anita B.; Håkansson, Katrin

Purpose: The delineation of elective clinical target volumes in head and neck cancer (HNC) is important; however, the extent of lymph node levels necessary to include is debated. A comprehensive analysis of recurrence patterns in a large cohort of patients with HNC was performed, with an emphasis on recurrence in the retropharyngeal region and level IB. Methods and Materials: From 2005 to 2012, 942 patients with oropharyngeal, hypopharyngeal, laryngeal or oral cavity carcinomas were curatively treated with primary radiation therapy. The median follow-up period was 34 months, and 77% of the patients underwent intensity modulated radiation therapy. The retropharyngeal region wasmore » only routinely included in cases of involvement of the posterior pharynx wall and level IB only in cases of involvement of the oral cavity. In patients with regional recurrence, the anatomic site of the recurrence was assessed from the surgical descriptions or computed tomography scans and compared with the original radiation treatment plan (available from 2007 onward). The p16 status was available for 282 oropharynx carcinoma cases, with 65% p16-positive. Results: Of the 942 patients, 376 (40%) developed recurrences: 228 (24.2%) local, 123 (13.1%) regional, and 109 (11.6%) distant. In 700 patients with available treatment plans, retropharyngeal and level IB recurrence was observed in 2 and 7 patients, respectively. Eight patients (1.1%) had recurrence in a lymph node level not included in their primary treatment plan. For oropharynx carcinoma, the locoregional control rate (90% vs 70%) but not distant control rate (92% vs 87%), was significantly better in the p16-positive than in the p16-negative patients. Although fewer recurrences developed in the p16-positive group, patients with recurrence of p16-positive tumors were more likely to develop recurrence in distant sites. Conclusions: Retropharyngeal or level IB recurrence after primary HNC radiation therapy is rare. Thus, inclusion of these regions in the elective treatment volumes should be limited to patients with involvement of the posterior pharyngeal wall or oral cavity.« less

Assessment of the Initial Response from Tsunami Monitoring Services Provided to the Northeastern Caribbean

NASA Astrophysics Data System (ADS)

Soto-Cordero, L.; Meltzer, A.

2014-12-01

A mag 6.4 earthquake offshore northern Puerto Rico earlier this year (1/13/14) is a reminder of the high risk of earthquakes and tsunamis in the northeastern Caribbean. Had the magnitude of this event been 0.1 larger (M 6.5) a tsunami warning would have been issued for the Puerto Rico-Virgin Islands (PRVI) region based on the West Coast Alaska Tsunami Warning Center (WCATWC) and Puerto Rico Seismic Network (PRSN) response procedures at the time. Such an alert level would have led local authorities to issue evacuation orders for all PRVI coastal areas. Since the number of deaths associated with tsunamis in the Caribbean region is greater than the total casualties from tsunamis in the entire US (including Hawaii and Alaska coasts) having an effective and redundant warning system is critical in order to save lives and to minimize false alarms that could result in significant economic costs and loss of confidence of Caribbean residents. We are evaluating three fundamental components of tsunami monitoring protocols currently in place in the northeastern Caribbean: 1) preliminary earthquake parameters (used to determine the potential that a tsunami will be generated and the basis of tsunami alert levels), 2) adequacy of the tsunami alert levels, and 3) tsunami message dissemination. We compiled a catalog of earthquake locations (2007-2014) and dissemination times from the PTWC, WCATWC and NEIC (final locations). The events were classified into 3 categories: local [17°-20°N, 63.5°-69°W], regional (Caribbean basin) and distant/teleseismic (Atlantic basin). A total of 104 local earthquakes, 31 regional and 25 distant events were analyzed. We found that in general preliminary epicentral locations have an accuracy of 40 km. 64% of local events were located with an accuracy of 20 km. The depth accuracy of local events shallower than 50 km, regional and distant earthquakes is usually smaller than 30 km. For deeper local events the error distribution shows more variability (-32 to 81 km); preliminary locations tend to underestimate depth. A trade-off between epicentral location and depth was observed for several local events deeper than 50 km.

Control-related systems in the human brain

PubMed Central

Power, Jonathan D; Petersen, Steven E

2013-01-01

A fundamental question in cognitive neuroscience is how the human brain self-organizes to perform tasks. Multiple accounts of this self-organization are currently influential and in this article we survey one of these accounts. We begin by introducing a psychological model of task control and several neuroimaging signals it predicts. We then discuss where such signals are found across tasks with emphasis on brain regions where multiple control signals are present. We then present results derived from spontaneous task-free functional connectivity between control-related regions that dovetail with distinctions made by control signals present in these regions, leading to a proposal that there are at least two task control systems in the brain. This prompts consideration of whether and how such control systems distinguish themselves from other brain regions in a whole-brain context. We present evidence from whole-brain networks that such distinctions do occur and that control systems comprise some of the basic system-level organizational elements of the human brain. We close with observations from the whole-brain networks that may suggest parsimony between multiple accounts of cognitive control. PMID:23347645

Describing functional diversity of brain regions and brain networks

PubMed Central

Anderson, Michael L.; Kinnison, Josh; Pessoa, Luiz

2013-01-01

Despite the general acceptance that functional specialization plays an important role in brain function, there is little consensus about its extent in the brain. We sought to advance the understanding of this question by employing a data-driven approach that capitalizes on the existence of large databases of neuroimaging data. We quantified the diversity of activation in brain regions as a way to characterize the degree of functional specialization. To do so, brain activations were classified in terms of task domains, such as vision, attention, and language, which determined a region’s functional fingerprint. We found that the degree of diversity varied considerably across the brain. We also quantified novel properties of regions and of networks that inform our understanding of several task-positive and task-negative networks described in the literature, including defining functional fingerprints for entire networks and measuring their functional assortativity, namely the degree to which they are composed of regions with similar functional fingerprints. Our results demonstrate that some brain networks exhibit strong assortativity, whereas other networks consist of relatively heterogeneous parts. In sum, rather than characterizing the contributions of individual brain regions using task-based functional attributions, we instead quantified their dispositional tendencies, and related those to each region’s affiliative properties in both task-positive and task-negative contexts. PMID:23396162

Transcriptional regulation of brain gene expression in response to a territorial intrusion

PubMed Central

Sanogo, Yibayiri O.; Band, Mark; Blatti, Charles; Sinha, Saurabh; Bell, Alison M.

2012-01-01

Aggressive behaviour associated with territorial defence is widespread and has fitness consequences. However, excess aggression can interfere with other important biological functions such as immunity and energy homeostasis. How the expression of complex behaviours such as aggression is regulated in the brain has long intrigued ethologists, but has only recently become amenable for molecular dissection in non-model organisms. We investigated the transcriptomic response to territorial intrusion in four brain regions in breeding male threespined sticklebacks using expression microarrays and quantitative polymerase chain reaction (qPCR). Each region of the brain had a distinct genomic response to a territorial challenge. We identified a set of genes that were upregulated in the diencephalon and downregulated in the cerebellum and the brain stem. Cis-regulatory network analysis suggested transcription factors that regulated or co-regulated genes that were consistently regulated in all brain regions and others that regulated gene expression in opposing directions across brain regions. Our results support the hypothesis that territorial animals respond to social challenges via transcriptional regulation of genes in different brain regions. Finally, we found a remarkably close association between gene expression and aggressive behaviour at the individual level. This study sheds light on the molecular mechanisms in the brain that underlie the response to social challenges. PMID:23097509

Segmentation and texture analysis of structural biomarkers using neighborhood-clustering-based level set in MRI of the schizophrenic brain.

PubMed

Latha, Manohar; Kavitha, Ganesan

2018-02-03

Schizophrenia (SZ) is a psychiatric disorder that especially affects individuals during their adolescence. There is a need to study the subanatomical regions of SZ brain on magnetic resonance images (MRI) based on morphometry. In this work, an attempt was made to analyze alterations in structure and texture patterns in images of the SZ brain using the level-set method and Laws texture features. T1-weighted MRI of the brain from Center of Biomedical Research Excellence (COBRE) database were considered for analysis. Segmentation was carried out using the level-set method. Geometrical and Laws texture features were extracted from the segmented brain stem, corpus callosum, cerebellum, and ventricle regions to analyze pattern changes in SZ. The level-set method segmented multiple brain regions, with higher similarity and correlation values compared with an optimized method. The geometric features obtained from regions of the corpus callosum and ventricle showed significant variation (p < 0.00001) between normal and SZ brain. Laws texture feature identified a heterogeneous appearance in the brain stem, corpus callosum and ventricular regions, and features from the brain stem were correlated with Positive and Negative Syndrome Scale (PANSS) score (p < 0.005). A framework of geometric and Laws texture features obtained from brain subregions can be used as a supplement for diagnosis of psychiatric disorders.

Millimeter wavelength observations of solar active regions

NASA Technical Reports Server (NTRS)

Kundu, M. R.

1973-01-01

Polarization properties of active regions at 9 mm are discussed, and the observed degree of polarization is used to obtain an estimate of chromospheric magnetic fields. Also discussed is the polarization structure at 9 mm of an active region that produced a minor flare around 1900 UT on September 28, 1971. Total power observations indicate that new regions develop, or weak regions intensify at millimeter wavelengths as a result of bursts at distant sites. The spectra of the peak flux density of moderately strong bursts observed at 9 mm show a sharp drop toward the shorter millimeter wavelengths. The weak bursts at 3.5 mm are manifest mainly as heating phenomena.

Relationship between brain R(2) and liver and serum iron concentrations in elderly men.

PubMed

House, Michael J; St Pierre, Timothy G; Milward, Elizabeth A; Bruce, David G; Olynyk, John K

2010-02-01

Studies of iron overload in humans and animals suggest that brain iron concentrations may be related in a regionally specific way to body iron status. However, few quantitative studies have investigated the associations between peripheral and regional brain iron in a normal elderly cohort. To examine these relationships, we used MRI to measure the proton transverse relaxation rate (R(2)) in 13 gray and white matter brain regions in 18 elderly men (average age, 75.5 years) with normal cognition. Brain R(2) values were compared with liver iron concentrations measured using the FerriScan MRI technique and serum iron indices. R(2) values in high-iron gray matter regions were significantly correlated (positively) with liver iron concentrations (globus pallidus, ventral pallidum) and serum transferrin saturation (caudate nucleus, globus pallidus, putamen) measured concurrently with brain R(2), and with serum iron concentrations (caudate nucleus, globus pallidus) measured three years before the current study. Our results suggest that iron levels in specific gray matter brain regions are influenced by systemic iron status in elderly men.

Distant, delayed and ancient earthquake-induced landslides

NASA Astrophysics Data System (ADS)

Havenith, Hans-Balder; Torgoev, Almaz; Braun, Anika; Schlögel, Romy; Micu, Mihai

2016-04-01

On the basis of a new classification of seismically induced landslides we outline particular effects related to the delayed and distant triggering of landslides. Those cannot be predicted by state-of-the-art methods. First, for about a dozen events the 'predicted' extension of the affected area is clearly underestimated. The most problematic cases are those for which far-distant triggering of landslides had been reported, such as for the 1988 Saguenay earthquake. In Central Asia reports for such cases are known for areas marked by a thick cover of loess. One possible contributing effect could be a low-frequency resonance of the thick soils induced by distant earthquakes, especially those in the Pamir - Hindu Kush seismic region. Such deep focal and high magnitude (>>7) earthquakes are also found in Europe, first of all in the Vrancea region (Romania). For this area and others in Central Asia we computed landslide event sizes related to scenario earthquakes with M>7.5. The second particular and challenging type of triggering is the one delayed with respect to the main earthquake event: case histories have been reported for the Racha earthquake in 1991 when several larger landslides only started moving 2 or 3 days after the main shock. Similar observations were also made after other earthquake events in the U.S., such as after the 1906 San Francisco, the 1949 Tacoma, the 1959 Hebgen Lake and the 1983 Bora Peak earthquakes. Here, we will present a series of detailed examples of (partly monitored) mass movements in Central Asia that mainly developed after earthquakes, some even several weeks after the main shock: e.g. the Tektonik and Kainama landslides triggered in 1992 and 2004, respectively. We believe that the development of the massive failures is a consequence of the opening of tension cracks during the seismic shaking and their filling up with water during precipitations that followed the earthquakes. The third particular aspect analysed here is the use of large ancient landslides for paleoseismic studies. As Central Asian mountain regions are marked by a relatively high ratio of seismically versus climatically triggered landslides, they represent a prime test area for such studies. This observation is contrasting with known landslide activity in Europe where by far most landslides are triggered by climatic factors, besides for some seismically active regions in the Eastern Alps, around the Mediterranean Sea and in the Carpathians (Vrancea, Romania). We will discuss how we may identify such earthquake-triggered landslides and how we may distinguish them from rainfall-induced slope failures.

Detection of Local, Regional, and Distant Recurrence in Patients With PSA Relapse After External-Beam Radiotherapy Using {sup 11}C-Choline Positron Emission Tomography

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

Breeuwsma, Anthonius J., E-mail: a.j.breeuwsma@uro.umcg.n; Departments of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen; Pruim, Jan

2010-05-01

Purpose: An elevated serum prostate-specific antigen (PSA) level cannot distinguish between local-regional recurrences and the presence of distant metastases after treatment with curative intent for prostate cancer. With the advent of salvage treatment such as cryotherapy, it has become important to localize the site of recurrence (local or distant). In this study, the potential of {sup 11}C-choline positron emission tomography (PET) to identify site of recurrence was investigated in patients with rising PSA after external-beam radiotherapy (EBRT). Methods and Materials: Seventy patients with histologically proven prostate cancer treated with EBRT and showing biochemical recurrence as defined by American Society formore » Therapeutic Radiology and Oncology consensus statement and 10 patients without recurrence underwent a PET scan using 400 MBq {sup 11}C-choline intravenously. Biopsy-proven histology from the site of suspicion, findings with other imaging modalities, clinical follow-up and/or response to adjuvant therapy were used as comparative references. Results: None of the 10 patients without biochemical recurrence had a positive PET scan. Fifty-seven of 70 patients with biochemical recurrence (median PSA 9.1 ng/mL; mean PSA 12.3 ng/mL) showed an abnormal uptake pattern (sensitivity 81%). The site of recurrence was only local in 41 of 57 patients (mean PSA 11.1 ng/mL at scan), locoregionally and/or distant in 16 of 57 patients (mean PSA 17.7 ng/mL). Overall the positive predictive value and negative predictive value for {sup 11}C-choline PET scan were 1.0 and 0.44 respectively. Accuracy was 84%. Conclusions: {sup 11}C-choline PET scan is a sensitive technique to identify the site of recurrence in patients with PSA relapse after EBRT for prostate cancer.« less

Skeleton-based region competition for automated gray matter and white matter segmentation of human brain MR images

NASA Astrophysics Data System (ADS)

Chu, Yong; Chen, Ya-Fang; Su, Min-Ying; Nalcioglu, Orhan

2005-04-01

Image segmentation is an essential process for quantitative analysis. Segmentation of brain tissues in magnetic resonance (MR) images is very important for understanding the structural-functional relationship for various pathological conditions, such as dementia vs. normal brain aging. Different brain regions are responsible for certain functions and may have specific implication for diagnosis. Segmentation may facilitate the analysis of different brain regions to aid in early diagnosis. Region competition has been recently proposed as an effective method for image segmentation by minimizing a generalized Bayes/MDL criterion. However, it is sensitive to initial conditions - the "seeds", therefore an optimal choice of "seeds" is necessary for accurate segmentation. In this paper, we present a new skeleton-based region competition algorithm for automated gray and white matter segmentation. Skeletons can be considered as good "seed regions" since they provide the morphological a priori information, thus guarantee a correct initial condition. Intensity gradient information is also added to the global energy function to achieve a precise boundary localization. This algorithm was applied to perform gray and white matter segmentation using simulated MRI images from a realistic digital brain phantom. Nine different brain regions were manually outlined for evaluation of the performance in these separate regions. The results were compared to the gold-standard measure to calculate the true positive and true negative percentages. In general, this method worked well with a 96% accuracy, although the performance varied in different regions. We conclude that the skeleton-based region competition is an effective method for gray and white matter segmentation.

A comprehensive analysis on preservation patterns of gene co-expression networks during Alzheimer's disease progression.

PubMed

Ray, Sumanta; Hossain, Sk Md Mosaddek; Khatun, Lutfunnesa; Mukhopadhyay, Anirban

2017-12-20

Alzheimer's disease (AD) is a chronic neuro-degenerative disruption of the brain which involves in large scale transcriptomic variation. The disease does not impact every regions of the brain at the same time, instead it progresses slowly involving somewhat sequential interaction with different regions. Analysis of the expression patterns of the genes in different regions of the brain influenced in AD surely contribute for a enhanced comprehension of AD pathogenesis and shed light on the early characterization of the disease. Here, we have proposed a framework to identify perturbation and preservation characteristics of gene expression patterns across six distinct regions of the brain ("EC", "HIP", "PC", "MTG", "SFG", and "VCX") affected in AD. Co-expression modules were discovered considering a couple of regions at once. These are then analyzed to know the preservation and perturbation characteristics. Different module preservation statistics and a rank aggregation mechanism have been adopted to detect the changes of expression patterns across brain regions. Gene ontology (GO) and pathway based analysis were also carried out to know the biological meaning of preserved and perturbed modules. In this article, we have extensively studied the preservation patterns of co-expressed modules in six distinct brain regions affected in AD. Some modules are emerged as the most preserved while some others are detected as perturbed between a pair of brain regions. Further investigation on the topological properties of preserved and non-preserved modules reveals a substantial association amongst "betweenness centrality" and "degree" of the involved genes. Our findings may render a deeper realization of the preservation characteristics of gene expression patterns in discrete brain regions affected by AD.

Localized delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat brain using focused ultrasound.

PubMed

Mulik, Rohit S; Bing, Chenchen; Ladouceur-Wodzak, Michelle; Munaweera, Imalka; Chopra, Rajiv; Corbin, Ian R

2016-03-01

Focused ultrasound exposures in the presence of microbubbles can achieve transient, non-invasive, and localized blood-brain barrier (BBB) opening, offering a method for targeted delivery of therapeutic agents into the brain. Low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) could have significant therapeutic value in the brain, since DHA is known to be neuroprotective. BBB opening was achieved using pulsed ultrasound exposures in a localized brain region in normal rats, after which LDL nanoparticles containing the fluorescent probe DiR (1,1'-Dioctadecyl-3,3,3',3'-Tetramethylindotricarbocyanine Iodide) or DHA were administered intravenously. Fluorescent imaging of brain tissue from rats administered LDL-DiR demonstrated strong localization of fluorescence signal in the exposed hemisphere. LDL-DHA administration produced 2 × more DHA in the exposed region of the brain, with a corresponding increase in Resolvin D1 levels, indicating DHA was incorporated into cells and metabolized. Histological evaluation did not indicate any evidence of increased tissue damage in exposed brain regions compared to normal brain. This work demonstrates that localized delivery of DHA to the brain is possible using systemically-administered LDL nanoparticles combined with pulsed focused ultrasound exposures in the brain. This technology could be used in regions of acute brain injury or as a means to target infiltrating tumor cells in the brain. Copyright © 2016 Elsevier Ltd. All rights reserved.

Localized Delivery of Low-Density Lipoprotein Docosahexaenoic Acid Nanoparticles to the Rat Brain using Focused Ultrasound

PubMed Central

Mulik, Rohit S.; Bing, Chenchen; Ladouceur-Wodzak, Michelle; Munaweera, Imalka; Chopra, Rajiv; Corbin, Ian R.

2016-01-01

Focused ultrasound exposures in the presence of microbubbles can achieve transient, non-invasive, and localized blood-brain barrier (BBB) opening, offering a method for targeted delivery of therapeutic agents into the brain. Low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) could have significant therapeutic value in the brain, since DHA is known to be neuroprotective. BBB opening was achieved using pulsed ultrasound exposures in a localized brain region in normal rats, after which LDL nanoparticles containing the fluorescent probe DiR (1,1′-Dioctadecyl-3,3,3′,3′-Tetramethylindotricarbocyanine Iodide) or DHA were administered intravenously. Fluorescent imaging of brain tissue from rats administered LDL-DiR demonstrated strong localization of fluorescence signal in the exposed hemisphere. LDL-DHA administration produced 2× more DHA in the exposed region of the brain, with a corresponding increase in Resolvin D1 levels, indicating DHA was incorporated into cells and metabolized. Histological evaluation did not indicate any evidence of increased tissue damage in exposed brain regions compared to normal brain. This work demonstrates that localized delivery of DHA to the brain is possible using systemically-administered LDL nanoparticles combined with pulsed focused ultrasound exposures in the brain. This technology could be used in regions of acute brain injury or as a means to target infiltrating tumor cells in the brain. PMID:26790145

Lateralized theta wave connectivity and language performance in 2- to 5-year-old children.

PubMed

Kikuchi, Mitsuru; Shitamichi, Kiyomi; Yoshimura, Yuko; Ueno, Sanae; Remijn, Gerard B; Hirosawa, Tetsu; Munesue, Toshio; Tsubokawa, Tsunehisa; Haruta, Yasuhiro; Oi, Manabu; Higashida, Haruhiro; Minabe, Yoshio

2011-10-19

Recent neuroimaging studies support the view that a left-lateralized brain network is crucial for language development in children. However, no previous studies have demonstrated a clear link between lateralized brain functional network and language performance in preschool children. Magnetoencephalography (MEG) is a noninvasive brain imaging technique and is a practical neuroimaging method for use in young children. MEG produces a reference-free signal, and is therefore an ideal tool to compute coherence between two distant cortical rhythms. In the present study, using a custom child-sized MEG system, we investigated brain networks while 78 right-handed preschool human children (32-64 months; 96% were 3-4 years old) listened to stories with moving images. The results indicated that left dominance of parietotemporal coherence in theta band activity (6-8 Hz) was specifically correlated with higher performance of language-related tasks, whereas this laterality was not correlated with nonverbal cognitive performance, chronological age, or head circumference. Power analyses did not reveal any specific frequencies that contributed to higher language performance. Our results suggest that it is not the left dominance in theta oscillation per se, but the left-dominant phase-locked connectivity via theta oscillation that contributes to the development of language ability in young children.

PET evaluation of late cerebral effect in advanced radiation therapy techniques for cranial base tumors.

PubMed

Alongi, Pierpaolo; Iaccarino, Leonardo; Losa, Marco; Del Vecchio, Antonella; Gerevini, Simonetta; Plebani, Valentina; Di Muzio, Nadia; Mortini, Pietro; Gianolli, Luigi; Perani, Daniela

2018-05-25

Even though the benefits of radiation therapy are well established, it is important to recognize the broad spectrum of radiation-induced changes, particularly in the central nervous system. The possible damage to the brain parenchyma may have clinical consequences and in particular cognitive impairment might be one of the major complication of radiotherapy. To date, no studies have investigated the effects of focal radiation therapy on brain structure and function together with the assessment of their clinical outcomes at a long follow-up. In this prospective study, we evaluated in six patients the possible brain late effects after radiation therapy, using a standardized neuropsychological battery, MRI and 18F-FDG PET using SPM and semi-quantitative methods, in patients affected by cranial base tumors who underwent gamma knife or tomotherapy. Neuropsychological examinations showed no cognitive impairment after the treatment. In all patients, both MRI assessment and 18F-FDG-PET did not reveal any local or distant anatomical and metabolic late effects. The present study support the safety of advanced radiation therapy techniques. 18F-FDG-PET, using SPM and semi-quantitative methods, might be a valuable tool to evaluate the cerebral radiotoxicity in patients treated for brain neoplasms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Genome-wide introgression among distantly related Heliconius butterfly species.

PubMed

Zhang, Wei; Dasmahapatra, Kanchon K; Mallet, James; Moreira, Gilson R P; Kronforst, Marcus R

2016-02-27

Although hybridization is thought to be relatively rare in animals, the raw genetic material introduced via introgression may play an important role in fueling adaptation and adaptive radiation. The butterfly genus Heliconius is an excellent system to study hybridization and introgression but most studies have focused on closely related species such as H. cydno and H. melpomene. Here we characterize genome-wide patterns of introgression between H. besckei, the only species with a red and yellow banded 'postman' wing pattern in the tiger-striped silvaniform clade, and co-mimetic H. melpomene nanna. We find a pronounced signature of putative introgression from H. melpomene into H. besckei in the genomic region upstream of the gene optix, known to control red wing patterning, suggesting adaptive introgression of wing pattern mimicry between these two distantly related species. At least 39 additional genomic regions show signals of introgression as strong or stronger than this mimicry locus. Gene flow has been on-going, with evidence of gene exchange at multiple time points, and bidirectional, moving from the melpomene to the silvaniform clade and vice versa. The history of gene exchange has also been complex, with contributions from multiple silvaniform species in addition to H. besckei. We also detect a signature of ancient introgression of the entire Z chromosome between the silvaniform and melpomene/cydno clades. Our study provides a genome-wide portrait of introgression between distantly related butterfly species. We further propose a comprehensive and efficient workflow for gene flow identification in genomic data sets.

Literature-Related Discovery (LRD)

DTIC Science & Technology

2007-11-01

accepted) water purification literature. The annular region between the inner and outer circles represents literatures related directly and...procedures (thalamotomy and pallidotomy) destroy regions of the brain that produce the uncontrolled spasmodic movements in PD patients [11]. A...more recent procedure, deep brain stimulation, sends electricity through a probe to normalize electrical activity in the brain region , reversing the

Neuronal survival in the brain: neuron type-specific mechanisms.

PubMed

Pfisterer, Ulrich; Khodosevich, Konstantin

2017-03-02

Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation. Furthermore, pro-survival factors and intracellular responses depend on the type of neuron and region of the brain. Thus, in addition to some common neuronal pro-survival signaling, different types of neurons possess a variety of 'neuron type-specific' pro-survival constituents that might help them to adapt for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various types of immature neurons. Importantly, we mainly focus on in vivo data to describe neuronal survival specifically in the brain, without extrapolating data obtained in the PNS or spinal cord, and thus emphasize the influence of the complex brain environment on neuronal survival during development.

Brain region and epilepsy-associated differences in inflammatory mediator levels in medically refractory mesial temporal lobe epilepsy.

PubMed

Strauss, Kenneth I; Elisevich, Kost V

2016-10-13

Epilepsy patients have distinct immune/inflammatory cell profiles and inflammatory mediator levels in the blood. Although the neural origin of inflammatory cells and mediators has been implied, few studies have measured these inflammatory components in the human brain itself. This study examines the brain levels of chemokines (8), cytokines (14), and vascular injury mediators (3) suspected of being altered in epilepsy. Soluble protein extracts of fresh frozen resected hippocampus, entorhinal cortex, and temporal cortex from 58 medically refractory mesial temporal lobe epilepsy subjects and 4 nonepileptic neurosurgical subjects were assayed for 25 inflammation-related mediators using ultrasensitive low-density arrays. Brain mediator levels were compared between regions and between epileptic and nonepileptic cases, showing a number of regional and possible epilepsy-associated differences. Eotaxin, interferon-γ, interleukin (IL)-2, IL-4, IL-12 p70, IL-17A, tumor necrosis factor-α, and intercellular adhesion molecule (ICAM)-1 levels were highest in the hippocampus, the presumptive site of epileptogenesis. Surprisingly, IL-1β and IL-1α were lowest in the hippocampus, compared to cortical regions. In the temporal cortex, IL-1β, IL-8, and MIP-1α levels were highest, compared to the entorhinal cortex and the hippocampus. The most pronounced epilepsy-associated differences were decreased levels of eotaxin, IL-1β, C-reactive protein, and vascular cell adhesion molecule (VCAM)-1 and increased IL-12 p70 levels. Caution must be used in interpreting these results, however, because nonepileptic subjects were emergent neurosurgical cases, not a control group. Correlation analyses of each mediator in each brain region yielded valuable insights into the regulation of these mediator levels in the brain. Over 70 % of the associations identified were between different mediators in a single brain region, providing support for local control of mediator levels. Correlations of different mediators in different brain regions suggested more distributed control mechanisms, particularly in the hippocampus. Interestingly, only four mediators showed robust correlations between the brain regions, yet levels in three of these were significantly different between regions, indicating both global and local controls for these mediators. Both brain region-specific and epilepsy-associated changes in inflammation-related mediators were detected. Correlations in mediator levels within and between brain regions indicated local and global regulation, respectively. The hippocampus showed the majority of interregional associations, suggesting a focus of inflammatory control between these regions.

Serial or Parallel Metastasis of Cutaneous Melanoma? A Study of the German Central Malignant Melanoma Registry.

PubMed

Gassenmaier, Maximilian; Eigentler, Thomas Kurt; Keim, Ulrike; Goebeler, Matthias; Fiedler, Eckhard; Schuler, Gerold; Leiter, Ulrike; Weide, Benjamin; Grischke, Eva-Maria; Martus, Peter; Garbe, Claus

2017-12-01

For more than a century the Halstedian hypothesis of contiguous metastasis from the primary tumor through the lymphatics to distant sites shaped lymph node surgery for melanoma. We challenge this dogma of serial metastatic dissemination. A single-center series of 2,299 patients with cutaneous metastatic melanoma was investigated to analyze overall survival and distant metastasis-free survival of stage IV patients with or without primary lymphatic metastasis. Results were then compared with those of 2,134 patients from three independent centers of the German Central Malignant Melanoma Registry. A multivariate binary logistic regression model was used to identify risk factors for the initial metastatic pathway. Distant metastasis-free survival (hazard ratio = 1.02; 95% confidence interval = 0.91-1.14; P = 0.76) and overall survival (HR = 1.09; 95% CI = 0.96-1.23; P = 0.177) did not differ between stage IV patients with primary hematogenous or primary lymphatic metastasis. Melanoma localization was the only significant risk factor for the initial metastatic pathway. These findings indicate that regional and distant metastases originate from the primary tumor itself in a rather parallel than serial fashion and could explain the lack of survival benefit associated with immediate complete lymph node dissection in sentinel lymph node-positive melanoma patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Remote Synchronization Reveals Network Symmetries and Functional Modules

NASA Astrophysics Data System (ADS)

Nicosia, Vincenzo; Valencia, Miguel; Chavez, Mario; Díaz-Guilera, Albert; Latora, Vito

2013-04-01

We study a Kuramoto model in which the oscillators are associated with the nodes of a complex network and the interactions include a phase frustration, thus preventing full synchronization. The system organizes into a regime of remote synchronization where pairs of nodes with the same network symmetry are fully synchronized, despite their distance on the graph. We provide analytical arguments to explain this result, and we show how the frustration parameter affects the distribution of phases. An application to brain networks suggests that anatomical symmetry plays a role in neural synchronization by determining correlated functional modules across distant locations.

Modeling the relationship between the environment and human experiences.

PubMed

Vink, P; Bazley, C; Jacobs, K

2016-08-12

Within this special issue, different aspects of the environment are studied: aspects that are distant from the human body, close to the body and touching the human body. Consequently, different human senses are involved in these studies as well as the different consequences and effects on the brain and human behaviour. This special issue also highlights many remaining questions about the effects and relationships between environments and human beings and the need for more studies and research. In particular, future studies are needed that address long-term effects and the effects of the combinations of elements which provide comfort or discomfort.

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.

Regional rat brain noradrenaline turnover in response to restraint stress.

PubMed

Glavin, G B; Tanaka, M; Tsuda, A; Kohno, Y; Hoaki, Y; Nagasaki, N

1983-08-01

Male Wistar rats were starved for 12 hr and then subjected to either 2 hr of wire mesh "envelope" restraint at room temperature; 2 hr of supine restraint in a specially constructed harness at room temperature or were not restrained. Eight brain regions were examined for NA level and the level of its major metabolite, MHPG-SO4. Plasma corticosterone and gastric ulcer incidence were also measured. All restrained rats displayed marked elevations in MHPG-SO4 levels in most brain regions. In addition, several brain regions in restrained animals showed a reduction in NA level. All restrained rats showed elevated plasma corticosterone levels and evidence of gastric lesions. In general, supine restraint produced greater alterations in regional brain NA turnover, greater evidence of ulcer disease, and higher plasma corticosterone levels than did wire mesh restraint. These data suggest that acute but intense stress in the form of restraint causes markedly altered brain NA activity--a possible neurochemical mechanism underlying the phenomenon of stress-induced disease.

Regional deficiencies in chaperone-mediated autophagy underlie α-synuclein aggregation and neurodegeneration

PubMed Central

Malkus, Kristen A.; Ischiropoulos, Harry

2012-01-01

In neurodegenerative diseases, it remains unclear why certain brain regions are selectively vulnerable to protein aggregation. In transgenic mice expressing human A53T α-synuclein, the brainstem and spinal cord develop the most prominent α-synuclein inclusions which correlate with age-dependent motor dysfunction. Herein we present the novel finding that this selective aggregation is in part dependent on the inability of chaperone-mediated autophagy (CMA) to effectively degrade α-synuclein in these brain regions. Lysosomal assays revealed that CMA activity was significantly decreased in aggregation-prone regions compared to the remainder of the brain. Previously, CMA activity has been shown to be proportional to levels of the CMA receptor Lamp-2a. Using antibodies, brain tissue from Lamp-2a null mice, enzymatic deglycosylation, and mass spectrometry, we identified Lamp2a as a novel 72 kDa glycoprotein in the mouse brain. Examination of Lamp-2a levels revealed differences in expression across brain regions. The brainstem and the spinal cord had a more than three-fold greater levels of Lamp-2a as compared to regions less vulnerable to aggregation and exhibited a selective upregulation of Lamp-2a during development of α-synuclein inclusions. Despite this dynamic response of Lamp-2a, the levels of substrates bound to the brain lysosomes as well as the rates of substrate uptake and degradation were not proportional to the levels of Lamp-2a. These regional differences in CMA activity and Lamp-2a expression were found in both non-transgenic mice as well as A53T α-syn mice. Therefore, these are inherent variations and not a transgene-specific effect. However, differences in CMA activity may render select brain regions vulnerable to homeostatic dysfunction in the presence of stressors such as overexpression of human A53T α-syn. Collectively, the data provide a potential mechanism to explain the dichotomy of vulnerability or resistance that underlies brain regions during aggregate formation in neurodegenerative disease. PMID:22426402

Effect of bupropion treatment on brain activation induced by cigarette-related cues in smokers.

PubMed

Culbertson, Christopher S; Bramen, Jennifer; Cohen, Mark S; London, Edythe D; Olmstead, Richard E; Gan, Joanna J; Costello, Matthew R; Shulenberger, Stephanie; Mandelkern, Mark A; Brody, Arthur L

2011-05-01

Nicotine-dependent smokers exhibit craving and brain activation in the prefrontal and limbic regions when presented with cigarette-related cues. Bupropion hydrochloride treatment reduces cue-induced craving in cigarette smokers; however, the mechanism by which bupropion exerts this effect has not yet been described. To assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo). Randomized, double-blind, before-after controlled trial. Academic brain imaging center. Thirty nicotine-dependent smokers (paid volunteers). Participants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind). Subjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos. Bupropion-treated participants reported less craving and exhibited reduced activation in the left ventral striatum, right medial orbitofrontal cortex, and bilateral anterior cingulate cortex from before to after treatment when actively resisting craving compared with placebo-treated participants. When resisting craving, reduction in self-reported craving correlated with reduced regional brain activation in the bilateral medial orbitofrontal and left anterior cingulate cortices in all participants. Treatment with bupropion is associated with improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions, while a reduction in craving, regardless of treatment type, is associated with reduced activation in prefrontal brain regions.

Cortical Oscillatory Mechanisms Supporting the Control of Human Social-Emotional Actions.

PubMed

Bramson, Bob; Jensen, Ole; Toni, Ivan; Roelofs, Karin

2018-06-20

The human anterior prefrontal cortex (aPFC) is involved in regulating social-emotional behavior, presumably by modulating effective connectivity with downstream parietal, limbic, and motor cortices. Regulating that connectivity might rely on theta-band oscillations (4-8 Hz), a brain rhythm known to create overlapping periods of excitability between distant regions by temporally releasing neurons from inhibition. Here, we used MEG to understand how aPFC theta-band oscillations implement control over prepotent social-emotional behaviors; that is, the control over automatically elicited approach and avoidance actions. Forty human male participants performed a social approach-avoidance task in which they approached or avoided visually displayed emotional faces (happy or angry) by pulling or pushing a joystick. Approaching angry and avoiding happy faces (incongruent condition) requires rapid application of cognitive control to override prepotent habitual action tendencies to approach appetitive and to avoid aversive situations. In the time window before response delivery, trial-by-trial variations in aPFC theta-band power (6 Hz) predicted reaction time increases during emotional control and were inversely related to beta-band power (14-22 Hz) over parietofrontal cortex. In sensorimotor areas contralateral to the moving hand, premovement gamma-band rhythms (60-90 Hz) were stronger during incongruent than congruent trials, with power increases phase locked to peaks of the aPFC theta-band oscillations. These findings define a mechanistic relation between cortical areas involved in implementing rapid control over human social-emotional behavior. The aPFC may bias neural processing toward rule-driven actions and away from automatic emotional tendencies by coordinating tonic disinhibition and phasic enhancement of parietofrontal circuits involved in action selection. SIGNIFICANCE STATEMENT Being able to control social-emotional behavior is crucial for successful participation in society, as is illustrated by the severe social and occupational difficulties experienced by people suffering from social motivational disorders such as social anxiety. In this study, we show that theta-band oscillations in the anterior prefrontal cortex (aPFC), which are thought to provide temporal organization for neural firing during communication between distant brain areas, facilitate this control by linking aPFC to parietofrontal beta-band and sensorimotor gamma-band oscillations involved in action selection. These results contribute to a mechanistic understanding of cognitive control over automatic social-emotional action and point to frontal theta-band oscillations as a possible target of rhythmic neurostimulation techniques during treatment for social anxiety. Copyright © 2018 the authors 0270-6474/18/385739-11$15.00/0.

History of Chandra X-Ray Observatory

NASA Image and Video Library

2000-10-01

This most distant x-ray cluster of galaxies yet has been found by astronomers using Chandra X-ray Observatory (CXO). Approximately 10 billion light-years from Earth, the cluster 3C294 is 40 percent farther than the next most distant x-ray galaxy cluster. The existence of such a faraway cluster is important for understanding how the universe evolved. CXO's image reveals an hourglass-shaped region of x-ray emissions centered on the previously known central radio source (seen in this image as the blue central object) that extends outward for 60,000 light- years. The vast clouds of hot gas that surround such galaxies in clusters are thought to be heated by collapse toward the center of the cluster. Until CXO, x-ray telescopes have not had the needed sensitivity to identify such distant clusters of galaxies. Galaxy clusters are the largest gravitationally bound structures in the universe. The intensity of the x-rays in this CXO image of 3C294 is shown as red for low energy x-rays, green for intermediate, and blue for the most energetic x-rays. (Photo credit: NASA/loA/A. Fabian et al)

Extrinsic Origins of the Somatostatin and Neuropeptide Y innervation of the Rat Basolateral Amygdala

PubMed Central

McDonald, Alexander J.; Zaric, Violeta

2015-01-01

The amygdalar basolateral nuclear complex (BLC) is a cortex-like structure that receives inputs from many cortical areas. It has long been assumed that cortico-amygdalar projections, as well as inter-areal intracortical connections, arise from cortical pyramidal cells. However, recent studies have shown that GABAergic long-range nonpyramidal neurons (LRNP neurons) in the cortex also contribute to inter-areal connections. The present study combined Fluorogold (FG) retrograde tract tracing with immunohistochemistry for cortical nonpyramidal neuronal markers to determine if cortical LRNP neurons project to the BLC in the rat. Injections of FG into the BLC produced widespread retrograde labeling in the cerebral hemispheres and diencephalon. Triple-labeling for FG, somatostatin (SOM), and neuropeptide Y (NPY) revealed a small number of FG+/SOM+/NPY+ neurons and FG+/SOM+/NPY− neurons in the lateral entorhinal area, amygdalopiriform transition area, and piriform cortex, but not in the prefrontal and insular cortices, or in the diencephalon. In addition, FG+/SOM+/NPY+ neurons were observed in the amygdalostriatal transition area and in a zone surrounding the intercalated nuclei. About half of the SOM+ neurons in the lateral entorhinal area labeled by FG were GABA+. FG+ neurons containing parvalbumin were only seen in the basal forebrain, and no FG+ neurons containing vasoactive intestinal peptide were observed in any brain region. Since LRNP neurons involved in corticocortical connections are critical for synchronous oscillations that allow temporal coordination between distant cortical regions, the LRNP neurons identified in this study may play a role in the synchronous oscillations of the BLC and hippocampal region that are involved in the retrieval of fear memories. PMID:25769940

Potential surrogate endpoints for prostate cancer survival: analysis of a phase III randomized trial.

PubMed

Ray, Michael E; Bae, Kyounghwa; Hussain, Maha H A; Hanks, Gerald E; Shipley, William U; Sandler, Howard M

2009-02-18

The identification of surrogate endpoints for prostate cancer-specific survival may shorten the length of clinical trials for prostate cancer. We evaluated distant metastasis and general clinical treatment failure as potential surrogates for prostate cancer-specific survival by use of data from the Radiation Therapy and Oncology Group 92-02 randomized trial. Patients (n = 1554 randomly assigned and 1521 evaluable for this analysis) with locally advanced prostate cancer had been treated with 4 months of neoadjuvant and concurrent androgen deprivation therapy with external beam radiation therapy and then randomly assigned to no additional therapy (control arm) or 24 additional months of androgen deprivation therapy (experimental arm). Data from landmark analyses at 3 and 5 years for general clinical treatment failure (defined as documented local disease progression, regional or distant metastasis, initiation of androgen deprivation therapy, or a prostate-specific antigen level of 25 ng/mL or higher after radiation therapy) and/or distant metastasis were tested as surrogate endpoints for prostate cancer-specific survival at 10 years by use of Prentice's four criteria. All statistical tests were two-sided. At 3 years, 1364 patients were alive and contributed data for analysis. Both distant metastasis and general clinical treatment failure at 3 years were consistent with all four of Prentice's criteria for being surrogate endpoints for prostate cancer-specific survival at 10 years. At 5 years, 1178 patients were alive and contributed data for analysis. Although prostate cancer-specific survival was not statistically significantly different between treatment arms at 5 years (P = .08), both endpoints were consistent with Prentice's remaining criteria. Distant metastasis and general clinical treatment failure at 3 years may be candidate surrogate endpoints for prostate cancer-specific survival at 10 years. These endpoints, however, must be validated in other datasets.

Omitting elective nodal irradiation during thoracic irradiation in limited-stage small cell lung cancer--evidence from a phase II trial.

PubMed

Colaco, Rovel; Sheikh, Hamid; Lorigan, Paul; Blackhall, Fiona; Hulse, Paul; Califano, Raffaele; Ashcroft, Linda; Taylor, Paul; Thatcher, Nicholas; Faivre-Finn, Corinne

2012-04-01

Omitting elective nodal irradiation (ENI) in limited-stage disease small cell lung cancer (LD-SCLC) is expected to result in smaller radiation fields. We report on data from a randomised phase II trial that omitted ENI in patients receiving concurrent chemo-radiotherapy for LD-SCLC. 38 patients with LD-SCLC were randomised to receive once-daily (66 Gy in 33 fractions) or twice-daily (45 Gy in 30 fractions) radiotherapy (RT). 3D-conformal RT was given concurrently with cisplatin and etoposide starting with the second cycle of a total of four cycles. The gross tumour volume was defined as primary tumour with involved lymph nodes (nodes ≥1 cm in short axis) identifiable with CT imaging. ENI was not used. Six recurrence patterns were identified: recurrence within planning target volume (PTV) only, recurrence within PTV+regional nodal recurrence and/or distant recurrence, isolated nodal recurrence outside PTV, nodal recurrence outside PTV+distant recurrence, distant metastases only and no recurrence. At median follow-up 16.9 months, 31/38 patients were evaluable and 14/31 patients had relapsed. There were no isolated nodal recurrences. Eight patients relapsed with intra-thoracic disease: 2 within PTV only, 4 within PTV and distantly and 2 with nodal recurrence outside PTV plus distant metastases. Rates of grade 3+ acute oesophagitis and pneumonitis in the 31 evaluable patients were 23 and 3% respectively. In our study of LD-SCLC, omitting ENI based on CT imaging was not associated with a high risk of isolated nodal recurrence, although further prospective studies are needed to confirm this. Routine ENI omission will be further evaluated prospectively in the ongoing phase III CONVERT trial (NCT00433563). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer.

PubMed

Cheng, Skye Hung-Chun; Huang, Tzu-Ting; Cheng, Yu-Hao; Tan, Tee Benita Kiat; Horng, Chen-Fang; Wang, Yong Alison; Brian, Nicholas Shannon; Shih, Li-Sun; Yu, Ben-Long

2017-01-01

We validated an 18-gene classifier (GC) initially developed to predict local/regional recurrence after mastectomy in estimating distant metastasis risk. The 18-gene scoring algorithm defines scores as: <21, low risk; ≥21, high risk. Six hundred eighty-three patients with primary operable breast cancer and fresh frozen tumor tissues available were included. The primary outcome was the 5-year probability of freedom from distant metastasis (DMFP). Two external datasets were used to test the predictive accuracy of 18-GC. The 5-year rates of DMFP for patients classified as low-risk (n = 146, 21.7%) and high-risk (n = 537, 78.6%) were 96.2% (95% CI, 91.1%-98.8%) and 80.9% (74.6%-81.9%), respectively (median follow-up interval, 71.8 months). The 5-year rates of DMFP of the low-risk group in stage I (n = 62, 35.6%), stage II (n = 66, 20.1%), and stage III (n = 18, 10.3%) were 100%, 94.2% (78.5%-98.5%), and 90.9% (50.8%-98.7%), respectively. Multivariate analysis revealed that 18-GC is an independent prognostic factor of distant metastasis (adjusted hazard ratio, 5.1; 95% CI, 1.8-14.1; p = 0.0017) for scores of ≥21. External validation showed that the 5-year rate of DMFP in the low- and high-risk patients was 94.1% (82.9%-100%) and 80.3% (70.7%-89.9%, p = 0.06) in a Singapore dataset, and 89.5% (81.9%-94.1%) and 73.6% (67.2%-79.0%, p = 0.0039) in the GEO-GSE20685 dataset, respectively. In conclusion, 18-GC is a viable prognostic biomarker for breast cancer to estimate distant metastasis risk.

Survival Outcomes and Patterns of Recurrence in Patients with Stage III or IV Oropharyngeal Cancer Treated with Primary Surgery or Radiotherapy.

PubMed

Debenham, Brock J; Banerjee, Robyn; Warkentin, Heather; Ghosh, Sunita; Scrimger, Rufus; Jha, Naresh; Parliament, Matthew

2016-07-26

To compare and contrast the patterns of failure in patients with locally advanced squamous cell oropharyngeal cancers undergoing curative-intent treatment with primary surgery or radiotherapy +/- chemotherapy. Two hundred and thirty-three patients with stage III or IV oropharyngeal squamous cell carcinoma who underwent curative-intent treatment from 2006-2012, were reviewed. The median length of follow-up for patients still alive at the time of analysis was 4.4 years. Data was collected retrospectively from a chart review. One hundred and thirty-nine patients underwent primary surgery +/- adjuvant therapy, and 94 patients underwent primary radiotherapy +/- chemotherapy (CRT). Demographics were similar between the two groups, except primary radiotherapy patients had a higher age-adjusted Charleston co-morbidity score (CCI). Twenty-nine patients from the surgery group recurred; 15 failed distantly only, seven failed locoregionally, and seven failed both distantly and locoregionally. Twelve patients recurred who underwent chemoradiotherapy; ten distantly alone, and two locoregionally. One patient who underwent radiotherapy (RT) alone failed distantly. Two and five-year recurrence-free survival rates for patients undergoing primary RT were 86.6% and 84.9% respectively. Two and five-year recurrence-free survival rates for primary surgery was 80.9% and 76.3% respectively (p=0.21). There was no significant difference in either treatment when they were stratified by p16 status or smoking status. Our analysis does not show any difference in outcomes for patients treated with primary surgery or radiotherapy. Although the primary pattern of failure in both groups was distant metastatic disease, some local failures may be preventable with careful delineation of target volumes, especially near the base of skull region.

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.

Morphological brain measures of cortico-limbic inhibition related to resilience.

PubMed

Gupta, Arpana; Love, Aubrey; Kilpatrick, Lisa A; Labus, Jennifer S; Bhatt, Ravi; Chang, Lin; Tillisch, Kirsten; Naliboff, Bruce; Mayer, Emeran A

2017-09-01

Resilience is the ability to adequately adapt and respond to homeostatic perturbations. Although resilience has been associated with positive health outcomes, the neuro-biological basis of resilience is poorly understood. The aim of the study was to identify associations between regional brain morphology and trait resilience with a focus on resilience-related morphological differences in brain regions involved in cortico-limbic inhibition. The relationship between resilience and measures of affect were also investigated. Forty-eight healthy subjects completed structural MRI scans. Self-reported resilience was measured using the Connor and Davidson Resilience Scale. Segmentation and regional parcellation of images was performed to yield a total of 165 regions. Gray matter volume (GMV), cortical thickness, surface area, and mean curvature were calculated for each region. Regression models were used to identify associations between morphology of regions belonging to executive control and emotional arousal brain networks and trait resilience (total and subscales) while controlling for age, sex, and total GMV. Correlations were also conducted between resilience scores and affect scores. Significant associations were found between GM changes in hypothesized brain regions (subparietal sulcus, intraparietal sulcus, amygdala, anterior mid cingulate cortex, and subgenual cingulate cortex) and resilience scores. There were significant positive correlations between resilience and positive affect and negative correlations with negative affect. Resilience was associated with brain morphology of regions involved in cognitive and affective processes related to cortico-limbic inhibition. Brain signatures associated with resilience may be a biomarker of vulnerability to disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Action of cholinergic poisons on the central nervous system and effectiveness of potential antidotes. Annual report 1 Jul 81-30 Jun 82

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

Samson, F.; Nelson, S.

The research aim was to determine the effects of soman, related organophosphate toxins and potential antidotes on brain regional functions in rats: The (/sup 14/C)-2-deoxyglucose procedure (2-DG) was used for mapping brain regional glucose use. Quantitative autoradiography was used for muscarinic and nicotinic cholinergic receptors. The 2-DG procedure gives a quantitative measure of glucose utilization in brain regions and is in index of the 'functional activity' in brain regions and systems. Values were determined in controls, rats with soman induced seizures, seizures induced by convulsants (DFP, strychnine, picrotoxin, pentylenetetrazol, penicillin) and soman pretreated with TAB. Brain regional cholinergic receptor mapsmore » were prepared and some regional muscarinic and nicotinic receptor densities have been quantified. Soman (112 micrograms/kg i.m.) causes strong, continuous seizures and a dramatic (2-6 fold) increase in the rate of glucose use in 10 major brain regions. Most intense increases were in septum, substants nigra reticularis and outer layer of hippcampal dendata gyrus. The overt seizures of rats induced by convulsants DFP, strychnine, picrotoxin, pentylenetetrazol and penicillin (in hippocampus) were strikingly different from that of rats with soman seizures. High doses (2X LD50) of soman in rats protected with TAB caused a 50% depression of glucose use in most brain regions. The effects of repeated soman exposure on muscarinic and nicotinic receptors are under study.« less

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

Redies, C.; Hoffer, L.J.; Beil, C.

In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone bodies, beta-hydroxybutyrate and acetoacetate, thereby reducing whole body glucose consumption. Energy substrate utilization differs regionally in the brain of fasting rat, but comparable information has hitherto been unavailable in humans. We used positron emission tomography (PET) to study regional brain glucose and oxygen metabolism, blood flow, and blood volume in four obese subjects before and after a 3-wk total fast. Whole brain glucose utilization fell to 54% of control (postabsorptive) values (P less than 0.002). The whole brain rate constant for glucose tracer phosphorylationmore » fell to 51% of control values (P less than 0.002). Both parameters decreased uniformly throughout the brain. The 2-fluoro-2-deoxy-D-glucose lumped constant decreased from a control value of 0.57 to 0.43 (P less than 0.01). Regional blood-brain barrier transfer coefficients for glucose tracer, regional oxygen utilization, blood flow, and blood volume were unchanged.« less

Lesion Analysis of the Brain Areas Involved in Language Comprehension

ERIC Educational Resources Information Center

Dronkers, Nina F.; Wilkins, David P.; Van Valin, Robert D., Jr.; Redfern, Brenda B.; Jaeger, Jeri J.

2004-01-01

The cortical regions of the brain traditionally associated with the comprehension of language are Wernicke's area and Broca's area. However, recent evidence suggests that other brain regions might also be involved in this complex process. This paper describes the opportunity to evaluate a large number of brain-injured patients to determine which…

The Association between Lifelong Greenspace Exposure and 3-Dimensional Brain Magnetic Resonance Imaging in Barcelona Schoolchildren.

PubMed

Dadvand, Payam; Pujol, Jesus; Macià, Dídac; Martínez-Vilavella, Gerard; Blanco-Hinojo, Laura; Mortamais, Marion; Alvarez-Pedrerol, Mar; Fenoll, Raquel; Esnaola, Mikel; Dalmau-Bueno, Albert; López-Vicente, Mónica; Basagaña, Xavier; Jerrett, Michael; Nieuwenhuijsen, Mark J; Sunyer, Jordi

2018-02-23

Proponents of the biophilia hypothesis believe that contact with nature, including green spaces, has a crucial role in brain development in children. Currently, however, we are not aware of evidence linking such exposure with potential effects on brain structure. We determined whether lifelong exposure to residential surrounding greenness is associated with regional differences in brain volume based on 3-dimensional magnetic resonance imaging (3D MRI) among children attending primary school. We performed a series of analyses using data from a subcohort of 253 Barcelona schoolchildren from the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) project. We averaged satellite-based normalized difference vegetation index (NDVI) across 100-m buffers around all residential addresses since birth to estimate each participant's lifelong exposure to residential surrounding greenness, and we used high-resolution 3D MRIs of brain anatomy to identify regional differences in voxel-wise brain volume associated with greenness exposure. In addition, we performed a supporting substudy to identify regional differences in brain volume associated with measures of working memory ( d' from computerized n -back tests) and inattentiveness (hit reaction time standard error from the Attentional Network Task instrument) that were repeated four times over one year. We also performed a second supporting substudy to determine whether peak voxel tissue volumes in brain regions associated with residential greenness predicted cognitive function test scores. Lifelong exposure to greenness was positively associated with gray matter volume in the left and right prefrontal cortex and in the left premotor cortex and with white matter volume in the right prefrontal region, in the left premotor region, and in both cerebellar hemispheres. Some of these regions partly overlapped with regions associated with cognitive test scores (prefrontal cortex and cerebellar and premotor white matter), and peak volumes in these regions predicted better working memory and reduced inattentiveness. Our findings from a study population of urban schoolchildren in Barcelona require confirmation, but they suggest that being raised in greener neighborhoods may have beneficial effects on brain development and cognitive function. https://doi.org/10.1289/EHP1876.

Pharmacokinetics of aniracetam and its metabolites in rat brain.

PubMed

Ogiso, T; Uchiyama, K; Suzuki, H; Yoshimoro, M; Tanino, T; Iwakai, M; Uno, S

2000-04-01

The pharmacokinetics of aniracetam (AP) and its main metabolites, 4-p-anisamidobutyric acid (ABA), 2-pyrrolidinone (PD) and p-anisic acid (AA), in 3 brain regions (cerebral cortex, hippocampus and thalamus) was investigated after single intravenous (i.v.) and oral administrations of AP to rats. AP, AA and PD were rapidly distributed into the 3 brain regions after i.v. administration of AP, but the amounts of AP were low. The concentrations of AP and AA in brain regions rapidly declined, whereas PD levels were higher and more sustained than those of AP and AA. ABA levels in the regions were below the detection limit. There were no significant differences in the distribution of these compounds in the 3 brain regions. The AUCbrain/AUCplasma ratio of PD was 53--55%, in contrast to the low ratio of AP (2.4--3.2%) and AA (3.9--4.2%). On oral administration of AP, the AUCbrain/AUCplasma ratio of PD was also higher than that of AA. When the transport of PD was tested using the in situ brain perfusion technique, it was clarified that PD was not transported across the blood-brain barrier (BBB) by a neutral amino acid carrier system. The high brain levels of PD and the low levels of AP suggest that the clinical efficacy of dosed AP may partly result from PD penetrating into the brain.

Brain functional network connectivity based on a visual task: visual information processing-related brain regions are significantly activated in the task state.

PubMed

Yang, Yan-Li; Deng, Hong-Xia; Xing, Gui-Yang; Xia, Xiao-Luan; Li, Hai-Fang

2015-02-01

It is not clear whether the method used in functional brain-network related research can be applied to explore the feature binding mechanism of visual perception. In this study, we investigated feature binding of color and shape in visual perception. Functional magnetic resonance imaging data were collected from 38 healthy volunteers at rest and while performing a visual perception task to construct brain networks active during resting and task states. Results showed that brain regions involved in visual information processing were obviously activated during the task. The components were partitioned using a greedy algorithm, indicating the visual network existed during the resting state. Z-values in the vision-related brain regions were calculated, confirming the dynamic balance of the brain network. Connectivity between brain regions was determined, and the result showed that occipital and lingual gyri were stable brain regions in the visual system network, the parietal lobe played a very important role in the binding process of color features and shape features, and the fusiform and inferior temporal gyri were crucial for processing color and shape information. Experimental findings indicate that understanding visual feature binding and cognitive processes will help establish computational models of vision, improve image recognition technology, and provide a new theoretical mechanism for feature binding in visual perception.

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.

Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain

PubMed Central

Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

2013-01-01

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain. PMID:23440889

Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain.

PubMed

Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

2013-01-01

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain.

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

Organization and hierarchy of the human functional brain network lead to a chain-like core.

PubMed

Mastrandrea, Rossana; Gabrielli, Andrea; Piras, Fabrizio; Spalletta, Gianfranco; Caldarelli, Guido; Gili, Tommaso

2017-07-07

The brain is a paradigmatic example of a complex system: its functionality emerges as a global property of local mesoscopic and microscopic interactions. Complex network theory allows to elicit the functional architecture of the brain in terms of links (correlations) between nodes (grey matter regions) and to extract information out of the noise. Here we present the analysis of functional magnetic resonance imaging data from forty healthy humans at rest for the investigation of the basal scaffold of the functional brain network organization. We show how brain regions tend to coordinate by forming a highly hierarchical chain-like structure of homogeneously clustered anatomical areas. A maximum spanning tree approach revealed the centrality of the occipital cortex and the peculiar aggregation of cerebellar regions to form a closed core. We also report the hierarchy of network segregation and the level of clusters integration as a function of the connectivity strength between brain regions.

Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

PubMed

Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

2016-07-01

Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels.

Hemispheric Asymmetry of Human Brain Anatomical Network Revealed by Diffusion Tensor Tractography

PubMed Central

Liu, Yaou; Duan, Yunyun; Li, Kuncheng

2015-01-01

The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. However, few studies have investigated the hemispheric asymmetries of the human brain from the perspective of the network model, and little is known about the asymmetries of the connection patterns of brain regions, which may reflect the functional integration and interaction between different regions. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 72 right-handed healthy adult subjects. We established the existence of structural connections between any pair of the 90 cortical and subcortical regions using deterministic tractography. To investigate the hemispheric asymmetries of the brain, statistical analyses were performed to reveal the brain regions with significant differences between bilateral topological properties, such as degree of connectivity, characteristic path length, and betweenness centrality. Furthermore, local structural connections were also investigated to examine the local asymmetries of some specific white matter tracts. From the perspective of both the global and local connection patterns, we identified the brain regions with hemispheric asymmetries. Combined with the previous studies, we suggested that the topological asymmetries in the anatomical network may reflect the functional lateralization of the human brain. PMID:26539535

Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels

PubMed Central

Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F.; Eszes, Marika; Faull, Richard L.M.; Curtis, Maurice A.; Waldvogel, Henry J.; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V.; Coppola, Giovanni; Yang, X. William

2016-01-01

Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=−0.41, p=5.5×10−8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels. PMID:27479945

Alteration of diffusion-tensor MRI measures in brain regions involved in early stages of Parkinson's disease.

PubMed

Chen, Nan-Kuei; Chou, Ying-Hui; Sundman, Mark; Hickey, Patrick; Kasoff, Willard S; Bernstein, Adam; Trouard, Theodore P; Lin, Tanya; Rapcsak, Steven Z; Sherman, Scott J; Weingarten, Carol

2018-06-07

Many non-motor symptoms (e.g., hyposmia) appear years before the cardinal motor features of Parkinson's disease (PD). It is thus desirable to be able to use noninvasive brain imaging methods, such as magnetic resonance imaging (MRI), to detect brain abnormalities in early PD stages. Among the MRI modalities, diffusion tensor imaging (DTI) is suitable for detecting changes of brain tissue structure due to neurological diseases. The main purpose of this study was to investigate whether DTI signals measured from brain regions involved in early stages of PD differ from those of healthy controls. To answer this question, we analyzed whole-brain DTI data of 30 early-stage PD patients and 30 controls using improved ROI based analysis methods. Results showed that 1) the fractional anisotropy (FA) values in the olfactory tract (connected with the olfactory bulb: one of the first structures affected by PD) are lower in PD patients than healthy controls; 2) FA values are higher in PD patients than healthy controls in the following brain regions: corticospinal tract, cingulum (near hippocampus), and superior longitudinal fasciculus (temporal part). Experimental results suggest that the tissue property, measured by FA, in olfactory regions is structurally modulated by PD with a mechanism that is different from other brain regions.

Globally conditioned Granger causality in brain–brain and brain–heart interactions: a combined heart rate variability/ultra-high-field (7 T) functional magnetic resonance imaging study

PubMed Central

Passamonti, Luca; Wald, Lawrence L.; Barbieri, Riccardo

2016-01-01

The causal, directed interactions between brain regions at rest (brain–brain networks) and between resting-state brain activity and autonomic nervous system (ANS) outflow (brain–heart links) have not been completely elucidated. We collected 7 T resting-state functional magnetic resonance imaging (fMRI) data with simultaneous respiration and heartbeat recordings in nine healthy volunteers to investigate (i) the causal interactions between cortical and subcortical brain regions at rest and (ii) the causal interactions between resting-state brain activity and the ANS as quantified through a probabilistic, point-process-based heartbeat model which generates dynamical estimates for sympathetic and parasympathetic activity as well as sympathovagal balance. Given the high amount of information shared between brain-derived signals, we compared the results of traditional bivariate Granger causality (GC) with a globally conditioned approach which evaluated the additional influence of each brain region on the causal target while factoring out effects concomitantly mediated by other brain regions. The bivariate approach resulted in a large number of possibly spurious causal brain–brain links, while, using the globally conditioned approach, we demonstrated the existence of significant selective causal links between cortical/subcortical brain regions and sympathetic and parasympathetic modulation as well as sympathovagal balance. In particular, we demonstrated a causal role of the amygdala, hypothalamus, brainstem and, among others, medial, middle and superior frontal gyri, superior temporal pole, paracentral lobule and cerebellar regions in modulating the so-called central autonomic network (CAN). In summary, we show that, provided proper conditioning is employed to eliminate spurious causalities, ultra-high-field functional imaging coupled with physiological signal acquisition and GC analysis is able to quantify directed brain–brain and brain–heart interactions reflecting central modulation of ANS outflow. PMID:27044985

Gender Differences of Brain Glucose Metabolic Networks Revealed by FDG-PET: Evidence from a Large Cohort of 400 Young Adults

PubMed Central

Li, Kai; Zhu, Hong; Qi, Rongfeng; Zhang, Zhiqiang; Lu, Guangming

2013-01-01

Background Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. Materials and Methods FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25∼45 years, mean age±SD: 40.9±3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. Results Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. Conclusion This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients. PMID:24358312

Gender differences of brain glucose metabolic networks revealed by FDG-PET: evidence from a large cohort of 400 young adults.

PubMed

Hu, Yuxiao; Xu, Qiang; Li, Kai; Zhu, Hong; Qi, Rongfeng; Zhang, Zhiqiang; Lu, Guangming

2013-01-01

Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25:45 years, mean age ± SD: 40.9 ± 3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients.

Brain in situ hybridization maps as a source for reverse-engineering transcriptional regulatory networks: Alzheimer's disease insights

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

Acquaah-Mensah, George K.; Taylor, Ronald C.

Microarray data have been a valuable resource for identifying transcriptional regulatory relationships among genes. As an example, brain region-specific transcriptional regulatory events have the potential of providing etiological insights into Alzheimer Disease (AD). However, there is often a paucity of suitable brain-region specific expression data obtained via microarrays or other high throughput means. The Allen Brain Atlas in situ hybridization (ISH) data sets (Jones et al., 2009) represent a potentially valuable alternative source of high-throughput brain region-specific gene expression data for such purposes. In this study, Allen BrainAtlasmouse ISH data in the hippocampal fields were extracted, focusing on 508 genesmore » relevant to neurodegeneration. Transcriptional regulatory networkswere learned using three high-performing network inference algorithms. Only 17% of regulatory edges from a network reverse-engineered based on brain region-specific ISH data were also found in a network constructed upon gene expression correlations inmousewhole brain microarrays, thus showing the specificity of gene expression within brain sub-regions. Furthermore, the ISH data-based networks were used to identify instructive transcriptional regulatory relationships. Ncor2, Sp3 and Usf2 form a unique three-party regulatory motif, potentially affecting memory formation pathways. Nfe2l1, Egr1 and Usf2 emerge among regulators of genes involved in AD (e.g. Dhcr24, Aplp2, Tia1, Pdrx1, Vdac1, andSyn2). Further, Nfe2l1, Egr1 and Usf2 are sensitive to dietary factors and could be among links between dietary influences and genes in the AD etiology. Thus, this approach of harnessing brain region-specific ISH data represents a rare opportunity for gleaning unique etiological insights for diseases such as AD.« less

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.

Lesions causing freezing of gait localize to a cerebellar functional network

PubMed Central

Fasano, Alfonso; Laganiere, Simon E.; Lam, Susy; Fox, Michael D.

2016-01-01

Objective Freezing of gait is a disabling symptom in Parkinson’s disease and related disorders, but the brain regions involved in symptom generation remain unclear. Here we analyze brain lesions causing acute onset freezing of gait to identify regions causally involved in symptom generation. Methods Fourteen cases of lesion-induced freezing of gait were identified from the literature and lesions were mapped to a common brain atlas. Because lesion-induced symptoms can come from sites connected to the lesion location, not just the lesion location itself, we also identified brain regions functionally connected to each lesion location. This technique, termed lesion network mapping, has been recently shown to identify regions involved in symptom generation across a variety of lesion-induced disorders. Results Lesion location was heterogeneous and no single region could be considered necessary for symptom generation. However, over 90% (13/14) of lesions were functionally connected to a focal area in the dorsal medial cerebellum. This cerebellar area overlapped previously recognized regions that are activated by locomotor tasks, termed the cerebellar locomotor region. Connectivity to this region was specific to lesions causing freezing of gait compared to lesions causing other movement disorders (hemichorea or asterixis). Interpretation Lesions causing freezing of gait are located within a common functional network characterized by connectivity to the cerebellar locomotor region. These results based on causal brain lesions complement prior neuroimaging studies in Parkinson’s disease patients, advancing our understanding of the brain regions involved in freezing of gait. PMID:28009063

Neurophysiological Basis of Multi-Scale Entropy of Brain Complexity and Its Relationship With Functional Connectivity.

PubMed

Wang, Danny J J; Jann, Kay; Fan, Chang; Qiao, Yang; Zang, Yu-Feng; Lu, Hanbing; Yang, Yihong

2018-01-01

Recently, non-linear statistical measures such as multi-scale entropy (MSE) have been introduced as indices of the complexity of electrophysiology and fMRI time-series across multiple time scales. In this work, we investigated the neurophysiological underpinnings of complexity (MSE) of electrophysiology and fMRI signals and their relations to functional connectivity (FC). MSE and FC analyses were performed on simulated data using neural mass model based brain network model with the Brain Dynamics Toolbox, on animal models with concurrent recording of fMRI and electrophysiology in conjunction with pharmacological manipulations, and on resting-state fMRI data from the Human Connectome Project. Our results show that the complexity of regional electrophysiology and fMRI signals is positively correlated with network FC. The associations between MSE and FC are dependent on the temporal scales or frequencies, with higher associations between MSE and FC at lower temporal frequencies. Our results from theoretical modeling, animal experiment and human fMRI indicate that (1) Regional neural complexity and network FC may be two related aspects of brain's information processing: the more complex regional neural activity, the higher FC this region has with other brain regions; (2) MSE at high and low frequencies may represent local and distributed information processing across brain regions. Based on literature and our data, we propose that the complexity of regional neural signals may serve as an index of the brain's capacity of information processing-increased complexity may indicate greater transition or exploration between different states of brain networks, thereby a greater propensity for information processing.

Main effect and interactions of brain regions and gender in the calculation of volumetric asymmetry indices in healthy human brains: ANCOVA analyses of in vivo 3T MRI data.

PubMed

Roldan-Valadez, Ernesto; Rios, Camilo; Suarez-May, Marcela A; Favila, Rafel; Aguilar-Castañeda, Erika

2013-12-01

Macroanatomical right-left hemispheric differences in the brain are termed asymmetries, although there is no clear information on the global influence of gender and brain-regions. The aim of this study was to evaluate the main effects and interactions of these variables on the measurement of volumetric asymmetry indices (VAIs). Forty-seven healthy young-adult volunteers (23 males, 24 females) agreed to undergo brain magnetic resonance imaging in a 3T scanner. Image post processing using voxel-based volumetry allowed the calculation of 54 VAIs from the frontal, temporal, parietal and occipital lobes, limbic system, basal ganglia, and cerebellum for each cerebral hemisphere. Multivariate ANCOVA analysis calculated the main effects and interactions on VAIs of gender and brain regions controlling the effect of age. The only significant finding was the main effect of brain regions (F (6, 9373.605) 44.369, P < .001; partial η2 = .101, and power of 1.0), with no significant interaction between gender and brain regions (F (6, 50.517) .239, P = .964). Volumetric asymmetries are present across all brain regions, with larger values found in the limbic system and parietal lobe. The absence of a significant influence of gender and age in the evaluation of the numerous measurements generated by multivariate analyses in this study should not discourage researchers to report and interpret similar results, as this topic still deserves further assessment. Copyright © 2013 Wiley Periodicals, Inc.

Hubble’s cross-section of the cosmos

NASA Image and Video Library

2014-04-17

This new Hubble image showcases a remarkable variety of objects at different distances from us, extending back over halfway to the edge of the observable Universe. The galaxies in this image mostly lie about five billion light-years from Earth but the field also contains other objects, both significantly closer and far more distant. Studies of this region of the sky have shown that many of the objects that appear to lie close together may actually be billions of light-years apart. This is because several groups of galaxies lie along our line of sight, creating something of an optical illusion. Hubble’s cross-section of the Universe is completed by distorted images of galaxies in the very distant background. These objects are sometimes distorted due to a process called gravitational lensing, an extremely valuable technique in astronomy for studying very distant objects [1]. This lensing is caused by the bending of the space-time continuum by massive galaxies lying close to our line of sight to distant objects. One of the lens systems visible here is called CLASS B1608+656, which appears as a small loop in the centre of the image. It features two foreground galaxies distorting and amplifying the light of a distant quasar the known as QSO-160913+653228. The light from this bright disc of matter, which is currently falling into a black hole, has taken nine billion years to reach us — two thirds of the age of the Universe. As well as CLASS B1608+656, astronomers have identified two other gravitational lenses within this image. Two galaxies, dubbed Fred and Ginger by the researchers who studied them, contain enough mass to visibly distort the light from objects behind them. Fred, also known more prosaically as [FMK2006] ACS J160919+6532, lies near the lens galaxies in CLASS B1608+656, while Ginger ([FMK2006] ACS J160910+6532) is markedly closer to us. Despite their different distances from us, both can be seen near to CLASS B1608+656 in the central region of this Hubble image. To capture distant and dim objects like these, Hubble required a long exposure. The image is made up of visible and infrared observations with a total exposure time of 14 hours. More info: www.spacetelescope.org/news/heic1408/ Credit: NASA/ESA/Hubble NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Functional atlas of the awake rat brain: A neuroimaging study of rat brain specialization and integration.

PubMed

Ma, Zhiwei; Perez, Pablo; Ma, Zilu; Liu, Yikang; Hamilton, Christina; Liang, Zhifeng; Zhang, Nanyin

2018-04-15

Connectivity-based parcellation approaches present an innovative method to segregate the brain into functionally specialized regions. These approaches have significantly advanced our understanding of the human brain organization. However, parallel progress in animal research is sparse. Using resting-state fMRI data and a novel, data-driven parcellation method, we have obtained robust functional parcellations of the rat brain. These functional parcellations reveal the regional specialization of the rat brain, which exhibited high within-parcel homogeneity and high reproducibility across animals. Graph analysis of the whole-brain network constructed based on these functional parcels indicates that the rat brain has a topological organization similar to humans, characterized by both segregation and integration. Our study also provides compelling evidence that the cingulate cortex is a functional hub region conserved from rodents to humans. Together, this study has characterized the rat brain specialization and integration, and has significantly advanced our understanding of the rat brain organization. In addition, it is valuable for studies of comparative functional neuroanatomy in mammalian brains. Copyright © 2016 Elsevier Inc. All rights reserved.

Social representations and contextual adjustments as two distinct components of the Theory of Mind brain network: Evidence from the REMICS task.

PubMed

Lavoie, Marie-Audrey; Vistoli, Damien; Sutliff, Stephanie; Jackson, Philip L; Achim, Amélie M

2016-08-01

Theory of mind (ToM) refers to the ability to infer the mental states of others. Behavioral measures of ToM usually present information about both a character and the context in which this character is placed, and these different pieces of information can be used to infer the character's mental states. A set of brain regions designated as the ToM brain network is recognized to support (ToM) inferences. Different brain regions within that network could however support different ToM processes. This functional magnetic resonance imaging (fMRI) study aimed to distinguish the brain regions supporting two aspects inherent to many ToM tasks, i.e., the ability to infer or represent mental states and the ability to use the context to adjust these inferences. Nineteen healthy subjects were scanned during the REMICS task, a novel task designed to orthogonally manipulate mental state inferences (as opposed to physical inferences) and contextual adjustments of inferences (as opposed to inferences that do not require contextual adjustments). We observed that mental state inferences and contextual adjustments, which are important aspects of most behavioral ToM tasks, rely on distinct brain regions or subregions within the classical brain network activated in previous ToM research. Notably, an interesting dissociation emerged within the medial prefrontal cortex (mPFC) and temporo-parietal junctions (TPJ) such that the inferior part of these brain regions responded to mental state inferences while the superior part of these brain regions responded to the requirement for contextual adjustments. This study provides evidence that the overall set of brain regions activated during ToM tasks supports different processes, and highlights that cognitive processes related to contextual adjustments have an important role in ToM and should be further studied. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of brain regions predicting epileptogenesis by serial [18F]GE-180 positron emission tomography imaging of neuroinflammation in a rat model of temporal lobe epilepsy.

PubMed

Russmann, Vera; Brendel, Matthias; Mille, Erik; Helm-Vicidomini, Angela; Beck, Roswitha; Günther, Lisa; Lindner, Simon; Rominger, Axel; Keck, Michael; Salvamoser, Josephine D; Albert, Nathalie L; Bartenstein, Peter; Potschka, Heidrun

2017-01-01

Excessive activation of inflammatory signaling pathways seems to be a hallmark of epileptogenesis. Positron emission tomography (PET) allows in vivo detection of brain inflammation with spatial information and opportunities for longitudinal follow-up scanning protocols. Here, we assessed whether molecular imaging of the 18 kDa translocator protein (TSPO) can serve as a biomarker for the development of epilepsy. Therefore, brain uptake of [ 18 F]GE-180, a highly selective radioligand of TSPO, was investigated in a longitudinal PET study in a chronic rat model of temporal lobe epilepsy. Analyses revealed that the influence of the epileptogenic insult on [ 18 F]GE-180 brain uptake was most pronounced in the earlier phase of epileptogenesis. Differences were evident in various brain regions during earlier phases of epileptogenesis with [ 18 F]GE-180 standardized uptake value enhanced by 2.1 to 2.7fold. In contrast, brain regions exhibiting differences seemed to be more restricted with less pronounced increases of tracer uptake by 1.8-2.5fold four weeks following status epilepticus and by 1.5-1.8fold in the chronic phase. Based on correlation analysis, we were able to identify regions with a predictive value showing a correlation with seizure development. These regions include the amygdala as well as a cluster of brain areas. This cluster comprises parts of different brain regions, e.g. the hippocampus, parietal cortex, thalamus, and somatosensory cortex. In conclusion, the data provide evidence that [ 18 F]GE-180 PET brain imaging can serve as a biomarker of epileptogenesis. The identification of brain regions with predictive value might facilitate the development of preventive concepts as well as the early assessment of the interventional success. Future studies are necessary to further confirm the predictivity of the approach.

Abnormalities in Structural Covariance of Cortical Gyrification in Parkinson's Disease.

PubMed

Xu, Jinping; Zhang, Jiuquan; Zhang, Jinlei; Wang, Yue; Zhang, Yanling; Wang, Jian; Li, Guanglin; Hu, Qingmao; Zhang, Yuanchao

2017-01-01

Although abnormal cortical morphology and connectivity between brain regions (structural covariance) have been reported in Parkinson's disease (PD), the topological organizations of large-scale structural brain networks are still poorly understood. In this study, we investigated large-scale structural brain networks in a sample of 37 PD patients and 34 healthy controls (HC) by assessing the structural covariance of cortical gyrification with local gyrification index (lGI). We demonstrated prominent small-world properties of the structural brain networks for both groups. Compared with the HC group, PD patients showed significantly increased integrated characteristic path length and integrated clustering coefficient, as well as decreased integrated global efficiency in structural brain networks. Distinct distributions of hub regions were identified between the two groups, showing more hub regions in the frontal cortex in PD patients. Moreover, the modular analyses revealed significantly decreased integrated regional efficiency in lateral Fronto-Insula-Temporal module, and increased integrated regional efficiency in Parieto-Temporal module in the PD group as compared to the HC group. In summary, our study demonstrated altered topological properties of structural networks at a global, regional and modular level in PD patients. These findings suggests that the structural networks of PD patients have a suboptimal topological organization, resulting in less effective integration of information between brain regions.

Differential Impact of Whole-Brain Radiotherapy Added to Radiosurgery for Brain Metastases

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

Kong, Doo-Sik; Lee, Jung-Il, E-mail: jilee@skku.ed; Im, Yong-Seok

2010-10-01

Purpose: The authors investigated whether the addition of whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) provided any therapeutic benefit according to recursive partitioning analysis (RPA) class. Methods and Materials: Two hundred forty-five patients with 1 to 10 metastases who underwent SRS between January 2002 and December 2007 were included in the study. Of those, 168 patients were treated with SRS alone and 77 patients received SRS followed by WBRT. Actuarial curves were estimated using the Kaplan-Meier method regarding overall survival (OS), distant brain control (DC), and local brain control (LC) stratified by RPA class. Analyses for known prognostic variables weremore » performed using the Cox proportional hazards model. Results: Univariate and multivariate analysis revealed that control of the primary tumor, small number of brain metastases, Karnofsky performance scale (KPS) > 70, and initial treatment modalities were significant predictors for survival. For RPA class 1, SRS plus WBRT was associated with a longer survival time compared with SRS alone (854 days vs. 426 days, p = 0.042). The SRS plus WBRT group also showed better LC rate than did the SRS-alone group (p = 0.021), although they did not show a better DC rate (p = 0.079). By contrast, for RPA class 2 or 3, no significant difference in OS, LC, or DC was found between the two groups. Conclusions: These results suggest that RPA classification should determine whether or not WBRT is added to SRS. WBRT may be recommended to be added to SRS for patients in whom long-term survival is expected on the basis of RPA classification.« less

The Ghosts of Brain States Past: Remembering Reactivates the Brain Regions Engaged during Encoding

ERIC Educational Resources Information Center

Danker, Jared F.; Anderson, John R.

2010-01-01

There is growing evidence that the brain regions involved in encoding an episode are partially reactivated when that episode is later remembered. That is, the process of remembering an episode involves literally returning to the brain state that was present during that episode. This article reviews studies of episodic and associative memory that…

Theory of Mind Performance in Children Correlates with Functional Specialization of a Brain Region for Thinking about Thoughts

ERIC Educational Resources Information Center

Gweon, Hyowon; Dodell-Feder, David; Bedny, Marina; Saxe, Rebecca

2012-01-01

Thinking about other people's thoughts recruits a specific group of brain regions, including the temporo-parietal junctions (TPJ), precuneus (PC), and medial prefrontal cortex (MPFC). The same brain regions were recruited when children (N = 20, 5-11 years) and adults (N = 8) listened to descriptions of characters' mental states, compared to…

Profound and Sexually Dimorphic Effects of Clinically-Relevant Low Dose Scatter Irradiation on the Brain and Behavior

PubMed Central

Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Yaroslav; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kolb, Bryan; Kovalchuk, Olga

2016-01-01

Irradiated cells can signal damage and distress to both close and distant neighbors that have not been directly exposed to the radiation (naïve bystanders). While studies have shown that such bystander effects occur in the shielded brain of animals upon body irradiation, their mechanism remains unexplored. Observed effects may be caused by some blood-borne factors; however they may also be explained, at least in part, by very small direct doses received by the brain that result from scatter or leakage. In order to establish the roles of low doses of scatter irradiation in the brain response, we developed a new model for scatter irradiation analysis whereby one rat was irradiated directly at the liver and the second rat was placed adjacent to the first and received a scatter dose to its body and brain. This work focuses specifically on the response of the latter rat brain to the low scatter irradiation dose. Here, we provide the first experimental evidence that very low, clinically relevant doses of scatter irradiation alter gene expression, induce changes in dendritic morphology, and lead to behavioral deficits in exposed animals. The results showed that exposure to radiation doses as low as 0.115 cGy caused changes in gene expression and reduced spine density, dendritic complexity, and dendritic length in the prefrontal cortex tissues of females, but not males. In the hippocampus, radiation altered neuroanatomical organization in males, but not in females. Moreover, low dose radiation caused behavioral deficits in the exposed animals. This is the first study to show that low dose scatter irradiation influences the brain and behavior in a sex-specific way. PMID:27375442

Effect of Bupropion Treatment on Brain Activation Induced by Cigarette-Related Cues in Smokers

PubMed Central

Culbertson, Christopher S.; Bramen, Jennifer; Cohen, Mark S.; London, Edythe D.; Olmstead, Richard E.; Gan, Joanna J.; Costello, Matthew R.; Shulenberger, Stephanie; Mandelkern, Mark A.; Brody, Arthur L.

2011-01-01

Context Nicotine-dependent smokers exhibit craving and brain activation in the prefrontal and limbic regions when presented with cigarette-related cues. Bupropion hydrochloride treatment reduces cue-induced craving in cigarette smokers; however, the mechanism by which bupropion exerts this effect has not yet been described. Objective To assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo). Design Randomized, double-blind, before-after controlled trial. Setting Academic brain imaging center. Participants Thirty nicotine-dependent smokers (paid volunteers). Interventions Participants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind). Main Outcome Measures Subjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos. Results Bupropion-treated participants reported less craving and exhibited reduced activation in the left ventral striatum, right medial orbitofrontal cortex, and bilateral anterior cingulate cortex from before to after treatment when actively resisting craving compared with placebo-treated participants. When resisting craving, reduction in self-reported craving correlated with reduced regional brain activation in the bilateral medial orbitofrontal and left anterior cingulate cortices in all participants. Conclusions Treatment with bupropion is associated with improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions, while a reduction in craving, regardless of treatment type, is associated with reduced activation in prefrontal brain regions. PMID:21199957

Mechanisms of Zero-Lag Synchronization in Cortical Motifs

PubMed Central

Gollo, Leonardo L.; Mirasso, Claudio; Sporns, Olaf; Breakspear, Michael

2014-01-01

Zero-lag synchronization between distant cortical areas has been observed in a diversity of experimental data sets and between many different regions of the brain. Several computational mechanisms have been proposed to account for such isochronous synchronization in the presence of long conduction delays: Of these, the phenomenon of “dynamical relaying” – a mechanism that relies on a specific network motif – has proven to be the most robust with respect to parameter mismatch and system noise. Surprisingly, despite a contrary belief in the community, the common driving motif is an unreliable means of establishing zero-lag synchrony. Although dynamical relaying has been validated in empirical and computational studies, the deeper dynamical mechanisms and comparison to dynamics on other motifs is lacking. By systematically comparing synchronization on a variety of small motifs, we establish that the presence of a single reciprocally connected pair – a “resonance pair” – plays a crucial role in disambiguating those motifs that foster zero-lag synchrony in the presence of conduction delays (such as dynamical relaying) from those that do not (such as the common driving triad). Remarkably, minor structural changes to the common driving motif that incorporate a reciprocal pair recover robust zero-lag synchrony. The findings are observed in computational models of spiking neurons, populations of spiking neurons and neural mass models, and arise whether the oscillatory systems are periodic, chaotic, noise-free or driven by stochastic inputs. The influence of the resonance pair is also robust to parameter mismatch and asymmetrical time delays amongst the elements of the motif. We call this manner of facilitating zero-lag synchrony resonance-induced synchronization, outline the conditions for its occurrence, and propose that it may be a general mechanism to promote zero-lag synchrony in the brain. PMID:24763382

Modulation of connexin expression and gap junction communication in astrocytes by the gram-positive bacterium S. aureus.

PubMed

Esen, Nilufer; Shuffield, Debbie; Syed, Mohsin M D; Kielian, Tammy

2007-01-01

Gap junctions establish direct intercellular conduits between adjacent cells and are formed by the hexameric organization of protein subunits called connexins (Cx). It is unknown whether the proinflammatory milieu that ensues during CNS infection with S. aureus, one of the main etiologic agents of brain abscess in humans, is capable of eliciting regional changes in astrocyte homocellular gap junction communication (GJC) and, by extension, influencing neuron homeostasis at sites distant from the primary focus of infection. Here we investigated the effects of S. aureus and its cell wall product peptidoglycan (PGN) on Cx43, Cx30, and Cx26 expression, the main Cx isoforms found in astrocytes. Both bacterial stimuli led to a time-dependent decrease in Cx43 and Cx30 expression; however, Cx26 levels were elevated following bacterial exposure. Functional examination of dye coupling, as revealed by single-cell microinjections of Lucifer yellow, demonstrated that both S. aureus and PGN inhibited astrocyte GJC. Inhibition of protein synthesis with cyclohexamide (CHX) revealed that S. aureus directly modulates, in part, Cx43 and Cx30 expression, whereas Cx26 levels appear to be regulated by a factor(s) that requires de novo protein production; however, CHX did not alter the inhibitory effects of S. aureus on astrocyte GJC. The p38 MAPK inhibitor SB202190 was capable of partially restoring the S. aureus-mediated decrease in astrocyte GJC to that of unstimulated cells, suggesting the involvement of p38 MAPK-dependent pathway(s). These findings could have important implications for limiting the long-term detrimental effects of abscess formation in the brain which may include seizures and cognitive deficits. Copyright 2006 Wiley-Liss, Inc.

Adaptive Evolution of Eel Fluorescent Proteins from Fatty Acid Binding Proteins Produces Bright Fluorescence in the Marine Environment.

PubMed

Gruber, David F; Gaffney, Jean P; Mehr, Shaadi; DeSalle, Rob; Sparks, John S; Platisa, Jelena; Pieribone, Vincent A

2015-01-01

We report the identification and characterization of two new members of a family of bilirubin-inducible fluorescent proteins (FPs) from marine chlopsid eels and demonstrate a key region of the sequence that serves as an evolutionary switch from non-fluorescent to fluorescent fatty acid-binding proteins (FABPs). Using transcriptomic analysis of two species of brightly fluorescent Kaupichthys eels (Kaupichthys hyoproroides and Kaupichthys n. sp.), two new FPs were identified, cloned and characterized (Chlopsid FP I and Chlopsid FP II). We then performed phylogenetic analysis on 210 FABPs, spanning 16 vertebrate orders, and including 163 vertebrate taxa. We show that the fluorescent FPs diverged as a protein family and are the sister group to brain FABPs. Our results indicate that the evolution of this family involved at least three gene duplication events. We show that fluorescent FABPs possess a unique, conserved tripeptide Gly-Pro-Pro sequence motif, which is not found in non-fluorescent fatty acid binding proteins. This motif arose from a duplication event of the FABP brain isoforms and was under strong purifying selection, leading to the classification of this new FP family. Residues adjacent to the motif are under strong positive selection, suggesting a further refinement of the eel protein's fluorescent properties. We present a phylogenetic reconstruction of this emerging FP family and describe additional fluorescent FABP members from groups of distantly related eels. The elucidation of this class of fish FPs with diverse properties provides new templates for the development of protein-based fluorescent tools. The evolutionary adaptation from fatty acid-binding proteins to fluorescent fatty acid-binding proteins raises intrigue as to the functional role of bright green fluorescence in this cryptic genus of reclusive eels that inhabit a blue, nearly monochromatic, marine environment.

Permeabilization of brain tissue in situ enables multiregion analysis of mitochondrial function in a single mouse brain.

PubMed

Herbst, Eric A F; Holloway, Graham P

2015-02-15

Mitochondrial function in the brain is traditionally assessed through analysing respiration in isolated mitochondria, a technique that possesses significant tissue and time requirements while also disrupting the cooperative mitochondrial reticulum. We permeabilized brain tissue in situ to permit analysis of mitochondrial respiration with the native mitochondrial morphology intact, removing the need for isolation time and minimizing tissue requirements to ∼2 mg wet weight. The permeabilized brain technique was validated against the traditional method of isolated mitochondria and was then further applied to assess regional variation in the mouse brain with ischaemia-reperfusion injuries. A transgenic mouse model overexpressing catalase within mitochondria was applied to show the contribution of mitochondrial reactive oxygen species to ischaemia-reperfusion injuries in different brain regions. This technique enhances the accessibility of addressing physiological questions in small brain regions and in applying transgenic mouse models to assess mechanisms regulating mitochondrial function in health and disease. Mitochondria function as the core energy providers in the brain and symptoms of neurodegenerative diseases are often attributed to their dysregulation. Assessing mitochondrial function is classically performed in isolated mitochondria; however, this process requires significant isolation time, demand for abundant tissue and disruption of the cooperative mitochondrial reticulum, all of which reduce reliability when attempting to assess in vivo mitochondrial bioenergetics. Here we introduce a method that advances the assessment of mitochondrial respiration in the brain by permeabilizing existing brain tissue to grant direct access to the mitochondrial reticulum in situ. The permeabilized brain preparation allows for instant analysis of mitochondrial function with unaltered mitochondrial morphology using significantly small sample sizes (∼2 mg), which permits the analysis of mitochondrial function in multiple subregions within a single mouse brain. Here this technique was applied to assess regional variation in brain mitochondrial function with acute ischaemia-reperfusion injuries and to determine the role of reactive oxygen species in exacerbating dysfunction through the application of a transgenic mouse model overexpressing catalase within mitochondria. Through creating accessibility to small regions for the investigation of mitochondrial function, the permeabilized brain preparation enhances the capacity for examining regional differences in mitochondrial regulation within the brain, as the majority of genetic models used for unique approaches exist in the mouse model. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Intensity-Modulated Radiotherapy for Sinonasal Tumors: Ghent University Hospital Update

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

Madani, Indira; Bonte, Katrien; Vakaet, Luc

2009-02-01

Purpose: To report the long-term outcome of intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between July 1998 and November 2006, 84 patients with sinonasal tumors were treated with IMRT to a median dose of 70 Gy in 35 fractions. Of the 84 patients, 73 had a primary tumor and 11 had local recurrence. The tumor histologic type was adenocarcinoma in 54, squamous cell carcinoma in 17, esthesioneuroblastoma in 9, and adenoid cystic carcinoma in 4. The tumors were located in the ethmoid sinus in 47, maxillary sinus in 19, nasal cavity in 16, and multiple sites in 2.more » Postoperative IMRT was performed in 75 patients and 9 patients received primary IMRT. Results: The median follow-up of living patients was 40 months (range, 8-106). The 5-year local control, overall survival, disease-specific survival, disease-free survival, and freedom from distant metastasis rate was 70.7%, 58.5%, 67%, 59.3%, and 82.2%, respectively. No difference was found in local control and survival between patients with primary or recurrent tumors. On multivariate analysis, invasion of the cribriform plate was significantly associated with lower local control (p = 0.0001) and overall survival (p = 0.0001). Local and distant recurrence was detected in 19 and 10 patients, respectively. Radiation-induced blindness was not observed. One patient developed Grade 3 radiation-induced retinopathy and neovascular glaucoma. Nonocular late radiation-induced toxicity comprised complete lacrimal duct stenosis in 1 patient and brain necrosis in 3 patients. Osteoradionecrosis of the maxilla and brain necrosis were detected in 1 of the 5 reirradiated patients. Conclusion: IMRT for sinonasal tumors provides low rates of radiation-induced toxicity without blindness with high local control and survival. IMRT could be considered as the treatment of choi0008.« less

From pulses to pain relief: an update on the mechanisms of rTMS-induced analgesic effects.

PubMed

Moisset, X; de Andrade, D C; Bouhassira, D

2016-05-01

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that allows cortical stimulation. Recent studies have shown that rTMS of the primary motor cortex or dorsolateral prefrontal cortex decreases pain in various pain conditions. The aim of this review was to summarize the main characteristics of rTMS-induced analgesic effects and to analyse the current data on its mechanisms of action. Medline, PubMed and Web of Science were searched for studies on the analgesic effects and mechanisms of rTMS-induced analgesic effects. Studies on epidural motor cortex stimulation (EMCS) were also included when required, as several mechanisms of action are probably shared between both techniques. Stimulation site and stimulation parameters have a major impact on rTMS-related analgesic effects. Local cortical stimulation is able to elicit changes in the functioning of distant brain areas. These modifications outlast the duration of the rTMS session and probably involve LTP-like mechanisms via its influence on glutamatergic networks. Analgesic effects seem to be correlated to restoration of normal cortical excitability in chronic pain patients and depend on pain modulatory systems, in particular endogenous opioids. Dopamine, serotonin, norepinephrine and GABAergic circuitry may also be involved in its effects, as well as rostrocaudal projections. rTMS activates brain areas distant from the stimulation site. LTP-like mechanisms, dependence on endogenous opioids and increase in concentration of neurotransmitters (monoamines, GABA) have all been implicated in its analgesic effects, although more studies are needed to fill in the still existing gaps in the understanding of its mechanisms of action. © 2015 European Pain Federation - EFIC®

Greater preference consistency during the Willingness-to-Pay task is related to higher resting state connectivity between the ventromedial prefrontal cortex and the ventral striatum.

PubMed

Mackey, Scott; Olafsson, Valur; Aupperle, Robin L; Lu, Kun; Fonzo, Greg A; Parnass, Jason; Liu, Thomas; Paulus, Martin P

2016-09-01

The significance of why a similar set of brain regions are associated with the default mode network and value-related neural processes remains to be clarified. Here, we examined i) whether brain regions exhibiting willingness-to-pay (WTP) task-related activity are intrinsically connected when the brain is at rest, ii) whether these regions overlap spatially with the default mode network, and iii) whether individual differences in choice behavior during the WTP task are reflected in functional brain connectivity at rest. Blood-oxygen-level dependent (BOLD) signal was measured by functional magnetic resonance imaging while subjects performed the WTP task and at rest with eyes open. Brain regions that tracked the value of bids during the WTP task were used as seed regions in an analysis of functional connectivity in the resting state data. The seed in the ventromedial prefrontal cortex was functionally connected to core regions of the WTP task-related network. Brain regions within the WTP task-related network, namely the ventral precuneus, ventromedial prefrontal and posterior cingulate cortex overlapped spatially with publically available maps of the default mode network. Also, those individuals with higher functional connectivity during rest between the ventromedial prefrontal cortex and the ventral striatum showed greater preference consistency during the WTP task. Thus, WTP task-related regions are an intrinsic network of the brain that corresponds spatially with the default mode network, and individual differences in functional connectivity within the WTP network at rest may reveal a priori biases in choice behavior.

Greater preference consistency during the Willingness-to-Pay task is related to higher resting state connectivity between the ventromedial prefrontal cortex and the ventral striatum

PubMed Central

Mackey, Scott; Olafsson, Valur; Aupperle, Robin; Lu, Kun; Fonzo, Greg; Parnass, Jason; Liu, Thomas; Paulus, Martin P.

2015-01-01

The significance of why a similar set of brain regions are associated with the default mode network and value-related neural processes remains to be clarified. Here, we examined i) whether brain regions exhibiting willingness-to-pay (WTP) task-related activity are intrinsically connected when the brain is at rest, ii) whether these regions overlap spatially with the default mode network, and iii) whether individual differences in choice behavior during the WTP task are reflected in functional brain connectivity at rest. Blood-oxygen-level dependent (BOLD) signal was measured by functional magnetic resonance imaging while subjects performed the WTP task and at rest with eyes open. Brain regions that tracked the value of bids during the WTP task were used as seed regions in an analysis of functional connectivity in the resting state data. The seed in the ventromedial prefrontal cortex was functionally connected to core regions of the WTP task-related network. Brain regions within the WTP task-related network, namely the ventral precuneus, ventromedial prefrontal and posterior cingulate cortex overlapped spatially with publically available maps of the default mode network. Also, those individuals with higher functional connectivity during rest between the ventromedial prefrontal cortex and the ventral striatum showed greater preference consistency during the WTP task. Thus, WTP task-related regions are an intrinsic network of the brain that corresponds spatially with the default mode network, and individual differences in functional connectivity within the WTP network at rest may reveal a priori biases in choice behavior. PMID:26271206

Common biology of craving across legal and illegal drugs - a quantitative meta-analysis of cue-reactivity brain response.

PubMed

Kühn, Simone; Gallinat, Jürgen

2011-04-01

The present quantitative meta-analysis set out to test whether cue-reactivity responses in humans differ across drugs of abuse and whether these responses constitute the biological basis of drug craving as a core psychopathology of addiction. By means of activation likelihood estimation, we investigated the concurrence of brain regions activated by cue-induced craving paradigms across studies on nicotine, alcohol and cocaine addicts. Furthermore, we analysed the concurrence of brain regions positively correlated with self-reported craving in nicotine and alcohol studies. We found direct overlap between nicotine, alcohol and cocaine cue reactivity in the ventral striatum. In addition, regions of close proximity were observed in the anterior cingulate cortex (ACC; nicotine and cocaine) and amygdala (alcohol, nicotine and cocaine). Brain regions of concurrence in drug cue-reactivity paradigms that overlapped with brain regions of concurrence in self-reported craving correlations were found in the ACC, ventral striatum and right pallidum (for alcohol). This first quantitative meta-analysis on drug cue reactivity identifies brain regions underlying nicotine, alcohol and cocaine dependency, i.e. the ventral striatum. The ACC, right pallidum and ventral striatum were related to drug cue reactivity as well as self-reported craving, suggesting that this set of brain regions constitutes the core circuit of drug craving in nicotine and alcohol addiction. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Watershed microinfarct pathology and cognition in older persons.

PubMed

Kapasi, Alifiya; Leurgans, Sue E; James, Bryan D; Boyle, Patricia A; Arvanitakis, Zoe; Nag, Sukriti; Bennett, David A; Buchman, Aron S; Schneider, Julie A

2018-05-30

Brain microinfarcts are common in aging and are associated with cognitive impairment. Anterior and posterior watershed border zones lie at the territories of the anterior, middle, and posterior cerebral arteries, and are more vulnerable to hypoperfusion than brain regions outside the watershed areas. However, little is known about microinfarcts in these regions and how they relate to cognition in aging. Participants from the Rush Memory and Aging Project, a community-based clinical-pathologic study of aging, underwent detailed annual cognitive evaluations. We examined 356 consecutive autopsy cases (mean age-at-death, 91 years [SD = 6.16]; 28% men) for microinfarcts from 3 watershed brain regions (2 anterior and 1 posterior) and 8 brain regions outside the watershed regions. Linear regression models were used to examine the association of cortical watershed microinfarcts with cognition, including global cognition and 5 cognitive domains. Microinfarcts in any region were present in 133 (37%) participants, of which 50 had microinfarcts in watershed regions. Persons with multiple microinfarcts in cortical watershed regions had lower global cognition (estimate = -0.56, standard error (SE) = 0.26, p = 0.03) and lower cognitive function in the specific domains of working memory (estimate = -0.58, SE = 0.27, p = 0.03) and visuospatial abilities (estimate = -0.57, SE = 0.27, p = 0.03), even after controlling for microinfarcts in other brain regions, demographics, and age-related pathologies. Neither the presence nor multiplicity of microinfarcts in brain regions outside the cortical watershed regions were related to global cognition or any of the 5 cognitive domains. These findings suggest that multiple microinfarcts in watershed regions contribute to age-related cognitive impairment. Copyright © 2018 Elsevier Inc. All rights reserved.

Regional brain volumes and cognition in childhood epilepsy: does size really matter?

PubMed

Zelko, Frank A; Pardoe, Heath R; Blackstone, Sarah R; Jackson, Graeme D; Berg, Anne T

2014-05-01

Recent studies have correlated neurocognitive function and regional brain volumes in children with epilepsy. We tested whether brain volume differences between children with and without epilepsy explained differences in neurocognitive function. The study sample included 108 individuals with uncomplicated non-syndromic epilepsy (NSE) and 36 healthy age- and gender-matched controls. Participants received a standardized cognitive battery. Whole brain T1-weighted MRI was obtained and volumes analyzed with FreeSurfer (TM). Total brain volume (TBV) was significantly smaller in cases. After adjustment for TBV, cases had significantly larger regional grey matter volumes for total, frontal, parietal, and precentral cortex. Cases had poorer performance on neurocognitive indices of intelligence and variability of sustained attention. In cases, TBV showed small associations with intellectual indices of verbal and perceptual ability, working memory, and overall IQ. In controls, TBV showed medium associations with working memory and variability of sustained attention. In both groups, small associations were seen between some TBV-adjusted regional brain volumes and neurocognitive indices, but not in a consistent pattern. Brain volume differences did not account for cognitive differences between the groups. Patients with uncomplicated NSE have smaller brains than controls but areas of relative grey matter enlargement. That this relative regional enlargement occurs in the context of poorer overall neurocognitive functioning suggests that it is not adaptive. However, the lack of consistent associations between case-control differences in brain volumes and cognitive functioning suggests that brain volumes have limited explanatory value for cognitive functioning in childhood epilepsy. Copyright © 2014 Elsevier B.V. All rights reserved.

An automated method measures variability in P-glycoprotein and ABCG2 densities across brain regions and brain matter.

PubMed

Kannan, Pavitra; Schain, Martin; Kretzschmar, Warren W; Weidner, Lora; Mitsios, Nicholas; Gulyás, Balázs; Blom, Hans; Gottesman, Michael M; Innis, Robert B; Hall, Matthew D; Mulder, Jan

2017-06-01

Changes in P-glycoprotein and ABCG2 densities may play a role in amyloid-beta accumulation in Alzheimer's disease. However, previous studies report conflicting results from different brain regions, without correcting for changes in vessel density. We developed an automated method to measure transporter density exclusively within the vascular space, thereby correcting for vessel density. We then examined variability in transporter density across brain regions, matter, and disease using two cohorts of post-mortem brains from Alzheimer's disease patients and age-matched controls. Changes in transporter density were also investigated in capillaries near plaques and on the mRNA level. P-glycoprotein density varied with brain region and matter, whereas ABCG2 density varied with brain matter. In temporal cortex, P-glycoprotein density was 53% lower in Alzheimer's disease samples than in controls, and was reduced by 35% in capillaries near plaque deposits within Alzheimer's disease samples. ABCG2 density was unaffected in Alzheimer's disease. No differences were detected at the transcript level. Our study indicates that region-specific changes in transporter densities can occur globally and locally near amyloid-beta deposits in Alzheimer's disease, providing an explanation for conflicting results in the literature. When differences in region and matter are accounted for, changes in density can be reproducibly measured using our automated method.

Evaluation of metabolites extraction strategies for identifying different brain regions and their relationship with alcohol preference and gender difference using NMR metabolomics.

PubMed

Wang, Jie; Zeng, Hao-Long; Du, Hongying; Liu, Zeyuan; Cheng, Ji; Liu, Taotao; Hu, Ting; Kamal, Ghulam Mustafa; Li, Xihai; Liu, Huili; Xu, Fuqiang

2018-03-01

Metabolomics generate a profile of small molecules from cellular/tissue metabolism, which could directly reflect the mechanisms of complex networks of biochemical reactions. Traditional metabolomics methods, such as OPLS-DA, PLS-DA are mainly used for binary class discrimination. Multiple groups are always involved in the biological system, especially for brain research. Multiple brain regions are involved in the neuronal study of brain metabolic dysfunctions such as alcoholism, Alzheimer's disease, etc. In the current study, 10 different brain regions were utilized for comparative studies between alcohol preferring and non-preferring rats, male and female rats respectively. As many classes are involved (ten different regions and four types of animals), traditional metabolomics methods are no longer efficient for showing differentiation. Here, a novel strategy based on the decision tree algorithm was employed for successfully constructing different classification models to screen out the major characteristics of ten brain regions at the same time. Subsequently, this method was also utilized to select the major effective brain regions related to alcohol preference and gender difference. Compared with the traditional multivariate statistical methods, the decision tree could construct acceptable and understandable classification models for multi-class data analysis. Therefore, the current technology could also be applied to other general metabolomics studies involving multi class data. Copyright © 2017 Elsevier B.V. All rights reserved.

Regional growth and atlasing of the developing human brain

PubMed Central

Makropoulos, Antonios; Aljabar, Paul; Wright, Robert; Hüning, Britta; Merchant, Nazakat; Arichi, Tomoki; Tusor, Nora; Hajnal, Joseph V.; Edwards, A. David; Counsell, Serena J.; Rueckert, Daniel

2016-01-01

Detailed morphometric analysis of the neonatal brain is required to characterise brain development and define neuroimaging biomarkers related to impaired brain growth. Accurate automatic segmentation of neonatal brain MRI is a prerequisite to analyse large datasets. We have previously presented an accurate and robust automatic segmentation technique for parcellating the neonatal brain into multiple cortical and subcortical regions. In this study, we further extend our segmentation method to detect cortical sulci and provide a detailed delineation of the cortical ribbon. These detailed segmentations are used to build a 4-dimensional spatio-temporal structural atlas of the brain for 82 cortical and subcortical structures throughout this developmental period. We employ the algorithm to segment an extensive database of 420 MR images of the developing brain, from 27 to 45 weeks post-menstrual age at imaging. Regional volumetric and cortical surface measurements are derived and used to investigate brain growth and development during this critical period and to assess the impact of immaturity at birth. Whole brain volume, the absolute volume of all structures studied, cortical curvature and cortical surface area increased with increasing age at scan. Relative volumes of cortical grey matter, cerebellum and cerebrospinal fluid increased with age at scan, while relative volumes of white matter, ventricles, brainstem and basal ganglia and thalami decreased. Preterm infants at term had smaller whole brain volumes, reduced regional white matter and cortical and subcortical grey matter volumes, and reduced cortical surface area compared with term born controls, while ventricular volume was greater in the preterm group. Increasing prematurity at birth was associated with a reduction in total and regional white matter, cortical and subcortical grey matter volume, an increase in ventricular volume, and reduced cortical surface area. PMID:26499811

Regional growth and atlasing of the developing human brain.

PubMed

Makropoulos, Antonios; Aljabar, Paul; Wright, Robert; Hüning, Britta; Merchant, Nazakat; Arichi, Tomoki; Tusor, Nora; Hajnal, Joseph V; Edwards, A David; Counsell, Serena J; Rueckert, Daniel

2016-01-15

Detailed morphometric analysis of the neonatal brain is required to characterise brain development and define neuroimaging biomarkers related to impaired brain growth. Accurate automatic segmentation of neonatal brain MRI is a prerequisite to analyse large datasets. We have previously presented an accurate and robust automatic segmentation technique for parcellating the neonatal brain into multiple cortical and subcortical regions. In this study, we further extend our segmentation method to detect cortical sulci and provide a detailed delineation of the cortical ribbon. These detailed segmentations are used to build a 4-dimensional spatio-temporal structural atlas of the brain for 82 cortical and subcortical structures throughout this developmental period. We employ the algorithm to segment an extensive database of 420 MR images of the developing brain, from 27 to 45weeks post-menstrual age at imaging. Regional volumetric and cortical surface measurements are derived and used to investigate brain growth and development during this critical period and to assess the impact of immaturity at birth. Whole brain volume, the absolute volume of all structures studied, cortical curvature and cortical surface area increased with increasing age at scan. Relative volumes of cortical grey matter, cerebellum and cerebrospinal fluid increased with age at scan, while relative volumes of white matter, ventricles, brainstem and basal ganglia and thalami decreased. Preterm infants at term had smaller whole brain volumes, reduced regional white matter and cortical and subcortical grey matter volumes, and reduced cortical surface area compared with term born controls, while ventricular volume was greater in the preterm group. Increasing prematurity at birth was associated with a reduction in total and regional white matter, cortical and subcortical grey matter volume, an increase in ventricular volume, and reduced cortical surface area. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan.

PubMed

Nomi, Jason S; Bolt, Taylor S; Ezie, C E Chiemeka; Uddin, Lucina Q; Heller, Aaron S

2017-05-31

Variability of neuronal responses is thought to underlie flexible and optimal brain function. Because previous work investigating BOLD signal variability has been conducted within task-based fMRI contexts on adults and older individuals, very little is currently known regarding regional changes in spontaneous BOLD signal variability in the human brain across the lifespan. The current study used resting-state fMRI data from a large sample of male and female human participants covering a wide age range (6-85 years) across two different fMRI acquisition parameters (TR = 0.645 and 1.4 s). Variability in brain regions including a key node of the salience network (anterior insula) increased linearly across the lifespan across datasets. In contrast, variability in most other large-scale networks decreased linearly over the lifespan. These results demonstrate unique lifespan trajectories of BOLD variability related to specific regions of the brain and add to a growing literature demonstrating the importance of identifying normative trajectories of functional brain maturation. SIGNIFICANCE STATEMENT Although brain signal variability has traditionally been considered a source of unwanted noise, recent work demonstrates that variability in brain signals during task performance is related to brain maturation in old age as well as individual differences in behavioral performance. The current results demonstrate that intrinsic fluctuations in resting-state variability exhibit unique maturation trajectories in specific brain regions and systems, particularly those supporting salience detection. These results have implications for investigations of brain development and aging, as well as interpretations of brain function underlying behavioral changes across the lifespan. Copyright © 2017 the authors 0270-6474/17/375539-10$15.00/0.

Reduced activities of thiamine-dependent and cytochrome c oxidase enzymes in cerebral cortex of cattle affected by sulfur-induced polioencephalomalacia

PubMed Central

Amat, Samat; Hendrick, Steve; Moshynskyy, Igor; Simko, Elemir

2017-01-01

Sulfur-induced polioencephalomalacia (PEM) is an important disease affecting cattle in certain geographical regions. However, the pathogenesis of brain damage is not completely understood. We previously observed that excess dietary sulfur may influence thiamine status and altered thiamine metabolism may be involved in the pathogenesis of sulfur-induced PEM in cattle. In this study, we evaluated the activities of thiamine-dependent enzymes [α-ketogluterate dehydrogenase (α-KGDH) and pyruvate dehydrogenase (PDH)] and cytochrome c oxidase (COX) in the cerebral cortex of sulfur-induced PEM-affected cattle (n = 9) and clinically normal cattle (n = 8, each group) exposed to low or high dietary sulfur [LS = 0.30% versus HS = 0.67% sulfur on a dry matter (DM) basis]. Enzyme activities in PEM brains were measured from the brain tissue regions and examined using ultraviolent (UV) light illumination to show fluorescence or non-fluorescence regions. No gross changes under regular or UV light, or histopathological changes indicative of PEM were detected in the brains of cattle exposed to LS or HS diets. The PDH, α-KGDH, and COX activities did not differ between LS and HS brains, but all enzymes showed significantly lower (P < 0.05) activities in UV-positive region of PEM brains compared with LS and HS brains. The UV-negative regions of PEM brain had similar PDH activities to LS and HS brains, but the activities of α-KGDH and COX were significantly lower than in LS and HS brains. The results of this study suggest that reduced enzyme activities of brain PHD, α-KGDH, and COX are associated with the pathogenesis of sulfur-induced PEM. PMID:29081580

The effect of education on regional brain metabolism and its functional connectivity in an aged population utilizing positron emission tomography.

PubMed

Kim, Jaeik; Chey, Jeanyung; Kim, Sang-Eun; Kim, Hoyoung

2015-05-01

Education involves learning new information and acquiring cognitive skills. These require various cognitive processes including learning, memory, and language. Since cognitive processes activate associated brain areas, we proposed that the brains of elderly people with longer education periods would show traces of repeated activation as increased synaptic connectivity and capillary in brain areas involved in learning, memory, and language. Utilizing positron emission topography (PET), this study examined the effect of education in the human brain utilizing the regional cerebral glucose metabolism rates (rCMRglcs). 26 elderly women with high-level education (HEG) and 26 with low-level education (LEG) were compared with regard to their regional brain activation and association between the regions. Further, graphical theoretical analysis using rCMRglcs was applied to examine differences in the functional network properties of the brain. The results showed that the HEG had higher rCMRglc in the ventral cerebral regions that are mainly involved in memory, language, and neurogenesis, while the LEG had higher rCMRglc in apical areas of the cerebrum mainly involved in motor and somatosensory functions. Functional connectivity investigated with graph theoretical analysis illustrated that the brain of the HEG compared to those of the LEG were overall more efficient, more resilient, and characterized by small-worldness. This may be one of the brain's mechanisms mediating the reserve effects found in people with higher education. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Global loss of acetylcholinesterase activity with mitochondrial complexes inhibition and inflammation in brain of hypercholesterolemic mice.

PubMed

Paul, Rajib; Borah, Anupom

2017-12-20

There exists an intricate relationship between hypercholesterolemia (elevated plasma cholesterol) and brain functions. The present study aims to understand the impact of hypercholesterolemia on pathological consequences in mouse brain. A chronic mouse model of hypercholesterolemia was induced by giving high-cholesterol diet for 12 weeks. The hypercholesterolemic mice developed cognitive impairment as evident from object recognition memory test. Cholesterol accumulation was observed in four discrete brain regions, such as cortex, striatum, hippocampus and substantia nigra along with significantly damaged blood-brain barrier by hypercholesterolemia. The crucial finding is the loss of acetylcholinesterase activity with mitochondrial dysfunction globally in the brain of hypercholesterolemic mice, which is related to the levels of cholesterol. Moreover, the levels of hydroxyl radical were elevated in the regions of brain where the activity of mitochondrial complexes was found to be reduced. Intriguingly, elevations of inflammatory stress markers in the cholesterol-rich brain regions were observed. As cognitive impairment, diminished brain acetylcholinesterase activity, mitochondrial dysfunctions, and inflammation are the prima facie pathologies of neurodegenerative diseases, the findings impose hypercholesterolemia as potential risk factor towards brain dysfunction.

Spatial patterns of brain amyloid-beta burden and atrophy rate associations in mild cognitive impairment.

PubMed

Tosun, Duygu; Schuff, Norbert; Mathis, Chester A; Jagust, William; Weiner, Michael W

2011-04-01

Amyloid-β accumulation in the brain is thought to be one of the earliest events in Alzheimer's disease, possibly leading to synaptic dysfunction, neurodegeneration and cognitive/functional decline. The earliest detectable changes seen with neuroimaging appear to be amyloid-β accumulation detected by (11)C-labelled Pittsburgh compound B positron emission tomography imaging. However, some individuals tolerate high brain amyloid-β loads without developing symptoms, while others progressively decline, suggesting that events in the brain downstream from amyloid-β deposition, such as regional brain atrophy rates, play an important role. The main purpose of this study was to understand the relationship between the regional distributions of increased amyloid-β and the regional distribution of increased brain atrophy rates in patients with mild cognitive impairment. To simultaneously capture the spatial distributions of amyloid-β and brain atrophy rates, we employed the statistical concept of parallel independent component analysis, an effective method for joint analysis of multimodal imaging data. Parallel independent component analysis identified significant relationships between two patterns of amyloid-β deposition and atrophy rates: (i) increased amyloid-β burden in the left precuneus/cuneus and medial-temporal regions was associated with increased brain atrophy rates in the left medial-temporal and parietal regions; and (ii) in contrast, increased amyloid-β burden in bilateral precuneus/cuneus and parietal regions was associated with increased brain atrophy rates in the right medial temporal regions. The spatial distribution of increased amyloid-β and the associated spatial distribution of increased brain atrophy rates embrace a characteristic pattern of brain structures known for a high vulnerability to Alzheimer's disease pathology, encouraging for the use of (11)C-labelled Pittsburgh compound B positron emission tomography measures as early indicators of Alzheimer's disease. These results may begin to shed light on the mechanisms by which amyloid-β deposition leads to neurodegeneration and cognitive decline and the development of a more specific Alzheimer's disease-specific imaging signature for diagnosis and use of this knowledge in the development of new anti-therapies for Alzheimer's disease.

Build-a-Brain Project: Students Design and Model the Brain of an Imaginary Animal

ERIC Educational Resources Information Center

Demetrikopoulos, Melissa K.; Pecore, John; Rose, Jordan D.; Fobbs, Archibald J., Jr.; Johnson, John I.; Carruth, Laura L.

2006-01-01

The brain is a truly fascinating structure! It controls the body and allows everyone to think, learn, speak, move, feel, remember, and experience emotions. Although the brain is a single organ, it is very complex and has several regions, each having a specific function. These functionally diverse regions work together to allow for coordination of…

Selective vulnerability of Rich Club brain regions is an organizational principle of structural connectivity loss in Huntington's disease.

PubMed

McColgan, Peter; Seunarine, Kiran K; Razi, Adeel; Cole, James H; Gregory, Sarah; Durr, Alexandra; Roos, Raymund A C; Stout, Julie C; Landwehrmeyer, Bernhard; Scahill, Rachael I; Clark, Chris A; Rees, Geraint; Tabrizi, Sarah J

2015-11-01

Huntington's disease can be predicted many years before symptom onset, and thus makes an ideal model for studying the earliest mechanisms of neurodegeneration. Diffuse patterns of structural connectivity loss occur in the basal ganglia and cortex early in the disease. However, the organizational principles that underlie these changes are unclear. By understanding such principles we can gain insight into the link between the cellular pathology caused by mutant huntingtin and its downstream effect at the macroscopic level. The 'rich club' is a pattern of organization established in healthy human brains, where specific hub 'rich club' brain regions are more highly connected to each other than other brain regions. We hypothesized that selective loss of rich club connectivity might represent an organizing principle underlying the distributed pattern of structural connectivity loss seen in Huntington's disease. To test this hypothesis we performed diffusion tractography and graph theoretical analysis in a pseudo-longitudinal study of 50 premanifest and 38 manifest Huntington's disease participants compared with 47 healthy controls. Consistent with our hypothesis we found that structural connectivity loss selectively affected rich club brain regions in premanifest and manifest Huntington's disease participants compared with controls. We found progressive network changes across controls, premanifest Huntington's disease and manifest Huntington's disease characterized by increased network segregation in the premanifest stage and loss of network integration in manifest disease. These regional and whole brain network differences were highly correlated with cognitive and motor deficits suggesting they have pathophysiological relevance. We also observed greater reductions in the connectivity of brain regions that have higher network traffic and lower clustering of neighbouring regions. This provides a potential mechanism that results in a characteristic pattern of structural connectivity loss targeting highly connected brain regions with high network traffic and low clustering of neighbouring regions. Our findings highlight the role of the rich club as a substrate for the structural connectivity loss seen in Huntington's disease and have broader implications for understanding the connection between molecular and systems level pathology in neurodegenerative disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Does Growth Impairment Underlie the Adverse Effects of Dexamethasone on Development of Noradrenergic Systems?

PubMed

Slotkin, Theodore A; Ko, Ashley; Seidler, Frederic J

2018-06-20

Glucocorticoids are given in preterm labor to prevent respiratory distress but these agents evoke neurobehavioral deficits in association with reduced brain region volumes. To determine whether the neurodevelopmental effects are distinct from growth impairment, we gave developing rats dexamethasone at doses below or within the therapeutic range (0.05, 0.2 or 0.8 mg/kg) at different stages: gestational days (GD) 17-19, postnatal days (PN) 1-3 or PN7-9. In adolescence and adulthood, we assessed the impact on noradrenergic systems in multiple brain regions, comparing the effects to those on somatic growth or on brain region growth. Somatic growth was reduced with exposure in all three stages, with greater sensitivity for the postnatal regimens; brain region growth was impaired to a lesser extent. Norepinephrine content and concentration were reduced depending on the treatment regimen, with a rank order of deficits of PN7-9 > PN1-3 > GD17-19. However, brain growth impairment did not parallel reduced norepinephrine content in magnitude, dose threshold, sex or regional selectivity, or temporal pattern, and even when corrected for reduced brain region weights (norepinephrine per g tissue), the dexamethasone-exposed animals showed subnormal values. Regression analysis showed that somatic growth impairment accounted for an insubstantial amount of the reduction in norepinephrine content, and brain growth impairment accounted for only 12%, whereas specific effects on norepinephrine accounted for most of the effect. The adverse effects of dexamethasone on noradrenergic system development are not simply related to impaired somatic or brain region growth, but rather include specific targeting of neurodifferentiation. Copyright © 2018. Published by Elsevier B.V.

Population structure of the stable fly, Stomoxys calcitrans (L.) (Diptera: Muscidae) assessed on a global scale using Amplified Fragment Length Polymorphism

USDA-ARS?s Scientific Manuscript database

The stable fly, Stomoxys calcitrans (L.) (Diptera: Muscidae), is a major pest of livestock in the United States and worldwide. To assess the genetic variability in geographically distant stable flies, samples were obtained from four biogeographical regions: Nearctic, Neotropical, Palearctic, and Aus...

Regional distribution of introduced plant species in the forests of the Northeastern United States

Treesearch

Beth Schulz; W. Keith Moser; Cassandra Olson; Katherine Johnson

2013-01-01

Many plant species have been introduced to the United States by humans since European settlement, sometimes deliberately and sometimes inadvertently, such as in contaminated crop seed or soil. Some species have successfully escaped cultivation and become invasive, spreading and establishing new populations distant from original population centers. Indeed, introduced...

Knowledge Transfer between Two Geographically Distant Action Research Teams

ERIC Educational Resources Information Center

Desmarais, Lise; Parent, Robert; Leclerc, Louise; Raymond, Lysanne; MacKinnon, Scott; Vezina, Nicole

2009-01-01

Purpose: The objective of this study is to observe and document the transfer of a train the trainers program in knife sharpening and steeling. This knowledge transfer involved two groups of researchers: the experts and the learners. These groups are from geographically dispersed regions and evolve in distinct contexts by their language and…

Relationships of red pine seed source, seed weight, seedling weight, and height growth in Kane test plantation

Treesearch

A. F. Hough

1952-01-01

In 1928 the Lake States Forest Experiment Station of the U. S. Forest Service began studies of various races or strains of red pine (Pinus resinosa Ait.), to find out how well red pine is adapted to climatic regions distant from its natural seed sources.

Rich club network analysis shows distinct patterns of disruption in frontotemporal dementia and Alzheimer’s disease

PubMed Central

Daianu, Madelaine; Jahanshad, Neda; Villalon-Reina, Julio E.; Mendez, Mario F.; Bartzokis, George; Jimenez, Elvira E.; Joshi, Aditi; Barsuglia, Joseph; Thompson, Paul M.

2015-01-01

Diffusion imaging and brain connectivity analyses can reveal the underlying organizational patterns of the human brain, described as complex networks of densely interlinked regions. Here, we analyzed 1.5-Tesla whole-brain diffusion-weighted images from 64 participants – 15 patients with behavioral variant frontotemporal (bvFTD) dementia, 19 with early-onset Alzheimer’s disease (EOAD), and 30 healthy elderly controls. Based on whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We examined how bvFTD and EOAD disrupt the weighted ‘rich club’ – a network property where high-degree network nodes are more interconnected than expected by chance. bvFTD disrupts both the nodal and global organization of the network in both low- and high-degree regions of the brain. EOAD targets the global connectivity of the brain, mainly affecting the fiber density of high-degree (highly connected) regions that form the rich club network. These rich club analyses suggest distinct patterns of disruptions among different forms of dementia. PMID:26161050

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.

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.

Single-phase Whole-body 64-MDCT Split-bolus Protocol for Pediatric Oncology: Diagnostic Efficacy and Dose Radiation.

PubMed

Scialpi, Michele; Schiavone, Raffaele; D'Andrea, Alfredo; Palumbo, Isabella; Magli, Michelle; Gravante, Sabrina; Falcone, Giuseppe; De Filippi, Claudio; Manganaro, Lucia; Palumbo, Barbara

2015-05-01

To evaluate the image quality and the diagnostic efficacy by single-phase whole-body 64-slice multidetector CT (MDCT) for pediatric oncology. Chest-abdomen-pelvis CT examinations with single-phase split-bolus technique were evaluated for T: detection and delineation of primary tumor (assessment of the extent of the lesion to neighboring tissues), N: regional lymph nodes and M: distant metastasis. Quality scores (5-point scale) were assessed by two radiologists on parenchymal and vascular enhancement. Accurate TNM staging in term of detection and delineation of primary tumor, regional lymph nodes and distant metastasis was obtained in all cases. On the image quality and severity artifact, the Kappa value for the interobserver agreement measure obtained from the analysis was 0.754, (p<0.001), characterizing a very good agreement between observers. Single-pass total body CT split-bolus technique reached the highest overall image quality and an accurate TNM staging in pediatric patients with cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Quantitative representations of an exaggerated anxiety response in the brain of female spider phobics-a parametric fMRI study.

PubMed

Zilverstand, Anna; Sorger, Bettina; Kaemingk, Anita; Goebel, Rainer

2017-06-01

We employed a novel parametric spider picture set in the context of a parametric fMRI anxiety provocation study, designed to tease apart brain regions involved in threat monitoring from regions representing an exaggerated anxiety response in spider phobics. For the stimulus set, we systematically manipulated perceived proximity of threat by varying a depicted spider's context, size, and posture. All stimuli were validated in a behavioral rating study (phobics n = 20; controls n = 20; all female). An independent group participated in a subsequent fMRI anxiety provocation study (phobics n = 7; controls n = 7; all female), in which we compared a whole-brain categorical to a whole-brain parametric analysis. Results demonstrated that the parametric analysis provided a richer characterization of the functional role of the involved brain networks. In three brain regions-the mid insula, the dorsal anterior cingulate, and the ventrolateral prefrontal cortex-activation was linearly modulated by perceived proximity specifically in the spider phobia group, indicating a quantitative representation of an exaggerated anxiety response. In other regions (e.g., the amygdala), activation was linearly modulated in both groups, suggesting a functional role in threat monitoring. Prefrontal regions, such as dorsolateral prefrontal cortex, were activated during anxiety provocation but did not show a stimulus-dependent linear modulation in either group. The results confirm that brain regions involved in anxiety processing hold a quantitative representation of a pathological anxiety response and more generally suggest that parametric fMRI designs may be a very powerful tool for clinical research in the future, particularly when developing novel brain-based interventions (e.g., neurofeedback training). Hum Brain Mapp 38:3025-3038, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Small-worldness and gender differences of large scale brain metabolic covariance networks in young adults: a FDG PET study of 400 subjects.

PubMed

Hu, Yuxiao; Xu, Qiang; Shen, Junkang; Li, Kai; Zhu, Hong; Zhang, Zhiqiang; Lu, Guangming

2015-02-01

Many studies have demonstrated the small-worldness of the human brain, and have revealed a sexual dimorphism in brain network properties. However, little is known about the gender effects on the topological organization of the brain metabolic covariance networks. To investigate the small-worldness and the gender differences in the topological architectures of human brain metabolic networks. FDG-PET data of 400 healthy right-handed subjects (200 women and 200 age-matched men) were involved in the present study. Metabolic networks of each gender were constructed by calculating the covariance of regional cerebral glucose metabolism (rCMglc) across subjects on the basis of AAL parcellation. Gender differences of network and nodal properties were investigated by using the graph theoretical approaches. Moreover, the gender-related difference of rCMglc in each brain region was tested for investigating the relationships between the hub regions and the brain regions showing significant gender-related differences in rCMglc. We found prominent small-world properties in the domain of metabolic networks in each gender. No significant gender difference in the global characteristics was found. Gender differences of nodal characteristic were observed in a few brain regions. We also found bilateral and lateralized distributions of network hubs in the females and males. Furthermore, we first reported that some hubs of a gender located in the brain regions showing weaker rCMglc in this gender than the other gender. The present study demonstrated that small-worldness was existed in metabolic networks, and revealed gender differences of organizational patterns in metabolic network. These results maybe provided insights into the understanding of the metabolic substrates underlying individual differences in cognition and behaviors. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

A Single Primary Blast-Induced Traumatic Brain Injury in a Rodent Model Causes Cell-Type Dependent Increase in Nicotinamide Adenine Dinucleotide Phosphate Oxidase Isoforms in Vulnerable Brain Regions.

PubMed

Rama Rao, Kakulavarapu V; Iring, Stephanie; Younger, Daniel; Kuriakose, Matthew; Skotak, Maciej; Alay, Eren; Gupta, Raj K; Chandra, Namas

2018-06-12

Blast-induced traumatic brain injury (bTBI) is a leading cause of morbidity in soldiers on the battlefield and in training sites with long-term neurological and psychological pathologies. Previous studies from our laboratory demonstrated activation of oxidative stress pathways after blast injury, but their distribution among different brain regions and their impact on the pathogenesis of bTBI have not been explored. The present study examined the protein expression of two isoforms: nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 and 2 (NOX1, NOX2), corresponding superoxide production, a downstream event of NOX activation, and the extent of lipid peroxidation adducts of 4-hydroxynonenal (4HNE) to a range of proteins. Brain injury was evaluated 4 h after the shock-wave exposure, and immunofluorescence signal quantification was performed in different brain regions. Expression of NOX isoforms displayed a differential increase in various brain regions: in hippocampus and thalamus, there was the highest increase of NOX1, whereas in the frontal cortex, there was the highest increase of NOX2 expression. Cell-specific analysis of changes in NOX expression with respect to corresponding controls revealed that blast resulted in a higher increase of NOX1 and NOX 2 levels in neurons compared with astrocytes and microglia. Blast exposure also resulted in increased superoxide levels in different brain regions, and such changes were reflected in 4HNE protein adduct formation. Collectively, this study demonstrates that primary blast TBI induces upregulation of NADPH oxidase isoforms in different regions of the brain parenchyma and that neurons appear to be at higher risk for oxidative damage compared with other neural cells.

Was the exposed continental shelf a long-distance colonization route in the ice age? The Southeast Asia origin of Hainan and Taiwan partridges.

PubMed

Chen, De; Chang, Jiang; Li, Shou-Hsien; Liu, Yang; Liang, Wei; Zhou, Fang; Yao, Cheng-Te; Zhang, Zhengwang

2015-02-01

Research on island biotas has greatly contributed to the development of modern evolutionary and biogeographic theories. Until now, most studies have suggested that continental islands received their biotas directly from the adjacent mainland. However, only a few studies have indicated that species on continental islands might originate from other distantly non-adjacent regions. Here, we used the hill partridges (genus Arborophila) that are widely distributed in the southwest and southeast China mainland, Indochina, Hainan and Taiwan islands to test whether species on continental islands might originate from distant regions rather than the adjacent mainland. Based on molecular phylogenies inferred from three mitochondrial fragments and three nuclear introns, together with ancestral area reconstruction, we found that the ancestors of the endemic Hainan and Taiwan partridges (A. ardens and A. crudigularis) likely originated from Indochina, rather than the nearby southeast China mainland. The divergence time estimates demonstrate that their ancestors likely colonized Hainan and Taiwan islands using the long exposed continental shelf between Indochina, Hainan and Taiwan islands during glacial periods, which had not been demonstrated before. Thus, integrating distribution data with phylogenetic information can shed new lights on the historical biogeography of continental islands and surrounding mainland regions. Copyright © 2014 Elsevier Inc. All rights reserved.

Altered Whole-Brain and Network-Based Functional Connectivity in Parkinson's Disease.

PubMed

de Schipper, Laura J; Hafkemeijer, Anne; van der Grond, Jeroen; Marinus, Johan; Henselmans, Johanna M L; van Hilten, Jacobus J

2018-01-01

Background: Functional imaging methods, such as resting-state functional magnetic resonance imaging, reflect changes in neural connectivity and may help to assess the widespread consequences of disease-specific network changes in Parkinson's disease. In this study we used a relatively new graph analysis approach in functional imaging: eigenvector centrality mapping. This model-free method, applied to all voxels in the brain, identifies prominent regions in the brain network hierarchy and detects localized differences between patient populations. In other neurological disorders, eigenvector centrality mapping has been linked to changes in functional connectivity in certain nodes of brain networks. Objectives: Examining changes in functional brain connectivity architecture on a whole brain and network level in patients with Parkinson's disease. Methods: Whole brain resting-state functional architecture was studied with a recently introduced graph analysis approach (eigenvector centrality mapping). Functional connectivity was further investigated in relation to eight known resting-state networks. Cross-sectional analyses included group comparison of functional connectivity measures of Parkinson's disease patients ( n = 107) with control subjects ( n = 58) and correlations with clinical data, including motor and cognitive impairment and a composite measure of predominantly non-dopaminergic symptoms. Results: Eigenvector centrality mapping revealed that frontoparietal regions were more prominent in the whole-brain network function in patients compared to control subjects, while frontal and occipital brain areas were less prominent in patients. Using standard resting-state networks, we found predominantly increased functional connectivity, namely within sensorimotor system and visual networks in patients. Regional group differences in functional connectivity of both techniques between patients and control subjects partly overlapped for highly connected posterior brain regions, in particular in the posterior cingulate cortex and precuneus. Clinico-functional imaging relations were not found. Conclusions: Changes on the level of functional brain connectivity architecture might provide a different perspective of pathological consequences of Parkinson's disease. The involvement of specific, highly connected (hub) brain regions may influence whole brain functional network architecture in Parkinson's disease.

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

Climate Impacts Already Affect Every Region of the United States, Report Warns

NASA Astrophysics Data System (ADS)

Showstack, Randy

2014-05-01

"Climate change, once considered an issue for a distant future, has moved firmly into the present," according to the third iteration of the U.S. National Climate Assessment (NCA), issued by the White House on 6 May. "The observed warming and other climatic changes are triggering wide-ranging impacts in every region of our country and throughout our economy," states the report, titled Climate Change Impacts in the United States, issued through the federal interagency U.S. Global Change Research Program.

CANDELS: A Cosmic Quest for Distant Galaxies Offering Live Views of Galaxy Evolution

NASA Astrophysics Data System (ADS)

Koo, David C.; CANDELS

2017-06-01

For decades, the study of distant galaxies has been pushing the frontiers of extra-galactic research, with observations from the best suite of telescopes and instruments and with theory from the most advanced computer simulations. This talk will focus on observations taken within the CANDELS fields to reveal the richness and complexity of this still-growing field. CANDELS (Cosmic Assembly Near-IR Deep Extragalactic Legacy Survey) itself is the largest project ever taken by Hubble and is composed of optical and near-infrared images of five tiny regions of sky containing over 200,000 distant galaxies. All these regions, two of which are GOODS North and South, were already outstanding in possessing years of prior surveys taken by many teams worldwide and have continued to attract more and better spectra and panchromatic images from Keck, Hubble, Chandra, Spitzer, and other telescopes ranging from X-ray to radio. Combined together, the rich data within the CANDELS fields offer live views of galaxy evolution from “Cosmic Dawn” when the first infant galaxies and cosmic black holes were born, through “Cosmic Noon” during the peak of galaxy and black hole growth, and then to “Cosmic Afternoon” when star formation and black hole activities, morphologies, motions, and contents settled to those of our Milky Way and its zoo of cousins today. The talk will highlight some interesting discoveries from the last two periods and close with new mysteries challenging our field in the 21st century and future prospects for solving them.

Brain Connectivity Networks and the Aesthetic Experience of Music.

PubMed

Reybrouck, Mark; Vuust, Peter; Brattico, Elvira

2018-06-12

Listening to music is above all a human experience, which becomes an aesthetic experience when an individual immerses himself/herself in the music, dedicating attention to perceptual-cognitive-affective interpretation and evaluation. The study of these processes where the individual perceives, understands, enjoys and evaluates a set of auditory stimuli has mainly been focused on the effect of music on specific brain structures, as measured with neurophysiology and neuroimaging techniques. The very recent application of network science algorithms to brain research allows an insight into the functional connectivity between brain regions. These studies in network neuroscience have identified distinct circuits that function during goal-directed tasks and resting states. We review recent neuroimaging findings which indicate that music listening is traceable in terms of network connectivity and activations of target regions in the brain, in particular between the auditory cortex, the reward brain system and brain regions active during mind wandering.

Prediction of human errors by maladaptive changes in event-related brain networks.

PubMed

Eichele, Tom; Debener, Stefan; Calhoun, Vince D; Specht, Karsten; Engel, Andreas K; Hugdahl, Kenneth; von Cramon, D Yves; Ullsperger, Markus

2008-04-22

Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional MRI and applying independent component analysis followed by deconvolution of hemodynamic responses, we studied error preceding brain activity on a trial-by-trial basis. We found a set of brain regions in which the temporal evolution of activation predicted performance errors. These maladaptive brain activity changes started to evolve approximately 30 sec before the error. In particular, a coincident decrease of deactivation in default mode regions of the brain, together with a decline of activation in regions associated with maintaining task effort, raised the probability of future errors. Our findings provide insights into the brain network dynamics preceding human performance errors and suggest that monitoring of the identified precursor states may help in avoiding human errors in critical real-world situations.

Prediction of human errors by maladaptive changes in event-related brain networks

PubMed Central

Eichele, Tom; Debener, Stefan; Calhoun, Vince D.; Specht, Karsten; Engel, Andreas K.; Hugdahl, Kenneth; von Cramon, D. Yves; Ullsperger, Markus

2008-01-01

Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional MRI and applying independent component analysis followed by deconvolution of hemodynamic responses, we studied error preceding brain activity on a trial-by-trial basis. We found a set of brain regions in which the temporal evolution of activation predicted performance errors. These maladaptive brain activity changes started to evolve ≈30 sec before the error. In particular, a coincident decrease of deactivation in default mode regions of the brain, together with a decline of activation in regions associated with maintaining task effort, raised the probability of future errors. Our findings provide insights into the brain network dynamics preceding human performance errors and suggest that monitoring of the identified precursor states may help in avoiding human errors in critical real-world situations. PMID:18427123

Diagnosis of metastases from postoperative differentiated thyroid cancer: comparison between FDG and FLT PET/CT studies.

PubMed

Nakajo, Masatoyo; Nakajo, Masayuki; Jinguji, Megumi; Tani, Atsushi; Kajiya, Yoriko; Tanabe, Hiroaki; Fukukura, Yoshihiko; Nakabeppu, Yoshiaki; Koriyama, Chihaya

2013-06-01

To compare positron emission tomography (PET)/computed tomography (CT) studies performed with the glucose analog fluorine 18 ((18)F) fluorodeoxyglucose (FDG) and the cell proliferation tracer (18)F fluorothymidine (FLT) in the diagnosis of metastases from postoperative differentiated thyroid cancer. The institutional ethics review board approved this prospective study. From March 2010 to February 2012, 20 patients (mean age, 53 years; age range, 22-79 years) with postoperative differentiated thyroid cancer underwent both FDG and FLT PET/CT as a staging work-up before radioiodine therapy. In each patient, 28 anatomic areas were set and analyzed for lymph node and distant metastases. The McNemar exact or χ(2) test was used to examine differences in diagnostic indexes in the detection of lymph node and distant metastases between both tracer PET/CT studies. There were 34 lymph node metastases and/or 73 distant metastases (70 metastases in lung and one each in bone, nasopharynx, and brain) in 13 patients. At patient-based analysis, the sensitivity, specificity, and accuracy were 92% (12 of 13 patients), 86% (six of seven patients), and 90% (18 of 20 patients), respectively, for FDG PET/CT and 69% (nine of 13 patients), 29% (two of seven patients), and 55% (11 of 20 patients) for FLT PET/CT. The accuracy of FDG PET/CT was significantly better than that of FLT PET/CT (P = .023). At lesion-based analysis, the sensitivity, specificity, and accuracy for diagnosing lymph node metastases were 85% (29 of 34 lesions), 99.6% (245 of 246 lesions), and 97.9% (274 of 280 lesions), respectively, for FDG PET/CT and 50% (17 of 34 lesions), 90.7% (223 of 246 lesions), and 85.7% (240 of 280 lesions) for FLT PET/CT. The sensitivity, specificity, and accuracy for diagnosing distant metastases were 45% (33 of 73 lesions), 100% (207 of 207 lesions), and 85.7% (240 of 280 lesions), respectively, for FDG PET/CT and 6.8% (five of 73 lesions), 100% (207 of 207 lesions), and 75.7% (212 of 280 lesions) for FLT PET/CT. The sensitivity (P = .002), specificity (P < .001), and accuracy (P < .001) of FDG PET/CT in the diagnosis of lymph node metastases were superior to those of FLT PET, as were the sensitivity (P < .001) and accuracy (P < .001) in the diagnosis of distant metastases. FDG PET/CT is superior to FLT PET/CT in the diagnosis of postoperative differentiated thyroid cancer lymph node and distant metastases. Thus, FDG PET/CT is more suitable than FLT PET/CT for examining recurrence of postoperative differentiated thyroid cancer.

Impacts of artificial reservoirs on floristic diversity and plant functional traits in dry forests after 15 years.

PubMed

Lopes, S F; Vale, V S; Prado Júnior, J A; Schiavini, I

2015-08-01

Dams are of paramount importance to a wide variety of human services and many of their environmental problems are known; however, there are few studies in the world addressing the impacts on the native vegetation previously distant from water bodies which became close to the lakeshore created by a dam. Thus, this paper aims to analyze the responses of a dry forest to a dam after 15 years. For this, 20 random samples of 40 trees were made, 10 close to the lakeshore and 10 distant from it, by applying the central square point method. Close to the dam, we found higher values regarding basal area, number of trees, number of evergreen trees, and zoochoric syndrome, but there were lower values of Shannon's diversity index. Therefore, the impacts of the dam after 15 years caused several changes to the tree community. The greater basal area close to the dam suggests that water deficit during the dry season was decreased and plants have thicker trunks. On the other hand, this sector had much more zoochoric syndrome and a larger number of evergreen trees than plots which are distant from water, suggesting changes with regard to the community's ecological functions. Furthermore, structural floristic data shows that the sector close to the dam is less similar to other deciduous forests within the same geographical region than the sector distant from water, thus providing evidence of the impacts of dams on the tree community.