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.

Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.

PubMed

Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Lorsch, Zachary S; Walker, Deena M; Wang, Junshi; Huang, Xiaojie; Schlüter, Oliver M; Maze, Ian; Peña, Catherine J; Heller, Elizabeth A; Issler, Orna; Wang, Minghui; Song, Won-Min; Stein, Jason L; Liu, Xiaochuan; Doyle, Marie A; Scobie, Kimberly N; Sun, Hao Sheng; Neve, Rachael L; Geschwind, Daniel; Dong, Yan; Shen, Li; Zhang, Bin; Nestler, Eric J

2016-06-01

Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

Mapping Resting-State Brain Networks in Conscious Animals

PubMed Central

Zhang, Nanyin; Rane, Pallavi; Huang, Wei; Liang, Zhifeng; Kennedy, David; Frazier, Jean A.; King, Jean

2010-01-01

In the present study we mapped brain functional connectivity in the conscious rat at the “resting state” based on intrinsic blood-oxygenation-level dependent (BOLD) fluctuations. The conscious condition eliminated potential confounding effects of anesthetic agents on the connectivity between brain regions. Indeed, using correlational analysis we identified multiple cortical and subcortical regions that demonstrated temporally synchronous variation with anatomically well-defined regions that are crucial to cognitive and emotional information processing including the prefrontal cortex (PFC), thalamus and retrosplenial cortex. The functional connectivity maps created were stringently validated by controlling for false positive detection of correlation, the physiologic basis of the signal source, as well as quantitatively evaluating the reproducibility of maps. Taken together, the present study has demonstrated the feasibility of assessing functional connectivity in conscious animals using fMRI and thus provided a convenient and non-invasive tool to systematically investigate the connectional architecture of selected brain networks in multiple animal models. PMID:20382183

Reorganization of Functional Connectivity as a Correlate of Cognitive Recovery in Acquired Brain Injury

ERIC Educational Resources Information Center

Castellanos, Nazareth P.; Paul, Nuria; Ordonez, Victoria E.; Demuynck, Olivier; Bajo, Ricardo; Campo, Pablo; Bilbao, Alvaro; Ortiz, Tomas; del-Pozo, Francisco; Maestu, Fernando

2010-01-01

Cognitive processes require a functional interaction between specialized multiple, local and remote brain regions. Although these interactions can be strongly altered by an acquired brain injury, brain plasticity allows network reorganization to be principally responsible for recovery. The present work evaluates the impact of brain injury on…

Differential recruitment of brain networks in single-digit addition and multiplication: Evidence from EEG oscillations in theta and lower alpha bands.

PubMed

Wang, Lihan; Gan, John Q; Zhang, Li; Wang, Haixian

2018-06-01

Previous neuroimaging research investigating dissociation between single-digit addition and multiplication has suggested that the former placed more reliance on the visuo-spatial processing whereas the latter on the verbal processing. However, there has been little exploration into the disassociation in spatio-temporal dynamics of the oscillatory brain activity in specific frequency bands during the two arithmetic operations. To address this issue, the electroencephalogram (EEG) data were recorded from 19 participants engaged in a delayed verification arithmetic task. By analyzing oscillatory EEG activity in theta (5-7 Hz) and lower alpha frequency (9-10 Hz) bands, we found different patterns of oscillatory brain activity between single-digit addition and multiplication during the early processing stage (0-400 ms post-operand onset). Experiment results in this study showed a larger phasic increase of theta-band power for addition than for multiplication in the midline and the right frontal and central regions during the operator and operands presentation intervals, which was extended to the right parietal and the right occipito-temporal regions during the interval immediately after the operands presentation. In contrast, during multiplication higher phase-locking in lower alpha band was evident in the centro-parietal regions during the operator presentation, which was extended to the left fronto-central and anterior regions during the operands presentation. Besides, we found stronger theta phase synchrony between the parietal areas and the right occipital areas for single-digit addition than for multiplication during operands encoding. These findings of oscillatory brain activity extend the previous observations on functional dissociation between the two arithmetic operations. Copyright © 2018 Elsevier B.V. All rights reserved.

Accelerated echo-planar J-resolved spectroscopic imaging in the human brain using compressed sensing: a pilot validation in obstructive sleep apnea.

PubMed

Sarma, M K; Nagarajan, R; Macey, P M; Kumar, R; Villablanca, J P; Furuyama, J; Thomas, M A

2014-06-01

Echo-planar J-resolved spectroscopic imaging is a fast spectroscopic technique to record the biochemical information in multiple regions of the brain, but for clinical applications, time is still a constraint. Investigations of neural injury in obstructive sleep apnea have revealed structural changes in the brain, but determining the neurochemical changes requires more detailed measurements across multiple brain regions, demonstrating a need for faster echo-planar J-resolved spectroscopic imaging. Hence, we have extended the compressed sensing reconstruction of prospectively undersampled 4D echo-planar J-resolved spectroscopic imaging to investigate metabolic changes in multiple brain locations of patients with obstructive sleep apnea and healthy controls. Nonuniform undersampling was imposed along 1 spatial and 1 spectral dimension of 4D echo-planar J-resolved spectroscopic imaging, and test-retest reliability of the compressed sensing reconstruction of the nonuniform undersampling data was tested by using a brain phantom. In addition, 9 patients with obstructive sleep apnea and 11 healthy controls were investigated by using a 3T MR imaging/MR spectroscopy scanner. Significantly reduced metabolite differences were observed between patients with obstructive sleep apnea and healthy controls in multiple brain regions: NAA/Cr in the left hippocampus; total Cho/Cr and Glx/Cr in the right hippocampus; total NAA/Cr, taurine/Cr, scyllo-Inositol/Cr, phosphocholine/Cr, and total Cho/Cr in the occipital gray matter; total NAA/Cr and NAA/Cr in the medial frontal white matter; and taurine/Cr and total Cho/Cr in the left frontal white matter regions. The 4D echo-planar J-resolved spectroscopic imaging technique using the nonuniform undersampling-based acquisition and compressed sensing reconstruction in patients with obstructive sleep apnea and healthy brain is feasible in a clinically suitable time. In addition to brain metabolite changes previously reported by 1D MR spectroscopy, our results show changes of additional metabolites in patients with obstructive sleep apnea compared with healthy controls. © 2014 by American Journal of Neuroradiology.

Development of a high angular resolution diffusion imaging human brain template.

PubMed

Varentsova, Anna; Zhang, Shengwei; Arfanakis, Konstantinos

2014-05-01

Brain diffusion templates contain rich information about the microstructure of the brain, and are used as references in spatial normalization or in the development of brain atlases. The accuracy of diffusion templates constructed based on the diffusion tensor (DT) model is limited in regions with complex neuronal micro-architecture. High angular resolution diffusion imaging (HARDI) overcomes limitations of the DT model and is capable of resolving intravoxel heterogeneity. However, when HARDI is combined with multiple-shot sequences to minimize image artifacts, the scan time becomes inappropriate for human brain imaging. In this work, an artifact-free HARDI template of the human brain was developed from low angular resolution multiple-shot diffusion data. The resulting HARDI template was produced in ICBM-152 space based on Turboprop diffusion data, was shown to resolve complex neuronal micro-architecture in regions with intravoxel heterogeneity, and contained fiber orientation information consistent with known human brain anatomy. Copyright © 2014 Elsevier Inc. All rights reserved.

Whole Brain Irradiation With Hippocampal Sparing and Dose Escalation on Multiple Brain Metastases: A Planning Study on Treatment Concepts

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

Prokic, Vesna, E-mail: vesna.prokic@uniklinik-freiburg.de; Wiedenmann, Nicole; Fels, Franziska

2013-01-01

Purpose: To develop a new treatment planning strategy in patients with multiple brain metastases. The goal was to perform whole brain irradiation (WBI) with hippocampal sparing and dose escalation on multiple brain metastases. Two treatment concepts were investigated: simultaneously integrated boost (SIB) and WBI followed by stereotactic fractionated radiation therapy sequential concept (SC). Methods and Materials: Treatment plans for both concepts were calculated for 10 patients with 2-8 brain metastases using volumetric modulated arc therapy. In the SIB concept, the prescribed dose was 30 Gy in 12 fractions to the whole brain and 51 Gy in 12 fractions to individualmore » brain metastases. In the SC concept, the prescription was 30 Gy in 12 fractions to the whole brain followed by 18 Gy in 2 fractions to brain metastases. All plans were optimized for dose coverage of whole brain and lesions, simultaneously minimizing dose to the hippocampus. The treatment plans were evaluated on target coverage, homogeneity, and minimal dose to the hippocampus and organs at risk. Results: The SIB concept enabled more successful sparing of the hippocampus; the mean dose to the hippocampus was 7.55 {+-} 0.62 Gy and 6.29 {+-} 0.62 Gy, respectively, when 5-mm and 10-mm avoidance regions around the hippocampus were used, normalized to 2-Gy fractions. In the SC concept, the mean dose to hippocampus was 9.8 {+-} 1.75 Gy. The mean dose to the whole brain (excluding metastases) was 33.2 {+-} 0.7 Gy and 32.7 {+-} 0.96 Gy, respectively, in the SIB concept, for 5-mm and 10-mm hippocampus avoidance regions, and 37.23 {+-} 1.42 Gy in SC. Conclusions: Both concepts, SIB and SC, were able to achieve adequate whole brain coverage and radiosurgery-equivalent dose distributions to individual brain metastases. The SIB technique achieved better sparing of the hippocampus, especially when a10-mm hippocampal avoidance region was used.« less

Developmental vitamin D deficiency alters multiple neurotransmitter systems in the neonatal rat brain.

PubMed

Kesby, James P; Turner, Karly M; Alexander, Suzanne; Eyles, Darryl W; McGrath, John J; Burne, Thomas H J

2017-11-01

Epidemiological evidence suggests that developmental vitamin D (DVD) deficiency is a risk factor for neuropsychiatric disorders, such as schizophrenia. DVD deficiency in rats is associated with altered brain structure and adult behaviours indicating alterations in dopamine and glutamate signalling. Developmental alterations in dopamine neurotransmission have also been observed in DVD-deficient rats but a comprehensive assessment of brain neurochemistry has not been undertaken. Thus, the current study determined the regional concentrations of dopamine, noradrenaline, serotonin, glutamine, glutamate and γ-aminobutyric acid (GABA), and associated metabolites, in DVD-deficient neonates. Sprague-Dawley rats were fed a vitamin D deficient diet or control diet six weeks prior to mating until birth and housed under UVB-free lighting conditions. Neurotransmitter concentration was assessed by high-performance liquid chromatography on post-mortem neonatal brain tissue. Ubiquitous reductions in the levels of glutamine (12-24%) were observed in DVD-deficient neonates compared with control neonates. Similarly, in multiple brain regions DVD-deficient neonates had increased levels of noradrenaline and serine compared with control neonates. In contrast, increased levels of dopamine and decreased levels of serotonin in DVD-deficient neonates were limited to striatal subregions compared with controls. Our results confirm that DVD deficiency leads to changes in multiple neurotransmitter systems in the neonate brain. Importantly, this regionally-based assessment in DVD-deficient neonates identified both widespread neurotransmitter changes (glutamine/noradrenaline) and regionally selective neurotransmitter changes (dopamine/serotonin). Thus, vitamin D may have both general and local actions depending on the neurotransmitter system being investigated. Taken together, these data suggest that DVD deficiency alters neurotransmitter systems relevant to schizophrenia in the developing rat brain. Copyright © 2017 ISDN. All rights reserved.

Habit formation.

PubMed

Smith, Kyle S; Graybiel, Ann M

2016-03-01

Habits, both good ones and bad ones, are pervasive in animal behavior. Important frameworks have been developed to understand habits through psychological and neurobiological studies. This work has given us a rich understanding of brain networks that promote habits, and has also helped us to understand what constitutes a habitual behavior as opposed to a behavior that is more flexible and prospective. Mounting evidence from studies using neural recording methods suggests that habit formation is not a simple process. We review this evidence and take the position that habits could be sculpted from multiple dissociable changes in neural activity. These changes occur across multiple brain regions and even within single brain regions. This strategy of classifying components of a habit based on different brain signals provides a potentially useful new way to conceive of disorders that involve overly fixed behaviors as arising from different potential dysfunctions within the brain's habit network.

Habit formation

PubMed Central

Smith, Kyle S.; Graybiel, Ann M.

2016-01-01

Habits, both good ones and bad ones, are pervasive in animal behavior. Important frameworks have been developed to understand habits through psychological and neurobiological studies. This work has given us a rich understanding of brain networks that promote habits, and has also helped us to understand what constitutes a habitual behavior as opposed to a behavior that is more flexible and prospective. Mounting evidence from studies using neural recording methods suggests that habit formation is not a simple process. We review this evidence and take the position that habits could be sculpted from multiple dissociable changes in neural activity. These changes occur across multiple brain regions and even within single brain regions. This strategy of classifying components of a habit based on different brain signals provides a potentially useful new way to conceive of disorders that involve overly fixed behaviors as arising from different potential dysfunctions within the brain's habit network. PMID:27069378

Doubly Selective Multiple Quantum Chemical Shift Imaging and T1 Relaxation Time Measurement of Glutathione (GSH) in the Human Brain In Vivo

PubMed Central

Choi, In-Young; Lee, Phil

2012-01-01

Mapping of a major antioxidant, glutathione (GSH), was achieved in the human brain in vivo using a doubly selective multiple quantum filtering based chemical shift imaging (CSI) of GSH at 3 T. Both in vivo and phantom tests in CSI and single voxel measurements were consistent with excellent suppression of overlapping signals from creatine, γ-Amino butyric acid (GABA) and macromolecules. The GSH concentration in the fronto-parietal region was 1.20 ± 0.16 µmol/g (mean ± SD, n = 7). The longitudinal relaxation time (T1) of GSH in the human brain was 397 ± 44 ms (mean ± SD, n = 5), which was substantially shorter than those of other metabolites. This GSH CSI method permits us to address regional differences of GSH in the human brain with conditions where oxidative stress has been implicated, including multiple sclerosis, aging and neurodegenerative diseases. PMID:22730142

Functional grouping and cortical–subcortical interactions in emotion: A meta-analysis of neuroimaging studies

PubMed Central

Kober, Hedy; Barrett, Lisa Feldman; Joseph, Josh; Bliss-Moreau, Eliza; Lindquist, Kristen; Wager, Tor D.

2009-01-01

We performed an updated quantitative meta-analysis of 162 neuroimaging studies of emotion using a novel multi-level kernel-based approach, focusing on locating brain regions consistently activated in emotional tasks and their functional organization into distributed functional groups, independent of semantically defined emotion category labels (e.g., “anger,” “fear”). Such brain-based analyses are critical if our ways of labeling emotions are to be evaluated and revised based on consistency with brain data. Consistent activations were limited to specific cortical sub-regions, including multiple functional areas within medial, orbital, and inferior lateral frontal cortices. Consistent with a wealth of animal literature, multiple subcortical activations were identified, including amygdala, ventral striatum, thalamus, hypothalamus, and periaqueductal gray. We used multivariate parcellation and clustering techniques to identify groups of co-activated brain regions across studies. These analyses identified six distributed functional groups, including medial and lateral frontal groups, two posterior cortical groups, and paralimbic and core limbic/brainstem groups. These functional groups provide information on potential organization of brain regions into large-scale networks. Specific follow-up analyses focused on amygdala, periaqueductal gray (PAG), and hypothalamic (Hy) activations, and identified frontal cortical areas co-activated with these core limbic structures. While multiple areas of frontal cortex co-activated with amygdala sub-regions, a specific region of dorsomedial prefrontal cortex (dmPFC, Brodmann’s Area 9/32) was the only area co-activated with both PAG and Hy. Subsequent mediation analyses were consistent with a pathway from dmPFC through PAG to Hy. These results suggest that medial frontal areas are more closely associated with core limbic activation than their lateral counterparts, and that dmPFC may play a particularly important role in the cognitive generation of emotional states. PMID:18579414

Greater regional brain atrophy rate in healthy elders with a history of cigarette smoking

PubMed Central

Durazzo, Timothy C.; Insel, Philip S.; Weiner, Michael W.; Initiative, the Alzheimer Disease Neuroimaging

2011-01-01

Background Little is known about the effects of cigarette smoking on brain morphological changes in the elderly. This study investigated the effects of a history of cigarette smoking on changes in regional brain volumes over 2-years in healthy, cognitively-intact elderly individuals. We predicted individuals with a history of cigarette smoking, compared to never smokers, demonstrate greater rate of atrophy over 2-years in regions that manifest morphological abnormalities in the early stages of Alzheimer Disease (AD), as well as the extended brain reward system (BRS), which is implicated in the development and maintenance of substance use disorders. Methods Participants were healthy, cognitively normal elderly controls (75.9±4.8 years of age) with any lifetime history of cigarette smoking (n = 68) and no history of smoking (n = 118). Data was obtained via the Alzheimer Disease Neuroimaging Initiative from 2005–2010. Participants completed four magnetic resonance scans over 2-years. A standardized protocol employing high resolution 3D T1-weighted sequences at 1.5 Tesla was used for structural imaging and regional brain volumetric analyses. Results Smokers demonstrated significantly greater rate atrophy over 2-years than non-smokers in multiple brain regions associated with the early stages of AD as well as in the BRS. Groups were not different on rate of global cortical atrophy. Conclusions A history of cigarette smoking in this healthy elderly cohort was associated with decreased structural integrity of multiple brain regions, which was manifest as a greater rate of atrophy over 2-years in regions specifically affected by incipient AD as well as chronic substance abuse. PMID:23102121

Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma.

PubMed

Simonsen, Trude G; Gaustad, Jon-Vidar; Rofstad, Einar K

2016-06-01

A majority of patients with melanoma brain metastases develop multiple lesions, and these patients show particularly poor prognosis. To develop improved treatment strategies, detailed insights into the biology of melanoma brain metastases, and particularly the development of multiple lesions, are needed. The purpose of this preclinical investigation was to study melanoma cell migration within the brain after cell injection into a well-defined intracerebral site. A-07, D-12, R-18, and U-25 human melanoma cells transfected with green fluorescent protein were injected stereotactically into the right cerebral hemisphere of nude mice. Moribund mice were killed and autopsied, and the brain was evaluated by fluorescence imaging or histological examination. Intracerebral inoculation of melanoma cells produced multiple lesions involving all regions of the brain, suggesting that the cells were able to migrate over substantial distances within the brain. Multiple modes of transport were identified, and all transport modes were observed in all four melanoma lines. Thus, the melanoma cells were passively transported via the flow of cerebrospinal fluid in the meninges and ventricles, they migrated actively along leptomeningeal and brain parenchymal blood vessels, and they migrated actively along the surfaces separating different brain compartments. Migration of melanoma cells after initial arrest, extravasation, and growth at a single location within the brain may contribute significantly to the development of multiple melanoma brain metastases. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Frontal parenchymal atrophy measures in multiple sclerosis.

PubMed

Locatelli, Laura; Zivadinov, Robert; Grop, Attilio; Zorzon, Marino

2004-10-01

The aim of this study was to establish whether, in a cross-sectional study, the normalized measures of whole and regional brain atrophy correlate better with tests assessing the cognitive function than the absolute brain atrophy measures. The neuropsychological performances and disability have been assessed in 39 patients with relapsing-remitting multiple sclerosis (MS). T1- and T2-lesion load (LL) of total brain and frontal lobes (FLs) were measured using a reproducible semiautomated technique. The whole brain volume and the regional brain parenchymal volume (RBPV) of FLs were obtained using a computerized interactive program, which incorporates semiautomated and automated segmentation processes. Normalized measures of brain atrophy, i.e., brain parenchymal fraction (BPF) and regional brain parenchymal fraction (RBPF) of FLs, were calculated. The scan-rescan, inter- and intrarater coefficient of variation (COV) and intraclass correlation coefficient (ICC) have been estimated. The RBPF of FLs showed an acceptable level of reproducibility which ranged from 1.7% for intrarater variability to 3.2% for scan-rescan variability. The mean ICC was 0.88 (CI 0.82-0.93). The RBPF of FLs demonstrated stronger magnitudes of correlation with neuropsychological functioning, disability and quantitative MRI lesion measures than RBPV. These differences were statistically significant: P<0.001 for Stroop Color Word Interference test, P<0.001 for Paced Auditory Serial Addition Test, P=0.04 for Standard Raven Progressive Matrices, P=0.049 for Expanded Disability Status Scale, P=0.01 for T2-LL of FLs and P<0.001 for T1-LL of FLs. BPF demonstrated significant correlations with tests assessing cognitive functions, whereas BPAV did not. The correlation analysis results were supported by the results of multiple regression analysis which showed that only the normalized brain atrophy measures were associated with tests exploring the cognitive functions. These data suggest that RBPF is a reproducible and sensitive method for measuring frontal parenchymal atrophy. The normalized measures of whole and regional brain parenchymal atrophy should be preferred to absolute measures in future studies that correlate neuropsychological performances and brain atrophy measures in patients with MS.

The multisensory brain and its ability to learn music.

PubMed

Zimmerman, Emily; Lahav, Amir

2012-04-01

Playing a musical instrument requires a complex skill set that depends on the brain's ability to quickly integrate information from multiple senses. It has been well documented that intensive musical training alters brain structure and function within and across multisensory brain regions, supporting the experience-dependent plasticity model. Here, we argue that this experience-dependent plasticity occurs because of the multisensory nature of the brain and may be an important contributing factor to musical learning. This review highlights key multisensory regions within the brain and discusses their role in the context of music learning and rehabilitation. © 2012 New York Academy of Sciences.

Cerebellar contribution to motor and cognitive performance in multiple sclerosis: An MRI sub-regional volumetric analysis.

PubMed

D'Ambrosio, Alessandro; Pagani, Elisabetta; Riccitelli, Gianna C; Colombo, Bruno; Rodegher, Mariaemma; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo; Rocca, Maria A

2017-08-01

To investigate the role of cerebellar sub-regions on motor and cognitive performance in multiple sclerosis (MS) patients. Whole and sub-regional cerebellar volumes, brain volumes, T2 hyperintense lesion volumes (LV), and motor performance scores were obtained from 95 relapse-onset MS patients and 32 healthy controls (HC). MS patients also underwent an evaluation of working memory and processing speed functions. Cerebellar anterior and posterior lobes were segmented using the Spatially Unbiased Infratentorial Toolbox (SUIT) from Statistical Parametric Mapping (SPM12). Multivariate linear regression models assessed the relationship between magnetic resonance imaging (MRI) measures and motor/cognitive scores. Compared to HC, only secondary progressive multiple sclerosis (SPMS) patients had lower cerebellar volumes (total and posterior cerebellum). In MS patients, lower anterior cerebellar volume and brain T2 LV predicted worse motor performance, whereas lower posterior cerebellar volume and brain T2 LV predicted poor cognitive performance. Global measures of brain volume and infratentorial T2 LV were not selected by the final multivariate models. Cerebellar volumetric abnormalities are likely to play an important contribution to explain motor and cognitive performance in MS patients. Consistently with functional mapping studies, cerebellar posterior-inferior volume accounted for variance in cognitive measures, whereas anterior cerebellar volume accounted for variance in motor performance, supporting the assessment of cerebellar damage at sub-regional level.

Art and brain: insights from neuropsychology, biology and evolution.

PubMed

Zaidel, Dahlia W

2010-02-01

Art is a uniquely human activity associated fundamentally with symbolic and abstract cognition. Its practice in human societies throughout the world, coupled with seeming non-functionality, has led to three major brain theories of art. (1) The localized brain regions and pathways theory links art to multiple neural regions. (2) The display of art and its aesthetics theory is tied to the biological motivation of courtship signals and mate selection strategies in animals. (3) The evolutionary theory links the symbolic nature of art to critical pivotal brain changes in Homo sapiens supporting increased development of language and hierarchical social grouping. Collectively, these theories point to art as a multi-process cognition dependent on diverse brain regions and on redundancy in art-related functional representation.

Art and brain: insights from neuropsychology, biology and evolution

PubMed Central

Zaidel, Dahlia W

2010-01-01

Art is a uniquely human activity associated fundamentally with symbolic and abstract cognition. Its practice in human societies throughout the world, coupled with seeming non-functionality, has led to three major brain theories of art. (1) The localized brain regions and pathways theory links art to multiple neural regions. (2) The display of art and its aesthetics theory is tied to the biological motivation of courtship signals and mate selection strategies in animals. (3) The evolutionary theory links the symbolic nature of art to critical pivotal brain changes in Homo sapiens supporting increased development of language and hierarchical social grouping. Collectively, these theories point to art as a multi-process cognition dependent on diverse brain regions and on redundancy in art-related functional representation. PMID:19490399

Differences between child and adult large-scale functional brain networks for reading tasks.

PubMed

Liu, Xin; Gao, Yue; Di, Qiqi; Hu, Jiali; Lu, Chunming; Nan, Yun; Booth, James R; Liu, Li

2018-02-01

Reading is an important high-level cognitive function of the human brain, requiring interaction among multiple brain regions. Revealing differences between children's large-scale functional brain networks for reading tasks and those of adults helps us to understand how the functional network changes over reading development. Here we used functional magnetic resonance imaging data of 17 adults (19-28 years old) and 16 children (11-13 years old), and graph theoretical analyses to investigate age-related changes in large-scale functional networks during rhyming and meaning judgment tasks on pairs of visually presented Chinese characters. We found that: (1) adults had stronger inter-regional connectivity and nodal degree in occipital regions, while children had stronger inter-regional connectivity in temporal regions, suggesting that adults rely more on visual orthographic processing whereas children rely more on auditory phonological processing during reading. (2) Only adults showed between-task differences in inter-regional connectivity and nodal degree, whereas children showed no task differences, suggesting the topological organization of adults' reading network is more specialized. (3) Children showed greater inter-regional connectivity and nodal degree than adults in multiple subcortical regions; the hubs in children were more distributed in subcortical regions while the hubs in adults were more distributed in cortical regions. These findings suggest that reading development is manifested by a shift from reliance on subcortical to cortical regions. Taken together, our study suggests that Chinese reading development is supported by developmental changes in brain connectivity properties, and some of these changes may be domain-general while others may be specific to the reading domain. © 2017 Wiley Periodicals, Inc.

GABA and glutamate levels correlate with MTR and clinical disability: Insights from multiple sclerosis.

PubMed

Nantes, Julia C; Proulx, Sébastien; Zhong, Jidan; Holmes, Scott A; Narayanan, Sridar; Brown, Robert A; Hoge, Richard D; Koski, Lisa

2017-08-15

Converging areas of research have implicated glutamate and γ-aminobutyric acid (GABA) as key players in neuronal signalling and other central functions. Further research is needed, however, to identify microstructural and behavioral links to regional variability in levels of these neurometabolites, particularly in the presence of demyelinating disease. Thus, we sought to investigate the extent to which regional glutamate and GABA levels are related to a neuroimaging marker of microstructural damage and to motor and cognitive performance. Twenty-one healthy volunteers and 47 people with multiple sclerosis (all right-handed) participated in this study. Motor and cognitive abilities were assessed with standard tests used in the study of multiple sclerosis. Proton magnetic resonance spectroscopy data were acquired from sensorimotor and parietal regions of the brains' left cerebral hemisphere using a MEGA-PRESS sequence. Our analysis protocol for the spectroscopy data was designed to account for confounding factors that could contaminate the measurement of neurometabolite levels due to disease, such as the macromolecule signal, partial volume effects, and relaxation effects. Glutamate levels in both regions of interest were lower in people with multiple sclerosis. In the sensorimotor (though not the parietal) region, GABA concentration was higher in the multiple sclerosis group compared to controls. Lower magnetization transfer ratio within grey and white matter regions from which spectroscopy data were acquired was linked to neurometabolite levels. When adjusting for age, normalized brain volume, MTR, total N-acetylaspartate level, and glutamate level, significant relationships were found between lower sensorimotor GABA level and worse performance on several tests, including one of upper limb motor function. This work highlights important methodological considerations relevant to analysis of spectroscopy data, particularly in the afflicted human brain. These findings support that regional neurotransmitter levels are linked to local microstructural integrity and specific behavioral abilities that can be affected in diseases such as multiple sclerosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Altered structural connectivity of pain-related brain network in burning mouth syndrome-investigation by graph analysis of probabilistic tractography.

PubMed

Wada, Akihiko; Shizukuishi, Takashi; Kikuta, Junko; Yamada, Haruyasu; Watanabe, Yusuke; Imamura, Yoshiki; Shinozaki, Takahiro; Dezawa, Ko; Haradome, Hiroki; Abe, Osamu

2017-05-01

Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome featuring idiopathic oral pain and burning discomfort despite clinically normal oral mucosa. The etiology of chronic pain syndrome is unclear, but preliminary neuroimaging research has suggested the alteration of volume, metabolism, blood flow, and diffusion at multiple brain regions. According to the neuromatrix theory of Melzack, pain sense is generated in the brain by the network of multiple pain-related brain regions. Therefore, the alteration of pain-related network is also assumed as an etiology of chronic pain. In this study, we investigated the brain network of BMS brain by using probabilistic tractography and graph analysis. Fourteen BMS patients and 14 age-matched healthy controls underwent 1.5T MRI. Structural connectivity was calculated in 83 anatomically defined regions with probabilistic tractography of 60-axis diffusion tensor imaging and 3D T1-weighted imaging. Graph theory network analysis was used to evaluate the brain network at local and global connectivity. In BMS brain, a significant difference of local brain connectivity was recognized at the bilateral rostral anterior cingulate cortex, right medial orbitofrontal cortex, and left pars orbitalis which belong to the medial pain system; however, no significant difference was recognized at the lateral system including the somatic sensory cortex. A strengthened connection of the anterior cingulate cortex and medial prefrontal cortex with the basal ganglia, thalamus, and brain stem was revealed. Structural brain network analysis revealed the alteration of the medial system of the pain-related brain network in chronic pain syndrome.

Benefits from an autobiographical memory facilitation programme in relapsing-remitting multiple sclerosis patients: a clinical and neuroimaging study.

PubMed

Ernst, Alexandra; Sourty, Marion; Roquet, Daniel; Noblet, Vincent; Gounot, Daniel; Blanc, Frédéric; de Seze, Jérôme; Manning, Liliann

2016-10-09

While the efficacy of mental visual imagery (MVI) to alleviate autobiographical memory (AM) impairment in multiple sclerosis (MS) patients has been documented, nothing is known about the brain changes sustaining that improvement. To explore this issue, 20 relapsing-remitting MS patients showing AM impairment were randomly assigned to two groups, experimental (n = 10), who underwent the MVI programme, and control (n = 10), who followed a sham verbal programme. Besides the stringent AM assessment, the patients underwent structural and functional MRI sessions, consisting in retrieving personal memories, within a pre-/post-facilitation study design. Only the experimental group showed a significant AM improvement in post-facilitation, accompanied by changes in brain activation (medial and lateral frontal regions), functional connectivity (posterior brain regions), and grey matter volume (parahippocampal gyrus). Minor activations and functional connectivity changes were observed in the control group. The MVI programme improved AM in MS patients leading to functional and structural changes reflecting (1) an increase reliance on brain regions sustaining a self-referential process; (2) a decrease of those reflecting an effortful research process; and (3) better use of neural resources in brain regions sustaining MVI. Functional changes reported in the control group likely reflected ineffective attempts to use the sham strategy in AM.

Brain MRI volumetry in a single patient with mild traumatic brain injury.

PubMed

Ross, David E; Castelvecchi, Cody; Ochs, Alfred L

2013-01-01

This letter to the editor describes the case of a 42 year old man with mild traumatic brain injury and multiple neuropsychiatric symptoms which persisted for a few years after the injury. Initial CT scans and MRI scans of the brain showed no signs of atrophy. Brain volume was measured using NeuroQuant®, an FDA-approved, commercially available software method. Volumetric cross-sectional (one point in time) analysis also showed no atrophy. However, volumetric longitudinal (two points in time) analysis showed progressive atrophy in several brain regions. This case illustrated in a single patient the principle discovered in multiple previous group studies, namely that the longitudinal design is more powerful than the cross-sectional design for finding atrophy in patients with traumatic brain injury.

Inferring consistent functional interaction patterns from natural stimulus FMRI data

PubMed Central

Sun, Jiehuan; Hu, Xintao; Huang, Xiu; Liu, Yang; Li, Kaiming; Li, Xiang; Han, Junwei; Guo, Lei

2014-01-01

There has been increasing interest in how the human brain responds to natural stimulus such as video watching in the neuroimaging field. Along this direction, this paper presents our effort in inferring consistent and reproducible functional interaction patterns under natural stimulus of video watching among known functional brain regions identified by task-based fMRI. Then, we applied and compared four statistical approaches, including Bayesian network modeling with searching algorithms: greedy equivalence search (GES), Peter and Clark (PC) analysis, independent multiple greedy equivalence search (IMaGES), and the commonly used Granger causality analysis (GCA), to infer consistent and reproducible functional interaction patterns among these brain regions. It is interesting that a number of reliable and consistent functional interaction patterns were identified by the GES, PC and IMaGES algorithms in different participating subjects when they watched multiple video shots of the same semantic category. These interaction patterns are meaningful given current neuroscience knowledge and are reasonably reproducible across different brains and video shots. In particular, these consistent functional interaction patterns are supported by structural connections derived from diffusion tensor imaging (DTI) data, suggesting the structural underpinnings of consistent functional interactions. Our work demonstrates that specific consistent patterns of functional interactions among relevant brain regions might reflect the brain's fundamental mechanisms of online processing and comprehension of video messages. PMID:22440644

Brain mediators of the effects of noxious heat on pain

PubMed Central

Atlas, Lauren Y.; Lindquist, Martin A.; Bolger, Niall; Wager, Tor D.

2014-01-01

Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. While useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this paper, we used multi-level mediation analysis to identify brain mediators of pain—regions whose trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across four levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including: a) somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and b) two networks co-localized with ‘default mode’ regions in which stimulus intensity-related decreases mediated increased pain. We also identified ‘thermosensory’ regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. PMID:24845572

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

Multiple sclerosis patients lacking oligoclonal bands in the cerebrospinal fluid have less global and regional brain atrophy.

PubMed

Ferreira, Daniel; Voevodskaya, Olga; Imrell, Kerstin; Stawiarz, Leszek; Spulber, Gabriela; Wahlund, Lars-Olof; Hillert, Jan; Westman, Eric; Karrenbauer, Virginija Danylaité

2014-09-15

To investigate whether multiple sclerosis (MS) patients with and without cerebrospinal fluid (CSF) oligoclonal immunoglobulin G bands (OCB) differ in brain atrophy. Twenty-eight OCB-negative and thirty-five OCB-positive patients were included. Larger volumes of total CSF and white matter (WM) lesions; smaller gray matter (GM) volume in the basal ganglia, diencephalon, cerebellum, and hippocampus; and smaller WM volume in corpus callosum, periventricular-deep WM, brainstem, and cerebellum, were observed in OCB-positives. OCB-negative patients, known to differ genetically from OCB-positives, are characterized by less global and regional brain atrophy. This finding supports the notion that OCB-negative MS patients may represent a clinically relevant MS subgroup. Copyright © 2014 Elsevier B.V. All rights reserved.

Neural Representation of Subjective Sexual Arousal in Men and Women.

PubMed

Parada, Mayte; Gérard, Marina; Larcher, Kevin; Dagher, Alain; Binik, Yitzchak M

2016-10-01

Studies investigating brain indices of sexual arousal have begun to elucidate the brain's role in processing subjective arousal; however, most research has focused on men, used discrete ratings of subjective arousal, and used stimuli too short to induce significant arousal in women. To examine brain regions modulated by changes in subjective sexual arousal (SSA) rating intensity in men and women. Two groups (20 men, 20 women) viewed movie clips (erotic or humorous) while continuously evaluating changes in their SSA using a Likert-like scale (0 = not aroused, 10 = most aroused) and answering discrete questions about liking the movies and wanting sexual stimulation. Brain activity was measured using functional magnetic resonance imaging. Blood oxygen level-dependent responses and continuous and discrete measurements of sexual arousal. Erotic movies induced significant SSA in men and women. No sex difference in mean SSA was found in response to the erotic movies on continuous or discrete measurements. Several brain regions were correlated with changes in SSA. Parametric modulation with rating intensity showed a specific group of regions within the parietal lobe that showed significant differences in activity among low, medium, and high SSA. Multiple regions were concordant with changes in SSA; however, a subset of regions in men and women was modulated by SSA intensity, a subset previously linked to attentional processes, monitoring of internal body representation, and processing of sensory information from the genitals. This study highlights that similar brain regions are activated during subjective assessment of sexual arousal in men and women. The data further highlight the fact that SSA is a complex phenomenon made up of multiple interoceptive and attentional processes. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Region-specific deletions of RIM1 reproduce a subset of global RIM1α−/− phenotypes

PubMed Central

Haws, M E; Kaeser, P S; Jarvis, D L; Südhof, T C; Powell, C M

2012-01-01

The presynaptic protein RIM1α mediates multiple forms of presynaptic plasticity at both excitatory and inhibitory synapses. Previous studies of mice lacking RIM1α (RIM1α−/− throughout the brain showed that deletion of RIM1α results in multiple behavioral abnormalities. In an effort to begin to delineate the brain regions in which RIM1 deletion mediates these abnormal behaviors, we used conditional (floxed) RIM1 knockout mice (fRIM1). By crossing these fRIM1 mice to previously characterized transgenic cre lines, we aimed to delete RIM1 selectively in the dentate gyrus (DG), using a specific preproopiomelanocortin promoter driving cre recombinase (POMC-cre) line , and in pyramidal neurons of the CA3 region of hippocampus, using the kainate receptor subunit 1 promoter driving cre recombinase (KA-cre). Neither of these cre driver lines was uniquely selective to the targeted regions. In spite of this, we were able to reproduce a subset of the global RIM1α−/− behavioral abnormalities, thereby narrowing the brain regions in which loss of RIM1 is sufficient to produce these behavioral differences. Most interestingly, hypersensitivity to the pyschotomimetic MK-801 was shown in mice lacking RIM1 selectively in the DG, arcuate nucleus of the hypothalamus and select cerebellar neurons, implicating novel brain regions and neuronal subtypes in this behavior. PMID:22103334

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

Multi-scale integration and predictability in resting state brain activity

PubMed Central

Kolchinsky, Artemy; van den Heuvel, Martijn P.; Griffa, Alessandra; Hagmann, Patric; Rocha, Luis M.; Sporns, Olaf; Goñi, Joaquín

2014-01-01

The human brain displays heterogeneous organization in both structure and function. Here we develop a method to characterize brain regions and networks in terms of information-theoretic measures. We look at how these measures scale when larger spatial regions as well as larger connectome sub-networks are considered. This framework is applied to human brain fMRI recordings of resting-state activity and DSI-inferred structural connectivity. We find that strong functional coupling across large spatial distances distinguishes functional hubs from unimodal low-level areas, and that this long-range functional coupling correlates with structural long-range efficiency on the connectome. We also find a set of connectome regions that are both internally integrated and coupled to the rest of the brain, and which resemble previously reported resting-state networks. Finally, we argue that information-theoretic measures are useful for characterizing the functional organization of the brain at multiple scales. PMID:25104933

Noninvasive monitoring of treatment response in a rabbit cyanide toxicity model reveals differences in brain and muscle metabolism

NASA Astrophysics Data System (ADS)

Kim, Jae G.; Lee, Jangwoen; Mahon, Sari B.; Mukai, David; Patterson, Steven E.; Boss, Gerry R.; Tromberg, Bruce J.; Brenner, Matthew

2012-10-01

Noninvasive near infrared spectroscopy measurements were performed to monitor cyanide (CN) poisoning and recovery in the brain region and in foreleg muscle simultaneously, and the effects of a novel CN antidote, sulfanegen sodium, on tissue hemoglobin oxygenation changes were compared using a sub-lethal rabbit model. The results demonstrated that the brain region is more susceptible to CN poisoning and slower in endogenous CN detoxification following exposure than peripheral muscles. However, sulfanegen sodium rapidly reversed CN toxicity, with brain region effects reversing more quickly than muscle. In vivo monitoring of multiple organs may provide important clinical information regarding the extent of CN toxicity and subsequent recovery, and facilitate antidote drug development.

Beamspace fast fully adaptive brain source localization for limited data sequences

NASA Astrophysics Data System (ADS)

Ravan, Maryam

2017-05-01

In the electroencephalogram (EEG) or magnetoencephalogram (MEG) context, brain source localization methods that rely on estimating second order statistics often fail when the observations are taken over a short time interval, especially when the number of electrodes is large. To address this issue, in previous study, we developed a multistage adaptive processing called fast fully adaptive (FFA) approach that can significantly reduce the required sample support while still processing all available degrees of freedom (DOFs). This approach processes the observed data in stages through a decimation procedure. In this study, we introduce a new form of FFA approach called beamspace FFA. We first divide the brain into smaller regions and transform the measured data from the source space to the beamspace in each region. The FFA approach is then applied to the beamspaced data of each region. The goal of this modification is to benefit the correlation sensitivity reduction between sources in different brain regions. To demonstrate the performance of the beamspace FFA approach in the limited data scenario, simulation results with multiple deep and cortical sources as well as experimental results are compared with regular FFA and widely used FINE approaches. Both simulation and experimental results demonstrate that the beamspace FFA method can localize different types of multiple correlated brain sources in low signal to noise ratios more accurately with limited data.

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

A Technical Approach to Expedited Processing of NTPR Radiation Dose Assessments

DTIC Science & Technology

2011-10-01

Pharynx ET Region+ Surrogate Oral Cavity and Pharynx (140-149) None PNLGL Pineal Gland Brain Surrogate Other Endocrine Glands (194) PITTGL PITTGL...including brain); endocrine glands other than thyroid; other and ill-defined sites; lymphoma and multiple myeloma Risk depends on age at exposure...endocrine glands 14 45 Cancers of other and ill-defined sites 16 50 Lymphoma and multiple myeloma 22 61 Leukemia, excluding CLL 1.9 (5 years) 41

Brain mediators of the effects of noxious heat on pain.

PubMed

Atlas, Lauren Y; Lindquist, Martin A; Bolger, Niall; Wager, Tor D

2014-08-01

Recent human neuroimaging studies have investigated the neural correlates of either noxious stimulus intensity or reported pain. Although useful, analyzing brain relationships with stimulus intensity and behavior separately does not address how sensation and pain are linked in the central nervous system. In this study, we used multi-level mediation analysis to identify brain mediators of pain--regions in which trial-by-trial responses to heat explained variability in the relationship between noxious stimulus intensity (across 4 levels) and pain. This approach has the potential to identify multiple circuits with complementary roles in pain genesis. Brain mediators of noxious heat effects on pain included targets of ascending nociceptive pathways (anterior cingulate, insula, SII, and medial thalamus) and also prefrontal and subcortical regions not associated with nociceptive pathways per se. Cluster analysis revealed that mediators were grouped into several distinct functional networks, including the following: somatosensory, paralimbic, and striatal-cerebellar networks that increased with stimulus intensity; and 2 networks co-localized with "default mode" regions in which stimulus intensity-related decreases mediated increased pain. We also identified "thermosensory" regions that responded to increasing noxious heat but did not predict pain reports. Finally, several regions did not respond to noxious input, but their activity predicted pain; these included ventromedial prefrontal cortex, dorsolateral prefrontal cortex, cerebellar regions, and supplementary motor cortices. These regions likely underlie both nociceptive and non-nociceptive processes that contribute to pain, such as attention and decision-making processes. Overall, these results elucidate how multiple distinct brain systems jointly contribute to the central generation of pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

(±)3,4-Methylenedioxymethamphetamine (“Ecstasy”) Treatment Modulates Expression of Neurotrophins and Their Receptors in Multiple Regions of Adult Rat Brain

PubMed Central

Hemmerle, Ann M.; Dickerson, Jonathan W.; Herring, Nicole R.; Schaefer, Tori L.; Vorhees, Charles V.; Williams, Michael T.; Seroogy, Kim B.

2014-01-01

(±)3,4-Methylenedioxymethamphetamine (MDMA), a widely used drug of abuse, rapidly reduces serotonin levels in the brain when ingested or administered in sufficient quantities, resulting in deficits in complex route-based learning, spatial learning, and reference memory. Neurotrophins are important for survival and preservation of neurons in the adult brain, including serotonergic neurons. In this study, we examined the effects of MDMA on the expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and their respective high-affinity receptors, tropomyosin receptor kinase (trk)B and trkC, in multiple regions of the rat brain. A serotonergic-depleting dose of MDMA (10 mg/kg × 4 at 2-hour intervals on a single day) was administered to adult Sprague-Dawley rats, and brains were examined 1, 7, or 24 hours after the last dose. Messenger RNA levels of BDNF, NT-3, trkB, and trkC were analyzed by using in situ hybridization with cRNA probes. The prefrontal cortex was particularly vulnerable to MDMA-induced alterations in that BDNF, NT-3, trkB, and trkC mRNAs were all upregulated at multiple time points. MDMA-treated animals had increased BDNF expression in the frontal, parietal, piriform, and entorhinal cortices, increased NT-3 expression in the anterior cingulate cortex, and elevated trkC in the entorhinal cortex. In the nigrostriatal system, BDNF expression was upregulated in the substantia nigra pars compacta, and trkB was elevated in the striatum in MDMA-treated animals. Both neurotrophins and trkB were differentially regulated in several regions of the hippocampal formation. These findings suggest a possible role for neurotrophin signaling in the learning and memory deficits seen following MDMA treatment. PMID:22237931

FMRI activity during associative encoding is correlated with cardiorespiratory fitness and source memory performance in older adults

PubMed Central

Hayes, Scott M.; Hayes, Jasmeet P.; Williams, Victoria J.; Liu, Huiting; Verfaellie, Mieke

2017-01-01

Older adults (OA), relative to young adults (YA), exhibit age-related alterations in functional Magnetic Resonance Imaging (fMRI) activity during associative encoding, which contributes to deficits in source memory. Yet, there are remarkable individual differences in brain health and memory performance among OA. Cardiorespiratory fitness (CRF) is one individual difference factor that may attenuate brain aging, and thereby contribute to enhanced source memory in OA. To examine this possibility, 26 OA and 31 YA completed a treadmill-based exercise test to evaluate CRF (peak VO2) and fMRI to examine brain activation during a face-name associative encoding task. Our results indicated that in OA, peak VO2 was positively associated with fMRI activity during associative encoding in multiple regions including bilateral prefrontal cortex, medial frontal cortex, bilateral thalamus and left hippocampus. Next, a conjunction analysis was conducted to assess whether CRF influenced age-related differences in fMRI activation. We classified OA as high or low CRF and compared their activation to YA. High fit OA (HFOA) showed fMRI activation more similar to YA than low fit OA (LFOA) (i.e., reduced age-related differences) in multiple regions including thalamus, posterior and prefrontal cortex. Conversely, in other regions, primarily in prefrontal cortex, HFOA, but not LFOA, demonstrated greater activation than YA (i.e., increased age-related differences). Further, fMRI activity in these brain regions was positively associated with source memory among OA, with a mediation model demonstrating that associative encoding activation in medial frontal cortex indirectly influenced the relationship between peak VO2 and subsequent source memory performance. These results indicate that CRF may contribute to neuroplasticity among OA, reducing age-related differences in some brain regions, consistent with the brain maintenance hypothesis, but accentuating age-differences in other regions, consistent with the brain compensation hypothesis. PMID:28161031

FMRI activity during associative encoding is correlated with cardiorespiratory fitness and source memory performance in older adults.

PubMed

Hayes, Scott M; Hayes, Jasmeet P; Williams, Victoria J; Liu, Huiting; Verfaellie, Mieke

2017-06-01

Older adults (OA), relative to young adults (YA), exhibit age-related alterations in functional Magnetic Resonance Imaging (fMRI) activity during associative encoding, which contributes to deficits in source memory. Yet, there are remarkable individual differences in brain health and memory performance among OA. Cardiorespiratory fitness (CRF) is one individual difference factor that may attenuate brain aging, and thereby contribute to enhanced source memory in OA. To examine this possibility, 26 OA and 31 YA completed a treadmill-based exercise test to evaluate CRF (peak VO 2 ) and fMRI to examine brain activation during a face-name associative encoding task. Our results indicated that in OA, peak VO 2 was positively associated with fMRI activity during associative encoding in multiple regions including bilateral prefrontal cortex, medial frontal cortex, bilateral thalamus and left hippocampus. Next, a conjunction analysis was conducted to assess whether CRF influenced age-related differences in fMRI activation. We classified OA as high or low CRF and compared their activation to YA. High fit OA (HFOA) showed fMRI activation more similar to YA than low fit OA (LFOA) (i.e., reduced age-related differences) in multiple regions including thalamus, posterior and prefrontal cortex. Conversely, in other regions, primarily in prefrontal cortex, HFOA, but not LFOA, demonstrated greater activation than YA (i.e., increased age-related differences). Further, fMRI activity in these brain regions was positively associated with source memory among OA, with a mediation model demonstrating that associative encoding activation in medial frontal cortex indirectly influenced the relationship between peak VO 2 and subsequent source memory performance. These results indicate that CRF may contribute to neuroplasticity among OA, reducing age-related differences in some brain regions, consistent with the brain maintenance hypothesis, but accentuating age-differences in other regions, consistent with the brain compensation hypothesis. Published by Elsevier Ltd.

Impact of playing American professional football on long-term brain function.

PubMed

Amen, Daniel G; Newberg, Andrew; Thatcher, Robert; Jin, Yi; Wu, Joseph; Keator, David; Willeumier, Kristen

2011-01-01

The authors recruited 100 active and former National Football League players, representing 27 teams and all positions. Players underwent a clinical history, brain SPECT imaging, qEEG, and multiple neuropsychological measures, including MicroCog. Relative to a healthy-comparison group, players showed global decreased perfusion, especially in the prefrontal, temporal, parietal, and occipital lobes, and cerebellar regions. Quantitative EEG findings were consistent, showing elevated slow waves in the frontal and temporal regions. Significant decreases from normal values were found in most neuropsychological tests. This is the first large-scale brain-imaging study to demonstrate significant differences consistent with a chronic brain trauma pattern in professional football players.

Normative brain size variation and brain shape diversity in humans.

PubMed

Reardon, P K; Seidlitz, Jakob; Vandekar, Simon; Liu, Siyuan; Patel, Raihaan; Park, Min Tae M; Alexander-Bloch, Aaron; Clasen, Liv S; Blumenthal, Jonathan D; Lalonde, Francois M; Giedd, Jay N; Gur, Ruben C; Gur, Raquel E; Lerch, Jason P; Chakravarty, M Mallar; Satterthwaite, Theodore D; Shinohara, Russell T; Raznahan, Armin

2018-06-15

Brain size variation over primate evolution and human development is associated with shifts in the proportions of different brain regions. Individual brain size can vary almost twofold among typically developing humans, but the consequences of this for brain organization remain poorly understood. Using in vivo neuroimaging data from more than 3000 individuals, we find that larger human brains show greater areal expansion in distributed frontoparietal cortical networks and related subcortical regions than in limbic, sensory, and motor systems. This areal redistribution recapitulates cortical remodeling across evolution, manifests by early childhood in humans, and is linked to multiple markers of heightened metabolic cost and neuronal connectivity. Thus, human brain shape is systematically coupled to naturally occurring variations in brain size through a scaling map that integrates spatiotemporally diverse aspects of neurobiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Integrated Analysis and Visualization of Group Differences in Structural and Functional Brain Connectivity: Applications in Typical Ageing and Schizophrenia.

PubMed

Langen, Carolyn D; White, Tonya; Ikram, M Arfan; Vernooij, Meike W; Niessen, Wiro J

2015-01-01

Structural and functional brain connectivity are increasingly used to identify and analyze group differences in studies of brain disease. This study presents methods to analyze uni- and bi-modal brain connectivity and evaluate their ability to identify differences. Novel visualizations of significantly different connections comparing multiple metrics are presented. On the global level, "bi-modal comparison plots" show the distribution of uni- and bi-modal group differences and the relationship between structure and function. Differences between brain lobes are visualized using "worm plots". Group differences in connections are examined with an existing visualization, the "connectogram". These visualizations were evaluated in two proof-of-concept studies: (1) middle-aged versus elderly subjects; and (2) patients with schizophrenia versus controls. Each included two measures derived from diffusion weighted images and two from functional magnetic resonance images. The structural measures were minimum cost path between two anatomical regions according to the "Statistical Analysis of Minimum cost path based Structural Connectivity" method and the average fractional anisotropy along the fiber. The functional measures were Pearson's correlation and partial correlation of mean regional time series. The relationship between structure and function was similar in both studies. Uni-modal group differences varied greatly between connectivity types. Group differences were identified in both studies globally, within brain lobes and between regions. In the aging study, minimum cost path was highly effective in identifying group differences on all levels; fractional anisotropy and mean correlation showed smaller differences on the brain lobe and regional levels. In the schizophrenia study, minimum cost path and fractional anisotropy showed differences on the global level and within brain lobes; mean correlation showed small differences on the lobe level. Only fractional anisotropy and mean correlation showed regional differences. The presented visualizations were helpful in comparing and evaluating connectivity measures on multiple levels in both studies.

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.

High-resolution temporal and regional mapping of MAPT expression and splicing in human brain development.

PubMed

Hefti, Marco M; Farrell, Kurt; Kim, SoongHo; Bowles, Kathryn R; Fowkes, Mary E; Raj, Towfique; Crary, John F

2018-01-01

The microtubule associated protein tau plays a critical role in the pathogenesis of neurodegenerative disease. Recent studies suggest that tau also plays a role in disorders of neuronal connectivity, including epilepsy and post-traumatic stress disorder. Animal studies have shown that the MAPT gene, which codes for the tau protein, undergoes complex pre-mRNA alternative splicing to produce multiple isoforms during brain development. Human data, particularly on temporal and regional variation in tau splicing during development are however lacking. In this study, we present the first detailed examination of the temporal and regional sequence of MAPT alternative splicing in the developing human brain. We used a novel computational analysis of large transcriptomic datasets (total n = 502 patients), quantitative polymerase chain reaction (qPCR) and western blotting to examine tau expression and splicing in post-mortem human fetal, pediatric and adult brains. We found that MAPT exons 2 and 10 undergo abrupt shifts in expression during the perinatal period that are unique in the canonical human microtubule-associated protein family, while exon 3 showed small but significant temporal variation. Tau isoform expression may be a marker of neuronal maturation, temporally correlated with the onset of axonal growth. Immature brain regions such as the ganglionic eminence and rhombic lip had very low tau expression, but within more mature regions, there was little variation in tau expression or splicing. We thus demonstrate an abrupt, evolutionarily conserved shift in tau isoform expression during the human perinatal period that may be due to tau expression in maturing neurons. Alternative splicing of the MAPT pre-mRNA may play a vital role in normal brain development across multiple species and provides a basis for future investigations into the developmental and pathological functions of the tau protein.

Importance of Multimodal MRI in Characterizing Brain Tissue and Its Potential Application for Individual Age Prediction.

PubMed

Cherubini, Andrea; Caligiuri, Maria Eugenia; Peran, Patrice; Sabatini, Umberto; Cosentino, Carlo; Amato, Francesco

2016-09-01

This study presents a voxel-based multiple regression analysis of different magnetic resonance image modalities, including anatomical T1-weighted, T2(*) relaxometry, and diffusion tensor imaging. Quantitative parameters sensitive to complementary brain tissue alterations, including morphometric atrophy, mineralization, microstructural damage, and anisotropy loss, were compared in a linear physiological aging model in 140 healthy subjects (range 20-74 years). The performance of different predictors and the identification of the best biomarker of age-induced structural variation were compared without a priori anatomical knowledge. The best quantitative predictors in several brain regions were iron deposition and microstructural damage, rather than macroscopic tissue atrophy. Age variations were best resolved with a combination of markers, suggesting that multiple predictors better capture age-induced tissue alterations. The results of the linear model were used to predict apparent age in different regions of individual brain. This approach pointed to a number of novel applications that could potentially help highlighting areas particularly vulnerable to disease.

The Face-Processing Network Is Resilient to Focal Resection of Human Visual Cortex

PubMed Central

Jonas, Jacques; Gomez, Jesse; Maillard, Louis; Brissart, Hélène; Hossu, Gabriela; Jacques, Corentin; Loftus, David; Colnat-Coulbois, Sophie; Stigliani, Anthony; Barnett, Michael A.; Grill-Spector, Kalanit; Rossion, Bruno

2016-01-01

Human face perception requires a network of brain regions distributed throughout the occipital and temporal lobes with a right hemisphere advantage. Present theories consider this network as either a processing hierarchy beginning with the inferior occipital gyrus (occipital face area; IOG-faces/OFA) or a multiple-route network with nonhierarchical components. The former predicts that removing IOG-faces/OFA will detrimentally affect downstream stages, whereas the latter does not. We tested this prediction in a human patient (Patient S.P.) requiring removal of the right inferior occipital cortex, including IOG-faces/OFA. We acquired multiple fMRI measurements in Patient S.P. before and after a preplanned surgery and multiple measurements in typical controls, enabling both within-subject/across-session comparisons (Patient S.P. before resection vs Patient S.P. after resection) and between-subject/across-session comparisons (Patient S.P. vs controls). We found that the spatial topology and selectivity of downstream ipsilateral face-selective regions were stable 1 and 8 month(s) after surgery. Additionally, the reliability of distributed patterns of face selectivity in Patient S.P. before versus after resection was not different from across-session reliability in controls. Nevertheless, postoperatively, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1 of the resected hemisphere. Diffusion weighted imaging in Patient S.P. and controls identifies white matter tracts connecting retinotopic areas to downstream face-selective regions, which may contribute to the stable and plastic features of the face network in Patient S.P. after surgery. Together, our results support a multiple-route network of face processing with nonhierarchical components and shed light on stable and plastic features of high-level visual cortex following focal brain damage. SIGNIFICANCE STATEMENT Brain networks consist of interconnected functional regions commonly organized in processing hierarchies. Prevailing theories predict that damage to the input of the hierarchy will detrimentally affect later stages. We tested this prediction with multiple brain measurements in a rare human patient requiring surgical removal of the putative input to a network processing faces. Surprisingly, the spatial topology and selectivity of downstream face-selective regions are stable after surgery. Nevertheless, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1. White matter connections from outside the face network may support these stable and plastic features. As processing hierarchies are ubiquitous in biological and nonbiological systems, our results have pervasive implications for understanding the construction of resilient networks. PMID:27511014

The Human Thalamus Is an Integrative Hub for Functional Brain Networks

PubMed Central

Bertolero, Maxwell A.

2017-01-01

The thalamus is globally connected with distributed cortical regions, yet the functional significance of this extensive thalamocortical connectivity remains largely unknown. By performing graph-theoretic analyses on thalamocortical functional connectivity data collected from human participants, we found that most thalamic subdivisions display network properties that are capable of integrating multimodal information across diverse cortical functional networks. From a meta-analysis of a large dataset of functional brain-imaging experiments, we further found that the thalamus is involved in multiple cognitive functions. Finally, we found that focal thalamic lesions in humans have widespread distal effects, disrupting the modular organization of cortical functional networks. This converging evidence suggests that the human thalamus is a critical hub region that could integrate diverse information being processed throughout the cerebral cortex as well as maintain the modular structure of cortical functional networks. SIGNIFICANCE STATEMENT The thalamus is traditionally viewed as a passive relay station of information from sensory organs or subcortical structures to the cortex. However, the thalamus has extensive connections with the entire cerebral cortex, which can also serve to integrate information processing between cortical regions. In this study, we demonstrate that multiple thalamic subdivisions display network properties that are capable of integrating information across multiple functional brain networks. Moreover, the thalamus is engaged by tasks requiring multiple cognitive functions. These findings support the idea that the thalamus is involved in integrating information across cortical networks. PMID:28450543

Integration of silicon-based neural probes and micro-drive arrays for chronic recording of large populations of neurons in behaving animals

NASA Astrophysics Data System (ADS)

Michon, Frédéric; Aarts, Arno; Holzhammer, Tobias; Ruther, Patrick; Borghs, Gustaaf; McNaughton, Bruce; Kloosterman, Fabian

2016-08-01

Objective. Understanding how neuronal assemblies underlie cognitive function is a fundamental question in system neuroscience. It poses the technical challenge to monitor the activity of populations of neurons, potentially widely separated, in relation to behaviour. In this paper, we present a new system which aims at simultaneously recording from a large population of neurons from multiple separated brain regions in freely behaving animals. Approach. The concept of the new device is to combine the benefits of two existing electrophysiological techniques, i.e. the flexibility and modularity of micro-drive arrays and the high sampling ability of electrode-dense silicon probes. Main results. Newly engineered long bendable silicon probes were integrated into a micro-drive array. The resulting device can carry up to 16 independently movable silicon probes, each carrying 16 recording sites. Populations of neurons were recorded simultaneously in multiple cortical and/or hippocampal sites in two freely behaving implanted rats. Significance. Current approaches to monitor neuronal activity either allow to flexibly record from multiple widely separated brain regions (micro-drive arrays) but with a limited sampling density or to provide denser sampling at the expense of a flexible placement in multiple brain regions (neural probes). By combining these two approaches and their benefits, we present an alternative solution for flexible and simultaneous recordings from widely distributed populations of neurons in freely behaving rats.

Cognitive decline and brain volume loss are signatures of cerebral Aβ deposition identified with PIB

PubMed Central

Storandt, Martha; Mintun, Mark A.; Head, Denise; Morris, John C.

2009-01-01

Objective To examine the relation of amyloid-beta (Aβ) levels in cerebral cortex with structural brain integrity and cognitive performance in older people with a Clinical Dementia Rating (CDR) of 0 (cognitively normal). Methods The relations between mean cortical [11C] PIB binding potential values, proportional to the density of fibrillar Aβ binding sites in the brain, concurrent regional brain volumes as assessed by magnetic resonance imaging, and both concurrent and longitudinal (up to 19 years) cognitive performance in multiple domains were examined in 135 CDR 0 individuals aged 65 to 88 years. Results Elevated cerebral Aβ levels, in some cases comparable to that seen in individuals with Alzheimer's disease, were observed in 29 CDR 0 individuals. Significantly smaller regional volumes in the hippocampus, temporal neocortex, anterior cingulate, and posterior cingulate were observed in these CDR 0 individuals with elevated Aβ levels. Concurrent cognitive performance was unrelated to Aβ levels but was related to regional brain volumes with the exception of caudate. Longitudinal cognitive decline was associated with elevated Aβ levels and decreased hippocampal volume. Decline was not limited to episodic memory but included working memory and visuospatial abilities as well. Interpretation [11C] PIB, an in vivo measure of cerebral amyloidosis, is associated with regionally specific brain atrophy cross-sectionally and a pattern of longitudinal cognitive decline in multiple cognitive domains that occurs prior to the clinical diagnosis of Alzheimer' disease. These findings contribute to the understanding of the cognitive and structural consequences of Aβ levels in CDR 0 older adults. PMID:20008651

Moral values are associated with individual differences in regional brain volume

PubMed Central

Lewis, G. J.; Kanai, R.; Bates, T. C.; Rees, G.

2012-01-01

Moral sentiment has been hypothesized to reflect evolved adaptations to social living. If so, individual differences in moral values may relate to regional variation in brain structure. We tested this hypothesis in a sample of 70 young, healthy adults examining whether differences on two major dimensions of moral values were significantly associated with regional gray matter volume. The two clusters of moral values assessed were “individualizing” (values of harm/care and fairness), and “binding” (deference to authority, in-group loyalty, and purity/sanctity). Individualizing was positively associated with left dorsomedial prefrontal cortex volume, and negatively associated with bilateral precuneus volume. For binding, a significant positive association was found for bilateral subcallosal gyrus and a trend to significance for the left anterior insula volume. These findings demonstrate that variation in moral sentiment reflects individual differences in brain structure and suggest a biological basis for moral sentiment, distributed across multiple brain regions. PMID:22571458

Moral values are associated with individual differences in regional brain volume.

PubMed

Lewis, Gary J; Kanai, Ryota; Bates, Timothy C; Rees, Geraint

2012-08-01

Moral sentiment has been hypothesized to reflect evolved adaptations to social living. If so, individual differences in moral values may relate to regional variation in brain structure. We tested this hypothesis in a sample of 70 young, healthy adults examining whether differences on two major dimensions of moral values were significantly associated with regional gray matter volume. The two clusters of moral values assessed were "individualizing" (values of harm/care and fairness) and "binding" (deference to authority, in-group loyalty, and purity/sanctity). Individualizing was positively associated with left dorsomedial pFC volume and negatively associated with bilateral precuneus volume. For binding, a significant positive association was found for bilateral subcallosal gyrus and a trend to significance for the left anterior insula volume. These findings demonstrate that variation in moral sentiment reflects individual differences in brain structure and suggest a biological basis for moral sentiment, distributed across multiple brain regions.

Stable functional networks exhibit consistent timing in the human brain.

PubMed

Chapeton, Julio I; Inati, Sara K; Zaghloul, Kareem A

2017-03-01

Despite many advances in the study of large-scale human functional networks, the question of timing, stability, and direction of communication between cortical regions has not been fully addressed. At the cellular level, neuronal communication occurs through axons and dendrites, and the time required for such communication is well defined and preserved. At larger spatial scales, however, the relationship between timing, direction, and communication between brain regions is less clear. Here, we use a measure of effective connectivity to identify connections between brain regions that exhibit communication with consistent timing. We hypothesized that if two brain regions are communicating, then knowledge of the activity in one region should allow an external observer to better predict activity in the other region, and that such communication involves a consistent time delay. We examine this question using intracranial electroencephalography captured from nine human participants with medically refractory epilepsy. We use a coupling measure based on time-lagged mutual information to identify effective connections between brain regions that exhibit a statistically significant increase in average mutual information at a consistent time delay. These identified connections result in sparse, directed functional networks that are stable over minutes, hours, and days. Notably, the time delays associated with these connections are also highly preserved over multiple time scales. We characterize the anatomic locations of these connections, and find that the propagation of activity exhibits a preferred posterior to anterior temporal lobe direction, consistent across participants. Moreover, networks constructed from connections that reliably exhibit consistent timing between anatomic regions demonstrate features of a small-world architecture, with many reliable connections between anatomically neighbouring regions and few long range connections. Together, our results demonstrate that cortical regions exhibit functional relationships with well-defined and consistent timing, and the stability of these relationships over multiple time scales suggests that these stable pathways may be reliably and repeatedly used for large-scale cortical communication. Published by Oxford University Press on behalf of the Guarantors of Brain 2017. This work is written by US Government employees and is in the public domain in the United States.

Endogenous CNS Expression of Neurotensin and Neurotensin Receptors Is Altered during the Postpartum Period in Outbred Mice

PubMed Central

Driessen, Terri M.; Zhao, Changjiu; Whittlinger, Anna; Williams, Horecia; Gammie, Stephen C.

2014-01-01

Neurotensin (NT) is a neuropeptide identical in mice and humans that is produced and released in many CNS regions associated with maternal behavior. NT has been linked to aspects of maternal care and previous studies have indirectly suggested that endogenous NT signaling is altered in the postpartum period. In the present study, we directly examine whether NT and its receptors exhibit altered gene expression in maternal relative to virgin outbred mice using real time quantitative PCR (qPCR) across multiple brain regions. We also examine NT protein levels using anti-NT antibodies and immunohistochemistry in specific brain regions. In the medial preoptic area (MPOA), which is critical for maternal behaviors, mRNA of NT and NT receptor 3 (Sort1) were significantly up-regulated in postpartum mice compared to virgins. NT mRNA was also elevated in postpartum females in the bed nucleus of the stria terminalis dorsal. However, in the lateral septum, NT mRNA was down-regulated in postpartum females. In the paraventricular nucleus of the hypothalamus (PVN), Ntsr1 expression was down-regulated in postpartum females. Neurotensin receptor 2 (Ntsr2) expression was not altered in any brain region tested. In terms of protein expression, NT immunohistochemistry results indicated that NT labeling was elevated in the postpartum brain in the MPOA, lateral hypothalamus, and two subregions of PVN. Together, these findings indicate that endogenous changes occur in NT and its receptors across multiple brain regions, and these likely support the emergence of some maternal behaviors. PMID:24416154

Selecting the most relevant brain regions to discriminate Alzheimer's disease patients from healthy controls using multiple kernel learning: A comparison across functional and structural imaging modalities and atlases.

PubMed

Rondina, Jane Maryam; Ferreira, Luiz Kobuti; de Souza Duran, Fabio Luis; Kubo, Rodrigo; Ono, Carla Rachel; Leite, Claudia Costa; Smid, Jerusa; Nitrini, Ricardo; Buchpiguel, Carlos Alberto; Busatto, Geraldo F

2018-01-01

Machine learning techniques such as support vector machine (SVM) have been applied recently in order to accurately classify individuals with neuropsychiatric disorders such as Alzheimer's disease (AD) based on neuroimaging data. However, the multivariate nature of the SVM approach often precludes the identification of the brain regions that contribute most to classification accuracy. Multiple kernel learning (MKL) is a sparse machine learning method that allows the identification of the most relevant sources for the classification. By parcelating the brain into regions of interest (ROI) it is possible to use each ROI as a source to MKL (ROI-MKL). We applied MKL to multimodal neuroimaging data in order to: 1) compare the diagnostic performance of ROI-MKL and whole-brain SVM in discriminating patients with AD from demographically matched healthy controls and 2) identify the most relevant brain regions to the classification. We used two atlases (AAL and Brodmann's) to parcelate the brain into ROIs and applied ROI-MKL to structural (T1) MRI, 18 F-FDG-PET and regional cerebral blood flow SPECT (rCBF-SPECT) data acquired from the same subjects (20 patients with early AD and 18 controls). In ROI-MKL, each ROI received a weight (ROI-weight) that indicated the region's relevance to the classification. For each ROI, we also calculated whether there was a predominance of voxels indicating decreased or increased regional activity (for 18 F-FDG-PET and rCBF-SPECT) or volume (for T1-MRI) in AD patients. Compared to whole-brain SVM, the ROI-MKL approach resulted in better accuracies (with either atlas) for classification using 18 F-FDG-PET (92.5% accuracy for ROI-MKL versus 84% for whole-brain), but not when using rCBF-SPECT or T1-MRI. Although several cortical and subcortical regions contributed to discrimination, high ROI-weights and predominance of hypometabolism and atrophy were identified specially in medial parietal and temporo-limbic cortical regions. Also, the weight of discrimination due to a pattern of increased voxel-weight values in AD individuals was surprisingly high (ranging from approximately 20% to 40% depending on the imaging modality), located mainly in primary sensorimotor and visual cortices and subcortical nuclei. The MKL-ROI approach highlights the high discriminative weight of a subset of brain regions of known relevance to AD, the selection of which contributes to increased classification accuracy when applied to 18 F-FDG-PET data. Moreover, the MKL-ROI approach demonstrates that brain regions typically spared in mild stages of AD also contribute substantially in the individual discrimination of AD patients from controls.

Neuropsychological and structural brain lesions in multiple sclerosis: a regional analysis.

PubMed

Swirsky-Sacchetti, T; Mitchell, D R; Seward, J; Gonzales, C; Lublin, F; Knobler, R; Field, H L

1992-07-01

Quantified lesion scores derived from MRI correlate significantly with neuropsychological testing in patients with multiple sclerosis (MS). Variables used to reflect disease severity include total lesion area (TLA), ventricular-brain ratio, and size of the corpus callosum. We used these general measures of cerebral lesion involvement as well as specific ratings of lesion involvement by frontal, temporal, and parieto-occipital regions to quantify the topographic distribution of lesions and consequent effects upon cognitive function. Lesions were heavily distributed in the parieto-occipital regions bilaterally. Neuropsychological tests were highly related to all generalized measures of cerebral involvement, with TLA being the best predictor of neuropsychological deficit. Mean TLA for the cognitively impaired group was 28.30 cm2 versus 7.41 cm2 for the cognitively intact group (p less than 0.0001). Multiple regression analyses revealed that left frontal lobe involvement best predicted impaired abstract problem solving, memory, and word fluency. Left parieto-occipital lesion involvement best predicted deficits in verbal learning and complex visual-integrative skills. Analysis of regional cerebral lesion load may assist in understanding the particular pattern and course of cognitive deficits in MS.

Male and female voices activate distinct regions in the male brain.

PubMed

Sokhi, Dilraj S; Hunter, Michael D; Wilkinson, Iain D; Woodruff, Peter W R

2005-09-01

In schizophrenia, auditory verbal hallucinations (AVHs) are likely to be perceived as gender-specific. Given that functional neuro-imaging correlates of AVHs involve multiple brain regions principally including auditory cortex, it is likely that those brain regions responsible for attribution of gender to speech are invoked during AVHs. We used functional magnetic resonance imaging (fMRI) and a paradigm utilising 'gender-apparent' (unaltered) and 'gender-ambiguous' (pitch-scaled) male and female voice stimuli to test the hypothesis that male and female voices activate distinct brain areas during gender attribution. The perception of female voices, when compared with male voices, affected greater activation of the right anterior superior temporal gyrus, near the superior temporal sulcus. Similarly, male voice perception activated the mesio-parietal precuneus area. These different gender associations could not be explained by either simple pitch perception or behavioural response because the activations that we observed were conjointly activated by both 'gender-apparent' and 'gender-ambiguous' voices. The results of this study demonstrate that, in the male brain, the perception of male and female voices activates distinct brain regions.

Human-specific features of spatial gene expression and regulation in eight brain regions.

PubMed

Xu, Chuan; Li, Qian; Efimova, Olga; He, Liu; Tatsumoto, Shoji; Stepanova, Vita; Oishi, Takao; Udono, Toshifumi; Yamaguchi, Katsushi; Shigenobu, Shuji; Kakita, Akiyoshi; Nawa, Hiroyuki; Khaitovich, Philipp; Go, Yasuhiro

2018-06-13

Molecular maps of the human brain alone do not inform us of the features unique to humans. Yet, the identification of these features is important for understanding both the evolution and nature of human cognition. Here, we approached this question by analyzing gene expression and H3K27ac chromatin modification data collected in eight brain regions of humans, chimpanzees, gorillas, a gibbon and macaques. An analysis of spatial transcriptome trajectories across eight brain regions in four primate species revealed 1,851 genes showing human-specific transcriptome differences in one or multiple brain regions, in contrast to 240 chimpanzee-specific ones. More than half of these human-specific differences represented elevated expression of genes enriched in neuronal and astrocytic markers in the human hippocampus, while the rest were enriched in microglial markers and displayed human-specific expression in several frontal cortical regions and the cerebellum. An analysis of the predicted regulatory interactions driving these differences revealed the role of transcription factors in species-specific transcriptome changes, while epigenetic modifications were linked to spatial expression differences conserved across species. Published by Cold Spring Harbor Laboratory Press.

Functional connectivity in the mouse brain imaged by B-mode photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Nasiriavanaki, Mohammadreza; Xing, Wenxin; Xia, Jun; Wang, Lihong V.

2014-03-01

The increasing use of mouse models for human brain disease studies, coupled with the fact that existing functional imaging modalities cannot be easily applied to mice, presents an emerging need for a new functional imaging modality. Utilizing acoustic-resolution photoacoustic microscopy (AR-PAM), we imaged spontaneous cerebral hemodynamic fluctuations and their associated functional connections in the mouse brain. The images were acquired noninvasively in B-scan mode with a fast frame rate, a large field of view, and a high spatial resolution. At a location relative to the bregma 0, correlations were investigated inter-hemispherically between bilaterally homologous regions, as well as intra-hemispherically within the same functional regions. The functional connectivity in different functional regions was studied. The locations of these regions agreed well with the Paxinos mouse brain atlas. The functional connectivity map obtained in this study can then be used in the investigation of brain disorders such as stroke, Alzheimer's, schizophrenia, multiple sclerosis, autism, and epilepsy. Our experiments show that photoacoustic microscopy is capable to detect connectivities between different functional regions in B-scan mode, promising a powerful functional imaging modality for future brain research.

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.

Neuroimaging studies of social cognition in schizophrenia.

PubMed

Fujiwara, Hironobu; Yassin, Walid; Murai, Toshiya

2015-05-01

Impaired social cognition is considered a core contributor to unfavorable psychosocial functioning in schizophrenia. Rather than being a unitary process, social cognition is a collection of multifaceted processes that recruit multiple brain structures, thus structural and functional neuroimaging techniques are ideal methodologies for revealing the underlying pathophysiology of impaired social cognition. Many neuroimaging studies have suggested that in addition to white-matter deficits, schizophrenia is associated with decreased gray-matter volume in multiple brain areas, especially fronto-temporal and limbic regions. However, few schizophrenia studies have examined associations between brain abnormalities and social cognitive disabilities. During the last decade, we have investigated structural brain abnormalities in schizophrenia using high-resolution magnetic resonance imaging, and our findings have been confirmed by us and others. By assessing different types of social cognitive abilities, structural abnormalities in multiple brain regions have been found to be associated with disabilities in social cognition, such as recognition of facial emotion, theory of mind, and empathy. These structural deficits have also been associated with alexithymia and quality of life in ways that are closely related to the social cognitive disabilities found in schizophrenia. Here, we overview a series of neuroimaging studies from our laboratory that exemplify current research into this topic, and discuss how it can be further tackled using recent advances in neuroimaging technology. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

ABAEnrichment: an R package to test for gene set expression enrichment in the adult and developing human brain.

PubMed

Grote, Steffi; Prüfer, Kay; Kelso, Janet; Dannemann, Michael

2016-10-15

We present ABAEnrichment, an R package that tests for expression enrichment in specific brain regions at different developmental stages using expression information gathered from multiple regions of the adult and developing human brain, together with ontologically organized structural information about the brain, both provided by the Allen Brain Atlas. We validate ABAEnrichment by successfully recovering the origin of gene sets identified in specific brain cell-types and developmental stages. ABAEnrichment was implemented as an R package and is available under GPL (≥ 2) from the Bioconductor website (http://bioconductor.org/packages/3.3/bioc/html/ABAEnrichment.html). steffi_grote@eva.mpg.de, kelso@eva.mpg.de or michael_dannemann@eva.mpg.deSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Multiple brain atlas database and atlas-based neuroimaging system.

PubMed

Nowinski, W L; Fang, A; Nguyen, B T; Raphel, J K; Jagannathan, L; Raghavan, R; Bryan, R N; Miller, G A

1997-01-01

For the purpose of developing multiple, complementary, fully labeled electronic brain atlases and an atlas-based neuroimaging system for analysis, quantification, and real-time manipulation of cerebral structures in two and three dimensions, we have digitized, enhanced, segmented, and labeled the following print brain atlases: Co-Planar Stereotaxic Atlas of the Human Brain by Talairach and Tournoux, Atlas for Stereotaxy of the Human Brain by Schaltenbrand and Wahren, Referentially Oriented Cerebral MRI Anatomy by Talairach and Tournoux, and Atlas of the Cerebral Sulci by Ono, Kubik, and Abernathey. Three-dimensional extensions of these atlases have been developed as well. All two- and three-dimensional atlases are mutually preregistered and may be interactively registered with an actual patient's data. An atlas-based neuroimaging system has been developed that provides support for reformatting, registration, visualization, navigation, image processing, and quantification of clinical data. The anatomical index contains about 1,000 structures and over 400 sulcal patterns. Several new applications of the brain atlas database also have been developed, supported by various technologies such as virtual reality, the Internet, and electronic publishing. Fusion of information from multiple atlases assists the user in comprehensively understanding brain structures and identifying and quantifying anatomical regions in clinical data. The multiple brain atlas database and atlas-based neuroimaging system have substantial potential impact in stereotactic neurosurgery and radiotherapy by assisting in visualization and real-time manipulation in three dimensions of anatomical structures, in quantitative neuroradiology by allowing interactive analysis of clinical data, in three-dimensional neuroeducation, and in brain function studies.

Memory in multiple sclerosis is linked to glutamate concentration in grey matter regions

PubMed Central

Muhlert, Nils; Atzori, Matteo; De Vita, Enrico; Thomas, David L; Samson, Rebecca S; Wheeler-Kingshott, Claudia A M; Geurts, Jeroen J G; Miller, David H; Thompson, Alan J; Ciccarelli, Olga

2014-01-01

Objective Glutamate is the principal excitatory neurotransmitter and is involved in normal brain function. Cognitive impairment is common in multiple sclerosis (MS), and understanding its mechanisms is crucial for developing effective treatments. We used structural and metabolic brain imaging to test two hypotheses: (i) glutamate levels in grey matter regions are abnormal in MS, and (ii) patients show a relationship between glutamate concentration and memory performance. Methods Eighteen patients with relapsing-remitting MS and 17 healthy controls were cognitively assessed and underwent 1H-magnetic resonance spectroscopy at 3 T to assess glutamate levels in the hippocampus, thalamus, cingulate and parietal cortices. Regression models investigated the association between glutamate concentration and memory performance independently of magnetisation transfer ratio values and grey matter lesions withint he same regions, and whole-brain grey matter volume. Results Patients had worse visual and verbal memory than controls. A positive relationship between glutamate levels in the hippocampal, thalamic and cingulate regions and visuospatial memory was detected in patients, but not in healthy controls. Conclusions The relationship between memory and glutamate concentration, which is unique to MS patients, suggests the reliance of memory on glutamatergic systems in MS. PMID:24431465

The hearing ear is always found close to the speaking tongue: Review of the role of the motor system in speech perception.

PubMed

Skipper, Jeremy I; Devlin, Joseph T; Lametti, Daniel R

2017-01-01

Does "the motor system" play "a role" in speech perception? If so, where, how, and when? We conducted a systematic review that addresses these questions using both qualitative and quantitative methods. The qualitative review of behavioural, computational modelling, non-human animal, brain damage/disorder, electrical stimulation/recording, and neuroimaging research suggests that distributed brain regions involved in producing speech play specific, dynamic, and contextually determined roles in speech perception. The quantitative review employed region and network based neuroimaging meta-analyses and a novel text mining method to describe relative contributions of nodes in distributed brain networks. Supporting the qualitative review, results show a specific functional correspondence between regions involved in non-linguistic movement of the articulators, covertly and overtly producing speech, and the perception of both nonword and word sounds. This distributed set of cortical and subcortical speech production regions are ubiquitously active and form multiple networks whose topologies dynamically change with listening context. Results are inconsistent with motor and acoustic only models of speech perception and classical and contemporary dual-stream models of the organization of language and the brain. Instead, results are more consistent with complex network models in which multiple speech production related networks and subnetworks dynamically self-organize to constrain interpretation of indeterminant acoustic patterns as listening context requires. Copyright © 2016. Published by Elsevier Inc.

Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity.

PubMed

Napadow, Vitaly; LaCount, Lauren; Park, Kyungmo; As-Sanie, Sawsan; Clauw, Daniel J; Harris, Richard E

2010-08-01

Fibromyalgia (FM) is considered to be the prototypical central chronic pain syndrome and is associated with widespread pain that fluctuates spontaneously. Multiple studies have demonstrated altered brain activity in these patients. The objective of this study was to investigate the degree of connectivity between multiple brain networks in patients with FM, as well as how activity in these networks correlates with the level of spontaneous pain. Resting-state functional magnetic resonance imaging (FMRI) data from 18 patients with FM and 18 age-matched healthy control subjects were analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic, or resting-state, connectivity was evaluated in multiple brain networks: the default mode network (DMN), the executive attention network (EAN), and the medial visual network (MVN), with the MVN serving as a negative control. Spontaneous pain levels were also analyzed for covariance with intrinsic connectivity. Patients with FM had greater connectivity within the DMN and right EAN (corrected P [P(corr)] < 0.05 versus controls), and greater connectivity between the DMN and the insular cortex, which is a brain region known to process evoked pain. Furthermore, greater intensity of spontaneous pain at the time of the FMRI scan correlated with greater intrinsic connectivity between the insula and both the DMN and right EAN (P(corr) < 0.05). These findings indicate that resting brain activity within multiple networks is associated with spontaneous clinical pain in patients with FM. These findings may also have broader implications for how subjective experiences such as pain arise from a complex interplay among multiple brain networks.

Intrinsic Brain Connectivity in Fibromyalgia is Associated with Chronic Pain Intensity

PubMed Central

Napadow, Vitaly; LaCount, Lauren; Park, Kyungmo; As-Sanie, Suzie; Clauw, Daniel J; Harris, Richard E

2010-01-01

OBJECTIVE Fibromyalgia (FM) is considered to be the prototypical central chronic pain syndrome and is associated with widespread pain that fluctuates spontaneously. Multiple studies have demonstrated altered brain activity in these patients. Our objective was to investigate the degree of connectivity between multiple brain networks in FM, as well as how activity in these networks correlates with spontaneous pain. METHODS Resting functional magnetic resonance imaging (fMRI) data in FM patients (n=18) and age-matched healthy controls (HC, n=18) were analyzed using dual regression independent component analysis (ICA) - a data driven approach used to identify independent brain networks. We evaluated intrinsic, or resting, connectivity in multiple brain networks: the default mode network (DMN), the executive attention network (EAN), and the medial visual network (MVN), with the MVN serving as a negative control. Spontaneous pain levels were also covaried with intrinsic connectivity. RESULTS We found that FM patients had greater connectivity within the DMN and right EAN (rEAN; p<0.05, corrected), and greater connectivity between the DMN and the insular cortex – a brain region known to process evoked pain. Furthermore, greater spontaneous pain at the time of the scan correlated with greater intrinsic connectivity between the insula and both the DMN and rEAN (p<0.05, corrected). CONCLUSION Our findings indicate that resting brain activity within multiple networks is associated with spontaneous clinical pain in FM. These findings may also have broader implications for how subjective experiences such as pain arise from a complex interplay amongst multiple brain networks. PMID:20506181

Three-dimensional brain reconstruction of in vivo electrode tracks for neuroscience and neural prosthetic applications

PubMed Central

Markovitz, Craig D.; Tang, Tien T.; Edge, David P.; Lim, Hubert H.

2012-01-01

The brain is a densely interconnected network that relies on populations of neurons within and across multiple nuclei to code for features leading to perception and action. However, the neurophysiology field is still dominated by the characterization of individual neurons, rather than simultaneous recordings across multiple regions, without consistent spatial reconstruction of their locations for comparisons across studies. There are sophisticated histological and imaging techniques for performing brain reconstructions. However, what is needed is a method that is relatively easy and inexpensive to implement in a typical neurophysiology lab and provides consistent identification of electrode locations to make it widely used for pooling data across studies and research groups. This paper presents our initial development of such an approach for reconstructing electrode tracks and site locations within the guinea pig inferior colliculus (IC) to identify its functional organization for frequency coding relevant for a new auditory midbrain implant (AMI). Encouragingly, the spatial error associated with different individuals reconstructing electrode tracks for the same midbrain was less than 65 μm, corresponding to an error of ~1.5% relative to the entire IC structure (~4–5 mm diameter sphere). Furthermore, the reconstructed frequency laminae of the IC were consistently aligned across three sampled midbrains, demonstrating the ability to use our method to combine location data across animals. Hopefully, through further improvements in our reconstruction method, it can be used as a standard protocol across neurophysiology labs to characterize neural data not only within the IC but also within other brain regions to help bridge the gap between cellular activity and network function. Clinically, correlating function with location within and across multiple brain regions can guide optimal placement of electrodes for the growing field of neural prosthetics. PMID:22754502

Multichannel optical mapping: investigation of depth information

NASA Astrophysics Data System (ADS)

Sase, Ichiro; Eda, Hideo; Seiyama, Akitoshi; Tanabe, Hiroki C.; Takatsuki, Akira; Yanagida, Toshio

2001-06-01

Near infrared (NIR) light has become a powerful tool for non-invasive imaging of human brain activity. Many systems have been developed to capture the changes in regional brain blood flow and hemoglobin oxygenation, which occur in the human cortex in response to neural activity. We have developed a multi-channel reflectance imaging system, which can be used as a `mapping device' and also as a `multi-channel spectrophotometer'. In the present study, we visualized changes in the hemodynamics of the human occipital region in multiple ways. (1) Stimulating left and right primary visual cortex independently by showing sector shaped checkerboards sequentially over the contralateral visual field, resulted in corresponding changes in the hemodynamics observed by `mapping' measurement. (2) Simultaneous measurement of functional-MRI and NIR (changes in total hemoglobin) during visual stimulation showed good spatial and temporal correlation with each other. (3) Placing multiple channels densely over the occipital region demonstrated spatial patterns more precisely, and depth information was also acquired by placing each pair of illumination and detection fibers at various distances. These results indicate that optical method can provide data for 3D analysis of human brain functions.

Early developmental gene enhancers affect subcortical volumes in the adult human brain.

PubMed

Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

2016-05-01

Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder

PubMed Central

Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina

2018-01-01

Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC–vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder. PMID:28944772

Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder.

PubMed

Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina

2018-04-01

Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC-vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder.

Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T.

PubMed

Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; van der Zwaag, Wietske

2018-06-01

External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and negative BOLD responses (NBRs) to visual checkerboard stimulation, occurring in various brain regions within and beyond the visual cortex. Recently-proposed accelerated fMRI techniques were employed for data acquisition, and procedures for exclusion of large draining vein contributions, together with ICA-assisted denoising, were included in the analysis to improve response estimation. Besides the visual cortex, significant PBRs were found in the lateral geniculate nucleus and superior colliculus, as well as the pre-central sulcus; in these regions, response durations increased monotonically with stimulus duration, in tight covariation with the visual PBR duration. Significant NBRs were found in the visual cortex, auditory cortex, default-mode network (DMN) and superior parietal lobule; NBR durations also tended to increase with stimulus duration, but were significantly less sustained than the visual PBR, especially for the DMN and superior parietal lobule. Responses in visual and auditory cortex were further studied for checkerboard contrast dependence, and their amplitudes were found to increase monotonically with contrast, linearly correlated with the visual PBR amplitude. Overall, these findings suggest the presence of dynamic neuronal interactions across multiple brain regions, sensitive to stimulus intensity and duration, and demonstrate the richness of information obtainable when jointly mapping positive and negative BOLD responses at a whole-brain scale, with ultra-high field fMRI. © 2018 Wiley Periodicals, Inc.

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.

Atypical Laterality of Resting Gamma Oscillations in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Maxwell, Christina R.; Villalobos, Michele E.; Schultz, Robert T.; Herpertz-Dahlmann, Beate; Konrad, Kerstin; Kohls, Gregor

2015-01-01

Abnormal brain oscillatory activity has been found in autism spectrum disorders (ASD) and proposed as a potential biomarker. While several studies have investigated gamma oscillations in ASD, none have examined resting gamma power across multiple brain regions. This study investigated resting gamma power using EEG in 15 boys with ASD and 18 age…

Clock Drawing Performance and Brain Morphology in Mild Cognitive Impairment and Alzheimer's Disease

ERIC Educational Resources Information Center

Thomann, Philipp A.; Toro, Pablo; Santos, Vasco Dos; Essig, Marco; Schroder, Johannes

2008-01-01

The Clock Drawing Test (CDT) is a widely used instrument in the neuropsychological assessment of Alzheimer's disease (AD). As CDT performance necessitates several cognitive functions (e.g., visuospatial and constructional abilities, executive functioning), an interaction of multiple brain regions is likely. Fifty-one subjects with mild cognitive…

Perceptual grouping in the human brain: common processing of different cues.

PubMed

Seymour, Kiley; Karnath, Hans-Otto; Himmelbach, Marc

2008-12-03

The perception of global scenes and objects consisting of multiple constituents is based on the integration of local elements or features. Gestalt grouping cues, such as proximity or similarity, can aid this process. Using functional MRI we investigated whether grouping guided by different gestalt cues rely on distinct networks in the brain or share a common network. Our study revealed that gestalt grouping involved the inferior parietal cortex, middle temporal gyrus and prefrontal cortex irrespective of the specific cue used. These findings agree with observations in neurological patients, which suggest that inferior parietal regions may aid the integration of local features into a global gestalt. Damage to this region results in simultanagnosia, a deficit in perceiving multiple objects and global scenes.

The Face-Processing Network Is Resilient to Focal Resection of Human Visual Cortex.

PubMed

Weiner, Kevin S; Jonas, Jacques; Gomez, Jesse; Maillard, Louis; Brissart, Hélène; Hossu, Gabriela; Jacques, Corentin; Loftus, David; Colnat-Coulbois, Sophie; Stigliani, Anthony; Barnett, Michael A; Grill-Spector, Kalanit; Rossion, Bruno

2016-08-10

Human face perception requires a network of brain regions distributed throughout the occipital and temporal lobes with a right hemisphere advantage. Present theories consider this network as either a processing hierarchy beginning with the inferior occipital gyrus (occipital face area; IOG-faces/OFA) or a multiple-route network with nonhierarchical components. The former predicts that removing IOG-faces/OFA will detrimentally affect downstream stages, whereas the latter does not. We tested this prediction in a human patient (Patient S.P.) requiring removal of the right inferior occipital cortex, including IOG-faces/OFA. We acquired multiple fMRI measurements in Patient S.P. before and after a preplanned surgery and multiple measurements in typical controls, enabling both within-subject/across-session comparisons (Patient S.P. before resection vs Patient S.P. after resection) and between-subject/across-session comparisons (Patient S.P. vs controls). We found that the spatial topology and selectivity of downstream ipsilateral face-selective regions were stable 1 and 8 month(s) after surgery. Additionally, the reliability of distributed patterns of face selectivity in Patient S.P. before versus after resection was not different from across-session reliability in controls. Nevertheless, postoperatively, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1 of the resected hemisphere. Diffusion weighted imaging in Patient S.P. and controls identifies white matter tracts connecting retinotopic areas to downstream face-selective regions, which may contribute to the stable and plastic features of the face network in Patient S.P. after surgery. Together, our results support a multiple-route network of face processing with nonhierarchical components and shed light on stable and plastic features of high-level visual cortex following focal brain damage. Brain networks consist of interconnected functional regions commonly organized in processing hierarchies. Prevailing theories predict that damage to the input of the hierarchy will detrimentally affect later stages. We tested this prediction with multiple brain measurements in a rare human patient requiring surgical removal of the putative input to a network processing faces. Surprisingly, the spatial topology and selectivity of downstream face-selective regions are stable after surgery. Nevertheless, representations of visual space were typical in dorsal face-selective regions but atypical in ventral face-selective regions and V1. White matter connections from outside the face network may support these stable and plastic features. As processing hierarchies are ubiquitous in biological and nonbiological systems, our results have pervasive implications for understanding the construction of resilient networks. Copyright © 2016 the authors 0270-6474/16/368426-16$15.00/0.

Early Parallel Activation of Semantics and Phonology in Picture Naming: Evidence from a Multiple Linear Regression MEG Study

PubMed Central

Miozzo, Michele; Pulvermüller, Friedemann; Hauk, Olaf

2015-01-01

The time course of brain activation during word production has become an area of increasingly intense investigation in cognitive neuroscience. The predominant view has been that semantic and phonological processes are activated sequentially, at about 150 and 200–400 ms after picture onset. Although evidence from prior studies has been interpreted as supporting this view, these studies were arguably not ideally suited to detect early brain activation of semantic and phonological processes. We here used a multiple linear regression approach to magnetoencephalography (MEG) analysis of picture naming in order to investigate early effects of variables specifically related to visual, semantic, and phonological processing. This was combined with distributed minimum-norm source estimation and region-of-interest analysis. Brain activation associated with visual image complexity appeared in occipital cortex at about 100 ms after picture presentation onset. At about 150 ms, semantic variables became physiologically manifest in left frontotemporal regions. In the same latency range, we found an effect of phonological variables in the left middle temporal gyrus. Our results demonstrate that multiple linear regression analysis is sensitive to early effects of multiple psycholinguistic variables in picture naming. Crucially, our results suggest that access to phonological information might begin in parallel with semantic processing around 150 ms after picture onset. PMID:25005037

An edge-centric perspective on the human connectome: link communities in the brain.

PubMed

de Reus, Marcel A; Saenger, Victor M; Kahn, René S; van den Heuvel, Martijn P

2014-10-05

Brain function depends on efficient processing and integration of information within a complex network of neural interactions, known as the connectome. An important aspect of connectome architecture is the existence of community structure, providing an anatomical basis for the occurrence of functional specialization. Typically, communities are defined as groups of densely connected network nodes, representing clusters of brain regions. Looking at the connectome from a different perspective, instead focusing on the interconnecting links or edges, we find that the white matter pathways between brain regions also exhibit community structure. Eleven link communities were identified: five spanning through the midline fissure, three through the left hemisphere and three through the right hemisphere. We show that these link communities are consistently identifiable and investigate the network characteristics of their underlying white matter pathways. Furthermore, examination of the relationship between link communities and brain regions revealed that the majority of brain regions participate in multiple link communities. In particular, the highly connected and central hub regions showed a rich level of community participation, supporting the notion that these hubs play a pivotal role as confluence zones in which neural information from different domains merges. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Repetition priming influences distinct brain systems: evidence from task-evoked data and resting-state correlations.

PubMed

Wig, Gagan S; Buckner, Randy L; Schacter, Daniel L

2009-05-01

Behavioral dissociations suggest that a single experience can separately influence multiple processing components. Here we used a repetition priming functional magnetic resonance imaging paradigm that directly contrasted the effects of stimulus and decision changes to identify the underlying brain systems. Direct repetition of stimulus features caused marked reductions in posterior regions of the inferior temporal lobe that were insensitive to whether the decision was held constant or changed between study and test. By contrast, prefrontal cortex showed repetition effects that were sensitive to the exact stimulus-to-decision mapping. Analysis of resting-state functional connectivity revealed that the dissociated repetition effects are embedded within distinct brain systems. Regions that were sensitive to changes in the stimulus correlated with perceptual cortices, whereas the decision changes attenuated activity in regions correlated with middle-temporal regions and a frontoparietal control system. These results thus explain the long-known dissociation between perceptual and conceptual components of priming by revealing how a single experience can separately influence distinct, concurrently active brain systems.

Global gene expression profiles in brain regions reflecting abnormal neuronal and glial functions targeting myelin sheaths after 28-day exposure to cuprizone in rats

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

Abe, Hajime

Both developmental and postpubertal cuprizone (CPZ) exposure impairs hippocampal neurogenesis in rats. We previously found that developmental CPZ exposure alters the expression of genes related to neurogenesis, myelination, and synaptic transmission in specific brain regions of offspring. Here, we examined neuronal and glial toxicity profiles in response to postpubertal CPZ exposure by using expression microarray analysis in the hippocampal dentate gyrus, corpus callosum, cerebral cortex, and cerebellar vermis of 5-week-old male rats exposed to 0, 120, and 600 mg/kg CPZ for 28 days. Genes showing transcript upregulation were subjected to immunohistochemical analysis. We found transcript expression alterations at 600 mg/kgmore » for genes related to synaptic transmission, Ache and Prima1, and cell cycle regulation, Tfap4 and Cdkn1a, in the dentate gyrus, which showed aberrant neurogenesis in the subgranular zone. This dose downregulated myelination-related genes in multiple brain regions, whereas KLOTHO{sup +} oligodendrocyte density was decreased only in the corpus callosum. The corpus callosum showed an increase in transcript levels for inflammatory response-related genes and in the number of CD68{sup +} microglia, MT{sup +} astrocytes, and TUNEL{sup +} apoptotic cells. These results suggest that postpubertal CPZ exposure targets synaptic transmission and cell cycle regulation to affect neurogenesis in the dentate gyrus. CPZ suppressed myelination in multiple brain regions and KLOTHO-mediated oligodendrocyte maturation only in the corpus callosum. The increased number of CD68{sup +} microglia, MT{sup +} astrocytes, and TUNEL{sup +} apoptotic cells in the corpus callosum may be involved in the induction of KLOTHO{sup +} oligodendrocyte death and be a protective mechanism against myelin damage following CPZ exposure. - Highlights: • Target gene expression profiles were examined in rats after 28-day CPZ exposure. • Multiple brain region-specific global gene expression profiling was performed. • CPZ affected synaptic function and cell cycling in the hippocampal dentate gyrus. • CPZ suppressed KLOTHO-mediated oligodendrocyte maturation in the corpus callosum. • CPZ increased metallothionein-mediated protective mechanism against myelin damage.« less

Neuropathology of Cervical Dystonia

PubMed Central

Prudente, C.N.; Pardo, C.A.; Xiao, J.; Hanfelt, J.; Hess, E.J.; LeDoux, M.S.; Jinnah, H.A.

2012-01-01

The aim of this study was to search for neuropathological changes in postmortem brain tissue of individuals with cervical dystonia (CD). Multiple regions of formalin-preserved brains were collected from patients with CD and controls and examined with an extensive battery of histopathological stains in a two-stage study design. In stage one, 4 CD brains underwent a broad screening neuropathological examination. In stage two, these 4 CD brains were combined with 2 additional CD brains, and the subjective findings were quantified and compared to 16 age-matched controls. The initial subjective neuropathological assessment revealed only two regions with relatively consistent changes. The substantia nigra had frequent ubiquitin-positive intranuclear inclusions known as Marinesco bodies. Additionally, the cerebellum showed patchy loss of Purkinje cells, areas of focal gliosis and torpedo bodies. Other brain regions showed minor or inconsistent changes. In the second stage of the analysis, quantitative studies failed to reveal significant differences in the numbers of Marinesco bodies in CD versus controls, but confirmed a significantly lower Purkinje cell density in CD. Molecular investigations revealed 4 of the CD cases and 2 controls to harbor sequence variants in non-coding regions of THAP1, and these cases had lower Purkinje cell densities regardless of whether they had CD. The findings suggest that subtle neuropathological changes such as lower Purkinje cell density may be found in primary CD when relevant brain regions are investigated with appropriate methods. PMID:23195594

Multivariate dynamical modelling of structural change during development.

PubMed

Ziegler, Gabriel; Ridgway, Gerard R; Blakemore, Sarah-Jayne; Ashburner, John; Penny, Will

2017-02-15

Here we introduce a multivariate framework for characterising longitudinal changes in structural MRI using dynamical systems. The general approach enables modelling changes of states in multiple imaging biomarkers typically observed during brain development, plasticity, ageing and degeneration, e.g. regional gray matter volume of multiple regions of interest (ROIs). Structural brain states follow intrinsic dynamics according to a linear system with additional inputs accounting for potential driving forces of brain development. In particular, the inputs to the system are specified to account for known or latent developmental growth/decline factors, e.g. due to effects of growth hormones, puberty, or sudden behavioural changes etc. Because effects of developmental factors might be region-specific, the sensitivity of each ROI to contributions of each factor is explicitly modelled. In addition to the external effects of developmental factors on regional change, the framework enables modelling and inference about directed (potentially reciprocal) interactions between brain regions, due to competition for space, or structural connectivity, and suchlike. This approach accounts for repeated measures in typical MRI studies of development and aging. Model inversion and posterior distributions are obtained using earlier established variational methods enabling Bayesian evidence-based comparisons between various models of structural change. Using this approach we demonstrate dynamic cortical changes during brain maturation between 6 and 22 years of age using a large openly available longitudinal paediatric dataset with 637 scans from 289 individuals. In particular, we model volumetric changes in 26 bilateral ROIs, which cover large portions of cortical and subcortical gray matter. We account for (1) puberty-related effects on gray matter regions; (2) effects of an early transient growth process with additional time-lag parameter; (3) sexual dimorphism by modelling parameter differences between boys and girls. There is evidence that the regional pattern of sensitivity to dynamic hidden growth factors in late childhood is similar across genders and shows a consistent anterior-posterior gradient with strongest impact to prefrontal cortex (PFC) brain changes. Finally, we demonstrate the potential of the framework to explore the coupling of structural changes across a priori defined subnetworks using an example of previously established resting state functional connectivity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Predictive Utility of Marketed Volumetric Software Tools in Subjects at Risk for Alzheimer Disease: Do Regions Outside the Hippocampus Matter?

PubMed

Tanpitukpongse, T P; Mazurowski, M A; Ikhena, J; Petrella, J R

2017-03-01

Alzheimer disease is a prevalent neurodegenerative disease. Computer assessment of brain atrophy patterns can help predict conversion to Alzheimer disease. Our aim was to assess the prognostic efficacy of individual-versus-combined regional volumetrics in 2 commercially available brain volumetric software packages for predicting conversion of patients with mild cognitive impairment to Alzheimer disease. Data were obtained through the Alzheimer's Disease Neuroimaging Initiative. One hundred ninety-two subjects (mean age, 74.8 years; 39% female) diagnosed with mild cognitive impairment at baseline were studied. All had T1-weighted MR imaging sequences at baseline and 3-year clinical follow-up. Analysis was performed with NeuroQuant and Neuroreader. Receiver operating characteristic curves assessing the prognostic efficacy of each software package were generated by using a univariable approach using individual regional brain volumes and 2 multivariable approaches (multiple regression and random forest), combining multiple volumes. On univariable analysis of 11 NeuroQuant and 11 Neuroreader regional volumes, hippocampal volume had the highest area under the curve for both software packages (0.69, NeuroQuant; 0.68, Neuroreader) and was not significantly different ( P > .05) between packages. Multivariable analysis did not increase the area under the curve for either package (0.63, logistic regression; 0.60, random forest NeuroQuant; 0.65, logistic regression; 0.62, random forest Neuroreader). Of the multiple regional volume measures available in FDA-cleared brain volumetric software packages, hippocampal volume remains the best single predictor of conversion of mild cognitive impairment to Alzheimer disease at 3-year follow-up. Combining volumetrics did not add additional prognostic efficacy. Therefore, future prognostic studies in mild cognitive impairment, combining such tools with demographic and other biomarker measures, are justified in using hippocampal volume as the only volumetric biomarker. © 2017 by American Journal of Neuroradiology.

Untangling the Effect of Head Acceleration on Brain Responses to Blast Waves

PubMed Central

Mao, Haojie; Unnikrishnan, Ginu; Rakesh, Vineet; Reifman, Jaques

2015-01-01

Multiple injury-causing mechanisms, such as wave propagation, skull flexure, cavitation, and head acceleration, have been proposed to explain blast-induced traumatic brain injury (bTBI). An accurate, quantitative description of the individual contribution of each of these mechanisms may be necessary to develop preventive strategies against bTBI. However, to date, despite numerous experimental and computational studies of bTBI, this question remains elusive. In this study, using a two-dimensional (2D) rat head model, we quantified the contribution of head acceleration to the biomechanical response of brain tissues when exposed to blast waves in a shock tube. We compared brain pressure at the coup, middle, and contre-coup regions between a 2D rat head model capable of simulating all mechanisms (i.e., the all-effects model) and an acceleration-only model. From our simulations, we determined that head acceleration contributed 36–45% of the maximum brain pressure at the coup region, had a negligible effect on the pressure at the middle region, and was responsible for the low pressure at the contre-coup region. Our findings also demonstrate that the current practice of measuring rat brain pressures close to the center of the brain would record only two-thirds of the maximum pressure observed at the coup region. Therefore, to accurately capture the effects of acceleration in experiments, we recommend placing a pressure sensor near the coup region, especially when investigating the acceleration mechanism using different experimental setups. PMID:26458125

Spatial distribution of resting-state BOLD regional homogeneity as a predictor of brain glucose uptake: A study in healthy aging.

PubMed

Bernier, Michaël; Croteau, Etienne; Castellano, Christian-Alexandre; Cunnane, Stephen C; Whittingstall, Kevin

2017-04-15

Positron emission tomography using [18F]-fluorodeoxyglucose (PET-FDG) is the primary imaging modality used to measure glucose metabolism in the brain (CMRGlu). CMRGlu has been used as a biomarker of brain aging and neurodegenerative diseases, but the complexity and invasive nature of PET often limits its use in research. There is therefore great interest in developing non-invasive metrics for estimating brain CMRGlu. We therefore investigated resting state fMRI metrics such as regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF) and regional global connectivity (Closeness) with multiple analytical approaches to determine their relationship to CMRGlu. We investigated this relation in two distinct cognitively healthy populations separated by age (27 young adults and 35 older adults). Overall, we found that both regionally and across participants, ReHo strongly correlated with CMRGlu in healthy young and older adults. Moreover, ReHo demonstrated the same age-related differences as CMRGlu throughout all cortical regions, particularly in the default network and frontal areas. Copyright © 2017 Elsevier Inc. All rights reserved.

Prediction of Biological Motion Perception Performance from Intrinsic Brain Network Regional Efficiency

PubMed Central

Wang, Zengjian; Zhang, Delong; Liang, Bishan; Chang, Song; Pan, Jinghua; Huang, Ruiwang; Liu, Ming

2016-01-01

Biological motion perception (BMP) refers to the ability to perceive the moving form of a human figure from a limited amount of stimuli, such as from a few point lights located on the joints of a moving body. BMP is commonplace and important, but there is great inter-individual variability in this ability. This study used multiple regression model analysis to explore the association between BMP performance and intrinsic brain activity, in order to investigate the neural substrates underlying inter-individual variability of BMP performance. The resting-state functional magnetic resonance imaging (rs-fMRI) and BMP performance data were collected from 24 healthy participants, for whom intrinsic brain networks were constructed, and a graph-based network efficiency metric was measured. Then, a multiple linear regression model was used to explore the association between network regional efficiency and BMP performance. We found that the local and global network efficiency of many regions was significantly correlated with BMP performance. Further analysis showed that the local efficiency rather than global efficiency could be used to explain most of the BMP inter-individual variability, and the regions involved were predominately located in the Default Mode Network (DMN). Additionally, discrimination analysis showed that the local efficiency of certain regions such as the thalamus could be used to classify BMP performance across participants. Notably, the association pattern between network nodal efficiency and BMP was different from the association pattern of static directional/gender information perception. Overall, these findings show that intrinsic brain network efficiency may be considered a neural factor that explains BMP inter-individual variability. PMID:27853427

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.

Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: preliminary comparative PET studies with [11C]vinpocetine and [11C]PK11195 in patients.

PubMed

Vas, Adám; Shchukin, Yevgeni; Karrenbauer, Virginija D; Cselényi, Zsolt; Kostulas, Kosta; Hillert, Jan; Savic, Ivanka; Takano, Akihiro; Halldin, Christer; Gulyás, Balázs

2008-01-15

With the purpose of demonstrating the use of positron emission tomography (PET) and radiolabelled glia markers to indicate regional cerebral damage, we measured with PET in four young multiplex sclerosis (MS) patients in two consecutive measurements the global and regional brain uptake as well as regional distribution and binding potential (BP) of [(11)C]vinpocetine and [(11)C]PK11195. Both ligands showed increased uptake and BP in the regions of local brain damage. However, regional BP values for [(11)C]vinpocetine were markedly higher than those for [(11)C]PK11195. This feature of the former radioligand may be related to its high brain uptake and marked affinity to the peripheral benzodiazepine receptor binding sites (PBBS), characteristic for glia cells. As local brain traumas entail reactive glia accumulation in and around the site of the damage, the present findings may indicate that [(11)C]vinpocetine marks the place or boundaries of local brain damage by binding to the PBBS present in glia cells, which, in turn, accumulate in the region of the damage. The present findings (i) confirm earlier observations with [(11)C]PK11195 as a potential glia marker in PET studies and (ii) support the working hypothesis that [(11)C]vinpocetine is a potentially useful PET marker of regional and global brain damage resulting in glia accumulation locally or globally in the human brain. The comparative analysis of the two ligands indicate that [(11)C]vinpocetine shows a number of characteristics favourable in comparison with [(11)C]PK11195.

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

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

Wang Silun; Tryggestad, Erik; Zhou Tingting

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

Multivariate pattern dependence

PubMed Central

Saxe, Rebecca

2017-01-01

When we perform a cognitive task, multiple brain regions are engaged. Understanding how these regions interact is a fundamental step to uncover the neural bases of behavior. Most research on the interactions between brain regions has focused on the univariate responses in the regions. However, fine grained patterns of response encode important information, as shown by multivariate pattern analysis. In the present article, we introduce and apply multivariate pattern dependence (MVPD): a technique to study the statistical dependence between brain regions in humans in terms of the multivariate relations between their patterns of responses. MVPD characterizes the responses in each brain region as trajectories in region-specific multidimensional spaces, and models the multivariate relationship between these trajectories. We applied MVPD to the posterior superior temporal sulcus (pSTS) and to the fusiform face area (FFA), using a searchlight approach to reveal interactions between these seed regions and the rest of the brain. Across two different experiments, MVPD identified significant statistical dependence not detected by standard functional connectivity. Additionally, MVPD outperformed univariate connectivity in its ability to explain independent variance in the responses of individual voxels. In the end, MVPD uncovered different connectivity profiles associated with different representational subspaces of FFA: the first principal component of FFA shows differential connectivity with occipital and parietal regions implicated in the processing of low-level properties of faces, while the second and third components show differential connectivity with anterior temporal regions implicated in the processing of invariant representations of face identity. PMID:29155809

Endogenous opioidergic dysregulation of pain in fibromyalgia: a PET and fMRI study.

PubMed

Schrepf, Andrew; Harper, Daniel E; Harte, Steven E; Wang, Heng; Ichesco, Eric; Hampson, Johnson P; Zubieta, Jon-Kar; Clauw, Daniel J; Harris, Richard E

2016-10-01

Endogenous opioid system dysfunction potentially contributes to chronic pain in fibromyalgia (FM), but it is unknown if this dysfunction is related to established neurobiological markers of hyperalgesia. We previously reported that µ-opioid receptor (MOR) availability was reduced in patients with FM as compared with healthy controls in several pain-processing brain regions. In the present study, we compared pain-evoked functional magnetic resonance imaging with endogenous MOR binding and clinical pain ratings in female opioid-naive patients with FM (n = 18) using whole-brain analyses and regions of interest from our previous research. Within antinociceptive brain regions, including the dorsolateral prefrontal cortex (r = 0.81, P < 0.001) and multiple regions of the anterior cingulate cortex (all r > 0.67; all P < 0.02), reduced MOR availability was associated with decreased pain-evoked neural activity. Additionally, reduced MOR availability was associated with lower brain activation in the nucleus accumbens (r = 0.47, P = 0.050). In many of these regions, pain-evoked activity and MOR binding potential were also associated with lower clinical affective pain ratings. These findings are the first to link endogenous opioid system tone to regional pain-evoked brain activity in a clinical pain population. Our data suggest that dysregulation of the endogenous opioid system in FM could lead to less excitation in antinociceptive brain regions by incoming noxious stimulation, resulting in the hyperalgesia and allodynia commonly observed in this population. We propose a conceptual model of affective pain dysregulation in FM.

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.

Using large-scale Granger causality to study changes in brain network properties in the Clinically Isolated Syndrome (CIS) stage of multiple sclerosis

NASA Astrophysics Data System (ADS)

Abidin, Anas Z.; Chockanathan, Udaysankar; DSouza, Adora M.; Inglese, Matilde; Wismüller, Axel

2017-03-01

Clinically Isolated Syndrome (CIS) is often considered to be the first neurological episode associated with Multiple sclerosis (MS). At an early stage the inflammatory demyelination occurring in the CNS can manifest as a change in neuronal metabolism, with multiple asymptomatic white matter lesions detected in clinical MRI. Such damage may induce topological changes of brain networks, which can be captured by advanced functional MRI (fMRI) analysis techniques. We test this hypothesis by capturing the effective relationships of 90 brain regions, defined in the Automated Anatomic Labeling (AAL) atlas, using a large-scale Granger Causality (lsGC) framework. The resulting networks are then characterized using graph-theoretic measures that quantify various network topology properties at a global as well as at a local level. We study for differences in these properties in network graphs obtained for 18 subjects (10 male and 8 female, 9 with CIS and 9 healthy controls). Global network properties captured trending differences with modularity and clustering coefficient (p<0.1). Additionally, local network properties, such as local efficiency and the strength of connections, captured statistically significant (p<0.01) differences in some regions of the inferior frontal and parietal lobe. We conclude that multivariate analysis of fMRI time-series can reveal interesting information about changes occurring in the brain in early stages of MS.

From Whole-Brain Data to Functional Circuit Models: The Zebrafish Optomotor Response.

PubMed

Naumann, Eva A; Fitzgerald, James E; Dunn, Timothy W; Rihel, Jason; Sompolinsky, Haim; Engert, Florian

2016-11-03

Detailed descriptions of brain-scale sensorimotor circuits underlying vertebrate behavior remain elusive. Recent advances in zebrafish neuroscience offer new opportunities to dissect such circuits via whole-brain imaging, behavioral analysis, functional perturbations, and network modeling. Here, we harness these tools to generate a brain-scale circuit model of the optomotor response, an orienting behavior evoked by visual motion. We show that such motion is processed by diverse neural response types distributed across multiple brain regions. To transform sensory input into action, these regions sequentially integrate eye- and direction-specific sensory streams, refine representations via interhemispheric inhibition, and demix locomotor instructions to independently drive turning and forward swimming. While experiments revealed many neural response types throughout the brain, modeling identified the dimensions of functional connectivity most critical for the behavior. We thus reveal how distributed neurons collaborate to generate behavior and illustrate a paradigm for distilling functional circuit models from whole-brain data. Copyright © 2016 Elsevier Inc. All rights reserved.

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

PubMed

Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer's disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing.

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing

PubMed Central

Neltner, Janna H.; Abner, Erin L.; Baker, Steven; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Hammack, Eleanor; Kukull, Walter A.; Brenowitz, Willa D.; Van Eldik, Linda J.

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer’s Disease Centre, Nun Study, and National Alzheimer’s Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case–control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer’s disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing. PMID:24271328

Dendritic Spine Pathology in Schizophrenia

PubMed Central

Glausier, Jill R.; Lewis, David A.

2012-01-01

Schizophrenia is a neurodevelopmental disorder whose clinical features include impairments in perception, cognition and motivation. These impairments reflect alterations in neuronal circuitry within and across multiple brain regions that are due, at least in part, to deficits in dendritic spines, the site of most excitatory synaptic connections. Dendritic spine alterations have been identified in multiple brain regions in schizophrenia, but are best characterized in layer 3 of the neocortex, where pyramidal cell spine density is lower. These spine deficits appear to arise during development, and thus are likely the result of disturbances in the molecular mechanisms that underlie spine formation, pruning, and/or maintenance. Each of these mechanisms may provide insight into novel therapeutic targets for preventing or repairing the alterations in neural circuitry that mediate the debilitating symptoms of schizophrenia. PMID:22546337

Regional Slow Waves and Spindles in Human Sleep

PubMed Central

Nir, Yuval; Staba, Richard J.; Andrillon, Thomas; Vyazovskiy, Vladyslav V.; Cirelli, Chiara; Fried, Itzhak; Tononi, Giulio

2011-01-01

SUMMARY The most prominent EEG events in sleep are slow waves, reflecting a slow (<1 Hz) oscillation between up and down states in cortical neurons. It is unknown whether slow oscillations are synchronous across the majority or the minority of brain regions—are they a global or local phenomenon? To examine this, we recorded simultaneously scalp EEG, intracerebral EEG, and unit firing in multiple brain regions of neurosurgical patients. We find that most sleep slow waves and the underlying active and inactive neuronal states occur locally. Thus, especially in late sleep, some regions can be active while others are silent. We also find that slow waves can propagate, usually from medial prefrontal cortex to the medial temporal lobe and hippocampus. Sleep spindles, the other hallmark of NREM sleep EEG, are likewise predominantly local. Thus, intracerebral communication during sleep is constrained because slow and spindle oscillations often occur out-of-phase in different brain regions. PMID:21482364

Early life predictors of brain development at term-equivalent age in infants born across the gestational age spectrum.

PubMed

Thompson, Deanne K; Kelly, Claire E; Chen, Jian; Beare, Richard; Alexander, Bonnie; Seal, Marc L; Lee, Katherine; Matthews, Lillian G; Anderson, Peter J; Doyle, Lex W; Spittle, Alicia J; Cheong, Jeanie L Y

2018-04-13

It is well established that preterm infants have altered brain development compared with full-term (FT; ≥37 weeks' gestational age [GA]) infants, however the perinatal factors associated with brain development in preterm infants have not been fully elucidated. In particular, perinatal predictors of brain development may differ between very preterm infants (VP; <32 weeks' GA) and infants born moderate (MP; 32-33 weeks' GA) and late (LP; 34-36 weeks' GA) preterm, but this has not been studied. This study aimed to investigate the effects of early life predictors on brain volume and microstructure at term-equivalent age (TEA; 38-44 weeks), and whether these effects differ for GA groups (VP, MP, LP or FT). Structural images from 328 infants (91 VP, 63 MP, 104 LP and 70 FT) were segmented into white matter, cortical grey matter, cerebrospinal fluid, subcortical grey matter, brainstem and cerebellum. Cortical grey matter and white matter images were analysed using voxel-based morphometry. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) images from 361 infants (92 VP, 69 MP, 120 LP and 80 FT) were analysed using Tract-Based Spatial Statistics. Relationships between early life predictors (birthweight standard deviation score [BWSDS], multiple birth, sex, postnatal growth and social risk) and global brain volumes were analysed using linear regressions. Relationships between early life predictors and regional brain volumes and diffusion measures were analysed using voxelwise non-parametric permutation testing. Male sex was associated with higher global volumes of all tissues and higher regional volumes throughout much of the cortical grey matter and white matter, particularly in the FT group. Male sex was also associated with lower FA and higher AD, RD and MD in the optic radiation, external and internal capsules and corona radiata, and these associations were generally similar between GA groups. Higher BWSDS was associated with higher global volumes of all tissues and higher regional volumes in much of the cortical grey matter and white matter in all GA groups, as well as higher FA and lower RD and MD in many major tracts (corpus callosum, optic radiation, internal and external capsules and corona radiata), particularly in the MP and LP groups. Multiple birth and social risk also showed associations with global and regional volumes and regional diffusion values which varied by GA group, but these associations were not independent of the other early life predictors. Postnatal growth was not associated with brain volumes or diffusion values. Early life predictors of brain volumes and microstructure at TEA include sex, BWSDS, multiple birth and social risk, which have different effects based on GA group at birth. This study improves knowledge of the perinatal factors associated with brain abnormalities in infants born across the prematurity spectrum. Copyright © 2018. Published by Elsevier Inc.

A Putative Multiple-Demand System in the Macaque Brain.

PubMed

Mitchell, Daniel J; Bell, Andrew H; Buckley, Mark J; Mitchell, Anna S; Sallet, Jerome; Duncan, John

2016-08-17

In humans, cognitively demanding tasks of many types recruit common frontoparietal brain areas. Pervasive activation of this "multiple-demand" (MD) network suggests a core function in supporting goal-oriented behavior. A similar network might therefore be predicted in nonhuman primates that readily perform similar tasks after training. However, an MD network in nonhuman primates has not been described. Single-cell recordings from macaque frontal and parietal cortex show some similar properties to human MD fMRI responses (e.g., adaptive coding of task-relevant information). Invasive recordings, however, come from limited prespecified locations, so they do not delineate a macaque homolog of the MD system and their positioning could benefit from knowledge of where MD foci lie. Challenges of scanning behaving animals mean that few macaque fMRI studies specifically contrast levels of cognitive demand, so we sought to identify a macaque counterpart to the human MD system using fMRI connectivity in 35 rhesus macaques. Putative macaque MD regions, mapped from frontoparietal MD regions defined in humans, were found to be functionally connected under anesthesia. To further refine these regions, an iterative process was used to maximize their connectivity cross-validated across animals. Finally, whole-brain connectivity analyses identified voxels that were robustly connected to MD regions, revealing seven clusters across frontoparietal and insular cortex comparable to human MD regions and one unexpected cluster in the lateral fissure. The proposed macaque MD regions can be used to guide future electrophysiological investigation of MD neural coding and in task-based fMRI to test predictions of similar functional properties to human MD cortex. In humans, a frontoparietal "multiple-demand" (MD) brain network is recruited during a wide range of cognitively demanding tasks. Because this suggests a fundamental function, one might expect a similar network to exist in nonhuman primates, but this remains controversial. Here, we sought to identify a macaque counterpart to the human MD system using fMRI connectivity. Putative macaque MD regions were functionally connected under anesthesia and were further refined by iterative optimization. The result is a network including lateral frontal, dorsomedial frontal, and insular and inferior parietal regions closely similar to the human counterpart. The proposed macaque MD regions can be useful in guiding electrophysiological recordings or in task-based fMRI to test predictions of similar functional properties to human MD cortex. Copyright © 2016 Mitchell et al.

Primate Brain Anatomy: New Volumetric MRI Measurements for Neuroanatomical Studies.

PubMed

Navarrete, Ana F; Blezer, Erwin L A; Pagnotta, Murillo; de Viet, Elizabeth S M; Todorov, Orlin S; Lindenfors, Patrik; Laland, Kevin N; Reader, Simon M

2018-06-12

Since the publication of the primate brain volumetric dataset of Stephan and colleagues in the early 1980s, no major new comparative datasets covering multiple brain regions and a large number of primate species have become available. However, technological and other advances in the last two decades, particularly magnetic resonance imaging (MRI) and the creation of institutions devoted to the collection and preservation of rare brain specimens, provide opportunities to rectify this situation. Here, we present a new dataset including brain region volumetric measurements of 39 species, including 20 species not previously available in the literature, with measurements of 16 brain areas. These volumes were extracted from MRI of 46 brains of 38 species from the Netherlands Institute of Neuroscience Primate Brain Bank, scanned at high resolution with a 9.4-T scanner, plus a further 7 donated MRI of 4 primate species. Partial measurements were made on an additional 8 brains of 5 species. We make the dataset and MRI scans available online in the hope that they will be of value to researchers conducting comparative studies of primate evolution. © 2018 S. Karger AG, Basel.

Predictive Utility of Marketed Volumetric Software Tools in Subjects at Risk for Alzheimer's: Do Regions Outside the Hippocampus Matter?

PubMed Central

Tanpitukpongse, Teerath P.; Mazurowski, Maciej A.; Ikhena, John; Petrella, Jeffrey R.

2016-01-01

Background and Purpose To assess prognostic efficacy of individual versus combined regional volumetrics in two commercially-available brain volumetric software packages for predicting conversion of patients with mild cognitive impairment to Alzheimer's disease. Materials and Methods Data was obtained through the Alzheimer's Disease Neuroimaging Initiative. 192 subjects (mean age 74.8 years, 39% female) diagnosed with mild cognitive impairment at baseline were studied. All had T1WI MRI sequences at baseline and 3-year clinical follow-up. Analysis was performed with NeuroQuant® and Neuroreader™. Receiver operating characteristic curves assessing the prognostic efficacy of each software package were generated using a univariable approach employing individual regional brain volumes, as well as two multivariable approaches (multiple regression and random forest), combining multiple volumes. Results On univariable analysis of 11 NeuroQuant® and 11 Neuroreader™ regional volumes, hippocampal volume had the highest area under the curve for both software packages (0.69 NeuroQuant®, 0.68 Neuroreader™), and was not significantly different (p > 0.05) between packages. Multivariable analysis did not increase the area under the curve for either package (0.63 logistic regression, 0.60 random forest NeuroQuant®; 0.65 logistic regression, 0.62 random forest Neuroreader™). Conclusion Of the multiple regional volume measures available in FDA-cleared brain volumetric software packages, hippocampal volume remains the best single predictor of conversion of mild cognitive impairment to Alzheimer's disease at 3-year follow-up. Combining volumetrics did not add additional prognostic efficacy. Therefore, future prognostic studies in MCI, combining such tools with demographic and other biomarker measures, are justified in using hippocampal volume as the only volumetric biomarker. PMID:28057634

A Stimulus-Locked Vector Autoregressive Model for Slow Event-Related fMRI Designs

PubMed Central

Siegle, Greg

2009-01-01

Summary Neuroscientists have become increasingly interested in exploring dynamic relationships among brain regions. Such a relationship, when directed from one region toward another, is denoted by “effective connectivity.” An fMRI experimental paradigm which is well-suited for examination of effective connectivity is the slow event-related design. This design presents stimuli at sufficient temporal spacing for determining within-trial trajectories of BOLD activation, allowing for the analysis of stimulus-locked temporal covariation of brain responses in multiple regions. This may be especially important for emotional stimuli processing, which can evolve over the course of several seconds, if not longer. However, while several methods have been devised for determining fMRI effective connectivity, few are adapted to event-related designs, which include non-stationary BOLD responses and multiple levels of nesting. We propose a model tailored for exploring effective connectivity of multiple brain regions in event-related fMRI designs - a semi-parametric adaptation of vector autoregressive (VAR) models, termed “stimulus-locked VAR” (SloVAR). Connectivity coefficients vary as a function of time relative to stimulus onset, are regularized via basis expansions, and vary randomly across subjects. SloVAR obtains flexible, data-driven estimates of effective connectivity and hence is useful for building connectivity models when prior information on dynamic regional relationships is sparse. Indices derived from the coefficient estimates can also be used to relate effective connectivity estimates to behavioral or clinical measures. We demonstrate the SloVAR model on a sample of clinically depressed and normal controls, showing that early but not late cortico-amygdala connectivity appears crucial to emotional control and early but not late cortico-cortico connectivity predicts depression severity in the depressed group, relationships that would have been missed in a more traditional VAR analysis. PMID:19236927

Exploring the relationship between white matter and gray matter damage in early primary progressive multiple sclerosis: an in vivo study with TBSS and VBM.

PubMed

Bodini, Benedetta; Khaleeli, Zhaleh; Cercignani, Mara; Miller, David H; Thompson, Alan J; Ciccarelli, Olga

2009-09-01

We investigated the relationship between the damage occurring in the brain normal-appearing white matter (NAWM) and in the gray matter (GM) in patients with early Primary Progressive multiple sclerosis (PPMS), using Tract-Based Spatial Statistics (TBSS) and an optimized voxel-based morphometry (VBM) approach. Thirty-five patients with early PPMS underwent diffusion tensor and conventional imaging and were clinically assessed. TBSS and VBM were employed to localize regions of lower fractional anisotropy (FA) and lower GM volume in patients compared with controls. Areas of anatomical and quantitative correlation between NAWM and GM damage were detected. Multiple regression analyses were performed to investigate whether NAWM FA or GM volume of regions correlated with clinical scores independently from the other and from age and gender. In patients, we found 11 brain regions that showed an anatomical correspondence between reduced NAWM FA and GM atrophy; of these, four showed a quantitative correlation (i.e., the right sensory motor region with the adjacent corticospinal tract, the left and right thalamus with the corresponding thalamic radiations and the left insula with the adjacent WM). Either the NAWM FA or the GM volume in each of these regions correlated with disability. These results demonstrate a link between the pathological processes occurring in the NAWM and in the GM in PPMS in specific, clinically relevant brain areas. Longitudinal studies will determine whether the GM atrophy precedes or follows the NAWM damage. The methodology that we described may be useful to investigate other neurological disorders affecting both the WM and the GM. 2009 Wiley-Liss, Inc.

Correlation between diffusion kurtosis and NODDI metrics in neonates and young children

NASA Astrophysics Data System (ADS)

Ahmed, Shaheen; Wang, Zhiyue J.; Chia, Jonathan M.; Rollins, Nancy K.

2016-03-01

Diffusion Tensor Imaging (DTI) uses single shell gradient encoding scheme for studying brain tissue diffusion. NODDI (Neurite Orientation Dispersion and Density Imaging) incorporates a gradient scheme with multiple b-values which is used to characterize neurite density and coherence of neuron fiber orientations. Similarly, the diffusion kurtosis imaging also uses a multiple shell scheme to quantify non-Gaussian diffusion but does not assume a tissue model like NODDI. In this study we investigate the connection between metrics derived by NODDI and DKI in children with ages from 46 weeks to 6 years. We correlate the NODDI metrics and Kurtosis measures from the same ROIs in multiple brain regions. We compare the range of these metrics between neonates (46 - 47 weeks), infants (2 -10 months) and young children (2 - 6 years). We find that there exists strong correlation between neurite density vs. mean kurtosis, orientation dispersion vs. kurtosis fractional anisotropy (FA) in pediatric brain imaging.

Association between resting-state brain network topological organization and creative ability: Evidence from a multiple linear regression model.

PubMed

Jiao, Bingqing; Zhang, Delong; Liang, Aiying; Liang, Bishan; Wang, Zengjian; Li, Junchao; Cai, Yuxuan; Gao, Mengxia; Gao, Zhenni; Chang, Song; Huang, Ruiwang; Liu, Ming

2017-10-01

Previous studies have indicated a tight linkage between resting-state functional connectivity of the human brain and creative ability. This study aimed to further investigate the association between the topological organization of resting-state brain networks and creativity. Therefore, we acquired resting-state fMRI data from 22 high-creativity participants and 22 low-creativity participants (as determined by their Torrance Tests of Creative Thinking scores). We then constructed functional brain networks for each participant and assessed group differences in network topological properties before exploring the relationships between respective network topological properties and creative ability. We identified an optimized organization of intrinsic brain networks in both groups. However, compared with low-creativity participants, high-creativity participants exhibited increased global efficiency and substantially decreased path length, suggesting increased efficiency of information transmission across brain networks in creative individuals. Using a multiple linear regression model, we further demonstrated that regional functional integration properties (i.e., the betweenness centrality and global efficiency) of brain networks, particularly the default mode network (DMN) and sensorimotor network (SMN), significantly predicted the individual differences in creative ability. Furthermore, the associations between network regional properties and creative performance were creativity-level dependent, where the difference in the resource control component may be important in explaining individual difference in creative performance. These findings provide novel insights into the neural substrate of creativity and may facilitate objective identification of creative ability. Copyright © 2017 Elsevier B.V. All rights reserved.

I know I've seen you before: Distinguishing recent-single-exposure-based familiarity from pre-existing familiarity

PubMed Central

Gimbel, Sarah I.; Brewer, James B.; Maril, Anat

2018-01-01

This study examines how individuals differentiate recent-single-exposure-based familiarity from pre-existing familiarity. If these are two distinct cognitive processes, are they supported by the same neural bases? This study examines how recent-single-exposure-based familiarity and multiple-previous-exposure-based familiarity are supported and represented in the brain using functional MRI. In a novel approach, we first behaviorally show that subjects can divide retrieval of items in pre-existing memory into judgments of recollection and familiarity. Then, using functional magnetic resonance imaging, we examine the differences in blood oxygen level dependent activity and regional connectivity during judgments of recent-single-exposure-based and pre-existing familiarity. Judgments of these two types of familiarity showed distinct regions of activation in a whole-brain analysis, in medial temporal lobe (MTL) substructures, and in MTL substructure functional-correlations with other brain regions. Specifically, within the MTL, perirhinal cortex showed increased activation during recent-single-exposure-based familiarity while parahippocampal cortex showed increased activation during judgments of pre-existing familiarity. We find that recent-single-exposure-based and pre-existing familiarity are represented as distinct neural processes in the brain; this is supported by differing patterns of brain activation and regional correlations. This spatially distinct regional brain involvement suggests that the two separate experiences of familiarity, recent-exposure-based familiarity and pre-existing familiarity, may be cognitively distinct. PMID:28073651

Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury

PubMed Central

Jolly, Amy; de Simoni, Sara; Bourke, Niall; Patel, Maneesh C; Scott, Gregory; Sharp, David J

2018-01-01

Abstract Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of MRI. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions; and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 patients with moderate-severe traumatic brain injury (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (1-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterized using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarized regionally and compared with clinical and neuropsychological measures. Patients with traumatic brain injury showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over 1 year was pronounced following traumatic brain injury. Patients with traumatic brain injury lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates were related to memory performance at the end of the follow-up period, as well as to changes in memory performance, prior to multiple comparison correction. In conclusion, traumatic brain injury results in progressive loss of brain tissue volume, which continues for many years post-injury. Atrophy is most prominent in the white matter, but is also more pronounced in cortical sulci compared to gyri. These findings suggest the Jacobian determinant provides a method of quantifying brain atrophy following a traumatic brain injury and is informative in determining the long-term neurodegenerative effects after injury. Power calculations indicate that Jacobian determinant images are an efficient surrogate marker in clinical trials of neuroprotective therapeutics. PMID:29309542

ATPP: A Pipeline for Automatic Tractography-Based Brain Parcellation

PubMed Central

Li, Hai; Fan, Lingzhong; Zhuo, Junjie; Wang, Jiaojian; Zhang, Yu; Yang, Zhengyi; Jiang, Tianzi

2017-01-01

There is a longstanding effort to parcellate brain into areas based on micro-structural, macro-structural, or connectional features, forming various brain atlases. Among them, connectivity-based parcellation gains much emphasis, especially with the considerable progress of multimodal magnetic resonance imaging in the past two decades. The Brainnetome Atlas published recently is such an atlas that follows the framework of connectivity-based parcellation. However, in the construction of the atlas, the deluge of high resolution multimodal MRI data and time-consuming computation poses challenges and there is still short of publically available tools dedicated to parcellation. In this paper, we present an integrated open source pipeline (https://www.nitrc.org/projects/atpp), named Automatic Tractography-based Parcellation Pipeline (ATPP) to realize the framework of parcellation with automatic processing and massive parallel computing. ATPP is developed to have a powerful and flexible command line version, taking multiple regions of interest as input, as well as a user-friendly graphical user interface version for parcellating single region of interest. We demonstrate the two versions by parcellating two brain regions, left precentral gyrus and middle frontal gyrus, on two independent datasets. In addition, ATPP has been successfully utilized and fully validated in a variety of brain regions and the human Brainnetome Atlas, showing the capacity to greatly facilitate brain parcellation. PMID:28611620

Electrical Stimulation Modulates High γ Activity and Human Memory Performance

PubMed Central

Berry, Brent M.; Miller, Laura R.; Khadjevand, Fatemeh; Ezzyat, Youssef; Wanda, Paul; Sperling, Michael R.; Lega, Bradley; Stead, S. Matt

2018-01-01

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62–118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with “poor” memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation. PMID:29404403

Genomic and Epigenomic Insights into Nutrition and Brain Disorders

PubMed Central

Dauncey, Margaret Joy

2013-01-01

Considerable evidence links many neuropsychiatric, neurodevelopmental and neurodegenerative disorders with multiple complex interactions between genetics and environmental factors such as nutrition. Mental health problems, autism, eating disorders, Alzheimer’s disease, schizophrenia, Parkinson’s disease and brain tumours are related to individual variability in numerous protein-coding and non-coding regions of the genome. However, genotype does not necessarily determine neurological phenotype because the epigenome modulates gene expression in response to endogenous and exogenous regulators, throughout the life-cycle. Studies using both genome-wide analysis of multiple genes and comprehensive analysis of specific genes are providing new insights into genetic and epigenetic mechanisms underlying nutrition and neuroscience. This review provides a critical evaluation of the following related areas: (1) recent advances in genomic and epigenomic technologies, and their relevance to brain disorders; (2) the emerging role of non-coding RNAs as key regulators of transcription, epigenetic processes and gene silencing; (3) novel approaches to nutrition, epigenetics and neuroscience; (4) gene-environment interactions, especially in the serotonergic system, as a paradigm of the multiple signalling pathways affected in neuropsychiatric and neurological disorders. Current and future advances in these four areas should contribute significantly to the prevention, amelioration and treatment of multiple devastating brain disorders. PMID:23503168

Regional homogeneity of the resting-state brain activity correlates with individual intelligence.

PubMed

Wang, Leiqiong; Song, Ming; Jiang, Tianzi; Zhang, Yunting; Yu, Chunshui

2011-01-25

Resting-state functional magnetic resonance imaging has confirmed that the strengths of the long distance functional connectivity between different brain areas are correlated with individual differences in intelligence. However, the association between the local connectivity within a specific brain region and intelligence during rest remains largely unknown. The aim of this study is to investigate the relationship between local connectivity and intelligence. Fifty-nine right-handed healthy adults participated in the study. The regional homogeneity (ReHo) was used to assess the strength of local connectivity. The associations between ReHo and full-scale intelligence quotient (FSIQ) scores were studied in a voxel-wise manner using partial correlation analysis controlling for age and sex. We found that the FSIQ scores were positively correlated with the ReHo values of the bilateral inferior parietal lobules, middle frontal, parahippocampal and inferior temporal gyri, the right thalamus, superior frontal and fusiform gyri, and the left superior parietal lobule. The main findings are consistent with the parieto-frontal integration theory (P-FIT) of intelligence, supporting the view that general intelligence involves multiple brain regions throughout the brain. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Evaluation of Cross-Protocol Stability of a Fully Automated Brain Multi-Atlas Parcellation Tool.

PubMed

Liang, Zifei; He, Xiaohai; Ceritoglu, Can; Tang, Xiaoying; Li, Yue; Kutten, Kwame S; Oishi, Kenichi; Miller, Michael I; Mori, Susumu; Faria, Andreia V

2015-01-01

Brain parcellation tools based on multiple-atlas algorithms have recently emerged as a promising method with which to accurately define brain structures. When dealing with data from various sources, it is crucial that these tools are robust for many different imaging protocols. In this study, we tested the robustness of a multiple-atlas, likelihood fusion algorithm using Alzheimer's Disease Neuroimaging Initiative (ADNI) data with six different protocols, comprising three manufacturers and two magnetic field strengths. The entire brain was parceled into five different levels of granularity. In each level, which defines a set of brain structures, ranging from eight to 286 regions, we evaluated the variability of brain volumes related to the protocol, age, and diagnosis (healthy or Alzheimer's disease). Our results indicated that, with proper pre-processing steps, the impact of different protocols is minor compared to biological effects, such as age and pathology. A precise knowledge of the sources of data variation enables sufficient statistical power and ensures the reliability of an anatomical analysis when using this automated brain parcellation tool on datasets from various imaging protocols, such as clinical databases.

Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic decision making.

PubMed

Coulthard, Elizabeth J; Bogacz, Rafal; Javed, Shazia; Mooney, Lucy K; Murphy, Gillian; Keeley, Sophie; Whone, Alan L

2012-12-01

Even simple behaviour requires us to make decisions based on combining multiple pieces of learned and new information. Making such decisions requires both learning the optimal response to each given stimulus as well as combining probabilistic information from multiple stimuli before selecting a response. Computational theories of decision making predict that learning individual stimulus-response associations and rapid combination of information from multiple stimuli are dependent on different components of basal ganglia circuitry. In particular, learning and retention of memory, required for optimal response choice, are significantly reliant on dopamine, whereas integrating information probabilistically is critically dependent upon functioning of the glutamatergic subthalamic nucleus (computing the 'normalization term' in Bayes' theorem). Here, we test these theories by investigating 22 patients with Parkinson's disease either treated with deep brain stimulation to the subthalamic nucleus and dopaminergic therapy or managed with dopaminergic therapy alone. We use computerized tasks that probe three cognitive functions-information acquisition (learning), memory over a delay and information integration when multiple pieces of sequentially presented information have to be combined. Patients performed the tasks ON or OFF deep brain stimulation and/or ON or OFF dopaminergic therapy. Consistent with the computational theories, we show that stopping dopaminergic therapy impairs memory for probabilistic information over a delay, whereas deep brain stimulation to the region of the subthalamic nucleus disrupts decision making when multiple pieces of acquired information must be combined. Furthermore, we found that when participants needed to update their decision on the basis of the last piece of information presented in the decision-making task, patients with deep brain stimulation of the subthalamic nucleus region did not slow down appropriately to revise their plan, a pattern of behaviour that mirrors the impulsivity described clinically in some patients with subthalamic nucleus deep brain stimulation. Thus, we demonstrate distinct mechanisms for two important facets of human decision making: first, a role for dopamine in memory consolidation, and second, the critical importance of the subthalamic nucleus in successful decision making when multiple pieces of information must be combined.

Brain intra- and extracellular sodium concentration in multiple sclerosis: a 7 T MRI study.

PubMed

Petracca, Maria; Vancea, Roxana O; Fleysher, Lazar; Jonkman, Laura E; Oesingmann, Niels; Inglese, Matilde

2016-03-01

Intra-axonal accumulation of sodium ions is one of the key mechanisms of delayed neuro-axonal degeneration that contributes to disability accrual in multiple sclerosis. In vivo sodium magnetic resonance imaging studies have demonstrated an increase of brain total sodium concentration in patients with multiple sclerosis, especially in patients with greater disability. However, total sodium concentration is a weighted average of intra- and extra-cellular sodium concentration whose changes reflect different tissue pathophysiological processes. The in vivo, non-invasive measurement of intracellular sodium concentration is quite challenging and the few applications in patients with neurological diseases are limited to case reports and qualitative assessments. In the present study we provide first evidence of the feasibility of triple quantum filtered (23)Na magnetic resonance imaging at 7 T, and provide in vivo quantification of global and regional brain intra- and extra-cellular sodium concentration in 19 relapsing-remitting multiple sclerosis patients and 17 heathy controls. Global grey matter and white matter total sodium concentration (respectively P < 0.05 and P < 0.01), and intracellular sodium concentration (both P < 0.001) were higher while grey matter and white matter intracellular sodium volume fraction (indirect measure of extracellular sodium concentration) were lower (respectively P = 0.62 and P < 0.001) in patients compared with healthy controls. At a brain regional level, clusters of increased total sodium concentration and intracellular sodium concentration and decreased intracellular sodium volume fraction were found in several cortical, subcortical and white matter regions when patients were compared with healthy controls (P < 0.05 family-wise error corrected for total sodium concentration, P < 0.05 uncorrected for multiple comparisons for intracellular sodium concentration and intracellular sodium volume fraction). Measures of total sodium concentration and intracellular sodium volume fraction, but not measures of intracellular sodium concentration were correlated with T2-weighted and T1-weighted lesion volumes (0.05 < P < 0.01) and with Expanded Disability Status Scale (P < 0.05). Thus, suggesting that while intracellular sodium volume fraction decrease could reflect expansion of extracellular space due to tissue loss, intracellular sodium concentration increase could reflect neuro-axonal metabolic dysfunction. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Individual Morphological Brain Network Construction Based on Multivariate Euclidean Distances Between Brain Regions.

PubMed

Yu, Kaixin; Wang, Xuetong; Li, Qiongling; Zhang, Xiaohui; Li, Xinwei; Li, Shuyu

2018-01-01

Morphological brain network plays a key role in investigating abnormalities in neurological diseases such as mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, most of the morphological brain network construction methods only considered a single morphological feature. Each type of morphological feature has specific neurological and genetic underpinnings. A combination of morphological features has been proven to have better diagnostic performance compared with a single feature, which suggests that an individual morphological brain network based on multiple morphological features would be beneficial in disease diagnosis. Here, we proposed a novel method to construct individual morphological brain networks for two datasets by calculating the exponential function of multivariate Euclidean distance as the evaluation of similarity between two regions. The first dataset included 24 healthy subjects who were scanned twice within a 3-month period. The topological properties of these brain networks were analyzed and compared with previous studies that used different methods and modalities. Small world property was observed in all of the subjects, and the high reproducibility indicated the robustness of our method. The second dataset included 170 patients with MCI (86 stable MCI and 84 progressive MCI cases) and 169 normal controls (NC). The edge features extracted from the individual morphological brain networks were used to distinguish MCI from NC and separate MCI subgroups (progressive vs. stable) through the support vector machine in order to validate our method. The results showed that our method achieved an accuracy of 79.65% (MCI vs. NC) and 70.59% (stable MCI vs. progressive MCI) in a one-dimension situation. In a multiple-dimension situation, our method improved the classification performance with an accuracy of 80.53% (MCI vs. NC) and 77.06% (stable MCI vs. progressive MCI) compared with the method using a single feature. The results indicated that our method could effectively construct an individual morphological brain network based on multiple morphological features and could accurately discriminate MCI from NC and stable MCI from progressive MCI, and may provide a valuable tool for the investigation of individual morphological brain networks.

Increased 5S rRNA oxidation in Alzheimer's disease.

PubMed

Ding, Qunxing; Zhu, Haiyan; Zhang, Bing; Soriano, Augusto; Burns, Roxanne; Markesbery, William R

2012-01-01

It is widely accepted that oxidative stress is involved in neurodegenerative disorders such as Alzheimer's disease (AD). Ribosomal RNA (rRNA) is one of the most abundant molecules in most cells and is affected by oxidative stress in the human brain. Previous data have indicated that total rRNA levels were decreased in the brains of subjects with AD and mild cognitive impairment concomitant with an increase in rRNA oxidation. In addition, level of 5S rRNA, one of the essential components of the ribosome complex, was significantly lower in the inferior parietal lobule (IP) brain area of subjects with AD compared with control subjects. To further evaluate the alteration of 5S rRNA in neurodegenerative human brains, multiple brain regions from both AD and age-matched control subjects were used in this study, including IP, superior and middle temporal gyro, temporal pole, and cerebellum. Different molecular pools including 5S rRNA integrated into ribosome complexes, free 5S rRNA, cytoplasmic 5S rRNA, and nuclear 5S rRNA were studied. Free 5S rRNA levels were significantly decreased in the temporal pole region of AD subjects and the oxidation of ribosome-integrated and free 5S rRNA was significantly increased in multiple brain regions in AD subjects compared with controls. Moreover, a greater amount of oxidized 5S rRNA was detected in the cytoplasm and nucleus of AD subjects compared with controls. These results suggest that the increased oxidation of 5S rRNA, especially the oxidation of free 5S rRNA, may be involved in the neurodegeneration observed in AD.

Aberrant Network Activity in Schizophrenia.

PubMed

Hunt, Mark J; Kopell, Nancy J; Traub, Roger D; Whittington, Miles A

2017-06-01

Brain dynamic changes associated with schizophrenia are largely equivocal, with interpretation complicated by many factors, such as the presence of therapeutic agents and the complex nature of the syndrome itself. Evidence for a brain-wide change in individual network oscillations, shared by all patients, is largely equivocal, but stronger for lower (delta) than for higher (gamma) bands. However, region-specific changes in rhythms across multiple, interdependent, nested frequencies may correlate better with pathology. Changes in synaptic excitation and inhibition in schizophrenia disrupt delta rhythm-mediated cortico-cortical communication, while enhancing thalamocortical communication in this frequency band. The contrasting relationships between delta and higher frequencies in thalamus and cortex generate frequency mismatches in inter-regional connectivity, leading to a disruption in temporal communication between higher-order brain regions associated with mental time travel. Copyright © 2017 Elsevier Ltd. All rights reserved.

Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

PubMed Central

Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark

2015-01-01

Abstract Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting. PMID:25285363

Children with mathematical learning disability fail in recruiting verbal and numerical brain regions when solving simple multiplication problems.

PubMed

Berteletti, Ilaria; Prado, Jérôme; Booth, James R

2014-08-01

Greater skill in solving single-digit multiplication problems requires a progressive shift from a reliance on numerical to verbal mechanisms over development. Children with mathematical learning disability (MD), however, are thought to suffer from a specific impairment in numerical mechanisms. Here we tested the hypothesis that this impairment might prevent MD children from transitioning toward verbal mechanisms when solving single-digit multiplication problems. Brain activations during multiplication problems were compared in MD and typically developing (TD) children (3rd to 7th graders) in numerical and verbal regions which were individuated by independent localizer tasks. We used small (e.g., 2 × 3) and large (e.g., 7 × 9) problems as these problems likely differ in their reliance on verbal versus numerical mechanisms. Results indicate that MD children have reduced activations in both the verbal (i.e., left inferior frontal gyrus and left middle temporal to superior temporal gyri) and the numerical (i.e., right superior parietal lobule including intra-parietal sulcus) regions suggesting that both mechanisms are impaired. Moreover, the only reliable activation observed for MD children was in the numerical region when solving small problems. This suggests that MD children could effectively engage numerical mechanisms only for the easier problems. Conversely, TD children showed a modulation of activation with problem size in the verbal regions. This suggests that TD children were effectively engaging verbal mechanisms for the easier problems. Moreover, TD children with better language skills were more effective at engaging verbal mechanisms. In conclusion, results suggest that the numerical- and language-related processes involved in solving multiplication problems are impaired in MD children. Published by Elsevier Ltd.

Endothelial cells are critical regulators of iron transport in a model of the human blood-brain barrier.

PubMed

Chiou, Brian; Neal, Emma H; Bowman, Aaron B; Lippmann, Ethan S; Simpson, Ian A; Connor, James R

2018-01-01

Iron delivery to the brain is essential for multiple neurological processes such as myelination, neurotransmitter synthesis, and energy production. Loss of brain iron homeostasis is a significant factor in multiple neurological disorders. Understanding the mechanism by which the transport of iron across the blood-brain barrier (BBB) is regulated is crucial to address the impact of iron deficiency on brain development and excessive accumulation of iron in neurodegenerative diseases. Using induced pluripotent stem cell (iPSC)-derived brain endothelial cells (huECs) as a human BBB model, we demonstrate the ability of transferrin, hepcidin, and DMT1 to impact iron transport and release. Our model reveals a new function for H-ferritin to transport iron across the BBB by binding to the T-cell immunoglobulin and mucin receptor 1. We show that huECs secrete both transferrin and H-ferritin, which can serve as iron sources for the brain. Based on our data, brain iron status can exert control of iron transport across the endothelial cells that constitute the BBB. These data address a number of pertinent questions such as how brain iron uptake is regulated at the regional level, the source of iron delivery to the brain, and the clinical strategies for attempting to treat brain iron deficiency.

Abnormal functional connectivity and cortical integrity influence dominant hand motor disability in multiple sclerosis: a multimodal analysis.

PubMed

Zhong, Jidan; Nantes, Julia C; Holmes, Scott A; Gallant, Serge; Narayanan, Sridar; Koski, Lisa

2016-12-01

Functional reorganization and structural damage occur in the brains of people with multiple sclerosis (MS) throughout the disease course. However, the relationship between resting-state functional connectivity (FC) reorganization in the sensorimotor network and motor disability in MS is not well understood. This study used resting-state fMRI, T1-weighted and T2-weighted, and magnetization transfer (MT) imaging to investigate the relationship between abnormal FC in the sensorimotor network and upper limb motor disability in people with MS, as well as the impact of disease-related structural abnormalities within this network. Specifically, the differences in FC of the left hemisphere hand motor region between MS participants with preserved (n = 17) and impaired (n = 26) right hand function, compared with healthy controls (n = 20) was investigated. Differences in brain atrophy and MT ratio measured at the global and regional levels were also investigated between the three groups. Motor preserved MS participants had stronger FC in structurally intact visual information processing regions relative to motor impaired MS participants. Motor impaired MS participants showed weaker FC in the sensorimotor and somatosensory association cortices and more severe structural damage throughout the brain compared with the other groups. Logistic regression analysis showed that regional MTR predicted motor disability beyond the impact of global atrophy whereas regional grey matter volume did not. More importantly, as the first multimodal analysis combining resting-state fMRI, T1-weighted, T2-weighted and MTR images in MS, we demonstrate how a combination of structural and functional changes may contribute to motor impairment or preservation in MS. Hum Brain Mapp 37:4262-4275, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

sLORETA current source density analysis of evoked potentials for spatial updating in a virtual navigation task

PubMed Central

Nguyen, Hai M.; Matsumoto, Jumpei; Tran, Anh H.; Ono, Taketoshi; Nishijo, Hisao

2014-01-01

Previous studies have reported that multiple brain regions are activated during spatial navigation. However, it is unclear whether these activated brain regions are specifically associated with spatial updating or whether some regions are recruited for parallel cognitive processes. The present study aimed to localize current sources of event related potentials (ERPs) associated with spatial updating specifically. In the control phase of the experiment, electroencephalograms (EEGs) were recorded while subjects sequentially traced 10 blue checkpoints on the streets of a virtual town, which were sequentially connected by a green line, by manipulating a joystick. In the test phase of the experiment, the checkpoints and green line were not indicated. Instead, a tone was presented when the subjects entered the reference points where they were then required to trace the 10 invisible spatial reference points corresponding to the checkpoints. The vertex-positive ERPs with latencies of approximately 340 ms from the moment when the subjects entered the unmarked reference points were significantly larger in the test than in the control phases. Current source density analysis of the ERPs by standardized low-resolution brain electromagnetic tomography (sLORETA) indicated activation of brain regions in the test phase that are associated with place and landmark recognition (entorhinal cortex/hippocampus, parahippocampal and retrosplenial cortices, fusiform, and lingual gyri), detecting self-motion (posterior cingulate and posterior insular cortices), motor planning (superior frontal gyrus, including the medial frontal cortex), and regions that process spatial attention (inferior parietal lobule). The present results provide the first identification of the current sources of ERPs associated with spatial updating, and suggest that multiple systems are active in parallel during spatial updating. PMID:24624067

Infants and adults have similar regional functional brain organization for the perception of emotions.

PubMed

Rotem-Kohavi, N; Oberlander, T F; Virji-Babul, N

2017-05-22

An infant's ability to perceive emotional facial expressions is critical for developing social skills. Infants are tuned to faces from early in life, however the functional organization of the brain that supports the processing of emotional faces in infants is still not well understood. We recorded electroencephalography (EEG) brain responses in 8-10 month old infants and adults and applied graph theory analysis on the functional connections to compare the network organization at the global and the regional levels underlying the perception of negative and positive dynamic facial expressions (happiness and sadness). We first show that processing of dynamic emotional faces occurs across multiple brain regions in both infants and adults. Across all brain regions, at the global level, network density was higher in the infant group in comparison with adults suggesting that the overall brain organization in relation to emotion perception is still immature in infancy. In contrast, at the regional levels, the functional characteristics of the frontal and parietal nodes were similar between infants and adults, suggesting that functional regional specialization for emotion perception is already established at this age. In addition, in both groups the occipital, parietal and temporal nodes appear to have the strongest influence on information flow within the network. These results suggest that while the global organization for the emotion perception of sad and happy emotions is still under development, the basic functional network organization at the regional level is already in place early in infancy. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanisms of interactive specialization and emergence of functional brain circuits supporting cognitive development in children

NASA Astrophysics Data System (ADS)

Battista, Christian; Evans, Tanya M.; Ngoon, Tricia J.; Chen, Tianwen; Chen, Lang; Kochalka, John; Menon, Vinod

2018-01-01

Cognitive development is thought to depend on the refinement and specialization of functional circuits over time, yet little is known about how this process unfolds over the course of childhood. Here we investigated growth trajectories of functional brain circuits and tested an interactive specialization model of neurocognitive development which posits that the refinement of task-related functional networks is driven by a shared history of co-activation between cortical regions. We tested this model in a longitudinal cohort of 30 children with behavioral and task-related functional brain imaging data at multiple time points spanning childhood and adolescence, focusing on the maturation of parietal circuits associated with numerical problem solving and learning. Hierarchical linear modeling revealed selective strengthening as well as weakening of functional brain circuits. Connectivity between parietal and prefrontal cortex decreased over time, while connectivity within posterior brain regions, including intra-hemispheric and inter-hemispheric parietal connectivity, as well as parietal connectivity with ventral temporal occipital cortex regions implicated in quantity manipulation and numerical symbol recognition, increased over time. Our study provides insights into the longitudinal maturation of functional circuits in the human brain and the mechanisms by which interactive specialization shapes children's cognitive development and learning.

The Metastable Brain

PubMed Central

Tognoli, Emmanuelle; Kelso, J. A. Scott

2014-01-01

Neural ensembles oscillate across a broad range of frequencies and are transiently coupled or “bound” together when people attend to a stimulus, perceive, think and act. This is a dynamic, self-assembling process, with parts of the brain engaging and disengaging in time. But how is it done? The theory of Coordination Dynamics proposes a mechanism called metastability, a subtle blend of integration and segregation. Tendencies for brain regions to express their individual autonomy and specialized functions (segregation, modularity) coexist with tendencies to couple and coordinate globally for multiple functions (integration). Although metastability has garnered increasing attention, it has yet to be demonstrated and treated within a fully spatiotemporal perspective. Here, we illustrate metastability in continuous neural and behavioral recordings, and we discuss theory and experiments at multiple scales suggesting that metastable dynamics underlie the real-time coordination necessary for the brain's dynamic cognitive, behavioral and social functions. PMID:24411730

Whole-brain ex-vivo quantitative MRI of the cuprizone mouse model

PubMed Central

Hurley, Samuel A.; Vernon, Anthony C.; Torres, Joel; Dell’Acqua, Flavio; Williams, Steve C.R.; Cash, Diana

2016-01-01

Myelin is a critical component of the nervous system and a major contributor to contrast in Magnetic Resonance (MR) images. However, the precise contribution of myelination to multiple MR modalities is still under debate. The cuprizone mouse is a well-established model of demyelination that has been used in several MR studies, but these have often imaged only a single slice and analysed a small region of interest in the corpus callosum. We imaged and analyzed the whole brain of the cuprizone mouse ex-vivo using high-resolution quantitative MR methods (multi-component relaxometry, Diffusion Tensor Imaging (DTI) and morphometry) and found changes in multiple regions, including the corpus callosum, cerebellum, thalamus and hippocampus. The presence of inflammation, confirmed with histology, presents difficulties in isolating the sensitivity and specificity of these MR methods to demyelination using this model. PMID:27833805

Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

PubMed

Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

2017-02-01

Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas of interest for future intervention. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Dynamic changes in DNA demethylation in the tree shrew (Tupaia belangeri chinensis) brain during postnatal development and aging.

PubMed

Wei, Shu; Hua, Hai-Rong; Chen, Qian-Quan; Zhang, Ying; Chen, Fei; Li, Shu-Qing; Li, Fan; Li, Jia-Li

2017-03-18

Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5-hydroxymethylcytosine (5hmC) ten-eleven translocation (TET) enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews ( Tupaia belangeri chinensis ). The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.

Evaluation of multiple comparison correction procedures in drug assessment studies using LORETA maps.

PubMed

Alonso, Joan Francesc; Romero, Sergio; Mañanas, Miguel Ángel; Rojas, Mónica; Riba, Jordi; Barbanoj, Manel José

2015-10-01

The identification of the brain regions involved in the neuropharmacological action is a potential procedure for drug development. These regions are commonly determined by the voxels showing significant statistical differences after comparing placebo-induced effects with drug-elicited effects. LORETA is an electroencephalography (EEG) source imaging technique frequently used to identify brain structures affected by the drug. The aim of the present study was to evaluate different methods for the correction of multiple comparisons in the LORETA maps. These methods which have been commonly used in neuroimaging and also simulated studies have been applied on a real case of pharmaco-EEG study where the effects of increasing benzodiazepine doses on the central nervous system measured by LORETA were investigated. Data consisted of EEG recordings obtained from nine volunteers who received single oral doses of alprazolam 0.25, 0.5, and 1 mg, and placebo in a randomized crossover double-blind design. The identification of active regions was highly dependent on the selected multiple test correction procedure. The combined criteria approach known as cluster mass was useful to reveal that increasing drug doses led to higher intensity and spread of the pharmacologically induced changes in intracerebral current density.

SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

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

Algan, O; Giem, J; Young, J

Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-testmore » analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.« less

Regional gray matter volumetric changes in autism associated with social and repetitive behavior symptoms

PubMed Central

Rojas, Donald C; Peterson, Eric; Winterrowd, Erin; Reite, Martin L; Rogers, Sally J; Tregellas, Jason R

2006-01-01

Background Although differences in brain anatomy in autism have been difficult to replicate using manual tracing methods, automated whole brain analyses have begun to find consistent differences in regions of the brain associated with the social cognitive processes that are often impaired in autism. We attempted to replicate these whole brain studies and to correlate regional volume changes with several autism symptom measures. Methods We performed MRI scans on 24 individuals diagnosed with DSM-IV autistic disorder and compared those to scans from 23 healthy comparison subjects matched on age. All participants were male. Whole brain, voxel-wise analyses of regional gray matter volume were conducted using voxel-based morphometry (VBM). Results Controlling for age and total gray matter volume, the volumes of the medial frontal gyri, left pre-central gyrus, right post-central gyrus, right fusiform gyrus, caudate nuclei and the left hippocampus were larger in the autism group relative to controls. Regions exhibiting smaller volumes in the autism group were observed exclusively in the cerebellum. Significant partial correlations were found between the volumes of the caudate nuclei, multiple frontal and temporal regions, the cerebellum and a measure of repetitive behaviors, controlling for total gray matter volume. Social and communication deficits in autism were also associated with caudate, cerebellar, and precuneus volumes, as well as with frontal and temporal lobe regional volumes. Conclusion Gray matter enlargement was observed in areas that have been functionally identified as important in social-cognitive processes, such as the medial frontal gyri, sensorimotor cortex and middle temporal gyrus. Additionally, we have shown that VBM is sensitive to associations between social and repetitive behaviors and regional brain volumes in autism. PMID:17166273

Voxelwise Spectral Diffusional Connectivity and its Applications to Alzheimer’s Disease and Intelligence Prediction

PubMed Central

Li, Junning; Jin, Yan; Shi, Yonggang; Dinov, Ivo D.; Wang, Danny J.; Toga, Arthur W.; Thompson, Paul M.

2014-01-01

Human brain connectivity can be studied using graph theory. Many connectivity studies parcellate the brain into regions and count fibres extracted between them. The resulting network analyses require validation of the tractography, as well as region and parameter selection. Here we investigate whole brain connectivity from a different perspective. We propose a mathematical formulation based on studying the eigenvalues of the Laplacian matrix of the diffusion tensor field at the voxel level. This voxelwise matrix has over a million parameters, but we derive the Kirchhoff complexity and eigen-spectrum through elegant mathematical theorems, without heavy computation. We use these novel measures to accurately estimate the voxelwise connectivity in multiple biomedical applications such as Alzheimer’s disease and intelligence prediction. PMID:24505723

Linked 4-Way Multimodal Brain Differences in Schizophrenia in a Large Chinese Han Population.

PubMed

Liu, Shengfeng; Wang, Haiying; Song, Ming; Lv, Luxian; Cui, Yue; Liu, Yong; Fan, Lingzhong; Zuo, Nianming; Xu, Kaibin; Du, Yuhui; Yu, Qingbao; Luo, Na; Qi, Shile; Yang, Jian; Xie, Sangma; Li, Jian; Chen, Jun; Chen, Yunchun; Wang, Huaning; Guo, Hua; Wan, Ping; Yang, Yongfeng; Li, Peng; Lu, Lin; Yan, Hao; Yan, Jun; Wang, Huiling; Zhang, Hongxing; Zhang, Dai; Calhoun, Vince D; Jiang, Tianzi; Sui, Jing

2018-04-20

Multimodal fusion has been regarded as a promising tool to discover covarying patterns of multiple imaging types impaired in brain diseases, such as schizophrenia (SZ). In this article, we aim to investigate the covarying abnormalities underlying SZ in a large Chinese Han population (307 SZs, 298 healthy controls [HCs]). Four types of magnetic resonance imaging (MRI) features, including regional homogeneity (ReHo) from resting-state functional MRI, gray matter volume (GM) from structural MRI, fractional anisotropy (FA) from diffusion MRI, and functional network connectivity (FNC) resulted from group independent component analysis, were jointly analyzed by a data-driven multivariate fusion method. Results suggest that a widely distributed network disruption appears in SZ patients, with synchronous changes in both functional and structural regions, especially the basal ganglia network, salience network (SAN), and the frontoparietal network. Such a multimodal coalteration was also replicated in another independent Chinese sample (40 SZs, 66 HCs). Our results on auditory verbal hallucination (AVH) also provide evidence for the hypothesis that prefrontal hypoactivation and temporal hyperactivation in SZ may lead to failure of executive control and inhibition, which is relevant to AVH. In addition, impaired working memory performance was found associated with GM reduction and FA decrease in SZ in prefrontal and superior temporal area, in both discovery and replication datasets. In summary, by leveraging multiple imaging and clinical information into one framework to observe brain in multiple views, we can integrate multiple inferences about SZ from large-scale population and offer unique perspectives regarding the missing links between the brain function and structure that may not be achieved by separate unimodal analyses.

Neurocognitive Basis of Racial Ingroup Bias in Empathy.

PubMed

Han, Shihui

2018-05-01

Racial discrimination in social behavior, although disapproved of by many contemporary cultures, has been widely reported. Because empathy plays a key functional role in social behavior, brain imaging researchers have extensively investigated the neurocognitive underpinnings of racial ingroup bias in empathy. This research has revealed consistent evidence for increased neural responses to the perceived pain of same-race compared with other-race individuals in multiple brain regions and across multiple time-windows. Researchers have also examined neurocognitive, sociocultural, and environmental influences on racial ingroup bias in empathic neural responses, as well as explored possible interventions to reduce racial ingroup bias in empathic brain activity. These findings have important implications for understanding racial ingroup favoritism in social behavior and for improving interracial communication. Copyright © 2018 Elsevier Ltd. All rights reserved.

Abnormal resting-state connectivity of motor and cognitive networks in early manifest Huntington's disease.

PubMed

Wolf, R C; Sambataro, F; Vasic, N; Depping, M S; Thomann, P A; Landwehrmeyer, G B; Süssmuth, S D; Orth, M

2014-11-01

Functional magnetic resonance imaging (fMRI) of multiple neural networks during the brain's 'resting state' could facilitate biomarker development in patients with Huntington's disease (HD) and may provide new insights into the relationship between neural dysfunction and clinical symptoms. To date, however, very few studies have examined the functional integrity of multiple resting state networks (RSNs) in manifest HD, and even less is known about whether concomitant brain atrophy affects neural activity in patients. Using MRI, we investigated brain structure and RSN function in patients with early HD (n = 20) and healthy controls (n = 20). For resting-state fMRI data a group-independent component analysis identified spatiotemporally distinct patterns of motor and prefrontal RSNs of interest. We used voxel-based morphometry to assess regional brain atrophy, and 'biological parametric mapping' analyses to investigate the impact of atrophy on neural activity. Compared with controls, patients showed connectivity changes within distinct neural systems including lateral prefrontal, supplementary motor, thalamic, cingulate, temporal and parietal regions. In patients, supplementary motor area and cingulate cortex connectivity indices were associated with measures of motor function, whereas lateral prefrontal connectivity was associated with cognition. This study provides evidence for aberrant connectivity of RSNs associated with motor function and cognition in early manifest HD when controlling for brain atrophy. This suggests clinically relevant changes of RSN activity in the presence of HD-associated cortical and subcortical structural abnormalities.

Use of Multichannel Near Infrared Spectroscopy to Study Relationships Between Brain Regions and Neurocognitive Tasks of Selective/Divided Attention and 2-Back Working Memory.

PubMed

Tomita, Nozomi; Imai, Shoji; Kanayama, Yusuke; Kawashima, Issaku; Kumano, Hiroaki

2017-06-01

While dichotic listening (DL) was originally intended to measure bottom-up selective attention, it has also become a tool for measuring top-down selective attention. This study investigated the brain regions related to top-down selective and divided attention DL tasks and a 2-back task using alphanumeric and Japanese numeric sounds. Thirty-six healthy participants underwent near-infrared spectroscopy scanning while performing a top-down selective attentional DL task, a top-down divided attentional DL task, and a 2-back task. Pearson's correlations were calculated to show relationships between oxy-Hb concentration in each brain region and the score of each cognitive task. Different brain regions were activated during the DL and 2-back tasks. Brain regions activated in the top-down selective attention DL task were the left inferior prefrontal gyrus and left pars opercularis. The left temporopolar area was activated in the top-down divided attention DL task, and the left frontopolar area and left dorsolateral prefrontal cortex were activated in the 2-back task. As further evidence for the finding that each task measured different cognitive and brain area functions, neither the percentages of correct answers for the three tasks nor the response times for the selective attentional task and the divided attentional task were correlated to one another. Thus, the DL and 2-back tasks used in this study can assess multiple areas of cognitive, brain-related dysfunction to explore their relationship to different psychiatric and neurodevelopmental disorders.

I know I've seen you before: Distinguishing recent-single-exposure-based familiarity from pre-existing familiarity.

PubMed

Gimbel, Sarah I; Brewer, James B; Maril, Anat

2017-03-01

This study examines how individuals differentiate recent-single-exposure-based familiarity from pre-existing familiarity. If these are two distinct cognitive processes, are they supported by the same neural bases? This study examines how recent-single-exposure-based familiarity and multiple-previous-exposure-based familiarity are supported and represented in the brain using functional MRI. In a novel approach, we first behaviorally show that subjects can divide retrieval of items in pre-existing memory into judgments of recollection and familiarity. Then, using functional magnetic resonance imaging, we examine the differences in blood oxygen level dependent activity and regional connectivity during judgments of recent-single-exposure-based and pre-existing familiarity. Judgments of these two types of familiarity showed distinct regions of activation in a whole-brain analysis, in medial temporal lobe (MTL) substructures, and in MTL substructure functional-correlations with other brain regions. Specifically, within the MTL, perirhinal cortex showed increased activation during recent-single-exposure-based familiarity while parahippocampal cortex showed increased activation during judgments of pre-existing familiarity. We find that recent-single-exposure-based and pre-existing familiarity are represented as distinct neural processes in the brain; this is supported by differing patterns of brain activation and regional correlations. This spatially distinct regional brain involvement suggests that the two separate experiences of familiarity, recent-exposure-based familiarity and pre-existing familiarity, may be cognitively distinct. Copyright © 2017 Elsevier B.V. All rights reserved.

The polygenic risk for bipolar disorder influences brain regional function relating to visual and default state processing of emotional information.

PubMed

Dima, Danai; de Jong, Simone; Breen, Gerome; Frangou, Sophia

2016-01-01

Genome-wise association studies have identified a number of common single-nucleotide polymorphisms (SNPs), each of small effect, associated with risk to bipolar disorder (BD). Several risk-conferring SNPs have been individually shown to influence regional brain activation thus linking genetic risk for BD to altered brain function. The current study examined whether the polygenic risk score method, which models the cumulative load of all known risk-conferring SNPs, may be useful in the identification of brain regions whose function may be related to the polygenic architecture of BD. We calculated the individual polygenic risk score for BD (PGR-BD) in forty-one patients with the disorder, twenty-five unaffected first-degree relatives and forty-six unrelated healthy controls using the most recent Psychiatric Genomics Consortium data. Functional magnetic resonance imaging was used to define task-related brain activation patterns in response to facial affect and working memory processing. We found significant effects of the PGR-BD score on task-related activation irrespective of diagnostic group. There was a negative association between the PGR-BD score and activation in the visual association cortex during facial affect processing. In contrast, the PGR-BD score was associated with failure to deactivate the ventromedial prefrontal region of the default mode network during working memory processing. These results are consistent with the threshold-liability model of BD, and demonstrate the usefulness of the PGR-BD score in identifying brain functional alternations associated with vulnerability to BD. Additionally, our findings suggest that the polygenic architecture of BD is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions.

VoxelStats: A MATLAB Package for Multi-Modal Voxel-Wise Brain Image Analysis.

PubMed

Mathotaarachchi, Sulantha; Wang, Seqian; Shin, Monica; Pascoal, Tharick A; Benedet, Andrea L; Kang, Min Su; Beaudry, Thomas; Fonov, Vladimir S; Gauthier, Serge; Labbe, Aurélie; Rosa-Neto, Pedro

2016-01-01

In healthy individuals, behavioral outcomes are highly associated with the variability on brain regional structure or neurochemical phenotypes. Similarly, in the context of neurodegenerative conditions, neuroimaging reveals that cognitive decline is linked to the magnitude of atrophy, neurochemical declines, or concentrations of abnormal protein aggregates across brain regions. However, modeling the effects of multiple regional abnormalities as determinants of cognitive decline at the voxel level remains largely unexplored by multimodal imaging research, given the high computational cost of estimating regression models for every single voxel from various imaging modalities. VoxelStats is a voxel-wise computational framework to overcome these computational limitations and to perform statistical operations on multiple scalar variables and imaging modalities at the voxel level. VoxelStats package has been developed in Matlab(®) and supports imaging formats such as Nifti-1, ANALYZE, and MINC v2. Prebuilt functions in VoxelStats enable the user to perform voxel-wise general and generalized linear models and mixed effect models with multiple volumetric covariates. Importantly, VoxelStats can recognize scalar values or image volumes as response variables and can accommodate volumetric statistical covariates as well as their interaction effects with other variables. Furthermore, this package includes built-in functionality to perform voxel-wise receiver operating characteristic analysis and paired and unpaired group contrast analysis. Validation of VoxelStats was conducted by comparing the linear regression functionality with existing toolboxes such as glim_image and RMINC. The validation results were identical to existing methods and the additional functionality was demonstrated by generating feature case assessments (t-statistics, odds ratio, and true positive rate maps). In summary, VoxelStats expands the current methods for multimodal imaging analysis by allowing the estimation of advanced regional association metrics at the voxel level.

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.

Influence of the segmentation on the characterization of cerebral networks of structural damage for patients with disorders of consciousness

NASA Astrophysics Data System (ADS)

Martínez, Darwin; Mahalingam, Jamuna J.; Soddu, Andrea; Franco, Hugo; Lepore, Natasha; Laureys, Steven; Gómez, Francisco

2015-01-01

Disorders of consciousness (DOC) are a consequence of a variety of severe brain injuries. DOC commonly results in anatomical brain modifications, which can affect cortical and sub-cortical brain structures. Postmortem studies suggest that severity of brain damage correlates with level of impairment in DOC. In-vivo studies in neuroimaging mainly focus in alterations on single structures. Recent evidence suggests that rather than one, multiple brain regions can be simultaneously affected by this condition. In other words, DOC may be linked to an underlying cerebral network of structural damage. Recently, geometrical spatial relationships among key sub-cortical brain regions, such as left and right thalamus and brain stem, have been used for the characterization of this network. This approach is strongly supported on automatic segmentation processes, which aim to extract regions of interests without human intervention. Nevertheless, patients with DOC usually present massive structural brain changes. Therefore, segmentation methods may highly influence the characterization of the underlying cerebral network structure. In this work, we evaluate the level of characterization obtained by using the spatial relationships as descriptor of a sub-cortical cerebral network (left and right thalamus) in patients with DOC, when different segmentation approaches are used (FSL, Free-surfer and manual segmentation). Our results suggest that segmentation process may play a critical role for the construction of robust and reliable structural characterization of DOC conditions.

Cerebral Blood Flow during Rest Associates with General Intelligence and Creativity

PubMed Central

Takeuchi, Hikaru; Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Nagase, Tomomi; Nouchi, Rui; Kawashima, Ryuta

2011-01-01

Recently, much scientific attention has been focused on resting brain activity and its investigation through such methods as the analysis of functional connectivity during rest (the temporal correlation of brain activities in different regions). However, investigation of the magnitude of brain activity during rest has focused on the relative decrease of brain activity during a task, rather than on the absolute resting brain activity. It is thus necessary to investigate the association between cognitive factors and measures of absolute resting brain activity, such as cerebral blood flow (CBF), during rest (rest-CBF). In this study, we examined this association using multiple regression analyses. Rest-CBF was the dependent variable and the independent variables included two essential components of cognitive functions, psychometric general intelligence and creativity. CBF was measured using arterial spin labeling and there were three analyses for rest-CBF; namely mean gray matter rest-CBF, mean white matter rest-CBF, and regional rest-CBF. The results showed that mean gray and white matter rest-CBF were significantly and positively correlated with individual psychometric intelligence. Furthermore, mean white matter rest-CBF was significantly and positively correlated with creativity. After correcting the effect of mean gray matter rest-CBF the significant and positive correlation between regional rest-CBF in the perisylvian anatomical cluster that includes the left superior temporal gyrus and insula and individual psychometric intelligence was found. Also, regional rest-CBF in the precuneus was significantly and negatively correlated with individual creativity. Significance of these results of regional rest-CBF did not change when the effect of regional gray matter density was corrected. The findings showed mean and regional rest-CBF in healthy young subjects to be correlated with cognitive functions. The findings also suggest that, even in young cognitively intact subjects, resting brain activity (possibly underlain by default cognitive activity or metabolic demand from developed brain structures) is associated with cognitive functions. PMID:21980485

An in vivo model of functional and vascularized human brain organoids.

PubMed

Mansour, Abed AlFatah; Gonçalves, J Tiago; Bloyd, Cooper W; Li, Hao; Fernandes, Sarah; Quang, Daphne; Johnston, Stephen; Parylak, Sarah L; Jin, Xin; Gage, Fred H

2018-06-01

Differentiation of human pluripotent stem cells to small brain-like structures known as brain organoids offers an unprecedented opportunity to model human brain development and disease. To provide a vascularized and functional in vivo model of brain organoids, we established a method for transplanting human brain organoids into the adult mouse brain. Organoid grafts showed progressive neuronal differentiation and maturation, gliogenesis, integration of microglia, and growth of axons to multiple regions of the host brain. In vivo two-photon imaging demonstrated functional neuronal networks and blood vessels in the grafts. Finally, in vivo extracellular recording combined with optogenetics revealed intragraft neuronal activity and suggested graft-to-host functional synaptic connectivity. This combination of human neural organoids and an in vivo physiological environment in the animal brain may facilitate disease modeling under physiological conditions.

Magnetic Resonance Spectroscopy of Regional Brain Metabolite Markers in FALS Mice and the Effects of Dietary Creatine Supplementation

PubMed Central

Choi, JiKyung; Kustermann, Ekkehard; Dedeoglu, Alpaslan; Jenkins, Bruce G.

2010-01-01

We investigated the effects of disease progression on brain regional neurochemistry in a mutant mouse model of familial amyotrophic lateral sclerosis (FALS; the G93A model) using in vivo and in vitro magnetic resonance spectroscopy (MRS). There were numerous changes in the brain spectra that were brain region dependent. At early time points starting around 80 days of age there were increases in brain glutamate. At later time points there were more extensive changes including decreased NAA, decreased glutamate and increased glutamine, taurine and myo-inositol. The effects of the disease were most severe in spinal cord followed by medulla and then sensorimotor cortex. There were no changes noted in cerebellum as a control region. The effects of creatine supplementation in the diet (2%) were measured in wild-type and FALS animals in medulla, cerebellum and cortex. The increase in brain creatine was largest in cerebellum (25%) followed by medulla (11%) and then cortex (4%) reflecting the ordering of creatine kinase activity. There was a protective effect of creatine on NAA loss in the medulla at late stages. Creatine supplementation had a positive effect on weight retention leading to a 13% increase in weight between 120-130 days. MRS shows promise in monitoring multiple facets of neuroprotective strategies in ALS and ALS models. PMID:19930399

A regional consensus recommendation on brain atrophy as an outcome measure in multiple sclerosis.

PubMed

Alroughani, Raed; Deleu, Dirk; El Salem, Khalid; Al-Hashel, Jasem; Alexander, K John; Abdelrazek, Mohamed Assem; Aljishi, Adel; Alkhaboori, Jaber; Al Azri, Faisal; Al Zadjali, Nahida; Hbahbih, Majed; Sokrab, Tag Eldin; Said, Mohamed; Rovira, Àlex

2016-11-24

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory and neurodegenerative processes leading to irreversible neurological impairment. Brain atrophy occurs early in the course of the disease at a rate greater than the general population. Brain volume loss (BVL) is associated with disability progression and cognitive impairment in patients with MS; hence its value as a potential target in monitoring and treating MS is discussed. A group of MS neurologists and neuro-radiologists reviewed the current literature on brain atrophy and discussed the challenges in assessing and implementing brain atrophy measurements in clinical practice. The panel used a voting system to reach a consensus and the votes were counted for the proposed set of questions for cognitive and brain atrophy assessments. The panel of experts was able to identify recent studies, which demonstrated the correlation between BVL and future worsening of disability and cognition. The current evidence revealed that reduction of BVL could be achieved with different disease-modifying therapies (DMTs). BVL provided a better treatment and monitoring strategy when it is combined to the composite measures of "no evidence of disease activity" (NEDA). The panel recommended a set of cognitive assessment tools and MRI methods and software applications that may help in capturing and measuring the underlying MS pathology with high degree of specificity. BVL was considered to be a useful measurement to longitudinally assess disease progression and cognitive function in patients with MS. Brain atrophy measurement was recommended to be incorporated into the concept of NEDA. Consequently, a consensus recommendation was reached in anticipation for implementation of the use of cognitive assessment and brain atrophy measurements on a regional level.

Regional Homogeneity Predicts Creative Insight: A Resting-State fMRI Study.

PubMed

Lin, Jiabao; Cui, Xuan; Dai, Xiaoying; Mo, Lei

2018-01-01

Creative insight plays an important role in our daily life. Previous studies have investigated the neural correlates of creative insight by functional magnetic resonance imaging (fMRI), however, the intrinsic resting-state brain activity associated with creative insight is still unclear. In the present study, we used regional homogeneity (ReHo) as an index in resting-state fMRI (rs-fMRI) to identify brain regions involved in individual differences in creative insight, which was compued by the response time (RT) of creative Chinese character chunk decomposition. The findings indicated that ReHo in the anterior cingulate cortex (ACC)/caudate nucleus (CN) and angular gyrus (AG)/superior temporal gyrus (STG)/inferior parietal lobe (IPL) negatively predicted creative insight. Furthermore, these findings suggested that spontaneous brain activity in multiple regions related to breaking and establishing mental sets, goal-directed solutions exploring, shifting attention, forming new associations and emotion experience contributes to creative insight. In conclusion, the present study provides new evidence to further understand the cognitive processing and neural correlates of creative insight.

Neural bases of human mate choice: multiple value dimensions, sex difference, and self-assessment system.

PubMed

Funayama, Risa; Sugiura, Motoaki; Sassa, Yuko; Jeong, Hyeonjeong; Wakusawa, Keisuke; Horie, Kaoru; Sato, Shigeru; Kawashima, Ryuta

2012-01-01

Mate choice is an example of sophisticated daily decision making supported by multiple componential processes. In mate-choice literature, different characteristics of the value dimensions, including the sex difference in the value dimensions, and the involvement of self-assessment due to the mutual nature of the choice, have been suggested. We examined whether the brain-activation pattern during virtual mate choice would be congruent with these characteristics in terms of stimulus selectivity and activated brain regions. In measuring brain activity, young men and women were shown two pictures of either faces or behaviors, and they indicated which person they would choose either as a spouse or as a friend. Activation selective to spouse choice was observed face-selectively in men's amygdala and behavior-selectively in women's motor system. During both partner-choice conditions, behavior-selective activation was observed in the temporoparietal regions. Taking the available knowledge of these regions into account, these results are congruent with the suggested characteristics of value dimensions for physical attractiveness, parenting resources, and beneficial personality traits for a long-lasting relationship, respectively. The medial prefrontal and posterior cingulate cortices were nonselectively activated during the partner choices, suggesting the involvement of a self-assessment process. The results thus provide neuroscientific support for the multi-component mate-choice mechanism.

Selective attention to temporal features on nested time scales.

PubMed

Henry, Molly J; Herrmann, Björn; Obleser, Jonas

2015-02-01

Meaningful auditory stimuli such as speech and music often vary simultaneously along multiple time scales. Thus, listeners must selectively attend to, and selectively ignore, separate but intertwined temporal features. The current study aimed to identify and characterize the neural network specifically involved in this feature-selective attention to time. We used a novel paradigm where listeners judged either the duration or modulation rate of auditory stimuli, and in which the stimulation, working memory demands, response requirements, and task difficulty were held constant. A first analysis identified all brain regions where individual brain activation patterns were correlated with individual behavioral performance patterns, which thus supported temporal judgments generically. A second analysis then isolated those brain regions that specifically regulated selective attention to temporal features: Neural responses in a bilateral fronto-parietal network including insular cortex and basal ganglia decreased with degree of change of the attended temporal feature. Critically, response patterns in these regions were inverted when the task required selectively ignoring this feature. The results demonstrate how the neural analysis of complex acoustic stimuli with multiple temporal features depends on a fronto-parietal network that simultaneously regulates the selective gain for attended and ignored temporal features. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Magnetic Resonance T2-Relaxometry and 2D L-Correlated Spectroscopy in Patients with Minimal Hepatic Encephalopathy

PubMed Central

Singhal, Aparna; Nagarajan, Rajakumar; Kumar, Rajesh; Huda, Amir; Gupta, Rakesh K.; Thomas, M. Albert

2010-01-01

Purpose To evaluate T2-relaxation changes in patients with minimal hepatic encephalopathy (MHE) using T2-relaxometry and to correlate T2 values with brain metabolites evaluated using two-dimensional (2D) magnetic resonance spectroscopy (MRS). Materials and Methods Eight MHE patients and 13 healthy subjects were evaluated using T2-relaxometry, and 8 patients and 9 healthy subjects underwent 2D MRS in right frontal and left occipital regions. Whole brain T2-relaxation maps were compared between MHE and control subjects using analysis-of-covariance, with age and gender included as covariates. T2 values derived from the right frontal and left occipital lobes were correlated with the metabolite ratios. Results Multiple brain regions including anterior and mid cingulate cortices, right anterior and left posterior insular cortices, right prefrontal, medial frontal, and right superior temporal cortices showed significantly increased T2 values in MHE patients compared to control subjects. MRS showed significantly increased ratios of glutamine/glutamate (Glx) and decreased ratios of myo-inositol, taurine, choline, and myo-inositol/choline (mICh) with respect to creatine (Cr_d) in patients compared to controls. Frontal Glx/Cr_d showed significantly positive correlation with T2 values. Conclusion MHE patients showed significantly increased T2 values in multiple brain regions reflecting increased free water content and T2 values in frontal lobe correlated with the increased Glx/Cr_d ratio. PMID:19856435

Progression of regional grey matter atrophy in multiple sclerosis

PubMed Central

Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-01-01

Abstract See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article. Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple sclerosis and late atrophy in primary-progressive multiple sclerosis. Patients with secondary-progressive multiple sclerosis showed the highest event-based model stage (the highest number of atrophic regions, P < 0.001) at the study entry. All multiple sclerosis phenotypes, but clinically isolated syndrome, showed a faster rate of increase in the event-based model stage than healthy controls. T2 lesion load and disease duration in all patients were associated with increased event-based model stage, but no effects of disease-modifying treatments and comorbidity on event-based model stage were observed. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting multiple sclerosis, independent of disease duration (P < 0.0001). The data-driven staging of atrophy progression in a large multiple sclerosis sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across multiple sclerosis phenotypes. The spread of atrophy was associated with disease duration and with disability accumulation over time in relapsing-remitting multiple sclerosis. PMID:29741648

Progression of regional grey matter atrophy in multiple sclerosis.

PubMed

Eshaghi, Arman; Marinescu, Razvan V; Young, Alexandra L; Firth, Nicholas C; Prados, Ferran; Jorge Cardoso, M; Tur, Carmen; De Angelis, Floriana; Cawley, Niamh; Brownlee, Wallace J; De Stefano, Nicola; Laura Stromillo, M; Battaglini, Marco; Ruggieri, Serena; Gasperini, Claudio; Filippi, Massimo; Rocca, Maria A; Rovira, Alex; Sastre-Garriga, Jaume; Geurts, Jeroen J G; Vrenken, Hugo; Wottschel, Viktor; Leurs, Cyra E; Uitdehaag, Bernard; Pirpamer, Lukas; Enzinger, Christian; Ourselin, Sebastien; Gandini Wheeler-Kingshott, Claudia A; Chard, Declan; Thompson, Alan J; Barkhof, Frederik; Alexander, Daniel C; Ciccarelli, Olga

2018-06-01

See Stankoff and Louapre (doi:10.1093/brain/awy114) for a scientific commentary on this article.Grey matter atrophy is present from the earliest stages of multiple sclerosis, but its temporal ordering is poorly understood. We aimed to determine the sequence in which grey matter regions become atrophic in multiple sclerosis and its association with disability accumulation. In this longitudinal study, we included 1417 subjects: 253 with clinically isolated syndrome, 708 with relapsing-remitting multiple sclerosis, 128 with secondary-progressive multiple sclerosis, 125 with primary-progressive multiple sclerosis, and 203 healthy control subjects from seven European centres. Subjects underwent repeated MRI (total number of scans 3604); the mean follow-up for patients was 2.41 years (standard deviation = 1.97). Disability was scored using the Expanded Disability Status Scale. We calculated the volume of brain grey matter regions and brainstem using an unbiased within-subject template and used an established data-driven event-based model to determine the sequence of occurrence of atrophy and its uncertainty. We assigned each subject to a specific event-based model stage, based on the number of their atrophic regions. Linear mixed-effects models were used to explore associations between the rate of increase in event-based model stages, and T2 lesion load, disease-modifying treatments, comorbidity, disease duration and disability accumulation. The first regions to become atrophic in patients with clinically isolated syndrome and relapse-onset multiple sclerosis were the posterior cingulate cortex and precuneus, followed by the middle cingulate cortex, brainstem and thalamus. A similar sequence of atrophy was detected in primary-progressive multiple sclerosis with the involvement of the thalamus, cuneus, precuneus, and pallidum, followed by the brainstem and posterior cingulate cortex. The cerebellum, caudate and putamen showed early atrophy in relapse-onset multiple sclerosis and late atrophy in primary-progressive multiple sclerosis. Patients with secondary-progressive multiple sclerosis showed the highest event-based model stage (the highest number of atrophic regions, P < 0.001) at the study entry. All multiple sclerosis phenotypes, but clinically isolated syndrome, showed a faster rate of increase in the event-based model stage than healthy controls. T2 lesion load and disease duration in all patients were associated with increased event-based model stage, but no effects of disease-modifying treatments and comorbidity on event-based model stage were observed. The annualized rate of event-based model stage was associated with the disability accumulation in relapsing-remitting multiple sclerosis, independent of disease duration (P < 0.0001). The data-driven staging of atrophy progression in a large multiple sclerosis sample demonstrates that grey matter atrophy spreads to involve more regions over time. The sequence in which regions become atrophic is reasonably consistent across multiple sclerosis phenotypes. The spread of atrophy was associated with disease duration and with disability accumulation over time in relapsing-remitting multiple sclerosis.

Combining Computational Modeling and Neuroimaging to Examine Multiple Category Learning Systems in the Brain

PubMed Central

Nomura, Emi M.; Reber, Paul J.

2012-01-01

Considerable evidence has argued in favor of multiple neural systems supporting human category learning, one based on conscious rule inference and one based on implicit information integration. However, there have been few attempts to study potential system interactions during category learning. The PINNACLE (Parallel Interactive Neural Networks Active in Category Learning) model incorporates multiple categorization systems that compete to provide categorization judgments about visual stimuli. Incorporating competing systems requires inclusion of cognitive mechanisms associated with resolving this competition and creates a potential credit assignment problem in handling feedback. The hypothesized mechanisms make predictions about internal mental states that are not always reflected in choice behavior, but may be reflected in neural activity. Two prior functional magnetic resonance imaging (fMRI) studies of category learning were re-analyzed using PINNACLE to identify neural correlates of internal cognitive states on each trial. These analyses identified additional brain regions supporting the two types of category learning, regions particularly active when the systems are hypothesized to be in maximal competition, and found evidence of covert learning activity in the “off system” (the category learning system not currently driving behavior). These results suggest that PINNACLE provides a plausible framework for how competing multiple category learning systems are organized in the brain and shows how computational modeling approaches and fMRI can be used synergistically to gain access to cognitive processes that support complex decision-making machinery. PMID:24962771

Spontaneous alterations of regional brain activity in patients with adult generalized anxiety disorder

PubMed Central

Xia, Likun; Li, Shumei; Wang, Tianyue; Guo, Yaping; Meng, Lihong; Feng, Yunping; Cui, Yu; Wang, Fan; Ma, Jian; Jiang, Guihua

2017-01-01

Objective We aimed to examine how spontaneous brain activity might be related to the pathophysiology of generalized anxiety disorder (GAD). Patients and methods Using resting-state functional MRI, we examined spontaneous regional brain activity in 31 GAD patients (mean age, 36.87±9.16 years) and 36 healthy control participants (mean age, 39.53±8.83 years) matched for age, education, and sex from December 2014 to October 2015. We performed a two-sample t-test on the voxel-based analysis of the regional homogeneity (ReHo) maps. We used Pearson correlation analysis to compare scores from the Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, State–Trait Anxiety Scale-Trait Scale, and mean ReHo values. Results We found abnormal spontaneous activity in multiple regions of brain in GAD patients, especially in the sensorimotor cortex and emotional regions. GAD patients showed decreased ReHo values in the right orbital middle frontal gyrus, left anterior cingulate cortex, right middle frontal gyrus, and bilateral supplementary motor areas, with increased ReHo values in the left middle temporal gyrus, left superior temporal gyrus, and right superior occipital gyrus. The ReHo value of the left middle temporal gyrus correlated positively with the Hamilton Anxiety Rating Scale scores. Conclusion These results suggest that altered local synchronization of spontaneous brain activity may be related to the pathophysiology of GAD. PMID:28790831

Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease

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

Maass, Anne; Landau, Susan; Baker, Suzanne L.

The recent development of tau-specific positron emission tomography (PET) tracers enables in vivo quantification of regional tau pathology, one of the key lesions in Alzheimer's disease (AD). Tau PET imaging may become a useful biomarker for clinical diagnosis and tracking of disease progression but there is no consensus yet on how tau PET signal is best quantified. The goal of the current paper was to evaluate multiple whole-brain and region-specific approaches to detect clinically relevant tau PET signal. Two independent cohorts of cognitively normal adults and amyloid-positive (Aβ +) patients with mild cognitive impairment (MCI) or AD-dementia underwent [ 18F]AV-1451more » PET. Methods for tau tracer quantification included: (i) in vivo Braak staging, (ii) regional uptake in Braak composite regions, (iii) several whole-brain measures of tracer uptake, (iv) regional uptake in AD-vulnerable voxels, and (v) uptake in a priori defined regions. Receiver operating curves characterized accuracy in distinguishing Aβ - controls from AD/MCI patients and yielded tau positivity cutoffs. Clinical relevance of tau PET measures was assessed by regressions against cognition and MR imaging measures. Key tracer uptake patterns were identified by a factor analysis and voxel-wise contrasts. Braak staging, global and region-specific tau measures yielded similar diagnostic accuracies, which differed between cohorts. While all tau measures were related to amyloid and global cognition, memory and hippocampal/entorhinal volume/thickness were associated with regional tracer retention in the medial temporal lobe. Key regions of tau accumulation included medial temporal and inferior/middle temporal regions, retrosplenial cortex, and banks of the superior temporal sulcus. Finally, our data indicate that whole-brain tau PET measures might be adequate biomarkers to detect AD-related tau pathology. However, regional measures covering AD-vulnerable regions may increase sensitivity to early tau PET signal, atrophy and memory decline.« less

Clustering Multiple Sclerosis Subgroups with Multifractal Methods and Self-Organizing Map Algorithm

NASA Astrophysics Data System (ADS)

Karaca, Yeliz; Cattani, Carlo

Magnetic resonance imaging (MRI) is the most sensitive method to detect chronic nervous system diseases such as multiple sclerosis (MS). In this paper, Brownian motion Hölder regularity functions (polynomial, periodic (sine), exponential) for 2D image, such as multifractal methods were applied to MR brain images, aiming to easily identify distressed regions, in MS patients. With these regions, we have proposed an MS classification based on the multifractal method by using the Self-Organizing Map (SOM) algorithm. Thus, we obtained a cluster analysis by identifying pixels from distressed regions in MR images through multifractal methods and by diagnosing subgroups of MS patients through artificial neural networks.

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

Lewis, M.E.; Khachaturian, H.; Watson, S.J.

Using adjacent section autoradiography-immunocytochemistry, the distribution of (TH)naloxone binding sites was studied in relation to neuronal systems containing (Leu)enkephalin, dynorphin A, or beta-endorphin immunoreactivity in rat brain. Brain sections from formaldehyde-perfused rats show robust specific binding of (TH)naloxone, the pharmacological (mu-like) properties of which appear unaltered. In contrast, specific binding of the delta ligand (TH)D-Ala2,D-Leu5-enkephalin was virtually totally eliminated as a result of formaldehyde perfusion. Using adjacent section analysis, the authors have noted associations between (TH)naloxone binding sites and one, two, or all three opioid systems in different brain regions; however, in some areas, no apparent relationship could be observed.more » Within regions, the relationship was complex. The complexity of the association between (TH)naloxone binding sites and the multiple opioid systems, and previous reports of co-localization of mu and kappa receptors in rat brain, are inconsistent with a simple-one-to-one relationship between a given opioid precursor and opioid receptor subtype. Instead, since differential processing of the three precursors gives rise to peptides of varying receptor subtype potencies and selectivities, the multiple peptide-receptor relationships may point to a key role of post-translational processing in determining the physiological consequences of opioid neurotransmission.« less

Typical cerebral metabolic patterns in neurodegenerative brain diseases.

PubMed

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

2010-10-30

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

Learning-based meta-algorithm for MRI brain extraction.

PubMed

Shi, Feng; Wang, Li; Gilmore, John H; Lin, Weili; Shen, Dinggang

2011-01-01

Multiple-segmentation-and-fusion method has been widely used for brain extraction, tissue segmentation, and region of interest (ROI) localization. However, such studies are hindered in practice by their computational complexity, mainly coming from the steps of template selection and template-to-subject nonlinear registration. In this study, we address these two issues and propose a novel learning-based meta-algorithm for MRI brain extraction. Specifically, we first use exemplars to represent the entire template library, and assign the most similar exemplar to the test subject. Second, a meta-algorithm combining two existing brain extraction algorithms (BET and BSE) is proposed to conduct multiple extractions directly on test subject. Effective parameter settings for the meta-algorithm are learned from the training data and propagated to subject through exemplars. We further develop a level-set based fusion method to combine multiple candidate extractions together with a closed smooth surface, for obtaining the final result. Experimental results show that, with only a small portion of subjects for training, the proposed method is able to produce more accurate and robust brain extraction results, at Jaccard Index of 0.956 +/- 0.010 on total 340 subjects under 6-fold cross validation, compared to those by the BET and BSE even using their best parameter combinations.

Distinct representations of configural and part information across multiple face-selective regions of the human brain

PubMed Central

Golarai, Golijeh; Ghahremani, Dara G.; Eberhardt, Jennifer L.; Gabrieli, John D. E.

2015-01-01

Several regions of the human brain respond more strongly to faces than to other visual stimuli, such as regions in the amygdala (AMG), superior temporal sulcus (STS), and the fusiform face area (FFA). It is unclear if these brain regions are similar in representing the configuration or natural appearance of face parts. We used functional magnetic resonance imaging of healthy adults who viewed natural or schematic faces with internal parts that were either normally configured or randomly rearranged. Response amplitudes were reduced in the AMG and STS when subjects viewed stimuli whose configuration of parts were digitally rearranged, suggesting that these regions represent the 1st order configuration of face parts. In contrast, response amplitudes in the FFA showed little modulation whether face parts were rearranged or if the natural face parts were replaced with lines. Instead, FFA responses were reduced only when both configural and part information were reduced, revealing an interaction between these factors, suggesting distinct representation of 1st order face configuration and parts in the AMG and STS vs. the FFA. PMID:26594191

Activation of the DLPFC Reveals an Asymmetric Effect in Risky Decision Making: Evidence from a tDCS Study

PubMed Central

Huang, Daqiang; Chen, Shu; Wang, Siqi; Shi, Jinchuan; Ye, Hang; Luo, Jun; Zheng, Haoli

2017-01-01

The phenomenon of loss aversion (the tendency for losses to have a greater impact than comparable gains) has long been observed in daily life. Neurocognitive studies and brain imaging studies have shed light on the correlation between the phenomenon of loss aversion and the brain region of the prefrontal cortex. Recent brain stimulation studies using bilateral transcranial magnetic stimulation or transcranial direct current stimulation (tDCS) have obtained various results showing the causal relationship between brain regions and decision making. With the goal of studying whether unilateral stimulation can change participants’ risky decision making in the frames of gains and losses, we applied different polarities of tDCS over the regions of the right or left prefrontal cortex. We also designed a risk measurement table (Multiple Price List) to reflect the participants’ attitudes toward risky decision making via the crossover point including the frames of gains and losses. The results of our experiment indicated that the participants tended to be more risk averse in the gain frame after receiving left anodal tDCS and more risk seeking in the loss frame after receiving right cathodal tDCS, which was consistent with the hypothesis that the process of risky decision making was correlated with the interaction of multiple systems in the brain. Our conclusion revealed an asymmetric effect of right/left DLPFC when the participants faced gains and losses, which partially provided the neural evidence and a feasible paradigm to help better understand risky decision making and loss aversion. The current study can not only expand the traditional understanding of the behavioral preferences of humans in economics but also accommodate empirical observations of behavioral economists on the preferences of humans. PMID:28174549

Causal mapping of emotion networks in the human brain: Framework and initial findings.

PubMed

Dubois, Julien; Oya, Hiroyuki; Tyszka, J Michael; Howard, Matthew; Eberhardt, Frederick; Adolphs, Ralph

2017-11-13

Emotions involve many cortical and subcortical regions, prominently including the amygdala. It remains unknown how these multiple network components interact, and it remains unknown how they cause the behavioral, autonomic, and experiential effects of emotions. Here we describe a framework for combining a novel technique, concurrent electrical stimulation with fMRI (es-fMRI), together with a novel analysis, inferring causal structure from fMRI data (causal discovery). We outline a research program for investigating human emotion with these new tools, and provide initial findings from two large resting-state datasets as well as case studies in neurosurgical patients with electrical stimulation of the amygdala. The overarching goal is to use causal discovery methods on fMRI data to infer causal graphical models of how brain regions interact, and then to further constrain these models with direct stimulation of specific brain regions and concurrent fMRI. We conclude by discussing limitations and future extensions. The approach could yield anatomical hypotheses about brain connectivity, motivate rational strategies for treating mood disorders with deep brain stimulation, and could be extended to animal studies that use combined optogenetic fMRI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Distributed affective space represents multiple emotion categories across the human brain

PubMed Central

Saarimäki, Heini; Ejtehadian, Lara Farzaneh; Jääskeläinen, Iiro P; Vuilleumier, Patrik; Sams, Mikko; Nummenmaa, Lauri

2018-01-01

Abstract The functional organization of human emotion systems as well as their neuroanatomical basis and segregation in the brain remains unresolved. Here, we used pattern classification and hierarchical clustering to characterize the organization of a wide array of emotion categories in the human brain. We induced 14 emotions (6 ‘basic’, e.g. fear and anger; and 8 ‘non-basic’, e.g. shame and gratitude) and a neutral state using guided mental imagery while participants' brain activity was measured with functional magnetic resonance imaging (fMRI). Twelve out of 14 emotions could be reliably classified from the haemodynamic signals. All emotions engaged a multitude of brain areas, primarily in midline cortices including anterior and posterior cingulate gyri and precuneus, in subcortical regions, and in motor regions including cerebellum and premotor cortex. Similarity of subjective emotional experiences was associated with similarity of the corresponding neural activation patterns. We conclude that different basic and non-basic emotions have distinguishable neural bases characterized by specific, distributed activation patterns in widespread cortical and subcortical circuits. Regionally differentiated engagement of these circuits defines the unique neural activity pattern and the corresponding subjective feeling associated with each emotion. PMID:29618125

Specialization in the Human Brain: The Case of Numbers

PubMed Central

Kadosh, Roi Cohen; Bahrami, Bahador; Walsh, Vincent; Butterworth, Brian; Popescu, Tudor; Price, Cathy J.

2011-01-01

How numerical representation is encoded in the adult human brain is important for a basic understanding of human brain organization, its typical and atypical development, its evolutionary precursors, cognitive architectures, education, and rehabilitation. Previous studies have shown that numerical processing activates the same intraparietal regions irrespective of the presentation format (e.g., symbolic digits or non-symbolic dot arrays). This has led to claims that there is a single format-independent, numerical representation. In the current study we used a functional magnetic resonance adaptation paradigm, and effective connectivity analysis to re-examine whether numerical processing in the intraparietal sulci is dependent or independent on the format of the stimuli. We obtained two novel results. First, the whole brain analysis revealed that format change (e.g., from dots to digits), in the absence of a change in magnitude, activated the same intraparietal regions as magnitude change, but to a greater degree. Second, using dynamic causal modeling as a tool to disentangle neuronal specialization across regions that are commonly activated, we found that the connectivity between the left and right intraparietal sulci is format-dependent. Together, this line of results supports the idea that numerical representation is subserved by multiple mechanisms within the same parietal regions. PMID:21808615

Fine-Granularity Functional Interaction Signatures for Characterization of Brain Conditions

PubMed Central

Hu, Xintao; Zhu, Dajiang; Lv, Peili; Li, Kaiming; Han, Junwei; Wang, Lihong; Shen, Dinggang; Guo, Lei; Liu, Tianming

2014-01-01

In the human brain, functional activity occurs at multiple spatial scales. Current studies on functional brain networks and their alterations in brain diseases via resting-state functional magnetic resonance imaging (rs-fMRI) are generally either at local scale (regionally confined analysis and inter-regional functional connectivity analysis) or at global scale (graph theoretic analysis). In contrast, inferring functional interaction at fine-granularity sub-network scale has not been adequately explored yet. Here our hypothesis is that functional interaction measured at fine-granularity subnetwork scale can provide new insight into the neural mechanisms of neurological and psychological conditions, thus offering complementary information for healthy and diseased population classification. In this paper, we derived fine-granularity functional interaction (FGFI) signatures in subjects with Mild Cognitive Impairment (MCI) and Schizophrenia by diffusion tensor imaging (DTI) and rsfMRI, and used patient-control classification experiments to evaluate the distinctiveness of the derived FGFI features. Our experimental results have shown that the FGFI features alone can achieve comparable classification performance compared with the commonly used inter-regional connectivity features. However, the classification performance can be substantially improved when FGFI features and inter-regional connectivity features are integrated, suggesting the complementary information achieved from the FGFI signatures. PMID:23319242

Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex.

PubMed

Scott, Gregory D; Karns, Christina M; Dow, Mark W; Stevens, Courtney; Neville, Helen J

2014-01-01

Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl's gyrus. In addition to reorganized auditory cortex (cross-modal plasticity), a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case), as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral vs. perifoveal visual stimulation (11-15° vs. 2-7°) in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl's gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl's gyrus) indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral vs. perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory, and multisensory and/or supramodal regions, such as posterior parietal cortex (PPC), frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal, and multisensory regions, to altered visual processing in congenitally deaf adults.

Current steering to activate targeted neural pathways during deep brain stimulation of the subthalamic region

PubMed Central

Chaturvedi, Ashutosh; Foutz, Thomas J.; McIntyre, Cameron C.

2012-01-01

Deep brain stimulation (DBS) has steadily evolved into an established surgical therapy for numerous neurological disorders, most notably Parkinson’s disease (PD). Traditional DBS technology relies on voltage-controlled stimulation with a single source; however, recent engineering advances are providing current-controlled devices with multiple independent sources. These new stimulators deliver constant current to the brain tissue, irrespective of impedance changes that occur around the electrode, and enable more specific steering of current towards targeted regions of interest. In this study, we examined the impact of current steering between multiple electrode contacts to directly activate three distinct neural populations in the subthalamic region commonly stimulated for the treatment of PD: projection neurons of the subthalamic nucleus (STN), globus pallidus internus (GPi) fibers of the lenticular fasiculus, and internal capsule (IC) fibers of passage. We used three-dimensional finite element electric field models, along with detailed multi-compartment cable models of the three neural populations to determine their activations using a wide range of stimulation parameter settings. Our results indicate that selective activation of neural populations largely depends on the location of the active electrode(s). Greater activation of the GPi and STN populations (without activating any side-effect related IC fibers) was achieved by current steering with multiple independent sources, compared to a single current source. Despite this potential advantage, it remains to be seen if these theoretical predictions result in a measurable clinical effect that outweighs the added complexity of the expanded stimulation parameter search space generated by the more flexible technology. PMID:22277548

Mechanisms of Neurodegeneration and Regeneration in Alcoholism

PubMed Central

Crews, Fulton T.; Nixon, Kim

2009-01-01

Aims: This is a review of preclinical studies covering alcohol-induced brain neuronal death and loss of neurogenesis as well as abstinence-induced brain cell genesis, e.g. brain regeneration. Efforts are made to relate preclinical studies to human studies. Methods: The studies described are preclinical rat experiments using a 4-day binge ethanol treatment known to induce physical dependence to ethanol. Neurodegeneration and cognitive deficits following binge treatment mimic the mild degeneration and cognitive deficits found in humans. Various histological methods are used to follow brain regional degeneration and regeneration. Results: Alcohol-induced degeneration occurs due to neuronal death during alcohol intoxication. Neuronal death is related to increases in oxidative stress in brain that coincide with the induction of proinflammatory cytokines and oxidative enzymes that insult brain. Degeneration is associated with increased NF-κB proinflammatory transcription and decreased CREB transcription. Corticolimbic brain regions are most sensitive to binge-induced degeneration and induce relearning deficits. Drugs that block oxidative stress and NF-κB transcription or increase CREB transcription block binge-induced neurodegeneration, inhibition of neurogenesis and proinflammatory enzyme induction. Regeneration of brain occurs during abstinence following binge ethanol treatment. Bursts of proliferating cells occur across multiple brain regions, with many new microglia across brain after months of abstinence and many new neurons in neurogenic hippocampal dentate gyrus. Brain regeneration may be important to sustain abstinence in humans. Conclusions: Alcohol-induced neurodegeneration occurs primarily during intoxication and is related to increased oxidative stress and proinflammatory proteins that are neurotoxic. Abstinence after binge ethanol intoxication results in brain cell genesis that could contribute to the return of brain function and structure found in abstinent humans. PMID:18940959

Regional brain activity that determines successful and unsuccessful working memory formation.

PubMed

Teramoto, Shohei; Inaoka, Tsubasa; Ono, Yumie

2016-08-01

Using EEG source reconstruction with Multiple Sparse Priors (MSP), we investigated the regional brain activity that determines successful memory encoding in two participant groups of high and low accuracy rates. Eighteen healthy young adults performed a sequential fashion of visual Sternberg memory task. The 32-channel EEG was continuously measured during participants performed two 70 trials of memory task. The regional brain activity corresponding to the oscillatory EEG activity in the alpha band (8-13 Hz) during encoding period was analyzed by MSP implemented in SPM8. We divided the data of all participants into 2 groups (low- and highperformance group) and analyzed differences in regional brain activity between trials in which participants answered correctly and incorrectly within each of the group. Participants in low-performance group showed significant activity increase in the visual cortices in their successful trials compared to unsuccessful ones. On the other hand, those in high-performance group showed a significant activity increase in widely distributed cortical regions in the frontal, temporal, and parietal areas including those suggested as Baddeley's working memory model. Further comparison of activated cortical volumes and mean current source intensities within the cortical regions of Baddeley's model during memory encoding demonstrated that participants in high-performance group showed enhanced activity in the right premotor cortex, which plays an important role in maintaining visuospatial attention, compared to those in low performance group. Our results suggest that better ability in memory encoding is associated with distributed and stronger regional brain activities including the premotor cortex, possibly indicating efficient allocation of cognitive load and maintenance of attention.

Multi-scale radiomic analysis of sub-cortical regions in MRI related to autism, gender and age

NASA Astrophysics Data System (ADS)

Chaddad, Ahmad; Desrosiers, Christian; Toews, Matthew

2017-03-01

We propose using multi-scale image textures to investigate links between neuroanatomical regions and clinical variables in MRI. Texture features are derived at multiple scales of resolution based on the Laplacian-of-Gaussian (LoG) filter. Three quantifier functions (Average, Standard Deviation and Entropy) are used to summarize texture statistics within standard, automatically segmented neuroanatomical regions. Significance tests are performed to identify regional texture differences between ASD vs. TDC and male vs. female groups, as well as correlations with age (corrected p < 0.05). The open-access brain imaging data exchange (ABIDE) brain MRI dataset is used to evaluate texture features derived from 31 brain regions from 1112 subjects including 573 typically developing control (TDC, 99 females, 474 males) and 539 Autism spectrum disorder (ASD, 65 female and 474 male) subjects. Statistically significant texture differences between ASD vs. TDC groups are identified asymmetrically in the right hippocampus, left choroid-plexus and corpus callosum (CC), and symmetrically in the cerebellar white matter. Sex-related texture differences in TDC subjects are found in primarily in the left amygdala, left cerebellar white matter, and brain stem. Correlations between age and texture in TDC subjects are found in the thalamus-proper, caudate and pallidum, most exhibiting bilateral symmetry.

Using text mining to link journal articles to neuroanatomical databases

PubMed Central

French, Leon; Pavlidis, Paul

2013-01-01

The electronic linking of neuroscience information, including data embedded in the primary literature, would permit powerful queries and analyses driven by structured databases. This task would be facilitated by automated procedures which can identify biological concepts in journals. Here we apply an approach for automatically mapping formal identifiers of neuroanatomical regions to text found in journal abstracts, and apply it to a large body of abstracts from the Journal of Comparative Neurology (JCN). The analyses yield over one hundred thousand brain region mentions which we map to 8,225 brain region concepts in multiple organisms. Based on the analysis of a manually annotated corpus, we estimate mentions are mapped at 95% precision and 63% recall. Our results provide insights into the patterns of publication on brain regions and species of study in the Journal, but also point to important challenges in the standardization of neuroanatomical nomenclatures. We find that many terms in the formal terminologies never appear in a JCN abstract, while conversely, many terms authors use are not reflected in the terminologies. To improve the terminologies we deposited 136 unrecognized brain regions into the Neuroscience Lexicon (NeuroLex). The training data, terminologies, normalizations, evaluations and annotated journal abstracts are freely available at http://www.chibi.ubc.ca/WhiteText/. PMID:22120205

Functional and structural cerebral changes in key brain regions after a facilitation programme for episodic future thought in relapsing-remitting multiple sclerosis patients.

PubMed

Ernst, Alexandra; Sourty, Marion; Roquet, Daniel; Noblet, Vincent; Gounot, Daniel; Blanc, Frédéric; De Seze, Jérôme; Manning, Liliann

2016-06-01

Increasingly studied, episodic future thought (EFT) impairment negatively affects patients' daily life. Along these lines, working with relapsing-remitting multiple sclerosis (RR-MS) patients, we documented the clinical effectiveness of a mental visual imagery (MVI)-based facilitation programme on EFT impairment related to executive function difficulties. We aimed at improving the characterisation of the cognitive and neural underpinnings of RR-MS patients' EFT amelioration, by exploring the structural and functional brain changes following the MVI programme. Seventeen non-depressed RR-MS patients were recruited and randomly assigned in the (i) experimental group (n=10), who followed the MVI programme or in the control group (n=7), who followed a verbal control programme. Using an adapted version of the Autobiographical Interview to assess EFT, after facilitation, significant improvement was observed in the experimental group only. This was accompanied by increased activation in the prefrontal region during the generation of future events and was positively correlated with grey matter volume increase in this same brain area. Increased activations in the parahippocampal and the middle temporal gyri were also observed in the experimental group in post-facilitation. Likewise, functional connectivity changes were observed in the posterior brain regions after facilitation. Only minor cerebral changes were observed in the control group, likely reflecting practice effects. Our study showed that EFT improvement following the MVI programme led to functional and structural changes in brain regions sustaining contextual processing, visual imagery, the integration and maintenance of multimodal information. Taken together, these findings suggest that a cognitive intervention focusing on scene construction can be efficient to alleviate EFT impairment related to executive dysfunction. As such, this study opens the way to the development of tailor-made rehabilitation programmes using the different cognitive mechanisms involved in EFT. Copyright © 2016 Elsevier Inc. All rights reserved.

Multiple brain networks for visual self-recognition with different sensitivity for motion and body part.

PubMed

Sugiura, Motoaki; Sassa, Yuko; Jeong, Hyeonjeong; Miura, Naoki; Akitsuki, Yuko; Horie, Kaoru; Sato, Shigeru; Kawashima, Ryuta

2006-10-01

Multiple brain networks may support visual self-recognition. It has been hypothesized that the left ventral occipito-temporal cortex processes one's own face as a symbol, and the right parieto-frontal network processes self-image in association with motion-action contingency. Using functional magnetic resonance imaging, we first tested these hypotheses based on the prediction that these networks preferentially respond to a static self-face and to moving one's whole body, respectively. Brain activation specifically related to self-image during familiarity judgment was compared across four stimulus conditions comprising a two factorial design: factor Motion contrasted picture (Picture) and movie (Movie), and factor Body part a face (Face) and whole body (Body). Second, we attempted to segregate self-specific networks using a principal component analysis (PCA), assuming an independent pattern of inter-subject variability in activation over the four stimulus conditions in each network. The bilateral ventral occipito-temporal and the right parietal and frontal cortices exhibited self-specific activation. The left ventral occipito-temporal cortex exhibited greater self-specific activation for Face than for Body, in Picture, consistent with the prediction for this region. The activation profiles of the right parietal and frontal cortices did not show preference for Movie Body predicted by the assumed roles of these regions. The PCA extracted two cortical networks, one with its peaks in the right posterior, and another in frontal cortices; their possible roles in visuo-spatial and conceptual self-representations, respectively, were suggested by previous findings. The results thus supported and provided evidence of multiple brain networks for visual self-recognition.

Control networks and hubs.

PubMed

Gratton, Caterina; Sun, Haoxin; Petersen, Steven E

2018-03-01

Executive control functions are associated with frontal, parietal, cingulate, and insular brain regions that interact through distributed large-scale networks. Here, we discuss how fMRI functional connectivity can shed light on the organization of control networks and how they interact with other parts of the brain. In the first section of our review, we present convergent evidence from fMRI functional connectivity, activation, and lesion studies that there are multiple dissociable control networks in the brain with distinct functional properties. In the second section, we discuss how graph theoretical concepts can help illuminate the mechanisms by which control networks interact with other brain regions to carry out goal-directed functions, focusing on the role of specialized hub regions for mediating cross-network interactions. Again, we use a combination of functional connectivity, lesion, and task activation studies to bolster this claim. We conclude that a large-scale network perspective provides important neurobiological constraints on the neural underpinnings of executive control, which will guide future basic and translational research into executive function and its disruption in disease. © 2017 Society for Psychophysiological Research.

Persistence of SIV in the brain of SIV-infected Chinese rhesus macaques with or without antiretroviral therapy.

PubMed

Perez, Stefanie; Johnson, Ann-Marie; Xiang, Shi-Hua; Li, Jian; Foley, Brian T; Doyle-Meyers, Lara; Panganiban, Antonito; Kaur, Amitinder; Veazey, Ronald S; Wu, Yuntao; Ling, Binhua

2018-02-01

Persistence of HIV-1 reservoirs in the central nervous system (CNS) is an obstacle to cure strategies. However, little is known about residual viral distribution, viral replication levels, and genetic diversity in different brain regions of HIV-infected individuals on combination antiretroviral therapy (cART). Because myeloid cells particularly microglia are likely major reservoirs in the brain, and more microglia exist in white matter than gray matter in a human brain, we hypothesized the major viral reservoirs in the brain are the white matter reflected by higher levels of viral DNA. To address the issue, we used the Chinese rhesus macaque (ChRM) model of SIV infection, and treated 11 SIVmac251-infected animals including long-term nonprogressors with cART for up to 24 weeks. SIV reservoirs were assessed by SIV DNA levels in 16 specific regions of the brain and 4 regions of spinal cord. We found relatively high frequencies of SIV in basal ganglia and brain stem compared to other regions. cART-receiving animals had significantly lower SIV DNA levels in the gray matter than white matter. Moreover, a shortened envelope gp120 with 21 nucleotide deletions and guanine-to-adenine hypermutations were observed. These results demonstrate that SIV enters the CNS in SIV-infected ChRM with a major reservoir in the white matter after cART; the SIV/ChRM/cART is an appropriate model for studying HIV CNS reservoirs and testing new eradication strategies. Further, examining multiple regions of the CNS may be needed when assessing whether an agent is successful in reducing the size of SIV reservoirs in the CNS.

The Neuropeptide Tac2 Controls a Distributed Brain State Induced by Chronic Social Isolation Stress.

PubMed

Zelikowsky, Moriel; Hui, May; Karigo, Tomomi; Choe, Andrea; Yang, Bin; Blanco, Mario R; Beadle, Keith; Gradinaru, Viviana; Deverman, Benjamin E; Anderson, David J

2018-05-17

Chronic social isolation causes severe psychological effects in humans, but their neural bases remain poorly understood. 2 weeks (but not 24 hr) of social isolation stress (SIS) caused multiple behavioral changes in mice and induced brain-wide upregulation of the neuropeptide tachykinin 2 (Tac2)/neurokinin B (NkB). Systemic administration of an Nk3R antagonist prevented virtually all of the behavioral effects of chronic SIS. Conversely, enhancing NkB expression and release phenocopied SIS in group-housed mice, promoting aggression and converting stimulus-locked defensive behaviors to persistent responses. Multiplexed analysis of Tac2/NkB function in multiple brain areas revealed dissociable, region-specific requirements for both the peptide and its receptor in different SIS-induced behavioral changes. Thus, Tac2 coordinates a pleiotropic brain state caused by SIS via a distributed mode of action. These data reveal the profound effects of prolonged social isolation on brain chemistry and function and suggest potential new therapeutic applications for Nk3R antagonists. Copyright © 2018 Elsevier Inc. All rights reserved.

Chronic Stress Modulates Regional Cerebral Glucose Transporter Expression in an Age-Specific and Sexually-Dimorphic Manner

PubMed Central

Kelly, Sean D.; Harrell, Constance S.; Neigh, Gretchen N.

2014-01-01

Facilitative glucose transporters (GLUT) mediate glucose uptake across the blood-brain-barrier into neurons and glia. Deficits in specific cerebral GLUT isoforms are linked to developmental and neurological dysfunction, but less is known about the range of variation in cerebral GLUT expression in normal conditions and the effects of environmental influences on cerebral GLUT expression. Knowing that puberty is a time of increased cerebral plasticity, metabolic demand, and shifts in hormonal balance for males and females, we first assessed gene expression of five GLUT subtypes in four brain regions in male and female adolescent and adult Wistar rats. The data indicated that sex differences in GLUT expression were most profound in the hypothalamus, and the transition from adolescence to adulthood had the most profound effect on GLUT expression in the hippocampus. Next, given the substantial energetic demands during adolescence and prior demonstrations of the adverse effects of adolescent stress, we determined the extent to which chronic stress altered GLUT expression in males and females in both adolescence and adulthood. Chronic stress significantly altered cerebral GLUT expression in males and females throughout both developmental stages but in a sexually dimorphic and brain region-specific manner. Collectively, our data demonstrate that cerebral GLUTs are expressed differentially based on brain region, sex, age, and stress exposure. These results suggest that developmental and environmental factors influence GLUT expression in multiple brain regions. Given the importance of appropriate metabolic balance within the brain, further assessment of the functional implications of life stage and environmentally-induced changes in GLUTs are warranted. PMID:24382486

Electrophysiology quantitative electroencephalography/low resolution brain electromagnetic tomography functional brain imaging (QEEG LORETA): Case report: Subjective idiopathic tinnitus - predominantly central type severe disabling tinnitus.

PubMed

Shulman, Abraham; Goldstein, Barbara

2014-01-01

The clinical significance of QEEG LORETA data analysis performed sequentially within 6 months is presented in a case report of a predominantly central type severe disabling subjective idiopathic tinnitus (SIT) before and following treatment. The QEEG LORETA data is reported as Z-scores of z = ± 2.54, p < 0.013. The focus is on demonstration of patterns of brain wave oscillations reflecting multiple brain functions in multiple ROIs in the presence of the tinnitus signal (SIT). The patterns of brain activity both high, middle and low frequencies are hypothesized to reflect connectivities within and between multiple neuronal networks in brain. The Loreta source localization non auditory ROI Images at the maximal abnormality in the very narrow band frequency spectra (24.21 Hz), showed the mathematically most probable underlying sources of the scalp recorded data to be greatest in the mid-cingulate, bilateral precuneus, cingulate and the bilateral caudate nucleus. Clinical correlation of the data with the history and course of the SIT is considered an objective demonstration of the affect, behavioral, and emotional component of the SIT. The correlation of the caudate activity, SIT as the traumatic event with the clinical course of PTSD, and the clinical diagnosis of PTSD is discussed. The clinical translation for patient care is highlighted in a SIT patient with multiple comorbidities by translation of QEEG/LORETA electrophysiologic data, as an adjunct to: provide an objectivity of patterns of brain wave activity in multiple regions of interest (ROIs) reflecting multiple brain functions, in response to and in the presence of the tinnitus signal, recorded from the scalp and analyzed with the metrics of absolute power, relative power, asymmetry, and coherence, for the subjective tinnitus complaint (SIT); 2) provide an increase in the accuracy of the tinnitus diagnosis; 3) assess/monitor treatment efficacy; 4) provide a rationale for selection of a combined tinnitus targeted therapy of behavioral, pharmacologic, sound therapy modalities of treatment attempting tinnitus relief; 5) provide insight into the medical significance of the SIT; 6) attempt discriminant function analysis for identification of a particular diagnostic clinical category of CNS neuropsychiatric disease; and 7) attempt to translate what is known of the neuroscience of sensation, brain function, QEEG/LORETA source localization, for the etiology and prognosis of the individual SIT patient.

Measuring the effects of aging and sex on regional brain stiffness with MR elastography in healthy older adults

PubMed Central

Arani, Arvin; Murphy, Matthew C; Glaser, Kevin J; Manduca, Armando; Lake, David S; Kruse, Scott; Jack, Clifford R; Ehman, Richard; Huston, John

2015-01-01

Changes in tissue composition and cellular architecture have been associated with neurological disease, and these in turn can affect biomechanical properties. Natural biological factors such as aging and an individual’s sex also affect underlying tissue biomechanics in different brain regions. Understanding the normal changes is necessary before determining the efficacy of stiffness imaging for neurological disease diagnosis and therapy monitoring. The objective of this study was to evaluate global and regional changes in brain stiffness as a function of age and sex, using improved MRE acquisition and processing that has been shown to provide median stiffness values that are typically reproducible to within 1% in global measurements and within 2% for regional measurements. Furthermore, this is the first study to report the effects of age and sex over the entire cerebrum volume and over the full frontal, occipital, parietal, temporal, deep gray matter/white matter (insula, deep gray nuclei and white matter tracts), and cerebellum volumes. In 45 volunteers, we observed a significant linear correlation between age and brain stiffness in the cerebrum (P<.0001), frontal lobes (P<.0001), occipital lobes (P=.0005), parietal lobes (P=.0002), and the temporal lobes (P<.0001) of the brain. No significant linear correlation between brain stiffness and age was observed in the cerebellum (P=.74), and the sensory-motor regions (P=.32) of the brain, and a weak linear trend was observed in the deep gray matter/white matter (P=.075). A multiple linear regression model predicted an annual decline of 0.011±0.002 kPa in cerebrum stiffness with a theoretical median age value (76 years old) of 2.56±0.08 kPa. Sexual dimorphism was observed in the temporal (P=.03) and occipital (P=.001) lobes of the brain, but no significant difference was observed in any of the other brain regions (P>.20 for all other regions). The model predicted female occipital and temporal lobes to be 0.23 kPa and 0.09 kPa stiffer than males of the same age, respectively. This study confirms that as the brain ages, there is softening; however, the changes are dependent on region. In addition, stiffness effects due to sex exist in the occipital and temporal lobes. PMID:25698157

Investigating Focal Connectivity Deficits in Alzheimer's Disease Using Directional Brain Networks Derived from Resting-State fMRI

PubMed Central

Zhao, Sinan; Rangaprakash, D; Venkataraman, Archana; Liang, Peipeng; Deshpande, Gopikrishna

2017-01-01

Connectivity analysis of resting-state fMRI has been widely used to identify biomarkers of Alzheimer's disease (AD) based on brain network aberrations. However, it is not straightforward to interpret such connectivity results since our understanding of brain functioning relies on regional properties (activations and morphometric changes) more than connections. Further, from an interventional standpoint, it is easier to modulate the activity of regions (using brain stimulation, neurofeedback, etc.) rather than connections. Therefore, we employed a novel approach for identifying focal directed connectivity deficits in AD compared to healthy controls. In brief, we present a model of directed connectivity (using Granger causality) that characterizes the coupling among different regions in healthy controls and Alzheimer's disease. We then characterized group differences using a (between-subject) generative model of pathology, which generates latent connectivity variables that best explain the (within-subject) directed connectivity. Crucially, our generative model at the second (between-subject) level explains connectivity in terms of local or regionally specific abnormalities. This allows one to explain disconnections among multiple regions in terms of regionally specific pathology; thereby offering a target for therapeutic intervention. Two foci were identified, locus coeruleus in the brain stem and right orbitofrontal cortex. Corresponding disrupted connectivity network associated with the foci showed that the brainstem is the critical focus of disruption in AD. We further partitioned the aberrant connectomic network into four unique sub-networks, which likely leads to symptoms commonly observed in AD. Our findings suggest that fMRI studies of AD, which have been largely cortico-centric, could in future investigate the role of brain stem in AD. PMID:28729831

Challenges and Opportunities in Mining Neuroscience Data

PubMed Central

Akil, Huda; Martone, Maryann E.; Van Essen, David C.

2011-01-01

Understanding the brain requires a broad range of approaches and methods from the domains of biology, psychology, chemistry, physics, and mathematics. The fundamental challenge is to decipher the “neural choreography” associated with complex behaviors and functions, including thoughts, memories, actions, and emotions. This demands the acquisition and integration of vast amounts of data of many types, at multiple scales in time and in space. Here, we discuss the need for neuroinformatics approaches to accelerate progress, using several illustrative examples. The nascent field of ‘connectomics’ aims to comprehensively describe neuronal connectivity at either a macroscopic level (long-distance pathways for the entire brain) or a microscopic level (axons, dendrites, synapses in a small brain region). The Neuroscience Information Framework encompasses all of neuroscience and facilitates integration of existing knowledge and databases of many types. These examples illustrate the opportunities and challenges of data mining across multiple tiers of neuroscience information and underscore the need for cultural and infrastructure changes if neuroinformatics is to fulfill its potential to advance our understanding of the brain. PMID:21311009

Neutralizing anti-interleukin-1β antibodies modulate fetal blood-brain barrier function after ischemia.

PubMed

Chen, Xiaodi; Sadowska, Grazyna B; Zhang, Jiyong; Kim, Jeong-Eun; Cummings, Erin E; Bodge, Courtney A; Lim, Yow-Pin; Makeyev, Oleksandr; Besio, Walter G; Gaitanis, John; Threlkeld, Steven W; Banks, William A; Stonestreet, Barbara S

2015-01-01

We have previously shown that increases in blood-brain barrier permeability represent an important component of ischemia-reperfusion related brain injury in the fetus. Pro-inflammatory cytokines could contribute to these abnormalities in blood-brain barrier function. We have generated pharmacological quantities of mouse anti-ovine interleukin-1β monoclonal antibody and shown that this antibody has very high sensitivity and specificity for interleukin-1β protein. This antibody also neutralizes the effects of interleukin-1β protein in vitro. In the current study, we hypothesized that the neutralizing anti-interleukin-1β monoclonal antibody attenuates ischemia-reperfusion related fetal blood-brain barrier dysfunction. Instrumented ovine fetuses at 127 days of gestation were studied after 30 min of carotid occlusion and 24h of reperfusion. Groups were sham operated placebo-control- (n=5), ischemia-placebo- (n=6), ischemia-anti-IL-1β antibody- (n=7), and sham-control antibody- (n=2) treated animals. Systemic infusions of placebo (0.154M NaCl) or anti-interleukin-1β monoclonal antibody (5.1±0.6 mg/kg) were given intravenously to the same sham or ischemic group of fetuses at 15 min and 4h after ischemia. Concentrations of interleukin-1β protein and anti-interleukin-1β monoclonal antibody were measured by ELISA in fetal plasma, cerebrospinal fluid, and parietal cerebral cortex. Blood-brain barrier permeability was quantified using the blood-to-brain transfer constant (Ki) with α-aminoisobutyric acid in multiple brain regions. Interleukin-1β protein was also measured in parietal cerebral cortices and tight junction proteins in multiple brain regions by Western immunoblot. Cerebral cortical interleukin-1β protein increased (P<0.001) after ischemia-reperfusion. After anti-interleukin-1β monoclonal antibody infusions, plasma anti-interleukin-1β monoclonal antibody was elevated (P<0.001), brain anti-interleukin-1β monoclonal antibody levels were higher (P<0.03), and interleukin-1β protein concentrations (P<0.03) and protein expressions (P<0.001) were lower in the monoclonal antibody-treated group than in placebo-treated-ischemia-reperfusion group. Monoclonal antibody infusions attenuated ischemia-reperfusion-related increases in Ki across the brain regions (P<0.04), and Ki showed an inverse linear correlation (r= -0.65, P<0.02) with anti-interleukin-1β monoclonal antibody concentrations in the parietal cortex, but had little effect on tight junction protein expression. We conclude that systemic anti-interleukin-1β monoclonal antibody infusions after ischemia result in brain anti-interleukin-1β antibody uptake, and attenuate ischemia-reperfusion-related interleukin-1β protein up-regulation and increases in blood-brain barrier permeability across brain regions in the fetus. The pro-inflammatory cytokine, interleukin-1β, contributes to impaired blood-brain barrier function after ischemia in the fetus. Copyright © 2014 Elsevier Inc. All rights reserved.

Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

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

Xia, Jing; Rocke, David M.; Perry, George

In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

DOE PAGES

Xia, Jing; Rocke, David M.; Perry, George; ...

2014-01-01

In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

Differences in interregional brain connectivity in children with unilateral hearing loss.

PubMed

Jung, Matthew E; Colletta, Miranda; Coalson, Rebecca; Schlaggar, Bradley L; Lieu, Judith E C

2017-11-01

To identify functional network architecture differences in the brains of children with unilateral hearing loss (UHL) using resting-state functional-connectivity magnetic resonance imaging (rs-fcMRI). Prospective observational study. Children (7 to 17 years of age) with severe to profound hearing loss in one ear, along with their normal hearing (NH) siblings, were recruited and imaged using rs-fcMRI. Eleven children had right UHL; nine had left UHL; and 13 had normal hearing. Forty-one brain regions of interest culled from established brain networks such as the default mode (DMN); cingulo-opercular (CON); and frontoparietal networks (FPN); as well as regions for language, phonological, and visual processing, were analyzed using regionwise correlations and conjunction analysis to determine differences in functional connectivity between the UHL and normal hearing children. When compared to the NH group, children with UHL showed increased connectivity patterns between multiple networks, such as between the CON and visual processing centers. However, there were decreased, as well as aberrant connectivity patterns with the coactivation of the DMN and FPN, a relationship that usually is negatively correlated. Children with UHL demonstrate multiple functional connectivity differences between brain networks involved with executive function, cognition, and language comprehension that may represent adaptive as well as maladaptive changes. These findings suggest that possible interventions or habilitation, beyond amplification, might be able to affect some children's requirement for additional help at school. 3b. Laryngoscope, 127:2636-2645, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Enhancing the Temporal Complexity of Distributed Brain Networks with Patterned Cerebellar Stimulation

PubMed Central

Farzan, Faranak; Pascual-Leone, Alvaro; Schmahmann, Jeremy D.; Halko, Mark

2016-01-01

Growing evidence suggests that sensory, motor, cognitive and affective processes map onto specific, distributed neural networks. Cerebellar subregions are part of these networks, but how the cerebellum is involved in this wide range of brain functions remains poorly understood. It is postulated that the cerebellum contributes a basic role in brain functions, helping to shape the complexity of brain temporal dynamics. We therefore hypothesized that stimulating cerebellar nodes integrated in different networks should have the same impact on the temporal complexity of cortical signals. In healthy humans, we applied intermittent theta burst stimulation (iTBS) to the vermis lobule VII or right lateral cerebellar Crus I/II, subregions that prominently couple to the dorsal-attention/fronto-parietal and default-mode networks, respectively. Cerebellar iTBS increased the complexity of brain signals across multiple time scales in a network-specific manner identified through electroencephalography (EEG). We also demonstrated a region-specific shift in power of cortical oscillations towards higher frequencies consistent with the natural frequencies of targeted cortical areas. Our findings provide a novel mechanism and evidence by which the cerebellum contributes to multiple brain functions: specific cerebellar subregions control the temporal dynamics of the networks they are engaged in. PMID:27009405

Decoding Articulatory Features from fMRI Responses in Dorsal Speech Regions.

PubMed

Correia, Joao M; Jansma, Bernadette M B; Bonte, Milene

2015-11-11

The brain's circuitry for perceiving and producing speech may show a notable level of overlap that is crucial for normal development and behavior. The extent to which sensorimotor integration plays a role in speech perception remains highly controversial, however. Methodological constraints related to experimental designs and analysis methods have so far prevented the disentanglement of neural responses to acoustic versus articulatory speech features. Using a passive listening paradigm and multivariate decoding of single-trial fMRI responses to spoken syllables, we investigated brain-based generalization of articulatory features (place and manner of articulation, and voicing) beyond their acoustic (surface) form in adult human listeners. For example, we trained a classifier to discriminate place of articulation within stop syllables (e.g., /pa/ vs /ta/) and tested whether this training generalizes to fricatives (e.g., /fa/ vs /sa/). This novel approach revealed generalization of place and manner of articulation at multiple cortical levels within the dorsal auditory pathway, including auditory, sensorimotor, motor, and somatosensory regions, suggesting the representation of sensorimotor information. Additionally, generalization of voicing included the right anterior superior temporal sulcus associated with the perception of human voices as well as somatosensory regions bilaterally. Our findings highlight the close connection between brain systems for speech perception and production, and in particular, indicate the availability of articulatory codes during passive speech perception. Sensorimotor integration is central to verbal communication and provides a link between auditory signals of speech perception and motor programs of speech production. It remains highly controversial, however, to what extent the brain's speech perception system actively uses articulatory (motor), in addition to acoustic/phonetic, representations. In this study, we examine the role of articulatory representations during passive listening using carefully controlled stimuli (spoken syllables) in combination with multivariate fMRI decoding. Our approach enabled us to disentangle brain responses to acoustic and articulatory speech properties. In particular, it revealed articulatory-specific brain responses of speech at multiple cortical levels, including auditory, sensorimotor, and motor regions, suggesting the representation of sensorimotor information during passive speech perception. Copyright © 2015 the authors 0270-6474/15/3515015-11$15.00/0.

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

NASA Astrophysics Data System (ADS)

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

2015-01-01

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

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

PubMed

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

2015-01-01

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

Learning about learning: Mining human brain sub-network biomarkers from fMRI data

PubMed Central

Dereli, Nazli; Dang, Xuan-Hong; Bassett, Danielle S.; Wymbs, Nicholas F.; Grafton, Scott T.; Singh, Ambuj K.

2017-01-01

Modeling the brain as a functional network can reveal the relationship between distributed neurophysiological processes and functional interactions between brain structures. Existing literature on functional brain networks focuses mainly on a battery of network properties in “resting state” employing, for example, modularity, clustering, or path length among regions. In contrast, we seek to uncover functionally connected subnetworks that predict or correlate with cohort differences and are conserved within the subjects within a cohort. We focus on differences in both the rate of learning as well as overall performance in a sensorimotor task across subjects and develop a principled approach for the discovery of discriminative subgraphs of functional connectivity based on imaging acquired during practice. We discover two statistically significant subgraph regions: one involving multiple regions in the visual cortex and another involving the parietal operculum and planum temporale. High functional coherence in the former characterizes sessions in which subjects take longer to perform the task, while high coherence in the latter is associated with high learning rate (performance improvement across trials). Our proposed methodology is general, in that it can be applied to other cognitive tasks, to study learning or to differentiate between healthy patients and patients with neurological disorders, by revealing the salient interactions among brain regions associated with the observed global state. The discovery of such significant discriminative subgraphs promises a better data-driven understanding of the dynamic brain processes associated with high-level cognitive functions. PMID:29016686

Learning about learning: Mining human brain sub-network biomarkers from fMRI data.

PubMed

Bogdanov, Petko; Dereli, Nazli; Dang, Xuan-Hong; Bassett, Danielle S; Wymbs, Nicholas F; Grafton, Scott T; Singh, Ambuj K

2017-01-01

Modeling the brain as a functional network can reveal the relationship between distributed neurophysiological processes and functional interactions between brain structures. Existing literature on functional brain networks focuses mainly on a battery of network properties in "resting state" employing, for example, modularity, clustering, or path length among regions. In contrast, we seek to uncover functionally connected subnetworks that predict or correlate with cohort differences and are conserved within the subjects within a cohort. We focus on differences in both the rate of learning as well as overall performance in a sensorimotor task across subjects and develop a principled approach for the discovery of discriminative subgraphs of functional connectivity based on imaging acquired during practice. We discover two statistically significant subgraph regions: one involving multiple regions in the visual cortex and another involving the parietal operculum and planum temporale. High functional coherence in the former characterizes sessions in which subjects take longer to perform the task, while high coherence in the latter is associated with high learning rate (performance improvement across trials). Our proposed methodology is general, in that it can be applied to other cognitive tasks, to study learning or to differentiate between healthy patients and patients with neurological disorders, by revealing the salient interactions among brain regions associated with the observed global state. The discovery of such significant discriminative subgraphs promises a better data-driven understanding of the dynamic brain processes associated with high-level cognitive functions.

The Use of Non-invasive Brain Stimulation Techniques to Facilitate Recovery from Post-stroke Aphasia

PubMed Central

Marchina, Sarah; Wan, Catherine Y.

2011-01-01

Aphasia is a common symptom after left hemispheric stroke. Neuroimaging techniques over the last 10–15 years have described two general trends: Patients with small left hemisphere strokes tend to recruit perilesional areas, while patients with large left hemisphere lesions recruit mainly homotopic regions in the right hemisphere. Non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have been employed to facilitate recovery by stimulating lesional and contralesional regions. The majority of these brain stimulation studies have attempted to block homotopic regions in the right posterior inferior frontal gyrus (IFG) to affect a presumed disinhibited right IFG (triangular portion). Other studies have used anodal or excitatory tDCS to stimulate the contralesional (right) fronto-temporal region or parts of the intact left IFG and perilesional regions to improve speech-motor output. It remains unclear whether the interhemispheric disinhibition model, which is the basis for motor cortex stimulation studies, also applies to the language system. Future studies could address a number of issues, including: the effect of lesion location on current density distribution, timing of the intervention with regard to stroke onset, whether brain stimulation should be combined with behavioral therapy, and whether multiple brain sites should be stimulated. A better understanding of the predictors of recovery from natural outcome studies would also help to inform study design, and the selection of clinically meaningful outcome measures in future studies. PMID:21842404

Fiber-array based optogenetic prosthetic system for stimulation therapy

NASA Astrophysics Data System (ADS)

Gu, Ling; Cote, Chris; Tejeda, Hector; Mohanty, Samarendra

2012-02-01

Recent advent of optogenetics has enabled activation of genetically-targeted neuronal cells using low intensity blue light with high temporal precision. Since blue light is attenuated rapidly due to scattering and absorption in neural tissue, optogenetic treatment of neurological disorders may require stimulation of specific cell types in multiple regions of the brain. Further, restoration of certain neural functions (vision, and auditory etc) requires accurate spatio-temporal stimulation patterns rather than just precise temporal stimulation. In order to activate multiple regions of the central nervous system in 3D, here, we report development of an optogenetic prosthetic comprising of array of fibers coupled to independently-controllable LEDs. This design avoids direct contact of LEDs with the brain tissue and thus does not require electrical and heat isolation, which can non-specifically stimulate and damage the local brain regions. The intensity, frequency, and duty cycle of light pulses from each fiber in the array was controlled independently using an inhouse developed LabView based program interfaced with a microcontroller driving the individual LEDs. While the temporal profile of the light pulses was controlled by varying the current driving the LED, the beam profile emanating from each fiber tip could be sculpted by microfabrication of the fiber tip. The fiber array was used to stimulate neurons, expressing channelrhodopsin-2, in different locations within the brain or retina. Control of neural activity in the mice cortex, using the fiber-array based prosthetic, is evaluated from recordings made with multi-electrode array (MEA). We also report construction of a μLED array based prosthetic for spatio-temporal stimulation of cortex.

Psychosocial Stress and Brain Function in Adolescent Psychopathology.

PubMed

Quinlan, Erin Burke; Cattrell, Anna; Jia, Tianye; Artiges, Eric; Banaschewski, Tobias; Barker, Gareth; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Brühl, Rüdiger; Conrod, Patricia J; Desrivieres, Sylvane; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Martinot, Jean-Luc; Paillère Martinot, Marie-Laure; Nees, Frauke; Papadopoulos-Orfanos, Dimitri; Paus, Tomáš; Poustka, Luise; Smolka, Michael N; Vetter, Nora C; Walter, Henrik; Whelan, Robert; Glennon, Jeffrey C; Buitelaar, Jan K; Happé, Francesca; Loth, Eva; Barker, Edward D; Schumann, Gunter

2017-08-01

The authors sought to explore how conduct, hyperactivity/inattention, and emotional symptoms are associated with neural reactivity to social-emotional stimuli, and the extent to which psychosocial stress modulates these relationships. Participants were community adolescents recruited as part of the European IMAGEN study. Bilateral amygdala regions of interest were used to assess the relationship between the three symptom domains and functional MRI neural reactivity during passive viewing of dynamic angry and neutral facial expressions. Exploratory functional connectivity and whole brain multiple regression approaches were used to analyze how the symptoms and psychosocial stress relate to other brain regions. In response to the social-emotional stimuli, adolescents with high levels of conduct or hyperactivity/inattention symptoms who had also experienced a greater number of stressful life events showed hyperactivity of the amygdala and several regions across the brain. This effect was not observed with emotional symptoms. A cluster in the midcingulate was found to be common to both conduct problems and hyperactivity symptoms. Exploratory functional connectivity analyses suggested that amygdala-precuneus connectivity is associated with hyperactivity/inattention symptoms. The results link hyperactive amygdala responses and regions critical for top-down emotional processing with high levels of psychosocial stress in individuals with greater conduct and hyperactivity/inattention symptoms. This work highlights the importance of studying how psychosocial stress affects functional brain responses to social-emotional stimuli, particularly in adolescents with externalizing symptoms.

Common brain regions underlying different arithmetic operations as revealed by conjunct fMRI-BOLD activation.

PubMed

Fehr, Thorsten; Code, Chris; Herrmann, Manfred

2007-10-03

The issue of how and where arithmetic operations are represented in the brain has been addressed in numerous studies. Lesion studies suggest that a network of different brain areas are involved in mental calculation. Neuroimaging studies have reported inferior parietal and lateral frontal activations during mental arithmetic using tasks of different complexities and using different operators (addition, subtraction, etc.). Indeed, it has been difficult to compare brain activation across studies because of the variety of different operators and different presentation modalities used. The present experiment examined fMRI-BOLD activity in participants during calculation tasks entailing different arithmetic operations -- addition, subtraction, multiplication and division -- of different complexities. Functional imaging data revealed a common activation pattern comprising right precuneus, left and right middle and superior frontal regions during all arithmetic operations. All other regional activations were operation specific and distributed in prominently frontal, parietal and central regions when contrasting complex and simple calculation tasks. The present results largely confirm former studies suggesting that activation patterns due to mental arithmetic appear to reflect a basic anatomical substrate of working memory, numerical knowledge and processing based on finger counting, and derived from a network originally related to finger movement. We emphasize that in mental arithmetic research different arithmetic operations should always be examined and discussed independently of each other in order to avoid invalid generalizations on arithmetics and involved brain areas.

Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke

PubMed Central

Zavaglia, Melissa; Forkert, Nils D.; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C.

2015-01-01

Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a ‘map of stroke’. PMID:26448908

Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke.

PubMed

Zavaglia, Melissa; Forkert, Nils D; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C

2015-01-01

Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a 'map of stroke'.

Nuclear microscopy in Parkinson's disease

NASA Astrophysics Data System (ADS)

Watt, F.; Lee, T.; Thong, P. S. P.; Tang, S. M.

1995-09-01

Rats have been subjected to unilateral lesioning with the selective neurotoxin 6-OHDA in order to induce Parkinsonism. Analysis using the NUS Nuclear Microscope facility have shown that iron levels are raised by an average of 26% in the lesioned subtantia nigra region of the brain compared with the non-lesioned side. In addition the background tissue level of iron is also elevated by 31% in the lesioned side, indicating that there is a general increase in iron levels as a result of the lesioning. This result is consistent with the other observations that other diseases of the brain are frequently associated with altered iron levels (eg. progressive nuclear palsy, multiple system atrophy, Alzheimers disease, multiple sclerosis).

A regularized clustering approach to brain parcellation from functional MRI data

NASA Astrophysics Data System (ADS)

Dillon, Keith; Wang, Yu-Ping

2017-08-01

We consider a data-driven approach for the subdivision of an individual subject's functional Magnetic Resonance Imaging (fMRI) scan into regions of interest, i.e., brain parcellation. The approach is based on a computational technique for calculating resolution from inverse problem theory, which we apply to neighborhood selection for brain connectivity networks. This can be efficiently calculated even for very large images, and explicitly incorporates regularization in the form of spatial smoothing and a noise cutoff. We demonstrate the reproducibility of the method on multiple scans of the same subjects, as well as the variations between subjects.

Normalization as a canonical neural computation

PubMed Central

Carandini, Matteo; Heeger, David J.

2012-01-01

There is increasing evidence that the brain relies on a set of canonical neural computations, repeating them across brain regions and modalities to apply similar operations to different problems. A promising candidate for such a computation is normalization, in which the responses of neurons are divided by a common factor that typically includes the summed activity of a pool of neurons. Normalization was developed to explain responses in the primary visual cortex and is now thought to operate throughout the visual system, and in many other sensory modalities and brain regions. Normalization may underlie operations such as the representation of odours, the modulatory effects of visual attention, the encoding of value and the integration of multisensory information. Its presence in such a diversity of neural systems in multiple species, from invertebrates to mammals, suggests that it serves as a canonical neural computation. PMID:22108672

Brain pathways for cognitive-emotional decision making in the human animal.

PubMed

Levine, Daniel S

2009-04-01

As roles for different brain regions become clearer, a picture emerges of how primate prefrontal cortex executive circuitry influences subcortical decision making pathways inherited from other mammals. The human's basic needs or drives can be interpreted as residing in an on-center off-surround network in motivational regions of the hypothalamus and brain stem. Such a network has multiple attractors that, in this case, represent the amount of satisfaction of these needs, and we consider and interpret neurally a continuous-time simulated annealing algorithm for moving between attractors under the influence of noise that represents "discontent" combined with "initiative." For decision making on specific tasks, we employ a variety of rules whose neural circuitry appears to involve the amygdala and the orbital, cingulate, and dorsolateral regions of prefrontal cortex. These areas can be interpreted as connected in a three-layer adaptive resonance network. The vigilance of the network, which is influenced by the state of the hypothalamic needs network, determines the level of sophistication of the rule being utilized.

Age-Related Differences in Memory and Executive Functions in Healthy "APOE"[epsilon]4 Carriers: The Contribution of Individual Differences in Prefrontal Volumes and Systolic Blood Pressure

ERIC Educational Resources Information Center

Bender, Andrew R.; Raz, Naftali

2012-01-01

Advanced age and vascular risk are associated with declines in the volumes of multiple brain regions, especially the prefrontal cortex, and the hippocampus. Older adults, even unencumbered by declining health, perform less well than their younger counterparts in multiple cognitive domains, such as episodic memory, executive functions, and speed of…

Glutathione in the human brain: Review of its roles and measurement by magnetic resonance spectroscopy.

PubMed

Rae, Caroline D; Williams, Stephen R

2017-07-15

We review the transport, synthesis and catabolism of glutathione in the brain as well as its compartmentation and biochemistry in different brain cells. The major reactions involving glutathione are reviewed and the factors limiting its availability in brain cells are discussed. We also describe and critique current methods for measuring glutathione in the human brain using magnetic resonance spectroscopy, and review the literature on glutathione measurements in healthy brains and in neurological, psychiatric, neurodegenerative and neurodevelopmental conditions In summary: Healthy human brain glutathione concentration is ∼1-2 mM, but it varies by brain region, with evidence of gender differences and age effects; in neurological disease glutathione appears reduced in multiple sclerosis, motor neurone disease and epilepsy, while being increased in meningiomas; in psychiatric disease the picture is complex and confounded by methodological differences, regional effects, length of disease and drug-treatment. Both increases and decreases in glutathione have been reported in depression and schizophrenia. In Alzheimer's disease and mild cognitive impairment there is evidence for a decrease in glutathione compared to age-matched healthy controls. Improved methods to measure glutathione in vivo will provide better precision in glutathione determination and help resolve the complex biochemistry of this molecule in health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Cannabis cue-induced brain activation correlates with drug craving in limbic and visual salience regions: Preliminary results

PubMed Central

Charboneau, Evonne J.; Dietrich, Mary S.; Park, Sohee; Cao, Aize; Watkins, Tristan J; Blackford, Jennifer U; Benningfield, Margaret M.; Martin, Peter R.; Buchowski, Maciej S.; Cowan, Ronald L.

2013-01-01

Craving is a major motivator underlying drug use and relapse but the neural correlates of cannabis craving are not well understood. This study sought to determine whether visual cannabis cues increase cannabis craving and whether cue-induced craving is associated with regional brain activation in cannabis-dependent individuals. Cannabis craving was assessed in 16 cannabis-dependent adult volunteers while they viewed cannabis cues during a functional MRI (fMRI) scan. The Marijuana Craving Questionnaire was administered immediately before and after each of three cannabis cue-exposure fMRI runs. FMRI blood-oxygenation-level-dependent (BOLD) signal intensity was determined in regions activated by cannabis cues to examine the relationship of regional brain activation to cannabis craving. Craving scores increased significantly following exposure to visual cannabis cues. Visual cues activated multiple brain regions, including inferior orbital frontal cortex, posterior cingulate gyrus, parahippocampal gyrus, hippocampus, amygdala, superior temporal pole, and occipital cortex. Craving scores at baseline and at the end of all three runs were significantly correlated with brain activation during the first fMRI run only, in the limbic system (including amygdala and hippocampus) and paralimbic system (superior temporal pole), and visual regions (occipital cortex). Cannabis cues increased craving in cannabis-dependent individuals and this increase was associated with activation in the limbic, paralimbic, and visual systems during the first fMRI run, but not subsequent fMRI runs. These results suggest that these regions may mediate visually cued aspects of drug craving. This study provides preliminary evidence for the neural basis of cue-induced cannabis craving and suggests possible neural targets for interventions targeted at treating cannabis dependence. PMID:24035535

Comparison of doses received by the hippocampus in patients treated with single isocenter– vs multiple isocenter–based stereotactic radiation therapy to the brain for multiple brain metastases

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

Algan, Ozer, E-mail: oalgan@ouhsc.edu; Giem, Jared; Young, Julie

To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)–based or multiple isocenter (MI)–based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A totalmore » of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63 mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V{sub 100}. All of the other measured dosimetric parameters including the V{sub 95}, V{sub 99}, and D{sub 100} were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.« less

Comparison of doses received by the hippocampus in patients treated with single isocenter- vs multiple isocenter-based stereotactic radiation therapy to the brain for multiple brain metastases.

PubMed

Algan, Ozer; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

2015-01-01

To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)-based or multiple isocenter (MI)-based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V100. All of the other measured dosimetric parameters including the V95, V99, and D100 were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

The hierarchical brain network for face recognition.

PubMed

Zhen, Zonglei; Fang, Huizhen; Liu, Jia

2013-01-01

Numerous functional magnetic resonance imaging (fMRI) studies have identified multiple cortical regions that are involved in face processing in the human brain. However, few studies have characterized the face-processing network as a functioning whole. In this study, we used fMRI to identify face-selective regions in the entire brain and then explore the hierarchical structure of the face-processing network by analyzing functional connectivity among these regions. We identified twenty-five regions mainly in the occipital, temporal and frontal cortex that showed a reliable response selective to faces (versus objects) across participants and across scan sessions. Furthermore, these regions were clustered into three relatively independent sub-networks in a face-recognition task on the basis of the strength of functional connectivity among them. The functionality of the sub-networks likely corresponds to the recognition of individual identity, retrieval of semantic knowledge and representation of emotional information. Interestingly, when the task was switched to object recognition from face recognition, the functional connectivity between the inferior occipital gyrus and the rest of the face-selective regions were significantly reduced, suggesting that this region may serve as an entry node in the face-processing network. In sum, our study provides empirical evidence for cognitive and neural models of face recognition and helps elucidate the neural mechanisms underlying face recognition at the network level.

ADOLESCENT INTERMITTENT ETHANOL EXPOSURE ENHANCES ETHANOL ACTIVATION OF THE NUCLEUS ACCUMBENS WHILE BLUNTING THE PREFRONTAL CORTEX RESPONSES IN ADULT RAT

PubMed Central

LIU, W.; CREWS, F. T.

2016-01-01

The brain continues to develop through adolescence when excessive alcohol consumption is prevalent in humans. We hypothesized that binge drinking doses of ethanol during adolescence will cause changes in brain ethanol responses that persist into adulthood. To test this hypothesis Wistar rats were treated with an adolescent intermittent ethanol (AIE; 5 g/kg, i.g. 2 days on–2 days off; P25–P54) model of underage drinking followed by 25 days of abstinence during maturation to young adulthood (P80). Using markers of neuronal activation c-Fos, EGR1, and phophorylated extracellar signal regulated kinase (pERK1/2), adult responses to a moderate and binge drinking ethanol challenge, e.g., 2 or 4 g/kg, were determined. Adult rats showed dose dependent increases in neuronal activation markers in multiple brain regions during ethanol challenge. Brain regional responses correlated are consistent with anatomical connections. AIE led to marked decreases in adult ethanol PFC (prefrontal cortex) and blunted responses in the amygdala. Binge drinking doses led to the nucleus accumbens (NAc) activation that correlated with the ventral tegmental area (VTA) activation. In contrast to other brain regions, AIE enhanced the adult NAc response to binge drinking doses. These studies suggest that adolescent alcohol exposure causes long-lasting changes in brain responses to alcohol that persist into adulthood. PMID:25727639

3D spatially encoded and accelerated TE-averaged echo planar spectroscopic imaging in healthy human brain.

PubMed

Iqbal, Zohaib; Wilson, Neil E; Thomas, M Albert

2016-03-01

Several different pathologies, including many neurodegenerative disorders, affect the energy metabolism of the brain. Glutamate, a neurotransmitter in the brain, can be used as a biomarker to monitor these metabolic processes. One method that is capable of quantifying glutamate concentration reliably in several regions of the brain is TE-averaged (1) H spectroscopic imaging. However, this type of method requires the acquisition of multiple TE lines, resulting in long scan durations. The goal of this experiment was to use non-uniform sampling, compressed sensing reconstruction and an echo planar readout gradient to reduce the scan time by a factor of eight to acquire TE-averaged spectra in three spatial dimensions. Simulation of glutamate and glutamine showed that the 2.2-2.4 ppm spectral region contained 95% glutamate signal using the TE-averaged method. Peak integration of this spectral range and home-developed, prior-knowledge-based fitting were used for quantitation. Gray matter brain phantom measurements were acquired on a Siemens 3 T Trio scanner. Non-uniform sampling was applied retrospectively to these phantom measurements and quantitative results of glutamate with respect to creatine 3.0 (Glu/Cr) ratios showed a coefficient of variance of 16% for peak integration and 9% for peak fitting using eight-fold acceleration. In vivo scans of the human brain were acquired as well and five different brain regions were quantified using the prior-knowledge-based algorithm. Glu/Cr ratios from these regions agreed with previously reported results in the literature. The method described here, called accelerated TE-averaged echo planar spectroscopic imaging (TEA-EPSI), is a significant methodological advancement and may be a useful tool for categorizing glutamate changes in pathologies where affected brain regions are not known a priori. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Intrinsic frequency biases and profiles across human cortex.

PubMed

Mellem, Monika S; Wohltjen, Sophie; Gotts, Stephen J; Ghuman, Avniel Singh; Martin, Alex

2017-11-01

Recent findings in monkeys suggest that intrinsic periodic spiking activity in selective cortical areas occurs at timescales that follow a sensory or lower order-to-higher order processing hierarchy (Murray JD, Bernacchia A, Freedman DJ, Romo R, Wallis JD, Cai X, Padoa-Schioppa C, Pasternak T, Seo H, Lee D, Wang XJ. Nat Neurosci 17: 1661-1663, 2014). It has not yet been fully explored if a similar timescale hierarchy is present in humans. Additionally, these measures in the monkey studies have not addressed findings that rhythmic activity within a brain area can occur at multiple frequencies. In this study we investigate in humans if regions may be biased toward particular frequencies of intrinsic activity and if a full cortical mapping still reveals an organization that follows this hierarchy. We examined the spectral power in multiple frequency bands (0.5-150 Hz) from task-independent data using magnetoencephalography (MEG). We compared standardized power across bands to find regional frequency biases. Our results demonstrate a mix of lower and higher frequency biases across sensory and higher order regions. Thus they suggest a more complex cortical organization that does not simply follow this hierarchy. Additionally, some regions do not display a bias for a single band, and a data-driven clustering analysis reveals a regional organization with high standardized power in multiple bands. Specifically, theta and beta are both high in dorsal frontal cortex, whereas delta and gamma are high in ventral frontal cortex and temporal cortex. Occipital and parietal regions are biased more narrowly toward alpha power, and ventral temporal lobe displays specific biases toward gamma. Thus intrinsic rhythmic neural activity displays a regional organization but one that is not necessarily hierarchical. NEW & NOTEWORTHY The organization of rhythmic neural activity is not well understood. Whereas it has been postulated that rhythms are organized in a hierarchical manner across brain regions, our novel analysis allows comparison of full cortical maps across different frequency bands, which demonstrate that the rhythmic organization is more complex. Additionally, data-driven methods show that rhythms of multiple frequencies or timescales occur within a particular region and that this nonhierarchical organization is widespread. Copyright © 2017 the American Physiological Society.

Insights into TREM2 biology by network analysis of human brain gene expression data

PubMed Central

Forabosco, Paola; Ramasamy, Adaikalavan; Trabzuni, Daniah; Walker, Robert; Smith, Colin; Bras, Jose; Levine, Adam P.; Hardy, John; Pocock, Jennifer M.; Guerreiro, Rita; Weale, Michael E.; Ryten, Mina

2013-01-01

Rare variants in TREM2 cause susceptibility to late-onset Alzheimer's disease. Here we use microarray-based expression data generated from 101 neuropathologically normal individuals and covering 10 brain regions, including the hippocampus, to understand TREM2 biology in human brain. Using network analysis, we detect a highly preserved TREM2-containing module in human brain, show that it relates to microglia, and demonstrate that TREM2 is a hub gene in 5 brain regions, including the hippocampus, suggesting that it can drive module function. Using enrichment analysis we show significant overrepresentation of genes implicated in the adaptive and innate immune system. Inspection of genes with the highest connectivity to TREM2 suggests that it plays a key role in mediating changes in the microglial cytoskeleton necessary not only for phagocytosis, but also migration. Most importantly, we show that the TREM2-containing module is significantly enriched for genes genetically implicated in Alzheimer's disease, multiple sclerosis, and motor neuron disease, implying that these diseases share common pathways centered on microglia and that among the genes identified are possible new disease-relevant genes. PMID:23855984

Alterations of brain activity in fibromyalgia patients.

PubMed

Sawaddiruk, Passakorn; Paiboonworachat, Sahattaya; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2017-04-01

Fibromyalgia is a chronic pain syndrome, characterized by widespread musculoskeletal pain with diffuse tenderness at multiple tender points. Despite intense investigations, the pathophysiology of fibromyalgia remains elusive. Evidence shows that it could be due to changes in either the peripheral or central nervous system (CNS). For the CNS changes, alterations in the high brain area of fibromyalgia patients have been investigated but the definite mechanisms are still unclear. Magnetic Resonance Imaging (MRI) and Functional Magnetic Resonance (fMRI) have been used to gather evidence regarding the changes of brain morphologies and activities in fibromyalgia patients. Nevertheless, due to few studies, limited knowledge for alterations in brain activities in fibromyalgia is currently available. In this review, the changes in brain activity in various brain areas obtained from reports in fibromyalgia patients are comprehensively summarized. Changes of the grey matter in multiple regions such as the superior temporal gyrus, posterior thalamus, amygdala, basal ganglia, cerebellum, cingulate cortex, SII, caudate and putamen from the MRI as well as the increase of brain activities in the cerebellum, prefrontal cortex, anterior cingulate cortex, thalamus, somatosensory cortex, insula in fMRI studies are presented and discussed. Moreover, evidence from pharmacological interventions offering benefits for fibromyalgia patients by reducing brain activity is presented. Because of limited knowledge regarding the roles of brain activity alterations in fibromyalgia, this summarized review will encourage more future studies to elucidate the underlying mechanisms involved in the brains of these patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evoked itch perception is associated with changes in functional brain connectivity.

PubMed

Desbordes, Gaëlle; Li, Ang; Loggia, Marco L; Kim, Jieun; Schalock, Peter C; Lerner, Ethan; Tran, Thanh N; Ring, Johannes; Rosen, Bruce R; Kaptchuk, Ted J; Pfab, Florian; Napadow, Vitaly

2015-01-01

Chronic itch, a highly debilitating condition, has received relatively little attention in the neuroimaging literature. Recent studies suggest that brain regions supporting itch in chronic itch patients encompass sensorimotor and salience networks, and corticostriatal circuits involved in motor preparation for scratching. However, how these different brain areas interact with one another in the context of itch is still unknown. We acquired BOLD fMRI scans in 14 atopic dermatitis patients to investigate resting-state functional connectivity before and after allergen-induced itch exacerbated the clinical itch perception in these patients. A seed-based analysis revealed decreased functional connectivity from baseline resting state to the evoked-itch state between several itch-related brain regions, particularly the insular and cingulate cortices and basal ganglia, where decreased connectivity was significantly correlated with increased levels of perceived itch. In contrast, evoked itch increased connectivity between key nodes of the frontoparietal control network (superior parietal lobule and dorsolateral prefrontal cortex), where higher increase in connectivity was correlated with a lesser increase in perceived itch, suggesting that greater interaction between nodes of this executive attention network serves to limit itch sensation via enhanced top-down regulation. Overall, our results provide the first evidence of itch-dependent changes in functional connectivity across multiple brain regions.

[Fetal neurosonography using 3-dimensional multiplanar sonography].

PubMed

Chaoui, R; Heling, K S; Kainer, F; Karl, K

2012-04-01

This review focuses on the examination of the fetal brain, using three-dimensional (3D) ultrasound and the multiplanar rendering mode (MPR). The routine examination of the brain is achieved with axial planes but a dedicated fetal neurosonogram requires additional coronal and sagittal views, in order to provide a complete view of the different brain structures. Because these planes are difficult to obtain under many conditions, the present paper shows how 3D MPR allows one to obtain 1 or multiple reconstructed images from a digital volume. The display can be either as orthogonal planes, tomographic planes with parallel slices or as one single plane of the region of interest, which can be selected by the examiner. This approach allows easily the demonstration of the corpus callosum, the cerebellar vermis, the three-horn view, the foetal hippocampus and other regions. In addition, early neurosonography of the developing brain from the 7th week of pregnancy onwards can be achieved. © Georg Thieme Verlag KG Stuttgart · New York.

A critical review of the allocentric spatial representation and its neural underpinnings: toward a network-based perspective

PubMed Central

Ekstrom, Arne D.; Arnold, Aiden E. G. F.; Iaria, Giuseppe

2014-01-01

While the widely studied allocentric spatial representation holds a special status in neuroscience research, its exact nature and neural underpinnings continue to be the topic of debate, particularly in humans. Here, based on a review of human behavioral research, we argue that allocentric representations do not provide the kind of map-like, metric representation one might expect based on past theoretical work. Instead, we suggest that almost all tasks used in past studies involve a combination of egocentric and allocentric representation, complicating both the investigation of the cognitive basis of an allocentric representation and the task of identifying a brain region specifically dedicated to it. Indeed, as we discuss in detail, past studies suggest numerous brain regions important to allocentric spatial memory in addition to the hippocampus, including parahippocampal, retrosplenial, and prefrontal cortices. We thus argue that although allocentric computations will often require the hippocampus, particularly those involving extracting details across temporally specific routes, the hippocampus is not necessary for all allocentric computations. We instead suggest that a non-aggregate network process involving multiple interacting brain areas, including hippocampus and extra-hippocampal areas such as parahippocampal, retrosplenial, prefrontal, and parietal cortices, better characterizes the neural basis of spatial representation during navigation. According to this model, an allocentric representation does not emerge from the computations of a single brain region (i.e., hippocampus) nor is it readily decomposable into additive computations performed by separate brain regions. Instead, an allocentric representation emerges from computations partially shared across numerous interacting brain regions. We discuss our non-aggregate network model in light of existing data and provide several key predictions for future experiments. PMID:25346679

Mesoscale brain explorer, a flexible python-based image analysis and visualization tool.

PubMed

Haupt, Dirk; Vanni, Matthieu P; Bolanos, Federico; Mitelut, Catalin; LeDue, Jeffrey M; Murphy, Tim H

2017-07-01

Imaging of mesoscale brain activity is used to map interactions between brain regions. This work has benefited from the pioneering studies of Grinvald et al., who employed optical methods to image brain function by exploiting the properties of intrinsic optical signals and small molecule voltage-sensitive dyes. Mesoscale interareal brain imaging techniques have been advanced by cell targeted and selective recombinant indicators of neuronal activity. Spontaneous resting state activity is often collected during mesoscale imaging to provide the basis for mapping of connectivity relationships using correlation. However, the information content of mesoscale datasets is vast and is only superficially presented in manuscripts given the need to constrain measurements to a fixed set of frequencies, regions of interest, and other parameters. We describe a new open source tool written in python, termed mesoscale brain explorer (MBE), which provides an interface to process and explore these large datasets. The platform supports automated image processing pipelines with the ability to assess multiple trials and combine data from different animals. The tool provides functions for temporal filtering, averaging, and visualization of functional connectivity relations using time-dependent correlation. Here, we describe the tool and show applications, where previously published datasets were reanalyzed using MBE.

Brain activity correlated with food preferences: a functional study comparing advanced non-small cell lung cancer patients with and without anorexia.

PubMed

Sánchez-Lara, Karla; Arrieta, Oscar; Pasaye, Eric; Laviano, Alessandro; Mercadillo, Roberto E; Sosa-Sánchez, Ricardo; Méndez-Sánchez, Nahum

2013-01-01

The aim of this study was to examine the brain activity manifested while non-small cell lung cancer (NSCLC) patients with and without anorexia were exposed to visual food stimuli. We included 26 treatment-naïve patients who had been recently diagnosed with advanced NSCLC. Patients with brain metastasis were excluded. The patients were classified into anorectic and non-anorectic groups. Data from functional magnetic resonance imaging based on blood oxygen level-dependent (BOLD) signals were analyzed while the patients perceived pleasant and unpleasant food pictures. The brain records were analyzed with SPM 5 using a voxelwise multiple regression analysis. The non-anorexic patients demonstrated BOLD activation, comprising frontal brain regions in the premotor and the prefrontal cortices, only while watching unpleasant stimuli. The anorectic patients demonstrated no activation while watching the pleasant and unpleasant food pictures. Anorectic patients with lung cancer present a lack of activation in the brain regions associated with food stimuli processing. These results are consistent with experiences in the clinical environment: Patients describe themselves as not experiencing sensations of hunger or having an appetite. Copyright © 2013 Elsevier Inc. All rights reserved.

Multiple-region directed functional connectivity based on phase delays.

PubMed

Goelman, Gadi; Dan, Rotem

2017-03-01

Network analysis is increasingly advancing the field of neuroimaging. Neural networks are generally constructed from pairwise interactions with an assumption of linear relations between them. Here, a high-order statistical framework to calculate directed functional connectivity among multiple regions, using wavelet analysis and spectral coherence has been presented. The mathematical expression for 4 regions was derived and used to characterize a quartet of regions as a linear, combined (nonlinear), or disconnected network. Phase delays between regions were used to obtain network's temporal hierarchy and directionality. The validity of the mathematical derivation along with the effects of coupling strength and noise on its outcomes were studied by computer simulations of the Kuramoto model. The simulations demonstrated correct directionality for a large range of coupling strength and low sensitivity to Gaussian noise compared with pairwise coherences. The analysis was applied to resting-state fMRI data of 40 healthy young subjects to characterize the ventral visual system, motor system and default mode network (DMN). It was shown that the ventral visual system was predominantly composed of linear networks while the motor system and the DMN were composed of combined (nonlinear) networks. The ventral visual system exhibits its known temporal hierarchy, the motor system exhibits center ↔ out hierarchy and the DMN has dorsal ↔ ventral and anterior ↔ posterior organizations. The analysis can be applied in different disciplines such as seismology, or economy and in a variety of brain data including stimulus-driven fMRI, electrophysiology, EEG, and MEG, thus open new horizons in brain research. Hum Brain Mapp 38:1374-1386, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Convergent transcriptional specializations in the brains of humans and song-learning birds

PubMed Central

Pfenning, Andreas R.; Hara, Erina; Whitney, Osceola; Rivas, Miriam V.; Wang, Rui; Roulhac, Petra L.; Howard, Jason T.; Wirthlin, Morgan; Lovell, Peter V.; Ganapathy, Ganeshkumar; Mouncastle, Jacquelyn; Moseley, M. Arthur; Thompson, J. Will; Soderblom, Erik J.; Iriki, Atsushi; Kato, Masaki; Gilbert, M. Thomas P.; Zhang, Guojie; Bakken, Trygve; Bongaarts, Angie; Bernard, Amy; Lein, Ed; Mello, Claudio V.; Hartemink, Alexander J.; Jarvis, Erich D.

2015-01-01

Song-learning birds and humans share independently evolved similarities in brain pathways for vocal learning that are essential for song and speech and are not found in most other species. Comparisons of brain transcriptomes of song-learning birds and humans relative to vocal nonlearners identified convergent gene expression specializations in specific song and speech brain regions of avian vocal learners and humans. The strongest shared profiles relate bird motor and striatal song-learning nuclei, respectively, with human laryngeal motor cortex and parts of the striatum that control speech production and learning. Most of the associated genes function in motor control and brain connectivity. Thus, convergent behavior and neural connectivity for a complex trait are associated with convergent specialized expression of multiple genes. PMID:25504733

Changes in Brain Resting-state Functional Connectivity Associated with Peripheral Nerve Block: A Pilot Study.

PubMed

Melton, M Stephen; Browndyke, Jeffrey N; Harshbarger, Todd B; Madden, David J; Nielsen, Karen C; Klein, Stephen M

2016-08-01

Limited information exists on the effects of temporary functional deafferentation (TFD) on brain activity after peripheral nerve block (PNB) in healthy humans. Increasingly, resting-state functional connectivity (RSFC) is being used to study brain activity and organization. The purpose of this study was to test the hypothesis that TFD through PNB will influence changes in RSFC plasticity in central sensorimotor functional brain networks in healthy human participants. The authors achieved TFD using a supraclavicular PNB model with 10 healthy human participants undergoing functional connectivity magnetic resonance imaging before PNB, during active PNB, and during PNB recovery. RSFC differences among study conditions were determined by multiple-comparison-corrected (false discovery rate-corrected P value less than 0.05) random-effects, between-condition, and seed-to-voxel analyses using the left and right manual motor regions. The results of this pilot study demonstrated disruption of interhemispheric left-to-right manual motor region RSFC (e.g., mean Fisher-transformed z [effect size] at pre-PNB 1.05 vs. 0.55 during PNB) but preservation of intrahemispheric RSFC of these regions during PNB. Additionally, there was increased RSFC between the left motor region of interest (PNB-affected area) and bilateral higher order visual cortex regions after clinical PNB resolution (e.g., Fisher z between left motor region of interest and right and left lingual gyrus regions during PNB, -0.1 and -0.6 vs. 0.22 and 0.18 after PNB resolution, respectively). This pilot study provides evidence that PNB has features consistent with other models of deafferentation, making it a potentially useful approach to investigate brain plasticity. The findings provide insight into RSFC of sensorimotor functional brain networks during PNB and PNB recovery and support modulation of the sensory-motor integration feedback loop as a mechanism for explaining the behavioral correlates of peripherally induced TFD through PNB.

Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain.

PubMed

Gerlofs-Nijland, Miriam E; van Berlo, Damien; Cassee, Flemming R; Schins, Roel P F; Wang, Kate; Campbell, Arezoo

2010-05-17

The etiology and progression of neurodegenerative disorders depends on the interactions between a variety of factors including: aging, environmental exposures, and genetic susceptibility factors. Enhancement of proinflammatory events appears to be a common link in different neurological impairments, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Studies have shown a link between exposure to particulate matter (PM), present in air pollution, and enhancement of central nervous system proinflammatory markers. In the present study, the association between exposure to air pollution (AP), derived from a specific source (diesel engine), and neuroinflammation was investigated. To elucidate whether specific regions of the brain are more susceptible to exposure to diesel-derived AP, various loci of the brain were separately analyzed. Rats were exposed for 6 hrs a day, 5 days a week, for 4 weeks to diesel engine exhaust (DEE) using a nose-only exposure chamber. The day after the final exposure, the brain was dissected into the following regions: cerebellum, frontal cortex, hippocampus, olfactory bulb and tubercles, and the striatum. Baseline levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 alpha (IL-1alpha) were dependent on the region analyzed and increased in the striatum after exposure to DEE. In addition, baseline level of activation of the transcription factors (NF-kappaB) and (AP-1) was also region dependent but the levels were not significantly altered after exposure to DEE. A similar, though not significant, trend was seen with the mRNA expression levels of TNF-alpha and TNF Receptor-subtype I (TNF-RI). Our results indicate that different brain regions may be uniquely responsive to changes induced by exposure to DEE. This study once more underscores the role of neuroinflammation in response to ambient air pollution, however, it is valuable to assess if and to what extent the observed changes may impact the normal function and cellular integrity of unique brain regions.

Multiple sparse volumetric priors for distributed EEG source reconstruction.

PubMed

Strobbe, Gregor; van Mierlo, Pieter; De Vos, Maarten; Mijović, Bogdan; Hallez, Hans; Van Huffel, Sabine; López, José David; Vandenberghe, Stefaan

2014-10-15

We revisit the multiple sparse priors (MSP) algorithm implemented in the statistical parametric mapping software (SPM) for distributed EEG source reconstruction (Friston et al., 2008). In the present implementation, multiple cortical patches are introduced as source priors based on a dipole source space restricted to a cortical surface mesh. In this note, we present a technique to construct volumetric cortical regions to introduce as source priors by restricting the dipole source space to a segmented gray matter layer and using a region growing approach. This extension allows to reconstruct brain structures besides the cortical surface and facilitates the use of more realistic volumetric head models including more layers, such as cerebrospinal fluid (CSF), compared to the standard 3-layered scalp-skull-brain head models. We illustrated the technique with ERP data and anatomical MR images in 12 subjects. Based on the segmented gray matter for each of the subjects, cortical regions were created and introduced as source priors for MSP-inversion assuming two types of head models. The standard 3-layered scalp-skull-brain head models and extended 4-layered head models including CSF. We compared these models with the current implementation by assessing the free energy corresponding with each of the reconstructions using Bayesian model selection for group studies. Strong evidence was found in favor of the volumetric MSP approach compared to the MSP approach based on cortical patches for both types of head models. Overall, the strongest evidence was found in favor of the volumetric MSP reconstructions based on the extended head models including CSF. These results were verified by comparing the reconstructed activity. The use of volumetric cortical regions as source priors is a useful complement to the present implementation as it allows to introduce more complex head models and volumetric source priors in future studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Disrupted white matter connectivity underlying developmental dyslexia: A machine learning approach.

PubMed

Cui, Zaixu; Xia, Zhichao; Su, Mengmeng; Shu, Hua; Gong, Gaolang

2016-04-01

Developmental dyslexia has been hypothesized to result from multiple causes and exhibit multiple manifestations, implying a distributed multidimensional effect on human brain. The disruption of specific white-matter (WM) tracts/regions has been observed in dyslexic children. However, it remains unknown if developmental dyslexia affects the human brain WM in a multidimensional manner. Being a natural tool for evaluating this hypothesis, the multivariate machine learning approach was applied in this study to compare 28 school-aged dyslexic children with 33 age-matched controls. Structural magnetic resonance imaging (MRI) and diffusion tensor imaging were acquired to extract five multitype WM features at a regional level: white matter volume, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. A linear support vector machine (LSVM) classifier achieved an accuracy of 83.61% using these MRI features to distinguish dyslexic children from controls. Notably, the most discriminative features that contributed to the classification were primarily associated with WM regions within the putative reading network/system (e.g., the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, thalamocortical projections, and corpus callosum), the limbic system (e.g., the cingulum and fornix), and the motor system (e.g., the cerebellar peduncle, corona radiata, and corticospinal tract). These results were well replicated using a logistic regression classifier. These findings provided direct evidence supporting a multidimensional effect of developmental dyslexia on WM connectivity of human brain, and highlighted the involvement of WM tracts/regions beyond the well-recognized reading system in dyslexia. Finally, the discriminating results demonstrated a potential of WM neuroimaging features as imaging markers for identifying dyslexic individuals. © 2016 Wiley Periodicals, Inc.

Brain region-specific activity patterns after recent or remote memory retrieval of auditory conditioned fear.

PubMed

Kwon, Jeong-Tae; Jhang, Jinho; Kim, Hyung-Su; Lee, Sujin; Han, Jin-Hee

2012-09-19

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 retrieval. To investigate this possibility, we systematically imaged the brain activity patterns in the lateral amygdala, MGm/PIN, and AuV/TeA using activity-dependent induction of immediate early gene zif268 after recent and remote memory retrieval of auditory conditioned fear. Consistent with the critical role of the amygdala in fear memory, the zif268 activity in the lateral amygdala was significantly increased after both recent and remote memory retrieval. Interesting, however, the density of zif268 (+) neurons in both MGm/PIN and AuV/TeA, particularly in layers IV and VI, was increased only after remote but not recent fear memory retrieval compared to control groups. Further analysis of zif268 signals in AuV/TeA revealed that conditioned tone induced stronger zif268 induction compared to familiar tone in each individual zif268 (+) neuron after recent memory retrieval. Taken together, our results support that the lateral amygdala is a key brain site for permanent fear memory storage and suggest that MGm/PIN and AuV/TeA might play a role for remote memory storage or retrieval of auditory conditioned fear, or, alternatively, that these auditory brain regions might have a different way of processing for familiar or conditioned tone information at recent and remote time phases.

Spatially aggregated multiclass pattern classification in functional MRI using optimally selected functional brain areas.

PubMed

Zheng, Weili; Ackley, Elena S; Martínez-Ramón, Manel; Posse, Stefan

2013-02-01

In previous works, boosting aggregation of classifier outputs from discrete brain areas has been demonstrated to reduce dimensionality and improve the robustness and accuracy of functional magnetic resonance imaging (fMRI) classification. However, dimensionality reduction and classification of mixed activation patterns of multiple classes remain challenging. In the present study, the goals were (a) to reduce dimensionality by combining feature reduction at the voxel level and backward elimination of optimally aggregated classifiers at the region level, (b) to compare region selection for spatially aggregated classification using boosting and partial least squares regression methods and (c) to resolve mixed activation patterns using probabilistic prediction of individual tasks. Brain activation maps from interleaved visual, motor, auditory and cognitive tasks were segmented into 144 functional regions. Feature selection reduced the number of feature voxels by more than 50%, leaving 95 regions. The two aggregation approaches further reduced the number of regions to 30, resulting in more than 75% reduction of classification time and misclassification rates of less than 3%. Boosting and partial least squares (PLS) were compared to select the most discriminative and the most task correlated regions, respectively. Successful task prediction in mixed activation patterns was feasible within the first block of task activation in real-time fMRI experiments. This methodology is suitable for sparsifying activation patterns in real-time fMRI and for neurofeedback from distributed networks of brain activation. Copyright © 2013 Elsevier Inc. All rights reserved.

Greater neural pattern similarity across repetitions is associated with better memory.

PubMed

Xue, Gui; Dong, Qi; Chen, Chuansheng; Lu, Zhonglin; Mumford, Jeanette A; Poldrack, Russell A

2010-10-01

Repeated study improves memory, but the underlying neural mechanisms of this improvement are not well understood. Using functional magnetic resonance imaging and representational similarity analysis of brain activity, we found that, compared with forgotten items, subsequently remembered faces and words showed greater similarity in neural activation across multiple study in many brain regions, including (but not limited to) the regions whose mean activities were correlated with subsequent memory. This result addresses a longstanding debate in the study of memory by showing that successful episodic memory encoding occurs when the same neural representations are more precisely reactivated across study episodes, rather than when patterns of activation are more variable across time.

Acute and Chronic Effects of Ethanol on Learning-Related Synaptic Plasticity

PubMed Central

Zorumski, Charles F.; Mennerick, Steven; Izumi, Yukitoshi

2014-01-01

Alcoholism is associated with acute and long-term cognitive dysfunction including memory impairment, resulting in substantial disability and cost to society. Thus, understanding how ethanol impairs cognition is essential for developing treatment strategies to dampen its adverse impact. Memory processing is thought to involve persistent, use-dependent changes in synaptic transmission, and ethanol alters the activity of multiple signaling molecules involved in synaptic processing, including modulation of the glutamate and gamma-aminobutyric acid (GABA) transmitter systems that mediate most fast excitatory and inhibitory transmission in the brain. Effects on glutamate and GABA receptors contribute to ethanol-induced changes in long-term potentiation (LTP) and long-term depression (LTD), forms of synaptic plasticity thought to underlie memory acquisition. In this paper, we review the effects of ethanol on learning-related forms of synaptic plasticity with emphasis on changes observed in the hippocampus, a brain region that is critical for encoding contextual and episodic memories. We also include studies in other brain regions as they pertain to altered cognitive and mental function. Comparison of effects in the hippocampus to other brain regions is instructive for understanding the complexities of ethanol’s acute and long-term pharmacological consequences. PMID:24447472

Mapping White Matter Microstructure in the One Month Human Brain.

PubMed

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

2017-08-29

White matter microstructure, essential for efficient and coordinated transmission of neural communications, undergoes pronounced development during the first years of life, while deviations to this neurodevelopmental trajectory likely result in alterations of brain connectivity relevant to behavior. Hence, systematic evaluation of white matter microstructure in the normative brain is critical for a neuroscientific approach to both typical and atypical early behavioral development. However, few studies have examined the infant brain in detail, particularly in infants under 3 months of age. Here, we utilize quantitative techniques of diffusion tensor imaging and neurite orientation dispersion and density imaging to investigate neonatal white matter microstructure in 104 infants. An optimized multiple b-value diffusion protocol was developed to allow for successful acquisition during non-sedated sleep. Associations between white matter microstructure measures and gestation corrected age, regional asymmetries, infant sex, as well as newborn growth measures were assessed. Results highlight changes of white matter microstructure during the earliest periods of development and demonstrate differential timing of developing regions and regional asymmetries. Our results contribute to a growing body of research investigating the neurobiological changes associated with neurodevelopment and suggest that characteristics of white matter microstructure are already underway in the weeks immediately following birth.

Measurement of light transmission and fluence rate in mouse brain in vivo(Conference Presentation)

NASA Astrophysics Data System (ADS)

Macklin, John J.; Graves, Austin R.; Stujenske, Joseph M.; Hantman, Adam W.; Bittner, Katie C.

2017-02-01

Optogenetic experiments require light delivery, typically using fiber optics, to light-gated ion channels genetically targeted to specific brain regions. Understanding where light is—and isn't—in an illuminated brain can be a confounding factor in designing experiments and interpreting results. While the transmission of light, i.e. survival of forward-directed and forward-scattered light, has been extensively measured in vitro, light scattering can be significantly different in vivo due to blood flow and other factors. To measure irradiance in vivo, we constructed a pipette photodetector tipped with fluorescent quantum dots that function as a light transducer. The quantum dot fluorescence is collected by a waveguide and sent to a fiber-coupled spectrometer. The device has a small photo-responsive area ( 10 um x 15 um), enabling collection of micron-resolution irradiance profiles, and can be calibrated to determine irradiance with detection limits of 0.001 mW/mm2. The photodetector has the footprint of a micro-injection pipette, so can be inserted into almost any brain region with minimal invasiveness. With this detector, we determined transverse and axial irradiance profiles in mice across multiple brain regions at 5 source wavelengths spanning the visible spectrum. This profile data is compared to in vitro measurements obtained on tissue slices, and provides a means to derive scattering coefficients for specific brain regions in vivo. The detector is straightforward to fabricate and calibrate, is stable in air storage > 9 months, and can be easily installed in an electrophysiology setup, thereby enabling direct measurement of light spread under conditions used in optogenetics experiments.

Disruptions of network connectivity predict impairment in multiple behavioral domains after stroke

PubMed Central

Ramsey, Lenny E.; Metcalf, Nicholas V.; Chacko, Ravi V.; Weinberger, Kilian; Baldassarre, Antonello; Hacker, Carl D.; Shulman, Gordon L.; Corbetta, Maurizio

2016-01-01

Deficits following stroke are classically attributed to focal damage, but recent evidence suggests a key role of distributed brain network disruption. We measured resting functional connectivity (FC), lesion topography, and behavior in multiple domains (attention, visual memory, verbal memory, language, motor, and visual) in a cohort of 132 stroke patients, and used machine-learning models to predict neurological impairment in individual subjects. We found that visual memory and verbal memory were better predicted by FC, whereas visual and motor impairments were better predicted by lesion topography. Attention and language deficits were well predicted by both. Next, we identified a general pattern of physiological network dysfunction consisting of decrease of interhemispheric integration and intrahemispheric segregation, which strongly related to behavioral impairment in multiple domains. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains. These results link key organizational features of brain networks to brain–behavior relationships in stroke. PMID:27402738

Brain Modulyzer: Interactive Visual Analysis of Functional Brain Connectivity

DOE PAGES

Murugesan, Sugeerth; Bouchard, Kristopher; Brown, Jesse A.; ...

2016-05-09

Here, we present Brain Modulyzer, an interactive visual exploration tool for functional magnetic resonance imaging (fMRI) brain scans, aimed at analyzing the correlation between different brain regions when resting or when performing mental tasks. Brain Modulyzer combines multiple coordinated views—such as heat maps, node link diagrams, and anatomical views—using brushing and linking to provide an anatomical context for brain connectivity data. Integrating methods from graph theory and analysis, e.g., community detection and derived graph measures, makes it possible to explore the modular and hierarchical organization of functional brain networks. Providing immediate feedback by displaying analysis results instantaneously while changing parametersmore » gives neuroscientists a powerful means to comprehend complex brain structure more effectively and efficiently and supports forming hypotheses that can then be validated via statistical analysis. In order to demonstrate the utility of our tool, we also present two case studies—exploring progressive supranuclear palsy, as well as memory encoding and retrieval« less

Brain Modulyzer: Interactive Visual Analysis of Functional Brain Connectivity

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

Murugesan, Sugeerth; Bouchard, Kristopher; Brown, Jesse A.

Here, we present Brain Modulyzer, an interactive visual exploration tool for functional magnetic resonance imaging (fMRI) brain scans, aimed at analyzing the correlation between different brain regions when resting or when performing mental tasks. Brain Modulyzer combines multiple coordinated views—such as heat maps, node link diagrams, and anatomical views—using brushing and linking to provide an anatomical context for brain connectivity data. Integrating methods from graph theory and analysis, e.g., community detection and derived graph measures, makes it possible to explore the modular and hierarchical organization of functional brain networks. Providing immediate feedback by displaying analysis results instantaneously while changing parametersmore » gives neuroscientists a powerful means to comprehend complex brain structure more effectively and efficiently and supports forming hypotheses that can then be validated via statistical analysis. In order to demonstrate the utility of our tool, we also present two case studies—exploring progressive supranuclear palsy, as well as memory encoding and retrieval« less

Brain size predicts problem-solving ability in mammalian carnivores

PubMed Central

Benson-Amram, Sarah; Dantzer, Ben; Stricker, Gregory; Swanson, Eli M.; Holekamp, Kay E.

2016-01-01

Despite considerable interest in the forces shaping the relationship between brain size and cognitive abilities, it remains controversial whether larger-brained animals are, indeed, better problem-solvers. Recently, several comparative studies have revealed correlations between brain size and traits thought to require advanced cognitive abilities, such as innovation, behavioral flexibility, invasion success, and self-control. However, the general assumption that animals with larger brains have superior cognitive abilities has been heavily criticized, primarily because of the lack of experimental support for it. Here, we designed an experiment to inquire whether specific neuroanatomical or socioecological measures predict success at solving a novel technical problem among species in the mammalian order Carnivora. We presented puzzle boxes, baited with food and scaled to accommodate body size, to members of 39 carnivore species from nine families housed in multiple North American zoos. We found that species with larger brains relative to their body mass were more successful at opening the boxes. In a subset of species, we also used virtual brain endocasts to measure volumes of four gross brain regions and show that some of these regions improve model prediction of success at opening the boxes when included with total brain size and body mass. Socioecological variables, including measures of social complexity and manual dexterity, failed to predict success at opening the boxes. Our results, thus, fail to support the social brain hypothesis but provide important empirical support for the relationship between relative brain size and the ability to solve this novel technical problem. PMID:26811470

Brain size predicts problem-solving ability in mammalian carnivores.

PubMed

Benson-Amram, Sarah; Dantzer, Ben; Stricker, Gregory; Swanson, Eli M; Holekamp, Kay E

2016-03-01

Despite considerable interest in the forces shaping the relationship between brain size and cognitive abilities, it remains controversial whether larger-brained animals are, indeed, better problem-solvers. Recently, several comparative studies have revealed correlations between brain size and traits thought to require advanced cognitive abilities, such as innovation, behavioral flexibility, invasion success, and self-control. However, the general assumption that animals with larger brains have superior cognitive abilities has been heavily criticized, primarily because of the lack of experimental support for it. Here, we designed an experiment to inquire whether specific neuroanatomical or socioecological measures predict success at solving a novel technical problem among species in the mammalian order Carnivora. We presented puzzle boxes, baited with food and scaled to accommodate body size, to members of 39 carnivore species from nine families housed in multiple North American zoos. We found that species with larger brains relative to their body mass were more successful at opening the boxes. In a subset of species, we also used virtual brain endocasts to measure volumes of four gross brain regions and show that some of these regions improve model prediction of success at opening the boxes when included with total brain size and body mass. Socioecological variables, including measures of social complexity and manual dexterity, failed to predict success at opening the boxes. Our results, thus, fail to support the social brain hypothesis but provide important empirical support for the relationship between relative brain size and the ability to solve this novel technical problem.

Tau, amyloid, and cascading network failure across the Alzheimer's disease spectrum.

PubMed

Jones, David T; Graff-Radford, Jonathan; Lowe, Val J; Wiste, Heather J; Gunter, Jeffrey L; Senjem, Matthew L; Botha, Hugo; Kantarci, Kejal; Boeve, Bradley F; Knopman, David S; Petersen, Ronald C; Jack, Clifford R

2017-12-01

Functionally related brain regions are selectively vulnerable to Alzheimer's disease pathophysiology. However, molecular markers of this pathophysiology (i.e., beta-amyloid and tau aggregates) have discrepant spatial and temporal patterns of progression within these selectively vulnerable brain regions. Existing reductionist pathophysiologic models cannot account for these large-scale spatiotemporal inconsistencies. Within the framework of the recently proposed cascading network failure model of Alzheimer's disease, however, these large-scale patterns are to be expected. This model postulates the following: 1) a tau-associated, circumscribed network disruption occurs in brain regions specific to a given phenotype in clinically normal individuals; 2) this disruption can trigger phenotype independent, stereotypic, and amyloid-associated compensatory brain network changes indexed by changes in the default mode network; 3) amyloid deposition marks a saturation of functional compensation and portends an acceleration of the inciting phenotype specific, and tau-associated, network failure. With the advent of in vivo molecular imaging of tau pathology, combined with amyloid and functional network imaging, it is now possible to investigate the relationship between functional brain networks, tau, and amyloid across the disease spectrum within these selectively vulnerable brain regions. In a large cohort (n = 218) spanning the Alzheimer's disease spectrum from young, amyloid negative, cognitively normal subjects to Alzheimer's disease dementia, we found several distinct spatial patterns of tau deposition, including 'Braak-like' and 'non-Braak-like', across functionally related brain regions. Rather than arising focally and spreading sequentially, elevated tau signal seems to occur system-wide based on inferences made from multiple cross-sectional analyses we conducted looking at regional patterns of tau signal. Younger age-of-disease-onset was associated with 'non-Braak-like' patterns of tau, suggesting an association with atypical clinical phenotypes. As predicted by the cascading network failure model of Alzheimer's disease, we found that amyloid is a partial mediator of the relationship between functional network failure and tau deposition in functionally connected brain regions. This study implicates large-scale brain networks in the pathophysiology of tau deposition and offers support to models incorporating large-scale network physiology into disease models linking tau and amyloid, such as the cascading network failure model of Alzheimer's disease. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

PubMed Central

2015-01-01

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

The Case for Musical Instrument Training in Cerebral Palsy for Neurorehabilitation

PubMed Central

2016-01-01

Recent imaging studies in cerebral palsy (CP) have described several brain structural changes, functional alterations, and neuroplastic processes that take place after brain injury during early development. These changes affect motor pathways as well as sensorimotor networks. Several of these changes correlate with behavioral measures of motor and sensory disability. It is now widely acknowledged that management of sensory deficits is relevant for rehabilitation in CP. Playing a musical instrument demands the coordination of hand movements with integrated auditory, visual, and tactile feedback, in a process that recruits multiple brain regions. These multiple demands during instrument playing, together with the entertaining character of music, have led to the development and investigation of music-supported therapies, especially for rehabilitation with motor disorders resulting from brain damage. We review scientific evidence that supports the use of musical instrument playing for rehabilitation in CP. We propose that active musical instrument playing may be an efficient means for triggering neuroplastic processes necessary for the development of sensorimotor skills in patients with early brain damage. We encourage experimental research on neuroplasticity and on its impact on the physical and personal development of individuals with CP. PMID:27867664

The Case for Musical Instrument Training in Cerebral Palsy for Neurorehabilitation.

PubMed

Alves-Pinto, Ana; Turova, Varvara; Blumenstein, Tobias; Lampe, Renée

2016-01-01

Recent imaging studies in cerebral palsy (CP) have described several brain structural changes, functional alterations, and neuroplastic processes that take place after brain injury during early development. These changes affect motor pathways as well as sensorimotor networks. Several of these changes correlate with behavioral measures of motor and sensory disability. It is now widely acknowledged that management of sensory deficits is relevant for rehabilitation in CP. Playing a musical instrument demands the coordination of hand movements with integrated auditory, visual, and tactile feedback, in a process that recruits multiple brain regions. These multiple demands during instrument playing, together with the entertaining character of music, have led to the development and investigation of music-supported therapies, especially for rehabilitation with motor disorders resulting from brain damage. We review scientific evidence that supports the use of musical instrument playing for rehabilitation in CP. We propose that active musical instrument playing may be an efficient means for triggering neuroplastic processes necessary for the development of sensorimotor skills in patients with early brain damage. We encourage experimental research on neuroplasticity and on its impact on the physical and personal development of individuals with CP.

In vivo single-shot three-dimensionally localized multiple quantum spectroscopy of GABA in the human brain with improved spectral selectivity

NASA Astrophysics Data System (ADS)

Choi, In-Young; Lee, Sang-Pil; Shen, Jun

2005-01-01

A single-shot multiple quantum filtering method is developed that uses two double-band frequency selective pulses for enhanced spectral selectivity in combination with a slice-selective 90°, a slice-selective universal rotator 90°, and a spectral-spatial pulse composed of two slice-selective universal rotator 45° pulses for single-shot three-dimensional localization. The use of this selective multiple quantum filtering method for C3 and C4 methylene protons of GABA resulted in improved spectral selectivity for GABA and effective suppression of overlapping signals such as creatine and glutathione in each single scan, providing reliable measurements of the GABA doublet in all subjects. The concentration of GABA was measured to be 0.7 ± 0.2 μmol/g (means ± SD, n = 15) in the fronto-parietal region of the human brain in vivo.

Single-digit arithmetic processing—anatomical evidence from statistical voxel-based lesion analysis

PubMed Central

Mihulowicz, Urszula; Willmes, Klaus; Karnath, Hans-Otto; Klein, Elise

2014-01-01

Different specific mechanisms have been suggested for solving single-digit arithmetic operations. However, the neural correlates underlying basic arithmetic (multiplication, addition, subtraction) are still under debate. In the present study, we systematically assessed single-digit arithmetic in a group of acute stroke patients (n = 45) with circumscribed left- or right-hemispheric brain lesions. Lesion sites significantly related to impaired performance were found only in the left-hemisphere damaged (LHD) group. Deficits in multiplication and addition were related to subcortical/white matter brain regions differing from those for subtraction tasks, corroborating the notion of distinct processing pathways for different arithmetic tasks. Additionally, our results further point to the importance of investigating fiber pathways in numerical cognition. PMID:24847238

Multiple imputation of missing fMRI data in whole brain analysis

PubMed Central

Vaden, Kenneth I.; Gebregziabher, Mulugeta; Kuchinsky, Stefanie E.; Eckert, Mark A.

2012-01-01

Whole brain fMRI analyses rarely include the entire brain because of missing data that result from data acquisition limits and susceptibility artifact, in particular. This missing data problem is typically addressed by omitting voxels from analysis, which may exclude brain regions that are of theoretical interest and increase the potential for Type II error at cortical boundaries or Type I error when spatial thresholds are used to establish significance. Imputation could significantly expand statistical map coverage, increase power, and enhance interpretations of fMRI results. We examined multiple imputation for group level analyses of missing fMRI data using methods that leverage the spatial information in fMRI datasets for both real and simulated data. Available case analysis, neighbor replacement, and regression based imputation approaches were compared in a general linear model framework to determine the extent to which these methods quantitatively (effect size) and qualitatively (spatial coverage) increased the sensitivity of group analyses. In both real and simulated data analysis, multiple imputation provided 1) variance that was most similar to estimates for voxels with no missing data, 2) fewer false positive errors in comparison to mean replacement, and 3) fewer false negative errors in comparison to available case analysis. Compared to the standard analysis approach of omitting voxels with missing data, imputation methods increased brain coverage in this study by 35% (from 33,323 to 45,071 voxels). In addition, multiple imputation increased the size of significant clusters by 58% and number of significant clusters across statistical thresholds, compared to the standard voxel omission approach. While neighbor replacement produced similar results, we recommend multiple imputation because it uses an informed sampling distribution to deal with missing data across subjects that can include neighbor values and other predictors. Multiple imputation is anticipated to be particularly useful for 1) large fMRI data sets with inconsistent missing voxels across subjects and 2) addressing the problem of increased artifact at ultra-high field, which significantly limit the extent of whole brain coverage and interpretations of results. PMID:22500925

Fusing Multiple Sensor Modalities for Complex Physiological State Monitoring

DTIC Science & Technology

2012-12-01

sleep-alpha variants (drowsiness alpha activity and REM -alpha bursts) over frontal, central, parietal and occipital regions. Note the higher spectral...contribution of the slowest components (7.8–8.6 Hz) during REM alpha bursts as compared with drowsiness-alpha activity (13...occipital regions of the brain during the drowsiness state as compared to REM sleep and other states, as seen in figure 1 (13). Furthermore, using EEG

Identification and classification of hubs in brain networks.

PubMed

Sporns, Olaf; Honey, Christopher J; Kötter, Rolf

2007-10-17

Brain regions in the mammalian cerebral cortex are linked by a complex network of fiber bundles. These inter-regional networks have previously been analyzed in terms of their node degree, structural motif, path length and clustering coefficient distributions. In this paper we focus on the identification and classification of hub regions, which are thought to play pivotal roles in the coordination of information flow. We identify hubs and characterize their network contributions by examining motif fingerprints and centrality indices for all regions within the cerebral cortices of both the cat and the macaque. Motif fingerprints capture the statistics of local connection patterns, while measures of centrality identify regions that lie on many of the shortest paths between parts of the network. Within both cat and macaque networks, we find that a combination of degree, motif participation, betweenness centrality and closeness centrality allows for reliable identification of hub regions, many of which have previously been functionally classified as polysensory or multimodal. We then classify hubs as either provincial (intra-cluster) hubs or connector (inter-cluster) hubs, and proceed to show that lesioning hubs of each type from the network produces opposite effects on the small-world index. Our study presents an approach to the identification and classification of putative hub regions in brain networks on the basis of multiple network attributes and charts potential links between the structural embedding of such regions and their functional roles.

Alterations of parenchymal microstructure, neuronal connectivity and cerebrovascular resistance at adolescence following mild to moderate traumatic brain injury in early development.

PubMed

Parent, Maxime; Li, Ying; Santhakumar, Vijayalakshmi; Hyder, Fahmeed; Sanganahalli, Basavaraju G; Kannurpatti, Sridhar

2018-06-01

TBI is a leading cause of morbidity in children. To investigate outcome of early developmental TBI during adolescence, a rat model of fluid percussion injury was developed, where previous work reported deficits in sensorimotor behavior and cortical blood flow at adolescence. 1 Based on the non-localized outcome, we hypothesized that multiple neurophysiological components of brain function, namely neuronal connectivity, synapse/axonal microstructural integrity and neurovascular function are altered and magnetic resonance imaging (MRI) methods could be used to determine regional alterations. Adolescent outcomes of developmental TBI were studied 2-months after injury, using functional MRI (fMRI) and Diffusion Tensor Imaging (DTI). fMRI based resting state functional connectivity (RSFC), representing neural connectivity, was significantly altered between sham and TBI. RSFC strength decreased in the cortex, hippocampus and thalamus accompanied by decrease in the spatial extent of their corresponding RSFC networks and inter-hemispheric asymmetry. Cerebrovascular reactivity to arterial CO2 changes diminished after TBI across both hemispheres, with a more pronounced decrease in the ipsilateral hippocampus, thalamus and motor cortex. DTI measures of fractional anisotropy (FA) and apparent diffusion coefficient (ADC), reporting on axonal and microstructural integrity of the brain, indicated similar inter-hemispheric asymmetry, with highest change in the ipsilateral hippocampus and regions adjoining the ipsilateral thalamus, hypothalamus and amygdala. TBI-induced corpus callosal microstructural alterations indicated measurable changes in inter-hemispheric structural connectivity. Hippocampus, thalamus and select cortical regions were most consistently affected in multiple imaging markers. The multi-modal MRI results demonstrate cortical and subcortical alterations in neural connectivity, cerebrovascular resistance and parenchymal microstructure in the adolescent brain, indicating the highly diffuse and persistent nature of the lateral fluid percussion TBI early in development.

Functional brain networks in schizophrenia: a review.

PubMed

Calhoun, Vince D; Eichele, Tom; Pearlson, Godfrey

2009-01-01

Functional magnetic resonance imaging (fMRI) has become a major technique for studying cognitive function and its disruption in mental illness, including schizophrenia. The major proportion of imaging studies focused primarily upon identifying regions which hemodynamic response amplitudes covary with particular stimuli and differentiate between patient and control groups. In addition to such amplitude based comparisons, one can estimate temporal correlations and compute maps of functional connectivity between regions which include the variance associated with event-related responses as well as intrinsic fluctuations of hemodynamic activity. Functional connectivity maps can be computed by correlating all voxels with a seed region when a spatial prior is available. An alternative are multivariate decompositions such as independent component analysis (ICA) which extract multiple components, each of which is a spatially distinct map of voxels with a common time course. Recent work has shown that these networks are pervasive in relaxed resting and during task performance and hence provide robust measures of intact and disturbed brain activity. This in turn bears the prospect of yielding biomarkers for schizophrenia, which can be described both in terms of disrupted local processing as well as altered global connectivity between large-scale networks. In this review we will summarize functional connectivity measures with a focus upon work with ICA and discuss the meaning of intrinsic fluctuations. In addition, examples of how brain networks have been used for classification of disease will be shown. We present work with functional network connectivity, an approach that enables the evaluation of the interplay between multiple networks and how they are affected in disease. We conclude by discussing new variants of ICA for extracting maximally group discriminative networks from data. In summary, it is clear that identification of brain networks and their inter-relationships with fMRI has great potential to improve our understanding of schizophrenia.

Neuronal Assemblies Evidence Distributed Interactions within a Tactile Discrimination Task in Rats

PubMed Central

Deolindo, Camila S.; Kunicki, Ana C. B.; da Silva, Maria I.; Lima Brasil, Fabrício; Moioli, Renan C.

2018-01-01

Accumulating evidence suggests that neural interactions are distributed and relate to animal behavior, but many open questions remain. The neural assembly hypothesis, formulated by Hebb, states that synchronously active single neurons may transiently organize into functional neural circuits—neuronal assemblies (NAs)—and that would constitute the fundamental unit of information processing in the brain. However, the formation, vanishing, and temporal evolution of NAs are not fully understood. In particular, characterizing NAs in multiple brain regions over the course of behavioral tasks is relevant to assess the highly distributed nature of brain processing. In the context of NA characterization, active tactile discrimination tasks with rats are elucidative because they engage several cortical areas in the processing of information that are otherwise masked in passive or anesthetized scenarios. In this work, we investigate the dynamic formation of NAs within and among four different cortical regions in long-range fronto-parieto-occipital networks (primary somatosensory, primary visual, prefrontal, and posterior parietal cortices), simultaneously recorded from seven rats engaged in an active tactile discrimination task. Our results first confirm that task-related neuronal firing rate dynamics in all four regions is significantly modulated. Notably, a support vector machine decoder reveals that neural populations contain more information about the tactile stimulus than the majority of single neurons alone. Then, over the course of the task, we identify the emergence and vanishing of NAs whose participating neurons are shown to contain more information about animal behavior than randomly chosen neurons. Taken together, our results further support the role of multiple and distributed neurons as the functional unit of information processing in the brain (NA hypothesis) and their link to active animal behavior. PMID:29375324

Peer Influence Via Instagram: Effects on Brain and Behavior in Adolescence and Young Adulthood.

PubMed

Sherman, Lauren E; Greenfield, Patricia M; Hernandez, Leanna M; Dapretto, Mirella

2018-01-01

Mobile social media often feature the ability to "Like" content posted by others. This study examined the effect of Likes on youths' neural and behavioral responses to photographs. High school and college students (N = 61, ages 13-21) viewed theirs and others' Instagram photographs while undergoing functional Magnetic Resonance Imaging (fMRI). Participants more often Liked photographs that appeared to have received many (vs. few) Likes. Popular photographs elicited greater activity in multiple brain regions, including the nucleus accumbens (NAcc), a hub of the brain's reward circuitry. NAcc responsivity increased with age for high school but not college students. When viewing images depicting risk-taking (vs. nonrisky photographs), high school students, but not college students, showed decreased activation of neural regions implicated in cognitive control. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

Neural mechanisms of movement planning: motor cortex and beyond.

PubMed

Svoboda, Karel; Li, Nuo

2018-04-01

Neurons in motor cortex and connected brain regions fire in anticipation of specific movements, long before movement occurs. This neural activity reflects internal processes by which the brain plans and executes volitional movements. The study of motor planning offers an opportunity to understand how the structure and dynamics of neural circuits support persistent internal states and how these states influence behavior. Recent advances in large-scale neural recordings are beginning to decipher the relationship of the dynamics of populations of neurons during motor planning and movements. New behavioral tasks in rodents, together with quantified perturbations, link dynamics in specific nodes of neural circuits to behavior. These studies reveal a neural network distributed across multiple brain regions that collectively supports motor planning. We review recent advances and highlight areas where further work is needed to achieve a deeper understanding of the mechanisms underlying motor planning and related cognitive processes. Copyright © 2017. Published by Elsevier Ltd.

Brain systems for visual perspective taking and action perception.

PubMed

Mazzarella, Elisabetta; Ramsey, Richard; Conson, Massimiliano; Hamilton, Antonia

2013-01-01

Taking another person's viewpoint and making sense of their actions are key processes that guide social behavior. Previous neuroimaging investigations have largely studied these processes separately. The current study used functional magnetic resonance imaging to examine how the brain incorporates another person's viewpoint and actions into visual perspective judgments. Participants made a left-right judgment about the location of a target object from their own (egocentric) or an actor's visual perspective (altercentric). Actor location varied around a table and the actor was either reaching or not reaching for the target object. Analyses examined brain regions engaged in the egocentric and altercentric tasks, brain regions where response magnitude tracked the orientation of the actor in the scene and brain regions sensitive to the action performed by the actor. The blood oxygen level-dependent (BOLD) response in dorsomedial prefrontal cortex (dmPFC) was sensitive to actor orientation in the altercentric task, whereas the response in right inferior frontal gyrus (IFG) was sensitive to actor orientation in the egocentric task. Thus, dmPFC and right IFG may play distinct but complementary roles in visual perspective taking (VPT). Observation of a reaching actor compared to a non-reaching actor yielded activation in lateral occipitotemporal cortex, regardless of task, showing that these regions are sensitive to body posture independent of social context. By considering how an observed actor's location and action influence the neural bases of visual perspective judgments, the current study supports the view that multiple neurocognitive "routes" operate during VPT.

Effect of Carotenoid Supplemented Formula on Carotenoid Bioaccumulation in Tissues of Infant Rhesus Macaques: A Pilot Study Focused on Lutein

PubMed Central

Jeon, Sookyoung; Neuringer, Martha; Johnson, Emily E.; Kuchan, Matthew J.; Pereira, Suzette L.; Johnson, Elizabeth J.; Erdman, John W.

2017-01-01

Lutein is the predominant carotenoid in the developing primate brain and retina, and may have important functional roles. However, its bioaccumulation pattern during early development is not understood. In this pilot study, we investigated whether carotenoid supplementation of infant formula enhanced lutein tissue deposition in infant rhesus macaques. Monkeys were initially breastfed; from 1 to 3 months of age they were fed either a formula supplemented with lutein, zeaxanthin, β-carotene and lycopene, or a control formula with low levels of these carotenoids, for 4 months (n = 2/group). All samples were analyzed by high pressure liquid chromatography (HPLC). Final serum lutein in the supplemented group was 5 times higher than in the unsupplemented group. All brain regions examined showed a selective increase in lutein deposition in the supplemented infants. Lutein differentially accumulated across brain regions, with highest amounts in occipital cortex in both groups. β-carotene accumulated, but zeaxanthin and lycopene were undetectable in any brain region. Supplemented infants had higher lutein concentrations in peripheral retina but not in macular retina. Among adipose sites, abdominal subcutaneous adipose tissue exhibited the highest lutein level and was 3-fold higher in the supplemented infants. The supplemented formula enhanced carotenoid deposition in several other tissues. In rhesus infants, increased intake of carotenoids from formula enhanced their deposition in serum and numerous tissues and selectively increased lutein in multiple brain regions. PMID:28075370

Cortical thickness and folding deficits in conduct-disordered adolescents

PubMed Central

Hyatt, Christopher J.; Haney-Caron, Emily; Stevens, Michael C.

2012-01-01

Background Studies of pediatric conduct disorder (CD) have described frontal and temporal lobe structural abnormalities that parallel findings in antisocial adults. The purpose of this study was to examine previously unexplored cortical thickness and folding as markers for brain abnormalities in “pure CD”-diagnosed adolescents. Based on current fronto-temporal theories, we hypothesized that CD youth would have thinner cortex or less cortical folding in temporal and frontal lobes than control subjects. Methods We obtained T1-weighted brain structure images from n=24 control and n=19 CD participants aged 12–18 years, matched by overall gender and age. We measured group differences in cortical thickness and local gyrification index (regional cortical folding measure) using surface-based morphometry with clusterwise correction for multiple comparisons. Results CD participants, when compared with controls, showed both reduced cortical thickness and folding. Thinner cortex was located primarily in posterior brain regions, including left superior temporal and parietal lobes, temporoparietal junction and paracentral lobule, right superior temporal and parietal lobes, temporoparietal junction and precuneus. Folding deficits were located mainly in anterior brain regions and included left insula, ventro- and dorsomedial prefrontal, anterior cingulate and orbitofrontal cortices, temporal lobe, right superior frontal and parietal lobes and paracentral lobule. Conclusions Our findings generally agree with previous CD volumetric studies, but here show the unique contributions of cortical thickness and folding to gray matter reductions in pure CD in different brain regions. PMID:22209639

Bridging animal and human models of exercise-induced brain plasticity

PubMed Central

Voss, Michelle W.; Vivar, Carmen; Kramer, Arthur F.; van Praag, Henriette

2015-01-01

Significant progress has been made in understanding the neurobiological mechanisms through which exercise protects and restores the brain. In this feature review, we integrate animal and human research, examining physical activity effects across multiple levels of description (neurons up to inter-regional pathways). We evaluate the influence of exercise on hippocampal structure and function, addressing common themes such as spatial memory and pattern separation, brain structure and plasticity, neurotrophic factors, and vasculature. Areas of research focused more within species, such as hippocampal neurogenesis in rodents, also provide crucial insight into the protective role of physical activity. Overall, converging evidence suggests exercise benefits brain function and cognition across the mammalian lifespan, which may translate into reduced risk for Alzheimer’s disease (AD) in humans. PMID:24029446

Comparative analysis of A-to-I editing in human and non-human primate brains reveals conserved patterns and context-dependent regulation of RNA editing.

PubMed

O'Neil, Richard T; Wang, Xiaojing; Morabito, Michael V; Emeson, Ronald B

2017-04-06

A-to-I RNA editing is an important process for generating molecular diversity in the brain through modification of transcripts encoding several proteins important for neuronal signaling. We investigated the relationships between the extent of editing at multiple substrate transcripts (5HT2C, MGLUR4, CADPS, GLUR2, GLUR4, and GABRA3) in brain tissue obtained from adult humans and rhesus macaques. Several patterns emerged from these studies revealing conservation of editing across primate species. Additionally, variability in the human population allows us to make novel inferences about the co-regulation of editing at different editing sites and even across different brain regions.

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

PubMed Central

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

1995-01-01

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

Mitochondria, oligodendrocytes and inflammation in bipolar disorder: evidence from transcriptome studies points to intriguing parallels with multiple sclerosis

PubMed Central

Konradi, Christine; Sillivan, Stephanie E.; Clay, Hayley B.

2011-01-01

Gene expression studies of bipolar disorder (BPD) have shown changes in transcriptome profiles in multiple brain regions. Here we summarize the most consistent findings in the scientific literature, and compare them to data from schizophrenia (SZ) and major depressive disorder (MDD). The transcriptome profiles of all three disorders overlap, making the existence of a BPD-specific profile unlikely. Three groups of functionally related genes are consistently expressed at altered levels in BPD, SZ and MDD. Genes involved in energy metabolism and mitochondrial function are downregulated, genes involved in immune response and inflammation are upregulated, and genes expressed in oligodendrocytes are downregulated. Experimental paradigms for multiple sclerosis demonstrate a tight link between energy metabolism, inflammation and demyelination. These studies also show variabilities in the extent of oligodendrocyte stress, which can vary from a downregulation of oligodendrocyte genes, such as observed in psychiatric disorders, to cell death and brain lesions seen in multiple sclerosis. We conclude that experimental models of multiple sclerosis could be of interest for the research of BPD, SZ and MDD. PMID:21310238

Is synaptic loss a unique hallmark of Alzheimer's disease?

PubMed Central

Scheff, Stephen W.; Neltner, Janna H.; Nelson, Peter T.

2014-01-01

Synapses may represent a key nidus for dementia including Alzheimer's disease (AD) pathogenesis. Here we review published studies and present new ideas related to the question of the specificity of synapse loss in AD. Currently, AD is defined by the regional presence of neuritic plaques and neurofibrillary tangles in the brain. The severity of involvement by those pathological hallmarks tends to correlate both with antemortem cognitive status, and also with synapse loss in multiple brain areas. Recent studies from large autopsy series have led to a new standard of excellence with regard to clinical–pathological correlation and to improved comprehension of the numerous brain diseases of the elderly. These studies have provided evidence that it is the rule rather than the exception for brains of aged individuals to demonstrate pathologies (often multiple) other than AD plaques and tangles. For many of these comorbid pathologies, the extent of synapse loss is imperfectly understood but could be substantial. These findings indicate that synapse loss is probably not a hallmark specific to AD but rather a change common to many diseases associated with dementia. PMID:24412275

Brain activation patterns elicited by the 'Faces Symbol Test' -- a pilot fMRI study.

PubMed

Grabner, Rh; Popotnig, F; Ropele, S; Neuper, C; Gorani, F; Petrovic, K; Ebner, F; Strasser-Fuchs, S; Fazekas, F; Enzinger, C

2008-04-01

The Faces Symbol Test (FST) has recently been proposed as a brief and patient-friendly screening instrument for the assessment of cognitive dysfunction in patients with multiple sclerosis (MS). However, in contrast to well-established MS screening tests such as the Paced Auditory Serial Addition Test, the neural correlates of the FST have not been investigated so far. In the present study, we developed a functional MRI (fMRI) version of the FST to provide first data on brain regions and networks involved in this test. A sample of 19 healthy participants completed a version of the FST adapted for fMRI, requiring matching of faces and symbols in a multiple choice test and two further experimental conditions drawing on cognitive subcomponents (face matching and symbol matching). Imaging data showed a differential involvement of a fronto-parieto-occipital network in the three conditions. The most demanding FST condition elicited brain activation patterns related with sustained attention and executive control. These results suggest that the FST recruits brain networks critical for higher-order cognitive functions often impaired in MS patients.

Intrinsic brain abnormalities in young healthy adults with childhood trauma: A resting-state functional magnetic resonance imaging study of regional homogeneity and functional connectivity.

PubMed

Lu, Shaojia; Gao, Weijia; Wei, Zhaoguo; Wang, Dandan; Hu, Shaohua; Huang, Manli; Xu, Yi; Li, Lingjiang

2017-06-01

Childhood trauma confers great risk for the development of multiple psychiatric disorders; however, the neural basis for this association is still unknown. The present resting-state functional magnetic resonance imaging study aimed to detect the effects of childhood trauma on brain function in a group of young healthy adults. In total, 24 healthy individuals with childhood trauma and 24 age- and sex-matched adults without childhood trauma were recruited. Each participant underwent resting-state functional magnetic resonance imaging scanning. Intra-regional brain activity was evaluated by regional homogeneity method and compared between groups. Areas with altered regional homogeneity were further selected as seeds in subsequent functional connectivity analysis. Statistical analyses were performed by setting current depression and anxiety as covariates. Adults with childhood trauma showed decreased regional homogeneity in bilateral superior temporal gyrus and insula, and the right inferior parietal lobule, as well as increased regional homogeneity in the right cerebellum and left middle temporal gyrus. Regional homogeneity values in the left middle temporal gyrus, right insula and right cerebellum were correlated with childhood trauma severity. In addition, individuals with childhood trauma also exhibited altered default mode network, cerebellum-default mode network and insula-default mode network connectivity when the left middle temporal gyrus, right cerebellum and right insula were selected as seed area, respectively. The present outcomes suggest that childhood trauma is associated with disturbed intrinsic brain function, especially the default mode network, in adults even without psychiatric diagnoses, which may mediate the relationship between childhood trauma and psychiatric disorders in later life.

Amyloid and Tau PET Demonstrate Region-Specific Associations in Normal Older People

PubMed Central

Lockhart, Samuel N.; Schöll, Michael; Baker, Suzanne L.; Ayakta, Nagehan; Swinnerton, Kaitlin N.; Bell, Rachel K.; Mellinger, Taylor J.; Shah, Vyoma D.; O’Neil, James P.; Janabi, Mustafa; Jagust, William J.

2017-01-01

β-amyloid (Aβ) and tau pathology become increasingly prevalent with age, however, the spatial relationship between the two pathologies remains unknown. We examined local (same region) and non-local (different region) associations between these 2 aggregated proteins in 46 normal older adults using [18F]AV-1451 (for tau) and [11C]PiB (for Aβ) positron emission tomography (PET) and 1.5T magnetic resonance imaging (MRI) images. While local voxelwise analyses showed associations between PiB and AV-1451 tracer largely in the temporal lobes, k-means clustering revealed that some of these associations were driven by regions with low tracer retention. We followed this up with a whole-brain region-by-region (local and non-local) partial correlational analysis. We calculated each participant’s mean AV-1451 and PiB uptake values within 87 regions of interest (ROI). Pairwise ROI analysis demonstrated many positive PiB—AV-1451 associations. Importantly, strong positive partial correlations (controlling for age, sex, and global gray matter fraction, p < .01) were identified between PiB in multiple regions of association cortex and AV-1451 in temporal cortical ROIs. There were also less frequent and weaker positive associations of regional PiB with frontoparietal AV-1451 uptake. Particularly in temporal lobe ROIs, AV-1451 uptake was strongly predicted by PiB across multiple ROI locations. These data indicate that Aβ and tau pathology show significant local and non-local regional associations among cognitively normal elderly, with increased PiB uptake throughout the cortex correlating with increased temporal lobe AV-1451 uptake. The spatial relationship between Aβ and tau accumulation does not appear to be specific to Aβ location, suggesting a regional vulnerability of temporal brain regions to tau accumulation regardless of where Aβ accumulates. PMID:28232190

Combined Diffusion Tensor and Magnetic Resonance Spectroscopic Imaging Methodology for Automated Regional Brain Analysis: Application in a Normal Pediatric Population.

PubMed

Ghosh, Nirmalya; Holshouser, Barbara; Oyoyo, Udo; Barnes, Stanley; Tong, Karen; Ashwal, Stephen

2017-01-01

During human brain development, anatomic regions mature at different rates. Quantitative anatomy-specific analysis of longitudinal diffusion tensor imaging (DTI) and magnetic resonance spectroscopic imaging (MRSI) data may improve our ability to quantify and categorize these maturational changes. Computational tools designed to quickly fuse and analyze imaging information from multiple, technically different datasets would facilitate research on changes during normal brain maturation and for comparison to disease states. In the current study, we developed a complete battery of computational tools to execute such data analyses that include data preprocessing, tract-based statistical analysis from DTI data, automated brain anatomy parsing from T1-weighted MR images, assignment of metabolite information from MRSI data, and co-alignment of these multimodality data streams for reporting of region-specific indices. We present statistical analyses of regional DTI and MRSI data in a cohort of normal pediatric subjects (n = 72; age range: 5-18 years; mean 12.7 ± 3.3 years) to establish normative data and evaluate maturational trends. Several regions showed significant maturational changes for several DTI parameters and MRSI ratios, but the percent change over the age range tended to be small. In the subcortical region (combined basal ganglia [BG], thalami [TH], and corpus callosum [CC]), the largest combined percent change was a 10% increase in fractional anisotropy (FA) primarily due to increases in the BG (12.7%) and TH (9%). The largest significant percent increase in N-acetylaspartate (NAA)/creatine (Cr) ratio was seen in the brain stem (BS) (18.8%) followed by the subcortical regions in the BG (11.9%), CC (8.9%), and TH (6.0%). We found consistent, significant (p < 0.01), but weakly positive correlations (r = 0.228-0.329) between NAA/Cr ratios and mean FA in the BS, BG, and CC regions. Age- and region-specific normative MR diffusion and spectroscopic metabolite ranges show brain maturation changes and are requisite for detecting abnormalities in an injured or diseased population. © 2017 S. Karger AG, Basel.

Sex differences in the developing brain as a source of inherent risk.

PubMed

McCarthy, Margaret M

2016-12-01

Brain development diverges in males and females in response to androgen production by the fetal testis. This sexual differentiation of the brain occurs during a sensitive window and induces enduring neuroanatomical and physiological changes that profoundly impact behavior. What we know about the contribution of sex chromosomes is still emerging, highlighting the need to integrate multiple factors into understanding sex differences, including the importance of context. The cellular mechanisms are best modeled in rodents and have provided both unifying principles and surprising specifics. Markedly distinct signaling pathways direct differentiation in specific brain regions, resulting in mosaicism of relative maleness, femaleness, and sameness through-out the brain, while canalization both exaggerates and constrains sex differences. Non-neuronal cells and inflammatory mediators are found in greater number and at higher levels in parts of male brains. This higher baseline of inflammation is speculated to increase male vulnerability to developmental neuropsychiatric disorders that are triggered by inflammation.

Chemical mapping of anxiety in the brain of healthy humans: an in vivo 1H-MRS study on the effects of sex, age, and brain region.

PubMed

Grachev, I D; Apkarian, A V

2000-12-01

We recently presented results in an in vivo study of human brain chemistry in 'physiologic' anxiety, i.e., the anxiety of normal everyday life. Normal subjects with high anxiety demonstrated increased concentration of chemicals in orbital frontal cortex (OFC) as compared to lower anxiety. In a separate study of aging we demonstrated a decrease of total chemical concentration in OFC of middle-aged subjects, as compared with younger age. This brain region also showed gender dependence; men demonstrating decreased chemical concentration compared to women. We hypothesized that these sex- and age-dependent differences in OFC chemistry changes are a result of anxiety effects on this brain region. In the present study we examined these sex- and age-differential regional brain chemistry changes (as identified by localized in vivo proton magnetic resonance spectroscopy [1H-MRS]) in relation to the state-trait-anxiety (as measured by the State-Trait Anxiety Inventory) in 35 healthy subjects. The concentrations for all nine chemicals of 1H-MRS spectra were measured relative to creatine across multiple brain regions, including OFC in the left hemisphere. Analysis of variance showed anxiety-specific effects on chemical concentration changes in OFC, which were different for both sexes and age groups. Male subjects showed larger effect of anxiety on OFC chemistry as compared to females when the same sex high-anxiety subjects were compared to lower anxiety. Similarly, middle-aged subjects showed larger effect of anxiety on OFC chemistry as compared to younger age when the same age subjects with high anxiety were compared to lower anxiety. Largest effect of anxiety on OFC chemistry was due to changes of N-Acetyl aspartate. The results indicate that the state-trait anxiety has sex- and age-differential patterns on OFC chemistry in healthy humans, providing new information about the neurobiological roots of anxiety.

Double-blind, placebo-controlled, multiple-ascending-dose study on the pharmacodynamics of ABIO-08/01, a new CNS drug with potential anxiolytic activity. 2. EEG-tomography findings based on LORETA (low-resolution brain electromagnetic tomography).

PubMed

Saletu, Bernd; Anderer, Peter; Wolzt, Michael; Nosiska, Dorothea; Assandri, Alessandro; Noseda, Emanuele; Nannipieri, Fabrizio; Saletu-Zyhlarz, Gerda M

2009-01-01

Effects of ABIO-08/01, a new potentially anxiolytic isoxazoline, on regional electrical brain generators were investigated by 3-dimensional EEG tomography. In a double- blind, placebo-controlled, multiple-ascending-dose study, 16 healthy males (30.2 +/- 5.7 years) received 3 oral drug doses (10, 20, 40 mg) and placebo for 7 days (8-day wash-out) in a randomized non-balanced design for phase-1 studies. A 3-min vigilance-controlled (V) EEG, a 4-min resting (R) EEG with eyes closed, a 1-min eyes-open (EO) EEG and psychometric tests were performed 0, 1 and 6 h after taking the drug on days 1 and 5. Low-resolution brain electromagnetic tomography (LORETA) was computed from the spectrally analyzed EEG data, and differences between drug and placebo were displayed as statistical parametric maps. Data were registered to the Talairach-Tournoux Human Brain Atlas available as a digitized MRI. An overall omnibus significance test followed by a voxel-by-voxel t test demonstrated significant regional EEG changes after ABIO-08/01 versus placebo, dependent on recording condition, dose and time. While in the EO-EEG specifically the lowest dose of ABIO-08/01 induced pronounced sedative effects (delta/theta and beta increase) 1 h after acute and slightly less so after superimposed administration, in the 6th hour a decrease in alpha and beta activity signaled less sedative and more relaxant action. In the V-EEG these changes were less pronounced, in the R-EEG partly opposite. Hemisphere-specific changes were observed, suggesting increases in LORETA power over the left temporal, parietal, superior frontal regions and decreases over the right prefrontal, temporal pole and occipital regions. These LORETA changes are discussed in the light of neuroimaging findings on anxiety and anxiolytics. 2009 S. Karger AG, Basel.

A multi-atlas based method for automated anatomical Macaca fascicularis brain MRI segmentation and PET kinetic extraction.

PubMed

Ballanger, Bénédicte; Tremblay, Léon; Sgambato-Faure, Véronique; Beaudoin-Gobert, Maude; Lavenne, Franck; Le Bars, Didier; Costes, Nicolas

2013-08-15

MRI templates and digital atlases are needed for automated and reproducible quantitative analysis of non-human primate PET studies. Segmenting brain images via multiple atlases outperforms single-atlas labelling in humans. We present a set of atlases manually delineated on brain MRI scans of the monkey Macaca fascicularis. We use this multi-atlas dataset to evaluate two automated methods in terms of accuracy, robustness and reliability in segmenting brain structures on MRI and extracting regional PET measures. Twelve individual Macaca fascicularis high-resolution 3DT1 MR images were acquired. Four individual atlases were created by manually drawing 42 anatomical structures, including cortical and sub-cortical structures, white matter regions, and ventricles. To create the MRI template, we first chose one MRI to define a reference space, and then performed a two-step iterative procedure: affine registration of individual MRIs to the reference MRI, followed by averaging of the twelve resampled MRIs. Automated segmentation in native space was obtained in two ways: 1) Maximum probability atlases were created by decision fusion of two to four individual atlases in the reference space, and transformation back into the individual native space (MAXPROB)(.) 2) One to four individual atlases were registered directly to the individual native space, and combined by decision fusion (PROPAG). Accuracy was evaluated by computing the Dice similarity index and the volume difference. The robustness and reproducibility of PET regional measurements obtained via automated segmentation was evaluated on four co-registered MRI/PET datasets, which included test-retest data. Dice indices were always over 0.7 and reached maximal values of 0.9 for PROPAG with all four individual atlases. There was no significant mean volume bias. The standard deviation of the bias decreased significantly when increasing the number of individual atlases. MAXPROB performed better when increasing the number of atlases used. When all four atlases were used for the MAXPROB creation, the accuracy of morphometric segmentation approached that of the PROPAG method. PET measures extracted either via automatic methods or via the manually defined regions were strongly correlated, with no significant regional differences between methods. Intra-class correlation coefficients for test-retest data were over 0.87. Compared to single atlas extractions, multi-atlas methods improve the accuracy of region definition. They also perform comparably to manually defined regions for PET quantification. Multiple atlases of Macaca fascicularis brains are now available and allow reproducible and simplified analyses. Copyright © 2013 Elsevier Inc. All rights reserved.

Multiprotocol MR image segmentation in multiple sclerosis: experience with over 1000 studies

NASA Astrophysics Data System (ADS)

Udupa, Jayaram K.; Nyul, Laszlo G.; Ge, Yulin; Grossman, Robert I.

2000-06-01

Multiple Sclerosis (MS) is an acquired disease of the central nervous system. Subjective cognitive and ambulatory test scores on a scale called EDSS are currently utilized to assess the disease severity. Various MRI protocols are being investigated to study the disease based on how it manifests itself in the images. In an attempt to eventually replace EDSS by an objective measure to assess the natural course of the disease and its response to therapy, we have developed image segmentation methods based on fuzzy connectedness to quantify various objects in multiprotocol MRI. These include the macroscopic objects such as lesions, the gray matter (GM), white matter (WM), cerebrospinal fluid (CSF), and brain parenchyma as well as the microscopic aspects of the diseased WM. Over 1000 studies have been processed to date. By far the strongest correlations with the clinical measures were demonstrated by the Magnetization Transfer Ratio (MTR) histogram parameters obtained for the various segmented tissue regions emphasizing the importance of considering the microscopic/diffused nature of the disease in the individual tissue regions. Brain parenchymal volume also demonstrated a strong correlation with the clinical measures indicating that brain atrophy is an important indicator of the disease. Fuzzy connectedness is a viable segmentation method for studying MS.

MRI-Based Measurement of Brain Stem Cross-Sectional Area in Relapsing-Remitting Multiple Sclerosis.

PubMed

Chivers, Tomos R; Constantinescu, Cris S; Tench, Christopher R

2015-01-01

To determine if patients with relapsing-remitting multiple sclerosis (RRMS) have a reduced brain stem cross-sectional area (CSA) compared to age- and sex-matched controls. The brain stem is a common site of involvement in MS. However, relatively few imaging studies have investigated brain stem atrophy. Brain magnetic resonance imaging (MRI) was performed on patients and controls using a 1.5T MRI scanner with a quadrature head coil. Three-dimensional magnetization-prepared rapid acquisition gradient-echo (MPRAGE) images with 128 contiguous slices, covering the whole brain and brain stem and a T2-weighted image with 3 mm transverse contiguous images were acquired. We measured the brain stem CSA at three sites, the midbrain, the pons, and the medulla oblongata in 35 RRMS patients and 35 controls using a semiautomated algorithm. CSA readings were normalized using the total external cranial volume to reduce normal population variance and increase statistical power. A significant CSA reduction was found in the midbrain (P ≤ .001), pons (P ≤ .001), and the medulla oblongata (P = .047) postnormalization. A CSA reduction of 9.3% was found in the midbrain, 8.7% in the pons, and 6.5% in the medulla oblongata. A significantly reduced, normalized brain stem CSA was detected in all areas of the brain stem of the RRMS patients, when compared to age- and gender-matched controls. Lack of detectable upper cervical cord atrophy in the same patients suggests some independence of the MS pathology in these regions. Copyright © 2015 by the American Society of Neuroimaging.

Theta and Alpha Oscillations in Attentional Interaction during Distracted Driving

PubMed Central

Wang, Yu-Kai; Jung, Tzyy-Ping; Lin, Chin-Teng

2018-01-01

Performing multiple tasks simultaneously usually affects the behavioral performance as compared with executing the single task. Moreover, processing multiple tasks simultaneously often involve more cognitive demands. Two visual tasks, lane-keeping task and mental calculation, were utilized to assess the brain dynamics through 32-channel electroencephalogram (EEG) recorded from 14 participants. A 400-ms stimulus onset asynchrony (SOA) factor was used to induce distinct levels of attentional requirements. In the dual-task conditions, the deteriorated behavior reflected the divided attention and the overlapping brain resources used. The frontal, parietal and occipital components were decomposed by independent component analysis (ICA) algorithm. The event- and response-related theta and alpha oscillations in selected brain regions were investigated first. The increased theta oscillation in frontal component and decreased alpha oscillations in parietal and occipital components reflect the cognitive demands and attentional requirements as executing the designed tasks. Furthermore, time-varying interactive over-additive (O-Add), additive (Add) and under-additive (U-Add) activations were explored and summarized through the comparison between the summation of the elicited spectral perturbations in two single-task conditions and the spectral perturbations in the dual task. Add and U-Add activations were observed while executing the dual tasks. U-Add theta and alpha activations dominated the posterior region in dual-task situations. Our results show that both deteriorated behaviors and interactive brain activations should be comprehensively considered for evaluating workload or attentional interaction precisely. PMID:29479310

The Relationship of Neurogenesis and Growth of Brain Regions to Song Learning

ERIC Educational Resources Information Center

Kirn, John R.

2010-01-01

Song learning, maintenance and production require coordinated activity across multiple auditory, sensory-motor, and neuromuscular structures. Telencephalic components of the sensory-motor circuitry are unique to avian species that engage in song learning. The song system shows protracted development that begins prior to hatching but continues well…

A Distributed Network for Social Cognition Enriched for Oxytocin Receptors

PubMed Central

Mitre, Mariela; Marlin, Bianca J.; Schiavo, Jennifer K.; Morina, Egzona; Norden, Samantha E.; Hackett, Troy A.; Aoki, Chiye J.

2016-01-01

Oxytocin is a neuropeptide important for social behaviors such as maternal care and parent–infant bonding. It is believed that oxytocin receptor signaling in the brain is critical for these behaviors, but it is unknown precisely when and where oxytocin receptors are expressed or which neural circuits are directly sensitive to oxytocin. To overcome this challenge, we generated specific antibodies to the mouse oxytocin receptor and examined receptor expression throughout the brain. We identified a distributed network of female mouse brain regions for maternal behaviors that are especially enriched for oxytocin receptors, including the piriform cortex, the left auditory cortex, and CA2 of the hippocampus. Electron microscopic analysis of the cerebral cortex revealed that oxytocin receptors were mainly expressed at synapses, as well as on axons and glial processes. Functionally, oxytocin transiently reduced synaptic inhibition in multiple brain regions and enabled long-term synaptic plasticity in the auditory cortex. Thus modulation of inhibition may be a general mechanism by which oxytocin can act throughout the brain to regulate parental behaviors and social cognition. SIGNIFICANCE STATEMENT Oxytocin is an important peptide hormone involved in maternal behavior and social cognition, but it has been unclear what elements of neural circuits express oxytocin receptors due to the paucity of suitable antibodies. Here, we developed new antibodies to the mouse oxytocin receptor. Oxytocin receptors were found in discrete brain regions and at cortical synapses for modulating excitatory-inhibitory balance and plasticity. These antibodies should be useful for future studies of oxytocin and social behavior. PMID:26911697

The Hierarchical Brain Network for Face Recognition

PubMed Central

Zhen, Zonglei; Fang, Huizhen; Liu, Jia

2013-01-01

Numerous functional magnetic resonance imaging (fMRI) studies have identified multiple cortical regions that are involved in face processing in the human brain. However, few studies have characterized the face-processing network as a functioning whole. In this study, we used fMRI to identify face-selective regions in the entire brain and then explore the hierarchical structure of the face-processing network by analyzing functional connectivity among these regions. We identified twenty-five regions mainly in the occipital, temporal and frontal cortex that showed a reliable response selective to faces (versus objects) across participants and across scan sessions. Furthermore, these regions were clustered into three relatively independent sub-networks in a face-recognition task on the basis of the strength of functional connectivity among them. The functionality of the sub-networks likely corresponds to the recognition of individual identity, retrieval of semantic knowledge and representation of emotional information. Interestingly, when the task was switched to object recognition from face recognition, the functional connectivity between the inferior occipital gyrus and the rest of the face-selective regions were significantly reduced, suggesting that this region may serve as an entry node in the face-processing network. In sum, our study provides empirical evidence for cognitive and neural models of face recognition and helps elucidate the neural mechanisms underlying face recognition at the network level. PMID:23527282

Repairing the brain with physical exercise: Cortical thickness and brain volume increases in long-term pediatric brain tumor survivors in response to a structured exercise intervention.

PubMed

Szulc-Lerch, Kamila U; Timmons, Brian W; Bouffet, Eric; Laughlin, Suzanne; de Medeiros, Cynthia B; Skocic, Jovanka; Lerch, Jason P; Mabbott, Donald J

2018-01-01

There is growing evidence that exercise induced experience dependent plasticity may foster structural and functional recovery following brain injury. We examined the efficacy of exercise training for neural and cognitive recovery in long-term pediatric brain tumor survivors treated with radiation. We conducted a controlled clinical trial with crossover of exercise training (vs. no training) in a volunteer sample of 28 children treated with cranial radiation for brain tumors (mean age = 11.5 yrs.; mean time since diagnosis = 5.7 yrs). The endpoints were anatomical T1 MRI data and multiple behavioral outcomes presenting a broader analysis of structural MRI data across the entire brain. This included an analysis of changes in cortical thickness and brain volume using automated, user unbiased approaches. A series of general linear mixed effects models evaluating the effects of exercise training on cortical thickness were performed in a voxel and vertex-wise manner, as well as for specific regions of interest. In exploratory analyses, we evaluated the relationship between changes in cortical thickness after exercise with multiple behavioral outcomes, as well as the relation of these measures at baseline. Exercise was associated with increases in cortical thickness within the right pre and postcentral gyri. Other notable areas of increased thickness related to training were present in the left pre and postcentral gyri, left temporal pole, left superior temporal gyrus, and left parahippocampal gyrus. Further, we observed that compared to a separate cohort of healthy children, participants displayed multiple areas with a significantly thinner cortex prior to training and fewer differences following training, indicating amelioration of anatomical deficits. Partial least squares analysis (PLS) revealed specific patterns of relations between cortical thickness and various behavioral outcomes both after training and at baseline. Overall, our results indicate that exercise training in pediatric brain tumor patients treated with radiation has a beneficial impact on brain structure. We argue that exercise training should be incorporated into the development of neuro-rehabilitative treatments for long-term pediatric brain tumor survivors and other populations with acquired brain injury. (ClinicalTrials.gov, NCT01944761).

Brain Regions Associated With Internalizing and Externalizing Psychiatric Symptoms in Patients With Penetrating Traumatic Brain Injury.

PubMed

Huey, Edward D; Lee, Seonjoo; Lieberman, Jeffrey A; Devanand, D P; Brickman, Adam M; Raymont, Vanessa; Krueger, Frank; Grafman, Jordan

2016-01-01

A factor structure underlying DSM-IV diagnoses has been previously reported in neurologically intact patients. The authors determined the brain regions associated with factors underlying DSM-IV diagnoses and compared the ability of DSM-IV diagnoses, factor scores, and self-report measures to account for the neuroanatomical findings in patients with penetrating brain injuries. This prospective cohort study included 254 Vietnam War veterans: 199 with penetrating brain injuries and 55 matched control participants. Measures include DSM-IV diagnoses (from a Structured Clinical Interview for DSM), self-report measures of depression and anxiety, and CT scans. Factors underlying DSM-IV diagnoses were determined using an exploratory factor analysis and correlated with percent of brain regions affected. The ability of the factor scores, DSM-IV diagnoses, and the self-report psychiatric measures to account for the anatomical variance was compared with multiple regressions. Internalizing and externalizing factors were identified in these brain-injured patients. Damage to the left amygdala and bilateral basal ganglia was associated with lower internalizing factor scores, and damage to the left medial orbitofrontal cortex (OFC) with higher, and bilateral hippocampi with lower, externalizing factor scores. Factor scores best predicted left amygdala and bilateral hippocampal involvement, whereas DSM-IV diagnoses best predicted bilateral basal ganglia and left OFC involvement. Damage to the limbic areas involved in the processing of emotional and reward information, including structures involved in the National Institute of Mental Health's Research Domain Criteria Negative Valence Domain, influences the development of internalizing and externalizing psychiatric symptoms. Self-report measures underperformed DSM-IV and factor scores in predicting neuroanatomical findings.

Mapping human temporal and parietal neuronal population activity and functional coupling during mathematical cognition

PubMed Central

Daitch, Amy L.; Foster, Brett L.; Schrouff, Jessica; Rangarajan, Vinitha; Kaşikçi, Itır; Gattas, Sandra; Parvizi, Josef

2016-01-01

Brain areas within the lateral parietal cortex (LPC) and ventral temporal cortex (VTC) have been shown to code for abstract quantity representations and for symbolic numerical representations, respectively. To explore the fast dynamics of activity within each region and the interaction between them, we used electrocorticography recordings from 16 neurosurgical subjects implanted with grids of electrodes over these two regions and tracked the activity within and between the regions as subjects performed three different numerical tasks. Although our results reconfirm the presence of math-selective hubs within the VTC and LPC, we report here a remarkable heterogeneity of neural responses within each region at both millimeter and millisecond scales. Moreover, we show that the heterogeneity of response profiles within each hub mirrors the distinct patterns of functional coupling between them. Our results support the existence of multiple bidirectional functional loops operating between discrete populations of neurons within the VTC and LPC during the visual processing of numerals and the performance of arithmetic functions. These findings reveal information about the dynamics of numerical processing in the brain and also provide insight into the fine-grained functional architecture and connectivity within the human brain. PMID:27821758

Brain noise is task dependent and region specific.

PubMed

Misić, Bratislav; Mills, Travis; Taylor, Margot J; McIntosh, Anthony R

2010-11-01

The emerging organization of anatomical and functional connections during human brain development is thought to facilitate global integration of information. Recent empirical and computational studies have shown that this enhanced capacity for information processing enables a diversified dynamic repertoire that manifests in neural activity as irregularity and noise. However, transient functional networks unfold over multiple time, scales and the embedding of a particular region depends not only on development, but also on the manner in which sensory and cognitive systems are engaged. Here we show that noise is a facet of neural activity that is also sensitive to the task context and is highly region specific. Children (6-16 yr) and adults (20-41 yr) performed a one-back face recognition task with inverted and upright faces. Neuromagnetic activity was estimated at several hundred sources in the brain by applying a beamforming technique to the magnetoencephalogram (MEG). During development, neural activity became more variable across the whole brain, with most robust increases in medial parietal regions, such as the precuneus and posterior cingulate cortex. For young children and adults, activity evoked by upright faces was more variable and noisy compared with inverted faces, and this effect was reliable only in the right fusiform gyrus. These results are consistent with the notion that upright faces engender a variety of integrative neural computations, such as the relations among facial features and their holistic constitution. This study shows that transient changes in functional integration modulated by task demand are evident in the variability of regional neural activity.

Structural growth trajectories and rates of change in the first 3 months of infant brain development.

PubMed

Holland, Dominic; Chang, Linda; Ernst, Thomas M; Curran, Megan; Buchthal, Steven D; Alicata, Daniel; Skranes, Jon; Johansen, Heather; Hernandez, Antonette; Yamakawa, Robyn; Kuperman, Joshua M; Dale, Anders M

2014-10-01

The very early postnatal period witnesses extraordinary rates of growth, but structural brain development in this period has largely not been explored longitudinally. Such assessment may be key in detecting and treating the earliest signs of neurodevelopmental disorders. To assess structural growth trajectories and rates of change in the whole brain and regions of interest in infants during the first 3 months after birth. Serial structural T1-weighted and/or T2-weighted magnetic resonance images were obtained for 211 time points from 87 healthy term-born or term-equivalent preterm-born infants, aged 2 to 90 days, between October 5, 2007, and June 12, 2013. We segmented whole-brain and multiple subcortical regions of interest using a novel application of Bayesian-based methods. We modeled growth and rate of growth trajectories nonparametrically and assessed left-right asymmetries and sexual dimorphisms. Whole-brain volume at birth was approximately one-third of healthy elderly brain volume, and did not differ significantly between male and female infants (347 388 mm3 and 335 509 mm3, respectively, P = .12). The growth rate was approximately 1%/d, slowing to 0.4%/d by the end of the first 3 months, when the brain reached just more than half of elderly adult brain volume. Overall growth in the first 90 days was 64%. There was a significant age-by-sex effect leading to widening separation in brain sizes with age between male and female infants (with male infants growing faster than females by 200.4 mm3/d, SE = 67.2, P = .003). Longer gestation was associated with larger brain size (2215 mm3/d, SE = 284, P = 4×10-13). The expected brain size of an infant born one week earlier than average was 5% smaller than average; at 90 days it will not have caught up, being 2% smaller than average. The cerebellum grew at the highest rate, more than doubling in 90 days, and the hippocampus grew at the slowest rate, increasing by 47% in 90 days. There was left-right asymmetry in multiple regions of interest, particularly the lateral ventricles where the left was larger than the right by 462 mm3 on average (approximately 5% of lateral ventricular volume at 2 months). We calculated volume-by-age percentile plots for assessing individual development. Normative trajectories for early postnatal brain structural development can be determined from magnetic resonance imaging and could be used to improve the detection of deviant maturational patterns indicative of neurodevelopmental disorders.

Structural Growth Trajectories and Rates of Change in the First 3 Months of Infant Brain Development

PubMed Central

Holland, Dominic; Chang, Linda; Ernst, Thomas M.; Curran, Megan; Buchthal, Steven D.; Alicata, Daniel; Skranes, Jon; Johansen, Heather; Hernandez, Antonette; Yamakawa, Robyn; Kuperman, Joshua M.; Dale, Anders M.

2016-01-01

IMPORTANCE The very early postnatal period witnesses extraordinary rates of growth, but structural brain development in this period has largely not been explored longitudinally. Such assessment may be key in detecting and treating the earliest signs of neurodevelopmental disorders. OBJECTIVE To assess structural growth trajectories and rates of change in the whole brain and regions of interest in infants during the first 3 months after birth. DESIGN, SETTING, AND PARTICIPANTS Serial structural T1-weighted and/or T2-weighted magnetic resonance images were obtained for 211 time points from 87 healthy term-born or term-equivalent preterm-born infants, aged 2 to 90 days, between October 5, 2007, and June 12, 2013. MAIN OUTCOMES AND MEASURES We segmented whole-brain and multiple subcortical regions of interest using a novel application of Bayesian-based methods. We modeled growth and rate of growth trajectories nonparametrically and assessed left-right asymmetries and sexual dimorphisms. RESULTS Whole-brain volume at birth was approximately one-third of healthy elderly brain volume, and did not differ significantly between male and female infants (347 388 mm3 and 335 509 mm3, respectively, P = .12). The growth rate was approximately 1%/d, slowing to 0.4%/d by the end of the first 3 months, when the brain reached just more than half of elderly adult brain volume. Overall growth in the first 90 days was 64%. There was a significant age-by-sex effect leading to widening separation in brain sizes with age between male and female infants (with male infants growing faster than females by 200.4 mm3/d, SE = 67.2, P = .003). Longer gestation was associated with larger brain size (2215 mm3/d, SE = 284, P = 4×10−13). The expected brain size of an infant born one week earlier than average was 5% smaller than average; at 90 days it will not have caught up, being 2% smaller than average. The cerebellum grew at the highest rate, more than doubling in 90 days, and the hippocampus grew at the slowest rate, increasing by 47% in 90 days. There was left-right asymmetry in multiple regions of interest, particularly the lateral ventricles where the left was larger than the right by 462 mm3 on average (approximately 5% of lateral ventricular volume at 2 months). We calculated volume-by-age percentile plots for assessing individual development. CONCLUSIONS AND RELEVANCE Normative trajectories for early postnatal brain structural development can be determined from magnetic resonance imaging and could be used to improve the detection of deviant maturational patterns indicative of neurodevelopmental disorders. PMID:25111045

Imaging deductive reasoning and the new paradigm

PubMed Central

Oaksford, Mike

2015-01-01

There has been a great expansion of research into human reasoning at all of Marr’s explanatory levels. There is a tendency for this work to progress within a level largely ignoring the others which can lead to slippage between levels (Chater et al., 2003). It is argued that recent brain imaging research on deductive reasoning—implementational level—has largely ignored the new paradigm in reasoning—computational level (Over, 2009). Consequently, recent imaging results are reviewed with the focus on how they relate to the new paradigm. The imaging results are drawn primarily from a recent meta-analysis by Prado et al. (2011) but further imaging results are also reviewed where relevant. Three main observations are made. First, the main function of the core brain region identified is most likely elaborative, defeasible reasoning not deductive reasoning. Second, the subtraction methodology and the meta-analytic approach may remove all traces of content specific System 1 processes thought to underpin much human reasoning. Third, interpreting the function of the brain regions activated by a task depends on theories of the function that a task engages. When there are multiple interpretations of that function, interpreting what an active brain region is doing is not clear cut. It is concluded that there is a need to more tightly connect brain activation to function, which could be achieved using formalized computational level models and a parametric variation approach. PMID:25774130

Repeated exposure to sublethal doses of the organophosphorus compound VX activates BDNF expression in mouse brain.

PubMed

Pizarro, Jose M; Chang, Wenling E; Bah, Mariama J; Wright, Linnzi K M; Saviolakis, George A; Alagappan, Arun; Robison, Christopher L; Shah, Jinesh D; Meyerhoff, James L; Cerasoli, Douglas M; Midboe, Eric G; Lumley, Lucille A

2012-04-01

The highly toxic organophosphorus compound VX [O-ethyl S-[2-(diisopropylamino)ethyl]methylphosphonate] is an irreversible inhibitor of the enzyme acetylcholinesterase (AChE). Prolonged inhibition of AChE increases endogenous levels of acetylcholine and is toxic at nerve synapses and neuromuscular junctions. We hypothesized that repeated exposure to sublethal doses of VX would affect genes associated with cell survival, neuronal plasticity, and neuronal remodeling, including brain-derived neurotrophic factor (BDNF). We examined the time course of BDNF expression in C57BL/6 mouse brain following repeated exposure (1/day × 5 days/week × 2 weeks) to sublethal doses of VX (0.2 LD(50) and 0.4 LD(50)). BDNF messenger RNA expression was significantly (p < 0.05) elevated in multiple brain regions, including the dentate gyrus, CA3, and CA1 regions of the hippocampal formation, as well as the piriform cortex, hypothalamus, amygdala, and thalamus, 72 h after the last 0.4 LD(50) VX exposure. BDNF protein expression, however, was only increased in the CA3 region of the hippocampus. Whether increased BDNF in response to sublethal doses of VX exposure is an adaptive response to prevent cellular damage or a precursor to impending brain damage remains to be determined. If elevated BDNF is an adaptive response, exogenous BDNF may be a potential therapeutic target to reduce the toxic effects of nerve agent exposure.

[Resting-state functional magnetic resonance study of brain function changes after TIPS operation in patients with liver cirrhosis].

PubMed

Liu, C; Wang, H B; Yu, Y Q; Wang, M Q; Zhang, G B; Xu, L Y; Wu, J M

2016-12-20

Objective: To investigate the brain function changes in cirrhosis patients after transjugular intrahepatic portosystemic shunt (TIPS), resting-state functional MRI (rs-fMRI) performed and fractional amplitude of low frequency fluctuation (fALFF) was analyzed. Methods: From January 2014 to February 2016, a total of 96 cirrhotic patients from invasive technology department and infection department in the First Affiliated Hospital of Anhui Medical University were selected , the blood ammonia data of 96 cirrhotic patients with TIPS operation in four groups were collected after 1, 3, 6 and 12 month, and all subjects performed rs-fMRI scans. The rs-fMRI data processed with DPARSF and SPM12 softwares, whole-brain fALFF values were calculated, and One-Way analysis of variance , multiple comparison analysis and correlation analysis were performed. Results: There were brain regions with significant function changes in four groups patients with TIPS operation after 1, 3, 6 and 12 month, including bilateral superior temporal gyrus, right middle temportal gyrus , right hippocampus, right island of inferior frontal gyrus, left fusiform gyrus, left olfactory cortex, left orbital superior frontal gyrus (all P <0.005). Multiple comparison analysis showed that compared with patients in the 1-month follow-up, patients in the 3-month follow-up showed that brain function areas increased in left olfactory cortex, left inferior temporal gyrus, left fusiform gyrus, left orbital middle frontal gyrus, left putamen, left cerebelum, and decreased in left lingual gyrus; patients in the 6-month follow-up showed that brain function areas increased in left middle temportal gyrus, right supramarginal gyrus, right temporal pole, right central operculum, and decreased in left top edge of angular gyrus, left postcentral gyrus; patients in the 12-month follow-up showed that brain function areas increased in right hippocampus, right middle cingulate gyrus, and decreased in right middle temportal gyrus.Compared with patients in the 3-month follow-up, patients in the 6-month follow-up showed that brain function areas increased in left superior temporal gyrus, left middle temporal gyrus, right temporal pole, right island of inferior frontal gyrus, and decreased in left cerebelum, left orbital inferior frontal gyrus; patients in the 12-month follow-up showed that there were no obvious increase and decrease brain function areas.Compared with patients in the 6-month follow-up, patients in the 12-month follow-up showed that there were no obvious increase brain function areas , but brain function areas decreased in bilateral middle temportal gyrus( P <0.001). Brain regions were positively related to blood ammonia in right middle cingulate gyrus, right central operculum, left parahippocampal gyrus, while as brain regions were negatively related to blood ammonia in bilateral medial prefrontal lobe, anterior cingulate and paracingulate gyrus, right top edge of angular gyrus, right middle temportal gyrus, left anterior central gyrus, left posterior central gyrus (all P <0.005). Conclusion: The resting state brain function increased or decreased with course of disease in cirrhosis patients after TIPS operation. The brain activity of limbic system and sensorimotor system all had significant correlation with blood ammonia levels. The blood ammonia level and the function of relative brain regions after 6-month with TIPS operation can be gradually improved.

Sex Differences in Gray Matter Changes and Brain-Behavior Relationships in Patients with Stimulant Dependence.

PubMed

Regner, Michael F; Dalwani, Manish; Yamamoto, Dorothy; Perry, Robert I; Sakai, Joseph T; Honce, Justin M; Tanabe, Jody

2015-12-01

To investigate whether sex modulates the effects of stimulant dependence on gray matter volume (GMV) in patients who have achieved long-term abstinence and to characterize how sex modulates GMV according to specific behavioral measures, such as dependence symptom count, behavioral approach, and impulsivity. Colorado Multiple Institutional Review Board approval and informed consent were obtained. In this prospective parallel group study, 127 age- and sex-matched participants (68 control subjects [28 women, 40 men] and 59 patients with stimulant dependence [28 women, 31 men]) underwent T1-weighted spoiled gradient-echo inversion recovery magnetic resonance imaging of the brain at 3 T. Images were segmented by using voxel-based morphometric software. After adjustment for age, education, and head size, the effects of group according to sex on GMV and main effects were analyzed throughout the whole brain by using an analysis of covariance family-wise cluster corrected for multiple comparisons, with a threshold P value of less than .05. Dependence symptom count and behavioral measurements were correlated with GMV in the whole brain and in five a priori regions of interest. The effects of group according to sex on GMV were significant in numerous regions (P < .001). Compared with female control subjects, women with stimulant dependence had significantly lower GMV in widespread brain regions (P < .001). There were no significant differences in GMV between male control subjects and men with stimulant dependence (P = .625). Dependence symptom count negatively correlated with GMV in the nucleus accumbens in women (left: r = -0.364, P = .047; right: r = -0.407, P = .031) but not in men (left: r = -0.063, P = .737; right: r = -0.174, P = .349). Behavioral approach (P = .002) and impulsivity (P = .013) correlated negatively with frontal and temporal GMV changes in women with stimulant dependence but not in the other groups. Vast changes in GMV were observed in women with stimulant dependence after prolonged abstinence, but were not observed in men. Sexual dimorphism in drug-related neuroanatomic changes and brain-behavior relationships may be mechanisms underlying the difference in clinical profiles of addiction between women and men.

Hindbrain regional growth in preterm newborns and its impairment in relation to brain injury.

PubMed

Kim, Hosung; Gano, Dawn; Ho, Mai-Lan; Guo, Xiaoyue M; Unzueta, Alisa; Hess, Christopher; Ferriero, Donna M; Xu, Duan; Barkovich, A James

2016-02-01

Premature birth globally affects about 11.1% of all newborns and is a risk factor for neurodevelopmental disability in surviving infants. Histology has suggested that hindbrain subdivisions grow differentially, especially in the third trimester. Prematurity-related brain injuries occurring in this period may selectively affect more rapidly developing areas of hindbrain, thus accompanying region-specific impairments in growth and ultimately neurodevelopmental deficits. The current study aimed to quantify regional growth of the cerebellum and the brainstem in preterm neonates (n = 65 with individually multiple scans). We probed associations of the regional volumes with severity of brain injury. In neonates with no imaging evidence of injury, our analysis using a mixed-effect linear model showed faster growth in the pons and the lateral convexity of anterior/posterior cerebellar lobes. Different patterns of growth impairment were found in relation to early cerebral intraventricular hemorrhage and cerebellar hemorrhage (P < 0.05), likely explaining different mechanisms through which neurogenesis is disrupted. The pattern of cerebellar growth identified in our study agreed excellently with details of cerebellar morphogenesis in perinatal development, which has only been observed in histological data. Our proposed analytic framework may provide predictive imaging biomarkers for neurodevelopmental outcome, enabling early identification and treatment of high-risk patients. Hum Brain Mapp 37:678-688, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Intrajugular Vein Delivery of AAV9-RNAi Prevents Neuropathological Changes and Weight Loss in Huntington's Disease Mice

PubMed Central

Dufour, Brett D; Smith, Catherine A; Clark, Randall L; Walker, Timothy R; McBride, Jodi L

2014-01-01

Huntington's disease (HD) is a fatal neurological disorder caused by a CAG repeat expansion in the HTT gene, which encodes a mutant huntingtin protein (mHTT). The mutation confers a toxic gain of function on huntingtin, leading to widespread neurodegeneration and inclusion formation in many brain regions. Although the hallmark symptom of HD is hyperkinesia stemming from striatal degeneration, several other brain regions are affected which cause psychiatric, cognitive, and metabolic symptoms. Additionally, mHTT expression in peripheral tissue is associated with skeletal muscle atrophy, cardiac failure, weight loss, and diabetes. We, and others, have demonstrated a prevention of motor symptoms in HD mice following direct striatal injection of adeno-associated viral vector (AAV) serotype 1 encoding an RNA interference (RNAi) construct targeting mutant HTT mRNA (mHTT). Here, we expand these efforts and demonstrate that an intrajugular vein injection of AAV serotype 9 (AAV9) expressing a mutant HTT-specific RNAi construct significantly reduced mHTT expression in multiple brain regions and peripheral tissues affected in HD. Correspondingly, this approach prevented atrophy and inclusion formation in key brain regions as well as the severe weight loss germane to HD transgenic mice. These results demonstrate that systemic delivery of AAV9-RNAi may provide more widespread clinical benefit for patients suffering from HD. PMID:24390280

Brain Bases of Morphological Processing in Young Children

PubMed Central

Arredondo, Maria M.; Ip, Ka I; Hsu, Lucy Shih-Ju; Tardif, Twila; Kovelman, Ioulia

2017-01-01

How does the developing brain support the transition from spoken language to print? Two spoken language abilities form the initial base of child literacy across languages: knowledge of language sounds (phonology) and knowledge of the smallest units that carry meaning (morphology). While phonology has received much attention from the field, the brain mechanisms that support morphological competence for learning to read remain largely unknown. In the present study, young English-speaking children completed an auditory morphological awareness task behaviorally (n = 69, ages 6–12) and in fMRI (n = 16). The data revealed two findings: First, children with better morphological abilities showed greater activation in left temporo-parietal regions previously thought to be important for supporting phonological reading skills, suggesting that this region supports multiple language abilities for successful reading acquisition. Second, children showed activation in left frontal regions previously found active in young Chinese readers, suggesting morphological processes for reading acquisition might be similar across languages. These findings offer new insights for developing a comprehensive model of how spoken language abilities support children’s reading acquisition across languages. PMID:25930011

Superior temporal sulcus--It's my area: or is it?

PubMed

Hein, Grit; Knight, Robert T

2008-12-01

The superior temporal sulcus (STS) is the chameleon of the human brain. Several research areas claim the STS as the host brain region for their particular behavior of interest. Some see it as one of the core structures for theory of mind. For others, it is the main region for audiovisual integration. It plays an important role in biological motion perception, but is also claimed to be essential for speech processing and processing of faces. We review the foci of activations in the STS from multiple functional magnetic resonance imaging studies, focusing on theory of mind, audiovisual integration, motion processing, speech processing, and face processing. The results indicate a differentiation of the STS region in an anterior portion, mainly involved in speech processing, and a posterior portion recruited by cognitive demands of all these different research areas. The latter finding argues against a strict functional subdivision of the STS. In line with anatomical evidence from tracer studies, we propose that the function of the STS varies depending on the nature of network coactivations with different regions in the frontal cortex and medial-temporal lobe. This view is more in keeping with the notion that the same brain region can support different cognitive operations depending on task-dependent network connections, emphasizing the role of network connectivity analysis in neuroimaging.

Histogram analysis of ADC in brain tumor patients

NASA Astrophysics Data System (ADS)

Banerjee, Debrup; Wang, Jihong; Li, Jiang

2011-03-01

At various stage of progression, most brain tumors are not homogenous. In this presentation, we retrospectively studied the distribution of ADC values inside tumor volume during the course of tumor treatment and progression for a selective group of patients who underwent an anti-VEGF trial. Complete MRI studies were obtained for this selected group of patients including pre- and multiple follow-up, post-treatment imaging studies. In each MRI imaging study, multiple scan series were obtained as a standard protocol which includes T1, T2, T1-post contrast, FLAIR and DTI derived images (ADC, FA etc.) for each visit. All scan series (T1, T2, FLAIR, post-contrast T1) were registered to the corresponding DTI scan at patient's first visit. Conventionally, hyper-intensity regions on T1-post contrast images are believed to represent the core tumor region while regions highlighted by FLAIR may overestimate tumor size. Thus we annotated tumor regions on the T1-post contrast scans and ADC intensity values for pixels were extracted inside tumor regions as defined on T1-post scans. We fit a mixture Gaussian (MG) model for the extracted pixels using the Expectation-Maximization (EM) algorithm, which produced a set of parameters (mean, various and mixture coefficients) for the MG model. This procedure was performed for each visits resulting in a series of GM parameters. We studied the parameters fitted for ADC and see if they can be used as indicators for tumor progression. Additionally, we studied the ADC characteristics in the peri-tumoral region as identified by hyper-intensity on FLAIR scans. The results show that ADC histogram analysis of the tumor region supports the two compartment model that suggests the low ADC value subregion corresponding to densely packed cancer cell while the higher ADC value region corresponding to a mixture of viable and necrotic cells with superimposed edema. Careful studies of the composition and relative volume of the two compartments in tumor region may provide some insights in the early assessment of tumor response to therapy for recurrence brain cancer patients.

The Brain Circuitry Underlying the Temporal Evolution of Nausea in Humans

PubMed Central

Sheehan, James D.; Kim, Jieun; LaCount, Lauren T.; Park, Kyungmo; Kaptchuk, Ted J.; Rosen, Bruce R.; Kuo, Braden

2013-01-01

Nausea is a universal human experience. It evolves slowly over time, and brain mechanisms underlying this evolution are not well understood. Our functional magnetic resonance imaging (fMRI) approach evaluated brain activity contributing to and arising from increasing motion sickness. Subjects rated transitions to increasing nausea, produced by visually induced vection within the fMRI environment. We evaluated parametrically increasing brain activity 1) precipitating increasing nausea and 2) following transition to stronger nausea. All subjects demonstrated visual stimulus–associated activation (P < 0.01) in primary and extrastriate visual cortices. In subjects experiencing motion sickness, increasing phasic activity preceding nausea was found in amygdala, putamen, and dorsal pons/locus ceruleus. Increasing sustained response following increased nausea was found in a broader network including insular, anterior cingulate, orbitofrontal, somatosensory and prefrontal cortices. Moreover, sustained anterior insula activation to strong nausea was correlated with midcingulate activation (r = 0.87), suggesting a closer linkage between these specific regions within the brain circuitry subserving nausea perception. Thus, while phasic activation in fear conditioning and noradrenergic brainstem regions precipitates transition to strong nausea, sustained activation following this transition occurs in a broader interoceptive, limbic, somatosensory, and cognitive network, reflecting the multiple dimensions of this aversive commonly occurring symptom. PMID:22473843

The brain circuitry underlying the temporal evolution of nausea in humans.

PubMed

Napadow, Vitaly; Sheehan, James D; Kim, Jieun; Lacount, Lauren T; Park, Kyungmo; Kaptchuk, Ted J; Rosen, Bruce R; Kuo, Braden

2013-04-01

Nausea is a universal human experience. It evolves slowly over time, and brain mechanisms underlying this evolution are not well understood. Our functional magnetic resonance imaging (fMRI) approach evaluated brain activity contributing to and arising from increasing motion sickness. Subjects rated transitions to increasing nausea, produced by visually induced vection within the fMRI environment. We evaluated parametrically increasing brain activity 1) precipitating increasing nausea and 2) following transition to stronger nausea. All subjects demonstrated visual stimulus-associated activation (P < 0.01) in primary and extrastriate visual cortices. In subjects experiencing motion sickness, increasing phasic activity preceding nausea was found in amygdala, putamen, and dorsal pons/locus ceruleus. Increasing sustained response following increased nausea was found in a broader network including insular, anterior cingulate, orbitofrontal, somatosensory and prefrontal cortices. Moreover, sustained anterior insula activation to strong nausea was correlated with midcingulate activation (r = 0.87), suggesting a closer linkage between these specific regions within the brain circuitry subserving nausea perception. Thus, while phasic activation in fear conditioning and noradrenergic brainstem regions precipitates transition to strong nausea, sustained activation following this transition occurs in a broader interoceptive, limbic, somatosensory, and cognitive network, reflecting the multiple dimensions of this aversive commonly occurring symptom.

A network approach for modulating memory processes via direct and indirect brain stimulation: Toward a causal approach for the neural basis of memory.

PubMed

Kim, Kamin; Ekstrom, Arne D; Tandon, Nitin

2016-10-01

Electrical stimulation of the brain is a unique tool to perturb endogenous neural signals, allowing us to evaluate the necessity of given neural processes to cognitive processing. An important issue, gaining increasing interest in the literature, is whether and how stimulation can be employed to selectively improve or disrupt declarative memory processes. Here, we provide a comprehensive review of both invasive and non-invasive stimulation studies aimed at modulating memory performance. The majority of past studies suggest that invasive stimulation of the hippocampus impairs memory performance; similarly, most non-invasive studies show that disrupting frontal or parietal regions also impairs memory performance, suggesting that these regions also play necessary roles in declarative memory. On the other hand, a handful of both invasive and non-invasive studies have also suggested modest improvements in memory performance following stimulation. These studies typically target brain regions connected to the hippocampus or other memory "hubs," which may affect endogenous activity in connected areas like the hippocampus, suggesting that to augment declarative memory, altering the broader endogenous memory network activity is critical. Together, studies reporting memory improvements/impairments are consistent with the idea that a network of distinct brain "hubs" may be crucial for successful memory encoding and retrieval rather than a single primary hub such as the hippocampus. Thus, it is important to consider neurostimulation from the network perspective, rather than from a purely localizationalist viewpoint. We conclude by proposing a novel approach to neurostimulation for declarative memory modulation that aims to facilitate interactions between multiple brain "nodes" underlying memory rather than considering individual brain regions in isolation. Copyright © 2016. Published by Elsevier Inc.

Functional Connectivity Parcellation of the Human Thalamus by Independent Component Analysis.

PubMed

Zhang, Sheng; Li, Chiang-Shan R

2017-11-01

As a key structure to relay and integrate information, the thalamus supports multiple cognitive and affective functions through the connectivity between its subnuclei and cortical and subcortical regions. Although extant studies have largely described thalamic regional functions in anatomical terms, evidence accumulates to suggest a more complex picture of subareal activities and connectivities of the thalamus. In this study, we aimed to parcellate the thalamus and examine whole-brain connectivity of its functional clusters. With resting state functional magnetic resonance imaging data from 96 adults, we used independent component analysis (ICA) to parcellate the thalamus into 10 components. On the basis of the independence assumption, ICA helps to identify how subclusters overlap spatially. Whole brain functional connectivity of each subdivision was computed for independent component's time course (ICtc), which is a unique time series to represent an IC. For comparison, we computed seed-region-based functional connectivity using the averaged time course across all voxels within a thalamic subdivision. The results showed that, at p < 10 -6 , corrected, 49% of voxels on average overlapped among subdivisions. Compared with seed-region analysis, ICtc analysis revealed patterns of connectivity that were more distinguished between thalamic clusters. ICtc analysis demonstrated thalamic connectivity to the primary motor cortex, which has eluded the analysis as well as previous studies based on averaged time series, and clarified thalamic connectivity to the hippocampus, caudate nucleus, and precuneus. The new findings elucidate functional organization of the thalamus and suggest that ICA clustering in combination with ICtc rather than seed-region analysis better distinguishes whole-brain connectivities among functional clusters of a brain region.

Expanding the spectrum of neuronal pathology in multiple system atrophy

PubMed Central

Cykowski, Matthew D.; Coon, Elizabeth A.; Powell, Suzanne Z.; Jenkins, Sarah M.; Benarroch, Eduardo E.; Low, Phillip A.; Schmeichel, Ann M.

2015-01-01

Multiple system atrophy is a sporadic alpha-synucleinopathy that typically affects patients in their sixth decade of life and beyond. The defining clinical features of the disease include progressive autonomic failure, parkinsonism, and cerebellar ataxia leading to significant disability. Pathologically, multiple system atrophy is characterized by glial cytoplasmic inclusions containing filamentous alpha-synuclein. Neuronal inclusions also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 patients with multiple system atrophy (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of patients, not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. Neuronal inclusions also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of patients with multiple system atrophy, including a patient with visual hallucinations. Further, the presence of Lewy body-like inclusions in neocortex, but not hippocampal alpha-synuclein pathology, was associated with cognitive impairment (P = 0.002). However, several cases had the presence of isolated Lewy body-like inclusions at atypical sites (e.g. thalamus, deep cerebellar nuclei) that are not typical for Lewy body-spectrum disease. Finally, interregional correlations (rho ≥ 0.6) in pathologic glial and neuronal lesion burden suggest shared mechanisms of disease progression between both discrete anatomic regions (e.g. basal forebrain and hippocampus) and cell types (neuronal and glial inclusions in frontal cortex and white matter, respectively). These findings suggest that in addition to glial inclusions, neuronal pathology plays an important role in the developmental and progression of multiple system atrophy. See Halliday (doi:10.1093/brain/awv151) for a scientific commentary on this article. PMID:25981961

Brain tissues atrophy is not always the best structural biomarker of physiological aging: A multimodal cross-sectional study.

PubMed

Cherubini, Andrea; Caligiuri, Maria Eugenia; Péran, Patrice; Sabatini, Umberto; Cosentino, Carlo; Amato, Francesco

2015-01-01

This study presents a voxel-based multiple regression analysis of different magnetic resonance image modalities, including anatomical T1-weighted, T2* relaxometry, and diffusion tensor imaging. Quantitative parameters sensitive to complementary brain tissue alterations, including morphometric atrophy, mineralization, microstructural damage, and anisotropy loss, were compared in a linear physiological aging model in 140 healthy subjects (range 20-74 years). The performance of different predictors and the identification of the best biomarker of age-induced structural variation were compared without a priori anatomical knowledge. The best quantitative predictors in several brain regions were iron deposition and microstructural damage, rather than macroscopic tissue atrophy. Age variations were best resolved with a combination of markers, suggesting that multiple predictors better capture age-induced tissue alterations. These findings highlight the importance of a combined evaluation of multimodal biomarkers for the study of aging and point to a number of novel applications for the method described.

Do glutathione levels decline in aging human brain?

PubMed

Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

2016-04-01

For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

A multiparametric evaluation of regional brain damage in patients with primary progressive multiple sclerosis.

PubMed

Ceccarelli, Antonia; Rocca, Maria A; Valsasina, Paola; Rodegher, Mariaemma; Pagani, Elisabetta; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

2009-09-01

The purpose of this study is to define the topographical distribution of gray matter (GM) and white matter (WM) damage in patients with primary progressive multiple sclerosis (PPMS), using a multiparametric MR-based approach. Using a 3 Tesla scanner, dual-echo, 3D fast-field echo (FFE), and diffusion tensor (DT) MRI scans were acquired from 18 PPMS patients and 17 matched healthy volunteers. An optimized voxel-based (VB) analysis was used to investigate the patterns of regional GM density changes and to quantify GM and WM diffusivity alterations of the entire brain. In PPMS patients, GM atrophy was found in the thalami and the right insula, while mean diffusivity (MD) changes involved several cortical-subcortical structures in all cerebral lobes and the cerebellum. An overlap between decreased WM fractional anisotropy (FA) and increased WM MD was found in the corpus callosum, the cingulate gyrus, the left short temporal fibers, the right short frontal fibers, the optic radiations, and the middle cerebellar peduncles. Selective MD increase, not associated with FA decrease, was found in the internal capsules, the corticospinal tracts, the superior longitudinal fasciculi, the fronto-occipital fasciculi, and the right cerebral peduncle. A discrepancy was found between regional WM diffusivity changes and focal lesions because several areas had DT MRI abnormalities but did not harbor T2-visible lesions. Our study allowed to detect tissue damage in brain areas associated with motor and cognitive functions, which are known to be impaired in PPMS patients. Combining regional measures derived from different MR modalities may be a valuable tool to improve our understanding of PPMS pathophysiology. 2009 Wiley-Liss, Inc.

Mean cortical curvature reflects cytoarchitecture restructuring in mild traumatic brain injury

PubMed Central

King, Jace B.; Lopez-Larson, Melissa P.; Yurgelun-Todd, Deborah A.

2016-01-01

In the United States alone, the number of persons living with the enduring consequences of traumatic brain injuries is estimated to be between 3.2 and 5 million. This number does not include individuals serving in the United States military or seeking care at Veterans Affairs hospitals. The importance of understanding the neurobiological consequences of mild traumatic brain injury (mTBI) has increased with the return of veterans from conflicts overseas, many of who have suffered this type of brain injury. However, identifying the neuroanatomical regions most affected by mTBI continues to prove challenging. The aim of this study was to assess the use of mean cortical curvature as a potential indicator of progressive tissue loss in a cross-sectional sample of 54 veterans with mTBI compared to 31 controls evaluated with MRI. It was hypothesized that mean cortical curvature would be increased in veterans with mTBI, relative to controls, due in part to cortical restructuring related to tissue volume loss. Mean cortical curvature was assessed in 60 bilateral regions (31 sulcal, 29 gyral). Of the 120 regions investigated, nearly 50% demonstrated significantly increased mean cortical curvature in mTBI relative to controls with 25% remaining significant following multiple comparison correction (all, pFDR < .05). These differences were most prominent in deep gray matter regions of the cortex. Additionally, significant relationships were found between mean cortical curvature and gray and white matter volumes (all, p < .05). These findings suggest potentially unique patterns of atrophy by region and indicate that changes in brain microstructure due to mTBI are sensitive to measures of mean curvature. PMID:26909332

Mean cortical curvature reflects cytoarchitecture restructuring in mild traumatic brain injury.

PubMed

King, Jace B; Lopez-Larson, Melissa P; Yurgelun-Todd, Deborah A

2016-01-01

In the United States alone, the number of persons living with the enduring consequences of traumatic brain injuries is estimated to be between 3.2 and 5 million. This number does not include individuals serving in the United States military or seeking care at Veterans Affairs hospitals. The importance of understanding the neurobiological consequences of mild traumatic brain injury (mTBI) has increased with the return of veterans from conflicts overseas, many of who have suffered this type of brain injury. However, identifying the neuroanatomical regions most affected by mTBI continues to prove challenging. The aim of this study was to assess the use of mean cortical curvature as a potential indicator of progressive tissue loss in a cross-sectional sample of 54 veterans with mTBI compared to 31 controls evaluated with MRI. It was hypothesized that mean cortical curvature would be increased in veterans with mTBI, relative to controls, due in part to cortical restructuring related to tissue volume loss. Mean cortical curvature was assessed in 60 bilateral regions (31 sulcal, 29 gyral). Of the 120 regions investigated, nearly 50% demonstrated significantly increased mean cortical curvature in mTBI relative to controls with 25% remaining significant following multiple comparison correction (all, pFDR < .05). These differences were most prominent in deep gray matter regions of the cortex. Additionally, significant relationships were found between mean cortical curvature and gray and white matter volumes (all, p < .05). These findings suggest potentially unique patterns of atrophy by region and indicate that changes in brain microstructure due to mTBI are sensitive to measures of mean curvature.

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

PubMed Central

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

2014-01-01

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

Single season changes in resting state network power and the connectivity between regions distinguish head impact exposure level in high school and youth football players

NASA Astrophysics Data System (ADS)

Murugesan, Gowtham; Saghafi, Behrouz; Davenport, Elizabeth; Wagner, Ben; Urban, Jillian; Kelley, Mireille; Jones, Derek; Powers, Alex; Whitlow, Christopher; Stitzel, Joel; Maldjian, Joseph; Montillo, Albert

2018-02-01

The effect of repetitive sub-concussive head impact exposure in contact sports like American football on brain health is poorly understood, especially in the understudied populations of youth and high school players. These players, aged 9-18 years old may be particularly susceptible to impact exposure as their brains are undergoing rapid maturation. This study helps fill the void by quantifying the association between head impact exposure and functional connectivity, an important aspect of brain health measurable via resting-state fMRI (rs-fMRI). The contributions of this paper are three fold. First, the data from two separate studies (youth and high school) are combined to form a high-powered analysis with 60 players. These players experience head acceleration within overlapping impact exposure making their combination particularly appropriate. Second, multiple features are extracted from rs-fMRI and tested for their association with impact exposure. One type of feature is the power spectral density decomposition of intrinsic, spatially distributed networks extracted via independent components analysis (ICA). Another feature type is the functional connectivity between brain regions known often associated with mild traumatic brain injury (mTBI). Third, multiple supervised machine learning algorithms are evaluated for their stability and predictive accuracy in a low bias, nested cross-validation modeling framework. Each classifier predicts whether a player sustained low or high levels of head impact exposure. The nested cross validation reveals similarly high classification performance across the feature types, and the Support Vector, Extremely randomized trees, and Gradboost classifiers achieve F1-score up to 75%.

Three-way parallel independent component analysis for imaging genetics using multi-objective optimization.

PubMed

Ulloa, Alvaro; Jingyu Liu; Vergara, Victor; Jiayu Chen; Calhoun, Vince; Pattichis, Marios

2014-01-01

In the biomedical field, current technology allows for the collection of multiple data modalities from the same subject. In consequence, there is an increasing interest for methods to analyze multi-modal data sets. Methods based on independent component analysis have proven to be effective in jointly analyzing multiple modalities, including brain imaging and genetic data. This paper describes a new algorithm, three-way parallel independent component analysis (3pICA), for jointly identifying genomic loci associated with brain function and structure. The proposed algorithm relies on the use of multi-objective optimization methods to identify correlations among the modalities and maximally independent sources within modality. We test the robustness of the proposed approach by varying the effect size, cross-modality correlation, noise level, and dimensionality of the data. Simulation results suggest that 3p-ICA is robust to data with SNR levels from 0 to 10 dB and effect-sizes from 0 to 3, while presenting its best performance with high cross-modality correlations, and more than one subject per 1,000 variables. In an experimental study with 112 human subjects, the method identified links between a genetic component (pointing to brain function and mental disorder associated genes, including PPP3CC, KCNQ5, and CYP7B1), a functional component related to signal decreases in the default mode network during the task, and a brain structure component indicating increases of gray matter in brain regions of the default mode region. Although such findings need further replication, the simulation and in-vivo results validate the three-way parallel ICA algorithm presented here as a useful tool in biomedical data decomposition applications.

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

A Network Model of the Emotional Brain.

PubMed

Pessoa, Luiz

2017-05-01

Emotion is often understood in terms of a circumscribed set of cortical and subcortical brain regions. I propose, instead, that emotion should be understood in terms of large-scale network interactions spanning the entire neuroaxis. I describe multiple anatomical and functional principles of brain organization that lead to the concept of 'functionally integrated systems', cortical-subcortical systems that anchor the organization of emotion in the brain. The proposal is illustrated by describing the cortex-amygdala integrated system and how it intersects with systems involving the ventral striatum/accumbens, septum, hippocampus, hypothalamus, and brainstem. The important role of the thalamus is also highlighted. Overall, the model clarifies why the impact of emotion is wide-ranging, and how emotion is interlocked with perception, cognition, motivation, and action. Copyright © 2017 Elsevier Ltd. All rights reserved.

An integrated modelling framework for neural circuits with multiple neuromodulators.

PubMed

Joshi, Alok; Youssofzadeh, Vahab; Vemana, Vinith; McGinnity, T M; Prasad, Girijesh; Wong-Lin, KongFatt

2017-01-01

Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours. Specifically, we propose a novel dynamical neural circuit model that integrates the effective neuromodulator-induced currents based on various experimental data (e.g. electrophysiology, neuropharmacology and voltammetry). The model can incorporate multiple interacting brain regions, including neuromodulator sources, simulate efficiently and easily extendable to large-scale brain models, e.g. for neuroimaging purposes. As an example, we model a network of mutually interacting neural populations in the lateral hypothalamus, dorsal raphe nucleus and locus coeruleus, which are major sources of neuromodulator orexin/hypocretin, serotonin and norepinephrine/noradrenaline, respectively, and which play significant roles in regulating many physiological functions. We demonstrate that such a model can provide predictions of systemic drug effects of the popular antidepressants (e.g. reuptake inhibitors), neuromodulator antagonists or their combinations. Finally, we developed user-friendly graphical user interface software for model simulation and visualization for both fundamental sciences and pharmacological studies. © 2017 The Authors.

An integrated modelling framework for neural circuits with multiple neuromodulators

PubMed Central

Vemana, Vinith

2017-01-01

Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours. Specifically, we propose a novel dynamical neural circuit model that integrates the effective neuromodulator-induced currents based on various experimental data (e.g. electrophysiology, neuropharmacology and voltammetry). The model can incorporate multiple interacting brain regions, including neuromodulator sources, simulate efficiently and easily extendable to large-scale brain models, e.g. for neuroimaging purposes. As an example, we model a network of mutually interacting neural populations in the lateral hypothalamus, dorsal raphe nucleus and locus coeruleus, which are major sources of neuromodulator orexin/hypocretin, serotonin and norepinephrine/noradrenaline, respectively, and which play significant roles in regulating many physiological functions. We demonstrate that such a model can provide predictions of systemic drug effects of the popular antidepressants (e.g. reuptake inhibitors), neuromodulator antagonists or their combinations. Finally, we developed user-friendly graphical user interface software for model simulation and visualization for both fundamental sciences and pharmacological studies. PMID:28100828

Sleep spindles in humans: insights from intracranial EEG and unit recordings

PubMed Central

Andrillon, Thomas; Nir, Yuval; Staba, Richard J.; Ferrarelli, Fabio; Cirelli, Chiara; Tononi, Giulio; Fried, Itzhak

2012-01-01

Sleep spindles are an electroencephalographic (EEG) hallmark of non-rapid eye movement (NREM) sleep and are believed to mediate many sleep-related functions, from memory consolidation to cortical development. Spindles differ in location, frequency, and association with slow waves, but whether this heterogeneity may reflect different physiological processes and potentially serve different functional roles remains unclear. Here we utilized a unique opportunity to record intracranial depth EEG and single-unit activity in multiple brain regions of neurosurgical patients to better characterize spindle activity in human sleep. We find that spindles occur across multiple neocortical regions, and less frequently also in the parahippocampal gyrus and hippocampus. Most spindles are spatially restricted to specific brain regions. In addition, spindle frequency is topographically organized with a sharp transition around the supplementary motor area between fast (13-15Hz) centroparietal spindles often occurring with slow wave up-states, and slow (9-12Hz) frontal spindles occurring 200ms later on average. Spindle variability across regions may reflect the underlying thalamocortical projections. We also find that during individual spindles, frequency decreases within and between regions. In addition, deeper sleep is associated with a reduction in spindle occurrence and spindle frequency. Frequency changes between regions, during individual spindles, and across sleep may reflect the same phenomenon, the underlying level of thalamocortical hyperpolarization. Finally, during spindles neuronal firing rates are not consistently modulated, although some neurons exhibit phase-locked discharges. Overall, anatomical considerations can account well for regional spindle characteristics, while variable hyperpolarization levels can explain differences in spindle frequency. PMID:22159098

Decoding negative affect personality trait from patterns of brain activation to threat stimuli.

PubMed

Fernandes, Orlando; Portugal, Liana C L; Alves, Rita de Cássia S; Arruda-Sanchez, Tiago; Rao, Anil; Volchan, Eliane; Pereira, Mirtes; Oliveira, Letícia; Mourao-Miranda, Janaina

2017-01-15

Pattern recognition analysis (PRA) applied to functional magnetic resonance imaging (fMRI) has been used to decode cognitive processes and identify possible biomarkers for mental illness. In the present study, we investigated whether the positive affect (PA) or negative affect (NA) personality traits could be decoded from patterns of brain activation in response to a human threat using a healthy sample. fMRI data from 34 volunteers (15 women) were acquired during a simple motor task while the volunteers viewed a set of threat stimuli that were directed either toward them or away from them and matched neutral pictures. For each participant, contrast images from a General Linear Model (GLM) between the threat versus neutral stimuli defined the spatial patterns used as input to the regression model. We applied a multiple kernel learning (MKL) regression combining information from different brain regions hierarchically in a whole brain model to decode the NA and PA from patterns of brain activation in response to threat stimuli. The MKL model was able to decode NA but not PA from the contrast images between threat stimuli directed away versus neutral with a significance above chance. The correlation and the mean squared error (MSE) between predicted and actual NA were 0.52 (p-value=0.01) and 24.43 (p-value=0.01), respectively. The MKL pattern regression model identified a network with 37 regions that contributed to the predictions. Some of the regions were related to perception (e.g., occipital and temporal regions) while others were related to emotional evaluation (e.g., caudate and prefrontal regions). These results suggest that there was an interaction between the individuals' NA and the brain response to the threat stimuli directed away, which enabled the MKL model to decode NA from the brain patterns. To our knowledge, this is the first evidence that PRA can be used to decode a personality trait from patterns of brain activation during emotional contexts. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Stem Cell Physics. Multiple-Laser-Beam Treatment of Parkinson's Disease

NASA Astrophysics Data System (ADS)

Stefan, V.

2013-03-01

A novel method for the treatment of Parkinson's disease is proposed. Pluripotent stem cells are laser cultured, using ultrashort wavelength, (around 0.1 micron-ultraviolet radiation-with intensities of a few mW/cm2) , multiple laser beams.[2] The multiple-energy laser photons[3] interact with the neuron DNA molecules to be cloned. The laser created dopaminergic substantia nigra neurons can be, (theoretically), laser transplanted, (a higher focusing precision as compared to a syringe method), into the striatum or substantia nigra regions of the brain, or both. Supported by Nikola Tesla Labs, Stefan University.

Glutamate System Genes and Brain Volume Alterations in Pediatric Obsessive-Compulsive Disorder: A Preliminary Study

PubMed Central

Wu, Ke; Hanna, Gregory L.; Easter, Philip; Kennedy, James L.; Rosenberg, David R.; Arnold, Paul D

2012-01-01

Obsessive-compulsive disorder (OCD) has been associated with regional volumetric brain abnormalities, which provide promising intermediate phenotypes of the disorder. In this study, volumes of brain regions selected for a priori evidence of association with OCD (orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), thalamus, caudate, putamen, globus pallidus and pituitary) were measured using structural magnetic resonance imaging (MRI) in 20 psychotropic-naïve pediatric OCD patients. We examined the association between these regional brain volumes and a total of 519 single nucleotide polymorphisms (SNPs) from nine glutamatergic candidate genes (DLGAP1, DLGAP2, DLGAP3, GRIN2B, SLC1A1, GRIK2, GRIK3, SLITRK1 and SLITRK5). These genes were selected based on either previous reported association with OCD in humans or evidence from animal models of OCD. After correcting for multiple comparisons by permutation testing, no SNP remained significantly associated with volumetric changes. The strongest trend toward association was identified between two SNPs in DLGAP2 (rs6558484 and rs7014992) and OFC white matter volume (P = 0.000565, Padjusted= 0.3071). Our other top ranked association findings were with ACC, OFC and thalamus. These preliminary results suggest that sequence variants in glutamate candidate genes may be associated with structural neuroimaging phenotypes of OCD. PMID:23154099

4-dimensional functional profiling in the convulsant-treated larval zebrafish brain.

PubMed

Winter, Matthew J; Windell, Dylan; Metz, Jeremy; Matthews, Peter; Pinion, Joe; Brown, Jonathan T; Hetheridge, Malcolm J; Ball, Jonathan S; Owen, Stewart F; Redfern, Will S; Moger, Julian; Randall, Andrew D; Tyler, Charles R

2017-07-26

Functional neuroimaging, using genetically-encoded Ca 2+ sensors in larval zebrafish, offers a powerful combination of high spatiotemporal resolution and higher vertebrate relevance for quantitative neuropharmacological profiling. Here we use zebrafish larvae with pan-neuronal expression of GCaMP6s, combined with light sheet microscopy and a novel image processing pipeline, for the 4D profiling of chemoconvulsant action in multiple brain regions. In untreated larvae, regions associated with autonomic functionality, sensory processing and stress-responsiveness, consistently exhibited elevated spontaneous activity. The application of drugs targeting different convulsant mechanisms (4-Aminopyridine, Pentylenetetrazole, Pilocarpine and Strychnine) resulted in distinct spatiotemporal patterns of activity. These activity patterns showed some interesting parallels with what is known of the distribution of their respective molecular targets, but crucially also revealed system-wide neural circuit responses to stimulation or suppression. Drug concentration-response curves of neural activity were identified in a number of anatomically-defined zebrafish brain regions, and in vivo larval electrophysiology, also conducted in 4dpf larvae, provided additional measures of neural activity. Our quantification of network-wide chemoconvulsant drug activity in the whole zebrafish brain illustrates the power of this approach for neuropharmacological profiling in applications ranging from accelerating studies of drug safety and efficacy, to identifying pharmacologically-altered networks in zebrafish models of human neurological disorders.

A Skew-t space-varying regression model for the spectral analysis of resting state brain activity.

PubMed

Ismail, Salimah; Sun, Wenqi; Nathoo, Farouk S; Babul, Arif; Moiseev, Alexader; Beg, Mirza Faisal; Virji-Babul, Naznin

2013-08-01

It is known that in many neurological disorders such as Down syndrome, main brain rhythms shift their frequencies slightly, and characterizing the spatial distribution of these shifts is of interest. This article reports on the development of a Skew-t mixed model for the spatial analysis of resting state brain activity in healthy controls and individuals with Down syndrome. Time series of oscillatory brain activity are recorded using magnetoencephalography, and spectral summaries are examined at multiple sensor locations across the scalp. We focus on the mean frequency of the power spectral density, and use space-varying regression to examine associations with age, gender and Down syndrome across several scalp regions. Spatial smoothing priors are incorporated based on a multivariate Markov random field, and the markedly non-Gaussian nature of the spectral response variable is accommodated by the use of a Skew-t distribution. A range of models representing different assumptions on the association structure and response distribution are examined, and we conduct model selection using the deviance information criterion. (1) Our analysis suggests region-specific differences between healthy controls and individuals with Down syndrome, particularly in the left and right temporal regions, and produces smoothed maps indicating the scalp topography of the estimated differences.

Neuroanatomy of pseudobulbar affect : a quantitative MRI study in multiple sclerosis.

PubMed

Ghaffar, Omar; Chamelian, Laury; Feinstein, Anthony

2008-03-01

Pseudobulbar affect (PBA) is defined as episodes of involuntary crying, laughing, or both in the absence of a matching subjective mood state. This neuropsychiatric syndrome can be found in a number of neurological disorders including multiple sclerosis (MS). The aim of this study was to identify neuroanatomical correlates of PBA in multiple sclerosis (MS) using a case-control 1.5T MRI study. MS patients with (n = 14) and without (n = 14) PBA were matched on demographic, disease course, and disability variables. Comorbid psychiatric disorders including depressive and anxiety disorders were absent. Hypo- and hyperintense lesion volumes plus measurements of atrophy were obtained and localized anatomically according to parcellated brain regions. Between-group statistical comparisons were undertaken with alpha set at 0.01 for the primary analysis. Discrete differences in lesion volume were noted in six regions: Brainstem hypointense lesions, bilateral inferior parietal and medial inferior frontal hyperintense lesions, and right medial superior frontal hyperintense lesions were all significantly higher in the PBA group. A logistic regression model identified four of these variables (brainstem hypointense, left inferior parietal hyperintense, and left and right medial inferior frontal hyperintense lesion volumes) that accounted for 70% of the variance when it came to explaining the presence of PBA. In conclusion, MS patients with PBA have a distinct distribution of brain lesions when compared to a matched MS sample without PBA. The lesion data support a widely-dispersed neural network involving frontal, parietal, and brainstem regions in the pathophysiology of PBA.

Re-emergence of modular brain networks in stroke recovery.

PubMed

Siegel, Joshua S; Seitzman, Benjamin A; Ramsey, Lenny E; Ortega, Mario; Gordon, Evan M; Dosenbach, Nico U F; Petersen, Steven E; Shulman, Gordon L; Corbetta, Maurizio

2018-04-01

Studies of stroke have identified local reorganization in perilesional tissue. However, because the brain is highly networked, strokes also broadly alter the brain's global network organization. Here, we assess brain network structure longitudinally in adult stroke patients using resting state fMRI. The topology and boundaries of cortical regions remain grossly unchanged across recovery. In contrast, the modularity of brain systems i.e. the degree of integration within and segregation between networks, was significantly reduced sub-acutely (n = 107), but partially recovered by 3 months (n = 85), and 1 year (n = 67). Importantly, network recovery correlated with recovery from language, spatial memory, and attention deficits, but not motor or visual deficits. Finally, in-depth single subject analyses were conducted using tools for visualization of changes in brain networks over time. This exploration indicated that changes in modularity during successful recovery reflect specific alterations in the relationships between different networks. For example, in a patient with left temporo-parietal stroke and severe aphasia, sub-acute loss of modularity reflected loss of association between frontal and temporo-parietal regions bi-hemispherically across multiple modules. These long-distance connections then returned over time, paralleling aphasia recovery. This work establishes the potential importance of normalization of large-scale modular brain systems in stroke recovery. Copyright © 2017. Published by Elsevier Ltd.

Distribution of Non-Persistent Endocrine Disruptors in Two Different Regions of the Human Brain

PubMed Central

van der Meer, Thomas P.; Artacho-Cordón, Francisco; Swaab, Dick F.; Struik, Dicky; Makris, Konstantinos C.; Wolffenbuttel, Bruce H. R.; Frederiksen, Hanne; van Vliet-Ostaptchouk, Jana V.

2017-01-01

Non-persistent endocrine disrupting chemicals (npEDCs) can affect multiple organs and systems in the body. Whether npEDCs can accumulate in the human brain is largely unknown. The major aim of this pilot study was to examine the presence of environmental phenols and parabens in two distinct brain regions: the hypothalamus and white-matter tissue. In addition, a potential association between these npEDCs concentrations and obesity was investigated. Post-mortem brain material was obtained from 24 individuals, made up of 12 obese and 12 normal-weight subjects (defined as body mass index (BMI) > 30 and BMI < 25 kg/m2, respectively). Nine phenols and seven parabens were measured by isotope dilution TurboFlow-LC-MS/MS. In the hypothalamus, seven suspect npEDCs (bisphenol A, triclosan, triclocarban and methyl-, ethyl-, n-propyl-, and benzyl paraben) were detected, while five npEDCs (bisphenol A, benzophenone-3, triclocarban, methyl-, and n-propyl paraben) were found in the white-matter brain tissue. We observed higher levels of methylparaben (MeP) in the hypothalamic tissue of obese subjects as compared to controls (p = 0.008). Our findings indicate that some suspected npEDCs are able to cross the blood–brain barrier. Whether the presence of npEDCs can adversely affect brain function and to which extent the detected concentrations are physiologically relevant needs to be further investigated. PMID:28902174

Glucose hypometabolism is highly localized, but lower cortical thickness and brain atrophy are widespread in cognitively normal older adults.

PubMed

Nugent, Scott; Castellano, Christian-Alexandre; Goffaux, Philippe; Whittingstall, Kevin; Lepage, Martin; Paquet, Nancy; Bocti, Christian; Fulop, Tamas; Cunnane, Stephen C

2014-06-01

Several studies have suggested that glucose hypometabolism may be present in specific brain regions in cognitively normal older adults and could contribute to the risk of subsequent cognitive decline. However, certain methodological shortcomings, including a lack of partial volume effect (PVE) correction or insufficient cognitive testing, confound the interpretation of most studies on this topic. We combined [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging to quantify cerebral metabolic rate of glucose (CMRg) as well as cortical volume and thickness in 43 anatomically defined brain regions from a group of cognitively normal younger (25 ± 3 yr old; n = 25) and older adults (71 ± 9 yr old; n = 31). After correcting for PVE, we observed 11-17% lower CMRg in three specific brain regions of the older group: the superior frontal cortex, the caudal middle frontal cortex, and the caudate (P ≤ 0.01 false discovery rate-corrected). In the older group, cortical volumes and cortical thickness were 13-33 and 7-18% lower, respectively, in multiple brain regions (P ≤ 0.01 FDR correction). There were no differences in CMRg between individuals who were or were not prescribed antihypertensive medication. There were no significant correlations between CMRg and cognitive performance or metabolic parameters measured in fasting plasma. We conclude that highly localized glucose hypometabolism and widespread cortical thinning and atrophy can be present in older adults who are cognitively normal, as assessed using age-normed neuropsychological testing measures. Copyright © 2014 the American Physiological Society.

Atlas based brain volumetry: How to distinguish regional volume changes due to biological or physiological effects from inherent noise of the methodology.

PubMed

Opfer, Roland; Suppa, Per; Kepp, Timo; Spies, Lothar; Schippling, Sven; Huppertz, Hans-Jürgen

2016-05-01

Fully-automated regional brain volumetry based on structural magnetic resonance imaging (MRI) plays an important role in quantitative neuroimaging. In clinical trials as well as in clinical routine multiple MRIs of individual patients at different time points need to be assessed longitudinally. Measures of inter- and intrascanner variability are crucial to understand the intrinsic variability of the method and to distinguish volume changes due to biological or physiological effects from inherent noise of the methodology. To measure regional brain volumes an atlas based volumetry (ABV) approach was deployed using a highly elastic registration framework and an anatomical atlas in a well-defined template space. We assessed inter- and intrascanner variability of the method in 51 cognitively normal subjects and 27 Alzheimer dementia (AD) patients from the Alzheimer's Disease Neuroimaging Initiative by studying volumetric results of repeated scans for 17 compartments and brain regions. Median percentage volume differences of scan-rescans from the same scanner ranged from 0.24% (whole brain parenchyma in healthy subjects) to 1.73% (occipital lobe white matter in AD), with generally higher differences in AD patients as compared to normal subjects (e.g., 1.01% vs. 0.78% for the hippocampus). Minimum percentage volume differences detectable with an error probability of 5% were in the one-digit percentage range for almost all structures investigated, with most of them being below 5%. Intrascanner variability was independent of magnetic field strength. The median interscanner variability was up to ten times higher than the intrascanner variability. Copyright © 2016 Elsevier Inc. All rights reserved.

The function of neurocognitive networks. Comment on “Understanding brain networks and brain organization” by Pessoa

NASA Astrophysics Data System (ADS)

Bressler, Steven L.

2014-09-01

Pessoa [5] has performed a valuable service by reviewing the extant literature on brain networks and making a number of interesting proposals about their cognitive function. The term function is at the core of understanding the brain networks of cognition, or neurocognitive networks (NCNs) [1]. The great Russian neuropsychologist, Luria [4], defined brain function as the common task executed by a distributed brain network of complex dynamic structures united by the demands of cognition. Casting Luria in a modern light, we can say that function emerges from the interactions of brain regions in NCNs as they dynamically self-organize according to cognitive demands. Pessoa rightly details the mapping between brain function and structure, emphasizing both its pluripotency (one structure having multiple functions) and degeneracy (many structures having the same function). However, he fails to consider the potential importance of a one-to-one mapping between NCNs and function. If NCNs are uniquely composed of specific collections of brain areas, then each NCN has a unique function determined by that composition.

Creative females have larger white matter structures: Evidence from a large sample study.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Yokoyama, Ryoichi; Kotozaki, Yuka; Nakagawa, Seishu; Sekiguchi, Atsushi; Iizuka, Kunio; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Makoto Miyauchi, Carlos; Shinada, Takamitsu; Sakaki, Kohei; Sassa, Yuko; Nozawa, Takayuki; Ikeda, Shigeyuki; Yokota, Susumu; Daniele, Magistro; Kawashima, Ryuta

2017-01-01

The importance of brain connectivity for creativity has been theoretically suggested and empirically demonstrated. Studies have shown sex differences in creativity measured by divergent thinking (CMDT) as well as sex differences in the structural correlates of CMDT. However, the relationships between regional white matter volume (rWMV) and CMDT and associated sex differences have never been directly investigated. In addition, structural studies have shown poor replicability and inaccuracy of multiple comparisons over the whole brain. To address these issues, we used the data from a large sample of healthy young adults (776 males and 560 females; mean age: 20.8 years, SD = 0.8). We investigated the relationship between CMDT and WMV using the newest version of voxel-based morphometry (VBM). We corrected for multiple comparisons over whole brain using the permutation-based method, which is known to be quite accurate and robust. Significant positive correlations between rWMV and CMDT scores were observed in widespread areas below the neocortex specifically in females. These associations with CMDT were not observed in analyses of fractional anisotropy using diffusion tensor imaging. Using rigorous methods, our findings further supported the importance of brain connectivity for creativity as well as its female-specific association. Hum Brain Mapp 38:414-430, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A physics link between venous stenosis and multiple sclerosis.

PubMed

Tucker, Trevor W

2011-12-01

This paper hypothesizes that a stenosis or obstruction at a lower extremity of an internal jugular vein (IJV) would, in accordance with the physics of fluid dynamics, cause a standing pressure wave within the vein. This pressure wave would possess regions of large pressure fluctuations and other regions of relatively little fluctuation which also have substantially lower peak pressure values. If the wavelength of the hypothesized pressure wave is comparable to the distance from the obstruction to the venule end of the capillary bed, then a region of high pressure fluctuation would exist at the venules. Depending on the degree of obstruction, the pressure fluctuations at the venules of the capillary bed would be substantially greater than those that would exist in a healthy unobstructed vein. This increase in blood pressure fluctuation located at the venule end of the capillary bed, which would be equivalent to local hypertension, is predicted to reduce the pressure drop across the bed which, in turn, would reduce blood flow through the bed in accordance with Darcy's Law. Such a reduction in blood flow through the bed would be accompanied by a reduction in the transfer of oxygen, glucose and other nutrients into the brain tissue in accordance with Fick's Principle. The reduction in oxygen levels in the brain tissue (i.e. hypoxia), would, in turn, be associated with increased fatigue and decreased mental acuity in the subject patient. Also the deprivation of oxygen in the brain tissue may result in the death of oligodendrocyte cells, which, in turn would result in the deterioration of the myelin surrounding the brain's neural axons. In addition, the paper also predicts that, in cases of extreme obstruction, the predicted localized hypertension at the venule end of the capillary bed may be sufficiently high to cause a localized disruption in the blood-brain barrier. Such a disruption of the blood-brain barrier could then allow the migration of leukocytes (auto-immune attack cells), from the blood into the brain tissue, enabling them to attack myelin, which has degenerated or deteriorated from the reduction in repair function normally provided by oligodendrocyte cells. Such leukocyte attack on myelin has long been associated with multiple sclerosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of cell phone radiofrequency signal exposure on brain glucose metabolism.

PubMed

Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Vaska, Paul; Fowler, Joanna S; Telang, Frank; Alexoff, Dave; Logan, Jean; Wong, Christopher

2011-02-23

The dramatic increase in use of cellular telephones has generated concern about possible negative effects of radiofrequency signals delivered to the brain. However, whether acute cell phone exposure affects the human brain is unclear. To evaluate if acute cell phone exposure affects brain glucose metabolism, a marker of brain activity. Randomized crossover study conducted between January 1 and December 31, 2009, at a single US laboratory among 47 healthy participants recruited from the community. Cell phones were placed on the left and right ears and positron emission tomography with ((18)F)fluorodeoxyglucose injection was used to measure brain glucose metabolism twice, once with the right cell phone activated (sound muted) for 50 minutes ("on" condition) and once with both cell phones deactivated ("off" condition). Statistical parametric mapping was used to compare metabolism between on and off conditions using paired t tests, and Pearson linear correlations were used to verify the association of metabolism and estimated amplitude of radiofrequency-modulated electromagnetic waves emitted by the cell phone. Clusters with at least 1000 voxels (volume >8 cm(3)) and P < .05 (corrected for multiple comparisons) were considered significant. Brain glucose metabolism computed as absolute metabolism (μmol/100 g per minute) and as normalized metabolism (region/whole brain). Whole-brain metabolism did not differ between on and off conditions. In contrast, metabolism in the region closest to the antenna (orbitofrontal cortex and temporal pole) was significantly higher for on than off conditions (35.7 vs 33.3 μmol/100 g per minute; mean difference, 2.4 [95% confidence interval, 0.67-4.2]; P = .004). The increases were significantly correlated with the estimated electromagnetic field amplitudes both for absolute metabolism (R = 0.95, P < .001) and normalized metabolism (R = 0.89; P < .001). In healthy participants and compared with no exposure, 50-minute cell phone exposure was associated with increased brain glucose metabolism in the region closest to the antenna. This finding is of unknown clinical significance.

Effects of Inter-Alpha Inhibitor Proteins on Neonatal Brain Injury: Age, Task and Treatment Dependent Neurobehavioral Outcomes

PubMed Central

Threlkeld, Steven W.; Gaudet, Cynthia M.; La Rue, Molly E.; Dugas, Ethan; Hill, Courtney A.; Lim, Yow-Pin; Stonestreet, Barbara S.

2014-01-01

Hypoxic-ischemic (HI) brain injury is frequently associated with premature and/or full term birth related complications. HI injury often results in learning and processing deficits that reflect widespread damage to an extensive range of cortical and sub-cortical brain structures. Further, inflammation has been implicated in the long-term progression and severity of HI injury. Recently, Inter-alpha Inhibitor Proteins (IAIPs) have been shown to attenuate inflammation in models of systemic infection. Importantly, preclinical studies of neonatal HI injury and neuroprotection often focus on single time windows of assessment or single behavioral domains. This approach limits translational validity, given evidence for a diverse spectrum of neurobehavioral deficits that may change across developmental windows following neonatal brain injury. Therefore, the aims of this research were to assess the effects of human IAIPs on early neocortical cell death (72 hours post insult), adult regional brain volume measurements (cerebral cortex, hippocampus, striatum, corpus callosum) and long-term behavioral outcomes in juvenile (P38-50) and adult (P80+) periods across two independent learning domains (spatial and non-spatial learning), after postnatal day 7 HI injury in rats. Here, for the first time, we show that IAIPs reduce acute neocortical neuronal cell death and improve brain weight outcome 72 hours following HI injury in the neonatal rat. Further, these longitudinal studies are the first to show age, task and treatment dependent improvements in behavioral outcome for both spatial and non-spatial learning following systemic administration of IAIPs in neonatal HI injured rats. Finally, results also show sparing of brain regions critical for spatial and non-spatial learning in adult animals treated with IAIPs at the time of injury onset. These data support the proposal that Inter-alpha Inhibitor Proteins may serve as novel therapeutics for brain injury associated with premature birth and/or neonatal brain injury and highlight the importance of assessing multiple ages, brain regions and behavioral domains when investigating experimental treatment efficacy. PMID:25084519

Complementary Roles for Amygdala and Periaqueductal Gray in Temporal-Difference Fear Learning

ERIC Educational Resources Information Center

Cole, Sindy; McNally, Gavan P.

2009-01-01

Pavlovian fear conditioning is not a unitary process. At the neurobiological level multiple brain regions and neurotransmitters contribute to fear learning. At the behavioral level many variables contribute to fear learning including the physical salience of the events being learned about, the direction and magnitude of predictive error, and the…

Synaptic genes are extensively downregulated across multiple brain regions in normal human aging and Alzheimer’s disease

PubMed Central

Berchtold, Nicole C.; Coleman, Paul D.; Cribbs, David H.; Rogers, Joseph; Gillen, Daniel L.; Cotman, Carl W.

2014-01-01

Synapses are essential for transmitting, processing, and storing information, all of which decline in aging and Alzheimer’s disease (AD). Because synapse loss only partially accounts for the cognitive declines seen in aging and AD, we hypothesized that existing synapses might undergo molecular changes that reduce their functional capacity. Microarrays were used to evaluate expression profiles of 340 synaptic genes in aging (20–99 years) and AD across 4 brain regions from 81 cases. The analysis revealed an unexpectedly large number of significant expression changes in synapse-related genes in aging, with many undergoing progressive downregulation across aging and AD. Functional classification of the genes showing altered expression revealed that multiple aspects of synaptic function are affected, notably synaptic vesicle trafficking and release, neurotransmitter receptors and receptor trafficking, postsynaptic density scaffolding, cell adhesion regulating synaptic stability, and neuromodulatory systems. The widespread declines in synaptic gene expression in normal aging suggests that function of existing synapses might be impaired, and that a common set of synaptic genes are vulnerable to change in aging and AD. PMID:23273601

Physiological and psychological individual differences influence resting brain function measured by ASL perfusion.

PubMed

Kano, M; Coen, S J; Farmer, A D; Aziz, Q; Williams, S C R; Alsop, D C; Fukudo, S; O'Gorman, R L

2014-09-01

Effects of physiological and/or psychological inter-individual differences on the resting brain state have not been fully established. The present study investigated the effects of individual differences in basal autonomic tone and positive and negative personality dimensions on resting brain activity. Whole-brain resting cerebral perfusion images were acquired from 32 healthy subjects (16 males) using arterial spin labeling perfusion MRI. Neuroticism and extraversion were assessed with the Eysenck Personality Questionnaire-Revised. Resting autonomic activity was assessed using a validated measure of baseline cardiac vagal tone (CVT) in each individual. Potential associations between the perfusion data and individual CVT (27 subjects) and personality score (28 subjects) were tested at the level of voxel clusters by fitting a multiple regression model at each intracerebral voxel. Greater baseline perfusion in the dorsal anterior cingulate cortex (ACC) and cerebellum was associated with lower CVT. At a corrected significance threshold of p < 0.01, strong positive correlations were observed between extraversion and resting brain perfusion in the right caudate, brain stem, and cingulate gyrus. Significant negative correlations between neuroticism and regional cerebral perfusion were identified in the left amygdala, bilateral insula, ACC, and orbitofrontal cortex. These results suggest that individual autonomic tone and psychological variability influence resting brain activity in brain regions, previously shown to be associated with autonomic arousal (dorsal ACC) and personality traits (amygdala, caudate, etc.) during active task processing. The resting brain state may therefore need to be taken into account when interpreting the neurobiology of individual differences in structural and functional brain activity.

Hyperconnectivity is a fundamental response to neurological disruption.

PubMed

Hillary, Frank G; Roman, Cristina A; Venkatesan, Umesh; Rajtmajer, Sarah M; Bajo, Ricardo; Castellanos, Nazareth D

2015-01-01

In the cognitive and clinical neurosciences, the past decade has been marked by dramatic growth in a literature examining brain "connectivity" using noninvasive methods. We offer a critical review of the blood oxygen level dependent functional MRI (BOLD fMRI) literature examining neural connectivity changes in neurological disorders with focus on brain injury and dementia. The goal is to demonstrate that there are identifiable shifts in local and large-scale network connectivity that can be predicted by the degree of pathology. We anticipate that the most common network response to neurological insult is hyperconnectivity but that this response depends upon demand and resource availability. To examine this hypothesis, we initially reviewed the results from 1,426 studies examining functional brain connectivity in individuals diagnosed with multiple sclerosis, traumatic brain injury, mild cognitive impairment, and Alzheimer's disease. Based upon inclusionary criteria, 126 studies were included for detailed analysis. RESULTS from 126 studies examining local and whole brain connectivity demonstrated increased connectivity in traumatic brain injury and multiple sclerosis. This finding is juxtaposed with findings in mild cognitive impairment and Alzheimer's disease where there is a shift to diminished connectivity as degeneration progresses. This summary of the functional imaging literature using fMRI methods reveals that hyperconnectivity is a common response to neurological disruption and that it may be differentially observable across brain regions. We discuss the factors contributing to both hyper- and hypoconnectivity results after neurological disruption and the implications these findings have for network plasticity. PsycINFO Database Record (c) 2015 APA, all rights reserved.

A Bayesian Model of Category-Specific Emotional Brain Responses

PubMed Central

Wager, Tor D.; Kang, Jian; Johnson, Timothy D.; Nichols, Thomas E.; Satpute, Ajay B.; Barrett, Lisa Feldman

2015-01-01

Understanding emotion is critical for a science of healthy and disordered brain function, but the neurophysiological basis of emotional experience is still poorly understood. We analyzed human brain activity patterns from 148 studies of emotion categories (2159 total participants) using a novel hierarchical Bayesian model. The model allowed us to classify which of five categories—fear, anger, disgust, sadness, or happiness—is engaged by a study with 66% accuracy (43-86% across categories). Analyses of the activity patterns encoded in the model revealed that each emotion category is associated with unique, prototypical patterns of activity across multiple brain systems including the cortex, thalamus, amygdala, and other structures. The results indicate that emotion categories are not contained within any one region or system, but are represented as configurations across multiple brain networks. The model provides a precise summary of the prototypical patterns for each emotion category, and demonstrates that a sufficient characterization of emotion categories relies on (a) differential patterns of involvement in neocortical systems that differ between humans and other species, and (b) distinctive patterns of cortical-subcortical interactions. Thus, these findings are incompatible with several contemporary theories of emotion, including those that emphasize emotion-dedicated brain systems and those that propose emotion is localized primarily in subcortical activity. They are consistent with componential and constructionist views, which propose that emotions are differentiated by a combination of perceptual, mnemonic, prospective, and motivational elements. Such brain-based models of emotion provide a foundation for new translational and clinical approaches. PMID:25853490

A voxelwise approach to determine consensus regions-of-interest for the study of brain network plasticity.

PubMed

Rajtmajer, Sarah M; Roy, Arnab; Albert, Reka; Molenaar, Peter C M; Hillary, Frank G

2015-01-01

Despite exciting advances in the functional imaging of the brain, it remains a challenge to define regions of interest (ROIs) that do not require investigator supervision and permit examination of change in networks over time (or plasticity). Plasticity is most readily examined by maintaining ROIs constant via seed-based and anatomical-atlas based techniques, but these approaches are not data-driven, requiring definition based on prior experience (e.g., choice of seed-region, anatomical landmarks). These approaches are limiting especially when functional connectivity may evolve over time in areas that are finer than known anatomical landmarks or in areas outside predetermined seeded regions. An ideal method would permit investigators to study network plasticity due to learning, maturation effects, or clinical recovery via multiple time point data that can be compared to one another in the same ROI while also preserving the voxel-level data in those ROIs at each time point. Data-driven approaches (e.g., whole-brain voxelwise approaches) ameliorate concerns regarding investigator bias, but the fundamental problem of comparing the results between distinct data sets remains. In this paper we propose an approach, aggregate-initialized label propagation (AILP), which allows for data at separate time points to be compared for examining developmental processes resulting in network change (plasticity). To do so, we use a whole-brain modularity approach to parcellate the brain into anatomically constrained functional modules at separate time points and then apply the AILP algorithm to form a consensus set of ROIs for examining change over time. To demonstrate its utility, we make use of a known dataset of individuals with traumatic brain injury sampled at two time points during the first year of recovery and show how the AILP procedure can be applied to select regions of interest to be used in a graph theoretical analysis of plasticity.

Effects of spatial variation of skull and cerebrospinal fluid layers on optical mapping of brain activities

NASA Astrophysics Data System (ADS)

Wang, Shuping; Shibahara, Nanae; Kuramashi, Daishi; Okawa, Shinpei; Kakuta, Naoto; Okada, Eiji; Maki, Atsushi; Yamada, Yukio

2010-07-01

In order to investigate the effects of anatomical variation in human heads on the optical mapping of brain activity, we perform simulations of optical mapping by solving the photon diffusion equation for layered-models simulating human heads using the finite element method (FEM). Particularly, the effects of the spatial variations in the thicknesses of the skull and cerebrospinal fluid (CSF) layers on mapping images are investigated. Mapping images of single active regions in the gray matter layer are affected by the spatial variations in the skull and CSF layer thicknesses, although the effects are smaller than those of the positions of the active region relative to the data points. The increase in the skull thickness decreases the sensitivity of the images to active regions, while the increase in the CSF layer thickness increases the sensitivity in general. The images of multiple active regions are also influenced by their positions relative to the data points and by their depths from the skin surface.

Acute stress evokes sexually dimorphic, stressor-specific patterns of neural activation across multiple limbic brain regions in adult rats.

PubMed

Sood, Ankit; Chaudhari, Karina; Vaidya, Vidita A

2018-03-01

Stress enhances the risk for psychiatric disorders such as anxiety and depression. Stress responses vary across sex and may underlie the heightened vulnerability to psychopathology in females. Here, we examined the influence of acute immobilization stress (AIS) and a two-day short-term forced swim stress (FS) on neural activation in multiple cortical and subcortical brain regions, implicated as targets of stress and in the regulation of neuroendocrine stress responses, in male and female rats using Fos as a neural activity marker. AIS evoked a sex-dependent pattern of neural activation within the cingulate and infralimbic subdivisions of the medial prefrontal cortex (mPFC), lateral septum (LS), habenula, and hippocampal subfields. The degree of neural activation in the mPFC, LS, and habenula was higher in males. Female rats exhibited reduced Fos positive cell numbers in the dentate gyrus hippocampal subfield, an effect not observed in males. We addressed whether the sexually dimorphic neural activation pattern noted following AIS was also observed with the short-term stress of FS. In the paraventricular nucleus of the hypothalamus and the amygdala, FS similar to AIS resulted in robust increases in neural activation in both sexes. The pattern of neural activation evoked by FS was distinct across sexes, with a heightened neural activation noted in the prelimbic mPFC subdivision and hippocampal subfields in females and differed from the pattern noted with AIS. This indicates that the sex differences in neural activation patterns observed within stress-responsive brain regions are dependent on the nature of stressor experience.

Investigation of human multiple sclerosis lesions using high resolution spectrally unmixed CARS microscopy

NASA Astrophysics Data System (ADS)

Poon, Kelvin W.; Brideau, Craig; Teo, Wulin; Schenk, Geert J.; Klaver, Roel; Klauser, Antoine M.; Kawasoe, Jean H.; Geurts, Jeroen J. G.; Stys, Peter K.

2013-03-01

The pathology of multiple sclerosis (MS) involves both the gray and white matter regions of the brain and spinal cord. It is characterized by various combinations of demyelination, inflammatory infiltration, axonal degeneration, and later gliosis in chronic lesions. While acute and chronic white matter plaques are well characterized and easily identified, evidence indicates that the CNS of MS patients may be globally altered, with subtle abnormalities found in grossly normal appearing white matter (NAWM) and in diffusely abnormal white matter (DAWM) where histochemical stains and advanced magnetic resonance imaging indicate altered tissue composition. Thus, the prototypical acute inflammatory lesion may merely represent the most obvious manifestation of a chronic widespread involvement of the CNS, which is difficult to examine reliably. The current study deals with the microstructure and biochemistry of demyelination, remyelination and axonal loss in various regions of post-mortem human MS brain, including NAWM, areas of remyelination and more typical acute and chronic lesions. The myelin sheath, neuroglia and perivascular spaces were investigated using a novel Coherent Anti-Stokes Raman Scattering (CARS) microscope with simultaneous Two-Photon Excited Fluorescence (TPEF) imaging. The active CH stretching region between 2800 and 3000 cm-1 was probed to provide chemically specific, high resolution, label-free imaging pertaining to the progression of the disease. CARS data were correlated with TPEF and conventional histochemical and immunohistochemical stains. Our novel CARS microscopy system provides detailed morphological and biochemical information regarding CNS pathology in MS and that may be applicable to a broad range of other human brain and spinal cord disorders.

The Cerebellar-Cerebral Microstructure Is Disrupted at Multiple Sites in Very Preterm Infants with Cerebellar Haemorrhage.

PubMed

Neubauer, Vera; Djurdjevic, Tanja; Griesmaier, Elke; Biermayr, Marlene; Gizewski, Elke Ruth; Kiechl-Kohlendorfer, Ursula

2018-01-01

Recent advances in magnetic resonance imaging (MRI) techniques have prompted reconsideration of the anatomical correlates of adverse outcomes in preterm infants. The importance of the contribution made by the cerebellum is now increasingly appreciated. The effect of cerebellar haemorrhage (CBH) on the microstructure of the cerebellar-cerebral circuit is largely unexplored. To investigate the effect of CBH on the microstructure of cerebellar-cerebral connections in preterm infants aged <32 gestational weeks. Infants underwent diffusion tensor MRI at term-equivalent age. MRI was evaluated for CBH and additional supratentorial brain injury using a validated scoring system. Region of interest-based measures of brain microstructure (fractional anisotropy [FA] and apparent diffusion coefficient) were quantified in 5 vulnerable regions (the centrum semiovale, posterior limb of the internal capsule, corpus callosum, and superior and middle cerebellar peduncles). Group differences between infants with CBH and infants without CBH were assessed. There were 267 infants included in the study. Infants with CBH (isolated and combined) had significantly lower FA values in all regions investigated. Infants with isolated CBH showed lower FA in the middle and superior cerebellar peduncles and in the posterior limb of the internal capsule. This study provides evidence that CBH causes alterations in localised and remote WM pathways in the developing brain. The disruption of the cerebellar-cerebral microstructure at multiple sites adds further support for the concept of developmental diaschisis, which is propagated as an explanation for the consequences of early cerebellar injury on cognitive and affective domains. © 2017 S. Karger AG, Basel.

Predicting individualized clinical measures by a generalized prediction framework and multimodal fusion of MRI data

PubMed Central

Meng, Xing; Jiang, Rongtao; Lin, Dongdong; Bustillo, Juan; Jones, Thomas; Chen, Jiayu; Yu, Qingbao; Du, Yuhui; Zhang, Yu; Jiang, Tianzi; Sui, Jing; Calhoun, Vince D.

2016-01-01

Neuroimaging techniques have greatly enhanced the understanding of neurodiversity (human brain variation across individuals) in both health and disease. The ultimate goal of using brain imaging biomarkers is to perform individualized predictions. Here we proposed a generalized framework that can predict explicit values of the targeted measures by taking advantage of joint information from multiple modalities. This framework also enables whole brain voxel-wise searching by combining multivariate techniques such as ReliefF, clustering, correlation-based feature selection and multiple regression models, which is more flexible and can achieve better prediction performance than alternative atlas-based methods. For 50 healthy controls and 47 schizophrenia patients, three kinds of features derived from resting-state fMRI (fALFF), sMRI (gray matter) and DTI (fractional anisotropy) were extracted and fed into a regression model, achieving high prediction for both cognitive scores (MCCB composite r = 0.7033, MCCB social cognition r = 0.7084) and symptomatic scores (positive and negative syndrome scale [PANSS] positive r = 0.7785, PANSS negative r = 0.7804). Moreover, the brain areas likely responsible for cognitive deficits of schizophrenia, including middle temporal gyrus, dorsolateral prefrontal cortex, striatum, cuneus and cerebellum, were located with different weights, as well as regions predicting PANSS symptoms, including thalamus, striatum and inferior parietal lobule, pinpointing the potential neuromarkers. Finally, compared to a single modality, multimodal combination achieves higher prediction accuracy and enables individualized prediction on multiple clinical measures. There is more work to be done, but the current results highlight the potential utility of multimodal brain imaging biomarkers to eventually inform clinical decision-making. PMID:27177764

Characterizing Brain Structures and Remodeling after TBI Based on Information Content, Diffusion Entropy

PubMed Central

Fozouni, Niloufar; Chopp, Michael; Nejad-Davarani, Siamak P.; Zhang, Zheng Gang; Lehman, Norman L.; Gu, Steven; Ueno, Yuji; Lu, Mei; Ding, Guangliang; Li, Lian; Hu, Jiani; Bagher-Ebadian, Hassan; Hearshen, David; Jiang, Quan

2013-01-01

Background To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat. Methods Thirteen healthy subjects were investigated using a Q-ball based DTI data sampling scheme. FA and entropy values were measured in white matter bundles, white matter fiber crossing areas, different gray matter (GM) regions and cerebrospinal fluid (CSF). Axonal densities' from the same regions of interest (ROIs) were evaluated in Bielschowsky and Luxol fast blue stained autopsy (n = 30) brain sections by light microscopy. As a case demonstration, a Wistar rat subjected to TBI and treated with bone marrow stromal cells (MSC) 1 week after TBI was employed to illustrate the superior ability of entropy over FA in detecting reorganized crossing axonal bundles as confirmed by histological analysis with Bielschowsky and Luxol fast blue staining. Results Unlike FA, entropy was less affected by axonal orientation and more affected by axonal density. A significant agreement (r = 0.91) was detected between entropy values from in vivo human brain and histologically measured axonal density from post mortum from the same brain structures. The MSC treated TBI rat demonstrated that the entropy approach is superior to FA in detecting axonal remodeling after injury. Compared with FA, entropy detected new axonal remodeling regions with crossing axons, confirmed with immunohistological staining. Conclusions Entropy measurement is more effective in distinguishing axonal remodeling after injury, when compared with FA. Entropy is also more sensitive to axonal density than axonal orientation, and thus may provide a more accurate reflection of axonal changes that occur in neurological injury and disease. PMID:24143186

Characterizing brain structures and remodeling after TBI based on information content, diffusion entropy.

PubMed

Fozouni, Niloufar; Chopp, Michael; Nejad-Davarani, Siamak P; Zhang, Zheng Gang; Lehman, Norman L; Gu, Steven; Ueno, Yuji; Lu, Mei; Ding, Guangliang; Li, Lian; Hu, Jiani; Bagher-Ebadian, Hassan; Hearshen, David; Jiang, Quan

2013-01-01

To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat. Thirteen healthy subjects were investigated using a Q-ball based DTI data sampling scheme. FA and entropy values were measured in white matter bundles, white matter fiber crossing areas, different gray matter (GM) regions and cerebrospinal fluid (CSF). Axonal densities' from the same regions of interest (ROIs) were evaluated in Bielschowsky and Luxol fast blue stained autopsy (n = 30) brain sections by light microscopy. As a case demonstration, a Wistar rat subjected to TBI and treated with bone marrow stromal cells (MSC) 1 week after TBI was employed to illustrate the superior ability of entropy over FA in detecting reorganized crossing axonal bundles as confirmed by histological analysis with Bielschowsky and Luxol fast blue staining. Unlike FA, entropy was less affected by axonal orientation and more affected by axonal density. A significant agreement (r = 0.91) was detected between entropy values from in vivo human brain and histologically measured axonal density from post mortum from the same brain structures. The MSC treated TBI rat demonstrated that the entropy approach is superior to FA in detecting axonal remodeling after injury. Compared with FA, entropy detected new axonal remodeling regions with crossing axons, confirmed with immunohistological staining. Entropy measurement is more effective in distinguishing axonal remodeling after injury, when compared with FA. Entropy is also more sensitive to axonal density than axonal orientation, and thus may provide a more accurate reflection of axonal changes that occur in neurological injury and disease.

Mitochondrial Mutations in Subjects with Psychiatric Disorders

PubMed Central

Magnan, Christophe; van Oven, Mannis; Baldi, Pierre; Myers, Richard M.; Barchas, Jack D.; Schatzberg, Alan F.; Watson, Stanley J.; Akil, Huda; Bunney, William E.; Vawter, Marquis P.

2015-01-01

A considerable body of evidence supports the role of mitochondrial dysfunction in psychiatric disorders and mitochondrial DNA (mtDNA) mutations are known to alter brain energy metabolism, neurotransmission, and cause neurodegenerative disorders. Genetic studies focusing on common nuclear genome variants associated with these disorders have produced genome wide significant results but those studies have not directly studied mtDNA variants. The purpose of this study is to investigate, using next generation sequencing, the involvement of mtDNA variation in bipolar disorder, schizophrenia, major depressive disorder, and methamphetamine use. MtDNA extracted from multiple brain regions and blood were sequenced (121 mtDNA samples with an average of 8,800x coverage) and compared to an electronic database containing 26,850 mtDNA genomes. We confirmed novel and rare variants, and confirmed next generation sequencing error hotspots by traditional sequencing and genotyping methods. We observed a significant increase of non-synonymous mutations found in individuals with schizophrenia. Novel and rare non-synonymous mutations were found in psychiatric cases in mtDNA genes: ND6, ATP6, CYTB, and ND2. We also observed mtDNA heteroplasmy in brain at a locus previously associated with schizophrenia (T16519C). Large differences in heteroplasmy levels across brain regions within subjects suggest that somatic mutations accumulate differentially in brain regions. Finally, multiplasmy, a heteroplasmic measure of repeat length, was observed in brain from selective cases at a higher frequency than controls. These results offer support for increased rates of mtDNA substitutions in schizophrenia shown in our prior results. The variable levels of heteroplasmic/multiplasmic somatic mutations that occur in brain may be indicators of genetic instability in mtDNA. PMID:26011537

Utilizing multiple scale models to improve predictions of extra-axial hemorrhage in the immature piglet.

PubMed

Scott, Gregory G; Margulies, Susan S; Coats, Brittany

2016-10-01

Traumatic brain injury (TBI) is a leading cause of death and disability in the USA. To help understand and better predict TBI, researchers have developed complex finite element (FE) models of the head which incorporate many biological structures such as scalp, skull, meninges, brain (with gray/white matter differentiation), and vasculature. However, most models drastically simplify the membranes and substructures between the pia and arachnoid membranes. We hypothesize that substructures in the pia-arachnoid complex (PAC) contribute substantially to brain deformation following head rotation, and that when included in FE models accuracy of extra-axial hemorrhage prediction improves. To test these hypotheses, microscale FE models of the PAC were developed to span the variability of PAC substructure anatomy and regional density. The constitutive response of these models were then integrated into an existing macroscale FE model of the immature piglet brain to identify changes in cortical stress distribution and predictions of extra-axial hemorrhage (EAH). Incorporating regional variability of PAC substructures substantially altered the distribution of principal stress on the cortical surface of the brain compared to a uniform representation of the PAC. Simulations of 24 non-impact rapid head rotations in an immature piglet animal model resulted in improved accuracy of EAH prediction (to 94 % sensitivity, 100 % specificity), as well as a high accuracy in regional hemorrhage prediction (to 82-100 % sensitivity, 100 % specificity). We conclude that including a biofidelic PAC substructure variability in FE models of the head is essential for improved predictions of hemorrhage at the brain/skull interface.

Global and Regional Brain Assessment with Quantitative MR Imaging in Patients with Prior Exposure to Linear Gadolinium-based Contrast Agents.

PubMed

Kuno, Hirofumi; Jara, Hernán; Buch, Karen; Qureshi, Muhammad Mustafa; Chapman, Margaret N; Sakai, Osamu

2017-04-01

Purpose To assess the association of global and regional brain relaxation times in patients with prior exposure to linear gadolinium-based contrast agents (GBCAs). Materials and Methods The institutional review board approved this cross-sectional study. Thirty-five patients (nine who had received GBCA gadopentetate dimeglumine injections previously [one to eight times] and 26 patients who did not) who underwent brain magnetic resonance (MR) imaging with a mixed fast spin-echo pulse sequence were assessed. The whole brain was segmented according to white and gray matter by using a dual-clustering algorithm. In addition, regions of interest were measured in the globus pallidus, dentate nucleus, thalamus, and pons. The Mann-Whitney U test was used to assess the difference between groups. Multiple regression analysis was performed to assess the association of T1 and T2 with prior GBCA exposure. Results T1 values of gray matter were significantly shorter for patients with than for patients without prior GBCA exposure (P = .022). T1 of the gray matter of the whole brain (P < .001), globus pallidus (P = .002), dentate nucleus (P = .046), and thalamus (P = .026) and T2 of the whole brain (P = .004), dentate nucleus (P = .023), and thalamus (P = .002) showed a significant correlation with the accumulated dose of previous GBCA administration. There was no significant correlation between T1 and the accumulated dose of previous GBCA injections in the white matter (P = .187). Conclusion Global and regional quantitative assessments of T1 and T2 demonstrated an association with prior GBCA exposure, especially for gray matter structures. The results of this study confirm previous research findings that there is gadolinium deposition in wider distribution throughout the brain. © RSNA, 2016 Online supplemental material is available for this article.

Circadian signaling in Homarus americanus: Region-specific de novo assembled transcriptomes show that both the brain and eyestalk ganglia possess the molecular components of a putative clock system.

PubMed

Christie, Andrew E; Yu, Andy; Pascual, Micah G; Roncalli, Vittoria; Cieslak, Matthew C; Warner, Amanda N; Lameyer, Tess J; Stanhope, Meredith E; Dickinson, Patsy S; Joe Hull, J

2018-04-11

Essentially all organisms exhibit recurring patterns of physiology/behavior that oscillate with a period of ~24-h and are synchronized to the solar day. Crustaceans are no exception, with robust circadian rhythms having been documented in many members of this arthropod subphylum. However, little is known about the molecular underpinnings of their circadian rhythmicity. Moreover, the location of the crustacean central clock has not been firmly established, although both the brain and eyestalk ganglia have been hypothesized as loci. The American lobster, Homarus americanus, is known to exhibit multiple circadian rhythms, and immunodetection data suggest that its central clock is located within the eyestalk ganglia rather than in the brain. Here, brain- and eyestalk ganglia-specific transcriptomes were generated and used to assess the presence/absence of transcripts encoding the commonly recognized protein components of arthropod circadian signaling systems in these two regions of the lobster central nervous system. Transcripts encoding putative homologs of the core clock proteins clock, cryptochrome 2, cycle, period and timeless were found in both the brain and eyestalk ganglia assemblies, as were transcripts encoding similar complements of putative clock-associated, clock input pathway and clock output pathway proteins. The presence and identity of transcripts encoding core clock proteins in both regions were confirmed using PCR. These findings suggest that both the brain and eyestalk ganglia possess all of the molecular components needed for the establishment of a circadian signaling system. Whether the brain and eyestalk clocks are independent of one another or represent a single timekeeping system remains to be determined. Interestingly, while most of the proteins deduced from the identified transcripts are shared by both the brain and eyestalk ganglia, assembly-specific isoforms were also identified, e.g., several period variants, suggesting the possibility of region-specific variation in clock function, especially if the brain and eyestalk clocks represent independent oscillators. Copyright © 2018 Elsevier B.V. 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

Individual identity and affective valence in marmoset calls: in vivo brain imaging with vocal sound playback.

PubMed

Kato, Masaki; Yokoyama, Chihiro; Kawasaki, Akihiro; Takeda, Chiho; Koike, Taku; Onoe, Hirotaka; Iriki, Atsushi

2018-05-01

As with humans, vocal communication is an important social tool for nonhuman primates. Common marmosets (Callithrix jacchus) often produce whistle-like 'phee' calls when they are visually separated from conspecifics. The neural processes specific to phee call perception, however, are largely unknown, despite the possibility that these processes involve social information. Here, we examined behavioral and whole-brain mapping evidence regarding the detection of individual conspecific phee calls using an audio playback procedure. Phee calls evoked sound exploratory responses when the caller changed, indicating that marmosets can discriminate between caller identities. Positron emission tomography with [ 18 F] fluorodeoxyglucose revealed that perception of phee calls from a single subject was associated with activity in the dorsolateral prefrontal, medial prefrontal, orbitofrontal cortices, and the amygdala. These findings suggest that these regions are implicated in cognitive and affective processing of salient social information. However, phee calls from multiple subjects induced brain activation in only some of these regions, such as the dorsolateral prefrontal cortex. We also found distinctive brain deactivation and functional connectivity associated with phee call perception depending on the caller change. According to changes in pupillary size, phee calls from a single subject induced a higher arousal level compared with those from multiple subjects. These results suggest that marmoset phee calls convey information about individual identity and affective valence depending on the consistency or variability of the caller. Based on the flexible perception of the call based on individual recognition, humans and marmosets may share some neural mechanisms underlying conspecific vocal perception.

Altered gray matter organization in children and adolescents with ADHD: a structural covariance connectome study

PubMed Central

Griffiths, K R; Grieve, S M; Kohn, M R; Clarke, S; Williams, L M; Korgaonkar, M S

2016-01-01

Although multiple studies have reported structural deficits in multiple brain regions in attention-deficit hyperactivity disorder (ADHD), we do not yet know if these deficits reflect a more systematic disruption to the anatomical organization of large-scale brain networks. Here we used a graph theoretical approach to quantify anatomical organization in children and adolescents with ADHD. We generated anatomical networks based on covariance of gray matter volumes from 92 regions across the brain in children and adolescents with ADHD (n=34) and age- and sex-matched healthy controls (n=28). Using graph theory, we computed metrics that characterize both the global organization of anatomical networks (interconnectivity (clustering), integration (path length) and balance of global integration and localized segregation (small-worldness)) and their local nodal measures (participation (degree) and interaction (betweenness) within a network). Relative to Controls, ADHD participants exhibited altered global organization reflected in more clustering or network segregation. Locally, nodal degree and betweenness were increased in the subcortical amygdalae in ADHD, but reduced in cortical nodes in the anterior cingulate, posterior cingulate, mid temporal pole and rolandic operculum. In ADHD, anatomical networks were disrupted and reflected an emphasis on subcortical local connections centered around the amygdala, at the expense of cortical organization. Brains of children and adolescents with ADHD may be anatomically configured to respond impulsively to the automatic significance of stimulus input without having the neural organization to regulate and inhibit these responses. These findings provide a novel addition to our current understanding of the ADHD connectome. PMID:27824356

Relationship Between Surface-Based Brain Morphometric Measures and Intelligence in Autism Spectrum Disorders: Influence of History of Language Delay.

PubMed

Balardin, Joana Bisol; Sato, João Ricardo; Vieira, Gilson; Feng, Yeu; Daly, Eileen; Murphy, Clodagh; Murphy, Declan; Ecker, Christine

2015-10-01

Autism spectrum disorders (ASD) are a group of conditions that show abnormalities in the neuroanatomy of multiple brain regions. The variability in the development of intelligence and language among individuals on the autism spectrum has long been acknowledged, but it remains unknown whether these differences impact on the neuropathology of ASD. In this study, we aimed to compare associations between surface-based regional brain measures and general intelligence (IQ) scores in ASD individuals with and without a history of language delay. We included 64 ASD adults of normal intelligence (37 without a history of language delay and 27 with a history of language delay and 80 neurotypicals). Regions with a significant association between verbal and nonverbal IQ and measures of cortical thickness (CT), surface area, and cortical volume were first identified in the combined sample of individuals with ASD and controls. Thicker dorsal frontal and temporal cortices, and thinner lateral orbital frontal and parieto-occipital cortices were associated with greater and lower verbal IQ scores, respectively. Correlations between cortical volume and verbal IQ were observed in similar regions as revealed by the CT analysis. A significant difference between ASD individuals with and without a history of language delay in the association between CT and verbal IQ was evident in the parieto-occipital region. These results indicate that ASD subgroups defined on the basis of differential language trajectories in childhood can have different associations between verbal IQ and brain measures in adulthood despite achieving similar levels of cognitive performance. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

The θ-γ neural code.

PubMed

Lisman, John E; Jensen, Ole

2013-03-20

Theta and gamma frequency oscillations occur in the same brain regions and interact with each other, a process called cross-frequency coupling. Here, we review evidence for the following hypothesis: that the dual oscillations form a code for representing multiple items in an ordered way. This form of coding has been most clearly demonstrated in the hippocampus, where different spatial information is represented in different gamma subcycles of a theta cycle. Other experiments have tested the functional importance of oscillations and their coupling. These involve correlation of oscillatory properties with memory states, correlation with memory performance, and effects of disrupting oscillations on memory. Recent work suggests that this coding scheme coordinates communication between brain regions and is involved in sensory as well as memory processes. Copyright © 2013 Elsevier Inc. All rights reserved.

Neural and Behavioral Responses During Self-Evaluative Processes Differ in Youth With and Without Autism

PubMed Central

Merchant, Junaid S.; Colich, Natalie L.; Hernandez, Leanna M.; Rudie, Jeff D.; Dapretto, Mirella

2012-01-01

This fMRI study investigated neural responses while making appraisals of self and other, across the social and academic domains, in children and adolescents with and without autism spectrum disorders (ASD). Compared to neurotypical youth, those with ASD exhibited hypoactivation of ventromedial prefrontal cortex during self-appraisals. Responses in middle cingulate cortex (MCC) and anterior insula (AI) also distinguished between groups. Stronger activity in MCC and AI during self-appraisals was associated with better social functioning in the ASD group. Although self-appraisals were significantly more positive in the neurotypical group, positivity was unrelated to brain activity in these regions. Together, these results suggest that multiple brain regions support making self-appraisals in neurotypical development, and function atypically in youth with ASD. PMID:22760337

Investigating the Intersession Reliability of Dynamic Brain-State Properties.

PubMed

Smith, Derek M; Zhao, Yrian; Keilholz, Shella D; Schumacher, Eric H

2018-06-01

Dynamic functional connectivity metrics have much to offer to the neuroscience of individual differences of cognition. Yet, despite the recent expansion in dynamic connectivity research, limited resources have been devoted to the study of the reliability of these connectivity measures. To address this, resting-state functional magnetic resonance imaging data from 100 Human Connectome Project subjects were compared across 2 scan days. Brain states (i.e., patterns of coactivity across regions) were identified by classifying each time frame using k means clustering. This was done with and without global signal regression (GSR). Multiple gauges of reliability indicated consistency in the brain-state properties across days and GSR attenuated the reliability of the brain states. Changes in the brain-state properties across the course of the scan were investigated as well. The results demonstrate that summary metrics describing the clustering of individual time frames have adequate test/retest reliability, and thus, these patterns of brain activation may hold promise for individual-difference research.

Sex differences in the developing brain as a source of inherent risk

PubMed Central

McCarthy, Margaret M.

2016-01-01

Brain development diverges in males and females in response to androgen production by the fetal testis. This sexual differentiation of the brain occurs during a sensitive window and induces enduring neuroanatomical and physiological changes that profoundly impact behavior. What we know about the contribution of sex chromosomes is still emerging, highlighting the need to integrate multiple factors into understanding sex differences, including the importance of context. The cellular mechanisms are best modeled in rodents and have provided both unifying principles and surprising specifics. Markedly distinct signaling pathways direct differentiation in specific brain regions, resulting in mosaicism of relative maleness, femaleness, and sameness through-out the brain, while canalization both exaggerates and constrains sex differences. Non-neuronal cells and inflammatory mediators are found in greater number and at higher levels in parts of male brains. This higher baseline of inflammation is speculated to increase male vulnerability to developmental neuropsychiatric disorders that are triggered by inflammation. PMID:28179808

Alzheimer disease alters the relationship of cardiorespiratory fitness with brain activity during the stroop task.

PubMed

Vidoni, Eric D; Gayed, Matthew R; Honea, Robyn A; Savage, Cary R; Hobbs, Derek; Burns, Jeffrey M

2013-07-01

Despite mounting evidence that physical activity has positive benefits for brain and cognitive health, there has been little characterization of the relationship between cardiorespiratory (CR) fitness and cognition-associated brain activity as measured by functional magnetic resonance imaging (fMRI). The lack of evidence is particularly glaring for diseases such as Alzheimer disease (AD) that degrade cognitive and functional performance. The aim of this study was to describe the relationship between regional brain activity during cognitive tasks and CR fitness level in people with and without AD. A case-control, single-observation study design was used. Thirty-four individuals (18 without dementia and 16 in the earliest stages of AD) completed maximal exercise testing and performed a Stroop task during fMRI. Cardiorespiratory fitness was inversely associated with anterior cingulate activity in the participants without dementia (r=-.48, P=.05) and unassociated with activation in those with AD (P>.7). Weak associations of CR fitness and middle frontal cortex were noted. The wide age range and the use of a single task in fMRI rather than multiple tasks challenging different cognitive capacities were limitations of the study. The results offer further support of the relationship between CR fitness and regional brain activity. However, this relationship may be attenuated by disease. Future work in this area may provide clinicians and researchers with interpretable and dependable regional fMRI biomarker signatures responsive to exercise intervention. It also may shed light on mechanisms by which exercise can support cognitive function.

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

PubMed

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

2012-07-01

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

Right lateralized white matter abnormalities in first-episode, drug-naive paranoid schizophrenia.

PubMed

Guo, Wenbin; Liu, Feng; Liu, Zhening; Gao, Keming; Xiao, Changqing; Chen, Huafu; Zhao, Jingping

2012-11-30

Numerous studies in first-episode schizophrenia suggest the involvement of white matter (WM) abnormalities in multiple regions underlying the pathogenesis of this condition. However, there has never been a neuroimaging study in patients with first-episode, drug-naive paranoid schizophrenia by using tract-based spatial statistics (TBSS) method. Here, we used diffusion tensor imaging (DTI) with TBSS method to investigate the brain WM integrity in patients with first-episode, drug-naive paranoid schizophrenia. Twenty patients with first-episode, drug-naive paranoid schizophrenia and 26 healthy subjects matched with age, gender, and education level were scanned with DTI. An automated TBSS approach was employed to analyze the data. Voxel-wise statistics revealed that patients with paranoid schizophrenia had decreased fractional anisotropy (FA) values in the right superior longitudinal fasciculus (SLF) II, the right fornix, the right internal capsule, and the right external capsule compared to healthy subjects. Patients did not have increased FA values in any brain regions compared to healthy subjects. There was no correlation between the FA values in any brain regions and patient demographics and the severity of illness. Our findings suggest right-sided alterations of WM integrity in the WM tracts of cortical and subcortical regions may play an important role in the pathogenesis of paranoid schizophrenia. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Hindbrain regional growth in preterm newborns and its impairment in relation to brain injury

PubMed Central

Kim, Hosung; Gano, Dawn; Ho, Mai-Lan; Guo, Xiaoyue M.; Unzueta, Alisa; Hess, Christopher; Ferriero, Donna M.; Xu, Duan; Barkovich, A. James

2016-01-01

Premature birth globally affects about 11.1% of all newborns and is a risk factor for neurodevelopmental disability in surviving infants. Histology has suggested that hindbrain subdivisions grow differentially, especially in the third trimester. Prematurity-related brain injuries occurring in this period may selectively affect more rapidly developing areas of hindbrain, thus accompanying region-specific impairments in growth and ultimately neurodevelopmental deficits. The current study aimed to quantify regional growth of the cerebellum and the brainstem in preterm neonates (n=65 with individually multiple scans). We probed associations of the regional volumes with severity of brain injury. In neonates with no imaging evidence of injury, our analysis using a mixed-effect linear model showed faster growth in the pons and the lateral convexity of anterior/posterior cerebellar lobes. Different patterns of growth impairment were found in relation to early cerebral intraventricular hemorrhage and cerebellar hemorrhage (p<0.05), likely explaining different mechanisms through which neurogenesis is disrupted. The pattern of cerebellar growth identified in our study agreed excellently with details of cerebellar morphogenesis in perinatal development, which has only been observed in histological data. Our proposed analytic framework may provide predictive imaging biomarkers for neurodevelopmental outcome, enabling early identification and treatment of high-risk patients. PMID:26589992

Brain Regions Involved in the Learning and Application of Reward Rules in a Two-Deck Gambling Task

ERIC Educational Resources Information Center

Hartstra, E.; Oldenburg, J. F. E.; Van Leijenhorst, L.; Rombouts, S. A. R. B.; Crone, E. A.

2010-01-01

Decision-making involves the ability to choose between competing actions that are associated with uncertain benefits and penalties. The Iowa Gambling Task (IGT), which mimics real-life decision-making, involves learning a reward-punishment rule over multiple trials. Patients with damage to ventromedial prefrontal cortex (VMPFC) show deficits…

Identification of Differentially Expressed Genes through Integrated Study of Alzheimer's Disease Affected Brain Regions.

PubMed

Puthiyedth, Nisha; Riveros, Carlos; Berretta, Regina; Moscato, Pablo

2016-01-01

Alzheimer's disease (AD) is the most common form of dementia in older adults that damages the brain and results in impaired memory, thinking and behaviour. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. In the past decade, several studies have reported many genes that are associated with AD. This wealth of information has become difficult to follow and interpret as most of the results are conflicting. In that case, it is worth doing an integrated study of multiple datasets that helps to increase the total number of samples and the statistical power in detecting biomarkers. In this study, we present an integrated analysis of five different brain region datasets and introduce new genes that warrant further investigation. The aim of our study is to apply a novel combinatorial optimisation based meta-analysis approach to identify differentially expressed genes that are associated to AD across brain regions. In this study, microarray gene expression data from 161 samples (74 non-demented controls, 87 AD) from the Entorhinal Cortex (EC), Hippocampus (HIP), Middle temporal gyrus (MTG), Posterior cingulate cortex (PC), Superior frontal gyrus (SFG) and visual cortex (VCX) brain regions were integrated and analysed using our method. The results are then compared to two popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained by analysing the individual datasets. We find genes related with AD that are consistent with existing studies, and new candidate genes not previously related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1, RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across all brain regions. Further investigation on these genes may provide new insights into the development of AD. In addition, we identified the presence of 23 non-coding features, including four miRNA precursors (miR-7, miR570, miR-1229 and miR-6821), dysregulated across the brain regions. Furthermore, we compared our results with two popular meta-analysis methods RankProd and GeneMeta to validate our findings and performed a sensitivity analysis by removing one dataset at a time to assess the robustness of our results. These new findings may provide new insights into the disease mechanisms and thus make a significant contribution in the near future towards understanding, prevention and cure of AD.

On the lorentzian versus Gaussian character of time-domain spin-echo signals from the brain as sampled by means of gradient-echoes: Implications for quantitative transverse relaxation studies.

PubMed

Mulkern, Robert V; Balasubramanian, Mukund; Mitsouras, Dimitrios

2014-07-30

To determine whether Lorentzian or Gaussian intra-voxel frequency distributions are better suited for modeling data acquired with gradient-echo sampling of single spin-echoes for the simultaneous characterization of irreversible and reversible relaxation rates. Clinical studies (e.g., of brain iron deposition) using such acquisition schemes have typically assumed Lorentzian distributions. Theoretical expressions of the time-domain spin-echo signal for intra-voxel Lorentzian and Gaussian distributions were used to fit data from a human brain scanned at both 1.5 Tesla (T) and 3T, resulting in maps of irreversible and reversible relaxation rates for each model. The relative merits of the Lorentzian versus Gaussian model were compared by means of quality of fit considerations. Lorentzian fits were equivalent to Gaussian fits primarily in regions of the brain where irreversible relaxation dominated. In the multiple brain regions where reversible relaxation effects become prominent, however, Gaussian fits were clearly superior. The widespread assumption that a Lorentzian distribution is suitable for quantitative transverse relaxation studies of the brain should be reconsidered, particularly at 3T and higher field strengths as reversible relaxation effects become more prominent. Gaussian distributions offer alternate fits of experimental data that should prove quite useful in general. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

The endocrine-brain-aging triad where many paths meet: female reproductive hormone changes at midlife and their influence on circuits important for learning and memory.

PubMed

Koebele, Stephanie V; Bimonte-Nelson, Heather A

2017-08-01

Female mammals undergo natural fluctuations in sex steroid hormone levels throughout life. These fluctuations span from early development, to cyclic changes associated with the menstrual or estrous cycle and pregnancy, to marked hormone flux during perimenopause, and a final decline at reproductive senescence. While the transition to reproductive senescence is not yet fully understood, the vast majority of mammals experience this spontaneous, natural phenomenon with age, which has broad implications for long-lived species. Indeed, this post-reproductive life stage, and its transition, involves significant and enduring physiological changes, including considerably altered sex steroid hormone and gonadotropin profiles that impact multiple body systems, including the brain. The endocrine-brain-aging triad is especially noteworthy, as many paths meet and interact. Many of the brain regions affected by aging are also sensitive to changes in ovarian hormone levels, and aging and reproductive senescence are both associated with changes in memory performance. This review explores how menopause is related to cognitive aging, and discusses some of the key neural systems and molecular factors altered with age and reproductive hormone level changes, with an emphasis on brain regions important for learning and memory. Copyright © 2017. Published by Elsevier Inc.

A novel tetrode microdrive for simultaneous multi-neuron recording from different regions of primate brain.

PubMed

Santos, Lucas; Opris, Ioan; Fuqua, Joshua; Hampson, Robert E; Deadwyler, Sam A

2012-04-15

A unique custom-made tetrode microdrive for recording from large numbers of neurons in several areas of primate brain is described as a means for assessing simultaneous neural activity in cortical and subcortical structures in nonhuman primates (NHPs) performing behavioral tasks. The microdrive device utilizes tetrode technology with up to six ultra-thin microprobe guide tubes (0.1mm) that can be independently positioned, each containing reduced diameter tetrode and/or hexatrode microwires (0.02 mm) for recording and isolating single neuron activity. The microdrive device is mounted within the standard NHP cranial well and allows traversal of brain depths up to 40.0 mm. The advantages of this technology are demonstrated via simultaneously recorded large populations of neurons with tetrode type probes during task performance from a) primary motor cortex and deep brain structures (caudate-putamen and hippocampus) and b) multiple layers within the prefrontal cortex. The means to characterize interactions of well-isolated ensembles of neurons recorded simultaneously from different regions, as shown with this device, has not been previously available for application in primate brain. The device has extensive application to primate models for the detection and study of inoperative or maladaptive neural circuits related to human neurological disorders. Published by Elsevier B.V.

Self-medication with sucrose

PubMed Central

Ulrich-Lai, Yvonne M.

2016-01-01

For many individuals, stress promotes the consumption of sweet, high-sugar foods relative to healthier alternatives. Daily life stressors stimulate the overeating of highly-palatable foods through multiple mechanisms, including altered glucocorticoid, relaxin-3, ghrelin and serotonin signaling in brain. In turn, a history of consuming high-sugar foods attenuates the psychological (anxiety and depressed mood) and physiological (HPA axis) effects of stress. Together the metabolic and hedonic properties of sucrose contribute to its stress relief, possibly via actions in both the periphery (e.g., glucocorticoid receptor signaling in adipose tissue) and in the brain (e.g., plasticity in brain reward regions). Emerging work continues to reveal the bidirectional mechanisms that underlie the use of high-sugar foods as ‘self-medication’ for stress relief. PMID:26977424

MRI correlates of general intelligence in neurotypical adults.

PubMed

Malpas, Charles B; Genc, Sila; Saling, Michael M; Velakoulis, Dennis; Desmond, Patricia M; O'Brien, Terence J

2016-02-01

There is growing interest in the neurobiological substrate of general intelligence. Psychometric estimates of general intelligence are reduced in a range of neurological disorders, leading to practical application as sensitive, but non-specific, markers of cerebral disorder. This study examined estimates of general intelligence in neurotypical adults using diffusion tensor imaging and resting-state functional connectivity analysis. General intelligence was related to white matter organisation across multiple brain regions, confirming previous work in older healthy adults. We also found that variation in general intelligence was related to a large functional sub-network involving all cortical lobes of the brain. These findings confirm that individual variance in general intelligence is related to diffusely represented brain networks. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sapphire implant based neuro-complex for deep-lying brain tumors phototheranostics

NASA Astrophysics Data System (ADS)

Sharova, A. S.; Maklygina, YU S.; Yusubalieva, G. M.; Shikunova, I. A.; Kurlov, V. N.; Loschenov, V. B.

2018-01-01

The neuro-complex as a combination of sapphire implant optical port and osteoplastic biomaterial "Collapan" as an Aluminum phthalocyanine nanoform photosensitizer (PS) depot was developed within the framework of this study. The main goals of such neuro-complex are to provide direct access of laser radiation to the brain tissue depth and to transfer PS directly to the pathological tissue location that will allow multiple optical phototheranostics of the deep-lying tumor region without repeated surgical intervention. The developed complex spectral-optical properties research was carried out by photodiagnostics method using the model sample: a brain tissue phantom. The optical transparency of sapphire implant allows obtaining a fluorescent signal with high accuracy, comparable to direct measurement "in contact" with the tissue.

Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI

DTIC Science & Technology

2015-10-01

Page | 2 AWARD NUMBER: W81XWH-13-1-0464 TITLE: Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI...Sep 2014 – 29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional...findings include: 1) detection of brain organization in a cohort of 24 pediatric onset multiple sclerosis patients (POMS) and 25 healthy controls

Discriminating Schizophrenia and Bipolar Disorder by Fusing FMRI and DTI in A Multimodal CCA+ Joint ICA Model

PubMed Central

Sui, Jing; Pearlson, Godfrey; Adali, Tülay; Kiehl, Kent A.; Caprihan, Arvind; Liu, Jingyu; Yamamoto, Jeremy; Calhoun, Vince D.

2011-01-01

Diverse structural and functional brain alterations have been identified in both schizophrenia and bipolar disorder, but with variable replicability, significant overlap and often in limited number of subjects. In this paper, we aimed to clarify differences between bipolar disorder and schizophrenia by combining fMRI (collected during an auditory oddball task) and diffusion tensor imaging (DTI) data. We proposed a fusion method, “multimodal CCA+ joint ICA’, which increases flexibility in statistical assumptions beyond existing approaches and can achieve higher estimation accuracy. The data collected from 164 participants (62 healthy controls, 54 schizophrenia and 48 bipolar) were extracted into “features” (contrast maps for fMRI and fractional anisotropy (FA) for DTI) and analyzed in multiple facets to investigate the group differences for each pair-wised groups and each modality. Specifically, both patient groups shared significant dysfunction in dorsolateral prefrontal cortex and thalamus, as well as reduced white matter (WM) integrity in anterior thalamic radiation and uncinate fasciculus. Schizophrenia and bipolar subjects were separated by functional differences in medial frontal and visual cortex, as well as WM tracts associated with occipital and frontal lobes. Both patients and controls showed similar spatial distributions in motor and parietal regions, but exhibited significant variations in temporal lobe. Furthermore, there were different group trends for age effects on loading parameters in motor cortex and multiple WM regions, suggesting brain dysfunction and WM disruptions occurred in identified regions for both disorders. Most importantly, we can visualize an underlying function-structure network by evaluating the joint components with strong links between DTI and fMRI. Our findings suggest that although the two patient groups showed several distinct brain patterns from each other and healthy controls, they also shared common abnormalities in prefrontal thalamic WM integrity and in frontal brain mechanisms. PMID:21640835

Neonatal Pain-Related Stress Predicts Cortical Thickness at Age 7 Years in Children Born Very Preterm

PubMed Central

Ranger, Manon; Chau, Cecil M. Y.; Garg, Amanmeet; Woodward, Todd S.; Beg, Mirza Faisal; Bjornson, Bruce; Poskitt, Kenneth; Fitzpatrick, Kevin; Synnes, Anne R.; Miller, Steven P.; Grunau, Ruth E.

2013-01-01

Background Altered brain development is evident in children born very preterm (24–32 weeks gestational age), including reduction in gray and white matter volumes, and thinner cortex, from infancy to adolescence compared to term-born peers. However, many questions remain regarding the etiology. Infants born very preterm are exposed to repeated procedural pain-related stress during a period of very rapid brain development. In this vulnerable population, we have previously found that neonatal pain-related stress is associated with atypical brain development from birth to term-equivalent age. Our present aim was to evaluate whether neonatal pain-related stress (adjusted for clinical confounders of prematurity) is associated with altered cortical thickness in very preterm children at school age. Methods 42 right-handed children born very preterm (24–32 weeks gestational age) followed longitudinally from birth underwent 3-D T1 MRI neuroimaging at mean age 7.9 yrs. Children with severe brain injury and major motor/sensory/cognitive impairment were excluded. Regional cortical thickness was calculated using custom developed software utilizing FreeSurfer segmentation data. The association between neonatal pain-related stress (defined as the number of skin-breaking procedures) accounting for clinical confounders (gestational age, illness severity, infection, mechanical ventilation, surgeries, and morphine exposure), was examined in relation to cortical thickness using constrained principal component analysis followed by generalized linear modeling. Results After correcting for multiple comparisons and adjusting for neonatal clinical factors, greater neonatal pain-related stress was associated with significantly thinner cortex in 21/66 cerebral regions (p-values ranged from 0.00001 to 0.014), predominately in the frontal and parietal lobes. Conclusions In very preterm children without major sensory, motor or cognitive impairments, neonatal pain-related stress appears to be associated with thinner cortex in multiple regions at school age, independent of other neonatal risk factors. PMID:24204657

The allostatic impact of chronic ethanol on gene expression: A genetic analysis of chronic intermittent ethanol treatment in the BXD cohort

PubMed Central

van der Vaart, Andrew D.; Wolstenholme, Jennifer T.; Smith, Maren L.; Harris, Guy M.; Lopez, Marcelo F.; Wolen, Aaron R.; Becker, Howard C.; Williams, Robert W.; Miles, Michael F.

2016-01-01

The transition from acute to chronic ethanol exposure leads to lasting behavioral and physiological changes such as increased consumption, dependence, and withdrawal. Changes in brain gene expression are hypothesized to underlie these adaptive responses to ethanol. Previous studies on acute ethanol identified genetic variation in brain gene expression networks and behavioral responses to ethanol across the BXD panel of recombinant inbred mice. In this work, we have performed the first joint genetic and genomic analysis of transcriptome shifts in response to chronic intermittent ethanol (CIE) by vapor chamber exposure in a BXD cohort. CIE treatment is known to produce significant and sustained changes in ethanol consumption with repeated cycles of ethanol vapor. Using Affymetrix microarray analysis of prefrontal cortex (PFC) and nucleus accumbens (NAC) RNA, we compared CIE expression responses to those seen following acute ethanol treatment, and to voluntary ethanol consumption. Gene expression changes in PFC and NAC after CIE overlapped significantly across brain regions and with previously published expression following acute ethanol. Genes highly modulated by CIE were enriched for specific biological processes including synaptic transmission, neuron ensheathment, intracellular signaling, and neuronal projection development. Expression quantitative trait locus (eQTL) analyses identified genomic loci associated with ethanol-induced transcriptional changes with largely distinct loci identified between brain regions. Correlating CIE-regulated genes to ethanol consumption data identified specific genes highly associated with variation in the increase in drinking seen with repeated cycles of CIE. In particular, multiple myelin-related genes were identified. Furthermore, genetic variance in or near dynamin3 (Dnm3) on Chr1 at ~164 Mb may have a major regulatory role in CIE-responsive gene expression. Dnm3 expression correlates significantly with ethanol consumption, is contained in a highly ranked functional group of CIE-regulated genes in the NAC, and has a cis-eQTL within a genomic region linked with multiple CIE-responsive genes. PMID:27838001

SLC9A9 Co-expression modules in autism-associated brain regions.

PubMed

Patak, Jameson; Hess, Jonathan L; Zhang-James, Yanli; Glatt, Stephen J; Faraone, Stephen V

2017-03-01

SLC9A9 is a sodium hydrogen exchanger present in the recycling endosome and highly expressed in the brain. It is implicated in neuropsychiatric disorders, including autism spectrum disorders (ASDs). Little research concerning its gene expression patterns and biological pathways has been conducted. We sought to investigate its possible biological roles in autism-associated brain regions throughout development. We conducted a weighted gene co-expression network analysis on RNA-seq data downloaded from Brainspan. We compared prenatal and postnatal gene expression networks for three ASD-associated brain regions known to have high SLC9A9 gene expression. We also performed an ASD-associated single nucleotide polymorphism enrichment analysis and a cell signature enrichment analysis. The modules showed differences in gene constituents (membership), gene number, and connectivity throughout time. SLC9A9 was highly associated with immune system functions, metabolism, apoptosis, endocytosis, and signaling cascades. Gene list comparison with co-immunoprecipitation data was significant for multiple modules. We found a disproportionately high autism risk signal among genes constituting the prenatal hippocampal module. The modules were enriched with astrocyte and oligodendrocyte markers. SLC9A9 is potentially involved in the pathophysiology of ASDs. Our investigation confirmed proposed functions for SLC9A9, such as endocytosis and immune regulation, while also revealing potential roles in mTOR signaling and cell survival.. By providing a concise molecular map and interactions, evidence of cell type and implicated brain regions we hope this will guide future research on SLC9A9. Autism Res 2017, 10: 414-429. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Female adolescents with severe substance and conduct problems have substantially less brain gray matter volume.

PubMed

Dalwani, Manish S; McMahon, Mary Agnes; Mikulich-Gilbertson, Susan K; Young, Susan E; Regner, Michael F; Raymond, Kristen M; McWilliams, Shannon K; Banich, Marie T; Tanabe, Jody L; Crowley, Thomas J; Sakai, Joseph T

2015-01-01

Structural neuroimaging studies have demonstrated lower regional gray matter volume in adolescents with severe substance and conduct problems. These research studies, including ours, have generally focused on male-only or mixed-sex samples of adolescents with conduct and/or substance problems. Here we compare gray matter volume between female adolescents with severe substance and conduct problems and female healthy controls of similar ages. Female adolescents with severe substance and conduct problems will show significantly less gray matter volume in frontal regions critical to inhibition (i.e. dorsolateral prefrontal cortex and ventrolateral prefrontal cortex), conflict processing (i.e., anterior cingulate), valuation of expected outcomes (i.e., medial orbitofrontal cortex) and the dopamine reward system (i.e. striatum). We conducted whole-brain voxel-based morphometric comparison of structural MR images of 22 patients (14-18 years) with severe substance and conduct problems and 21 controls of similar age using statistical parametric mapping (SPM) and voxel-based morphometric (VBM8) toolbox. We tested group differences in regional gray matter volume with analyses of covariance, adjusting for age and IQ at p<0.05, corrected for multiple comparisons at whole-brain cluster-level threshold. Female adolescents with severe substance and conduct problems compared to controls showed significantly less gray matter volume in right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, medial orbitofrontal cortex, anterior cingulate, bilateral somatosensory cortex, left supramarginal gyrus, and bilateral angular gyrus. Considering the entire brain, patients had 9.5% less overall gray matter volume compared to controls. Female adolescents with severe substance and conduct problems in comparison to similarly aged female healthy controls showed substantially lower gray matter volume in brain regions involved in inhibition, conflict processing, valuation of outcomes, decision-making, reward, risk-taking, and rule-breaking antisocial behavior.

A Cross-Sectional Voxel-Based Morphometric Study of Age- and Sex-Related Changes in Gray Matter Volume in the Normal Aging Brain.

PubMed

Peng, Fei; Wang, Lixin; Geng, Zuojun; Zhu, Qingfeng; Song, Zhenhu

2016-01-01

The aim of the study was to carry out a cross-sectional study of 124 cognitively normal Chinese adults using the voxel-based morphometry approach to delineate age-related changes in the gray matter volume of regions of interest (ROI) in the brain and further analyze their correlation with age. One hundred twenty-four cognitively normal adults were divided into the young age group, the middle age group, and the old age group. Conventional magnetic resonance imaging was performed with the Achieva 3.0 T system. Structural images were processed using VBM8 and SPM8. Regions of interest were obtained by WFU PickAtlas and all realigned images were spatially normalized. Females showed significantly greater total gray matter volume than males (t = 4.81, P = 0.0000, false discovery rate corrected). Compared with young subjects, old-aged subjects showed extensive reduction in gray matter volumes in all ROIs examined except the occipital lobe. In young- and middle-aged subjects, female and male subjects showed significant difference in the right middle temporal gyrus, right superior temporal gyrus, left angular gyrus, right middle occipital lobe, left middle cingulate gyrus, and the pars triangularis of the right inferior frontal gyrus, suggesting an interaction between age and sex (P < 0.001, uncorrected). Logistic regression analysis revealed linear negative correlation between the total gray matter volume and age (R = 0.529, P < 0.001). Significant age-related differences are present in gray matter volume across multiple brain regions during aging. The VPM approach may provide an emerging paradigm in the normal aging brain that may help differentiate underlying normal neurobiological aging changes of specific brain regions from neurodegenerative impairments.

The impact of ADHD persistence, recent cannabis use, and age of regular cannabis use onset on subcortical volume and cortical thickness in young adults.

PubMed

Lisdahl, Krista M; Tamm, Leanne; Epstein, Jeffery N; Jernigan, Terry; Molina, Brooke S G; Hinshaw, Stephen P; Swanson, James M; Newman, Erik; Kelly, Clare; Bjork, James M

2016-04-01

Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Impact of ADHD Persistence, Recent Cannabis Use, and Age of Regular Cannabis Use Onset on Subcortical Volume and Cortical Thickness in Young Adults

PubMed Central

Lisdahl, Krista M.; Tamm, Leanne; Epstein, Jeffery N.; Jernigan, Terry; Molina, Brooke S.G.; Hinshaw, Stephen P.; Swanson, James M.; Newman, Erik; Kelly, Clare; Bjork, James M.

2017-01-01

Background Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. Methods Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. Results After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. Discussion Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. PMID:26897585

Nicotine effects on brain function and functional connectivity in schizophrenia.

PubMed

Jacobsen, Leslie K; D'Souza, D Cyril; Mencl, W Einar; Pugh, Kenneth R; Skudlarski, Pawel; Krystal, John H

2004-04-15

Nicotine in tobacco smoke can improve functioning in multiple cognitive domains. High rates of smoking among schizophrenic patients may reflect an effort to remediate cognitive dysfunction. Our primary aim was to determine whether nicotine improves cognitive function by facilitating activation of brain regions mediating task performance or by facilitating functional connectivity. Thirteen smokers with schizophrenia and 13 smokers with no mental illness were withdrawn from tobacco and underwent functional magnetic resonance imaging (fMRI) scanning twice, once after placement of a placebo patch and once after placement of a nicotine patch. During scanning, subjects performed an n-back task with two levels of working memory load and of selective attention load. During the most difficult (dichotic 2-back) task condition, nicotine improved performance of schizophrenic subjects and worsened performance of control subjects. Nicotine also enhanced activation of a network of regions, including anterior cingulate cortex and bilateral thalamus, and modulated thalamocortical functional connectivity to a greater degree in schizophrenic than in control subjects during dichotic 2-back task performance. In tasks that tax working memory and selective attention, nicotine may improve performance in schizophrenia patients by enhancing activation of and functional connectivity between brain regions that mediate task performance.

Multiple White Matter Volume Reductions in Patients with Panic Disorder: Relationships between Orbitofrontal Gyrus Volume and Symptom Severity and Social Dysfunction

PubMed Central

Konishi, Jun; Asami, Takeshi; Hayano, Fumi; Yoshimi, Asuka; Hayasaka, Shunsuke; Fukushima, Hiroshi; Whitford, Thomas J.; Inoue, Tomio; Hirayasu, Yoshio

2014-01-01

Numerous brain regions are believed to be involved in the neuropathology of panic disorder (PD) including fronto-limbic regions, thalamus, brain stem, and cerebellum. However, while several previous studies have demonstrated volumetric gray matter reductions in these brain regions, there have been no studies evaluating volumetric white matter changes in the fiber bundles connecting these regions. In addition, although patients with PD typically exhibit social, interpersonal and occupational dysfunction, the neuropathologies underlying these dysfunctions remain unclear. A voxel-based morphometry study was conducted to evaluate differences in regional white matter volume between 40 patients with PD and 40 healthy control subjects (HC). Correlation analyses were performed between the regional white matter volumes and patients' scores on the Panic Disorder Severity Scale (PDSS) and the Global Assessment of Functioning (GAF). Patients with PD demonstrated significant volumetric reductions in widespread white matter regions including fronto-limbic, thalamo-cortical and cerebellar pathways (p<0.05, FDR corrected). Furthermore, there was a significant negative relationship between right orbitofrontal gyrus (OFG) white matter volume and the severity of patients' clinical symptoms, as assessed with the PDSS. A significant positive relationship was also observed between patients' right OFG volumes and their scores on the GAF. Our results suggest that volumetric reductions in widespread white matter regions may play an important role in the pathology of PD. In particular, our results suggest that structural white matter abnormalities in the right OFG may contribute to the social, personal and occupational dysfunction typically experienced by patients with PD. PMID:24663245

Characterization of anomalous relaxation using the time-fractional Bloch equation and multiple echo T2 *-weighted magnetic resonance imaging at 7 T.

PubMed

Qin, Shanlin; Liu, Fawang; Turner, Ian W; Yu, Qiang; Yang, Qianqian; Vegh, Viktor

2017-04-01

To study the utility of fractional calculus in modeling gradient-recalled echo MRI signal decay in the normal human brain. We solved analytically the extended time-fractional Bloch equations resulting in five model parameters, namely, the amplitude, relaxation rate, order of the time-fractional derivative, frequency shift, and constant offset. Voxel-level temporal fitting of the MRI signal was performed using the classical monoexponential model, a previously developed anomalous relaxation model, and using our extended time-fractional relaxation model. Nine brain regions segmented from multiple echo gradient-recalled echo 7 Tesla MRI data acquired from five participants were then used to investigate the characteristics of the extended time-fractional model parameters. We found that the extended time-fractional model is able to fit the experimental data with smaller mean squared error than the classical monoexponential relaxation model and the anomalous relaxation model, which do not account for frequency shift. We were able to fit multiple echo time MRI data with high accuracy using the developed model. Parameters of the model likely capture information on microstructural and susceptibility-induced changes in the human brain. Magn Reson Med 77:1485-1494, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Model for the computation of self-motion in biological systems

NASA Technical Reports Server (NTRS)

Perrone, John A.

1992-01-01

A technique is presented by which direction- and speed-tuned cells, such as those commonly found in the middle temporal region of the primate brain, can be utilized to analyze the patterns of retinal image motion that are generated during observer movement through the environment. The developed model determines heading by finding the peak response in a population of detectors or neurons each tuned to a particular heading direction. It is suggested that a complex interaction of multiple cell networks is required for the solution of the self-motion problem in the primate brain.

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

PubMed Central

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

2012-01-01

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

Brain representations for acquiring and recalling visual-motor adaptations

PubMed Central

Bédard, Patrick; Sanes, Jerome N.

2014-01-01

Humans readily learn and remember new motor skills, a process that likely underlies adaptation to changing environments. During adaptation, the brain develops new sensory-motor relationships, and if consolidation occurs, a memory of the adaptation can be retained for extended periods. Considerable evidence exists that multiple brain circuits participate in acquiring new sensory-motor memories, though the networks engaged in recalling these and whether the same brain circuits participate in their formation and recall has less clarity. To address these issues, we assessed brain activation with functional MRI while young healthy adults learned and recalled new sensory-motor skills by adapting to world-view rotations of visual feedback that guided hand movements. We found cerebellar activation related to adaptation rate, likely reflecting changes related to overall adjustments to the visual rotation. A set of parietal and frontal regions, including inferior and superior parietal lobules, premotor area, supplementary motor area and primary somatosensory cortex, exhibited non-linear learning-related activation that peaked in the middle of the adaptation phase. Activation in some of these areas, including the inferior parietal lobule, intra-parietal sulcus and somatosensory cortex, likely reflected actual learning, since the activation correlated with learning after-effects. Lastly, we identified several structures having recall-related activation, including the anterior cingulate and the posterior putamen, since the activation correlated with recall efficacy. These findings demonstrate dynamic aspects of brain activation patterns related to formation and recall of a sensory-motor skill, such that non-overlapping brain regions participate in distinctive behavioral events. PMID:25019676

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

PubMed

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

2012-12-04

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

Early fever after trauma: Does it matter?

PubMed

Hinson, Holly E; Rowell, Susan; Morris, Cynthia; Lin, Amber L; Schreiber, Martin A

2018-01-01

Fever is strongly associated with poor outcome after traumatic brain injury (TBI). We hypothesized that early fever is a direct result of brain injury and thus would be more common in TBI than in patients without brain injury and associated with inflammation. We prospectively enrolled patients with major trauma with and without TBI from a busy Level I trauma center intensive care unit (ICU). Patients were assigned to one of four groups based on their presenting Head Abbreviated Injury Severity Scale scores: multiple injuries: head Abbreviated Injury Scale (AIS) score greater than 2, one other region greater than 2; isolated head: head AIS score greater than 2, all other regions less than 3; isolated body: one region greater than 2, excluding head/face; minor injury: no region with AIS greater than 2. Early fever was defined as at least one recorded temperature greater than 38.3°C in the first 48 hours after admission. Outcome measures included neurologic deterioration, length of stay in the ICU, hospital mortality, discharge Glasgow Outcome Scale-Extended, and plasma levels of seven key cytokines at admission and 24 hours (exploratory). Two hundred sixty-eight patients were enrolled, including subjects with multiple injuries (n = 59), isolated head (n = 97), isolated body (n = 100), and minor trauma (n = 12). The incidence of fever was similar in all groups irrespective of injury (11-24%). In all groups, there was a significant association between the presence of early fever and death in the hospital (6-18% vs. 0-3%), as well as longer median ICU stays (3-7 days vs. 2-3 days). Fever was significantly associated with elevated IL-6 at admission (50.7 pg/dL vs. 16.9 pg/dL, p = 0.0067) and at 24 hours (83.1 pg/dL vs. 17.1 pg/dL, p = 0.0025) in the isolated head injury group. Contrary to our hypothesis, early fever was not more common in patients with brain injury, though fever was associated with longer ICU stays and death in all groups. Additionally, fever was associated with elevated IL-6 levels in isolated head injury. Prognostic and Epidemiological study, level III.

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.

Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: A pilot project of the ENIGMA–DTI working group

PubMed Central

Jahanshad, Neda; Kochunov, Peter; Sprooten, Emma; Mandl, René C.; Nichols, Thomas E.; Almassy, Laura; Blangero, John; Brouwer, Rachel M.; Curran, Joanne E.; de Zubicaray, Greig I.; Duggirala, Ravi; Fox, Peter T.; Hong, L. Elliot; Landman, Bennett A.; Martin, Nicholas G.; McMahon, Katie L.; Medland, Sarah E.; Mitchell, Braxton D.; Olvera, Rene L.; Peterson, Charles P.; Starr, John M.; Sussmann, Jessika E.; Toga, Arthur W.; Wardlaw, Joanna M.; Wright, Margaret J.; Hulshoff Pol, Hilleke E.; Bastin, Mark E.; McIntosh, Andrew M.; Deary, Ian J.; Thompson, Paul M.; Glahn, David C.

2013-01-01

The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA–DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18–85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/). PMID:23629049

Expanding the spectrum of neuronal pathology in multiple system atrophy.

PubMed

Cykowski, Matthew D; Coon, Elizabeth A; Powell, Suzanne Z; Jenkins, Sarah M; Benarroch, Eduardo E; Low, Phillip A; Schmeichel, Ann M; Parisi, Joseph E

2015-08-01

Multiple system atrophy is a sporadic alpha-synucleinopathy that typically affects patients in their sixth decade of life and beyond. The defining clinical features of the disease include progressive autonomic failure, parkinsonism, and cerebellar ataxia leading to significant disability. Pathologically, multiple system atrophy is characterized by glial cytoplasmic inclusions containing filamentous alpha-synuclein. Neuronal inclusions also have been reported but remain less well defined. This study aimed to further define the spectrum of neuronal pathology in 35 patients with multiple system atrophy (20 male, 15 female; mean age at death 64.7 years; median disease duration 6.5 years, range 2.2 to 15.6 years). The morphologic type, topography, and frequencies of neuronal inclusions, including globular cytoplasmic (Lewy body-like) neuronal inclusions, were determined across a wide spectrum of brain regions. A correlation matrix of pathologic severity also was calculated between distinct anatomic regions of involvement (striatum, substantia nigra, olivary and pontine nuclei, hippocampus, forebrain and thalamus, anterior cingulate and neocortex, and white matter of cerebrum, cerebellum, and corpus callosum). The major finding was the identification of widespread neuronal inclusions in the majority of patients, not only in typical disease-associated regions (striatum, substantia nigra), but also within anterior cingulate cortex, amygdala, entorhinal cortex, basal forebrain and hypothalamus. Neuronal inclusion pathology appeared to follow a hierarchy of region-specific susceptibility, independent of the clinical phenotype, and the severity of pathology was duration-dependent. Neuronal inclusions also were identified in regions not previously implicated in the disease, such as within cerebellar roof nuclei. Lewy body-like inclusions in multiple system atrophy followed the stepwise anatomic progression of Lewy body-spectrum disease inclusion pathology in 25.7% of patients with multiple system atrophy, including a patient with visual hallucinations. Further, the presence of Lewy body-like inclusions in neocortex, but not hippocampal alpha-synuclein pathology, was associated with cognitive impairment (P = 0.002). However, several cases had the presence of isolated Lewy body-like inclusions at atypical sites (e.g. thalamus, deep cerebellar nuclei) that are not typical for Lewy body-spectrum disease. Finally, interregional correlations (rho ≥ 0.6) in pathologic glial and neuronal lesion burden suggest shared mechanisms of disease progression between both discrete anatomic regions (e.g. basal forebrain and hippocampus) and cell types (neuronal and glial inclusions in frontal cortex and white matter, respectively). These findings suggest that in addition to glial inclusions, neuronal pathology plays an important role in the developmental and progression of multiple system atrophy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Health assessment of gasoline and fuel oxygenate vapors: Neurotoxicity evaluation

PubMed Central

O’Callaghan, James P.; Daughtrey, Wayne C.; Clark, Charles R.; Schreiner, Ceinwen A.; White, Russell

2016-01-01

Sprague–Dawley rats were exposed via inhalation to vapor condensates of either gasoline or gasoline combined with various fuel oxygenates to assess potential neurotoxicity of evaporative emissions. Test articles included vapor condensates prepared from “baseline gasoline” (BGVC), or gasoline combined with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA). Target concentrations were 0, 2000, 10,000 or 20,000 mg/mg3 and exposures were for 6 h/day, 5 days/week for 13 weeks. The functional observation battery (FOB) with the addition of motor activity (MA) testing, hematoxylin and eosin staining of brain tissue sections, and brain regional analysis of glial fibrillary acidic protein (GFAP) were used to assess behavioral changes, traditional neuropathology and astrogliosis, respectively. FOB and MA data for all agents, except G/TBA, were negative. G/TBA behavioral effects resolved during recovery. Neuropathology was negative for all groups. Analyses of GFAP revealed increases in multiple brain regions largely limited to males of the G/EtOH group, findings indicative of minor gliosis, most significantly in the cerebellum. Small changes (both increases and decreases) in GFAP were observed for other test agents but effects were not consistent across sex, brain region or exposure concentration. PMID:24879970

Temporal and Spatial Effects of Blast Overpressure on Blood-Brain Barrier Permeability in Traumatic Brain Injury.

PubMed

Kuriakose, Matthew; Rama Rao, Kakulavarapu V; Younger, Daniel; Chandra, Namas

2018-06-06

Blast-induced traumatic brain injury (bTBI) is a "signature wound" in soldiers during training and in combat and has also become a major cause of morbidity in civilians due to increased insurgency. This work examines the role of blood-brain barrier (BBB) disruption as a result of both primary biomechanical and secondary biochemical injury mechanisms in bTBI. Extravasation of sodium fluorescein (NaF) and Evans blue (EB) tracers were used to demonstrate that compromise of the BBB occurs immediately following shock loading, increases in intensity up to 4 hours and returns back to normal in 24 hours. This BBB compromise occurs in multiple regions of the brain in the anterior-posterior direction of the shock wave, with maximum extravasation seen in the frontal cortex. Compromise of the BBB is confirmed by (a) extravasation of tracers into the brain, (b) quantification of tight-junction proteins (TJPs) in the brain and the blood, and (c) tracking specific blood-borne molecules into the brain and brain-specific proteins into the blood. Taken together, this work demonstrates that the BBB compromise occurs as a part of initial biomechanical loading and is a function of increasing blast overpressures.

[Attenuated rabies virus, ERA strain, in cattle and dogs vaccinated with multiple doses].

PubMed

Titoli, F; Pestalozza, S; Irsara, A; Palliola, E; Frescura, T; Civardi, A

1982-01-01

Investigation on the vaccination of 18 cattle and 5 dogs against rabies is reported. Each animal received multiple doses of ERA strain vaccine intramuscularly in the gluteal or masseter region. The saliva, the brain and salivary glands of the vaccinated animals were examined to detect the presence of ERA virus using immunofluorescent test and mouse inoculation. The virus was never found in the saliva and organs of treated animals. Circulating antibodies against ERA rabies virus were detected in all vaccinated cattle and dogs.

Applications of the Morris water maze in translational traumatic brain injury research.

PubMed

Tucker, Laura B; Velosky, Alexander G; McCabe, Joseph T

2018-05-01

Acquired traumatic brain injury (TBI) is frequently accompanied by persistent cognitive symptoms, including executive function disruptions and memory deficits. The Morris Water Maze (MWM) is the most widely-employed laboratory behavioral test for assessing cognitive deficits in rodents after experimental TBI. Numerous protocols exist for performing the test, which has shown great robustness in detecting learning and memory deficits in rodents after infliction of TBI. We review applications of the MWM for the study of cognitive deficits following TBI in pre-clinical studies, describing multiple ways in which the test can be employed to examine specific aspects of learning and memory. Emphasis is placed on dependent measures that are available and important controls that must be considered in the context of TBI. Finally, caution is given regarding interpretation of deficits as being indicative of dysfunction of a single brain region (hippocampus), as experimental models of TBI most often result in more diffuse damage that disrupts multiple neural pathways and larger functional networks that participate in complex behaviors required in MWM performance. Published by Elsevier Ltd.

MRI Correlates of Disability in African-Americans with Multiple Sclerosis

PubMed Central

Howard, Jonathan; Battaglini, Marco; Babb, James Scott; Arienzo, Donatello; Holst, Brigitte; Omari, Mirza; De Stefano, Nicola; Herbert, Joseph; Inglese, Matilde

2012-01-01

Objectives Multiple sclerosis (MS) in African-Americans (AAs) is characterized by more rapid disease progression and poorer response to treatment than in Caucasian-Americans (CAs). MRI provides useful and non-invasive tools to investigate the pathological substrate of clinical progression. The aim of our study was to compare MRI measures of brain damage between AAs and CAs with MS. Methods Retrospective analysis of 97 AAs and 97 CAs with MS matched for age, gender, disease duration and age at MRI examination. Results AA patients had significantly greater T2- (p = 0.001) and T1-weighted (p = 0.0003) lesion volumes compared to CA patients. In contrast, measurements of global and regional brain volume did not significantly differ between the two ethnic groups (p>0.1). Conclusions By studying a quite large sample of well demographically and clinically matched CA and AA patients with a homogeneous MRI protocol we showed that higher lesion accumulation, rather than pronounced brain volume decrease might explain the early progress to ambulatory assistance of AAs with MS. PMID:22900088

Heterogeneity of reward mechanisms.

PubMed

Lajtha, A; Sershen, H

2010-06-01

The finding that many drugs that have abuse potential and other natural stimuli such as food or sexual activity cause similar chemical changes in the brain, an increase in extracellular dopamine (DA) in the shell of the nucleus accumbens (NAccS), indicated some time ago that the reward mechanism is at least very similar for all stimuli and that the mechanism is relatively simple. The presently available information shows that the mechanisms involved are more complex and have multiple elements. Multiple brain regions, multiple receptors, multiple distinct neurons, multiple transmitters, multiple transporters, circuits, peptides, proteins, metabolism of transmitters, and phosphorylation, all participate in reward mechanisms. The system is variable, is changed during development, is sex-dependent, and is influenced by genetic differences. Not all of the elements participate in the reward of all stimuli. Different set of mechanisms are involved in the reward of different drugs of abuse, yet different mechanisms in the reward of natural stimuli such as food or sexual activity; thus there are different systems that distinguish different stimuli. Separate functions of the reward system such as anticipation, evaluation, consummation and identification; all contain function-specific elements. The level of the stimulus also influences the participation of the elements of the reward system, there are possible reactions to even below threshold stimuli, and excessive stimuli can change reward to aversion involving parts of the system. Learning and memory of past reward is an important integral element of reward and addictive behavior. Many of the reward elements are altered by repeated or chronic stimuli, and chronic exposure to one drug is likely to alter the response to another stimulus. To evaluate and identify the reward stimulus thus requires heterogeneity of the reward components in the brain.

No association between hair cortisol or cortisone and brain morphology in children.

PubMed

Chen, Ruoqing; Muetzel, Ryan L; El Marroun, Hanan; Noppe, Gerard; van Rossum, Elisabeth F C; Jaddoe, Vincent W; Verhulst, Frank C; White, Tonya; Fang, Fang; Tiemeier, Henning

2016-12-01

Little is known about the relationship between the long-term hypothalamic-pituitary-adrenal (HPA) axis functioning and brain structure in children. Glucocorticoid in hair has emerged as an important biomarker of HPA activity. In this study, we investigated the associations of hair cortisol and cortisone concentrations with brain morphology in young children. We included 219 children aged 6-10 years from the Generation R Study in Rotterdam, the Netherlands. We examined cortisol and cortisone concentrations by hair analysis using liquid chromatography-tandem mass spectrometry, and assessed brain morphometric measures with structural magnetic resonance imaging. The relationships of hair cortisol and cortisone concentrations with brain volumetrics, cortical thickness, cortical surface area and gyrification were analyzed separately after adjustment for several potential confounding factors. We observed a positive association between cortisol concentrations and cortical surface area in the parietal lobe, positive associations of cortisone concentrations with thalamus volume, occipital lobe volume and cortical surface area in the parietal lobe, and a negative association between cortisone concentrations and cortical surface area in the temporal lobe in the regions of interest analyses. A negative association between cortisol or cortisone concentrations and hippocampal volume was observed in children with behavioral problems. The whole brain vertex-wise analyses did however not show any association between cortisol or cortisone concentration and brain morphometric measures after correction for multiple testing. Although some associations are noted in region of interest analyses, we do not observe clear association of hair cortisol or cortisone with brain morphometric measures in typically developing young children. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanical characterization of human brain tissue.

PubMed

Budday, S; Sommer, G; Birkl, C; Langkammer, C; Haybaeck, J; Kohnert, J; Bauer, M; Paulsen, F; Steinmann, P; Kuhl, E; Holzapfel, G A

2017-01-15

Mechanics are increasingly recognized to play an important role in modulating brain form and function. Computational simulations are a powerful tool to predict the mechanical behavior of the human brain in health and disease. The success of these simulations depends critically on the underlying constitutive model and on the reliable identification of its material parameters. Thus, there is an urgent need to thoroughly characterize the mechanical behavior of brain tissue and to identify mathematical models that capture the tissue response under arbitrary loading conditions. However, most constitutive models have only been calibrated for a single loading mode. Here, we perform a sequence of multiple loading modes on the same human brain specimen - simple shear in two orthogonal directions, compression, and tension - and characterize the loading-mode specific regional and directional behavior. We complement these three individual tests by combined multiaxial compression/tension-shear tests and discuss effects of conditioning and hysteresis. To explore to which extent the macrostructural response is a result of the underlying microstructural architecture, we supplement our biomechanical tests with diffusion tensor imaging and histology. We show that the heterogeneous microstructure leads to a regional but not directional dependence of the mechanical properties. Our experiments confirm that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry. Using our measurements, we compare the performance of five common constitutive models, neo-Hookean, Mooney-Rivlin, Demiray, Gent, and Ogden, and show that only the isotropic modified one-term Ogden model is capable of representing the hyperelastic behavior under combined shear, compression, and tension loadings: with a shear modulus of 0.4-1.4kPa and a negative nonlinearity parameter it captures the compression-tension asymmetry and the increase in shear stress under superimposed compression but not tension. Our results demonstrate that material parameters identified for a single loading mode fail to predict the response under arbitrary loading conditions. Our systematic characterization of human brain tissue will lead to more accurate computational simulations, which will allow us to determine criteria for injury, to develop smart protection systems, and to predict brain development and disease progression. There is a pressing need to characterize the mechanical behavior of human brain tissue under multiple loading conditions, and to identify constitutive models that are able to capture the tissue response under these conditions. We perform a sequence of experimental tests on the same brain specimen to characterize the regional and directional behavior, and we supplement our tests with DTI and histology to explore to which extent the macrostructural response is a result of the underlying microstructure. Results demonstrate that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry, and we show that the multiaxial data can best be captured by a modified version of the one-term Ogden model. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Alzheimer's disease Braak Stage progressions: reexamined and redefined as Borrelia infection transmission through neural circuits.

PubMed

MacDonald, Alan B

2007-01-01

Brain structure in health is a dynamic energized equation incorporating chemistry, neuronal structure, and circuitry components. The chemistry "piece" is represented by multiple neurotransmitters such as Acetylcholine, Serotonin, and Dopamine. The neuronal structure "piece" incorporates synapses and their connections. And finally circuits of neurons establish "architectural blueprints" of anatomic wiring diagrams of the higher order of brain neuron organizations. In Alzheimer's disease, there are progressive losses in all of these components. Brain structure crumbles. The deterioration in Alzheimer's is ordered, reproducible, and stepwise. Drs. Braak and Braak have described stages in the Alzheimer disease continuum. "Progressions" through Braak Stages benchmark "Regressions" in Cognitive function. Under the microscope, the Stages of Braak commence in brain regions near to the hippocampus, and over time, like a tsunami wave of destruction, overturn healthy brain regions, with neurofibrillary tangle damaged neurons "marching" through the temporal lobe, neocortex and occipital cortex. In effect the destruction ascends from the limbic regions to progressively destroy the higher brain centers. Rabies infection also "begins low and finishes high" in its wave of destruction of brain tissue. Herpes Zoster infections offer the paradigm of clinical latency of infection inside of nerves before the "marching commences". Varicella Zoster virus enters neurons in the pediatric years. Dormant virus remains inside the neurons for 50-80 years, tissue damage late in life (shingles) demonstrates the "march of the infection" down neural pathways (dermatomes) as linear areas of painful blisters loaded with virus from a childhood infection. Amalgamation of Zoster with Rabies models produces a hybrid model to explain all of the Braak Stages of Alzheimer's disease under a new paradigm, namely "Alzheimer's neuroborreliosis" in which latent Borrelia infections ascend neural circuits through the hippocampus to the higher brain centers, creating a trail of neurofibrillary tangle injured neurons in neural circuits of cholinergic neurons by transsynaptic transmission of infection from nerve to nerve.

Automatic Semantic Segmentation of Brain Gliomas from MRI Images Using a Deep Cascaded Neural Network.

PubMed

Cui, Shaoguo; Mao, Lei; Jiang, Jingfeng; Liu, Chang; Xiong, Shuyu

2018-01-01

Brain tumors can appear anywhere in the brain and have vastly different sizes and morphology. Additionally, these tumors are often diffused and poorly contrasted. Consequently, the segmentation of brain tumor and intratumor subregions using magnetic resonance imaging (MRI) data with minimal human interventions remains a challenging task. In this paper, we present a novel fully automatic segmentation method from MRI data containing in vivo brain gliomas. This approach can not only localize the entire tumor region but can also accurately segment the intratumor structure. The proposed work was based on a cascaded deep learning convolutional neural network consisting of two subnetworks: (1) a tumor localization network (TLN) and (2) an intratumor classification network (ITCN). The TLN, a fully convolutional network (FCN) in conjunction with the transfer learning technology, was used to first process MRI data. The goal of the first subnetwork was to define the tumor region from an MRI slice. Then, the ITCN was used to label the defined tumor region into multiple subregions. Particularly, ITCN exploited a convolutional neural network (CNN) with deeper architecture and smaller kernel. The proposed approach was validated on multimodal brain tumor segmentation (BRATS 2015) datasets, which contain 220 high-grade glioma (HGG) and 54 low-grade glioma (LGG) cases. Dice similarity coefficient (DSC), positive predictive value (PPV), and sensitivity were used as evaluation metrics. Our experimental results indicated that our method could obtain the promising segmentation results and had a faster segmentation speed. More specifically, the proposed method obtained comparable and overall better DSC values (0.89, 0.77, and 0.80) on the combined (HGG + LGG) testing set, as compared to other methods reported in the literature. Additionally, the proposed approach was able to complete a segmentation task at a rate of 1.54 seconds per slice.

Occupational brain cancer risks in Umbria (Italy), with a particular focus on steel foundry workers.

PubMed

Oddone, Enrico; Scaburri, Alessandra; Bai, Edoardo; Modonesi, Carlo; Stracci, Fabrizio; Marchionna, Giuliano; Crosignani, Paolo; Imbriani, Marcello

2014-01-01

As a part of the Occupational Cancer Monitoring (OCCAM) project, a routine analysis based on Umbria region cancer registry (RTUP) database in 2002-2008 was performed. Among other results, the incidental finding of brain cancer increased risk in steel foundry workers in Terni province (Italy), lead us to deepen the analysis, focusing on this specific industrial sector. A monitoring study, based on Umbria Regional Cancer Registry data, was recently carried out. Brain cancer cases and controls identified within this preliminary study were selected. Therefore, we considered all incident cases (in Umbria region 2002-2008) of brain cancer occurred among workers occupied for at least one year in private companies since 1974 and controls randomly sampled from the same population. Afterwards, taking in to account results from steel foundry in Terni province, we further deepened our analysis, focusing on this productive sector. Odds ratios (ORs) and corresponding 90% confidence intervals (CIs) were calculated using multiple logistic regression models, adjusted by age at diagnosis or sampling, sex and province of residence, when appropriate. Statistical analyses were carried out on 14913 subjects, 56 cases and 14857 controls. Significantly increased ORs were observed for garment, mechanical manufacturing and chemical industries. Moreover, the risk estimates were strongly correlated with exposures in iron and steel foundries and a cluster of 14 cases in the same foundry in Terni was observed (OR 9.59, 90% CI 2.76-33.34). Results of this explorative study showed increased ORs of brain cancer in some productive branches, involving possible exposures to chemical compounds and/or solvents. Moreover, our results pointed out a significantly increased risk in Terni foundry workers, determining an interesting brain cancer cluster (14 cases). Further studies on this industrial sector are needed with improved definitions of tasks and exposures.

Resting state brain network function in major depression - Depression symptomatology, antidepressant treatment effects, future research.

PubMed

Brakowski, Janis; Spinelli, Simona; Dörig, Nadja; Bosch, Oliver Gero; Manoliu, Andrei; Holtforth, Martin Grosse; Seifritz, Erich

2017-09-01

The alterations of functional connectivity brain networks in major depressive disorder (MDD) have been subject of a large number of studies. Using different methodologies and focusing on diverse aspects of the disease, research shows heterogeneous results lacking integration. Disrupted network connectivity has been found in core MDD networks like the default mode network (DMN), the central executive network (CEN), and the salience network, but also in cerebellar and thalamic circuitries. Here we review literature published on resting state brain network function in MDD focusing on methodology, and clinical characteristics including symptomatology and antidepressant treatment related findings. There are relatively few investigations concerning the qualitative aspects of symptomatology of MDD, whereas most studies associate quantitative aspects with distinct resting state functional connectivity alterations. Such depression severity associated alterations are found in the DMN, frontal, cerebellar and thalamic brain regions as well as the insula and the subgenual anterior cingulate cortex. Similarly, different therapeutical options in MDD and their effects on brain function showed patchy results. Herein, pharmaceutical treatments reveal functional connectivity alterations throughout multiple brain regions notably the DMN, fronto-limbic, and parieto-temporal regions. Psychotherapeutical interventions show significant functional connectivity alterations in fronto-limbic networks, whereas electroconvulsive therapy and repetitive transcranial magnetic stimulation result in alterations of the subgenual anterior cingulate cortex, the DMN, the CEN and the dorsal lateral prefrontal cortex. While it appears clear that functional connectivity alterations are associated with the pathophysiology and treatment of MDD, future research should also generate a common strategy for data acquisition and analysis, as a least common denominator, to set the basis for comparability across studies and implementation of functional connectivity as a scientifically and clinically useful biomarker. Copyright © 2017 Elsevier Ltd. All rights reserved.

SU-E-T-306: Dosimetric Comparison of Leaf with Or Without Interdigitation in Multiple Brain Metastasis VMAT Treatment Planning

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

NONE

Purpose: To evaluate the effects of leaf with or without interdigitation in multiple brain metastasis volumetric modulated arc therapy (VMAT) plans. Methods: Twenty patients with 2 to 6 brain metastases of our hospital were retrospectively studied to be planned with dual arc VMAT using Monaco 3.3 TPS on the Elekta Synergy linear accelerator. The prescription dose of PTV was 60Gy/30 fractions. Two plans with or without leaf interdigitation were designed. The homogeneity index (HI), conformity index (CI), dose volume histograms (DVHs), monitor unit (MU), treatment time (T), the segments, the dose coverage of the target, were all evaluated. Results: Themore » plans with leaf interdigitation could achieve better CI (p<0.05) than without leaf interdigitation, while no significant difference were found in HI (p> 0.05) and the dose coverage of the target (p> 0.05).The MU,T, and the segments of the plan with leaf interdigitation were more than the plan without leaf interdigitation (p<0.05). There was no significant difference found in radiation dose of spinal cord, lenses and parotids, while the maximum dose of brain stem of leaf without interdigitation was higher than leaf with interdigitation (p< 0.05). It was worth noting that the areas of low dose regions with leaf interdigitation plan were much less than the without leaf interdigitation plan in the doublication planes (p< 0.05). Conclusion: This study shows that leaf with interdigitation has some advantages than leaf without interdigitation in multiple brain metastasis VMAT plans although the clinical relevance remains to be proven.« less

Circadian rhythmicity and light sensitivity of the zebrafish brain.

PubMed

Moore, Helen A; Whitmore, David

2014-01-01

Traditionally, circadian clocks have been thought of as a neurobiological phenomenon. This view changed somewhat over recent years with the discovery of peripheral tissue circadian oscillators. In mammals, however, the suprachiasmatic nucleus (SCN) in the hypothalamus still retains the critical role of a central synchronizer of biological timing. Zebrafish, in contrast, have always reflected a more highly decentralized level of clock organization, as individual cells and tissues contain directly light responsive circadian pacemakers. As a consequence, clock function in the zebrafish brain has remained largely unexplored, and the precise organization of rhythmic and light-sensitive neurons within the brain is unknown. To address this issue, we used the period3 (per3)-luciferase transgenic zebrafish to confirm that multiple brain regions contain endogenous circadian oscillators that are directly light responsive. In addition, in situ hybridization revealed localised neural expression of several rhythmic and light responsive clock genes, including per3, cryptochrome1a (cry1a) and per2. Adult brain nuclei showing significant clock gene expression include the teleost equivalent of the SCN, as well as numerous hypothalamic nuclei, the periventricular grey zone (PGZ) of the optic tectum, and granular cells of the rhombencephalon. To further investigate the light sensitive properties of neurons, expression of c-fos, a marker for neuronal activity, was examined. c-fos mRNA was upregulated in response to changing light conditions in different nuclei within the zebrafish brain. Furthermore, under constant dark (DD) conditions, c-fos shows a significant circadian oscillation. Taken together, these results show that there are numerous areas of the zebrafish central nervous system, which contain deep brain photoreceptors and directly light-entrainable circadian pacemakers. However, there are also multiple brain nuclei, which possess neither, demonstrating a degree of pacemaker complexity that was not previously appreciated.

Circadian Rhythmicity and Light Sensitivity of the Zebrafish Brain

PubMed Central

Moore, Helen A.; Whitmore, David

2014-01-01

Traditionally, circadian clocks have been thought of as a neurobiological phenomenon. This view changed somewhat over recent years with the discovery of peripheral tissue circadian oscillators. In mammals, however, the suprachiasmatic nucleus (SCN) in the hypothalamus still retains the critical role of a central synchronizer of biological timing. Zebrafish, in contrast, have always reflected a more highly decentralized level of clock organization, as individual cells and tissues contain directly light responsive circadian pacemakers. As a consequence, clock function in the zebrafish brain has remained largely unexplored, and the precise organization of rhythmic and light-sensitive neurons within the brain is unknown. To address this issue, we used the period3 (per3)-luciferase transgenic zebrafish to confirm that multiple brain regions contain endogenous circadian oscillators that are directly light responsive. In addition, in situ hybridization revealed localised neural expression of several rhythmic and light responsive clock genes, including per3, cryptochrome1a (cry1a) and per2. Adult brain nuclei showing significant clock gene expression include the teleost equivalent of the SCN, as well as numerous hypothalamic nuclei, the periventricular grey zone (PGZ) of the optic tectum, and granular cells of the rhombencephalon. To further investigate the light sensitive properties of neurons, expression of c-fos, a marker for neuronal activity, was examined. c-fos mRNA was upregulated in response to changing light conditions in different nuclei within the zebrafish brain. Furthermore, under constant dark (DD) conditions, c-fos shows a significant circadian oscillation. Taken together, these results show that there are numerous areas of the zebrafish central nervous system, which contain deep brain photoreceptors and directly light-entrainable circadian pacemakers. However, there are also multiple brain nuclei, which possess neither, demonstrating a degree of pacemaker complexity that was not previously appreciated. PMID:24465943

Source-based neurofeedback methods using EEG recordings: training altered brain activity in a functional brain source derived from blind source separation

PubMed Central

White, David J.; Congedo, Marco; Ciorciari, Joseph

2014-01-01

A developing literature explores the use of neurofeedback in the treatment of a range of clinical conditions, particularly ADHD and epilepsy, whilst neurofeedback also provides an experimental tool for studying the functional significance of endogenous brain activity. A critical component of any neurofeedback method is the underlying physiological signal which forms the basis for the feedback. While the past decade has seen the emergence of fMRI-based protocols training spatially confined BOLD activity, traditional neurofeedback has utilized a small number of electrode sites on the scalp. As scalp EEG at a given electrode site reflects a linear mixture of activity from multiple brain sources and artifacts, efforts to successfully acquire some level of control over the signal may be confounded by these extraneous sources. Further, in the event of successful training, these traditional neurofeedback methods are likely influencing multiple brain regions and processes. The present work describes the use of source-based signal processing methods in EEG neurofeedback. The feasibility and potential utility of such methods were explored in an experiment training increased theta oscillatory activity in a source derived from Blind Source Separation (BSS) of EEG data obtained during completion of a complex cognitive task (spatial navigation). Learned increases in theta activity were observed in two of the four participants to complete 20 sessions of neurofeedback targeting this individually defined functional brain source. Source-based EEG neurofeedback methods using BSS may offer important advantages over traditional neurofeedback, by targeting the desired physiological signal in a more functionally and spatially specific manner. Having provided preliminary evidence of the feasibility of these methods, future work may study a range of clinically and experimentally relevant brain processes where individual brain sources may be targeted by source-based EEG neurofeedback. PMID:25374520

The Structure of Cognition: Attentional Episodes in Mind and Brain

PubMed Central

Duncan, John

2013-01-01

Cognition is organized in a structured series of attentional episodes, allowing complex problems to be addressed through solution of simpler subproblems. A “multiple-demand” (MD) system of frontal and parietal cortex is active in many different kinds of tasks, and using data from neuroimaging, electrophysiology, neuropsychology, and cognitive studies of intelligence, I propose a core role for MD regions in assembly of the attentional episode. Monkey and human data show dynamic neural coding of attended information across multiple MD regions, with rapid communication within and between regions. Neuropsychological and imaging data link MD function to fluid intelligence, explaining some but not all “executive” deficits after frontal lobe lesions. Cognitive studies link fluid intelligence to goal neglect, and the problem of dividing complex task requirements into focused parts. Like the innate releasing mechanism of ethology, I suggest that construction of the attentional episode provides a core organizational principle for complex, adaptive cognition. PMID:24094101

White matter disease severity of the brain and its association with geriatric syndromes.

PubMed

Alagiakrishnan, Kannayiram; Hsueh, Jenny; Zhang, Edwin; Khan, Khurshid; Senthilselvan, Ambikaipakan

2013-11-01

White matter disease (WMD) of the brain is considered to be secondary to small vessel ischemia and can be a single unifying risk factor for the development of geriatric syndromes. The aim of our study was to investigate the association of the global and regional severity of WMD in the brain with geriatric syndromes burden. In our retrospective study, consecutive outpatient charts from patients seen between January 2010 and June 2011 at University of Alberta Hospital Seniors Clinic were reviewed. Subjects with brain computed tomography (CT) scans were included in the study. Subjects with incomplete information or with diseases that confounded WMD assessment on CT were excluded. White matter disease was quantified on CT using Wahlund scoring. A multiple linear regression analysis was conducted to determine the association of WMD severity with geriatric syndromes burden after controlling for confounding vascular risk factors. Of the 505 subjects, 326 (64.6%) were women. Mean age of the study patients was 79.8 years (SD ± 7.04), prevalence of WMD disease was 79.4%, and mean WMD score was 5.1 (SD ± 4.4). In subjects aged < and > 80 years, the mean number of geriatric syndromes was 2.83 (standard error of the mean [SE] 0.08) and 3.22 (SE 0.08), respectively. In the adjusted regression analysis, there was a significant association between WMD severity, globally (regression coefficient (β) = 0.457, SE 0.155; P = 0.003), as well as WMD in specific regions: frontal (P < 0.001), parieto-occipital (P = 0.004), and infratentorial regions (P = 0.04) with geriatric syndromes burden. The association remains even after correcting for age, sex, and all vascular risk factors. In our study, there was a significant association between the severity of global and selected regional WMD of the brain with geriatric syndromes burden, thus raising the possibility of a shared biologic association through vascular pathology of the brain.

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer's Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET.

PubMed

Li, Xue-Yuan; Men, Wei-Wei; Zhu, Hua; Lei, Jian-Feng; Zuo, Fu-Xing; Wang, Zhan-Jing; Zhu, Zhao-Hui; Bao, Xin-Jie; Wang, Ren-Zhi

2016-10-18

Alzheimer's disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using 18 F-labed fluorodeoxyglucose ( 18 F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr). Morris water maze (MWM) was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD). By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD). Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer's cognition after cognitive decline, at least in animals.

Insulin Regulates Astrocytic Glucose Handling Through Cooperation With IGF-I.

PubMed

Fernandez, Ana M; Hernandez-Garzón, Edwin; Perez-Domper, Paloma; Perez-Alvarez, Alberto; Mederos, Sara; Matsui, Takashi; Santi, Andrea; Trueba-Saiz, Angel; García-Guerra, Lucía; Pose-Utrilla, Julia; Fielitz, Jens; Olson, Eric N; Fernandez de la Rosa, Ruben; Garcia Garcia, Luis; Pozo, Miguel Angel; Iglesias, Teresa; Araque, Alfonso; Soya, Hideaki; Perea, Gertrudis; Martin, Eduardo D; Torres Aleman, Ignacio

2017-01-01

Brain activity requires a flux of glucose to active regions to sustain increased metabolic demands. Insulin, the main regulator of glucose handling in the body, has been traditionally considered not to intervene in this process. However, we now report that insulin modulates brain glucose metabolism by acting on astrocytes in concert with IGF-I. The cooperation of insulin and IGF-I is needed to recover neuronal activity after hypoglycemia. Analysis of underlying mechanisms show that the combined action of IGF-I and insulin synergistically stimulates a mitogen-activated protein kinase/protein kinase D pathway resulting in translocation of GLUT1 to the cell membrane through multiple protein-protein interactions involving the scaffolding protein GAIP-interacting protein C terminus and the GTPase RAC1. Our observations identify insulin-like peptides as physiological modulators of brain glucose handling, providing further support to consider the brain as a target organ in diabetes. © 2017 by the American Diabetes Association.

Targeted, noninvasive blockade of cortical neuronal activity

NASA Astrophysics Data System (ADS)

McDannold, Nathan; Zhang, Yongzhi; Power, Chanikarn; Arvanitis, Costas D.; Vykhodtseva, Natalia; Livingstone, Margaret

2015-11-01

Here we describe a novel method to noninvasively modulate targeted brain areas through the temporary disruption of the blood-brain barrier (BBB) via focused ultrasound, enabling focal delivery of a neuroactive substance. Ultrasound was used to locally disrupt the BBB in rat somatosensory cortex, and intravenous administration of GABA then produced a dose-dependent suppression of somatosensory-evoked potentials in response to electrical stimulation of the sciatic nerve. No suppression was observed 1-5 days afterwards or in control animals where the BBB was not disrupted. This method has several advantages over existing techniques: it is noninvasive; it is repeatable via additional GABA injections; multiple brain regions can be affected simultaneously; suppression magnitude can be titrated by GABA dose; and the method can be used with freely behaving subjects. We anticipate that the application of neuroactive substances in this way will be a useful tool for noninvasively mapping brain function, and potentially for surgical planning or novel therapies.

Perfusion Neuroimaging Abnormalities Alone Distinguish National Football League Players from a Healthy Population.

PubMed

Amen, Daniel G; Willeumier, Kristen; Omalu, Bennet; Newberg, Andrew; Raghavendra, Cauligi; Raji, Cyrus A

2016-04-25

National Football League (NFL) players are exposed to multiple head collisions during their careers. Increasing awareness of the adverse long-term effects of repetitive head trauma has raised substantial concern among players, medical professionals, and the general public. To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls. A cohort of retired and current NFL players (n = 161) were recruited in a longitudinal study starting in 2009 with ongoing interval follow up. A healthy control group (n = 124) was separately recruited for comparison. Assessments included medical examinations, neuropsychological tests, and perfusion neuroimaging with single photon emission computed tomography (SPECT). Perfusion estimates of each scan were quantified using a standard atlas. We hypothesized that hypoperfusion particularly in the orbital frontal, anterior cingulate, anterior temporal, hippocampal, amygdala, insular, caudate, superior/mid occipital, and cerebellar sub-regions alone would reliably separate controls from NFL players. Cerebral perfusion differences were calculated using a one-way ANOVA and diagnostic separation was determined with discriminant and automatic linear regression predictive models. NFL players showed lower cerebral perfusion on average (p < 0.01) in 36 brain regions. The discriminant analysis subsequently distinguished NFL players from controls with 90% sensitivity, 86% specificity, and 94% accuracy (95% CI 95-99). Automatic linear modeling achieved similar results. Inclusion of age and clinical co-morbidities did not improve diagnostic classification. Specific brain regions commonly damaged in traumatic brain injury show abnormally low perfusion on SPECT in professional NFL players. These same regions alone can distinguish this group from healthy subjects with high diagnostic accuracy. This study carries implications for the neurological safety of NFL players.

Perfusion Neuroimaging Abnormalities Alone Distinguish National Football League Players from a Healthy Population

PubMed Central

Amen, Daniel G.; Willeumier, Kristen; Omalu, Bennet; Newberg, Andrew; Raghavendra, Cauligi; Raji, Cyrus A.

2016-01-01

Background: National Football League (NFL) players are exposed to multiple head collisions during their careers. Increasing awareness of the adverse long-term effects of repetitive head trauma has raised substantial concern among players, medical professionals, and the general public. Objective: To determine whether low perfusion in specific brain regions on neuroimaging can accurately separate professional football players from healthy controls. Method: A cohort of retired and current NFL players (n = 161) were recruited in a longitudinal study starting in 2009 with ongoing interval follow up. A healthy control group (n = 124) was separately recruited for comparison. Assessments included medical examinations, neuropsychological tests, and perfusion neuroimaging with single photon emission computed tomography (SPECT). Perfusion estimates of each scan were quantified using a standard atlas. We hypothesized that hypoperfusion particularly in the orbital frontal, anterior cingulate, anterior temporal, hippocampal, amygdala, insular, caudate, superior/mid occipital, and cerebellar sub-regions alone would reliably separate controls from NFL players. Cerebral perfusion differences were calculated using a one-way ANOVA and diagnostic separation was determined with discriminant and automatic linear regression predictive models. Results: NFL players showed lower cerebral perfusion on average (p < 0.01) in 36 brain regions. The discriminant analysis subsequently distinguished NFL players from controls with 90% sensitivity, 86% specificity, and 94% accuracy (95% CI 95-99). Automatic linear modeling achieved similar results. Inclusion of age and clinical co-morbidities did not improve diagnostic classification. Conclusion: Specific brain regions commonly damaged in traumatic brain injury show abnormally low perfusion on SPECT in professional NFL players. These same regions alone can distinguish this group from healthy subjects with high diagnostic accuracy. This study carries implications for the neurological safety of NFL players. PMID:27128374

Lateralized hippocampal oscillations underlie distinct aspects of human spatial memory and navigation.

PubMed

Miller, Jonathan; Watrous, Andrew J; Tsitsiklis, Melina; Lee, Sang Ah; Sheth, Sameer A; Schevon, Catherine A; Smith, Elliot H; Sperling, Michael R; Sharan, Ashwini; Asadi-Pooya, Ali Akbar; Worrell, Gregory A; Meisenhelter, Stephen; Inman, Cory S; Davis, Kathryn A; Lega, Bradley; Wanda, Paul A; Das, Sandhitsu R; Stein, Joel M; Gorniak, Richard; Jacobs, Joshua

2018-06-21

The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation. We show that in the left but not right hippocampus, the amplitude of oscillations in the 1-3-Hz "low theta" band increases when viewing subsequently remembered object-location pairs. In contrast, in the right but not left hippocampus, low-theta activity increases during periods of navigation. The frequencies of these hippocampal signals are slower than task-related signals in the neocortex. These results suggest that the human brain includes multiple lateralized oscillatory networks that support different aspects of cognition.

Multi-neuron intracellular recording in vivo via interacting autopatching robots

PubMed Central

Holst, Gregory L; Singer, Annabelle C; Han, Xue; Brown, Emery N

2018-01-01

The activities of groups of neurons in a circuit or brain region are important for neuronal computations that contribute to behaviors and disease states. Traditional extracellular recordings have been powerful and scalable, but much less is known about the intracellular processes that lead to spiking activity. We present a robotic system, the multipatcher, capable of automatically obtaining blind whole-cell patch clamp recordings from multiple neurons simultaneously. The multipatcher significantly extends automated patch clamping, or 'autopatching’, to guide four interacting electrodes in a coordinated fashion, avoiding mechanical coupling in the brain. We demonstrate its performance in the cortex of anesthetized and awake mice. A multipatcher with four electrodes took an average of 10 min to obtain dual or triple recordings in 29% of trials in anesthetized mice, and in 18% of the trials in awake mice, thus illustrating practical yield and throughput to obtain multiple, simultaneous whole-cell recordings in vivo. PMID:29297466

Multi-layer Cortical Ca2+ Imaging in Freely Moving Mice with Prism Probes and Miniaturized Fluorescence Microscopy

PubMed Central

Gulati, Srishti; Cao, Vania Y.; Otte, Stephani

2017-01-01

In vivo circuit and cellular level functional imaging is a critical tool for understanding the brain in action. High resolution imaging of mouse cortical neurons with two-photon microscopy has provided unique insights into cortical structure, function and plasticity. However, these studies are limited to head fixed animals, greatly reducing the behavioral complexity available for study. In this paper, we describe a procedure for performing chronic fluorescence microscopy with cellular-resolution across multiple cortical layers in freely behaving mice. We used an integrated miniaturized fluorescence microscope paired with an implanted prism probe to simultaneously visualize and record the calcium dynamics of hundreds of neurons across multiple layers of the somatosensory cortex as the mouse engaged in a novel object exploration task, over several days. This technique can be adapted to other brain regions in different animal species for other behavioral paradigms. PMID:28654056

The serotonin system in autism spectrum disorder: from biomarker to animal models

PubMed Central

Muller, Christopher L.; Anacker, Allison M.J.; Veenstra-VanderWeele, Jeremy

2015-01-01

Elevated whole blood serotonin, or hyperserotonemia, was the first biomarker identified in autism spectrum disorder (ASD) and is present in more than 25% of affected children. The serotonin system is a logical candidate for involvement in ASD due to its pleiotropic role across multiple brain systems both dynamically and across development. Tantalizing clues connect this peripheral biomarker with changes in brain and behavior in ASD, but the contribution of the serotonin system to ASD pathophysiology remains incompletely understood. Studies of whole blood serotonin levels in ASD and in a large founder population indicate greater heritability than for the disorder itself and suggest an association with recurrence risk. Emerging data from both neuroimaging and postmortem samples also indicate changes in the brain serotonin system in ASD. Genetic linkage and association studies of both whole blood serotonin levels and of ASD risk point to the chromosomal region containing the serotonin transporter (SERT) gene in males but not in females. In ASD families with evidence of linkage to this region, multiple rare SERT amino acid variants lead to a convergent increase in serotonin uptake in cell models. A knock-in mouse model of one of these variants, SERT Gly56Ala, recapitulates the hyperserotonemia biomarker and shows increased brain serotonin clearance, increased serotonin receptor sensitivity, and altered social, communication, and repetitive behaviors. Data from other rodent models also suggest an important role for the serotonin system in social behavior, in cognitive flexibility, and in sensory development. Recent work indicates that reciprocal interactions between serotonin and other systems, such as oxytocin, may be particularly important for social behavior. Collectively, these data point to the serotonin system as a prime candidate for treatment development in a subgroup of children defined by a robust, heritable biomarker. PMID:26577932

The tau positron-emission tomography tracer AV-1451 binds with similar affinities to tau fibrils and monoamine oxidases.

PubMed

Vermeiren, Céline; Motte, Philippe; Viot, Delphine; Mairet-Coello, Georges; Courade, Jean-Philippe; Citron, Martin; Mercier, Joël; Hannestad, Jonas; Gillard, Michel

2018-02-01

Lilly/Avid's AV-1451 is one of the most advanced tau PET tracers in the clinic. Although results obtained in Alzheimer's disease patients are compelling, discrimination of tracer uptake in healthy individuals and patients with supranuclear palsy (PSP) is less clear as there is substantial overlap of signal in multiple brain regions. Moreover, accurate quantification of [ 18 F]AV-1451 uptake in Alzheimer's disease may not be possible. The aim of the present study was to characterize the in vitro binding of AV-1451 to understand and identify potential off-target binding that could explain the poor discrimination observed in PSP patients. [ 3 H]AV-1451 and AV-1451 were characterized in in vitro binding assays using recombinant and native proteins/tissues from postmortem samples of controls and Alzheimer's disease and PSP patients. [ 3 H]AV-1451 binds to multiple sites with nanomolar affinities in brain homogenates and to tau fibrils isolated from Alzheimer's disease or PSP patients. [ 3 H]AV-1451 also binds with similarly high affinities in brain homogenates devoid of tau pathology. This unexpected binding was demonstrated to be because of nanomolar affinities of [ 3 H]AV-1451 for monoamine oxidase A and B enzymes. High affinity of AV-1451 for monoamine oxidase proteins may limit its utility as a tau PET tracer in PSP and Alzheimer's disease because of high levels of monoamine oxidase expression in brain regions also affected by tau deposition, especially if monoamine oxidase levels change over time or with a treatment intervention. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Cellular selectivity of AAV serotypes for gene delivery in neurons and astrocytes by neonatal intracerebroventricular injection

PubMed Central

Hammond, Sean L.; Leek, Ashley N.; Richman, Evan H.

2017-01-01

The non-pathogenic parvovirus, adeno-associated virus (AAV), is an efficient vector for transgene expression in vivo and shows promise for treatment of brain disorders in clinical trials. Currently, there are more than 100 AAV serotypes identified that differ in the binding capacity of capsid proteins to specific cell surface receptors that can transduce different cell types and brain regions in the CNS. In the current study, multiple AAV serotypes expressing a GFP reporter (AAV1, AAV2/1, AAVDJ, AAV8, AAVDJ8, AAV9, AAVDJ9) were screened for their infectivity in both primary murine astrocyte and neuronal cell cultures. AAV2/1, AAVDJ8 and AAV9 were selected for further investigation of their tropism throughout different brain regions and cell types. Each AAV was administered to P0-neonatal mice via intracerebroventricular injections (ICV). Brains were then systematically analyzed for GFP expression at 3 or 6 weeks post-infection in various regions, including the olfactory bulb, striatum, cortex, hippocampus, substantia nigra (SN) and cerebellum. Cell counting data revealed that AAV2/1 infections were more prevalent in the cortical layers but penetrated to the midbrain less than AAVDJ8 and AAV9. Additionally, there were differences in the persistence of viral transgene expression amongst the three serotypes examined in vivo at 3 and 6 weeks post-infection. Because AAV-mediated transgene expression is of interest in neurodegenerative diseases such as Parkinson’s Disease, we examined the SN with microscopy techniques, such as CLARITY tissue transmutation, to identify AAV serotypes that resulted in optimal transgene expression in either astrocytes or dopaminergic neurons. AAVDJ8 displayed more tropism in astrocytes compared to AAV9 in the SN region. We conclude that ICV injection results in lasting expression of virally encoded transgene when using AAV vectors and that specific AAV serotypes are required to selectively deliver transgenes of interest to different brain regions in both astrocytes and neurons. PMID:29244806

Linking brain-wide multivoxel activation patterns to behaviour: Examples from language and math.

PubMed

Raizada, Rajeev D S; Tsao, Feng-Ming; Liu, Huei-Mei; Holloway, Ian D; Ansari, Daniel; Kuhl, Patricia K

2010-05-15

A key goal of cognitive neuroscience is to find simple and direct connections between brain and behaviour. However, fMRI analysis typically involves choices between many possible options, with each choice potentially biasing any brain-behaviour correlations that emerge. Standard methods of fMRI analysis assess each voxel individually, but then face the problem of selection bias when combining those voxels into a region-of-interest, or ROI. Multivariate pattern-based fMRI analysis methods use classifiers to analyse multiple voxels together, but can also introduce selection bias via data-reduction steps as feature selection of voxels, pre-selecting activated regions, or principal components analysis. We show here that strong brain-behaviour links can be revealed without any voxel selection or data reduction, using just plain linear regression as a classifier applied to the whole brain at once, i.e. treating each entire brain volume as a single multi-voxel pattern. The brain-behaviour correlations emerged despite the fact that the classifier was not provided with any information at all about subjects' behaviour, but instead was given only the neural data and its condition-labels. Surprisingly, more powerful classifiers such as a linear SVM and regularised logistic regression produce very similar results. We discuss some possible reasons why the very simple brain-wide linear regression model is able to find correlations with behaviour that are as strong as those obtained on the one hand from a specific ROI and on the other hand from more complex classifiers. In a manner which is unencumbered by arbitrary choices, our approach offers a method for investigating connections between brain and behaviour which is simple, rigorous and direct. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Shorter-Course Whole-Brain Radiotherapy for Brain Metastases in Elderly Patients

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

Rades, Dirk, E-mail: rades.dirk@gmx.net; Department of Radiation Oncology, University Hospital Hamburg-Eppendorf, Hamburg; Evers, Jasmin N.

2011-11-15

Purpose: Many patients with brain metastases receive whole-brain radiotherapy (WBRT) alone. Using 10 Multiplication-Sign 3 Gy in 2 weeks is the standard regimen in most centers. Regarding the extraordinarily poor survival prognosis of elderly patients with multiple brain metastases, a shorter WBRT regimen would be preferable. This study compared 10 Multiplication-Sign 3 Gy with 5 Multiplication-Sign 4 Gy in elderly patients ({>=}65 years). Methods and Materials: Data from 455 elderly patients who received WBRT alone for brain metastases were retrospectively analyzed. Survival and local (= intracerebral) control of 293 patients receiving 10 Multiplication-Sign 3 Gy were compared with 162 patientsmore » receiving 5 Multiplication-Sign 4 Gy. Eight additional potential prognostic factors were investigated including age, gender, Karnofsky performance score (KPS), primary tumor, number of brain metastases, interval from tumor diagnosis to WBRT, extracerebral metastases, and recursive partitioning analysis (RPA) class. Results: The 6-month overall survival rates were 29% after 5 Multiplication-Sign 4 Gy and 21% after 10 Multiplication-Sign 3 Gy (p = 0.020). The 6-month local control rates were 12% and 10%, respectively (p = 0.32). On multivariate analysis, improved overall survival was associated with KPS {>=} 70 (p < 0.001), only one to three brain metastases (p = 0.029), no extracerebral metastasis (p = 0.012), and lower RPA class (p < 0.001). Improved local control was associated with KPS {>=} 70 (p < 0.001), breast cancer (p = 0.029), and lower RPA class (p < 0.001). Conclusions: Shorter-course WBRT with 5 Multiplication-Sign 4 Gy was not inferior to 10 Multiplication-Sign 3 Gy with respect to overall survival or local control in elderly patients. 5 Multiplication-Sign 4 Gy appears preferable for the majority of these patients.« less

Relating brain signal variability to knowledge representation.

PubMed

Heisz, Jennifer J; Shedden, Judith M; McIntosh, Anthony R

2012-11-15

We assessed the hypothesis that brain signal variability is a reflection of functional network reconfiguration during memory processing. In the present experiments, we use multiscale entropy to capture the variability of human electroencephalogram (EEG) while manipulating the knowledge representation associated with faces stored in memory. Across two experiments, we observed increased variability as a function of greater knowledge representation. In Experiment 1, individuals with greater familiarity for a group of famous faces displayed more brain signal variability. In Experiment 2, brain signal variability increased with learning after multiple experimental exposures to previously unfamiliar faces. The results demonstrate that variability increases with face familiarity; cognitive processes during the perception of familiar stimuli may engage a broader network of regions, which manifests as higher complexity/variability in spatial and temporal domains. In addition, effects of repetition suppression on brain signal variability were observed, and the pattern of results is consistent with a selectivity model of neural adaptation. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Her versus his migraine: multiple sex differences in brain function and structure

PubMed Central

Linnman, Clas; Brawn, Jennifer; Burstein, Rami; Becerra, Lino; Borsook, David

2012-01-01

Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a ‘sex phenotype’ in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs. PMID:22843414

Her versus his migraine: multiple sex differences in brain function and structure.

PubMed

Maleki, Nasim; Linnman, Clas; Brawn, Jennifer; Burstein, Rami; Becerra, Lino; Borsook, David

2012-08-01

Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a 'sex phenotype' in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs.

Neural Computations in a Dynamical System with Multiple Time Scales.

PubMed

Mi, Yuanyuan; Lin, Xiaohan; Wu, Si

2016-01-01

Neural systems display rich short-term dynamics at various levels, e.g., spike-frequency adaptation (SFA) at the single-neuron level, and short-term facilitation (STF) and depression (STD) at the synapse level. These dynamical features typically cover a broad range of time scales and exhibit large diversity in different brain regions. It remains unclear what is the computational benefit for the brain to have such variability in short-term dynamics. In this study, we propose that the brain can exploit such dynamical features to implement multiple seemingly contradictory computations in a single neural circuit. To demonstrate this idea, we use continuous attractor neural network (CANN) as a working model and include STF, SFA and STD with increasing time constants in its dynamics. Three computational tasks are considered, which are persistent activity, adaptation, and anticipative tracking. These tasks require conflicting neural mechanisms, and hence cannot be implemented by a single dynamical feature or any combination with similar time constants. However, with properly coordinated STF, SFA and STD, we show that the network is able to implement the three computational tasks concurrently. We hope this study will shed light on the understanding of how the brain orchestrates its rich dynamics at various levels to realize diverse cognitive functions.

Multiple sclerosis lesions affect intrinsic functional connectivity of the spinal cord.

PubMed

Conrad, Benjamin N; Barry, Robert L; Rogers, Baxter P; Maki, Satoshi; Mishra, Arabinda; Thukral, Saakshi; Sriram, Subramaniam; Bhatia, Aashim; Pawate, Siddharama; Gore, John C; Smith, Seth A

2018-06-01

Patients with multiple sclerosis present with focal lesions throughout the spinal cord. There is a clinical need for non-invasive measurements of spinal cord activity and functional organization in multiple sclerosis, given the cord's critical role in the disease. Recent reports of spontaneous blood oxygenation level-dependent fluctuations in the spinal cord using functional MRI suggest that, like the brain, cord activity at rest is organized into distinct, synchronized functional networks among grey matter regions, likely related to motor and sensory systems. Previous studies looking at stimulus-evoked activity in the spinal cord of patients with multiple sclerosis have demonstrated increased levels of activation as well as a more bilateral distribution of activity compared to controls. Functional connectivity studies of brain networks in multiple sclerosis have revealed widespread alterations, which may take on a dynamic trajectory over the course of the disease, with compensatory increases in connectivity followed by decreases associated with structural damage. We build upon this literature by examining functional connectivity in the spinal cord of patients with multiple sclerosis. Using ultra-high field 7 T imaging along with processing strategies for robust spinal cord functional MRI and lesion identification, the present study assessed functional connectivity within cervical cord grey matter of patients with relapsing-remitting multiple sclerosis (n = 22) compared to a large sample of healthy controls (n = 56). Patient anatomical images were rated for lesions by three independent raters, with consensus ratings revealing 19 of 22 patients presented with lesions somewhere in the imaged volume. Linear mixed models were used to assess effects of lesion location on functional connectivity. Analysis in control subjects demonstrated a robust pattern of connectivity among ventral grey matter regions as well as a distinct network among dorsal regions. A gender effect was also observed in controls whereby females demonstrated higher ventral network connectivity. Wilcoxon rank-sum tests detected no differences in average connectivity or power of low frequency fluctuations in patients compared to controls. The presence of lesions was, however, associated with local alterations in connectivity with differential effects depending on columnar location. The patient results suggest that spinal cord functional networks are generally intact in relapsing-remitting multiple sclerosis but that lesions are associated with focal abnormalities in intrinsic connectivity. These findings are discussed in light of the current literature on spinal cord functional MRI and the potential neurological underpinnings.

Effects of Cell Phone Radiofrequency Signal Exposure on Brain Glucos Metabolism

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

Volkow, N.D.; Wang, G.; Volkow, N.D.

The dramatic increase in use of cellular telephones has generated concern about possible negative effects of radiofrequency signals delivered to the brain. However, whether acute cell phone exposure affects the human brain is unclear. To evaluate if acute cell phone exposure affects brain glucose metabolism, a marker of brain activity. Randomized crossover study conducted between January 1 and December 31, 2009, at a single US laboratory among 47 healthy participants recruited from the community. Cell phones were placed on the left and right ears and positron emission tomography with ({sup 18}F)fluorodeoxyglucose injection was used to measure brain glucose metabolism twice,more » once with the right cell phone activated (sound muted) for 50 minutes ('on' condition) and once with both cell phones deactivated ('off' condition). Statistical parametric mapping was used to compare metabolism between on and off conditions using paired t tests, and Pearson linear correlations were used to verify the association of metabolism and estimated amplitude of radiofrequency-modulated electromagnetic waves emitted by the cell phone. Clusters with at least 1000 voxels (volume >8 cm{sup 3}) and P < .05 (corrected for multiple comparisons) were considered significant. Brain glucose metabolism computed as absolute metabolism ({micro}mol/100 g per minute) and as normalized metabolism (region/whole brain). Whole-brain metabolism did not differ between on and off conditions. In contrast, metabolism in the region closest to the antenna (orbitofrontal cortex and temporal pole) was significantly higher for on than off conditions (35.7 vs 33.3 {micro}mol/100 g per minute; mean difference, 2.4 [95% confidence interval, 0.67-4.2]; P = .004). The increases were significantly correlated with the estimated electromagnetic field amplitudes both for absolute metabolism (R = 0.95, P < .001) and normalized metabolism (R = 0.89; P < .001). In healthy participants and compared with no exposure, 50-minute cell phone exposure was associated with increased brain glucose metabolism in the region closest to the antenna. This finding is of unknown clinical significance.« less

Effects of Cell Phone Radiofrequency Signal Exposure on Brain Glucose Metabolism

PubMed Central

Volkow, Nora D.; Tomasi, Dardo; Wang, Gene-Jack; Vaska, Paul; Fowler, Joanna S.; Telang, Frank; Alexoff, Dave; Logan, Jean; Wong, Christopher

2011-01-01

Context The dramatic increase in use of cellular telephones has generated concern about possible negative effects of radiofrequency signals delivered to the brain. However, whether acute cell phone exposure affects the human brain is unclear. Objective To evaluate if acute cell phone exposure affects brain glucose metabolism, a marker of brain activity. Design, Setting, and Participants Randomized crossover study conducted between January 1 and December 31, 2009, at a single US laboratory among 47 healthy participants recruited from the community. Cell phones were placed on the left and right ears and positron emission tomography with (18F)fluorodeoxyglucose injection was used to measure brain glucose metabolism twice, once with the right cell phone activated (sound muted) for 50 minutes (“on” condition) and once with both cell phones deactivated (“off” condition). Statistical parametric mapping was used to compare metabolism between on and off conditions using paired t tests, and Pearson linear correlations were used to verify the association of metabolism and estimated amplitude of radiofrequency-modulated electromagnetic waves emitted by the cell phone. Clusters with at least 1000 voxels (volume >8 cm3) and P < .05 (corrected for multiple comparisons) were considered significant. Main Outcome Measure Brain glucose metabolism computed as absolute metabolism (µmol/100 g per minute) and as normalized metabolism (region/whole brain). Results Whole-brain metabolism did not differ between on and off conditions. In contrast, metabolism in the region closest to the antenna (orbitofrontal cortex and temporal pole) was significantly higher for on than off conditions (35.7 vs 33.3 µmol/100 g per minute; mean difference, 2.4 [95% confidence interval, 0.67–4.2]; P = .004). The increases were significantly correlated with the estimated electromagnetic field amplitudes both for absolute metabolism (R = 0.95, P < .001) and normalized metabolism (R = 0.89; P < .001). Conclusions In healthy participants and compared with no exposure, 50-minute cell phone exposure was associated with increased brain glucose metabolism in the region closest to the antenna. This finding is of unknown clinical significance. PMID:21343580

Alzheimer Disease Alters the Relationship of Cardiorespiratory Fitness With Brain Activity During the Stroop Task

PubMed Central

Gayed, Matthew R.; Honea, Robyn A.; Savage, Cary R.; Hobbs, Derek; Burns, Jeffrey M.

2013-01-01

Background Despite mounting evidence that physical activity has positive benefits for brain and cognitive health, there has been little characterization of the relationship between cardiorespiratory (CR) fitness and cognition-associated brain activity as measured by functional magnetic resonance imaging (fMRI). The lack of evidence is particularly glaring for diseases such as Alzheimer disease (AD) that degrade cognitive and functional performance. Objective The aim of this study was to describe the relationship between regional brain activity during cognitive tasks and CR fitness level in people with and without AD. Design A case-control, single-observation study design was used. Methods Thirty-four individuals (18 without dementia and 16 in the earliest stages of AD) completed maximal exercise testing and performed a Stroop task during fMRI. Results Cardiorespiratory fitness was inversely associated with anterior cingulate activity in the participants without dementia (r=−.48, P=.05) and unassociated with activation in those with AD (P>.7). Weak associations of CR fitness and middle frontal cortex were noted. Limitations The wide age range and the use of a single task in fMRI rather than multiple tasks challenging different cognitive capacities were limitations of the study. Conclusions The results offer further support of the relationship between CR fitness and regional brain activity. However, this relationship may be attenuated by disease. Future work in this area may provide clinicians and researchers with interpretable and dependable regional fMRI biomarker signatures responsive to exercise intervention. It also may shed light on mechanisms by which exercise can support cognitive function. PMID:23559521

Coactivation of cognitive control networks during task switching.

PubMed

Yin, Shouhang; Deák, Gedeon; Chen, Antao

2018-01-01

The ability to flexibly switch between tasks is considered an important component of cognitive control that involves frontal and parietal cortical areas. The present study was designed to characterize network dynamics across multiple brain regions during task switching. Functional magnetic resonance images (fMRI) were captured during a standard rule-switching task to identify switching-related brain regions. Multiregional psychophysiological interaction (PPI) analysis was used to examine effective connectivity between these regions. During switching trials, behavioral performance declined and activation of a generic cognitive control network increased. Concurrently, task-related connectivity increased within and between cingulo-opercular and fronto-parietal cognitive control networks. Notably, the left inferior frontal junction (IFJ) was most consistently coactivated with the 2 cognitive control networks. Furthermore, switching-dependent effective connectivity was negatively correlated with behavioral switch costs. The strength of effective connectivity between left IFJ and other regions in the networks predicted individual differences in switch costs. Task switching was supported by coactivated connections within cognitive control networks, with left IFJ potentially acting as a key hub between the fronto-parietal and cingulo-opercular networks. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Rescuing Perishable Neuroanatomical Information from a Threatened Biodiversity Hotspot: Remote Field Methods for Brain Tissue Preservation Validated by Cytoarchitectonic Analysis, Immunohistochemistry, and X-Ray Microcomputed Tomography.

PubMed

Hughes, Daniel F; Walker, Ellen M; Gignac, Paul M; Martinez, Anais; Negishi, Kenichiro; Lieb, Carl S; Greenbaum, Eli; Khan, Arshad M

2016-01-01

Biodiversity hotspots, which harbor more endemic species than elsewhere on Earth, are increasingly threatened. There is a need to accelerate collection efforts in these regions before threatened or endangered species become extinct. The diverse geographical, ecological, genetic, morphological, and behavioral data generated from the on-site collection of an individual specimen are useful for many scientific purposes. However, traditional methods for specimen preparation in the field do not permit researchers to retrieve neuroanatomical data, disregarding potentially useful data for increasing our understanding of brain diversity. These data have helped clarify brain evolution, deciphered relationships between structure and function, and revealed constraints and selective pressures that provide context about the evolution of complex behavior. Here, we report our field-testing of two commonly used laboratory-based techniques for brain preservation while on a collecting expedition in the Congo Basin and Albertine Rift, two poorly known regions associated with the Eastern Afromontane biodiversity hotspot. First, we found that transcardial perfusion fixation and long-term brain storage, conducted in remote field conditions with no access to cold storage laboratory equipment, had no observable impact on cytoarchitectural features of lizard brain tissue when compared to lizard brain tissue processed under laboratory conditions. Second, field-perfused brain tissue subjected to prolonged post-fixation remained readily compatible with subsequent immunohistochemical detection of neural antigens, with immunostaining that was comparable to that of laboratory-perfused brain tissue. Third, immersion-fixation of lizard brains, prepared under identical environmental conditions, was readily compatible with subsequent iodine-enhanced X-ray microcomputed tomography, which facilitated the non-destructive imaging of the intact brain within its skull. In summary, we have validated multiple approaches to preserving intact lizard brains in remote field conditions with limited access to supplies and a high degree of environmental exposure. This protocol should serve as a malleable framework for researchers attempting to rescue perishable and irreplaceable morphological and molecular data from regions of disappearing biodiversity. Our approach can be harnessed to extend the numbers of species being actively studied by the neuroscience community, by reducing some of the difficulty associated with acquiring brains of animal species that are not readily available in captivity.

Rescuing Perishable Neuroanatomical Information from a Threatened Biodiversity Hotspot: Remote Field Methods for Brain Tissue Preservation Validated by Cytoarchitectonic Analysis, Immunohistochemistry, and X-Ray Microcomputed Tomography

PubMed Central

Hughes, Daniel F.; Walker, Ellen M.; Gignac, Paul M.; Martinez, Anais; Negishi, Kenichiro; Lieb, Carl S.; Greenbaum, Eli

2016-01-01

Biodiversity hotspots, which harbor more endemic species than elsewhere on Earth, are increasingly threatened. There is a need to accelerate collection efforts in these regions before threatened or endangered species become extinct. The diverse geographical, ecological, genetic, morphological, and behavioral data generated from the on-site collection of an individual specimen are useful for many scientific purposes. However, traditional methods for specimen preparation in the field do not permit researchers to retrieve neuroanatomical data, disregarding potentially useful data for increasing our understanding of brain diversity. These data have helped clarify brain evolution, deciphered relationships between structure and function, and revealed constraints and selective pressures that provide context about the evolution of complex behavior. Here, we report our field-testing of two commonly used laboratory-based techniques for brain preservation while on a collecting expedition in the Congo Basin and Albertine Rift, two poorly known regions associated with the Eastern Afromontane biodiversity hotspot. First, we found that transcardial perfusion fixation and long-term brain storage, conducted in remote field conditions with no access to cold storage laboratory equipment, had no observable impact on cytoarchitectural features of lizard brain tissue when compared to lizard brain tissue processed under laboratory conditions. Second, field-perfused brain tissue subjected to prolonged post-fixation remained readily compatible with subsequent immunohistochemical detection of neural antigens, with immunostaining that was comparable to that of laboratory-perfused brain tissue. Third, immersion-fixation of lizard brains, prepared under identical environmental conditions, was readily compatible with subsequent iodine-enhanced X-ray microcomputed tomography, which facilitated the non-destructive imaging of the intact brain within its skull. In summary, we have validated multiple approaches to preserving intact lizard brains in remote field conditions with limited access to supplies and a high degree of environmental exposure. This protocol should serve as a malleable framework for researchers attempting to rescue perishable and irreplaceable morphological and molecular data from regions of disappearing biodiversity. Our approach can be harnessed to extend the numbers of species being actively studied by the neuroscience community, by reducing some of the difficulty associated with acquiring brains of animal species that are not readily available in captivity. PMID:27196138

Definition and characterization of an extended multiple-demand network.

PubMed

Camilleri, J A; Müller, V I; Fox, P; Laird, A R; Hoffstaedter, F; Kalenscher, T; Eickhoff, S B

2018-01-15

Neuroimaging evidence suggests that executive functions (EF) depend on brain regions that are not closely tied to specific cognitive demands but rather to a wide range of behaviors. A multiple-demand (MD) system has been proposed, consisting of regions showing conjoint activation across multiple demands. Additionally, a number of studies defining networks specific to certain cognitive tasks suggest that the MD system may be composed of a number of sub-networks each subserving specific roles within the system. We here provide a robust definition of an extended MDN (eMDN) based on task-dependent and task-independent functional connectivity analyses seeded from regions previously shown to be convergently recruited across neuroimaging studies probing working memory, attention and inhibition, i.e., the proposed key components of EF. Additionally, we investigated potential sub-networks within the eMDN based on their connectional and functional similarities. We propose an eMDN network consisting of a core whose integrity should be crucial to performance of most operations that are considered higher cognitive or EF. This then recruits additional areas depending on specific demands. Copyright © 2017 Elsevier Inc. All rights reserved.

Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects

PubMed Central

Schreiner, Simon J.; Liu, Xinyang; Gietl, Anton F.; Wyss, Michael; Steininger, Stefanie C.; Gruber, Esmeralda; Treyer, Valerie; Meier, Irene B.; Kälin, Andrea M.; Leh, Sandra E.; Buck, Alfred; Nitsch, Roger M.; Pruessmann, Klaas P.; Hock, Christoph; Unschuld, Paul G.

2014-01-01

Background: Accumulation of amyloid beta (Aβ) may occur during healthy aging and is a risk factor for Alzheimer Disease (AD). While individual Aβ-accumulation can be measured non-invasively using Pittsburgh Compund-B positron emission tomography (PiB-PET), Fluid-attenuated inversion recovery (FLAIR) is a Magnetic Resonance Imaging (MRI) sequence, capable of indicating heterogeneous age-related brain pathologies associated with tissue-edema. In the current study cognitively normal elderly subjects were investigated for regional correlation of PiB- and FLAIR intensity. Methods: Fourteen healthy elderly subjects without known history of cognitive impairment received 11C-PiB-PET for estimation of regional Aβ-load. In addition, whole brain T1-MPRAGE and FLAIR-MRI sequences were acquired at high field strength of 7 Tesla (7T). Volume-normalized intensities of brain regions were assessed by applying an automated subcortical segmentation algorithm for spatial definition of brain structures. Statistical dependence between FLAIR- and PiB-PET intensities was tested using Spearman's rank correlation coefficient (rho), followed by Holm–Bonferroni correction for multiple testing. Results: Neuropsychological testing revealed normal cognitive performance levels in all participants. Mean regional PiB-PET and FLAIR intensities were normally distributed and independent. Significant correlation between volume-normalized PiB-PET signals and FLAIR intensities resulted for Hippocampus (right: rho = 0.86; left: rho = 0.84), Brainstem (rho = 0.85) and left Basal Ganglia vessel region (rho = 0.82). Conclusions: Our finding of a significant relationship between PiB- and FLAIR intensity mainly observable in the Hippocampus and Brainstem, indicates regional Aβ associated tissue-edema in cognitively normal elderly subjects. Further studies including clinical populations are necessary to clarify the relevance of our findings for estimating individual risk for age-related neurodegenerative processes such as AD. PMID:25249977

Functional Connectivity During Exposure to Favorite-Food, Stress, and Neutral-Relaxing Imagery Differs Between Smokers and Nonsmokers.

PubMed

Garrison, Kathleen A; Sinha, Rajita; Lacadie, Cheryl M; Scheinost, Dustin; Jastreboff, Ania M; Constable, R Todd; Potenza, Marc N

2016-09-01

Tobacco-use disorder is a complex condition involving multiple brain networks and presenting with multiple behavioral correlates including changes in diet and stress. In a previous functional magnetic resonance imaging (fMRI) study of neural responses to favorite-food, stress, and neutral-relaxing imagery, smokers versus nonsmokers demonstrated blunted corticostriatal-limbic responses to favorite-food cues. Based on other recent reports of alterations in functional brain networks in smokers, the current study examined functional connectivity during exposure to favorite-food, stress, and neutral-relaxing imagery in smokers and nonsmokers, using the same dataset. The intrinsic connectivity distribution was measured to identify brain regions that differed in degree of functional connectivity between groups during each imagery condition. Resulting clusters were evaluated for seed-to-voxel connectivity to identify the specific connections that differed between groups during each imagery condition. During exposure to favorite-food imagery, smokers versus nonsmokers showed lower connectivity in the supramarginal gyrus, and differences in connectivity between the supramarginal gyrus and the corticostriatal-limbic system. During exposure to neutral-relaxing imagery, smokers versus nonsmokers showed greater connectivity in the precuneus, and greater connectivity between the precuneus and the posterior insula and rolandic operculum. During exposure to stress imagery, smokers versus nonsmokers showed lower connectivity in the cerebellum. These findings provide data-driven insights into smoking-related alterations in brain functional connectivity patterns related to appetitive, relaxing, and stressful states. This study uses a data-driven approach to demonstrate that smokers and nonsmokers show differential patterns of functional connectivity during guided imagery related to personalized favorite-food, stress, and neutral-relaxing cues, in brain regions implicated in attention, reward-related, emotional, and motivational processes. For smokers, these differences in connectivity may impact appetite, stress, and relaxation, and may interfere with smoking cessation. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Functional Connectivity During Exposure to Favorite-Food, Stress, and Neutral-Relaxing Imagery Differs Between Smokers and Nonsmokers

PubMed Central

Sinha, Rajita; Lacadie, Cheryl M.; Scheinost, Dustin; Jastreboff, Ania M.; Constable, R. Todd; Potenza, Marc N.

2016-01-01

Introduction: Tobacco-use disorder is a complex condition involving multiple brain networks and presenting with multiple behavioral correlates including changes in diet and stress. In a previous functional magnetic resonance imaging (fMRI) study of neural responses to favorite-food, stress, and neutral-relaxing imagery, smokers versus nonsmokers demonstrated blunted corticostriatal-limbic responses to favorite-food cues. Based on other recent reports of alterations in functional brain networks in smokers, the current study examined functional connectivity during exposure to favorite-food, stress, and neutral-relaxing imagery in smokers and nonsmokers, using the same dataset. Methods: The intrinsic connectivity distribution was measured to identify brain regions that differed in degree of functional connectivity between groups during each imagery condition. Resulting clusters were evaluated for seed-to-voxel connectivity to identify the specific connections that differed between groups during each imagery condition. Results: During exposure to favorite-food imagery, smokers versus nonsmokers showed lower connectivity in the supramarginal gyrus, and differences in connectivity between the supramarginal gyrus and the corticostriatal-limbic system. During exposure to neutral-relaxing imagery, smokers versus nonsmokers showed greater connectivity in the precuneus, and greater connectivity between the precuneus and the posterior insula and rolandic operculum. During exposure to stress imagery, smokers versus nonsmokers showed lower connectivity in the cerebellum. Conclusions: These findings provide data-driven insights into smoking-related alterations in brain functional connectivity patterns related to appetitive, relaxing, and stressful states. Implications: This study uses a data-driven approach to demonstrate that smokers and nonsmokers show differential patterns of functional connectivity during guided imagery related to personalized favorite-food, stress, and neutral-relaxing cues, in brain regions implicated in attention, reward-related, emotional, and motivational processes. For smokers, these differences in connectivity may impact appetite, stress, and relaxation, and may interfere with smoking cessation. PMID:26995796

A special form of cerebral lacunae: expanding lacunae.

PubMed Central

Homeyer, P; Cornu, P; Lacomblez, L; Chiras, J; Derouesné, C

1996-01-01

The case of a 42 year old man with headache, blurred vision, and diplopia allowed the description of a particular form of cerebral lacunae-that is, expanding lacunae. Brain MRI showed hydrocephalus and multiple lesions in the thalamomesencephalic region. The radiological features of these lesions were similar to the histological brain coronal section of a case reported in 1983 in which expanding lacunae were related to a dilatation of the perivascular spaces and a focal segmental necrotising angiitis. The role of the lymphatic drainage of the brain is discussed to explain the dilatation of the perivascular spaces. The hypothesis of a hydrodynamic factor being responsible for the expanding character of the lacunae was suggested by the location of the lesions and the influence of various clinical events on the symptomatology. Images PMID:8708692

Cellular mechanisms of estradiol-mediated sexual differentiation of the brain.

PubMed

Wright, Christopher L; Schwarz, Jaclyn S; Dean, Shannon L; McCarthy, Margaret M

2010-09-01

Gonadal steroids organize the developing brain during a perinatal sensitive period and have enduring consequences for adult behavior. In male rodents testicular androgens are aromatized in neurons to estrogens and initiate multiple distinct cellular processes that ultimately determine the masculine phenotype. Within specific brain regions, overall cell number and dendritic morphology are the principal targets for hormonal organization. Recent advances have been made in elucidating the cellular mechanisms by which the neurological underpinnings of sexually dimorphic physiology and behavior are determined. These include estradiol-mediated prostaglandin synthesis, presynaptic release of glutamate, postsynaptic changes in glutamate receptors and changes in cell adhesion molecules. Sex differences in cell death are mediated by hormonal modulation of survival and death factors such as TNFalpha and Bcl-2/BAX. Copyright 2010 Elsevier Ltd. All rights reserved.

Effects of Fructose vs Glucose on Regional Cerebral Blood Flow in Brain Regions Involved With Appetite and Reward Pathways

PubMed Central

Page, Kathleen A.; Chan, Owen; Arora, Jagriti; Belfort-DeAguiar, Renata; Dzuira, James; Roehmholdt, Brian; Cline, Gary W.; Naik, Sarita; Sinha, Rajita; Constable, R. Todd; Sherwin, Robert S.

2014-01-01

Importance Increases in fructose consumption have paralleled the increasing prevalence of obesity, and high-fructose diets are thought to promote weight gain and insulin resistance. Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion, and central administration of fructose provokes feeding in rodents, whereas centrally administered glucose promotes satiety. Objective To study neurophysiological factors that might underlie associations between fructose consumption and weight gain. Design, Setting, and Participants Twenty healthy adult volunteers underwent 2 magnetic resonance imaging sessions at Yale University in conjunction with fructose or glucose drink ingestion in a blinded, random-order, crossover design. Main Outcome Measures Relative changes in hypothalamic regional cerebral blood flow (CBF) after glucose or fructose ingestion. Secondary outcomes included whole-brain analyses to explore regional CBF changes, functional connectivity analysis to investigate correlations between the hypothalamus and other brain region responses, and hormone responses to fructose and glucose ingestion. Results There was a significantly greater reduction in hypothalamic CBF after glucose vs fructose ingestion (–5.45 vs 2.84 mL/g per minute, respectively; mean difference, 8.3 mL/g per minute [95% CI of mean difference, 1.87-14.70]; P=.01). Glucose ingestion (compared with baseline) increased functional connectivity between the hypothalamus and the thalamus and striatum. Fructose increased connectivity between the hypothalamus and thalamus but not the striatum. Regional CBF within the hypothalamus, thalamus, insula, anterior cingulate, and striatum (appetite and reward regions) was reduced after glucose ingestion compared with baseline (P<.05 significance threshold, family-wise error [FWE] whole-brain corrected). In contrast, fructose reduced regional CBF in the thalamus, hippocampus, posterior cingulate cortex, fusiform, and visual cortex (P<.05 significance threshold, FWE whole-brain corrected). In whole-brain voxel-level analyses, there were no significant differences between direct comparisons of fructose vs glucose sessions following correction for multiple comparisons. Fructose vs glucose ingestion resulted in lower peak levels of serum glucose (mean difference, 41.0 mg/dL [95% CI, 27.7-54.5]; P<.001), insulin (mean difference, 49.6 μU/mL [95% CI, 38.2-61.1]; P<.001), and glucagon-like polypep-tide 1 (mean difference, 2.1 pmol/L [95% CI, 0.9-3.2]; P=.01). Conclusion and Relevance In a series of exploratory analyses, consumption of fructose compared with glucose resulted in a distinct pattern of regional CBF and a smaller increase in systemic glucose, insulin, and glucagon-like polypeptide 1 levels. PMID:23280226

Brain Metabolic Changes in Rats following Acoustic Trauma

PubMed Central

He, Jun; Zhu, Yejin; Aa, Jiye; Smith, Paul F.; De Ridder, Dirk; Wang, Guangji; Zheng, Yiwen

2017-01-01

Acoustic trauma is the most common cause of hearing loss and tinnitus in humans. However, the impact of acoustic trauma on system biology is not fully understood. It has been increasingly recognized that tinnitus caused by acoustic trauma is unlikely to be generated by a single pathological source, but rather a complex network of changes involving not only the auditory system but also systems related to memory, emotion and stress. One obvious and significant gap in tinnitus research is a lack of biomarkers that reflect the consequences of this interactive “tinnitus-causing” network. In this study, we made the first attempt to analyse brain metabolic changes in rats following acoustic trauma using metabolomics, as a pilot study prior to directly linking metabolic changes to tinnitus. Metabolites in 12 different brain regions collected from either sham or acoustic trauma animals were profiled using a gas chromatography mass spectrometry (GC/MS)-based metabolomics platform. After deconvolution of mass spectra and identification of the molecules, the metabolomic data were processed using multivariate statistical analysis. Principal component analysis showed that metabolic patterns varied among different brain regions; however, brain regions with similar functions had a similar metabolite composition. Acoustic trauma did not change the metabolite clusters in these regions. When analyzed within each brain region using the orthogonal projection to latent structures discriminant analysis sub-model, 17 molecules showed distinct separation between control and acoustic trauma groups in the auditory cortex, inferior colliculus, superior colliculus, vestibular nucleus complex (VNC), and cerebellum. Further metabolic pathway impact analysis and the enrichment overview with network analysis suggested the primary involvement of amino acid metabolism, including the alanine, aspartate and glutamate metabolic pathways, the arginine and proline metabolic pathways and the purine metabolic pathway. Our results provide the first metabolomics evidence that acoustic trauma can induce changes in multiple metabolic pathways. This pilot study also suggests that the metabolomic approach has the potential to identify acoustic trauma-specific metabolic shifts in future studies where metabolic changes are correlated with the animal's tinnitus status. PMID:28392756

DHEA Enhances Emotion Regulation Neurocircuits and Modulates Memory for Emotional Stimuli

PubMed Central

Sripada, Rebecca K; Marx, Christine E; King, Anthony P; Rajaram, Nirmala; Garfinkel, Sarah N; Abelson, James L; Liberzon, Israel

2013-01-01

Dehydroepiandrosterone (DHEA) is a neurosteroid with anxiolytic, antidepressant, and antiglucocorticoid properties. It is endogenously released in response to stress, and may reduce negative affect when administered exogenously. Although there have been multiple reports of DHEA's antidepressant and anxiolytic effects, no research to date has examined the neural pathways involved. In particular, brain imaging has not been used to link neurosteroid effects to emotion neurocircuitry. To investigate the brain basis of DHEA's impact on emotion modulation, patients were administered 400 mg of DHEA (N=14) or placebo (N=15) and underwent 3T fMRI while performing the shifted-attention emotion appraisal task (SEAT), a test of emotional processing and regulation. Compared with placebo, DHEA reduced activity in the amygdala and hippocampus, enhanced connectivity between the amygdala and hippocampus, and enhanced activity in the rACC. These activation changes were associated with reduced negative affect. DHEA reduced memory accuracy for emotional stimuli, and also reduced activity in regions associated with conjunctive memory encoding. These results demonstrate that DHEA reduces activity in regions associated with generation of negative emotion and enhances activity in regions linked to regulatory processes. Considering that activity in these regions is altered in mood and anxiety disorders, our results provide initial neuroimaging evidence that DHEA may be useful as a pharmacological intervention for these conditions and invite further investigation into the brain basis of neurosteroid emotion regulatory effects. PMID:23552182

A Peptide Targeting Inflammatory CNS Lesions in the EAE Rat Model of Multiple Sclerosis.

PubMed

Boiziau, Claudine; Nikolski, Macha; Mordelet, Elodie; Aussudre, Justine; Vargas-Sanchez, Karina; Petry, Klaus G

2018-06-01

Multiple sclerosis is characterized by inflammatory lesions dispersed throughout the central nervous system (CNS) leading to severe neurological handicap. Demyelination, axonal damage, and blood brain barrier alterations are hallmarks of this pathology, whose precise processes are not fully understood. In the experimental autoimmune encephalomyelitis (EAE) rat model that mimics many features of human multiple sclerosis, the phage display strategy was applied to select peptide ligands targeting inflammatory sites in CNS. Due to the large diversity of sequences after phage display selection, a bioinformatics procedure called "PepTeam" designed to identify peptides mimicking naturally occurring proteins was used, with the goal to predict peptides that were not background noise. We identified a circular peptide CLSTASNSC called "Ph48" as an efficient binder of inflammatory regions of EAE CNS sections including small inflammatory lesions of both white and gray matter. Tested on human brain endothelial cells hCMEC/D3, Ph48 was able to bind efficiently when these cells were activated with IL1β to mimic inflammatory conditions. The peptide is therefore a candidate for further analyses of the molecular alterations in inflammatory lesions.

Development of global cortical networks in early infancy.

PubMed

Homae, Fumitaka; Watanabe, Hama; Otobe, Takayuki; Nakano, Tamami; Go, Tohshin; Konishi, Yukuo; Taga, Gentaro

2010-04-07

Human cognition and behaviors are subserved by global networks of neural mechanisms. Although the organization of the brain is a subject of interest, the process of development of global cortical networks in early infancy has not yet been clarified. In the present study, we explored developmental changes in these networks from several days to 6 months after birth by examining spontaneous fluctuations in brain activity, using multichannel near-infrared spectroscopy. We set up 94 measurement channels over the frontal, temporal, parietal, and occipital regions of the infant brain. The obtained signals showed complex time-series properties, which were characterized as 1/f fluctuations. To reveal the functional connectivity of the cortical networks, we calculated the temporal correlations of continuous signals between all the pairs of measurement channels. We found that the cortical network organization showed regional dependency and dynamic changes in the course of development. In the temporal, parietal, and occipital regions, connectivity increased between homologous regions in the two hemispheres and within hemispheres; in the frontal regions, it decreased progressively. Frontoposterior connectivity changed to a "U-shaped" pattern within 6 months: it decreases from the neonatal period to the age of 3 months and increases from the age of 3 months to the age of 6 months. We applied cluster analyses to the correlation coefficients and showed that the bilateral organization of the networks begins to emerge during the first 3 months of life. Our findings suggest that these developing networks, which form multiple clusters, are precursors of the functional cerebral architecture.

Coexisting cholinergic and parahippocampal degeneration: a key to memory loss in dementia and a challenge for transgenic models?

PubMed

Cassel, Jean-Christophe; Mathis, Chantal; Majchrzak, Monique; Moreau, Pierre-Henri; Dalrymple-Alford, John C

2008-01-01

One century after Alzheimer's initial report, a variety of animal models of Alzheimer's disease (AD) are being used to mimic one or more pathological signs viewed as critical for the evolution of cognitive decline in dementia. Among the most common are, (a) traditional lesion models aimed at reproducing the degeneration of one of two key brain regions affected in AD, namely the cholinergic basal forebrain (CBF) and the transentorhinal region, and (b) transgenic mouse models aimed at reproducing AD histopathological hallmarks, namely amyloid plaques and neurofibrillary tangles. These models have provided valuable insights into the development and consequences of the pathology, but they have not consistently reproduced the severity of memory deficits exhibited in AD. The reasons for this lack of correspondence with the severity of expected deficits may include the limited replication of multiple neuropathology in potentially key brain regions. A recent lesion model in the rat found that severe memory impairment was obtained only when the two traditional lesions were combined together (i.e. conjoint CBF and entorhinal cortex lesions), indicative of a dramatic impact on cognitive function when there is coexisting, rather than isolated, damage in these two brain regions. It is proposed that combining AD transgenic mouse models with additional experimental damage to both the CBF and entorhinal regions might provide a unique opportunity to further understand the evolution of the disease and improve treatments of severe cognitive dysfunction in neurodegenerative dementias. (c) 2008 S. Karger AG, Basel

Analysis of multiple quaternary ammonium compounds in the brain using tandem capillary column separation and high resolution mass spectrometric detection.

PubMed

Falasca, Sara; Petruzziello, Filomena; Kretz, Robert; Rainer, Gregor; Zhang, Xiaozhe

2012-06-08

Endogenous quaternary ammonium compounds are involved in various physiological processes in the central nervous system. In the present study, eleven quaternary ammonium compounds, including acetylcholine, choline, carnitine, acetylcarnitine and seven other acylcarnitines of low polarity, were analyzed from brain extracts using a two dimension capillary liquid chromatography-Fourier transform mass spectrometry method. To deal with their large difference in hydrophobicities, tandem coupling between reversed phase and hydrophilic interaction chromatography columns was used to separate all the targeted quaternary ammonium compounds. Using high accuracy mass spectrometry in selected ion monitoring mode, all the compounds could be detected from each brain sample with high selectivity. The developed method was applied for the relative quantification of these quaternary ammonium compounds in three different brain regions of tree shrews: prefrontal cortex, striatum, and hippocampus. The comparative analysis showed that quaternary ammonium compounds were differentially distributed across the three brain areas. The analytical method proved to be highly sensitive and reliable for simultaneous determination of all the targeted analytes from brain samples. Copyright © 2012 Elsevier B.V. All rights reserved.

Molecular, Cellular and Functional Effects of Radiation-Induced Brain Injury: A Review

PubMed Central

Balentova, Sona; Adamkov, Marian

2015-01-01

Radiation therapy is the most effective non-surgical treatment of primary brain tumors and metastases. Preclinical studies have provided valuable insights into pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced brain injury can damage neuronal, glial and vascular compartments of the brain and may lead to molecular, cellular and functional changes. Given its central role in memory and adult neurogenesis, the majority of studies have focused on the hippocampus. These findings suggested that hippocampal avoidance in cranial radiotherapy prevents radiation-induced cognitive impairment of patients. However, multiple rodent studies have shown that this problem is more complex. As the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is of critical importance to investigate molecular, cellular and functional modifications in various brain regions as well as their integration at clinically relevant doses and schedules. We here provide a literature overview, including our previously published results, in order to support the translation of preclinical findings to clinical practice, and improve the physical and mental status of patients with brain tumors. PMID:26610477

Neuroinflammation and its relationship to changes in brain volume and white matter lesions in multiple sclerosis.

PubMed

Datta, Gourab; Colasanti, Alessandro; Rabiner, Eugenii A; Gunn, Roger N; Malik, Omar; Ciccarelli, Olga; Nicholas, Richard; Van Vlierberghe, Eline; Van Hecke, Wim; Searle, Graham; Santos-Ribeiro, Andre; Matthews, Paul M

2017-11-01

Brain magnetic resonance imaging is an important tool in the diagnosis and monitoring of multiple sclerosis patients. However, magnetic resonance imaging alone provides limited information for predicting an individual patient's disability progression. In part, this is because magnetic resonance imaging lacks sensitivity and specificity for detecting chronic diffuse and multi-focal inflammation mediated by activated microglia/macrophages. The aim of this study was to test for an association between 18 kDa translocator protein brain positron emission tomography signal, which arises largely from microglial activation, and measures of subsequent disease progression in multiple sclerosis patients. Twenty-one patients with multiple sclerosis (seven with secondary progressive disease and 14 with a relapsing remitting disease course) underwent T1- and T2-weighted and magnetization transfer magnetic resonance imaging at baseline and after 1 year. Positron emission tomography scanning with the translocator protein radioligand 11C-PBR28 was performed at baseline. Brain tissue and lesion volumes were segmented from the T1- and T2-weighted magnetic resonance imaging and relative 11C-PBR28 uptake in the normal-appearing white matter was estimated as a distribution volume ratio with respect to a caudate pseudo-reference region. Normal-appearing white matter distribution volume ratio at baseline was correlated with enlarging T2-hyperintense lesion volumes over the subsequent year (ρ = 0.59, P = 0.01). A post hoc analysis showed that this association reflected behaviour in the subgroup of relapsing remitting patients (ρ = 0.74, P = 0.008). By contrast, in the subgroup of secondary progressive patients, microglial activation at baseline was correlated with later progression of brain atrophy (ρ = 0.86, P = 0.04). A regression model including the baseline normal-appearing white matter distribution volume ratio, T2 lesion volume and normal-appearing white matter magnetization transfer ratio for all of the patients combined explained over 90% of the variance in enlarging lesion volume over the subsequent 1 year. Glial activation in white matter assessed by translocator protein PET significantly improves predictions of white matter lesion enlargement in relapsing remitting patients and is associated with greater brain atrophy in secondary progressive disease over a period of short term follow-up. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Methamphetamine Causes Microglial Activation in the Brains of Human Abusers

PubMed Central

Sekine, Yoshimoto; Ouchi, Yasuomi; Sugihara, Genichi; Takei, Nori; Yoshikawa, Etsuji; Nakamura, Kazuhiko; Iwata, Yasuhide; Tsuchiya, Kenji J.; Suda, Shiro; Suzuki, Katsuaki; Kawai, Masayoshi; Takebayashi, Kiyokazu; Yamamoto, Shigeyuki; Matsuzaki, Hideo; Ueki, Takatoshi; Mori, Norio; Gold, Mark S.; Cadet, Jean L.

2008-01-01

Methamphetamine is a popular addictive drug whose use is associated with multiple neuropsychiatric adverse events and toxic to the dopaminergic and serotonergic systems of the brain. Methamphetamine-induced neuropathology is associated with increased expression of microglial cells that are thought to participate in either pro-toxic or protective mechanisms in the brain. Although reactive microgliosis has been observed in animal models of methamphetamine neurotoxicity, no study has reported on the status of microglial activation in human methamphetamine abusers. The present study reports on 12 abstinent methamphetamine abusers and 12 age-, gender-, education-matched control subjects who underwent positron emission tomography using a radiotracer for activated microglia, [11C](R)-(1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide) ([11C](R)-PK11195). Compartment analysis was used to estimate quantitative levels of binding potentials of [11C](R)-PK11195 in brain regions with dopaminergic and/or serotonergic innervation. The mean levels of [11C](R)-PK11195 binding were higher in methamphetamine abusers than those in control subjects in all brain regions (> 250% higher, p < 0.01 for all). In addition, the binding levels in the midbrain, striatum, thalamus, and orbitofrontal and insular cortices (p < 0.05) correlated inversely with the duration of methamphetamine abstinence. These results suggest that chronic self-administration of methamphetamine can cause reactive microgliosis in the brains of human methamphetamine abusers, a level of activation that appears to subside over longer periods of abstinence. PMID:18509037

Methamphetamine causes microglial activation in the brains of human abusers.

PubMed

Sekine, Yoshimoto; Ouchi, Yasuomi; Sugihara, Genichi; Takei, Nori; Yoshikawa, Etsuji; Nakamura, Kazuhiko; Iwata, Yasuhide; Tsuchiya, Kenji J; Suda, Shiro; Suzuki, Katsuaki; Kawai, Masayoshi; Takebayashi, Kiyokazu; Yamamoto, Shigeyuki; Matsuzaki, Hideo; Ueki, Takatoshi; Mori, Norio; Gold, Mark S; Cadet, Jean L

2008-05-28

Methamphetamine is a popular addictive drug whose use is associated with multiple neuropsychiatric adverse events and toxic to the dopaminergic and serotonergic systems of the brain. Methamphetamine-induced neuropathology is associated with increased expression of microglial cells that are thought to participate in either pro-toxic or protective mechanisms in the brain. Although reactive microgliosis has been observed in animal models of methamphetamine neurotoxicity, no study has reported on the status of microglial activation in human methamphetamine abusers. The present study reports on 12 abstinent methamphetamine abusers and 12 age-, gender-, and education-matched control subjects who underwent positron emission tomography using a radiotracer for activated microglia, [(11)C](R)-(1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide) ([(11)C](R)-PK11195). Compartment analysis was used to estimate quantitative levels of binding potentials of [(11)C](R)-PK11195 in brain regions with dopaminergic and/or serotonergic innervation. The mean levels of [(11)C](R)-PK11195 binding were higher in methamphetamine abusers than those in control subjects in all brain regions (>250% higher; p < 0.01 for all). In addition, the binding levels in the midbrain, striatum, thalamus, and orbitofrontal and insular cortices (p < 0.05) correlated inversely with the duration of methamphetamine abstinence. These results suggest that chronic self-administration of methamphetamine can cause reactive microgliosis in the brains of human methamphetamine abusers, a level of activation that appears to subside over longer periods of abstinence.

Distributed and opposing effects of incidental learning in the human brain.

PubMed

Hall, Michelle G; Naughtin, Claire K; Mattingley, Jason B; Dux, Paul E

2018-06-01

Incidental learning affords a behavioural advantage when sensory information matches regularities that have previously been encountered. Previous studies have taken a focused approach by probing the involvement of specific candidate brain regions underlying incidentally acquired memory representations, as well as expectation effects on early sensory representations. Here, we investigated the broader extent of the brain's sensitivity to violations and fulfilments of expectations, using an incidental learning paradigm in which the contingencies between target locations and target identities were manipulated without participants' overt knowledge. Multivariate analysis of functional magnetic resonance imaging data was applied to compare the consistency of neural activity for visual events that the contingency manipulation rendered likely versus unlikely. We observed widespread sensitivity to expectations across frontal, temporal, occipital, and sub-cortical areas. These activation clusters showed distinct response profiles, such that some regions displayed more reliable activation patterns under fulfilled expectations, whereas others showed more reliable patterns when expectations were violated. These findings reveal that expectations affect multiple stages of information processing during visual decision making, rather than early sensory processing stages alone. Copyright © 2018 Elsevier Inc. All rights reserved.

Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions

PubMed Central

Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

2017-01-01

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping. PMID:28700619

Truncated RAP-MUSIC (TRAP-MUSIC) for MEG and EEG source localization.

PubMed

Mäkelä, Niko; Stenroos, Matti; Sarvas, Jukka; Ilmoniemi, Risto J

2018-02-15

Electrically active brain regions can be located applying MUltiple SIgnal Classification (MUSIC) on magneto- or electroencephalographic (MEG; EEG) data. We introduce a new MUSIC method, called truncated recursively-applied-and-projected MUSIC (TRAP-MUSIC). It corrects a hidden deficiency of the conventional RAP-MUSIC algorithm, which prevents estimation of the true number of brain-signal sources accurately. The correction is done by applying a sequential dimension reduction to the signal-subspace projection. We show that TRAP-MUSIC significantly improves the performance of MUSIC-type localization; in particular, it successfully and robustly locates active brain regions and estimates their number. We compare TRAP-MUSIC and RAP-MUSIC in simulations with varying key parameters, e.g., signal-to-noise ratio, correlation between source time-courses, and initial estimate for the dimension of the signal space. In addition, we validate TRAP-MUSIC with measured MEG data. We suggest that with the proposed TRAP-MUSIC method, MUSIC-type localization could become more reliable and suitable for various online and offline MEG and EEG applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions.

PubMed

Gonen, Tal; Gazit, Tomer; Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

2017-01-01

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.

A systematic review of associations between functional MRI activity and polygenic risk for schizophrenia and bipolar disorder.

PubMed

Dezhina, Zalina; Ranlund, Siri; Kyriakopoulos, Marinos; Williams, Steve C R; Dima, Danai

2018-05-10

Genetic factors account for up to 80% of the liability for schizophrenia (SCZ) and bipolar disorder (BD). Genome-wide association studies have successfully identified several genes associated with increased risk for both disorders. This has allowed researchers to model the aggregate effect of genes associated with disease status and create a polygenic risk score (PGRS) for each individual. The interest in imaging genetics using PGRS has grown in recent years, with several studies now published. We have conducted a systematic review to examine the effects of PGRS of SCZ, BD and cross psychiatric disorders on brain function and connectivity using fMRI data. Results indicate that the effect of genetic load for SCZ and BD on brain function affects task-related recruitment, with frontal areas having a more prominent role, independent of task. Additionally, the results suggest that the polygenic architecture of psychotic disorders is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions. Future imaging genetics studies with large samples, especially population studies, would be uniquely informative in mapping the spatial distribution of the genetic risk to psychiatric disorders on brain processes during various cognitive tasks and may lead to the discovery of biological pathways that could be crucial in mediating the link between genetic factors and alterations in brain networks.

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

PubMed

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

2013-01-01

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

Gonadotropin-Releasing hormones in the brain and pituitary of the white sucker

USGS Publications Warehouse

Robinson, T. Craig; Tobet, Stuart A.; Chase, Cindy; Waldron, Travis; Sower, Stacia A.

2000-01-01

The present study investigated GnRH forms within the brain of a representative of the order Cypriniformes, the white sucker, Catostomus commersoni, using HPLC, RIA, andimmunocytochemistry. Several immunoreactive (ir) GnRH forms were identified in the brain of the white sucker by chromatography and radioimmunoassay, including ir-salmon GnRH, ir-lamprey GnRH-I and -III, and ir-chicken GnRH-II. Results from immunocytochemical studies were consistent with multiple GnRH forms distributed in different patterns, particularly for fibers. Neuronal perikarya containing ir-salmon GnRH and ir-lamprey-like GnRH were found laterally within the preoptic area and rostralhypothalamus. Cells containing exclusively ir-salmon GnRH appeared slightly more rostrally, but in the same region. Fibers containing ir-salmon GnRH and ir-lamprey-like GnRH were seen throughout the caudal telencephalon and extended into thediencephalon, toward the pituitary. Fibers containing ir-chicken-II-like GnRH were also seen in the caudal telencephalon, but were concentrated more dorsally in the diencephalon. Within the pituitary, fibers containing ir-salmon GnRH and ir-lamprey-like GnRH entered the neurohypophysis, but differed in their destinations. Fibers containing ir-salmon GnRH remained within the neurohypophysis, while fibers containing ir-lamprey-like GnRH targeted adenohypophyseal tissue. These findings are consistent with the hypothesis that multiple GnRH forms with multiple functions exist within the brain and pituitary of teleosts and provide further evidence of a lamprey-like GnRH within an early evolved teleost species.

Identification of Differentially Expressed Genes through Integrated Study of Alzheimer’s Disease Affected Brain Regions

PubMed Central

Berretta, Regina; Moscato, Pablo

2016-01-01

Background Alzheimer’s disease (AD) is the most common form of dementia in older adults that damages the brain and results in impaired memory, thinking and behaviour. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. In the past decade, several studies have reported many genes that are associated with AD. This wealth of information has become difficult to follow and interpret as most of the results are conflicting. In that case, it is worth doing an integrated study of multiple datasets that helps to increase the total number of samples and the statistical power in detecting biomarkers. In this study, we present an integrated analysis of five different brain region datasets and introduce new genes that warrant further investigation. Methods The aim of our study is to apply a novel combinatorial optimisation based meta-analysis approach to identify differentially expressed genes that are associated to AD across brain regions. In this study, microarray gene expression data from 161 samples (74 non-demented controls, 87 AD) from the Entorhinal Cortex (EC), Hippocampus (HIP), Middle temporal gyrus (MTG), Posterior cingulate cortex (PC), Superior frontal gyrus (SFG) and visual cortex (VCX) brain regions were integrated and analysed using our method. The results are then compared to two popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained by analysing the individual datasets. Results We find genes related with AD that are consistent with existing studies, and new candidate genes not previously related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1, RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across all brain regions. Further investigation on these genes may provide new insights into the development of AD. In addition, we identified the presence of 23 non-coding features, including four miRNA precursors (miR-7, miR570, miR-1229 and miR-6821), dysregulated across the brain regions. Furthermore, we compared our results with two popular meta-analysis methods RankProd and GeneMeta to validate our findings and performed a sensitivity analysis by removing one dataset at a time to assess the robustness of our results. These new findings may provide new insights into the disease mechanisms and thus make a significant contribution in the near future towards understanding, prevention and cure of AD. PMID:27050411

Deterioration of abstract reasoning ability in mild cognitive impairment and Alzheimer's disease: correlation with regional grey matter volume loss revealed by diffeomorphic anatomical registration through exponentiated lie algebra analysis.

PubMed

Yoshiura, Takashi; Hiwatashi, Akio; Yamashita, Koji; Ohyagi, Yasumasa; Monji, Akira; Takayama, Yukihisa; Kamano, Norihiro; Kawashima, Toshiro; Kira, Jun-Ichi; Honda, Hiroshi

2011-02-01

To determine which brain regions are relevant to deterioration in abstract reasoning as measured by Raven's Colored Progressive Matrices (CPM) in the context of dementia. MR images of 37 consecutive patients including 19 with Alzheimer's disease (AD) and 18 with amnestic mild cognitive impairment (aMCI) were retrospectively analyzed. All patients were administered the CPM. Regional grey matter (GM) volume was evaluated according to the regimens of voxel-based morphometry, during which a non-linear registration algorithm called Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra was employed. Multiple regression analyses were used to map the regions where GM volumes were correlated with CPM scores. The strongest correlation with CPM scores was seen in the left middle frontal gyrus while a region with the largest volume was identified in the left superior temporal gyrus. Significant correlations were seen in 14 additional regions in the bilateral cerebral hemispheres and right cerebellum. Deterioration of abstract reasoning ability in AD and aMCI measured by CPM is related to GM loss in multiple regions, which is in close agreement with the results of previous activation studies.

Highly scalable multichannel mesh electronics for stable chronic brain electrophysiology.

PubMed

Fu, Tian-Ming; Hong, Guosong; Viveros, Robert D; Zhou, Tao; Lieber, Charles M

2017-11-21

Implantable electrical probes have led to advances in neuroscience, brain-machine interfaces, and treatment of neurological diseases, yet they remain limited in several key aspects. Ideally, an electrical probe should be capable of recording from large numbers of neurons across multiple local circuits and, importantly, allow stable tracking of the evolution of these neurons over the entire course of study. Silicon probes based on microfabrication can yield large-scale, high-density recording but face challenges of chronic gliosis and instability due to mechanical and structural mismatch with the brain. Ultraflexible mesh electronics, on the other hand, have demonstrated negligible chronic immune response and stable long-term brain monitoring at single-neuron level, although, to date, it has been limited to 16 channels. Here, we present a scalable scheme for highly multiplexed mesh electronics probes to bridge the gap between scalability and flexibility, where 32 to 128 channels per probe were implemented while the crucial brain-like structure and mechanics were maintained. Combining this mesh design with multisite injection, we demonstrate stable 128-channel local field potential and single-unit recordings from multiple brain regions in awake restrained mice over 4 mo. In addition, the newly integrated mesh is used to validate stable chronic recordings in freely behaving mice. This scalable scheme for mesh electronics together with demonstrated long-term stability represent important progress toward the realization of ideal implantable electrical probes allowing for mapping and tracking single-neuron level circuit changes associated with learning, aging, and neurodegenerative diseases. Copyright © 2017 the Author(s). Published by PNAS.

Roadmap on neurophotonics

NASA Astrophysics Data System (ADS)

Cho, Yong Ku; Zheng, Guoan; Augustine, George J.; Hochbaum, Daniel; Cohen, Adam; Knöpfel, Thomas; Pisanello, Ferruccio; Pavone, Francesco S.; Vellekoop, Ivo M.; Booth, Martin J.; Hu, Song; Zhu, Jiang; Chen, Zhongping; Hoshi, Yoko

2016-09-01

Mechanistic understanding of how the brain gives rise to complex behavioral and cognitive functions is one of science’s grand challenges. The technical challenges that we face as we attempt to gain a systems-level understanding of the brain are manifold. The brain’s structural complexity requires us to push the limit of imaging resolution and depth, while being able to cover large areas, resulting in enormous data acquisition and processing needs. Furthermore, it is necessary to detect functional activities and ‘map’ them onto the structural features. The functional activity occurs at multiple levels, using electrical and chemical signals. Certain electrical signals are only decipherable with sub-millisecond timescale resolution, while other modes of signals occur in minutes to hours. For these reasons, there is a wide consensus that new tools are necessary to undertake this daunting task. Optical techniques, due to their versatile and scalable nature, have great potentials to answer these challenges. Optical microscopy can now image beyond the diffraction limit, record multiple types of brain activity, and trace structural features across large areas of tissue. Genetically encoded molecular tools opened doors to controlling and detecting neural activity using light in specific cell types within the intact brain. Novel sample preparation methods that reduce light scattering have been developed, allowing whole brain imaging in rodent models. Adaptive optical methods have the potential to resolve images from deep brain regions. In this roadmap article, we showcase a few major advances in this area, survey the current challenges, and identify potential future needs that may be used as a guideline for the next steps to be taken.

Brain network alterations in the inflammatory soup animal model of migraine.

PubMed

Becerra, Lino; Bishop, James; Barmettler, Gabi; Kainz, Vanessa; Burstein, Rami; Borsook, David

2017-04-01

Advances in our understanding of the human pain experience have shifted much of the focus of pain research from the periphery to the brain. Current hypotheses suggest that the progression of migraine depends on abnormal functioning of neurons in multiple brain regions. Accordingly, we sought to capture functional brain changes induced by the application of an inflammatory cocktail known as inflammatory soup (IS), to the dura mater across multiple brain networks. Specifically, we aimed to determine whether IS alters additional neural networks indirectly related to the primary nociceptive pathways via the spinal cord to the thalamus and cortex. IS comprises an acidic combination of bradykinin, serotonin, histamine and prostaglandin PGE2 and was introduced to basic pain research as a tool to activate and sensitize peripheral nociceptors when studying pathological pain conditions associated with allodynia and hyperalgesia. Using this model of intracranial pain, we found that dural application of IS in awake, fully conscious, rats enhanced thalamic, hypothalamic, hippocampal and somatosensory cortex responses to mechanical stimulation of the face (compared to sham synthetic interstitial fluid administration). Furthermore, resting state MRI data revealed altered functional connectivity in a number of networks previously identified in clinical chronic pain populations. These included the default mode, sensorimotor, interoceptive (Salience) and autonomic networks. The findings suggest that activation and sensitization of meningeal nociceptors by IS can enhance the extent to which the brain processes nociceptive signaling, define new level of modulation of affective and cognitive responses to pain; set new tone for hypothalamic regulation of autonomic outflow to the cranium; and change cerebellar functions. Copyright © 2017. Published by Elsevier B.V.

Brain network alterations in the inflammatory soup animal model of migraine

PubMed Central

Becerra, Lino; Bishop, James; Barmettler, Gabi; Kainz, Vanessa; Burstein, Rami; Borsook, David

2017-01-01

Advances in our understanding of the human pain experience have shifted much of the focus of pain research from the periphery to the brain. Current hypotheses suggest that the progression of migraine depends on abnormal functioning of neurons in multiple brain regions. Accordingly, we sought to capture functional brain changes induced by the application of an inflammatory cocktail known as inflammatory soup (IS), to the dura mater across multiple brain networks. Specifically, we aimed to determine whether IS alters additional neural networks indirectly related to the primary nociceptive pathways via the spinal cord to the thalamus and cortex. IS comprises an acidic combination of bradykinin, serotonin, histamine and prostaglandin PGE2 and was introduced to basic pain research as a tool to activate and sensitize peripheral nociceptors when studying pathological pain conditions associated with allodynia and hyperalgesia. Using this model of intracranial pain, we found that dural application of IS in awake, fully conscious, rats enhanced thalamic, hypothalamic, hippocampal and somatosensory cortex responses to mechanical stimulation of the face (compared to sham synthetic interstitial fluid administration). Furthermore, resting state MRI data revealed altered functional connectivity in a number of networks previously identified in clinical chronic pain populations. These included the default mode, sensorimotor, interoceptive (Salience) and autonomic networks. The findings suggest that activation and sensitization of meningeal nociceptors by IS can enhance the extent to which the brain processes nociceptive signaling, define new level of modulation of affective and cognitive responses to pain; set new tone for hypothalamic regulation of autonomic outflow to the cranium; and change cerebellar functions. PMID:28167076

Roadmap on neurophotonics

PubMed Central

Cho, Yong Ku; Zheng, Guoan; Augustine, George J; Hochbaum, Daniel; Cohen, Adam; Knöpfel, Thomas; Pisanello, Ferruccio; Pavone, Francesco S; Vellekoop, Ivo M; Booth, Martin J; Hu, Song; Zhu, Jiang; Chen, Zhongping; Hoshi, Yoko

2017-01-01

Mechanistic understanding of how the brain gives rise to complex behavioral and cognitive functions is one of science’s grand challenges. The technical challenges that we face as we attempt to gain a systems-level understanding of the brain are manifold. The brain’s structural complexity requires us to push the limit of imaging resolution and depth, while being able to cover large areas, resulting in enormous data acquisition and processing needs. Furthermore, it is necessary to detect functional activities and ‘map’ them onto the structural features. The functional activity occurs at multiple levels, using electrical and chemical signals. Certain electrical signals are only decipherable with sub-millisecond timescale resolution, while other modes of signals occur in minutes to hours. For these reasons, there is a wide consensus that new tools are necessary to undertake this daunting task. Optical techniques, due to their versatile and scalable nature, have great potentials to answer these challenges. Optical microscopy can now image beyond the diffraction limit, record multiple types of brain activity, and trace structural features across large areas of tissue. Genetically encoded molecular tools opened doors to controlling and detecting neural activity using light in specific cell types within the intact brain. Novel sample preparation methods that reduce light scattering have been developed, allowing whole brain imaging in rodent models. Adaptive optical methods have the potential to resolve images from deep brain regions. In this roadmap article, we showcase a few major advances in this area, survey the current challenges, and identify potential future needs that may be used as a guideline for the next steps to be taken. PMID:28386392

Postmortem evidence of cerebral inflammation in schizophrenia: a systematic review

PubMed Central

Trépanier, M O; Hopperton, K E; Mizrahi, R; Mechawar, N; Bazinet, R P

2016-01-01

Schizophrenia is a psychiatric disorder which has a lifetime prevalence of ~1%. Multiple candidate mechanisms have been proposed in the pathogenesis of schizophrenia. One such mechanism is the involvement of neuroinflammation. Clinical studies, including neuroimaging, peripheral biomarkers and randomized control trials, have suggested the presence of neuroinflammation in schizophrenia. Many studies have also measured markers of neuroinflammation in postmortem brain samples from schizophrenia patients. The objective of this study was to conduct a systematic search of the literature on neuroinflammation in postmortem brains of schizophrenia patients indexed in MEDLINE, Embase and PsycINFO. Databases were searched up until 20th March 2016 for articles published on postmortem brains in schizophrenia evaluating microglia, astrocytes, glia, cytokines, the arachidonic cascade, substance P and other markers of neuroinflammation. Two independent reviewers extracted the data. Out of 5385 articles yielded by the search, 119 articles were identified that measured neuroinflammatory markers in schizophrenic postmortem brains. Glial fibrillary acidic protein expression was elevated, lower or unchanged in 6, 6 and 21 studies, respectively, and similar results were obtained for glial cell densities. On the other hand, microglial markers were increased, lower or unchanged in schizophrenia in 11, 3 and 8 studies, respectively. Results were variable across all other markers, but SERPINA3 and IFITM were consistently increased in 4 and 5 studies, respectively. Despite the variability, some studies evaluating neuroinflammation in postmortem brains in schizophrenia suggest an increase in microglial activity and other markers such as SERPINA3 and IFITM. Variability across studies is partially explained by multiple factors including brain region evaluated, source of the brain, diagnosis, age at time of death, age of onset and the presence of suicide victims in the cohort. PMID:27271499

Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in Mitochondrial Neurogastrointestinal Encephalopathy.

PubMed

Gramegna, L L; Pisano, A; Testa, C; Manners, D N; D'Angelo, R; Boschetti, E; Giancola, F; Pironi, L; Caporali, L; Capristo, M; Valentino, M L; Plazzi, G; Casali, C; Dotti, M T; Cenacchi, G; Hirano, M; Giordano, C; Parchi, P; Rinaldi, R; De Giorgio, R; Lodi, R; Carelli, V; Tonon, C

2018-01-18

Mitochondrial neurogastrointestinal encephalopathy is a rare disorder due to recessive mutations in the thymidine phosphorylase gene, encoding thymidine phosphorylase protein required for mitochondrial DNA replication. Clinical manifestations include gastrointestinal dysmotility and diffuse asymptomatic leukoencephalopathy. This study aimed to elucidate the mechanisms underlying brain leukoencephalopathy in patients with mitochondrial neurogastrointestinal encephalopathy by correlating multimodal neuroradiologic features to postmortem pathology. Seven patients underwent brain MR imaging, including single-voxel proton MR spectroscopy and diffusion imaging. Absolute concentrations of metabolites calculated by acquiring unsuppressed water spectra at multiple TEs, along with diffusion metrics based on the tensor model, were compared with those of healthy controls using unpaired t tests in multiple white matters regions. Brain postmortem histologic, immunohistochemical, and molecular analyses were performed in 1 patient. All patients showed bilateral and nearly symmetric cerebral white matter hyperintensities on T2-weighted images, extending to the cerebellar white matter and brain stem in 4. White matter, N -acetylaspartate, creatine, and choline concentrations were significantly reduced compared with those in controls, with a prominent increase in the radial water diffusivity component. At postmortem examination, severe fibrosis of brain vessel smooth muscle was evident, along with mitochondrial DNA replication depletion in brain and vascular smooth-muscle and endothelial cells, without neuronal loss, myelin damage, or gliosis. Prominent periependymal cytochrome C oxidase deficiency was also observed. Vascular functional and histologic alterations account for leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy. Thymidine toxicity and mitochondrial DNA replication depletion may induce microangiopathy and blood-brain-barrier dysfunction, leading to increased water content in the white matter. Periependymal cytochrome C oxidase deficiency could explain prominent periventricular impairment. © 2018 by American Journal of Neuroradiology.

Strategy-based reasoning training modulates cortical thickness and resting-state functional connectivity in adults with chronic traumatic brain injury.

PubMed

Han, Kihwan; Davis, Rebecca A; Chapman, Sandra B; Krawczyk, Daniel C

2017-05-01

Prior studies have demonstrated training-induced changes in the healthy adult brain. Yet, it remains unclear how the injured brain responds to cognitive training months-to-years after injury. Sixty individuals with chronic traumatic brain injury (TBI) were randomized into either strategy-based ( N  = 31) or knowledge-based ( N  = 29) training for 8 weeks. We measured cortical thickness and resting-state functional connectivity (rsFC) before training, immediately posttraining, and 3 months posttraining. Relative to the knowledge-based training group, the cortical thickness of the strategy-based training group showed diverse temporal patterns of changes over multiple brain regions ( p vertex  < .05, p cluster  < .05): (1) increases followed by decreases, (2) monotonic increases, and (3) monotonic decreases. However, network-based statistics (NBS) analysis of rsFC among these regions revealed that the strategy-based training group induced only monotonic increases in connectivity, relative to the knowledge-based training group (| Z | > 1.96, p NBS  < 0.05). Complementing the rsFC results, the strategy-based training group yielded monotonic improvement in scores for the trail-making test ( p  <   .05). Analyses of brain-behavior relationships revealed that improvement in trail-making scores were associated with training-induced changes in cortical thickness ( p vertex  < .05, p cluster  < .05) and rsFC ( p vertex  < .05, p cluster  < .005) within the strategy-based training group. These findings suggest that training-induced brain plasticity continues through chronic phases of TBI and that brain connectivity and cortical thickness may serve as markers of plasticity.

Food portion size and energy density evoke different patterns of brain activation in children12

PubMed Central

Fearnbach, S Nicole; Wilson, Stephen J; Fisher, Jennifer O; Savage, Jennifer S; Rolls, Barbara J; Keller, Kathleen L

2017-01-01

Background: Large portions of food promote intake, but the mechanisms that drive this effect are unclear. Previous neuroimaging studies have identified the brain-reward and decision-making systems that are involved in the response to the energy density (ED) (kilocalories per gram) of foods, but few studies have examined the brain response to the food portion size (PS). Objective: We used functional MRI (fMRI) to determine the brain response to food images that differed in PSs (large and small) and ED (high and low). Design: Block-design fMRI was used to assess the blood oxygen level–dependent (BOLD) response to images in 36 children (7–10 y old; girls: 50%), which was tested after a 2-h fast. Pre-fMRI fullness and liking were rated on visual analog scales. A whole-brain cluster-corrected analysis was used to compare BOLD activation for main effects of the PS, ED, and their interaction. Secondary analyses were used to associate BOLD contrast values with appetitive traits and laboratory intake from meals for which the portions of all foods were increased. Results: Compared with small-PS cues, large-PS cues were associated with decreased activation in the inferior frontal gyrus (P < 0.01). Compared with low-ED cues, high-ED cues were associated with increased activation in multiple regions (e.g., in the caudate, cingulate, and precentral gyrus) and decreased activation in the insula and superior temporal gyrus (P < 0.01 for all). A PS × ED interaction was shown in the superior temporal gyrus (P < 0.01). BOLD contrast values for high-ED cues compared with low-ED cues in the insula, declive, and precentral gyrus were negatively related to appetitive traits (P < 0.05). There were no associations between the brain response to the PS and either appetitive traits or intake. Conclusions: Cues regarding food PS may be processed in the lateral prefrontal cortex, which is a region that is implicated in cognitive control, whereas ED activates multiple areas involved in sensory and reward processing. Possible implications include the development of interventions that target decision-making and reward systems differently to moderate overeating. PMID:27881393

Impaired behavior on real-world tasks following damage to the ventromedial prefrontal cortex.

PubMed

Tranel, Daniel; Hathaway-Nepple, Julie; Anderson, Steven W

2007-04-01

Patients with damage to the ventromedial prefrontal cortices (VMPC) commonly manifest blatant behavioral navigation defects in the real world, but it has been difficult to measure these impairments in the clinic or laboratory. Using a set of "strategy application" tasks, which were designed by Shallice and Burgess (1991) to be ecologically valid for detecting executive dysfunction, we investigated the hypothesis that VMPC damage would be associated with defective performance on such tasks, whereas damage outside the VMPC region would not. A group of 9 patients with bilateral VMPC damage was contrasted with comparison groups of participants with (a) prefrontal brain damage outside the VMPC region (n = 8); (b) nonprefrontal brain damage (n = 17); and (c) no brain damage (n = 20). We found support for the hypothesis: VMPC patients had more impaired performances on the strategy application tasks, especially on a Multiple Errands Test that required patients to execute a series of unstructured tasks in a real-world setting (shopping mall). The results are consistent with the notion that efficacious behavioral navigation is dependent on the VMPC region. However, the strategy application tasks were relatively time consuming and effortful, and their diagnostic yield over and above conventional executive functioning tests may not be sufficient to warrant their inclusion in standard clinical assessment.

Functional neuroanatomy of intuitive physical inference

PubMed Central

Mikhael, John G.; Tenenbaum, Joshua B.; Kanwisher, Nancy

2016-01-01

To engage with the world—to understand the scene in front of us, plan actions, and predict what will happen next—we must have an intuitive grasp of the world’s physical structure and dynamics. How do the objects in front of us rest on and support each other, how much force would be required to move them, and how will they behave when they fall, roll, or collide? Despite the centrality of physical inferences in daily life, little is known about the brain mechanisms recruited to interpret the physical structure of a scene and predict how physical events will unfold. Here, in a series of fMRI experiments, we identified a set of cortical regions that are selectively engaged when people watch and predict the unfolding of physical events—a “physics engine” in the brain. These brain regions are selective to physical inferences relative to nonphysical but otherwise highly similar scenes and tasks. However, these regions are not exclusively engaged in physical inferences per se or, indeed, even in scene understanding; they overlap with the domain-general “multiple demand” system, especially the parts of that system involved in action planning and tool use, pointing to a close relationship between the cognitive and neural mechanisms involved in parsing the physical content of a scene and preparing an appropriate action. PMID:27503892

Functional neuroanatomy of intuitive physical inference.

PubMed

Fischer, Jason; Mikhael, John G; Tenenbaum, Joshua B; Kanwisher, Nancy

2016-08-23

To engage with the world-to understand the scene in front of us, plan actions, and predict what will happen next-we must have an intuitive grasp of the world's physical structure and dynamics. How do the objects in front of us rest on and support each other, how much force would be required to move them, and how will they behave when they fall, roll, or collide? Despite the centrality of physical inferences in daily life, little is known about the brain mechanisms recruited to interpret the physical structure of a scene and predict how physical events will unfold. Here, in a series of fMRI experiments, we identified a set of cortical regions that are selectively engaged when people watch and predict the unfolding of physical events-a "physics engine" in the brain. These brain regions are selective to physical inferences relative to nonphysical but otherwise highly similar scenes and tasks. However, these regions are not exclusively engaged in physical inferences per se or, indeed, even in scene understanding; they overlap with the domain-general "multiple demand" system, especially the parts of that system involved in action planning and tool use, pointing to a close relationship between the cognitive and neural mechanisms involved in parsing the physical content of a scene and preparing an appropriate action.

Integrated feature extraction and selection for neuroimage classification

NASA Astrophysics Data System (ADS)

Fan, Yong; Shen, Dinggang

2009-02-01

Feature extraction and selection are of great importance in neuroimage classification for identifying informative features and reducing feature dimensionality, which are generally implemented as two separate steps. This paper presents an integrated feature extraction and selection algorithm with two iterative steps: constrained subspace learning based feature extraction and support vector machine (SVM) based feature selection. The subspace learning based feature extraction focuses on the brain regions with higher possibility of being affected by the disease under study, while the possibility of brain regions being affected by disease is estimated by the SVM based feature selection, in conjunction with SVM classification. This algorithm can not only take into account the inter-correlation among different brain regions, but also overcome the limitation of traditional subspace learning based feature extraction methods. To achieve robust performance and optimal selection of parameters involved in feature extraction, selection, and classification, a bootstrapping strategy is used to generate multiple versions of training and testing sets for parameter optimization, according to the classification performance measured by the area under the ROC (receiver operating characteristic) curve. The integrated feature extraction and selection method is applied to a structural MR image based Alzheimer's disease (AD) study with 98 non-demented and 100 demented subjects. Cross-validation results indicate that the proposed algorithm can improve performance of the traditional subspace learning based classification.

Impaired behavior on real-world tasks following damage to the ventromedial prefrontal cortex

PubMed Central

Tranel, Daniel; Hathaway-Nepple, Julie; Anderson, Steven W.

2008-01-01

Patients with damage to the ventromedial prefrontal cortices (VMPC) commonly manifest blatant behavioral navigation defects in the real world, but it has been difficult to measure these impairments in the clinic or laboratory. Using a set of “strategy application” tasks, which were designed by Shallice and Burgess (1991) to be ecologically valid for detecting executive dysfunction, we investigated the hypothesis that VMPC damage would be associated with defective performance on such tasks, whereas damage outside the VMPC region would not. A group of 9 patients with bilateral VMPC damage was contrasted with comparison groups of participants with (a) prefrontal brain damage outside the VMPC region (n=8); (b) nonprefrontal brain damage (n=17); and (c) no brain damage (n=20). We found support for the hypothesis: VMPC patients had more impaired performances on the strategy application tasks, especially on a Multiple Errands Test that required patients to execute a series of unstructured tasks in a real-world setting (shopping mall). The results are consistent with the notion that efficacious behavioral navigation is dependent on the VMPC region. However, the strategy application tasks were relatively time consuming and effortful, and their diagnostic yield over and above conventional executive functioning tests may not be sufficient to warrant their inclusion in standard clinical assessment. PMID:17454352

Cortical Circuit for Binding Object Identity and Location During Multiple-Object Tracking

PubMed Central

Nummenmaa, Lauri; Oksama, Lauri; Glerean, Erico; Hyönä, Jukka

2017-01-01

Abstract Sustained multifocal attention for moving targets requires binding object identities with their locations. The brain mechanisms of identity-location binding during attentive tracking have remained unresolved. In 2 functional magnetic resonance imaging experiments, we measured participants’ hemodynamic activity during attentive tracking of multiple objects with equivalent (multiple-object tracking) versus distinct (multiple identity tracking, MIT) identities. Task load was manipulated parametrically. Both tasks activated large frontoparietal circuits. MIT led to significantly increased activity in frontoparietal and temporal systems subserving object recognition and working memory. These effects were replicated when eye movements were prohibited. MIT was associated with significantly increased functional connectivity between lateral temporal and frontal and parietal regions. We propose that coordinated activity of this network subserves identity-location binding during attentive tracking. PMID:27913430

Network measures predict neuropsychological outcome after brain injury

PubMed Central

Warren, David E.; Power, Jonathan D.; Bruss, Joel; Denburg, Natalie L.; Waldron, Eric J.; Sun, Haoxin; Petersen, Steven E.; Tranel, Daniel

2014-01-01

Hubs are network components that hold positions of high importance for network function. Previous research has identified hubs in human brain networks derived from neuroimaging data; however, there is little consensus on the localization of such hubs. Moreover, direct evidence regarding the role of various proposed hubs in network function (e.g., cognition) is scarce. Regions of the default mode network (DMN) have been frequently identified as “cortical hubs” of brain networks. On theoretical grounds, we have argued against some of the methods used to identify these hubs and have advocated alternative approaches that identify different regions of cortex as hubs. Our framework predicts that our proposed hub locations may play influential roles in multiple aspects of cognition, and, in contrast, that hubs identified via other methods (including salient regions in the DMN) might not exert such broad influence. Here we used a neuropsychological approach to directly test these predictions by studying long-term cognitive and behavioral outcomes in 30 patients, 19 with focal lesions to six “target” hubs identified by our approaches (high system density and participation coefficient) and 11 with focal lesions to two “control” hubs (high degree centrality). In support of our predictions, we found that damage to target locations produced severe and widespread cognitive deficits, whereas damage to control locations produced more circumscribed deficits. These findings support our interpretation of how neuroimaging-derived network measures relate to cognition and augment classic neuroanatomically based predictions about cognitive and behavioral outcomes after focal brain injury. PMID:25225403

Neurobiology of Insight Deficits in Schizophrenia: An fMRI Study

PubMed Central

Shad, Mujeeb U.; Keshavan, Matcheri S.

2015-01-01

Prior research has shown insight deficits in schizophrenia to be associated with specific neuroimaging changes (primarily structural) especially in the prefrontal sub-regions. However, little is known about the functional correlates of impaired insight. Seventeen patients with schizophrenia (mean age 40.0±10.3; M/F= 14/3) underwent fMRI on a Philips 3.0 T Achieva system while performing on a self-awareness task containing self- vs. other-directed sentence stimuli. SPM5 was used to process the imaging data. Preprocessing consisted of realignment, coregistration, and normalization, and smoothing. A regression analysis was used to examine the relationship between brain activation in response to self-directed versus other-directed sentence stimuli and average scores on behavioral measures of awareness of symptoms and attribution of symptoms to the illness from Scale to Assess Unawareness of Mental Disorders. Family Wise Error correction was employed in the fMRI analysis. Average scores on awareness of symptoms (1 = aware; 5 = unaware) were associated with activation of multiple brain regions, including prefrontal, parietal and limbic areas as well as basal ganglia. However, average scores on correct attribution of symptoms (1 = attribute; 5 = misattribute) were associated with relatively more localized activation of prefrontal cortex and basal ganglia. These findings suggest that unawareness and misattribution of symptoms may have different neurobiological basis in schizophrenia. While symptom unawareness may be a function of a more complex brain network, symptom misattribution may be mediated by specific brain regions. PMID:25957484

Iron, transferrin and myelinogenesis

NASA Astrophysics Data System (ADS)

Sergeant, C.; Vesvres, M. H.; Devès, G.; Baron, B.; Guillou, F.

2003-09-01

Transferrin (Tf), the iron binding protein of vertebrates serum, is known to be synthesized by oligodendrocytes (Ols) in the central nervous system. It has been postulated that Tf is involved in Ols maturation and myelinogenesis. This link is particularly important in the understanding of a severe human pathology: the multiple sclerosis, which remains without efficient treatment. We generated transgenic mice containing the complete human Tf gene and extensive regulatory sequences from the 5 ' and 3 ' untranslated regions that specifically overexpress Tf in Ols. Brain cytoarchitecture of the transgenic mice appears to be normal in all brain regions examined, total myelin content is increased by 30% and motor coordination is significantly improved when compared with non-transgenic littermates. Tf role in the central nervous system may be related to its affinity for metallic cations. Normal and transgenic mice were used for determination of trace metals (iron, copper and zinc) and minerals (potassium and calcium) concentration in cerebellum and corpus callosum. The freeze-dried samples were prepared to allow proton-induced X-ray emission and Rutherford backscattering spectrometry analyses with the nuclear microprobe in Bordeaux. Preliminary results were obtained and carbon distribution was revealed as a very good analysis to distinguish precisely the white matter region. A comparison of metallic and mineral elements contents in brain between normal and transgenic mice shows that iron, copper and zinc levels remained constant. This result provides evidence that effects of Tf overexpression in the brain do not solely relate to iron transport.

Complex network inference from P300 signals: Decoding brain state under visual stimulus for able-bodied and disabled subjects

NASA Astrophysics Data System (ADS)

Gao, Zhong-Ke; Cai, Qing; Dong, Na; Zhang, Shan-Shan; Bo, Yun; Zhang, Jie

2016-10-01

Distinguishing brain cognitive behavior underlying disabled and able-bodied subjects constitutes a challenging problem of significant importance. Complex network has established itself as a powerful tool for exploring functional brain networks, which sheds light on the inner workings of the human brain. Most existing works in constructing brain network focus on phase-synchronization measures between regional neural activities. In contrast, we propose a novel approach for inferring functional networks from P300 event-related potentials by integrating time and frequency domain information extracted from each channel signal, which we show to be efficient in subsequent pattern recognition. In particular, we construct brain network by regarding each channel signal as a node and determining the edges in terms of correlation of the extracted feature vectors. A six-choice P300 paradigm with six different images is used in testing our new approach, involving one able-bodied subject and three disabled subjects suffering from multiple sclerosis, cerebral palsy, traumatic brain and spinal-cord injury, respectively. We then exploit global efficiency, local efficiency and small-world indices from the derived brain networks to assess the network topological structure associated with different target images. The findings suggest that our method allows identifying brain cognitive behaviors related to visual stimulus between able-bodied and disabled subjects.

The Differential Role of Verbal and Spatial Working Memory in the Neural Basis of Arithmetic

PubMed Central

Demir, Özlem Ece; Prado, Jérôme; Booth, James R.

2014-01-01

We examine the relations of verbal and spatial WM ability to the neural bases of arithmetic in school-age children. We independently localize brain regions subserving verbal versus spatial representations. For multiplication, higher verbal WM ability is associated with greater recruitment of the left temporal cortex, identified by the verbal localizer. For multiplication and subtraction, higher spatial WM ability is associated with greater recruitment of right parietal cortex, identified by the spatial localizer. Depending on their WM ability, children engage different neural systems that manipulate different representations to solve arithmetic problems. PMID:25144257

BI-31ANALYSIS AND QUANTIFICATION OF MULTIPLE ANTIGEN EXPRESSION IN GLIOBLASTOMA

PubMed Central

Weng, Lihong; Zhai, Yubo; D'Apuzzo, Massimo; Badie, Behnam; Forman, Stephen J.; Barish, Michael; Brown, Christine E.

2014-01-01

Glioblastoma (GBM), one of the most common and fatal types of brain tumor, is marked by significant antigenic heterogeneity. Identification and quantification of tumor related antigens in the context of GBM tissue is an essential step towards developing antigen- targeted therapies. Immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) clinical specimens is a valuable technique for evaluating antigen expression in large study cohorts. To overcome the limitations of manual semi-quantitative scoring and subjectivity in the evaluation of IHC staining, we analyzed and quantified multiple antigens across entire tumor sections using Image Pro Premier v9.1 (DAB plug-in). For each slide, dense tumor regions (DTRs, tumor cells >60%), tumor infiltration regions (TIRs, tumor cells <50%) and pseudopalisading necrosis regions (PPNs) were defined from HE section by a neuropathologist. We quantified the expression of tumor-associated antigens IL13Rα2, HER2, EGFR and the proliferation marker Ki67 within these defined regions for 44 brain tumor samples (35 stage IV and 9 stage III). Our results demonstrate the heterogeneous expression patterns of IL13Rα2, HER2 and EGFR in GBMs. For example, in dense tumor regions 52%, 61% and 77% of samples showed IL13Rα2, HER2 or EGFR positivity, respectively. In correlation studies, 25% of samples were triple positive, 11% of samples showed double positivity for IL13Rα2 and HER2 or IL13Rα2 and EGFR, and 25% of samples were double positive of EGFR and HER2. Less than 7% of samples were negative for all three antigens. Interestingly, a higher percentage of samples showed triple positive expression in PPN regions (43%) versus the DTR (25%) and TIR (25%) regions. Also, Ki67 positivity was higher in PPN and DTR regions. In this study we developed methods for combining pathological annotations with DAB-capturing software, which allowed us to quantify protein expression in a more precise, consistent and efficient manner.

Neurocutaneous melanocytosis presenting in a teenager: A case report and review of the literature.

PubMed

Monica, I; Kumar, L Pavan; Uppin, Megha S; Jagannath Rao Naidu, Kotiyala V

2015-01-01

Neuro cutaneous melanocytosis (NCM) is a non-familial, congenital disorder characterized by multiple congenital nevi and brain or leptomeningeal abnormal melanin deposits. Here, we present an adult onset NCM. A 17-year-old boy presented with headache and double vision for 1 month. Magnetic resonance imaging of the brain showed hydrocephalus and abnormal meningeal hyper intensities in supra and infratentorial regions predominantly in the posterior fossa. Para medullary region showed an 11×10 mm nodular contrast enhancing nodule. Resection of an intramedullary central nervous system lesion revealed melanoma while skin biopsy was benign melanocytic nevus. As per Kadonaga and Frieden criteria, a diagnosis of NCM was made. Planned for craniospinal irradiation by three-dimensional conformal radiotherapy with a dose of 36 Gy, in 18 fractions (2 Gy/fraction and 5 days in a week) along with steroids however patient progressed and developed quadriplegia with intradural metastasis.

Sensitivity to neurotoxic stress is not increased in progranulin-deficient mice.

PubMed

Petkau, Terri L; Zhu, Shanshan; Lu, Ge; Fernando, Sarah; Cynader, Max; Leavitt, Blair R

2013-11-01

Loss-of-function mutations in the progranulin (GRN) gene are a common cause of autosomal dominant frontotemporal lobar degeneration, a fatal and progressive neurodegenerative disorder common in people less than 65 years of age. In the brain, progranulin is expressed in multiple regions at varying levels, and has been hypothesized to play a neuroprotective or neurotrophic role. Four neurotoxic agents were injected in vivo into constitutive progranulin knockout (Grn(-/-)) mice and their wild-type (Grn(+/+)) counterparts to assess neuronal sensitivity to toxic stress. Administration of 3-nitropropionic acid, quinolinic acid, kainic acid, and pilocarpine induced robust and measurable neuronal cell death in affected brain regions, but no differential cell death was observed between Grn(+/+) and Grn(-/-) mice. Thus, constitutive progranulin knockout mice do not have increased sensitivity to neuronal cell death induced by the acute chemical models of neuronal injury used in this study. Copyright © 2013. Published by Elsevier Inc.

Neural Stem Cells: Implications for the Conventional Radiotherapy of Central Nervous System Malignancies

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

Barani, Igor J.; Benedict, Stanley H.; Lin, Peck-Sun

Advances in basic neuroscience related to neural stem cells and their malignant counterparts are challenging traditional models of central nervous system tumorigenesis and intrinsic brain repair. Neurogenesis persists into adulthood predominantly in two neurogenic centers: subventricular zone and subgranular zone. Subventricular zone is situated adjacent to lateral ventricles and subgranular zone is confined to the dentate gyrus of the hippocampus. Neural stem cells not only self-renew and differentiate along multiple lineages in these regions, but also contribute to intrinsic brain plasticity and repair. Ionizing radiation can depopulate these exquisitely sensitive regions directly or impair in situ neurogenesis by indirect, dose-dependentmore » and inflammation-mediated mechanisms, even at doses <2 Gy. This review discusses the fundamental neural stem cell concepts within the framework of cumulative clinical experience with the treatment of central nervous system malignancies using conventional radiotherapy.« less

Highly scalable multichannel mesh electronics for stable chronic brain electrophysiology

PubMed Central

Fu, Tian-Ming; Hong, Guosong; Viveros, Robert D.; Zhou, Tao

2017-01-01

Implantable electrical probes have led to advances in neuroscience, brain−machine interfaces, and treatment of neurological diseases, yet they remain limited in several key aspects. Ideally, an electrical probe should be capable of recording from large numbers of neurons across multiple local circuits and, importantly, allow stable tracking of the evolution of these neurons over the entire course of study. Silicon probes based on microfabrication can yield large-scale, high-density recording but face challenges of chronic gliosis and instability due to mechanical and structural mismatch with the brain. Ultraflexible mesh electronics, on the other hand, have demonstrated negligible chronic immune response and stable long-term brain monitoring at single-neuron level, although, to date, it has been limited to 16 channels. Here, we present a scalable scheme for highly multiplexed mesh electronics probes to bridge the gap between scalability and flexibility, where 32 to 128 channels per probe were implemented while the crucial brain-like structure and mechanics were maintained. Combining this mesh design with multisite injection, we demonstrate stable 128-channel local field potential and single-unit recordings from multiple brain regions in awake restrained mice over 4 mo. In addition, the newly integrated mesh is used to validate stable chronic recordings in freely behaving mice. This scalable scheme for mesh electronics together with demonstrated long-term stability represent important progress toward the realization of ideal implantable electrical probes allowing for mapping and tracking single-neuron level circuit changes associated with learning, aging, and neurodegenerative diseases. PMID:29109247

Hybrid ICA-Bayesian network approach reveals distinct effective connectivity differences in schizophrenia.

PubMed

Kim, D; Burge, J; Lane, T; Pearlson, G D; Kiehl, K A; Calhoun, V D

2008-10-01

We utilized a discrete dynamic Bayesian network (dDBN) approach (Burge, J., Lane, T., Link, H., Qiu, S., Clark, V.P., 2007. Discrete dynamic Bayesian network analysis of fMRI data. Hum Brain Mapp.) to determine differences in brain regions between patients with schizophrenia and healthy controls on a measure of effective connectivity, termed the approximate conditional likelihood score (ACL) (Burge, J., Lane, T., 2005. Learning Class-Discriminative Dynamic Bayesian Networks. Proceedings of the International Conference on Machine Learning, Bonn, Germany, pp. 97-104.). The ACL score represents a class-discriminative measure of effective connectivity by measuring the relative likelihood of the correlation between brain regions in one group versus another. The algorithm is capable of finding non-linear relationships between brain regions because it uses discrete rather than continuous values and attempts to model temporal relationships with a first-order Markov and stationary assumption constraint (Papoulis, A., 1991. Probability, random variables, and stochastic processes. McGraw-Hill, New York.). Since Bayesian networks are overly sensitive to noisy data, we introduced an independent component analysis (ICA) filtering approach that attempted to reduce the noise found in fMRI data by unmixing the raw datasets into a set of independent spatial component maps. Components that represented noise were removed and the remaining components reconstructed into the dimensions of the original fMRI datasets. We applied the dDBN algorithm to a group of 35 patients with schizophrenia and 35 matched healthy controls using an ICA filtered and unfiltered approach. We determined that filtering the data significantly improved the magnitude of the ACL score. Patients showed the greatest ACL scores in several regions, most markedly the cerebellar vermis and hemispheres. Our findings suggest that schizophrenia patients exhibit weaker connectivity than healthy controls in multiple regions, including bilateral temporal, frontal, and cerebellar regions during an auditory paradigm.

Regional differences in mitochondrial DNA methylation in human post-mortem brain tissue.

PubMed

Devall, Matthew; Smith, Rebecca G; Jeffries, Aaron; Hannon, Eilis; Davies, Matthew N; Schalkwyk, Leonard; Mill, Jonathan; Weedon, Michael; Lunnon, Katie

2017-01-01

DNA methylation is an important epigenetic mechanism involved in gene regulation, with alterations in DNA methylation in the nuclear genome being linked to numerous complex diseases. Mitochondrial DNA methylation is a phenomenon that is receiving ever-increasing interest, particularly in diseases characterized by mitochondrial dysfunction; however, most studies have been limited to the investigation of specific target regions. Analyses spanning the entire mitochondrial genome have been limited, potentially due to the amount of input DNA required. Further, mitochondrial genetic studies have been previously confounded by nuclear-mitochondrial pseudogenes. Methylated DNA Immunoprecipitation Sequencing is a technique widely used to profile DNA methylation across the nuclear genome; however, reads mapped to mitochondrial DNA are often discarded. Here, we have developed an approach to control for nuclear-mitochondrial pseudogenes within Methylated DNA Immunoprecipitation Sequencing data. We highlight the utility of this approach in identifying differences in mitochondrial DNA methylation across regions of the human brain and pre-mortem blood. We were able to correlate mitochondrial DNA methylation patterns between the cortex, cerebellum and blood. We identified 74 nominally significant differentially methylated regions ( p  < 0.05) in the mitochondrial genome, between anatomically separate cortical regions and the cerebellum in matched samples ( N  = 3 matched donors). Further analysis identified eight significant differentially methylated regions between the total cortex and cerebellum after correcting for multiple testing. Using unsupervised hierarchical clustering analysis of the mitochondrial DNA methylome, we were able to identify tissue-specific patterns of mitochondrial DNA methylation between blood, cerebellum and cortex. Our study represents a comprehensive analysis of the mitochondrial methylome using pre-existing Methylated DNA Immunoprecipitation Sequencing data to identify brain region-specific patterns of mitochondrial DNA methylation.

Grey matter volume loss is associated with specific clinical motor signs in Huntington's disease.

PubMed

Coppen, Emma M; Jacobs, Milou; van den Berg-Huysmans, Annette A; van der Grond, Jeroen; Roos, Raymund A C

2018-01-01

Motor disturbances are clinical hallmarks of Huntington's disease (HD) and involve chorea, dystonia, hypokinesia and visuomotor dysfunction. Investigating the association between specific motor signs and different regional volumes is important to understand the heterogeneity of HD. To investigate the motor phenotype of HD and associations with subcortical and cortical grey matter volume loss. Structural T1-weighted MRI scans of 79 HD patients and 30 healthy controls were used to calculate volumes of seven subcortical structures including the nucleus accumbens, hippocampus, thalamus, caudate nucleus, putamen, pallidum and amygdala. Multiple linear regression analyses, corrected for age, gender, CAG, MRI scan protocol and normalized brain volume, were performed to assess the relationship between subcortical volumes and different motor subdomains (i.e. eye movements, chorea, dystonia, hypokinesia/rigidity and gait/balance). Voxel-based morphometry analysis was used to investigate the relationship between cortical volume changes and motor signs. Subcortical volume loss of the accumbens nucleus, caudate nucleus, putamen, and pallidum were associated with higher chorea scores. No other subcortical region was significantly associated with motor symptoms after correction for multiple comparisons. Voxel-based cortical grey matter volume reductions in occipital regions were related with an increase in eye movement scores. In HD, chorea is mainly associated with subcortical volume loss, while eye movements are more related to cortical volume loss. Both subcortical and cortical degeneration has an impact on motor impairment in HD. This implies that there is a widespread contribution of different brain regions resulting in the clinical motor presentation seen in HD patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Family nurture intervention in preterm infants increases early development of cortical activity and independence of regional power trajectories.

PubMed

Welch, Martha G; Stark, Raymond I; Grieve, Philip G; Ludwig, Robert J; Isler, Joseph R; Barone, Joseph L; Myers, Michael M

2017-12-01

Premature delivery and maternal separation during hospitalisation increase infant neurodevelopmental risk. Previously, a randomised controlled trial of Family Nurture Intervention (FNI) in the neonatal intensive care unit demonstrated improvement across multiple mother and infant domains including increased electroencephalographic (EEG) power in the frontal polar region at term age. New aims were to quantify developmental changes in EEG power in all brain regions and frequencies and correlate developmental changes in EEG power among regions. EEG (128 electrodes) was obtained at 34-44 weeks postmenstrual age from preterm infants born 26-34 weeks. Forty-four infants were treated with Standard Care and 53 with FNI. EEG power was computed in 10 frequency bands (1-48 Hz) in 10 brain regions and in active and quiet sleep. Percent change/week in EEG power was increased in FNI in 132/200 tests (p < 0.05), 117 tests passed a 5% False Discovery Rate threshold. In addition, FNI demonstrated greater regional independence in those developmental rates of change. This study strengthens the conclusion that FNI promotes cerebral cortical development of preterm infants. The findings indicate that developmental changes in EEG may provide biomarkers for risk in preterm infants as well as proximal markers of effects of FNI. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Brain hyper-connectivity and operation-specific deficits during arithmetic problem solving in children with developmental dyscalculia

PubMed Central

Rosenberg-Lee, Miriam; Ashkenazi, Sarit; Chen, Tianwen; Young, Christina B.; Geary, David C.; Menon, Vinod

2014-01-01

Developmental dyscalculia (DD) is marked by specific deficits in processing numerical and mathematical information despite normal intelligence (IQ) and reading ability. We examined how brain circuits used by young children with DD to solve simple addition and subtraction problems differ from those used by typically developing (TD) children who were matched on age, IQ, reading ability, and working memory. Children with DD were slower and less accurate during problem solving than TD children, and were especially impaired on their ability to solve subtraction problems. Children with DD showed significantly greater activity in multiple parietal, occipito-temporal and prefrontal cortex regions while solving addition and subtraction problems. Despite poorer performance during subtraction, children with DD showed greater activity in multiple intra-parietal sulcus (IPS) and superior parietal lobule subdivisions in the dorsal posterior parietal cortex as well as fusiform gyrus in the ventral occipito-temporal cortex. Critically, effective connectivity analyses revealed hyper-connectivity, rather than reduced connectivity, between the IPS and multiple brain systems including the lateral fronto-parietal and default mode networks in children with DD during both addition and subtraction. These findings suggest the IPS and its functional circuits are a major locus of dysfunction during both addition and subtraction problem solving in DD, and that inappropriate task modulation and hyper-connectivity, rather than under-engagement and under-connectivity, are the neural mechanisms underlying problem solving difficulties in children with DD. We discuss our findings in the broader context of multiple levels of analysis and performance issues inherent in neuroimaging studies of typical and atypical development. PMID:25098903