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1

Specific monitoring of neonatal brain function with optimized frequency bands  

Microsoft Academic Search

Early detection of altered brain function can be helpful in preventing the development of serious brain damage. Power spectral analysis of continuous EEG is an established tool in corresponding clinical monitoring. The commonly used EEG power classifiers are based on the power within particular frequency bands. It can be supposed that individually adapted frequency bands allow a more specific monitoring

Dirk Hoyer; Reinhard Bauer; Kirsten Conrad; Mirek Galicki; Axel Döring; Heike Hoyer; Bernd Walter; H. Witie; Ulrich Zwiener

2001-01-01

2

Investigation of acupoint specificity by whole brain functional connectivity analysis from fMRI data  

Microsoft Academic Search

Previous neuroimaging studies on acupuncture have primarily adopted functional connectivity analysis associated with one or a few preselected brain regions. Few have investigated how these brain regions interacted at the whole brain level. In this study, we sought to investigate the acupoint specificity by exploring the whole brain functional connectivity analysis on the post-stimulus resting brain modulated by acupuncture at

Yuanyuan Feng; Lijun Bai; Wensheng Zhang; Yanshuang Ren; Ting Xue; Hu Wang; Chongguang Zhong; Jie Tian

2011-01-01

3

Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood  

PubMed Central

Background Dynamic changes to the epigenome play a critical role in establishing and maintaining cellular phenotype during differentiation, but little is known about the normal methylomic differences that occur between functionally distinct areas of the brain. We characterized intra- and inter-individual methylomic variation across whole blood and multiple regions of the brain from multiple donors. Results Distinct tissue-specific patterns of DNA methylation were identified, with a highly significant over-representation of tissue-specific differentially methylated regions (TS-DMRs) observed at intragenic CpG islands and low CG density promoters. A large proportion of TS-DMRs were located near genes that are differentially expressed across brain regions. TS-DMRs were significantly enriched near genes involved in functional pathways related to neurodevelopment and neuronal differentiation, including BDNF, BMP4, CACNA1A, CACA1AF, EOMES, NGFR, NUMBL, PCDH9, SLIT1, SLITRK1 and SHANK3. Although between-tissue variation in DNA methylation was found to greatly exceed between-individual differences within any one tissue, we found that some inter-individual variation was reflected across brain and blood, indicating that peripheral tissues may have some utility in epidemiological studies of complex neurobiological phenotypes. Conclusions This study reinforces the importance of DNA methylation in regulating cellular phenotype across tissues, and highlights genomic patterns of epigenetic variation across functionally distinct regions of the brain, providing a resource for the epigenetics and neuroscience research communities.

2012-01-01

4

CNS-specific T cells shape brain function via the choroid plexus.  

PubMed

Adaptive immunity was repeatedly shown to play a role in maintaining lifelong brain function. Under physiological conditions, this activity was associated with CD4+ T cells specific for brain self-antigens. Nevertheless, direct interactions of T cells with the healthy neuronal parenchyma are hardly detectable. Recent studies have identified the brain's choroid plexus (CP) as an active neuro-immunological interface, enriched with CNS-specific CD4+ T cells. Strategically positioned for receiving signals from both the central nervous system (CNS) through the cerebrospinal fluid (CSF), and from the circulation through epithelium-immune cell interactions, the CP has recently been recognized as an important immunological compartment in maintaining and restoring brain homeostasis/allostasis. Here, we propose that CNS-specific T cells shape brain function via the CP, and suggest this immunological control to be lost as part of aging, in general, and immune senescence, in particular. Accordingly, the CP may serve as a novel target for immunomodulation to restore brain equilibrium. PMID:23597431

Baruch, Kuti; Schwartz, Michal

2013-11-01

5

Co-Localisation of Abnormal Brain Structure and Function in Specific Language Impairment  

ERIC Educational Resources Information Center

We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior…

Badcock, Nicholas A.; Bishop, Dorothy V. M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

2012-01-01

6

Isolating human brain functional connectivity associated with a specific cognitive process  

NASA Astrophysics Data System (ADS)

The use of functional magnetic resonance imaging (fMRI) to measure functional connectivity among brain areas has the potential to identify neural networks associated with particular cognitive processes. However, fMRI signals are not a direct measure of neural activity but rather represent blood oxygenation level-dependent (BOLD) signals. Correlated BOLD signals between two brain regions are therefore a combination of neural, neurovascular, and vascular coupling. Here, we describe a procedure for isolating brain functional connectivity associated with a specific cognitive process. Coherency magnitude (measuring the strength of coupling between two time series) and phase (measuring the temporal latency differences between two time series) are computed during performance of a particular cognitive task and also for a control condition. Subtraction of the coherency magnitude and phase differences for the two conditions removes sources of correlated BOLD signals that do not modulate as a function of cognitive task, resulting in a more direct measure of functional connectivity associated with changes in neuronal activity. We present two applications of this task subtraction procedure, one to measure changes in strength of coupling associated with sustained visual spatial attention, and one to measure changes in temporal latencies between brain areas associated with voluntary visual spatial attention.

Silver, Michael A.; Landau, Ayelet N.; Lauritzen, Thomas Z.; Prinzmetal, William; Robertson, Lynn C.

2010-02-01

7

Molecular and functional characterization of riboflavin specific transport system in rat brain capillary endothelial cells.  

PubMed

Riboflavin is an important water soluble vitamin (B2) required for metabolic reactions, normal cellular growth, differentiation and function. Mammalian brain cells cannot synthesize riboflavin and must import from systemic circulation. However, the uptake mechanism, cellular translocation and intracellular trafficking of riboflavin in brain capillary endothelial cells are poorly understood. The primary objective of this study is to investigate the existence of a riboflavin-specific transport system and delineate the uptake and intracellular regulation of riboflavin in immortalized rat brain capillary endothelial cells (RBE4). The uptake of [3H]-riboflavin is sodium, temperature and energy dependent but pH independent. [3H]-Riboflavin uptake is saturable with K(m) and V(max) values of 19 ± 3 ?M and 0.235 ± 0.012 pmol/min/mg protein, respectively. The uptake process is inhibited by unlabelled structural analogs (lumiflavin, lumichrome) but not by structurally unrelated vitamins. Ca(++)/calmodulin and protein kinase A (PKA) pathways are found to play an important role in the intracellular regulation of [3H]-riboflavin. Apical and baso-lateral uptake of [3H]-riboflavin clearly indicates that a riboflavin specific transport system is predominantly localized on the apical side of RBE4 cells. A 628 bp band corresponding to a riboflavin transporter is revealed in RT-PCR analysis. These findings, for the first time report the existence of a specialized and high affinity transport system for riboflavin in RBE4 cells. The blood-brain barrier (BBB) is a major obstacle limiting drug transport inside the brain as it regulates drug permeation from systemic circulation. This transporter can be utilized for targeted delivery in enhancing brain permeation of highly potent drugs on systemic administration. PMID:22683359

Patel, Mitesh; Vadlapatla, Ramya Krishna; Pal, Dhananjay; Mitra, Ashim K

2012-08-15

8

Non-verbal emotion communication training induces specific changes in brain function and structure  

PubMed Central

The perception of emotional cues from voice and face is essential for social interaction. However, this process is altered in various psychiatric conditions along with impaired social functioning. Emotion communication trainings have been demonstrated to improve social interaction in healthy individuals and to reduce emotional communication deficits in psychiatric patients. Here, we investigated the impact of a non-verbal emotion communication training (NECT) on cerebral activation and brain structure in a controlled and combined functional magnetic resonance imaging (fMRI) and voxel-based morphometry study. NECT-specific reductions in brain activity occurred in a distributed set of brain regions including face and voice processing regions as well as emotion processing- and motor-related regions presumably reflecting training-induced familiarization with the evaluation of face/voice stimuli. Training-induced changes in non-verbal emotion sensitivity at the behavioral level and the respective cerebral activation patterns were correlated in the face-selective cortical areas in the posterior superior temporal sulcus and fusiform gyrus for valence ratings and in the temporal pole, lateral prefrontal cortex and midbrain/thalamus for the response times. A NECT-induced increase in gray matter (GM) volume was observed in the fusiform face area. Thus, NECT induces both functional and structural plasticity in the face processing system as well as functional plasticity in the emotion perception and evaluation system. We propose that functional alterations are presumably related to changes in sensory tuning in the decoding of emotional expressions. Taken together, these findings highlight that the present experimental design may serve as a valuable tool to investigate the altered behavioral and neuronal processing of emotional cues in psychiatric disorders as well as the impact of therapeutic interventions on brain function and structure.

Kreifelts, Benjamin; Jacob, Heike; Bruck, Carolin; Erb, Michael; Ethofer, Thomas; Wildgruber, Dirk

2013-01-01

9

Co-localisation of abnormal brain structure and function in specific language impairment.  

PubMed

We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. PMID:22137677

Badcock, Nicholas A; Bishop, Dorothy V M; Hardiman, Mervyn J; Barry, Johanna G; Watkins, Kate E

2012-03-01

10

Co-localisation of abnormal brain structure and function in specific language impairment  

PubMed Central

We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing.

Badcock, Nicholas A.; Bishop, Dorothy V.M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

2012-01-01

11

A simple view of the brain through a frequency-specific functional connectivity measure  

Microsoft Academic Search

Here we develop a measure of functional connectivity describing the degree of covariability between a brain region and the rest of the brain. This measure is based on previous formulas for the mutual information (MI) between clusters of regions in the frequency domain. Under the current scenario, the MI can be given as a simple monotonous function of the multiple

R. Salvador; A. Martínez; E. Pomarol-Clotet; J. Gomar; F. Vila; S. Sarró; A. Capdevila; E. Bullmore

2008-01-01

12

Abnormal Functional Lateralization and Activity of Language Brain Areas in Typical Specific Language Impairment (Developmental Dysphasia)  

ERIC Educational Resources Information Center

Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting…

de Guibert, Clement; Maumet, Camille; Jannin, Pierre; Ferre, Jean-Christophe; Treguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

2011-01-01

13

Columnar specificity of microvascular oxygenation and volume responses: implications for functional brain mapping.  

PubMed

Cortical neurons with similar properties are grouped in columnar structures and supplied by matching vascular networks. The hemodynamic response to neuronal activation, however, is not well described on a fine spatial scale. We investigated the spatiotemporal characteristics of microvascular responses to neuronal activation in rat barrel cortex using optical intrinsic signal imaging and spectroscopy. Imaging was performed at 570 nm to provide functional maps of cerebral blood volume (CBV) changes and at 610 nm to estimate oxygenation changes. To emphasize parenchymal rather than large vessel contributions to the functional hemodynamic responses, we developed an ANOVA-based statistical analysis technique. Perfusion-based maps were compared with underlying neuroanatomy with cytochrome oxidase staining. Statistically determined CBV responses localized accurately to individually stimulated barrel columns and could resolve neighboring columns with a resolution better than 400 microm. Both CBV and early oxygenation responses extended beyond anatomical boundaries of single columns, but this vascular point spread did not preclude spatial specificity. These results indicate that microvascular flow control structures providing targeted flow increases to metabolically active neuronal columns also produce finely localized changes in CBV. This spatial specificity, along with the high contrast/noise ratio, makes the CBV response an attractive mapping signal. We also found that functional oxygenation changes can achieve submillimeter specificity not only during the transient deoxygenation ("initial dip") but also during the early part of the hyperoxygenation. We, therefore, suggest that to optimize hemodynamic spatial specificity, appropriate response timing (using < or =2-3 sec changes) is more important than etiology (oxygenation or volume). PMID:14736849

Sheth, Sameer A; Nemoto, Masahito; Guiou, Michael; Walker, Melissa; Pouratian, Nader; Hageman, Nathan; Toga, Arthur W

2004-01-21

14

Assessing brain stem function.  

PubMed

Intraoperative neurophysiologic monitoring provides objective measures of nervous system function that are of value when operating in proximity to the brain stem. Real-time measurements of function can be correlated to operative manipulations in order to reduce the risk of damage in critically important regions. Techniques for evaluating brain stem function clinically and electrophysiologically are presented along with their applications during surgery of the brain stem. PMID:8353442

Sclabassi, R J; Kalia, K K; Sekhar, L; Jannetta, P J

1993-07-01

15

[Dehydroepiandrosterone and brain functioning].  

PubMed

The adrenal glands synthesize dehydroepiandrosterone (DHEA) and its sulphate form (DHEAS) more intensively than they do other steroid hormones. Researchers are interested in these hormones for several reasons. Firstly, for some years they have been trying to find the reason for DHEA and DHEAS to be synthesized and present in the organism in such high concentrations. Secondly, their attention have been attracted by age-dependent regression of DHEA, which is strictly determined. Thirdly, despite longstanding efforts of scientists, the physiological role and spectrum of the biological activity of DHEA is still unclear. Evidence of that DHEA and DHEAS can be synthesized in situ in the brain tissue, received in rat experiments, urged researchers to clarify the role of these neurosteroids in the CNS. The presented review covers ways of neurosteroid synthesis, possible mechanisms of the regulation of these processes, and their dynamics under the condition of stress. The authors analyze experimental and clinical observations undertaken with a goal to clarify a possible role of DHEA in the manifestation of various brain functions. Special attention is payed to ambiguous results of modern studies, dedicated to replacement therapy of various disorders of CNS functioning (Alzheimer's disease, depression, age-specific memory impairment, sleep disturbance etc.) with DHEAS. PMID:16149434

Goncharov, N P; Katsiia, G V; Nizhnik, A N

2005-01-01

16

A method for detecting functional activity related expression in gross brain regions, specific brain nuclei and individual neuronal cell bodies and their projections  

Microsoft Academic Search

We have developed a system to visualize functionally activated neurons and their projections in the brain. This system utilizes\\u000a a transgenic mouse, fos-tau-lacZ (FTL), which expresses the marker gene, lacZ, in neurons and their processes after activation by many different stimuli. This system allows the imaging of activation\\u000a from the level of the entire brain surface, through to individual neurons

Mark Murphy; Ursula Greferath; Yvette M. Wilson

2007-01-01

17

Brain Dynamics Promotes Function  

NASA Astrophysics Data System (ADS)

Dynamical structure in the brain promotes biological function. Natural scientists look for correlations between measured electrical signals and behavior or mental states. Computational scientists have new opportunities to receive ’algorithmic’ inspiration from brain processes and propose computational paradigms. Thus a tradition which dates back to the 1940s with neural nets research is renewed. Real processes in the brain are ’complex’ and withstand trivial descriptions. However, dynamical complexity need not be at odds with a computational description of the phenomena and with the inspiration for algorithms that actually compute something in an engineering sense. We engage this complexity from a computational viewpoint, not excluding dynamical regimes that a number of authors are willing to label as chaos. The key question is: what may we be missing computation-wise if we overlook brain dynamics? At this point in brain research, we are happy if we can at least provide a partial answer.

Lourenço, Carlos

18

Functional Brain Imaging  

PubMed Central

Executive Summary Objective The objective of this analysis is to review a spectrum of functional brain imaging technologies to identify whether there are any imaging modalities that are more effective than others for various brain pathology conditions. This evidence-based analysis reviews magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI) for the diagnosis or surgical management of the following conditions: Alzheimer’s disease (AD), brain tumours, epilepsy, multiple sclerosis (MS), and Parkinson’s disease (PD). Clinical Need: Target Population and Condition Alzheimer’s disease is a progressive, degenerative, neurologic condition characterized by cognitive impairment and memory loss. The Canadian Study on Health and Aging estimated that there will be 97,000 incident cases (about 60,000 women) of dementia (including AD) in Canada in 2006. In Ontario, there will be an estimated 950 new cases and 580 deaths due to brain cancer in 2006. Treatments for brain tumours include surgery and radiation therapy. However, one of the limitations of radiation therapy is that it damages tissue though necrosis and scarring. Computed tomography (CT) and magnetic resonance imaging (MRI) may not distinguish between radiation effects and resistant tissue, creating a potential role for functional brain imaging. Epilepsy is a chronic disorder that provokes repetitive seizures. In Ontario, the rate of epilepsy is estimated to be 5 cases per 1,000 people. Most people with epilepsy are effectively managed with drug therapy; but about 50% do not respond to drug therapy. Surgical resection of the seizure foci may be considered in these patients, and functional brain imaging may play a role in localizing the seizure foci. Multiple sclerosis is a progressive, inflammatory, demyelinating disease of the central nervous system (CNS). The cause of MS is unknown; however, it is thought to be due to a combination of etiologies, including genetic and environmental components. The prevalence of MS in Canada is 240 cases per 100,000 people. Parkinson’s disease is the most prevalent movement disorder; it affects an estimated 100,000 Canadians. Currently, the standard for measuring disease progression is through the use of scales, which are subjective measures of disease progression. Functional brain imaging may provide an objective measure of disease progression, differentiation between parkinsonian syndromes, and response to therapy. The Technology Being Reviewed Functional Brain Imaging Functional brain imaging technologies measure blood flow and metabolism. The results of these tests are often used in conjunction with structural imaging (e.g., MRI or CT). Positron emission tomography and MRS identify abnormalities in brain tissues. The former measures abnormalities through uptake of radiotracers in the brain, while the latter measures chemical shifts in metabolite ratios to identify abnormalities. The potential role of functional MRI (fMRI) is to identify the areas of the brain responsible for language, sensory and motor function (sensorimotor cortex), rather than identifying abnormalities in tissues. Magnetoencephalography measures magnetic fields of the electric currents in the brain, identifying aberrant activity. Magnetoencephalography may have the potential to localize seizure foci and to identify the sensorimotor cortex, visual cortex and auditory cortex. In terms of regulatory status, MEG and PET are licensed by Health Canada. Both MRS and fMRI use a MRI platform; thus, they do not have a separate licence from Health Canada. The radiotracers used in PET scanning are not licensed by Health Canada for general use but can be used through a Clinical Trials Application. Review Strategy The literature published up to September 2006 was searched in the following databases: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, and International Network of Agencies for H

2006-01-01

19

Brain foods: the effects of nutrients on brain function  

Microsoft Academic Search

It has long been suspected that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that are responsible for the action of diet on brain health and mental function. Several gut hormones that can enter the brain, or

Fernando Gómez-Pinilla

2008-01-01

20

Brain-specific small nucleolar RNAs  

Microsoft Academic Search

Small nucleolar RNAs (snoRNAs) are a group of noncoding RNAs that function mainly as guides for modification of ribosomal\\u000a RNAs (rRNAs) and small nuclear RNAs (snRNAs). A subgroup of snoRNAs was found to be predominantly expressed in the brain;\\u000a and interestingly, these brain-specific snoRNAs (b-snoRNAs) appear not to be involved in modification of rRNAs and snRNAs,\\u000a raising the question of

Boris Rogelj

2006-01-01

21

Synergetics of brain function.  

PubMed

Several brain functions such as movement coordination and visual perception are analysed in terms of synergetics, an interdisciplinary field of research dealing with spontaneous pattern formation. Accordingly, the brain is conceived as a self-organizing system operating close to instabilities where its activities are governed by collective variables, the order parameters, that enslave the individual parts, i.e., the neurons. In this approach, emphasis is laid on qualitative changes of behavioral and neuronal activities. These concepts are substantiated by detailed experimental and theoretical studies of the coordination of finger movements by direct observation of their changes and MEG measurements. In its main part, this paper deals with visual pattern recognition. Using general properties of order parameters, at the phenomenological level bistability, hysteresis and oscillations of visual perception can be modelled. Then, at the microscopic level, a network of pulse-coupled neurons is treated, where the dynamics of the dendritic currents as well as the axonic pulses (spikes) are taken into account. Both pulse-synchronization as well as pattern recognition are treated. In the high pulse frequency limit the attractor network of the synergetic computer is recovered. In the next step, the concept of quasi-attractors is mathematically formulated where due to saturation of attention attractors are closed. Depending on incoming signals, the visual system thus wanders from quasi-attractor to quasi-attractor. The paper includes an interpretation of consciousness in terms of order parameters as well as a discussion on linearity versus nonlinearity, the binding problem, and the psychological "present". PMID:16527368

Haken, Hermann

2006-05-01

22

Brain foods: the effects of nutrients on brain function  

PubMed Central

It has long been suspected that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that are responsible for the action of diet on brain health and mental function. Several gut hormones that can enter the brain, or that are produced in the brain itself, influence cognitive ability. In addition, well-established regulators of synaptic plasticity, such as brain-derived neurotrophic factor, can function as metabolic modulators, responding to peripheral signals such as food intake. Understanding the molecular basis of the effects of food on cognition will help us to determine how best to manipulate diet in order to increase the resistance of neurons to insults and promote mental fitness.

Gomez-Pinilla, Fernando

2009-01-01

23

Functional Lateralization of the Brain.  

ERIC Educational Resources Information Center

Research concerning lateralization of human brain functions is examined in light of the recent publication of the Kaufman Assessment Battery for Children. Following a review of research methodologies and functions ascribed to the hemispheres of the brain, differences are portrayed as complementary and coexisting modes of cognitive processing.…

Dean, Raymond S.

1984-01-01

24

Radiotracers for functional brain imaging  

SciTech Connect

The rapid growth of nuclear medicine 25 years ago was in large part related to the success of brain tumor imaging using radiopharmaceuticals designed to detect changes in the blood-brain barrier (BBB). The success of computed tomography, and more recently nuclear magnetic resonance, in imaging these lesions has all but eliminated the use of radioactive agents for brain tumor detection. But, in recent years there has been a new wave of interest in isotope studies of the brain. The recent emphasis has been on agents which enter the brain across the BBB and are designed to provide functional data ranging from regional perfusion and metabolism to the distribution of binding sites for neuroactive compounds. While none of these new radiopharmaceuticals has yet come into widespread clinical application, the research results already achieved clearly indicate that brain imaging will again be an important aspect of nuclear medicine practice. 51 references.

Blau, M.

1985-10-01

25

Brain-derived neurotrophic factor (BDNF) gene: a gender-specific role in cognitive function during normal cognitive aging of the MEMO-Study?  

PubMed

Cognitive aging processes are underpinned by multiple processes including genetic factors. The brain-derived neurotrophic factor (BDNF) has been suggested to be involved in age-related cognitive decline in otherwise healthy individuals. The gender-specific role of the BDNF gene in cognitive aging remains unclear. The identification of genetic biomarkers might be a useful approach to identify individuals at risk of cognitive decline during healthy aging processes. The aim of this study was to investigate the associations between three single-nucleotide polymorphisms (SNPs) in the BDNF gene and domains of cognitive functioning in normal cognitive aging. The sample, comprising 369 participants (M?=?72.7 years, SD?=?4.45 years), completed an extensive neuropsychological test battery measuring memory, motor function, and perceptual speed. The relationships between the SNPs rs6265, rs7103411, and rs7124442 and cognitive domains were examined. While significant main effects of BDNF SNPs on cognitive function were found for the association between rs7103411 and memory performance, gender-specific analyses revealed for females significant main effects of rs7103411 for memory and of rs6265 for perceptual speed independent of the APOE*E4 status and education. The finding for the association between rs6265 and perceptual speed in females remained significant after Bonferroni correction for multiple comparisons. None of the analyses showed significant results for males. This study is the first to implicate that the SNPs rs6265 and rs7103411 affect cognitive function in the elderly in a gender-specific way. PMID:21695421

Laing, Katharine R; Mitchell, David; Wersching, Heike; Czira, Maria E; Berger, Klaus; Baune, Bernhard T

2012-08-01

26

Functional brain mapping of psychopathology  

PubMed Central

In this paper, we consider the impact that the novel functional neuroimaging techniques may have upon psychiatric illness. Functional neuroimaging has rapidly developed as a powerful tool in cognitive neuroscience and, in recent years, has seen widespread application in psychiatry. Although such studies have produced evidence for abnormal patterns of brain response in association with some pathological conditions, the core pathophysiologies remain unresolved. Although imaging techniques provide an unprecedented opportunity for investigation of physiological function of the living human brain, there are fundamental questions and assumptions which remain to be addressed. In this review we examine these conceptual issues under three broad sections: (1) characterising the clinical population of interest, (2) defining appropriate levels of description of normal brain function, and (3) relating these models to pathophysiological conditions. Parallel advances in each of these questions will be required before imaging techniques can impact on clinical decisions in psychiatry.

Honey, G; Fletcher, P; Bullmore, E

2002-01-01

27

Functions of N-Acetyl-l-Aspartate and N-Acetyl-l-Aspartylglutamate in the Vertebrate Brain: Role in Glial Cell-Specific Signaling  

Microsoft Academic Search

N-Acetyl-L-aspartate (NAA) and its derivative N-acetylaspartylglutamate (NAAG) are major osmolytes present in the vertebrate brain. Although they are synthe- sized primarily in neurons, their function in these cells is unclear. In the brain, these substances undergo inter- compartmental cycles in which they are released by neu- rons in a regulated fashion and are then rapidly hydro- lyzed by catabolic enzymes

Morris H. Baslow

2002-01-01

28

Lead poisoning and brain cell function  

SciTech Connect

Exposure to excessive amounts of inorganic lead during the toddler years may produce lasting adverse effects upon brain function. Maximal ingestion of lead occurs at an age when major changes are occurring in the density of brain synaptic connections. The developmental reorganization of synapses is, in part, mediated by protein kinases, and these enzymes are particularly sensitive to stimulation by lead. By inappropriately activating specific protein kinases, lead poisoning may disrupt the development of neural networks without producing overt pathological alterations. The blood-brain barrier is another potential vulnerable site for the neurotoxic action of lead. protein kinases appear to regulate the development of brain capillaries and the expression of the blood-brain barrier properties. Stimulation of protein kinase by lead may disrupt barrier development and alter the precise regulation of the neuronal environment that is required for normal brain function. Together, these findings suggest that the sensitivity of protein kinases to lead may in part underlie the brain dysfunction observed in children poisoned by this toxicant.

Goldstein, G.W. (Johns Hopkins School of Medicine, Baltimore, MD (USA) Kennedy Institute, Baltimore, MD (USA))

1990-11-01

29

Development of the Brain’s Functional Network Architecture  

Microsoft Academic Search

A full understanding of the development of the brain’s functional network architecture requires not only an understanding\\u000a of developmental changes in neural processing in individual brain regions but also an understanding of changes in inter-regional\\u000a interactions. Resting state functional connectivity MRI (rs-fcMRI) is increasingly being used to study functional interactions\\u000a between brain regions in both adults and children. We briefly

Alecia C. Vogel; Jonathan D. Power; Steven E. Petersen; Bradley L. Schlaggar

2010-01-01

30

Brain organization and sleep function  

Microsoft Academic Search

A view of brain organization and sleep function is presented. Sleep is hypothesized to begin at the neuronal group level. Sleep results in the use and thus maintenance, of synapses that are insufficiently stimulated during wakefulness thereby serving to preserve a constancy of a synaptic superstructure. It is further hypothesized that sleep at the neuronal group level is regulated by

James M. Krueger; Ferenc Obál; Levente Kapás; Jidong Fang

1995-01-01

31

Selenium and selenoprotein function in brain disorders.  

PubMed

Selenoproteins are important for normal brain function, and decreased function of selenoproteins can lead to impaired cognitive function and neurological disorders. This review examines the possible roles of selenoproteins in Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and epilepsy. Selenium deficiency is associated with cognitive decline, and selenoproteins may be helpful in preventing neurodegeneration in AD. PD is associated with impaired function of glutathione peroxidase selenoenzymes. In HD, selenium deters lipid peroxidation by increasing specific glutathione peroxidases. Selenium deficiency increases risk of seizures in epilepsy, whereas supplementation may help to alleviate seizures. Further studies on the mechanisms of selenoprotein function will increase our understanding of how selenium and selenoproteins can be used in treatment and prevention of brain disorders. PMID:24668686

Pillai, Roshan; Uyehara-Lock, Jane H; Bellinger, Frederick P

2014-04-01

32

Functional Dissociation of Ongoing Oscillatory Brain States  

PubMed Central

The state of a neural assembly preceding an incoming stimulus is assumed to modulate the processing of subsequently presented stimuli. The nature of this state can differ with respect to the frequency of ongoing oscillatory activity. Oscillatory brain activity of specific frequency range such as alpha (8–12 Hz) and gamma (above 30 Hz) band oscillations are hypothesized to play a functional role in cognitive processing. Therefore, a selective modulation of this prestimulus activity could clarify the functional role of these prestimulus fluctuations. For this purpose, we adopted a novel non-invasive brain-computer-interface (BCI) strategy to selectively increase alpha or gamma band activity in the occipital cortex combined with an adaptive presentation of visual stimuli within specific brain states. During training, oscillatory brain activity was estimated online and fed back to the participants to enable a deliberate modulation of alpha or gamma band oscillations. Results revealed that volunteers selectively increased alpha and gamma frequency oscillations with a high level of specificity regarding frequency range and localization. At testing, alpha or gamma band activity was classified online and at defined levels of activity, visual objects embedded in noise were presented instantly and had to be detected by the volunteer. In experiment I, the effect of two levels of prestimulus gamma band activity on visual processing was examined. During phases of increased gamma band activity significantly more visual objects were detected. In experiment II, the effect was compared against increased levels of alpha band activity. An improvement of visual processing was only observed for enhanced gamma band activity. Both experiments demonstrate the specific functional role of prestimulus gamma band oscillations for perceptual processing. We propose that the BCI method permits the selective modulation of oscillatory activity and the direct assessment of behavioral consequences to test for functional dissociations of different oscillatory brain states.

Salari, Neda; Buchel, Christian; Rose, Michael

2012-01-01

33

[Localization of language function in the brain].  

PubMed

Since the first report of an aphasic patient by Paul Broca, the localization of brain function has been disputed for 150 years. In lesion studies, double dissociation has been a key concept to show the localization of particular cognitive functions. The advancement of non-invasive brain imaging methods enables us to investigate the brain activities under well-controlled conditions, further promoting the studies on the localization of the cognitive functions, including language function. Brain imaging studies, together with subtraction and correlation analyses, have accumulated evidence that syntax, phonology, and sentence comprehension are separately processed by modules in different cortical regions. More specifically, it has been clarified that the module for syntax localizes in the left lateral premotor cortex and the opercular/triangular parts of the left inferior frontal gyrus. This modular structure further suggests that aphasia is interpreted as deficits in either syntactic or phonological processing. Therefore, the classical model of contrasting speech production and comprehension should be updated. According to theoretical linguistics, on the other hand, the recursive computation of syntactic structures is an essential feature of human language faculty. One direction of research would be to contrast human beings and animals for the abilities of processing symbolic sequences. Another direction is to clarify that the human brain is indeed specialized in language processing, which can be revealed by well-controlled language tasks and functional imaging techniques. Here we will review recent studies that demonstrate the existence of grammar center in the left frontal cortex. The future studies in the neuroscience of language will eventually elucidate the cortical localization of language function in a more precise way, i.e., what is really computed in the human brain. PMID:22147453

Miyashita, Hiroyuki; Sakai, Kuniyoshi L

2011-12-01

34

Specific binding of atrial natriuretic factor in brain microvessels  

SciTech Connect

Cerebral capillaries constitute the blood-brain barrier. Studies of specific receptors (neurotransmitters or hormones) located on this structure can be performed by means of radioligand-binding techniques on isolated brain microvessels. The authors examined on pure bovine cerebral microvessel preparations the binding of atrial natriuretic factor (ANF), using /sup 125/I-labeled ANF. Saturation and competition experiments demonstrated the presence of a single class of ANF-binding sites with high affinity and with a binding capacity of 58 fmol/mg of protein. The binding of /sup 125/I-labeled ANF to brain microvessels is specific, reversible, and time dependent, as is shown by association-dissociation experiments. The demonstration of specific ANF-binding sites on brain microvessels supposes a physiological role of ANF on brain microvasculature. The coexistence of ANF and angiotensin II receptors on this cerebrovascular tissue suggests that the two circulating peptides may act as mutual antagonists in the regulation of brain microcirculation and/or blood-brain barrier function.

Chabrier, P.E.; Roubert, P.; Braquet, P.

1987-04-01

35

Functional modules of the brain.  

PubMed

Building on the view of massive modularity, a number of generalized assumptions lead to an entirely new concept of functional brain modules. In contrast to the nerve centers usually considered to be active in the brain, these modules, called symbions, are non-localized, non-hierarchical, and based on subcellular molecular mechanisms rather than on neurons. They act according to local rules that may be fundamentally nonlinear, potentially leading to strong interdependencies between parallel inputs, and they interact by information, not by force. The existence of inner states, feedback loops, internal models, and information encoding provide the basis for a higher complexity than is usually assumed in neuroscience. A map of the symbion world, showing functional rather than physical localization, can be used to illustrate symbion interaction patterns. Perceptual constancy, sensory illusions, visual cognition, and eye-hand coordination are used as examples of what can be explained by using the new theory. PMID:12051988

Philipson, Lars

2002-03-01

36

Brain-derived neurotrophic factor ( BDNF) gene: a gender-specific role in cognitive function during normal cognitive aging of the MEMO-Study?  

Microsoft Academic Search

Cognitive aging processes are underpinned by multiple processes including genetic factors. The brain-derived neurotrophic\\u000a factor (BDNF) has been suggested to be involved in age-related cognitive decline in otherwise healthy individuals. The gender-specific\\u000a role of the BDNF gene in cognitive aging remains unclear. The identification of genetic biomarkers might be a useful approach to identify\\u000a individuals at risk of cognitive decline

Katharine R. Laing; David Mitchell; Heike Wersching; Maria E. Czira; Klaus Berger; Bernhard T. Baune

37

Effects of cognitive-behavioral therapy on brain activation in specific phobia  

Microsoft Academic Search

Little is known about the effects of successful psychotherapy on brain function in subjects with anxiety disorders. The present study aimed to identify changes in brain activation following cognitive-behavioral therapy (CBT) in subjects suffering from specific phobia. Using functional magnetic resonance imaging (fMRI), brain activation to spider videos was measured in 28 spider phobic and 14 healthy control subjects. Phobics

Thomas Straube; Madlen Glauer; Stefan Dilger; Hans-Joachim Mentzel; Wolfgang H. R. Miltner

2006-01-01

38

Sex Hormones, Brain Development and Brain Function.  

National Technical Information Service (NTIS)

The view that gonadal hormones exert a double action on the central nervous system--inductive during development and excitatory in the adult--allows a direct comparison between the brain and genital tract as target organs for these hormones. In both cases...

G. W. Harris

1964-01-01

39

Non-invasive brain-to-brain interface (BBI): establishing functional links between two brains.  

PubMed

Transcranial focused ultrasound (FUS) is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI). In conjunction with the use of brain-to-computer interface (BCI) techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functional link between the brains of different species (i.e. human and Sprague-Dawley rat), thus creating a brain-to-brain interface (BBI). The implementation was aimed to non-invasively translate the human volunteer's intention to stimulate a rat's brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP) with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer's intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration) to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0±3.0% accuracy, with a time delay of 1.59±1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications. PMID:23573251

Yoo, Seung-Schik; Kim, Hyungmin; Filandrianos, Emmanuel; Taghados, Seyed Javid; Park, Shinsuk

2013-01-01

40

Non-Invasive Brain-to-Brain Interface (BBI): Establishing Functional Links between Two Brains  

PubMed Central

Transcranial focused ultrasound (FUS) is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI). In conjunction with the use of brain-to-computer interface (BCI) techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functional link between the brains of different species (i.e. human and Sprague-Dawley rat), thus creating a brain-to-brain interface (BBI). The implementation was aimed to non-invasively translate the human volunteer’s intention to stimulate a rat’s brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP) with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer’s intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration) to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0±3.0% accuracy, with a time delay of 1.59±1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications.

Yoo, Seung-Schik; Kim, Hyungmin; Filandrianos, Emmanuel; Taghados, Seyed Javid; Park, Shinsuk

2013-01-01

41

Brain Structure-function Couplings (FY11).  

National Technical Information Service (NTIS)

In FY11, a collaborative team of researchers began a new Director's Strategic Initiative (DSI) to examine brain structure-function couplings. The effort aims to develop a multidisciplinary, multiscale understanding of the relationship between the brain's ...

A. Dagro J. Vettel R. Kraft S. Gordon S. Kerick

2012-01-01

42

Cortical region-specific engraftment of embryonic stem cell-derived neural progenitor cells restores axonal sprouting to a subcortical target and achieves motor functional recovery in a mouse model of neonatal hypoxic-ischemic brain injury  

PubMed Central

Hypoxic-ischemic encephalopathy (HIE) at birth could cause cerebral palsy (CP), mental retardation, and epilepsy, which last throughout the individual's lifetime. However, few restorative treatments for ischemic tissue are currently available. Cell replacement therapy offers the potential to rescue brain damage caused by HI and to restore motor function. In the present study, we evaluated the ability of embryonic stem cell-derived neural progenitor cells (ES-NPCs) to become cortical deep layer neurons, to restore the neural network, and to repair brain damage in an HIE mouse model. ES cells stably expressing the reporter gene GFP are induced to a neural precursor state by stromal cell co-culture. Forty-hours after the induction of HIE, animals were grafted with ES-NPCs targeting the deep layer of the motor cortex in the ischemic brain. Motor function was evaluated 3 weeks after transplantation. Immunohistochemistry and neuroanatomical tracing with GFP were used to analyze neuronal differentiation and axonal sprouting. ES-NPCs could differentiate to cortical neurons with pyramidal morphology and expressed the deep layer-specific marker, Ctip2. The graft showed good survival and an appropriate innervation pattern via axonal sprouting from engrafted cells in the ischemic brain. The motor functions of the transplanted HIE mice also improved significantly compared to the sham-transplanted group. These findings suggest that cortical region specific engraftment of preconditioned cortical precursor cells could support motor functional recovery in the HIE model. It is not clear whether this is a direct effect of the engrafted cells or due to neurotrophic factors produced by these cells. These results suggest that cortical region-specific NPC engraftment is a promising therapeutic approach for brain repair.

Shinoyama, Mizuya; Ideguchi, Makoto; Kida, Hiroyuki; Kajiwara, Koji; Kagawa, Yoshiteru; Maeda, Yoshihiko; Nomura, Sadahiro; Suzuki, Michiyasu

2013-01-01

43

Aging and functional brain networks  

SciTech Connect

Aging is associated with changes in human brain anatomy and function and cognitive decline. Recent studies suggest the aging decline of major functional connectivity hubs in the 'default-mode' network (DMN). Aging effects on other networks, however, are largely unknown. We hypothesized that aging would be associated with a decline of short- and long-range functional connectivity density (FCD) hubs in the DMN. To test this hypothesis, we evaluated resting-state data sets corresponding to 913 healthy subjects from a public magnetic resonance imaging database using functional connectivity density mapping (FCDM), a voxelwise and data-driven approach, together with parallel computing. Aging was associated with pronounced long-range FCD decreases in DMN and dorsal attention network (DAN) and with increases in somatosensory and subcortical networks. Aging effects in these networks were stronger for long-range than for short-range FCD and were also detected at the level of the main functional hubs. Females had higher short- and long-range FCD in DMN and lower FCD in the somatosensory network than males, but the gender by age interaction effects were not significant for any of the networks or hubs. These findings suggest that long-range connections may be more vulnerable to aging effects than short-range connections and that, in addition to the DMN, the DAN is also sensitive to aging effects, which could underlie the deterioration of attention processes that occurs with aging.

Tomasi D.; Tomasi, D.; Volkow, N.D.

2011-07-11

44

Functional Connectivity MR Imaging Reveals Cortical Functional Connectivity in the Developing Brain  

Microsoft Academic Search

BACKGROUND AND PURPOSE: Unlike conventional functional MR imaging where external sensory\\/ cognitive paradigms are needed to specifically activate different regions of the brain, resting functional connectivity MR imaging acquires images in the absence of cognitive demands (a resting condition) and detects brain regions, which are highly temporally correlated. Therefore, resting functional MR imaging is highly suited for the study of

W. Lin; Q. Zhu; W. Gao; Y. Chen; C.-H. Toh; M. Styner; G. Gerig; J. K. Smith; B. Biswal; J. H. Gilmore

2008-01-01

45

Chemogenetic tools to interrogate brain functions.  

PubMed

Elucidating the roles of neuronal cell types for physiology and behavior is essential for understanding brain functions. Perturbation of neuron electrical activity can be used to probe the causal relationship between neuronal cell types and behavior. New genetically encoded neuron perturbation tools have been developed for remotely controlling neuron function using small molecules that activate engineered receptors that can be targeted to cell types using genetic methods. Here we describe recent progress for approaches using genetically engineered receptors that selectively interact with small molecules. Called "chemogenetics," receptors with diverse cellular functions have been developed that facilitate the selective pharmacological control over a diverse range of cell-signaling processes, including electrical activity, for molecularly defined cell types. These tools have revealed remarkably specific behavioral physiological influences for molecularly defined cell types that are often intermingled with populations having different or even opposite functions. PMID:25002280

Sternson, Scott M; Roth, Bryan L

2014-07-01

46

Promoting Motor Function by Exercising the Brain  

PubMed Central

Exercise represents a behavioral intervention that enhances brain health and motor function. The increase in cerebral blood volume in response to physical activity may be responsible for improving brain function. Among the various neuroimaging techniques used to monitor brain hemodynamic response during exercise, functional near-infrared spectroscopy could facilitate the measurement of task-related cortical responses noninvasively and is relatively robust with regard to the subjects’ motion. Although the components of optimal exercise interventions have not been determined, evidence from animal and human studies suggests that aerobic exercise with sufficiently high intensity has neuroprotective properties and promotes motor function. This review provides an insight into the effect of physical activity (based on endurance and resistance exercises) on brain function for producing movement. Since most progress in the study of brain function has come from patients with neurological disorders (e.g., stroke and Parkinson’s patients), this review presents some findings emphasizing training paradigms for restoring motor function.

Perrey, Stephane

2013-01-01

47

Insulin action in brain regulates systemic metabolism and brain function.  

PubMed

Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases. PMID:24931034

Kleinridders, André; Ferris, Heather A; Cai, Weikang; Kahn, C Ronald

2014-07-01

48

Functional Data Analysis in Brain Imaging Studies  

PubMed Central

Functional data analysis (FDA) considers the continuity of the curves or functions, and is a topic of increasing interest in the statistics community. FDA is commonly applied to time-series and spatial-series studies. The development of functional brain imaging techniques in recent years made it possible to study the relationship between brain and mind over time. Consequently, an enormous amount of functional data is collected and needs to be analyzed. Functional techniques designed for these data are in strong demand. This paper discusses three statistically challenging problems utilizing FDA techniques in functional brain imaging analysis. These problems are dimension reduction (or feature extraction), spatial classification in functional magnetic resonance imaging studies, and the inverse problem in magneto-encephalography studies. The application of FDA to these issues is relatively new but has been shown to be considerably effective. Future efforts can further explore the potential of FDA in functional brain imaging studies.

Tian, Tian Siva

2010-01-01

49

The development of Human Functional Brain Networks  

PubMed Central

Recent advances in MRI technology have enabled precise measurements of correlated activity throughout the brain, leading to the first comprehensive descriptions of functional brain networks in humans. This article reviews the growing literature on the development of functional networks, from infancy through adolescence, as measured by resting state functional connectivity MRI. We note several limitations of traditional approaches to describing brain networks, and describe a powerful framework for analyzing networks, called graph theory. We argue that characterization of the development of brain systems (e.g. the default mode network) should be comprehensive, considering not only relationships within a given system, but also how these relationships are situated within wider network contexts. We note that, despite substantial reorganization of functional connectivity, several large-scale network properties appear to be preserved across development, suggesting that functional brain networks, even in children, are organized in manners similar to other complex systems.

Power, Jonathan D; Fair, Damien A; Schlaggar, Bradley L

2010-01-01

50

Relationship Between Neurocognitive Function and Quality of Life After Whole-Brain Radiotherapy in Patients With Brain Metastasis  

Microsoft Academic Search

Purpose: To examine the relationship between neurocognitive function (NCF) and quality of life (QOL) in patients with brain metastases after whole-brain radiotherapy. Patients and Methods: A total of 208 patients from the whole-brain radiotherapy arm of a Phase III trial (PCI-P120-9801), who underwent regular NCF and QOL (ADL [activities of daily living] and FACT-Br [Functional Assessment of Cancer Therapy-Brain-specific]) testing,

Jing Li; Soren M. Bentzen; Jialiang Li; Markus Renschler; Minesh P. Mehta

2008-01-01

51

The Efficiency of a Small-World Functional Brain Network  

NASA Astrophysics Data System (ADS)

We investigate whether the small-world topology of a functional brain network means high information processing efficiency by calculating the correlation between the small-world measures of a functional brain network and behavioral reaction during an imagery task. Functional brain networks are constructed by multichannel event-related potential data, in which the electrodes are the nodes and the functional connectivities between them are the edges. The results show that the correlation between small-world measures and reaction time is task-specific, such that in global imagery, there is a positive correlation between the clustering coefficient and reaction time, while in local imagery the average path length is positively correlated with the reaction time. This suggests that the efficiency of a functional brain network is task-dependent.

Zhao, Qing-Bai; Zhang, Xiao-Fei; Sui, Dan-Ni; Zhou, Zhi-Jin; Chen, Qi-Cai; Tang, Yi-Yuan

2012-04-01

52

The gravitational field and brain function  

NASA Astrophysics Data System (ADS)

The frontal cortex is recognized as the highest adaptive control center of the human brain. The principle of the ``frontalization'' of human brain function offers new possibilities for brain research in space. There is evolutionary and experimental evidence indicating the validity of the principle, including it's role in nervous response to gravitational stimulation. The gravitational field is considered here as one of the more constant and comprehensive factors acting on brain evolution, which has undergone some successive crucial steps: ``encephalization'', ``corticalization'', ``lateralization'' and ``frontalization''. The dominating effects of electrical responses from the frontal cortex have been discovered 1) in experiments under gravitational stimulus; and 2) in processes potentially relating to gravitational adaptation, such as memory and learning, sensory information processing, motor programing, and brain state control. A brain research experiment during space flight is suggested to test the role of the frontal cortex in space adaptation and it's potentiality in brain control.

Mei, Lei; Zhou, Chuan-Dai; Lan, Jing-Quan; Wang, Zhi-Ging; Wu, Wen-Can; Xue, Xin-Min

53

Vertebrate-specific glutaredoxin is essential for brain development  

PubMed Central

Cellular functions and survival are dependent on a tightly controlled redox potential. Currently, an increasing amount of data supports the concept of local changes in the redox environment and specific redox signaling events controlling cell function. Specific protein thiol groups are the major targets of redox signaling and regulation. Thioredoxins and glutaredoxins catalyze reversible thiol-disulfide exchange reactions and are primary regulators of the protein thiol redox state. Here, we demonstrate that embryonic brain development depends on the enzymatic activity of glutaredoxin 2. Zebrafish with silenced expression of glutaredoxin 2 lost virtually all types of neurons by apoptotic cell death and the ability to develop an axonal scaffold. As demonstrated in zebrafish and in a human cellular model for neuronal differentiation, glutaredoxin 2 controls axonal outgrowth via thiol redox regulation of collapsin response mediator protein 2, a central component of the semaphorin pathway. This study provides an example of a specific thiol redox regulation essential for vertebrate embryonic development.

Brautigam, Lars; Schutte, Lena Dorothee; Godoy, Jose Rodrigo; Prozorovski, Timour; Gellert, Manuela; Hauptmann, Giselbert; Holmgren, Arne; Lillig, Christopher Horst; Berndt, Carsten

2011-01-01

54

Specific expression of long noncoding RNAs in the mouse brain  

PubMed Central

A major proportion of the mammalian transcriptome comprises long RNAs that have little or no protein-coding capacity (ncRNAs). Only a handful of such transcripts have been examined in detail, and it is unknown whether this class of transcript is generally functional or merely artifact. Using in situ hybridization data from the Allen Brain Atlas, we identified 849 ncRNAs (of 1,328 examined) that are expressed in the adult mouse brain and found that the majority were associated with specific neuroanatomical regions, cell types, or subcellular compartments. Examination of their genomic context revealed that the ncRNAs were expressed from diverse places including intergenic, intronic, and imprinted loci and that many overlap with, or are transcribed antisense to, protein-coding genes of neurological importance. Comparisons between the expression profiles of ncRNAs and their associated protein-coding genes revealed complex relationships that, in combination with the specific expression profiles exhibited at both regional and subcellular levels, are inconsistent with the notion that they are transcriptional noise or artifacts of chromatin remodeling. Our results show that the majority of ncRNAs are expressed in the brain and provide strong evidence that the majority of processed transcripts with no protein-coding capacity function intrinsically as RNAs.

Mercer, Tim R.; Dinger, Marcel E.; Sunkin, Susan M.; Mehler, Mark F.; Mattick, John S.

2008-01-01

55

Focused ultrasound modulates region-specific brain activity  

PubMed Central

We demonstrated the in vivo feasibility of using focused ultrasound (FUS) to transiently modulate (through either stimulation or suppression) the function of regional brain tissue in rabbits. FUS was delivered in a train of pulses at low acoustic energy, far below the cavitation threshold, to the animal's somatomotor and visual areas, as guided by anatomical and functional information from magnetic resonance imaging (MRI). The temporary alterations in the brain function affected by the sonication were characterized by both electrophysiological recordings and functional brain mapping achieved through the use of functional MRI (fMRI). The modulatory effects were bimodal, whereby the brain activity could either be stimulated or selectively suppressed. Histological analysis of the excised brain tissue after the sonication demonstrated that the FUS did not elicit any tissue damages. Unlike transcranial magnetic stimulation, FUS can be applied to deep structures in the brain with greater spatial precision. Transient modulation of brain function using image-guided and anatomically-targeted FUS would enable the investigation of functional connectivity between brain regions and will eventually lead to a better understanding of localized brain functions. It is anticipated that the use of this technology will have an impact on brain research and may offer novel therapeutic interventions in various neurological conditions and psychiatric disorders.

Yoo, Seung-Schik; Bystritsky, Alexander; Lee, Jong-Hwan; Zhang, Yongzhi; Fischer, Krisztina; Min, Byoung-Kyong; McDannold, Nathan J.; Pascual-Leone, Alvaro; Jolesz, Ferenc A.

2012-01-01

56

Focused ultrasound modulates region-specific brain activity.  

PubMed

We demonstrated the in vivo feasibility of using focused ultrasound (FUS) to transiently modulate (through either stimulation or suppression) the function of regional brain tissue in rabbits. FUS was delivered in a train of pulses at low acoustic energy, far below the cavitation threshold, to the animal's somatomotor and visual areas, as guided by anatomical and functional information from magnetic resonance imaging (MRI). The temporary alterations in the brain function affected by the sonication were characterized by both electrophysiological recordings and functional brain mapping achieved through the use of functional MRI (fMRI). The modulatory effects were bimodal, whereby the brain activity could either be stimulated or selectively suppressed. Histological analysis of the excised brain tissue after the sonication demonstrated that the FUS did not elicit any tissue damages. Unlike transcranial magnetic stimulation, FUS can be applied to deep structures in the brain with greater spatial precision. Transient modulation of brain function using image-guided and anatomically-targeted FUS would enable the investigation of functional connectivity between brain regions and will eventually lead to a better understanding of localized brain functions. It is anticipated that the use of this technology will have an impact on brain research and may offer novel therapeutic interventions in various neurological conditions and psychiatric disorders. PMID:21354315

Yoo, Seung-Schik; Bystritsky, Alexander; Lee, Jong-Hwan; Zhang, Yongzhi; Fischer, Krisztina; Min, Byoung-Kyong; McDannold, Nathan J; Pascual-Leone, Alvaro; Jolesz, Ferenc A

2011-06-01

57

Localizing Visual Function in the Brain.  

National Technical Information Service (NTIS)

A three day meeting, held in Rochester, discussed 'Localizing Visual Function in the Brain'. The meeting consisted of presentations by 15 prominent scientists of topics including; the anatomy of modular connections in the primate visual system, computatio...

W. H. Merigan

1992-01-01

58

Forthergillian Lecture. Imaging human brain function.  

PubMed

The non-invasive brain scanning techniques introduced a quarter of a century ago have become crucial for diagnosis in clinical neurology. They have also been used to investigate brain function and have provided information about normal activity and pathogenesis. They have been used to investigate functional specialization in the brain and how specialized areas communicate to generate complex integrated functions such as speech, memory, the emotions and so on. The phenomenon of brain plasticity is poorly understood and yet clinical neurologists are aware, from everyday observations, that spontaneous recovery from brain lesions is common. An improved understanding of the mechanisms of recovery may generate new therapeutic strategies and indicate ways of modulating mechanisms that promote plastic compensation for loss of function. The main methods used to investigate these issues are positron emission tomography and magnetic resonance imaging (M.R.I.). M.R.I. is also used to map brain structure. The techniques of functional brain mapping and computational morphometrics depend on high performance scanners and a validated set of analytic statistical procedures that generate reproducible data and meaningful inferences from brain scanning data. The motor system presents a good paradigm to illustrate advances made by scanning towards an understanding of plasticity at the level of brain areas. The normal motor system is organized in a nested hierarchy. Recovery from paralysis caused by internal capsule strokes involves functional reorganization manifesting itself as changed patterns of activity in the component brain areas of the normal motor system. The pattern of plastic modification depends in part on patterns of residual or disturbed connectivity after brain injury. Therapeutic manipulations in patients with Parkinson's disease using deep brain stimulation, dopaminergic agents or fetal mesencephalic transplantation provide a means to examine mechanisms underpinning plastic change. Other models of plastic change, such as normal visuospatial learning or re-establishing speech comprehension after cochlear implantation in the deaf illustrate how patterns of brain function adapt over time. Limitations of the scanning techniques and prospects for the future are discussed in relation to new developments in the neuroimaging field. PMID:14509213

Frackowiak, R S

59

Early Brain Stimulation May Help Stroke Survivors Recover Language Function  

MedlinePLUS

Early brain stimulation may help stroke survivors recover language function June 27, 2013 Study Highlights: Non-invasive brain stimulation ... Brain Stimulation copyright American Heart Association Infographic - Thiel-Brain Stimulation copyright American Heart Association Download (311.8 ...

60

Exercise Benefits Brain Function: The Monoamine Connection  

PubMed Central

The beneficial effects of exercise on brain function have been demonstrated in animal models and in a growing number of clinical studies on humans. There are multiple mechanisms that account for the brain-enhancing effects of exercise, including neuroinflammation, vascularization, antioxidation, energy adaptation, and regulations on neurotrophic factors and neurotransmitters. Dopamine (DA), noradrenaline (NE), and serotonin (5-HT) are the three major monoamine neurotransmitters that are known to be modulated by exercise. This review focuses on how these three neurotransmitters contribute to exercise affecting brain function and how it can work against neurological disorders.

Lin, Tzu-Wei; Kuo, Yu-Min

2013-01-01

61

Determination of Vascular Dementia Brain in Distinct Frequency Bands with Whole Brain Functional Connectivity Patterns  

PubMed Central

Recent studies have shown that multivariate pattern analysis (MVPA) can be useful for distinguishing brain disorders into categories. Such analyses can substantially enrich and facilitate clinical diagnoses. Using MPVA methods, whole brain functional networks, especially those derived using different frequency windows, can be applied to detect brain states. We constructed whole brain functional networks for groups of vascular dementia (VaD) patients and controls using resting state BOLD-fMRI (rsfMRI) data from three frequency bands - slow-5 (0.01?0.027 Hz), slow-4 (0.027?0.073 Hz), and whole-band (0.01?0.073 Hz). Then we used the support vector machine (SVM), a type of MVPA classifier, to determine the patterns of functional connectivity. Our results showed that the brain functional networks derived from rsfMRI data (19 VaD patients and 20 controls) in these three frequency bands appear to reflect neurobiological changes in VaD patients. Such differences could be used to differentiate the brain states of VaD patients from those of healthy individuals. We also found that the functional connectivity patterns of the human brain in the three frequency bands differed, as did their ability to differentiate brain states. Specifically, the ability of the functional connectivity pattern to differentiate VaD brains from healthy ones was more efficient in the slow-5 (0.01?0.027 Hz) band than in the other two frequency bands. Our findings suggest that the MVPA approach could be used to detect abnormalities in the functional connectivity of VaD patients in distinct frequency bands. Identifying such abnormalities may contribute to our understanding of the pathogenesis of VaD.

Zhang, Delong; Liu, Bo; Chen, Jun; Peng, Xiaoling; Liu, Xian; Fan, Yuanyuan; Liu, Ming; Huang, Ruiwang

2013-01-01

62

Network Analysis of Intrinsic Functional Brain Connectivity in Alzheimer's Disease  

PubMed Central

Functional brain networks detected in task-free (“resting-state”) functional magnetic resonance imaging (fMRI) have a small-world architecture that reflects a robust functional organization of the brain. Here, we examined whether this functional organization is disrupted in Alzheimer's disease (AD). Task-free fMRI data from 21 AD subjects and 18 age-matched controls were obtained. Wavelet analysis was applied to the fMRI data to compute frequency-dependent correlation matrices. Correlation matrices were thresholded to create 90-node undirected-graphs of functional brain networks. Small-world metrics (characteristic path length and clustering coefficient) were computed using graph analytical methods. In the low frequency interval 0.01 to 0.05 Hz, functional brain networks in controls showed small-world organization of brain activity, characterized by a high clustering coefficient and a low characteristic path length. In contrast, functional brain networks in AD showed loss of small-world properties, characterized by a significantly lower clustering coefficient (p<0.01), indicative of disrupted local connectivity. Clustering coefficients for the left and right hippocampus were significantly lower (p<0.01) in the AD group compared to the control group. Furthermore, the clustering coefficient distinguished AD participants from the controls with a sensitivity of 72% and specificity of 78%. Our study provides new evidence that there is disrupted organization of functional brain networks in AD. Small-world metrics can characterize the functional organization of the brain in AD, and our findings further suggest that these network measures may be useful as an imaging-based biomarker to distinguish AD from healthy aging.

Supekar, Kaustubh; Menon, Vinod; Rubin, Daniel; Musen, Mark; Greicius, Michael D.

2008-01-01

63

Scale-free brain functional networks  

Microsoft Academic Search

Functional magnetic resonance imaging is used to extract functional networks connecting correlated human brain sites. Analysis of the resulting networks in different tasks shows that (a) the distribution of functional connections, and the probability of finding a link versus distance are both scale-free, (b) the characteristic path length is small and comparable with those of equivalent random networks, and (c)

Neural Darwinism. Basic Books; G. A. Cecchi; M. Baliki; A. V. Apkarian

1987-01-01

64

Isoform-Specific Effects of Human Apolipoprotein E on Brain Function Revealed in ApoE Knockout Mice: Increased Susceptibility of Females  

Microsoft Academic Search

Apolipoprotein E (apoE) mediates the redistribution of lipids among cells and is expressed at highest levels in brain and liver. Human apoE exists in three major isoforms encoded by distinct alleles (? 2, ? 3, and ? 4). Compared with APOE ? 2 and ? 3, APOE ? 4 increases the risk of cognitive impairments, lowers the age of onset

Jacob Raber; Derek Wong; Manuel Buttini; Matthias Orth; Stefano Bellosta; Robert E. Pitas; Robert W. Mahley; Lennart Mucke

1998-01-01

65

Vitamins Deficiencies and Brain Function  

Microsoft Academic Search

\\u000a The consequences of malnutrition on the central nervous system are diverse and depend to a significant extent on the stage\\u000a of development or maturity of the brain as well as on the severity of the nutritional deficiency. For example, vitamin deficiencies\\u000a result in a wide range of neuropathology and neuropsychiatric symptomatology depending upon the nature and extent of the vitamin

Chantal Bémeur; Jane A. Montgomery; Roger F. Butterworth

66

Emerging roles of brain-specific angiogenesis inhibitor 1.  

PubMed

Brain-specific angiogenesis inhibitor 1 (BAI1) encodes a seven-transmembrane protein that belongs to the adhesion-GPCR family. Although BAI1 was named for the ability of its extracellular region to inhibit angiogenesis in tumor models, its function in physiological contexts was elusive and remained an orphan receptor until recently. BAI1 is now considered a phagocytic receptor that can recognize phosphatidylserine exposed on apoptotic cells. Moreover, BAI1 has been shown to function upstream of the signaling module comprised of ELMO/Dock180/Rac proteins, thereby facilitating the cytoskeletal reorganization necessary to mediate the phagocytic clearance of apoptotic cells. Here, we review the phylogeny, structure, associating proteins, as well as the known and proposed functions of BAI1. PMID:21618836

Park, Daeho; Ravichandran, Kodi S

2010-01-01

67

Cognitive fitness of cost-efficient brain functional networks  

PubMed Central

The human brain's capacity for cognitive function is thought to depend on coordinated activity in sparsely connected, complex networks organized over many scales of space and time. Recent work has demonstrated that human brain networks constructed from neuroimaging data have economical small-world properties that confer high efficiency of information processing at relatively low connection cost. However, it has been unclear how the architecture of complex brain networks functioning at different frequencies can be related to behavioral performance on cognitive tasks. Here, we show that impaired accuracy of working memory could be related to suboptimal cost efficiency of brain functional networks operating in the classical ? frequency band, 15–30 Hz. We analyzed brain functional networks derived from magnetoencephalography data recorded during working-memory task performance in 29 healthy volunteers and 28 people with schizophrenia. Networks functioning at higher frequencies had greater global cost efficiency than low-frequency networks in both groups. Superior task performance was positively correlated with global cost efficiency of the ?-band network and specifically with cost efficiency of nodes in left lateral parietal and frontal areas. These results are consistent with biophysical models highlighting the importance of ?-band oscillations for long-distance functional connections in brain networks and with pathophysiological models of schizophrenia as a dysconnection syndrome. More generally, they echo the saying that “less is more”: The information processing performance of a network can be enhanced by a sparse or low-cost configuration with disproportionately high efficiency.

Bassett, Danielle S.; Bullmore, Edward T.; Meyer-Lindenberg, Andreas; Apud, Jose A.; Weinberger, Daniel R.; Coppola, Richard

2009-01-01

68

Sensory stimulation induces tensor fields, which specifically transform brain activity.  

PubMed

It was recently shown that brain activity can be represented as a stimulation-specific vector field. Since the vector field of brain activity is specifically transformed by sensory input, we suggested that a tensor field that transforms brain activity reflects sensory input. We calculated the tensor fields that transform brain activity between visual baseline and auditory word processing in PET data and between environmental sounds and auditory word processing in fMRI data. In the first comparison, significant clusters formed a distributed network over the brain cortex. In the second comparison, clusters were more localised in the temporo-frontal network of speech processing. Our study therefore demonstrated that tensor fields reflect the sensory input that specifically transforms brain activity. PMID:24012681

Strelnikov, Kuzma

2013-10-25

69

Metabolism and functions of copper in brain.  

PubMed

Copper is an important trace element that is required for essential enzymes. However, due to its redox activity, copper can also lead to the generation of toxic reactive oxygen species. Therefore, cellular uptake, storage as well as export of copper have to be tightly regulated in order to guarantee sufficient copper supply for the synthesis of copper-containing enzymes but also to prevent copper-induced oxidative stress. In brain, copper is of importance for normal development. In addition, both copper deficiency as well as excess of copper can seriously affect brain functions. Therefore, this organ possesses ample mechanisms to regulate its copper metabolism. In brain, astrocytes are considered as important regulators of copper homeostasis. Impairments of homeostatic mechanisms in brain copper metabolism have been associated with neurodegeneration in human disorders such as Menkes disease, Wilson's disease and Alzheimer's disease. This review article will summarize the biological functions of copper in the brain and will describe the current knowledge on the mechanisms involved in copper transport, storage and export of brain cells. The role of copper in diseases that have been connected with disturbances in brain copper homeostasis will also be discussed. PMID:24440710

Scheiber, Ivo F; Mercer, Julian F B; Dringen, Ralf

2014-05-01

70

Toward discovery science of human brain function.  

PubMed

Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/. PMID:20176931

Biswal, Bharat B; Mennes, Maarten; Zuo, Xi-Nian; Gohel, Suril; Kelly, Clare; Smith, Steve M; Beckmann, Christian F; Adelstein, Jonathan S; Buckner, Randy L; Colcombe, Stan; Dogonowski, Anne-Marie; Ernst, Monique; Fair, Damien; Hampson, Michelle; Hoptman, Matthew J; Hyde, James S; Kiviniemi, Vesa J; Kötter, Rolf; Li, Shi-Jiang; Lin, Ching-Po; Lowe, Mark J; Mackay, Clare; Madden, David J; Madsen, Kristoffer H; Margulies, Daniel S; Mayberg, Helen S; McMahon, Katie; Monk, Christopher S; Mostofsky, Stewart H; Nagel, Bonnie J; Pekar, James J; Peltier, Scott J; Petersen, Steven E; Riedl, Valentin; Rombouts, Serge A R B; Rypma, Bart; Schlaggar, Bradley L; Schmidt, Sein; Seidler, Rachael D; Siegle, Greg J; Sorg, Christian; Teng, Gao-Jun; Veijola, Juha; Villringer, Arno; Walter, Martin; Wang, Lihong; Weng, Xu-Chu; Whitfield-Gabrieli, Susan; Williamson, Peter; Windischberger, Christian; Zang, Yu-Feng; Zhang, Hong-Ying; Castellanos, F Xavier; Milham, Michael P

2010-03-01

71

IMPLICATION OF ATP RECEPTORS IN BRAIN FUNCTIONS  

Microsoft Academic Search

The possible implication of P2-purinoceptors in brain functions is reviewed. Involvement of P2-purinoceptors in memory and learning (Section 2) is suggested by ATP release from hippocampal slices [Wieraszko et al. (1989)Brain Res. 485, 244–250], induction of fast synaptic currents in cultured hippocampal neurons [Inoue et al. (1992a)Neurosci. Lett. 134, 294–299] and long-lasting enhancement of the population spikes [Wieraszko and Seyfried

KAZUHIDE INOUE; SCHUICHI KOIZUMI; SHINYA UENO

1996-01-01

72

Imaging visual function of the human brain  

SciTech Connect

Imaging of human brain structure and activity with particular reference to visual function is reviewed along with methods of obtaining the data including computed tomographic (CT) scan, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET). The literature is reviewed and the potential for a new understanding of brain visual function is discussed. PET is reviewed from basic physical principles to the most recent visual brain findings with oxygen-15. It is shown that there is a potential for submillimeter localization of visual functions with sequentially different visual stimuli designed for the temporal separation of the responses. Single photon emission computed tomography (SPECT), a less expensive substitute for PET, is also discussed. MRS is covered from basic physical principles to the current state of the art of in vivo biochemical analysis. Future possible clinical applications are discussed. Improved understanding of the functional neural organization of vision and brain will open a window to maps and circuits of human brain function.119 references.

Marg, E.

1988-10-01

73

Entropy changes in brain function.  

PubMed

The traditional way of analyzing brain electrical activity, on the basis of electroencephalography (EEG) records, relies mainly on visual inspection and years of training. Although it is quite useful, of course, one has to acknowledge its subjective nature that hardly allows for a systematic protocol. In the present work quantifiers based on information theory and wavelet transform are reviewed. The "relative wavelet energy" provides information about the relative energy associated with different frequency bands present in the EEG and their corresponding degree of importance. The "normalized total wavelet entropy" carries information about the degree of order-disorder associated with a multi-frequency signal response. Their application in the analysis and quantification of short duration EEG signals (event-related potentials) and epileptic EEG records are summarized. PMID:17234291

Rosso, Osvaldo A

2007-04-01

74

Detecting disease-specific patterns of brain structure using cortical pattern matching and a population-based probabilistic brain atlas  

PubMed Central

The rapid creation of comprehensive brain image databases mandates the development of mathematical algorithms to uncover disease specific patterns of brain structure and function in human populations. We describe our construction of probabilistic atlases that store detailed information on how the brain varies across age and gender, across time, in health and disease, and in large human populations. Specifically, we introduce a mathematical framework based on covariant partial differential equations (PDEs), pull-backs of mappings under harmonic flows, and high-dimensional random tensor fields to encode variations in cortical patterning, asymmetry and tissue distribution in a population-based brain image database (N =94 scans). We use this information to detect disease-specific abnormalities in Alzheimer's disease and schizophrenia, including dynamic changes over time. Illustrative examples are chosen to show how group patterns of cortical organization, asymmetry, and disease-specific trends can be resolved that are not apparent in individual brain images. Finally, we create four-dimensional (4D) maps that store probabilistic information on the dynamics of brain change in development and disease. Digital atlases that generate these maps show considerable promise in identifying general patterns of structural and functional variation in diseased populations, and revealing how these features depend on demographic, genetic, clinical and therapeutic parameters.

Thompson, Paul M.; Mega, Michael S.; Vidal, Christine; Rapoport, Judith L.; Toga, Arthur W.

2008-01-01

75

Insulin in the brain: sources, localization and functions.  

PubMed

Historically, insulin is best known for its role in peripheral glucose homeostasis, and insulin signaling in the brain has received less attention. Insulin-independent brain glucose uptake has been the main reason for considering the brain as an insulin-insensitive organ. However, recent findings showing a high concentration of insulin in brain extracts, and expression of insulin receptors (IRs) in central nervous system tissues have gathered considerable attention over the sources, localization, and functions of insulin in the brain. This review summarizes the current status of knowledge of the peripheral and central sources of insulin in the brain, site-specific expression of IRs, and also neurophysiological functions of insulin including the regulation of food intake, weight control, reproduction, and cognition and memory formation. This review also considers the neuromodulatory and neurotrophic effects of insulin, resulting in proliferation, differentiation, and neurite outgrowth, introducing insulin as an attractive tool for neuroprotection against apoptosis, oxidative stress, beta amyloid toxicity, and brain ischemia. PMID:22956272

Ghasemi, Rasoul; Haeri, Ali; Dargahi, Leila; Mohamed, Zahurin; Ahmadiani, Abolhassan

2013-02-01

76

Progesterone Receptors: Form and Function in Brain  

PubMed Central

Emerging data indicate that progesterone has multiple non-reproductive functions in the central nervous system to regulate cognition, mood, inflammation, mitochondrial function, neurogenesis and regeneration, myelination and recovery from traumatic brain injury. Progesterone-regulated neural responses are mediated by an array of progesterone receptors (PR) that include the classic nuclear PRA and PRB receptors and splice variants of each, the seven transmembrane domain 7TMPR? and the membrane-associated 25-Dx PR (PGRMC1). These PRs induce classic regulation of gene expression while also transducing signaling cascades that originate at the cell membrane and ultimately activate transcription factors. Remarkably, PRs are broadly expressed throughout the brain and can be detected in every neural cell type. The distribution of PRs beyond hypothalamic borders, suggests a much broader role of progesterone in regulating neural function. Despite the large body of evidence regarding progesterone regulation of reproductive behaviors and estrogen-inducible responses as well as effects of progesterone metabolite neurosteroids, much remains to be discovered regarding the functional outcomes resulting from activation of the complex array of PRs in brain by gonadally and / or glial derived progesterone. Moreover, the impact of clinically used progestogens and developing selective PR modulators for targeted outcomes in brain is a critical avenue of investigation as the non-reproductive functions of PRs have far-reaching implications for hormone therapy to maintain neurological health and function throughout menopausal aging.

Brinton, Roberta Diaz; Thompson, Richard F.; Foy, Michael R.; Baudry, Michel; Wang, JunMing; Finch, Caleb E; Morgan, Todd E.; Stanczyk, Frank Z.; Pike, Christian J.; Nilsen, Jon

2008-01-01

77

Nicotine effects on brain function and functional connectivity in schizophrenia  

Microsoft Academic Search

BackgroundNicotine 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.

Leslie K Jacobsen; D. Cyril D'Souza; W. Einar Mencl; Kenneth R Pugh; Pawel Skudlarski; John H Krystal

2004-01-01

78

Functional Connectivity in Mild Traumatic Brain Injury  

PubMed Central

Objectives Research suggests that the majority of mild traumatic brain injury (mTBI) patients exhibit both cognitive and emotional dysfunction within the first weeks of injury, followed by symptom resolution 3–6 months post-injury. The neuronal correlates of said dysfunction are difficult to detect with standard clinical neuroimaging, complicating differential diagnosis and early identification of patients who may not recover. The current study examined whether resting state functional magnetic resonance imaging (FMRI) provides objective markers of injury and predicts cognitive, emotional and somatic complaints in mTBI patients semi-acutely (< 3 weeks post-injury) and in late recovery (3–5 month) phases. Methods Twenty seven semi-acute mTBI patients and 26 gender, age and education matched controls were studied. Fifteen out of 27 patients returned for a follow-up visit 3–5 months post-injury. The main dependent variables were spontaneous fluctuations (temporal correlation) in the default-mode (DMN) and fronto-parietal task-related (TRN) networks as measured by FMRI. Results Significant differences in self-reported cognitive, emotional and somatic complaints were observed (all p < .05), despite normal clinical (T1 and T2) imaging and neuropsychological testing results. Mild TBI patients demonstrated decreased functional connectivity within the DMN and hyper-connectivity between the DMN and lateral prefrontal cortex. Measures of functional connectivity exhibited high levels of sensitivity and specificity for patient classification and predicted cognitive complaints in the semi-acute injury stage. However, no changes in functional connectivity were observed across a four month recovery period. Conclusions Abnormal connectivity between the DMN and frontal cortex may provide objective biomarkers of mTBI and underlie cognitive impairment.

Mayer, Andrew R.; Mannell, Maggie V.; Ling, Josef; Gasparovic, Charles; Yeo, Ronald A.

2011-01-01

79

Optogenetic approaches for functional mouse brain mapping  

PubMed Central

To better understand the connectivity of the brain, it is important to map both structural and functional connections between neurons and cortical regions. In recent years, a set of optogenetic tools have been developed that permit selective manipulation and investigation of neural systems. These tools have enabled the mapping of functional connections between stimulated cortical targets and other brain regions. Advantages of the approach include the ability to arbitrarily stimulate brain regions that express opsins, allowing for brain mapping independent of behavior or sensory processing. The ability of opsins to be rapidly and locally activated allows for investigation of connectivity with spatial resolution on the order of single neurons and temporal resolution on the order of milliseconds. Optogenetic methods for functional mapping have been applied in experiments ranging from in vitro investigation of microcircuits, to in vivo probing of inter-regional cortical connections, to examination of global connections within the whole brain. We review recently developed functional mapping methods that use optogenetic single-point stimulation in the rodent brain and employ cellular electrophysiology, evoked motor movements, voltage sensitive dyes (VSDs), calcium indicators, or functional magnetic resonance imaging (fMRI) to assess activity. In particular we highlight results using red-shifted organic VSDs that permit high temporal resolution imaging in a manner spectrally separated from Channelrhodopsin-2 (ChR2) activation. VSD maps stimulated by ChR2 were dependent on intracortical synaptic activity and were able to reflect circuits used for sensory processing. Although the methods reviewed are powerful, challenges remain with respect to finding approaches that permit selective high temporal resolution assessment of stimulated activity in animals that can be followed longitudinally.

Lim, Diana H.; LeDue, Jeffrey; Mohajerani, Majid H.; Vanni, Matthieu P.; Murphy, Timothy H.

2013-01-01

80

Whole-Brain Functional Connectivity Identification of Functional Dyspepsia  

PubMed Central

Recent neuroimaging studies have shown local brain aberrations in functional dyspepsia (FD) patients, yet little attention has been paid to the whole-brain resting-state functional network abnormalities. The purpose of this study was to investigate whether FD disrupts the patterns of whole-brain networks and the abnormal functional connectivity could reflect the severity of the disease. The dysfunctional interactions between brain regions at rest were investigated in FD patients as compared with 40 age- and gender- matched healthy controls. Multivariate pattern analysis was used to evaluate the discriminative power of our results for classifying patients from controls. In our findings, the abnormal brain functional connections were mainly situated within or across the limbic/paralimbic system, the prefrontal cortex, the tempo-parietal areas and the visual cortex. About 96% of the subjects among the original dataset were correctly classified by a leave one-out cross-validation approach, and 88% accuracy was also validated in a replication dataset. The classification features were significantly associated with the patients’ dyspepsia symptoms, the self-rating depression scale and self-rating anxiety scale, but it was not correlated with duration of FD patients (p>0.05). Our results may indicate the effectiveness of the altered brain functional connections reflecting the disease pathophysiology underling FD. These dysfunctional connections may be the epiphenomena or causative agents of FD, which may be affected by clinical severity and its related emotional dimension of the disease rather than the clinical course.

Nan, Jiaofen; Liu, Jixin; Li, Guoying; Xiong, Shiwei; Yan, Xuemei; Yin, Qing; Zeng, Fang; von Deneen, Karen M.; Liang, Fanrong; Gong, Qiyong; Qin, Wei; Tian, Jie

2013-01-01

81

Metabolism and functions of glutathione in brain  

Microsoft Academic Search

The tripeptide glutathione is the thiol compound present in the highest concentration in cells of all organs. Glutathione has many physiological functions including its involvement in the defense against reactive oxygen species. The cells of the human brain consume about 20% of the oxygen utilized by the body but constitute only 2% of the body weight. Consequently, reactive oxygen species

Ralf Dringen

2000-01-01

82

The Berlin Brain-Computer Interface: Machine Learning Based Detection of User Specific Brain States  

Microsoft Academic Search

We outline the Berlin Brain-Computer Interface (BBCI), a system which enables us to translate brain signals from movements or movement intentions into control commands. The main contribution of the BBCI, which is a non-invasive EEG-based BCI system, is the use of advanced machine learning techniques that allow to adapt to the specific brain signatures of each user with literally no

Benjamin Blankertz; Guido Dornhege; Steven Lemm; Matthias Krauledat; Gabriel Curio; Klaus-robert Müller

2006-01-01

83

Regulatory RNAs in Brain Function and Disorders  

PubMed Central

Regulatory RNAs are being increasingly investigated in neurons, and important roles in brain function have been revealed. Regulatory RNAs are non-protein-coding RNAs (npcRNAs) that comprise a heterogeneous group of molecules, varying in size and mechanism of action. Regulatory RNAs often exert post-transcriptional control of gene expression, resulting in gene silencing or gene expression stimulation. Here, we review evidence that regulatory RNAs are implicated in neuronal development, differentiation, and plasticity. We will also discuss npcRNA dysregulation that may be involved in pathological states of the brain such as neurodevelopmental disorders, neurodegeneration, and epilepsy.

Iacoangeli, Anna; Bianchi, Riccardo; Tiedge, Henri

2012-01-01

84

Dissociations between behavioural and functional magnetic resonance imaging-based evaluations of cognitive function after brain injury  

PubMed Central

Functional neuroimaging methods hold promise for the identification of cognitive function and communication capacity in some severely brain-injured patients who may not retain sufficient motor function to demonstrate their abilities. We studied seven severely brain-injured patients and a control group of 14 subjects using a novel hierarchical functional magnetic resonance imaging assessment utilizing mental imagery responses. Whereas the control group showed consistent and accurate (for communication) blood-oxygen-level-dependent responses without exception, the brain-injured subjects showed a wide variation in the correlation of blood-oxygen-level-dependent responses and overt behavioural responses. Specifically, the brain-injured subjects dissociated bedside and functional magnetic resonance imaging-based command following and communication capabilities. These observations reveal significant challenges in developing validated functional magnetic resonance imaging-based methods for clinical use and raise interesting questions about underlying brain function assayed using these methods in brain-injured subjects.

Bardin, Jonathan C.; Fins, Joseph J.; Katz, Douglas I.; Hersh, Jennifer; Heier, Linda A.; Tabelow, Karsten; Dyke, Jonathan P.; Ballon, Douglas J.; Schiff, Nicholas D.

2011-01-01

85

Avoiding specific region of brain during whole-brain radiotherapy prevents memory loss  

Cancer.gov

Limiting the amount of radiation absorbed in the hippocampal portion of the brain during whole-brain radiotherapy (WBRT) for brain metastases preserves memory function in patients for up to six months after treatment, according to research presented at the American Society for Radiation Oncology's (ASTRO's) 55th Annual Meeting by researchers from the University of Wisconsin School of Medicine and Public Health, home of the UW Paul P. Carbone Comprehensive Cancer Center.

86

Electroencephalographic imaging of higher brain function  

NASA Technical Reports Server (NTRS)

High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. Electroencephalography (EEG) provides temporal resolution in the millisecond range. However, traditional EEG technology and practice provide insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. Recent advances help to overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical images, and by correcting the distortion caused by volume conduction of EEG signals through the skull and scalp. In addition, statistical measurements of sub-second interdependences between EEG time-series recorded from different locations can help to generate hypotheses about the instantaneous functional networks that form between different cortical regions during perception, thought and action. Example applications are presented from studies of language, attention and working memory. Along with its unique ability to monitor brain function as people perform everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.

Gevins, A.; Smith, M. E.; McEvoy, L. K.; Leong, H.; Le, J.

1999-01-01

87

Nicotine increases brain functional network efficiency.  

PubMed

Despite the use of cholinergic therapies in Alzheimer's disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network's tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer's disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function. PMID:22796985

Wylie, Korey P; Rojas, Donald C; Tanabe, Jody; Martin, Laura F; Tregellas, Jason R

2012-10-15

88

Nicotine Increases Brain Functional Network Efficiency  

PubMed Central

Despite the use of cholinergic therapies in Alzheimer’s disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting-state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network’s tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer’s disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function.

Wylie, Korey P.; Rojas, Donald C.; Tanabe, Jody; Martin, Laura F.; Tregellas, Jason R.

2012-01-01

89

Apoptosis in brain-specific autoimmune disease  

Microsoft Academic Search

Recent neuropathological studies of experimental autoimmune encephalomyelitis have focused attention on the high number of cells in the lesions that show typical morphological features of apoptosis. Surprisingly, it has turned out that the vast majority of apoptotic cells are T lymphocytes and that they actually represent the antigen-specific T-cell population responsible for the induction of the disease. Taken together, these

Jan Bauer; Hartmut Wekerle; Hans Lassmann

1995-01-01

90

Encoding and Retrieving Faces and Places: Distinguishing Process- and Stimulus-Specific Differences in Brain Activity  

ERIC Educational Resources Information Center

Among the most fundamental issues in cognitive neuroscience is how the brain may be organized into process-specific and stimulus-specific regions. In the episodic memory domain, most functional neuroimaging studies have focused on the former dimension, typically investigating the neural correlates of various memory processes. Thus, there is little…

Prince, Steven E.; Dennis, Nancy A.; Cabeza, Roberto

2009-01-01

91

Structural and functional brain imaging in schizophrenia.  

PubMed Central

We present an evaluation of the contribution of structural and functional brain imaging to our understanding of schizophrenia. Methodological influences on the validity of the data generated by these new technologies include problems with measurement and clinical and anatomic heterogeneity. These considerations greatly affect the interpretation of the data generated by these technologies. Work in these fields to date, however, has produced strong evidence which suggests that schizophrenia is a disease which involves abnormalities in the structure and function of many brain areas. Structural brain imaging studies of schizophrenia using computed tomography (CT) and magnetic resonance imaging (MRI) are reviewed and their contribution to current theories of the pathogenesis of schizophrenia are discussed. Positron emission tomography (PET) studies of brain metabolic activity and dopamine receptor binding in schizophrenia are summarized and the critical questions raised by these studies are outlined. Future studies in these fields have the potential to yield critical insights into the pathophysiology of schizophrenia; new directions for studies of schizophrenia using these technologies are identified.

Cleghorn, J M; Zipursky, R B; List, S J

1991-01-01

92

Retinoic Acid Signaling in the Functioning Brain  

NSDL National Science Digital Library

Retinoic acid, an active form of vitamin A, regulates gene expression throughout the body, and many components of the signaling system through which it acts are present in the brain. Very little is known, however, about how retinoic acid functions in neurobiological systems. Several studies have provided evidence that retinoic acid plays a role in sleep, learning, and memory, but the precise mechanisms through which it influences these processes remain unclear. All of these processes involve local or long-range inhibition and synchronized neuronal activity between separate locations in the brain. A critical component in the generation of the synchronized firing of cortical neurons (cortical synchrony) is a network of inhibitory interneurons containing parvalbumin, a cell population affected by retinoid perturbations, such as exposure to a vitamin A overdose. An understanding of the role of retinoids in normal brain function would provide clues to the long-standing question of whether abnormalities in retinoic acid signaling contribute to the pathogenesis of some brain diseases with uncertain etiologies that involve both genetic and environmental factors.

Ursula C. Drager (University of Massachusetts Medical School;Eunice Kennedy Shriver Center REV)

2006-02-28

93

Increases in Heart Disease Risk Factors May Decrease Brain Function  

MedlinePLUS

Increases in heart disease risk factors may decrease brain function May 02, 2013 Study Highlights: Increases in ... American Heart Association Infographic - H Joosten-Heart risks Brain function copyright American Heart Association Download (232.4 ...

94

Human-specific transcriptional networks in the brain  

PubMed Central

Summary Understanding human-specific patterns of brain gene expression and regulation can provide key insights into human brain evolution and speciation. Here, we use next generation sequencing, and Illumina and Affymetrix microarray platforms, to compare the transcriptome of human, chimpanzee, and macaque telencephalon. Our analysis reveals a predominance of genes differentially expressed within human frontal lobe and a striking increase in transcriptional complexity specific to the human lineage in the frontal lobe. In contrast, caudate nucleus gene expression is highly conserved. We also identify gene co-expression signatures related to either neuronal processes or neuropsychiatric diseases, including a human-specific module with CLOCK as its hub gene and another module enriched for neuronal morphological processes and genes co-expressed with FOXP2, a gene important for language evolution. These data demonstrate that transcriptional networks have undergone evolutionary remodeling even within a given brain region, providing a new window through which to view the foundation of uniquely human cognitive capacities.

Konopka, Genevieve; Friedrich, Tara; Davis-Turak, Jeremy; Winden, Kellen; Oldham, Michael C.; Gao, Fuying; Chen, Leslie; Wang, Guang-Zhong; Luo, Rui; Preuss, Todd M.; Geschwind, Daniel H.

2013-01-01

95

Brain function in social anxiety disorder.  

PubMed

What have these studies revealed about SAD? First, few studies have been performed so far, with even fewer replications. Most of the work has been exploratory in nature and follows the paradigms used in PD. This approach has been justifiably criticized. The use of psychological (naturalistic) challenges may be more appropriate in SP than chemical challenges. The paradigms of public speaking, autobiographical scripts, or similar behavioral challenges merit further use, exploration, and validation if symptoms resembling those of the condition proper are to be induced in experimental circumstances. However, some tentative conclusions can be drawn from the research performed so far. There is no enough evidence to support the presence of structural brain abnormality in SAD. Admittedly, such a finding would have been very unlikely. On the other hand, evidence of subtle functional abnormalities is accumulating. On the nosologic question, there appear to be differences from PD. While in some challenges (e.g., CO2 and pentagastrin) the two conditions differ only in degree, in others (e.g., lactate, caffeine, and flumazenil), the separation is clearer. Equally, there is a strong argument to differentiate the generalized from the specific form of social anxiety on the basis of substantial (albeit accidental) findings outlined earlier. More sophisticated neuroimaging techniques, directly comparing patients from both groups before and after pharmacologic or psychological treatment, should provide more conclusive evidence on this issue. What might also help future research is the integration of biological investigations with specific personality profiles. In one study, SAD patients scored low in novelty seeking, self-directedness and cooperativeness and high in harm avoidance. It has been hypothesized that such results indicate serotonergic and dopaminergic dysregulation, which is consistent with the findings described earlier. The best evidence for neurotransmitter abnormality so far is for altered dopamine function at the level of the basal ganglia, either pre- or postsynaptic, which may result in reduced basal ganglia function so that the normal fluidity of social motor functions (e.g., smiling, eye movements, and speech) are impaired, thus leading to the cognitive symptoms of social anxiety and the subsequent generation of avoidance behavior. Such patients should respond poorly to antipsychotics, and additional challenges with these drugs could be used to test this theory. Furthermore, more research needs to be done to elucidate the mechanism by which SSRIs work in SAD. Neuroanatomical models of social anxiety (Fig. 4) [see structure: Text], explaining the site of action of drugs and psychological treatments, have been proposed in recent years. Central to these models is the notion of an innate anxiety circuit, which could be tentatively identified with the behavioral inhibition system, the septohippocampal system. This area receives 5-HT, NE, and dopamine input and has connections with the cortex and limbic structures. The relevance of these models remains to be assessed in experiments that are specifically designed to test them. PMID:11723629

Argyropoulos, S V; Bell, C J; Nutt, D J

2001-12-01

96

Altered Resting Brain Function and Structure in Professional Badminton Players  

PubMed Central

Abstract Neuroimaging studies of professional athletic or musical training have demonstrated considerable practice-dependent plasticity in various brain structures, which may reflect distinct training demands. In the present study, structural and functional brain alterations were examined in professional badminton players and compared with healthy controls using magnetic resonance imaging (MRI) and resting-state functional MRI. Gray matter concentration (GMC) was assessed using voxel-based morphometry (VBM), and resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity. Results showed that the athlete group had greater GMC and ALFF in the right and medial cerebellar regions, respectively. The athlete group also demonstrated smaller ALFF in the left superior parietal lobule and altered functional connectivity between the left superior parietal and frontal regions. These findings indicate that badminton expertise is associated with not only plastic structural changes in terms of enlarged gray matter density in the cerebellum, but also functional alterations in fronto-parietal connectivity. Such structural and functional alterations may reflect specific experiences of badminton training and practice, including high-capacity visuo-spatial processing and hand-eye coordination in addition to refined motor skills.

Di, Xin; Zhu, Senhua; Wang, Pin; Ye, Zhuoer; Zhou, Ke; Zhuo, Yan

2012-01-01

97

Altered resting brain function and structure in professional badminton players.  

PubMed

Neuroimaging studies of professional athletic or musical training have demonstrated considerable practice-dependent plasticity in various brain structures, which may reflect distinct training demands. In the present study, structural and functional brain alterations were examined in professional badminton players and compared with healthy controls using magnetic resonance imaging (MRI) and resting-state functional MRI. Gray matter concentration (GMC) was assessed using voxel-based morphometry (VBM), and resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity. Results showed that the athlete group had greater GMC and ALFF in the right and medial cerebellar regions, respectively. The athlete group also demonstrated smaller ALFF in the left superior parietal lobule and altered functional connectivity between the left superior parietal and frontal regions. These findings indicate that badminton expertise is associated with not only plastic structural changes in terms of enlarged gray matter density in the cerebellum, but also functional alterations in fronto-parietal connectivity. Such structural and functional alterations may reflect specific experiences of badminton training and practice, including high-capacity visuo-spatial processing and hand-eye coordination in addition to refined motor skills. PMID:22840241

Di, Xin; Zhu, Senhua; Jin, Hua; Wang, Pin; Ye, Zhuoer; Zhou, Ke; Zhuo, Yan; Rao, Hengyi

2012-01-01

98

Common and specific brain responses to scenic emotional stimuli.  

PubMed

Processing of emotions has been an enduring topic of interest in neuroimaging research, but studies have mostly used facial emotional stimuli. The aim of this study was to determine neural networks involved in emotion processing using scenic emotional visual stimuli. One hundred and twenty photographs from the International Affective Picture System (IAPS), including ecological scenes of disgust, fear, happiness, and sadness, were presented to 40 healthy participants while they underwent functional magnetic imaging resonance (fMRI). Afterwards they evaluated the emotional content of the pictures in an offline task. The occipito-temporal cortex and the amygdala-hippocampal complex showed a non-specific emotion-related activation, which was more marked in response to negative emotions than to happiness. The temporo-parietal cortex and the ventral anterior cingulate gyrus showed deactivation, with the former being marked for all emotions except fear and the latter being most marked for disgust. The fusiform gyrus showed activation in response to disgust and deactivation in response to happiness or sadness. Brain regions involved in processing of scenic emotion therefore resemble those reported for facial expressions of emotion in that they respond to a range of different emotions, although there appears to be specificity in the intensity and direction of the response. PMID:23700105

Radua, Joaquim; Sarró, Salvador; Vigo, Teresa; Alonso-Lana, Silvia; Bonnín, C Mar; Ortiz-Gil, Jordi; Canales-Rodríguez, Erick J; Maristany, Teresa; Vieta, Eduard; Mckenna, Peter J; Salvador, Raymond; Pomarol-Clotet, Edith

2014-07-01

99

Functional Brain Networks in Schizophrenia: A Review  

PubMed Central

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.

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

2009-01-01

100

Impacts of Brain Serotonin Deficiency following Tph2 Inactivation on Development and Raphe Neuron Serotonergic Specification  

PubMed Central

Brain serotonin (5-HT) is implicated in a wide range of functions from basic physiological mechanisms to complex behaviors, including neuropsychiatric conditions, as well as in developmental processes. Increasing evidence links 5-HT signaling alterations during development to emotional dysregulation and psychopathology in adult age. To further analyze the importance of brain 5-HT in somatic and brain development and function, and more specifically differentiation and specification of the serotonergic system itself, we generated a mouse model with brain-specific 5-HT deficiency resulting from a genetically driven constitutive inactivation of neuronal tryptophan hydroxylase-2 (Tph2). Tph2 inactivation (Tph2?/?) resulted in brain 5-HT deficiency leading to growth retardation and persistent leanness, whereas a sex- and age-dependent increase in body weight was observed in Tph2+/? mice. The conserved expression pattern of the 5-HT neuron-specific markers (except Tph2 and 5-HT) demonstrates that brain 5-HT synthesis is not a prerequisite for the proliferation, differentiation and survival of raphe neurons subjected to the developmental program of serotonergic specification. Furthermore, although these neurons are unable to synthesize 5-HT from the precursor tryptophan, they still display electrophysiological properties characteristic of 5-HT neurons. Moreover, 5-HT deficiency induces an up-regulation of 5-HT1A and 5-HT1B receptors across brain regions as well as a reduction of norepinephrine concentrations accompanied by a reduced number of noradrenergic neurons. Together, our results characterize developmental, neurochemical, neurobiological and electrophysiological consequences of brain-specific 5-HT deficiency, reveal a dual dose-dependent role of 5-HT in body weight regulation and show that differentiation of serotonergic neuron phenotype is independent from endogenous 5-HT synthesis.

Gutknecht, Lise; Araragi, Naozumi; Merker, Soren; Waider, Jonas; Sommerlandt, Frank M. J.; Mlinar, Boris; Baccini, Gilda; Mayer, Ute; Proft, Florian; Hamon, Michel; Schmitt, Angelika G.; Corradetti, Renato; Lanfumey, Laurence; Lesch, Klaus-Peter

2012-01-01

101

Cell-specific posttranslational events affect functional expression at the plasma membrane but not tetrodotoxin sensitivity of the rat brain IIA sodium channel alpha-subunit expressed in mammalian cells.  

PubMed

The rat brain IIA Na+ channel alpha-subunit was expressed and studied in mammalian cells. Cells were infected with a recombinant vaccinia virus (VV) carrying the bacteriophage T7 RNA polymerase gene and were transfected with cDNA encoding the IIA Na+ channel alpha-subunit under control of a T7 promoter. Whole-cell patch-clamp recording showed that functional IIA channels were expressed efficiently (approximately 10 channels/microns2 in approximately 60% of cells) in Chinese hamster ovary (CHO) cells and in neonatal rat ventricular myocytes but were expressed poorly in undifferentiated BC3H1 cells and failed to express in Ltk- cells. However, voltage-dependent Drosophila Shaker H4 K+ channels and Escherichia coli beta-galactosidase were expressed efficiently in all four cell types with VV vectors. Because RNA synthesis probably occurs without major differences in the cytoplasm of all infected cell types under the control of the T7 promoter and T7 polymerase, we conclude that cell type-specific expression of the Na+ channel probably reflects differences at posttranslational steps. The gating properties of the IIA Na+ currents expressed in cardiac myocytes differed from those expressed in CHO cells; most noticeably, the IIA Na+ currents displayed more rapid macroscopic inactivation when expressed in cardiac myocytes. These differences also suggest cell-specific posttranslational modifications. IIA channels were blocked by approximately 90% by 90 nM TTX when expressed either in CHO cells or in cardiac myocytes; the latter also continued to display endogenous TTX-resistant Na+ currents. Therefore, the TTX binding site of the channel is not affected by cell-specific modifications and is encoded by the primary amino acid sequence. PMID:1309573

Yang, X C; Labarca, C; Nargeot, J; Ho, B Y; Elroy-Stein, O; Moss, B; Davidson, N; Lester, H A

1992-01-01

102

Towards a New Mapping of Brain Cortex Function  

Microsoft Academic Search

The aim of imaging neuroscience is to describe the functional organization of human brain at the level of large neuronal groupings, networks and systems. The systems level of description addresses how integrated brain functions are embodied in the physical structure of the brain. Magnetic resonance imaging is currently the technique of choice for the study of cerebral structure–function relationships and

Nick S. Ward; Richard S. J. Frackowiak

2004-01-01

103

Split My Brain: A Case Study of Seizure Disorder and Brain Function  

ERIC Educational Resources Information Center

This case involves a couple deciding whether or not their son should undergo brain surgery to treat a severe seizure disorder. In examining this dilemma, students apply knowledge of brain anatomy and function. They also learn about brain scanning techniques and discuss the plasticity of the brain.

Omarzu, Julia

2004-01-01

104

Brain function assessment in different conscious states  

PubMed Central

Background The study of brain functioning is a major challenge in neuroscience fields as human brain has a dynamic and ever changing information processing. Case is worsened with conditions where brain undergoes major changes in so-called different conscious states. Even though the exact definition of consciousness is a hard one, there are certain conditions where the descriptions have reached a consensus. The sleep and the anesthesia are different conditions which are separable from each other and also from wakefulness. The aim of our group has been to tackle the issue of brain functioning with setting up similar research conditions for these three conscious states. Methods In order to achieve this goal we have designed an auditory stimulation battery with changing conditions to be recorded during a 40 channel EEG polygraph (Nuamps) session. The stimuli (modified mismatch, auditory evoked etc.) have been administered both in the operation room and the sleep lab via Embedded Interactive Stimulus Unit which was developed in our lab. The overall study has provided some results for three domains of consciousness. In order to be able to monitor the changes we have incorporated Bispectral Index Monitoring to both sleep and anesthesia conditions. Results The first stage results have provided a basic understanding in these altered states such that auditory stimuli have been successfully processed in both light and deep sleep stages. The anesthesia provides a sudden change in brain responsiveness; therefore a dosage dependent anesthetic administration has proved to be useful. The auditory processing was exemplified targeting N1 wave, with a thorough analysis from spectrogram to sLORETA. The frequency components were observed to be shifting throughout the stages. The propofol administration and the deeper sleep stages both resulted in the decreasing of N1 component. The sLORETA revealed similar activity at BA7 in sleep (BIS 70) and target propofol concentration of 1.2 µg/mL. Conclusions The current study utilized similar stimulation and recording system and incorporated BIS dependent values to validate a common approach to sleep and anesthesia. Accordingly the brain has a complex behavior pattern, dynamically changing its responsiveness in accordance with stimulations and states.

2010-01-01

105

Functional Specificity of the Visual Word Form Area: General Activation for Words and Symbols but Specific Network Activation for Words  

ERIC Educational Resources Information Center

The functional specificity of the brain region known as the Visual Word Form Area (VWFA) was examined using fMRI. We explored whether this area serves a general role in processing symbolic stimuli, rather than being selective for the processing of words. Brain activity was measured during a visual 1-back task to English words, meaningful symbols…

Reinke, Karen; Fernandes, Myra; Schwindt, Graeme; O'Craven, Kathleen; Grady, Cheryl L.

2008-01-01

106

Violent Video Games Alter Brain Function in Young Men  

MedlinePLUS

... the RSNA Annual Meeting November 30, 2011 Violent Video Games Alter Brain Function in Young Men CHICAGO—A ... fMRI) analysis of long-term effects of violent video game play on the brain has found changes in ...

107

Assessing Functional Connectivity in the Human Brain by FMRI  

PubMed Central

Functional magnetic resonance imaging is widely used to detect and delineate regions of the brain that change their level of activation in response to specific stimuli and tasks. Simple activation maps depict only the average level of engagement of different regions within distributed systems. FMRI potentially can reveal additional information about the degree by which components of large-scale neural systems are functionally coupled together to achieve specific tasks. In order to better understand how brain regions contribute to functionally connected circuits, it is necessary to record activation maps either as a function of different conditions, at different times or in different subjects. Data obtained under different conditions may then be analyzed by a variety of techniques to infer correlations and couplings between nodes in networks. Several different multivariate statistical methods have been adapted and applied to analyze the variations within such data. An approach of particular interest that is suited to studies of connectivity within single subjects makes use of acquisitions of runs of MRI images obtained while the brain is in a so-called steady state, either at rest (i.e. without any specific stimulus or task) or in a condition of continuous activation. The interregional correlations between fluctuations of MRI signal potentially reveal functional connectivity. Recent studies have established that interregional correlations between different components of circuits in each of the visual, language, motor and working memory systems can be detected in the resting state. The correlations at baseline are changed during the performance of a continuous task. In this review the various methods available for assessing connectivity are described and evaluated.

Rogers, Baxter P.; Morgan, Victoria L.; Newton, Allen T.; Gore, John C.

2007-01-01

108

Site-specific opening of the blood-brain barrier  

PubMed Central

The blood-brain barrier (BBB) poses a significant impediment for the delivery of therapeutic drugs into the brain. This is particularly problematic for the treatment of malignant gliomas which are characterized by diffuse infiltration of tumor cells into normal brain where they are protected by a patent BBB. Selective disruption of the BBB, followed by administration of anti-cancer agents, represents a promising approach for the elimination of infiltrating glioma cells. A summary of the techniques (focused ultrasound, photodynamic therapy and photochemical internalization) for site-specific opening of the BBB will be discussed in this review. Each approach is capable of causing localized and transient opening of the BBB with minimal damage to surrounding normal brain as evidenced from magnetic resonance images and histology. T1-weighted MRI contrast enhanced images (a, b) showing focal enhancement in the area of light treatment. Fluence levels of 9 (a) and 17 J (b) at a fluence rate of 10 mW were performed 4 h following ALA administration (125 mg kg?1 i.p.). Scans were acquired 3–4 h post-PDT and 15 min following i.p. Gd contrast administration. Coronal H&E sections (c, d) taken from the brains of Fischer rats 14 days post-treatment. No significant pathology was observed following delivery of 9 J (c). At the high fluence (17 J), extensive infiltration of lymphocytes and macrophages was apparent as shown by the arrow in (d) [19]. Reprinted with permission.

Madsen, Steen J.; Hirschberg, Henry

2014-01-01

109

Dietary boron, brain function, and cognitive performance.  

PubMed

Although the trace element boron has yet to be recognized as an essential nutrient for humans, recent data from animal and human studies suggest that boron may be important for mineral metabolism and membrane function. To investigate further the functional role of boron, brain electrophysiology and cognitive performance were assessed in response to dietary manipulation of boron (approximately 0.25 versus approximately 3.25 mg boron/2000 kcal/day) in three studies with healthy older men and women. Within-subject designs were used to assess functional responses in all studies. Spectral analysis of electroencephalographic data showed effects of dietary boron in two of the three studies. When the low boron intake was compared to the high intake, there was a significant (p < 0.05) increase in the proportion of low-frequency activity, and a decrease in the proportion of higher-frequency activity, an effect often observed in response to general malnutrition and heavy metal toxicity. Performance (e.g., response time) on various cognitive and psychomotor tasks also showed an effect of dietary boron. When contrasted with the high boron intake, low dietary boron resulted in significantly poorer performance (p < 0.05) on tasks emphasizing manual dexterity (studies II and III); eye-hand coordination (study II); attention (all studies); perception (study III); encoding and short-term memory (all studies); and long-term memory (study I). Collectively, the data from these three studies indicate that boron may play a role in human brain function and cognitive performance, and provide additional evidence that boron is an essential nutrient for humans. PMID:7889884

Penland, J G

1994-11-01

110

Executive functioning and adaptive living skills after acquired brain injury.  

PubMed

Executive dysfunction is common following brain injury, with impairments involving attention, social pragmatics, higher-order thinking, judgment, and reasoning. Executive function impairments may have a direct impact on an individual's ability to return to instrumental activities of daily living (IADL), including employment, money management, driving, and maintaining a residence. Research has shown that neuropsychological executive function measures may be able to predict daily-living skills. There is limited research evaluating the relationship between executive functions and IADLs in adults with acquired brain injuries (ABI), with none investigating levels of proficiency as related to specific test scores. We hypothesize that neuropsychological executive function measures will have significant and moderate-to-strong correlations with participant-rated proficiency on functional tasks as measured by the Mayo-Portland Adaptability Inventory. Results support that IQ and some of the executive function measures (Processing Speed, Working Memory, and Trail-Making Test-Part B) correlated significantly and strongly and explained unique variance in all IADLs in this study. Data suggest that individuals with ABI who performed in the higher end of the low-average range or higher on measures of executive functioning tend to require little or no assistance to be independent with transportation, money management, living without support, and employment. Results also suggest that individuals with less executive dysfunction are likely to have greater overall community participation. PMID:23373638

Perna, Robert; Loughan, Ashlee R; Talka, Kristin

2012-01-01

111

Informing brain connectivity with optogenetic functional magnetic resonance imaging.  

PubMed

Optogenetic functional magnetic resonance imaging (ofMRI) is a novel approach that combines optogenetic control of neural circuits with high-field functional MRI. Optogenetics is a neuro-modulation technology in which light-activated trans-membrane conductance regulators are introduced into specifically targeted cell types to allow temporally precise, millisecond-scale activity modulation in vivo. By combining optogenetic control with fMRI readout, neural activity arising from specific circuit elements defined by genetic identity, cell body location, and axonal projection targets can be monitored in vivo across the whole brain. These unique features of ofMRI open new vistas for in vivo characterization of the dense plexus of neural connections according to their type and functionality. PMID:22326987

Lee, Jin Hyung

2012-10-01

112

Brain microvascular function during cardiopulmonary bypass  

SciTech Connect

Emboli in the brain microvasculature may inhibit brain activity during cardiopulmonary bypass. Such hypothetical blockade, if confirmed, may be responsible for the reduction of cerebral metabolic rate for glucose observed in animals subjected to cardiopulmonary bypass. In previous studies of cerebral blood flow during bypass, brain microcirculation was not evaluated. In the present study in animals (pigs), reduction of the number of perfused capillaries was estimated by measurements of the capillary diffusion capacity for hydrophilic tracers of low permeability. Capillary diffusion capacity, cerebral blood flow, and cerebral metabolic rate for glucose were measured simultaneously by the integral method, different tracers being used with different circulation times. In eight animals subjected to normothermic cardiopulmonary bypass, and seven subjected to hypothermic bypass, cerebral blood flow, cerebral metabolic rate for glucose, and capillary diffusion capacity decreased significantly: cerebral blood flow from 63 to 43 ml/100 gm/min in normothermia and to 34 ml/100 gm/min in hypothermia and cerebral metabolic rate for glucose from 43.0 to 23.0 mumol/100 gm/min in normothermia and to 14.1 mumol/100 gm/min in hypothermia. The capillary diffusion capacity declined markedly from 0.15 to 0.03 ml/100 gm/min in normothermia but only to 0.08 ml/100 gm/min in hypothermia. We conclude that the decrease of cerebral metabolic rate for glucose during normothermic cardiopulmonary bypass is caused by interruption of blood flow through a part of the capillary bed, possibly by microemboli, and that cerebral blood flow is an inadequate indicator of capillary blood flow. Further studies must clarify why normal microvascular function appears to be preserved during hypothermic cardiopulmonary bypass.

Sorensen, H.R.; Husum, B.; Waaben, J.; Andersen, K.; Andersen, L.I.; Gefke, K.; Kaarsen, A.L.; Gjedde, A.

1987-11-01

113

Executive functions and social skills in survivors of pediatric brain tumor  

Microsoft Academic Search

Medical advances have resulted in increased survival rates for children with brain tumors. Consequently, issues related to survivorship have become more critical. The use of multimodal treatment, in particular cranial radiation therapy, has been associated with subsequent cognitive decline. Specifically, deficits in executive functions have been reported in survivors of various types of pediatric brain tumor. Survivors are left with

Kelly R. Wolfe; Karin S. Walsh; Nina C. Reynolds; Frances Mitchell; Alyssa T. Reddy; Iris Paltin; Avi Madan-Swain

2012-01-01

114

Functional specificity among Hsp70 molecular chaperones.  

PubMed

Molecular chaperones of the 70-kilodalton heat shock protein (Hsp70) class bind to partially unfolded polypeptide substrates and participate in a wide variety of cellular processes. Differences in peptide-binding specificity among Hsp70s have led to the hypothesis that peptide binding determines specific Hsp70 functions. Protein domains were identified that were required for two separate functions of a yeast Hsp70 family. The peptide-binding domain was not required for either of these specific Hsp70 functions, which suggests that peptide-binding specificity plays little or no role in determining Hsp70 functions in vivo. PMID:8994035

James, P; Pfund, C; Craig, E A

1997-01-17

115

From Synchronisation to Networks: Assessment of Functional Connectivity in the Brain  

Microsoft Academic Search

\\u000a There is increasing evidence from basic research that statistical correlations between electroencephalographic (EEG) and magnetoencephalographic\\u000a (MEG) rhythms recorded from different brain areas, either ‘at rest’ or during a specific task, contain a wealth of information\\u000a on functional interactions between brain regions (Buzsaki, 2006; Varela et al., 2001). In fact, synchronisation of oscillatory\\u000a brain activity in various frequency bands may be

Cornelis J. Stam

116

Distribution and function of melanocortin receptors within the brain.  

PubMed

Biological responses to pro-opiomelanocortin (POMC)-derived peptides administered in the brain were documented in the 1950s but their molecular mechanisms of action only began to be resolved with the mapping of melanocortin receptor subtypes to specific brain regions in the 1990s. Out of the five melanocortin receptor subtypes, MC3R and MC4R are widely recognised as 'neural' melanocortin receptors. In situ hybridization anatomical mapping of these receptor subtypes to distinct hypothalamic nuclei first indicated their roles in energy homeostasis, roles that were later confirmed with the obese phenotypes exhibited by Mc3R and Mc4R knockout mice. It is perhaps less well known however, that all five melanocortin receptor subtypes have been detected in developing and/or adult brains of various species. This chapter provides a comprehensive summary of the detection and mapping of each melanocortin receptor subtype in mammalian, chicken and fish brains and relates the sites of expression to functions that are either known or proposed for each receptor subtype. PMID:21222258

Mountjoy, Kathleen G

2010-01-01

117

Maturation of Widely Distributed Brain Function Subserves Cognitive Development  

Microsoft Academic Search

Cognitive and brain maturational changes continue throughout late childhood and adolescence. During this time, increasing cognitive control over behavior enhances the voluntary suppression of reflexive\\/impulsive response tendencies. Recently, with the advent of functional MRI, it has become possible to characterize changes in brain activity during cognitive development. In order to investigate the cognitive and brain maturation subserving the ability to

Beatriz Luna; Keith R. Thulborn; Douglas P. Munoz; Elisha P. Merriam; Krista E. Garver; Nancy J. Minshew; Matcheri S. Keshavan; Christopher R. Genovese; William F. Eddy; John A. Sweeney

2001-01-01

118

Memory Function Before and After Whole Brain Radiotherapy in Patients With and Without Brain Metastases  

Microsoft Academic Search

Purpose: To prospectively compare the effect of prophylactic and therapeutic whole brain radiotherapy (WBRT) on memory function in patients with and without brain metastases. Methods and Materials: Adult patients with and without brain metastases (n = 44) were prospectively evaluated with serial cognitive testing, before RT (T0), after starting RT (T1), at the end of RT (T2), and 6-8 weeks

Grit Welzel; Katharina Fleckenstein; Joerg Schaefer; Brigitte Hermann; Uta Kraus-Tiefenbacher; Sabine K. Mai; Frederik Wenz

2008-01-01

119

Effects of the diet on brain function  

NASA Technical Reports Server (NTRS)

The rates of synthesis by brain neurons of the neurotransmitters serotonin, acetylcholine, and the catecholamines depend on the brain levels of the respective precursor molecules. Brain levels of each precursor are influenced by their blood concentration, and for the amino acid precursors, by the blood levels of other amino acids as well. Since diet readily alters blood concentrations of each of these precursors, it thereby also influences the brain formation of their neutrotransmitter products.

Fernstrom, J. D.

1981-01-01

120

The physiological and biochemical bases of functional brain imaging  

PubMed Central

Functional brain imaging is based on the display of computer-derived images of changes in physiological and/or biochemical functions altered by activation or depression of local functional activities in the brain. This article reviews the physiological and biochemical mechanisms involved.

2007-01-01

121

Exploring large-scale brain networks in functional MRI  

Microsoft Academic Search

Increasing emphasis has been recently put on large-scale network processing of brain functions. To explore these networks, many approaches have been proposed in functional magnetic resonance imaging (fMRI). Their objective is to answer the following two questions: (1) what brain regions are involved in the functional process under investigation? and (2) how do these regions interact? We review some of

Guillaume Marrelec; Pierre Bellec; Habib Benali

2006-01-01

122

Mapping distributed brain function and networks with diffuse optical tomography  

NASA Astrophysics Data System (ADS)

Mapping of human brain function has revolutionized systems neuroscience. However, traditional functional neuroimaging by positron emission tomography or functional magnetic resonance imaging cannot be used when applications require portability, or are contraindicated because of ionizing radiation (positron emission tomography) or implanted metal (functional magnetic resonance imaging). Optical neuroimaging offers a non-invasive alternative that is radiation free and compatible with implanted metal and electronic devices (for example, pacemakers). However, optical imaging technology has heretofore lacked the combination of spatial resolution and wide field of view sufficient to map distributed brain functions. Here, we present a high-density diffuse optical tomography imaging array that can map higher-order, distributed brain function. The system was tested by imaging four hierarchical language tasks and multiple resting-state networks including the dorsal attention and default mode networks. Finally, we imaged brain function in patients with Parkinson's disease and implanted deep brain stimulators that preclude functional magnetic resonance imaging.

Eggebrecht, Adam T.; Ferradal, Silvina L.; Robichaux-Viehoever, Amy; Hassanpour, Mahlega S.; Dehghani, Hamid; Snyder, Abraham Z.; Hershey, Tamara; Culver, Joseph P.

2014-06-01

123

Mapping distributed brain function and networks with diffuse optical tomography  

PubMed Central

Mapping of human brain function has revolutionized systems neuroscience. However, traditional functional neuroimaging by positron emission tomography or functional magnetic resonance imaging cannot be used when applications require portability, or are contraindicated because of ionizing radiation (positron emission tomography) or implanted metal (functional magnetic resonance imaging). Optical neuroimaging offers a non-invasive alternative that is radiation free and compatible with implanted metal and electronic devices (for example, pacemakers). However, optical imaging technology has heretofore lacked the combination of spatial resolution and wide field of view sufficient to map distributed brain functions. Here, we present a high-density diffuse optical tomography imaging array that can map higher-order, distributed brain function. The system was tested by imaging four hierarchical language tasks and multiple resting-state networks including the dorsal attention and default mode networks. Finally, we imaged brain function in patients with Parkinson’s disease and implanted deep brain stimulators that preclude functional magnetic resonance imaging.

Eggebrecht, Adam T.; Ferradal, Silvina L.; Robichaux-Viehoever, Amy; Hassanpour, Mahlega S.; Dehghani, Hamid; Snyder, Abraham Z.; Hershey, Tamara; Culver, Joseph P.

2014-01-01

124

A default mode of brain function  

Microsoft Academic Search

A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain

Marcus E. Raichle; Ann Mary MacLeod; Abraham Z. Snyder; William J. Powers; Debra A. Gusnard; Gordon L. Shulman

2001-01-01

125

Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks.  

PubMed

The ability to map the functional connectivity of discrete cell types in the intact mammalian brain during behavior is crucial for advancing our understanding of brain function in normal and disease states. We combined designer receptor exclusively activated by designer drug (DREADD) technology and behavioral imaging with ?PET and [18F]fluorodeoxyglucose (FDG) to generate whole-brain metabolic maps of cell-specific functional circuits during the awake, freely moving state. We have termed this approach DREADD-assisted metabolic mapping (DREAMM) and documented its ability in rats to map whole-brain functional anatomy. We applied this strategy to evaluating changes in the brain associated with inhibition of prodynorphin-expressing (Pdyn-expressing) and of proenkephalin-expressing (Penk-expressing) medium spiny neurons (MSNs) of the nucleus accumbens shell (NAcSh), which have been implicated in neuropsychiatric disorders. DREAMM revealed discrete behavioral manifestations and concurrent engagement of distinct corticolimbic networks associated with dysregulation of Pdyn and Penk in MSNs of the NAcSh. Furthermore, distinct neuronal networks were recruited in awake versus anesthetized conditions. These data demonstrate that DREAMM is a highly sensitive, molecular, high-resolution quantitative imaging approach. PMID:24231358

Michaelides, Michael; Anderson, Sarah Ann R; Ananth, Mala; Smirnov, Denis; Thanos, Panayotis K; Neumaier, John F; Wang, Gene-Jack; Volkow, Nora D; Hurd, Yasmin L

2013-12-01

126

Synchronization-based approach for detecting functional activation of brain  

NASA Astrophysics Data System (ADS)

In this paper, we investigate a synchronization-based, data-driven clustering approach for the analysis of functional magnetic resonance imaging (fMRI) data, and specifically for detecting functional activation from fMRI data. We first define a new measure of similarity between all pairs of data points (i.e., time series of voxels) integrating both complete phase synchronization and amplitude correlation. These pairwise similarities are taken as the coupling between a set of Kuramoto oscillators, which in turn evolve according to a nearest-neighbor rule. As the network evolves, similar data points naturally synchronize with each other, and distinct clusters will emerge. The clustering behavior of the interaction network of the coupled oscillators, therefore, mirrors the clustering property of the original multiple time series. The clustered regions whose cross-correlation coefficients are much greater than other regions are considered as the functionally activated brain regions. The analysis of fMRI data in auditory and visual areas shows that the recognized brain functional activations are in complete correspondence with those from the general linear model of statistical parametric mapping, but with a significantly lower time complexity. We further compare our results with those from traditional K-means approach, and find that our new clustering approach can distinguish between different response patterns more accurately and efficiently than the K-means approach, and therefore more suitable in detecting functional activation from event-related experimental fMRI data.

Hong, Lei; Cai, Shi-Min; Zhang, Jie; Zhuo, Zhao; Fu, Zhong-Qian; Zhou, Pei-Ling

2012-09-01

127

Synchronization-based approach for detecting functional activation of brain.  

PubMed

In this paper, we investigate a synchronization-based, data-driven clustering approach for the analysis of functional magnetic resonance imaging (fMRI) data, and specifically for detecting functional activation from fMRI data. We first define a new measure of similarity between all pairs of data points (i.e., time series of voxels) integrating both complete phase synchronization and amplitude correlation. These pairwise similarities are taken as the coupling between a set of Kuramoto oscillators, which in turn evolve according to a nearest-neighbor rule. As the network evolves, similar data points naturally synchronize with each other, and distinct clusters will emerge. The clustering behavior of the interaction network of the coupled oscillators, therefore, mirrors the clustering property of the original multiple time series. The clustered regions whose cross-correlation coefficients are much greater than other regions are considered as the functionally activated brain regions. The analysis of fMRI data in auditory and visual areas shows that the recognized brain functional activations are in complete correspondence with those from the general linear model of statistical parametric mapping, but with a significantly lower time complexity. We further compare our results with those from traditional K-means approach, and find that our new clustering approach can distinguish between different response patterns more accurately and efficiently than the K-means approach, and therefore more suitable in detecting functional activation from event-related experimental fMRI data. PMID:23020467

Hong, Lei; Cai, Shi-Min; Zhang, Jie; Zhuo, Zhao; Fu, Zhong-Qian; Zhou, Pei-Ling

2012-09-01

128

Modulation of Intercellular Calcium Signaling by Melatonin, in Avian and Mammalian Astrocytes, is Brain Region Specific  

PubMed Central

Calcium waves among glial cells impact many central nervous system functions, including neural integration and brain metabolism. Here, we have characterized the modulatory effects of melatonin, a pineal neurohormone that mediates circadian and seasonal processes, on glial calcium waves derived from different brain regions and species. Diencephalic and telencephalic astrocytes, from both chick and mouse brains, expressed melatonin receptor proteins. Further, using the calcium-sensitive dye Fluo-4, we conducted real-time imaging analyses of calcium waves propagated among mammalian and avian astrocytes. Mouse diencephalic astrocytic calcium waves spread to an area 2-5 fold larger than waves among avian astrocytes and application of 10 nM melatonin caused a 32% increase in the spread of these mammalian calcium waves, similar to the 23% increase observed in chick diencephalic astrocytes. In contrast, melatonin had no effect on calcium waves in either avian or mammalian telencephalic astrocytes. Mouse telencephalic calcium waves radially spread from their initiation site among untreated astrocytes. However, waves meandered among mouse diencephalic astrocytes, taking heterogeneous paths at variable rates of propagation. Brain regional differences in wave propagation were abolished by melatonin, as diencephalic astrocytes acquired more telencephalon-like wave characteristics. Astrocytes cultured from different brain regions, therefore, possess fundamentally disparate mechanisms of calcium wave propagation and responses to melatonin. These results suggest multiple roles for melatonin receptors in the regulation of astroglial function, impacting specific brain regions differentially.

Peters, Jennifer L.; Earnest, Barbara J.; Tjalkens, Ronald B.; Cassone, Vincent M.; Zoran, Mark J.

2008-01-01

129

Gender-specific impact of personal health parameters on individual brain aging in cognitively unimpaired elderly subjects  

PubMed Central

Aging alters brain structure and function. Personal health markers and modifiable lifestyle factors are related to individual brain aging as well as to the risk of developing Alzheimer's disease (AD). This study used a novel magnetic resonance imaging (MRI)-based biomarker to assess the effects of 17 health markers on individual brain aging in cognitively unimpaired elderly subjects. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE) score indicates accelerated atrophy and is considered a risk factor for developing AD. Within this cross-sectional, multi-center study 228 cognitively unimpaired elderly subjects (118 males) completed an MRI at 1.5Tesla, physiological and blood parameter assessments. The multivariate regression model combining all measured parameters was capable of explaining 39% of BrainAGE variance in males (p < 0.001) and 32% in females (p < 0.01). Furthermore, markers of the metabolic syndrome as well as markers of liver and kidney functions were profoundly related to BrainAGE scores in males (p < 0.05). In females, markers of liver and kidney functions as well as supply of vitamin B12 were significantly related to BrainAGE (p < 0.05). In conclusion, in cognitively unimpaired elderly subjects several clinical markers of poor health were associated with subtle structural changes in the brain that reflect accelerated aging, whereas protective effects on brain aging were observed for markers of good health. Additionally, the relations between individual brain aging and miscellaneous health markers show gender-specific patterns. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of subtly abnormal patterns of brain aging probably preceding cognitive decline and development of AD.

Franke, Katja; Ristow, Michael; Gaser, Christian

2014-01-01

130

Chemotherapy altered brain functional connectivity in women with breast cancer: a pilot study.  

PubMed

Adjuvant chemotherapy is associated with improvements in long-term cancer survival. However, reports of cognitive impairment following treatment emphasize the importance of understanding the long-term effects of chemotherapy on brain functioning. Cognitive deficits found in chemotherapy patients suggest a change in brain functioning that affects specific cognitive domains such as attentional processing and executive functioning. This study examined the processes potentially underlying these changes in cognition by examining brain functional connectivity pre- and post-chemotherapy in women with breast cancer. Functional connectivity examines the temporal correlation between spatially remote brain regions in an effort to understand how brain networks support specific cognitive functions. Nine women diagnosed with breast cancer completed a functional magnetic resonance imaging (fMRI) session before chemotherapy, 1 month after, and 1 year after the completion of chemotherapy. Seed-based functional connectivity analyses were completed using seeds in the intraparietal sulcus (IPS) to examine connectivity in the dorsal anterior attention network and in the posterior cingulate cortex (PCC) to examine connectivity in the default mode network. Results showed decreased functional connectivity 1 month after chemotherapy that partially returned to baseline at 1 year in the dorsal attention network. Decreased connectivity was seen in the default mode network at 1 month and 1 year following chemotherapy. In addition, increased subjective memory complaints were noted at 1 month and 1 year post-chemotherapy. These findings suggest a detrimental effect of chemotherapy on brain functional connectivity that is potentially related to subjective cognitive assessment. PMID:23852814

Dumas, Julie A; Makarewicz, Jenna; Schaubhut, Geoffrey J; Devins, Robert; Albert, Kimberly; Dittus, Kim; Newhouse, Paul A

2013-12-01

131

Laser technique for anatomical-functional study of the medial prefrontal cortex of the brain  

NASA Astrophysics Data System (ADS)

The brain represents one of the most complex systems that we know yet. In its study, non-destructive methods -- in particular, behavioral studies play an important role. By alteration of brain functioning (e.g. by pharmacological means) and observation of consequent behavior changes an important information on brain organization and functioning is obtained. For inducing local alterations, permanent brain lesions are employed. However, for correct results this technique has to be quasi-non-destructive, i.e. not to affect the normal brain function. Hence, the lesions should be very small, accurate and applied precisely over the structure (e.g. the brain nucleus) of interest. These specifications are difficult to meet with the existing techniques for brain lesions -- specifically, neurotoxical, mechanical and electrical means because they result in too extensive damage. In this paper, we present new laser technique for quasi-non- destructive anatomical-functional mapping in vivo of the medial prefrontal cortex (MPFC) of the rat. The technique is based on producing of small-size, well-controlled laser- induced lesions over some areas of the MPFC. The anesthetized animals are subjected to stereotactic surgery and certain points of the MPFC are exposed the confined radiation of the 10 W cw CO2 laser. Subsequent behavioral changes observed in neonatal and adult animals as well as histological data prove effectiveness of this technology for anatomical- functional studies of the brain by areas, and as a treatment method for some pathologies.

Sanchez-Huerta, Laura; Hernandez, Adan; Ayala, Griselda; Marroquin, Javier; Silva, Adriana B.; Khotiaintsev, Konstantin S.; Svirid, Vladimir A.; Flores, Gonzalo; Khotiaintsev, Sergei N.

1999-05-01

132

Estimation of premorbid functioning after traumatic brain injury.  

PubMed

Estimation of premorbid functioning in patients with traumatic brain injury (TBI) is a difficult but necessary step both in the assessment of neurological impairment and in planning treatment. Because the estimation process is almost always retrospective, its reliability is questionable. The use of multiple sources of information improves the likelihood of an accurate estimate. The effects of TBI cross a number of domains in the victim's life. Thus, premorbid functioning must be estimated in the physical, cognitive, emotional, social, financial and vocational spheres. Knowledge of baseline or premorbid functioning levels allows the clinician to appreciate the severity of injury, provide a prognosis, and shape treatment goals that are specific to the individual. In this article, we present the key questions to be addressed, suggest sources of information to obtain the answers, describe the processes through which answers should be obtained, and outline the uses for this important information in working with victims of TBI. PMID:24525805

Ruff, R M; Mueller, J; Jurica, P

1996-01-01

133

Efficiency of weak brain connections support general cognitive functioning.  

PubMed

Brain network topology provides valuable information on healthy and pathological brain functioning. Novel approaches for brain network analysis have shown an association between topological properties and cognitive functioning. Under the assumption that "stronger is better", the exploration of brain properties has generally focused on the connectivity patterns of the most strongly correlated regions, whereas the role of weaker brain connections has remained obscure for years. Here, we assessed whether the different strength of connections between brain regions may explain individual differences in intelligence. We analyzed-functional connectivity at rest in ninety-eight healthy individuals of different age, and correlated several connectivity measures with full scale, verbal, and performance Intelligent Quotients (IQs). Our results showed that the variance in IQ levels was mostly explained by the distributed communication efficiency of brain networks built using moderately weak, long-distance connections, with only a smaller contribution of stronger connections. The variability in individual IQs was associated with the global efficiency of a pool of regions in the prefrontal lobes, hippocampus, temporal pole, and postcentral gyrus. These findings challenge the traditional view of a prominent role of strong functional brain connections in brain topology, and highlight the importance of both strong and weak connections in determining the functional architecture responsible for human intelligence variability. Hum Brain Mapp 35:4566-4582, 2014. © 2014 Wiley Periodicals, Inc. PMID:24585433

Santarnecchi, Emiliano; Galli, Giulia; Polizzotto, Nicola Riccardo; Rossi, Alessandro; Rossi, Simone

2014-09-01

134

Imaging structural and functional brain networks in temporal lobe epilepsy.  

PubMed

Early imaging studies in temporal lobe epilepsy (TLE) focused on the search for mesial temporal sclerosis, as its surgical removal results in clinically meaningful improvement in about 70% of patients. Nevertheless, a considerable subgroup of patients continues to suffer from post-operative seizures. Although the reasons for surgical failure are not fully understood, electrophysiological and imaging data suggest that anomalies extending beyond the temporal lobe may have negative impact on outcome. This hypothesis has revived the concept of human epilepsy as a disorder of distributed brain networks. Recent methodological advances in non-invasive neuroimaging have led to quantify structural and functional networks in vivo. While structural networks can be inferred from diffusion MRI tractography and inter-regional covariance patterns of structural measures such as cortical thickness, functional connectivity is generally computed based on statistical dependencies of neurophysiological time-series, measured through functional MRI or electroencephalographic techniques. This review considers the application of advanced analytical methods in structural and functional connectivity analyses in TLE. We will specifically highlight findings from graph-theoretical analysis that allow assessing the topological organization of brain networks. These studies have provided compelling evidence that TLE is a system disorder with profound alterations in local and distributed networks. In addition, there is emerging evidence for the utility of network properties as clinical diagnostic markers. Nowadays, a network perspective is considered to be essential to the understanding of the development, progression, and management of epilepsy. PMID:24098281

Bernhardt, Boris C; Hong, Seokjun; Bernasconi, Andrea; Bernasconi, Neda

2013-01-01

135

Development of Large-Scale Functional Brain Networks in Children  

Microsoft Academic Search

The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7-9 y) and 22 young-adults (ages 19-22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains

Kaustubh Supekar; Mark Musen; Vinod Menon

2009-01-01

136

Brain serotonin and pituitary-adrenal functions  

NASA Technical Reports Server (NTRS)

It had been concluded by Scapagnini et al. (1971) that brain serotonin (5-HT) was involved in the regulation of the diurnal rhythm of the pituitary-adrenal system but not in the stress response. A study was conducted to investigate these findings further by evaluating the effects of altering brain 5-HT levels on the daily fluctuation of plasma corticosterone and on the response of the pituitary-adrenal system to a stressful or noxious stimulus in the rat. In a number of experiments brain 5-HT synthesis was inhibited with parachlorophenylalanine. In other tests it was tried to raise the level of brain 5-HT with precursors.

Vernikos-Danellis, J.; Berger, P.; Barchas, J. D.

1973-01-01

137

Infrared Imaging System for Studying Brain Function  

NASA Technical Reports Server (NTRS)

A proposed special-purpose infrared imaging system would be a compact, portable, less-expensive alternative to functional magnetic resonance imaging (fMRI) systems heretofore used to study brain function. Whereas a typical fMRI system fills a large room, and must be magnetically isolated, this system would fit into a bicycle helmet. The system would include an assembly that would be mounted inside the padding in a modified bicycle helmet or other suitable headgear. The assembly would include newly designed infrared photodetectors and data-acquisition circuits on integrated-circuit chips on low-thermal-conductivity supports in evacuated housings (see figure) arranged in multiple rows and columns that would define image coordinates. Each housing would be spring-loaded against the wearer s head. The chips would be cooled by a small Stirling Engine mounted contiguous to, but thermally isolated from, the portions of the assembly in thermal contact with the wearer s head. Flexible wires or cables for transmitting data from the aforementioned chips would be routed to an integrated, multichannel transmitter and thence through the top of the assembly to a patch antenna on the outside of the helmet. The multiple streams of data from the infrared-detector chips would be sent to a remote site, where they would be processed, by software, into a three-dimensional display of evoked potentials that would represent firing neuronal bundles and thereby indicate locations of neuronal activity associated with mental or physical activity. The 3D images will be analogous to current fMRI images. The data would also be made available, in real-time, for comparison with data in local or internationally accessible relational databases that already exist in universities and research centers. Hence, this system could be used in research on, and for the diagnosis of response from the wearer s brain to physiological, psychological, and environmental changes in real time. The images would also be stored in a relational database for comparison with corresponding responses previously observed in other subjects.

Mintz, Frederick; Mintz, Frederick; Gunapala, Sarath

2007-01-01

138

An Impairment Index of Brain Functions in Children.  

ERIC Educational Resources Information Center

An impairment index of brain functions in children was developed to summarize the performance on the Halstead-Reitan Neurological Test Battery for older children aged 9 through 14 years. Findings suggested that it may be a valid and objective indicator of brain functions in older children, although cross-validation is necessary. (Author/CL)

Reitan, Ralph M.

1984-01-01

139

Evolution of Cognitive Function via Redeployment of Brain Areas  

Microsoft Academic Search

Part of understanding the functional organization of the brain is understanding how it evolved. The current study suggests that although the brain may have originally emerged as an organ with functionally dedicated regions, the creative reuse of these regions has played a significant role in its evolutionary development. This would parallel the evolution of other capabilities wherein existing struc- tures,

MICHAEL L. ANDERSON

2007-01-01

140

Brain Research: The Necessity for Separating Sites, Actions and Functions.  

ERIC Educational Resources Information Center

Educators, as applied scientists, must work in partnership with investigative scientists who are researching brain functions in order to reach a better understanding of gifted students and students who are intelligent but do not learn. Improper understanding of brain functions can cause gross errors in educational placement. Until recently, the…

Meeker, Mary

141

Graph Analysis of Functional Brain Networks for Cognitive Control of Action in Traumatic Brain Injury  

ERIC Educational Resources Information Center

Patients with traumatic brain injury show clear impairments in behavioural flexibility and inhibition that often persist beyond the time of injury, affecting independent living and psychosocial functioning. Functional magnetic resonance imaging studies have shown that patients with traumatic brain injury typically show increased and more broadly…

Caeyenberghs, Karen; Leemans, Alexander; Heitger, Marcus H.; Leunissen, Inge; Dhollander, Thijs; Sunaert, Stefan; Dupont, Patrick; Swinnen, Stephan P.

2012-01-01

142

Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression  

PubMed Central

Tissue-specific alternative splicing is critical for the emergence of tissue identity during development, yet the role of this process in malignant transformation is undefined. Tissue-specific splicing involves evolutionarily conserved, alternative exons that represent only a minority of the total alternative exons identified. Many of these conserved exons have functional features that influence signaling pathways to profound biological effect. Here, we determined that lineage-specific splicing of a brain-enriched cassette exon in the membrane-binding tumor suppressor annexin A7 (ANXA7) diminishes endosomal targeting of the EGFR oncoprotein, consequently enhancing EGFR signaling during brain tumor progression. ANXA7 exon splicing was mediated by the ribonucleoprotein PTBP1, which is normally repressed during neuronal development. PTBP1 was highly expressed in glioblastomas due to loss of a brain-enriched microRNA (miR-124) and to PTBP1 amplification. The alternative ANXA7 splicing trait was present in precursor cells, suggesting that glioblastoma cells inherit the trait from a potential tumor-initiating ancestor and that these cells exploit this trait through accumulation of mutations that enhance EGFR signaling. Our data illustrate that lineage-specific splicing of a tissue-regulated alternative exon in a constituent of an oncogenic pathway eliminates tumor suppressor functions and promotes glioblastoma progression. This paradigm may offer a general model as to how tissue-specific regulatory mechanisms can reprogram normal developmental processes into oncogenic ones.

Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Dombrowski, Stephen M.; Miller, Tyler E.; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jurgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; von Elverfeldt, Dominik; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.; Bredel, Markus

2014-01-01

143

Understanding entangled cerebral networks: a prerequisite for restoring brain function with brain-computer interfaces  

PubMed Central

Historically, cerebral processing has been conceptualized as a framework based on statically localized functions. However, a growing amount of evidence supports a hodotopical (delocalized) and flexible organization. A number of studies have reported absence of a permanent neurological deficit after massive surgical resections of eloquent brain tissue. These results highlight the tremendous plastic potential of the brain. Understanding anatomo-functional correlates underlying this cerebral reorganization is a prerequisite to restore brain functions through brain-computer interfaces (BCIs) in patients with cerebral diseases, or even to potentiate brain functions in healthy individuals. Here, we review current knowledge of neural networks that could be utilized in the BCIs that enable movements and language. To this end, intraoperative electrical stimulation in awake patients provides valuable information on the cerebral functional maps, their connectomics and plasticity. Overall, these studies indicate that the complex cerebral circuitry that underpins interactions between action, cognition and behavior should be throughly investigated before progress in BCI approaches can be achieved.

Mandonnet, Emmanuel; Duffau, Hugues

2014-01-01

144

Network Analysis of Intrinsic Functional Brain Connectivity in Alzheimer's Disease  

Microsoft Academic Search

Functional brain networks detected in task-free (''resting-state'') functional magnetic resonance imaging (fMRI) have a small- world architecture that reflects a robust functional organization of the brain. Here, we examined whether this functional organization is disrupted in Alzheimer's disease (AD). Task-free fMRI data from 21 AD subjects and 18 age-matched controls were obtained. Wavelet analysis was applied to the fMRI data

Kaustubh Supekar; Vinod Menon; Daniel Rubin; Mark Musen; Michael D. Greicius

2008-01-01

145

Partial correlation for functional brain interactivity investigation in functional MRI.  

PubMed

Examination of functional interactions through effective connectivity requires the determination of three distinct levels of information: (1) the regions involved in the process and forming the spatial support of the network, (2) the presence or absence of interactions between each pair of regions, and (3) the directionality of the existing interactions. While many methods exist to select regions (Step 1), very little is available to complete Step 2. The two main methods developed so far, structural equation modeling (SEM) and dynamical causal modeling (DCM), usually require precise prior information to be used, while such information is sometimes lacking. Assuming that Step 1 was successfully completed, we here propose a data-driven method to deal with Step 2 and extract functional interactions from fMRI datasets through partial correlations. Partial correlation is more closely related to effective connectivity than marginal correlation and provides a convenient graphical representation for functional interactions. As an instance of brain interactivity investigation, we consider how simple hand movements are processed by the bihemispheric cortical motor network. In the proposed framework, Bayesian analysis makes it possible to estimate and test the partial statistical dependencies between regions without any prior model on the underlying functional interactions. We demonstrate the interest of this approach on real data. PMID:16777436

Marrelec, Guillaume; Krainik, Alexandre; Duffau, Hugues; Pélégrini-Issac, Mélanie; Lehéricy, Stéphane; Doyon, Julien; Benali, Habib

2006-08-01

146

Angiogenesis, neurogenesis and brain recovery of function following injury  

PubMed Central

Traumatic brain injury and stroke are major causes of mortality and morbidity worldwide. Unfortunately, almost all phase-III neuroprotective clinical trials for stroke and traumatic brain injury have shown no benefits; this has raised concerns regarding neuroprotective strategy alone as a therapy for acute brain injuries. There is therefore a compelling need to develop treatments that promote the repair and regeneration of injured brain tissue and functional recovery. Recent findings suggest that strategies to enhance angiogenesis and neurogenesis for brain injuries may provide promising opportunities to improve clinical outcomes during brain functional recovery. This article reviews current data on angiogenesis and neurogenesis in the adult brain after stroke and traumatic brain injury. Select cell-based and pharmacological therapies that promote angiogenesis and neurogenesis designed to restore neurological function after brain injuries are described. These findings highlight the need for a better understanding of injury- and therapy-induced angiogenesis and neurogenesis in the adult and suggest that the manipulation of endogenous neural precursors and endothelial cells is a potential therapy for brain injury.

Xiong, Ye; Mahmood, Asim; Chopp, Michael

2010-01-01

147

Symbolic functional vector generation for VHDL specifications  

Microsoft Academic Search

Verification of the functional correctness of VHDL specificationsis one of the primary and most time consumingtask of design. However, it must necessarily be an incompletetask since it is impossible to completely exercisethe specification by exhaustively applying all input patterns.The paper aims at presenting a two-step strategy based onsymbolic analysis of the VHDL specification, using a behavioralfault model. First, we generate

Fabrizio Ferrandi; Franco Fummi; Luca Gerli; Donatella Sciuto

1999-01-01

148

Comparison of Swallowing Functions Between Brain Tumor and Stroke Patients  

PubMed Central

Objective To compare the swallowing functions according to the lesion locations between brain tumor and stroke patients. Methods Forty brain tumor patients and the same number of age-, lesion-, and functional status-matching stroke patients were enrolled in this study. Before beginning the swallowing therapy, swallowing function was evaluated in all subjects by videofluoroscopic swallowing study. Brain lesions were classified as either supratentorial or in-fratentorial. We evaluated the following: the American Speech-Language-Hearing Association (ASHA) National Outcome Measurement System (NOMS) swallowing scale, clinical dysphagia scale, functional dysphagia scale (FDS), penetration-aspiration scale (PAS), oral transit time, pharyngeal transit time, the presence of vallecular pouch residue, pyriform sinus residue, laryngopharyngeal incoordination, premature spillage, a decreased swal-lowing reflex, pneumonia, and the feeding method at discharge. Results The incidence of dysphagia was similar in brain tumor and stroke patients. There were no differences in the results of the various swallowing scales and other parameters between the two groups. When compared brain tumor patients with supratentorial lesions, brain tumor patients with infratentorial lesions showed higher propor-tion of dysphagia (p=0.01), residue (p<0.01), FDS (p<0.01), PAS (p<0.01), and lower ASHA NOMS (p=0.02) at initial evaluation. However, there was no significant difference for the swallowing functions between benign and malig-nant brain tumor patients. Conclusion Swallowing function of brain tumor patients was not different from that of stroke patients according to matching age, location of lesion, and functional status. Similar to the stroke patients, brain tumor patients with infratentorial lesions present poor swallowing functions. However, the type of brain tumor as malignancy does not influence swallowing functions.

Park, Dae Hwan; Lee, Sook Joung; Song, Yoon Bum

2013-01-01

149

Decoding Lifespan Changes of the Human Brain Using Resting-State Functional Connectivity MRI  

PubMed Central

The development of large-scale functional brain networks is a complex, lifelong process that can be investigated using resting-state functional connectivity MRI (rs-fcMRI). In this study, we aimed to decode the developmental dynamics of the whole-brain functional network in seven decades (8–79 years) of the human lifespan. We first used parametric curve fitting to examine linear and nonlinear age effect on the resting human brain, and then combined manifold learning and support vector machine methods to predict individuals' “brain ages” from rs-fcMRI data. We found that age-related changes in interregional functional connectivity exhibited spatially and temporally specific patterns. During brain development from childhood to senescence, functional connections tended to linearly increase in the emotion system and decrease in the sensorimotor system; while quadratic trajectories were observed in functional connections related to higher-order cognitive functions. The complex patterns of age effect on the whole-brain functional network could be effectively represented by a low-dimensional, nonlinear manifold embedded in the functional connectivity space, which uncovered the inherent structure of brain maturation and aging. Regression of manifold coordinates with age further showed that the manifold representation extracted sufficient information from rs-fcMRI data to make prediction about individual brains' functional development levels. Our study not only gives insights into the neural substrates that underlie behavioral and cognitive changes over age, but also provides a possible way to quantitatively describe the typical and atypical developmental progression of human brain function using rs-fcMRI.

Wang, Lubin; Su, Longfei; Shen, Hui; Hu, Dewen

2012-01-01

150

Knockdown of brain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis  

PubMed Central

Depression has been associated with reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. In addition, animal studies suggest an association between reduced hippocampal neurogenesis and depressive-like behavior. These associations were predominantly established based on responses to antidepressant drugs and alterations in BDNF levels and neurogenesis in depressive patients or animal models for depressive behavior. Nevertheless, there is no direct evidence that the actual reduction of the BDNF protein in specific brain sites can induce depressive-like behaviors or affect neurogenesis in vivo. Using BDNF knockdown by RNA interference and lentiviral vectors injected into specific subregions of the hippocampus we show that a reduction in BDNF expression in the dentate gyrus, but not the CA3, reduces neurogenesis and affects behaviors associated with depression. Moreover, we show that BDNF has a critical function in neuronal differentiation, but not proliferation in vivo. Finally, we found that a specific BDNF knockdown in the ventral subiculum induces anhedonic-like behavior. These findings provide substantial support for the neurotrophic hypothesis of depression and specify anatomical and neurochemical targets for potential antidepressant interventions. Moreover, the specific effect of BDNF reduction on neuronal differentiation has broader implications for the study of neurodevelopment and neurodegenerative diseases.

Taliaz, D; Stall, N; Dar, D E; Zangen, A

2009-01-01

151

Regional brain atrophy development is related to specific aspects of clinical dysfunction in multiple sclerosis.  

PubMed

Brain atrophy in multiple sclerosis (MS) is thought to reflect irreversible tissue damage leading to persistent clinical deficit. Little is known about the rate of atrophy in specific brain regions in relation to specific clinical deficits. We determined the displacement of the brain surface between two T1-weighted MRI images obtained at baseline and after a median follow-up time of 2.2 years for 79 recently diagnosed, mildly disabled MS patients. Voxel- and cluster-wise permutation-based statistics were used to identify brain regions in which atrophy development was significantly related to Expanded Disability Status Scale (EDSS), Timed Walk Test (TWT), Paced Auditory Serial Addition Test (PASAT) and 9-Hole Peg Test (HPT). Clusters were considered significant at a corrected cluster-wise p-value of 0.05. Worse EDSS change-score and worse follow-up EDSS were related to atrophy development of periventricular and brainstem regions and right-sided parietal, occipital and temporal regions. Worse PASAT at follow-up was significantly related to atrophy of the ventricles. A worse TWT change-score and worse follow-up TWT were exclusively related to atrophy around the ventricles and of the brainstem. Worse HPT change-score and worse follow-up HPT of either arm were significantly related to the atrophy of widely distributed peripheral regions, as well as atrophy of periventricular and brainstem regions. Our findings suggest that decline in ambulatory function is related to atrophy of central brain regions exclusively, whereas decline in neurologically more complex tasks for coordinated hand function is related to atrophy of both central and peripheral brain regions. PMID:17889567

Jasperse, Bas; Vrenken, Hugo; Sanz-Arigita, Ernesto; de Groot, Vincent; Smith, Stephen M; Polman, Chris H; Barkhof, Frederik

2007-11-15

152

State-related functional integration and functional segregation brain networks in schizophrenia.  

PubMed

Altered topological properties of brain connectivity networks have emerged as important features of schizophrenia. The aim of this study was to investigate how the state-related modulations to graph measures of functional integration and functional segregation brain networks are disrupted in schizophrenia. Firstly, resting state and auditory oddball discrimination (AOD) fMRI data of healthy controls (HCs) and schizophrenia patients (SZs) were decomposed into spatially independent components (ICs) by group independent component analysis (ICA). Then, weighted positive and negative functional integration (inter-component networks) and functional segregation (intra-component networks) brain networks were built in each subject. Subsequently, connectivity strength, clustering coefficient, and global efficiency of all brain networks were statistically compared between groups (HCs and SZs) in each state and between states (rest and AOD) within group. We found that graph measures of negative functional integration brain network and several positive functional segregation brain networks were altered in schizophrenia during AOD task. The metrics of positive functional integration brain network and one positive functional segregation brain network were higher during the resting state than during the AOD task only in HCs. These findings imply that state-related characteristics of both functional integration and functional segregation brain networks are impaired in schizophrenia which provides new insight into the altered brain performance in this brain disorder. PMID:24094882

Yu, Qingbao; Sui, Jing; Kiehl, Kent A; Pearlson, Godfrey; Calhoun, Vince D

2013-11-01

153

NMDA receptor function, memory, and brain aging  

PubMed Central

An increasing level of N-methyl-D-aspartate (NMDA) receptor hypofunction within the brain is associated with memory and learning impairments, with psychosis, and ultimately with excitotoxic brain injury. As the brain ages, the NMDA receptor system becomes progressively hypofunctional, contributing to decreases in memory and learning performance. In those individuals destined to develop Alzheimer's disease, other abnormalities (eg, amyloidopathy and oxidative stress) interact to increase the NMDA receptor hypofunction (NRHypo) burden. In these vulnerable individuals, the brain then enters into a severe and persistent NRHypo state, which can lead to widespread neurodegeneration with accompanying mental symptoms and further cognitive deterioration. If the hypotheses described herein prove correct, treatment implications may be considerable. Pharmacological methods for preventing the overstimulation of vulnerable corticolimbic pyramidal neurons developed in an animal model may be applicable to the prevention and treatment of Alzheimer's disease.

Newcomer, John W.; Farber, Nuri B.; Olney, John W.

2000-01-01

154

The connected brain  

Microsoft Academic Search

The connected brain Martijn van den Heuvel, 2009 Our brain is a network. It is a network of different brain regions that are all functionally and structurally linked to each other. In the past decades, neuroimaging studies have provided a lot of information about the specific functions of each separate brain region, but how functional communication between brain regions is

M. P. van den Heuvel

2009-01-01

155

Functional specializations for music processing in the human newborn brain  

PubMed Central

In adults, specific neural systems with right-hemispheric weighting are necessary to process pitch, melody, and harmony as well as structure and meaning emerging from musical sequences. It is not known to what extent the specialization of these systems results from long-term exposure to music or from neurobiological constraints. One way to address this question is to examine how these systems function at birth, when auditory experience is minimal. We used functional MRI to measure brain activity in 1- to 3-day-old newborns while they heard excerpts of Western tonal music and altered versions of the same excerpts. Altered versions either included changes of the tonal key or were permanently dissonant. Music evoked predominantly right-hemispheric activations in primary and higher order auditory cortex. During presentation of the altered excerpts, hemodynamic responses were significantly reduced in the rig1ht auditory cortex, and activations emerged in the left inferior frontal cortex and limbic structures. These results demonstrate that the infant brain shows a hemispheric specialization in processing music as early as the first postnatal hours. Results also indicate that the neural architecture underlying music processing in newborns is sensitive to changes in tonal key as well as to differences in consonance and dissonance.

Perani, Daniela; Saccuman, Maria Cristina; Scifo, Paola; Spada, Danilo; Andreolli, Guido; Rovelli, Rosanna; Baldoli, Cristina; Koelsch, Stefan

2010-01-01

156

Specific trophic factor-receptor interactions. Key selective elements in brain development and "regeneration".  

PubMed

An hypothesis is presented which emphasizes the key role of specific trophic factor-receptor interactions in the development of the brain. We postulate that very early in development neurons become dependent on external factors (mainly neuropeptides) for guidance and survival. These requirements are the key to the selection process which results in the creation of a functional nervous system. These specific localized trophic factor requirements are postulated to persist throughout life. Disruptions in specific trophic factor-receptor systems are postulated to be responsible for a variety of age-related neurodegenerative diseases. The implications of recent animal and human transplant experiments in the context of the theoretical framework discussed above are profound. It would appear that the mature mammalian brain possesses an exquisite ability to regenerate specific connections to replace those lost due to death or injury to nerve cells. Unfortunately, it does not contain a population of undifferentiated stem cells to supply the necessary healthy neurons. The reason for this appears obvious based on the theoretical considerations given above, that the specific trophic factor-receptor interactions needed to produce a functional brain circuitry are necessarily stringently selective. Therefore, a significant stem cell population does not survive. However, if an appropriate stem cell population, ie, a fetal transplant, is provided, the brain will "heal itself" according to the program outlined above. In the future it may be technically feasible to perform genetic testing of newborns to determine to which genetic neurological diseases they are susceptible and at an appropriate time provide the appropriate fetal transplant. Obviously, society will have to deal with the profound ethical questions this technology will raise. PMID:2834427

Fine, R E; Rubin, J B

1988-05-01

157

Brain region-specific changes in oxidative stress and neurotrophin levels in autism spectrum disorders (ASD).  

PubMed

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by social and language deficits, stereotypic behavior, and abnormalities in motor functions. The particular set of behavioral impairments expressed in any given individual is variable across the spectrum. These behavioral abnormalities are consistent with our current understanding of the neuropathology of ASD which suggests abnormalities in the amygdala, temporal and frontal cortexes, hippocampus, and cerebellum. However, regions unrelated to these behavioral deficits appear largely intact. Both genetic predisposition and environmental toxins and toxicants have been implicated in the etiology of autism; the impact of these environmental triggers is associated with increases in oxidative stress, and is further exacerbated when combined with genetic susceptibility. We have previously reported increased levels of 3-nitrotyrosine (3-NT), a marker of oxidative stress, in ASD cerebella. We have also shown that this increase was associated with an elevation in neurotrophin-3 (NT-3) levels. The objectives of the current study were to determine whether the increase in oxidative stress in ASD is brain region-specific, to identify the specific brain regions affected by oxidative stress, and to compare brain region-specific NT-3 expression between ASD and control cases. The levels of 3-NT and NT-3 were measured with specific ELISAs in individual brain regions of two autistic and age- and postmortem interval (PMI)--matched control donors. In the control brain, the levels of 3-NT were uniformly low in all brain regions examined ranging from 1.6 to 12.0 pmol/g. On the other hand, there was a great variation in 3-NT levels between individual brain regions of the autistic brains ranging from 1.7 to 281.2 pmol/g. The particular brain regions with the increased 3-NT and the magnitude of the increase were both different in the two autistic cases. In the older autistic case, the brain regions with highest levels of 3-NT included the orbitofrontal cortex (214.5 pmol/g), Wernicke's area (171.7 pmol/g), cerebellar vermis (81.2 pmol/g), cerebellar hemisphere (37.2 pmol/g), and pons (13.6 pmol/g); these brain areas are associated with the speech processing, sensory and motor coordination, emotional and social behavior, and memory. Brain regions that showed 3-NT increase in both autistic cases included the cerebellar hemispheres and putamen. Consistent with our earlier report, we found an increase in NT-3 levels in the cerebellar hemisphere in both autistic cases. We also detected an increase in NT-3 level in the dorsolateral prefrontal cortex (BA46) in the older autistic case and in the Wernicke's area and cingulate gyrus in the younger case. These preliminary results reveal, for the first time, brain region-specific changes in oxidative stress marker 3-NT and neurotrophin-3 levels in ASD. PMID:20967576

Sajdel-Sulkowska, Elizabeth M; Xu, Ming; McGinnis, Woody; Koibuchi, Noriyuki

2011-03-01

158

Functional connectivity in the normal and injured brain.  

PubMed

The brain is neither uniform nor composed of similar modules but is rather a mosaic of different and highly interconnected regions. Accordingly, knowledge of functional connectivity between brain regions is crucial to understanding perception, cognition, and behavior. Functional connectivity methods estimate similarities between activity recorded in different regions of the brain. They are often applied to resting state activity, thus providing measures that are by nature task independent. The spatial patterns revealed by functional connectivity are not only shaped by the underlying anatomical structure of the brain but also partially depend on the history of task-driven coactivations. Inter-subject differences in functional connectivity may, at least to some degree, underlie variability observed in task performance across healthy subjects and in behavioral impairments in neurological patients. In this respect, recent studies have demonstrated that behavioral deficits in patients with brain injury are not only due to local tissue damage but also due to altered functional connectivity among structurally intact regions connected to the damaged site. Studies based on functional connectivity have the potential to advance basic understanding of how brain lesions induce neuropsychological syndromes. Furthermore, they may eventually suggest improved rehabilitation strategies for patients with brain injury, through the design of individualized treatment and recovery protocols. PMID:23064084

Gillebert, Céline R; Mantini, Dante

2013-10-01

159

Imaging emotional brain functions: Conceptual and methodological issues  

Microsoft Academic Search

This article reviews the psychophysiological and brain imaging literature on emotional brain function from a methodological point of view. The difficulties in defining, operationalising and measuring emotional activation and, in particular, aversive learning will be considered. Emotion is a response of the organism during an episode of major significance and involves physiological activation, motivational, perceptual, evaluative and learning processes, motor

Martin Peper

2006-01-01

160

From connections to function: the mouse brain connectome atlas.  

PubMed

Mapping synaptic connections and projections is crucial for understanding brain dynamics and function. In a recent issue of Nature, Oh et al. present a wiring diagram of the whole mouse brain, where standardized labeling, tracing, and imaging of axonal connections reveal new details in the network organization of neuronal connectivity. PMID:24813604

Sporns, Olaf; Bullmore, Edward T

2014-05-01

161

Magnetic resonance functional imaging of the brain at 4 t  

Microsoft Academic Search

Blood Oxygenation Level Dependent (BOLD) contrast imaging of human brain function using echo-planar imaging at 4 T gives good freedom from motion artifact, high signal-to-noise ratio\\/unit time, and adequate spatial resolution. Studies were made of brain activation associated with perceptual and cognitive tasks of several minutes duration.

P. Jezzard

1994-01-01

162

Mapping Functional Brain Development: Building a Social Brain Through Interactive Specialization  

Microsoft Academic Search

The authors review a viewpoint on human functional brain development, interactive specialization (IS), and its application to the emerging network of cortical regions referred to as the social brain. They advance the IS view in 2 new ways. First, they extend IS into a domain to which it has not previously been applied—the emergence of social cognition and mentalizing computations

Mark H. Johnson; Tobias Grossmann; Kathrin Cohen Kadosh

2009-01-01

163

Correlation between cognitive brain function and electrical brain activity in dementia of Alzheimer type  

Microsoft Academic Search

Summary Psychometric tests which assess cognitive brain function in dementia disorders are partly prone to artifacts, e.g., the experience of the investigator and the cooperation of the patient influences the results. An objective way to assess the degree of cognitive disturbance could be to measure neuronal activity represented by the electrical brain activity. The aim of the present study was

T. Dierks; L. Frölich; R. Ihl; K. Maurer

1995-01-01

164

Complex Networks - A Key to Understanding Brain Function  

ScienceCinema

The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life. How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood. In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

165

Complex Networks - A Key to Understanding Brain Function  

ScienceCinema

The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life.  How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood.  In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

Olaf Sporns

2010-01-08

166

Complex Networks - A Key to Understanding Brain Function  

SciTech Connect

The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life. How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood. In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

Sporns, Olaf (Indiana University) [Indiana University

2008-01-23

167

Generating Text from Functional Brain Images  

PubMed Central

Recent work has shown that it is possible to take brain images acquired during viewing of a scene and reconstruct an approximation of the scene from those images. Here we show that it is also possible to generate text about the mental content reflected in brain images. We began with images collected as participants read names of concrete items (e.g., “Apartment’’) while also seeing line drawings of the item named. We built a model of the mental semantic representation of concrete concepts from text data and learned to map aspects of such representation to patterns of activation in the corresponding brain image. In order to validate this mapping, without accessing information about the items viewed for left-out individual brain images, we were able to generate from each one a collection of semantically pertinent words (e.g., “door,” “window” for “Apartment’’). Furthermore, we show that the ability to generate such words allows us to perform a classification task and thus validate our method quantitatively.

Pereira, Francisco; Detre, Greg; Botvinick, Matthew

2011-01-01

168

Functional brain development in infants: elements of an interactive specialization framework.  

PubMed

One future direction for cognitive development research involves a closer integration with our knowledge about the developing brain. I present a framework for analyzing and interpreting postnatal functional brain development in human infants. Three specific hypotheses contribute to this framework, within which a variety of phenomena associated with the neural basis of perception and cognition in normal and abnormal development can be characterized. PMID:10836560

Johnson, M H

2000-01-01

169

Exploring memory functions by means of brain electrical topography: A review  

Microsoft Academic Search

Summary A series of experiments is reviewed which explored whether the functional brain state of long-term memory retrieval is correlated with specific changes in slow, DC-like event-related brain potentials. The main results are: (1) Retrieving associations from long-term memory is accompanied by a slow negative shift of 5–10 µV which prevails about as long as the retrieval process lasts, i.e.,

Frank Rösler; Martin Heil; Erwin Hennighausen

1995-01-01

170

Pattern Classification of Large-Scale Functional Brain Networks: Identification of Informative Neuroimaging Markers for Epilepsy  

PubMed Central

The accurate prediction of general neuropsychiatric disorders, on an individual basis, using resting-state functional magnetic resonance imaging (fMRI) is a challenging task of great clinical significance. Despite the progress to chart the differences between the healthy controls and patients at the group level, the pattern classification of functional brain networks across individuals is still less developed. In this paper we identify two novel neuroimaging measures that prove to be strongly predictive neuroimaging markers in pattern classification between healthy controls and general epileptic patients. These measures characterize two important aspects of the functional brain network in a quantitative manner: (i) coordinated operation among spatially distributed brain regions, and (ii) the asymmetry of bilaterally homologous brain regions, in terms of their global patterns of functional connectivity. This second measure offers a unique understanding of brain asymmetry at the network level, and, to the best of our knowledge, has not been previously used in pattern classification of functional brain networks. Using modern pattern-recognition approaches like sparse regression and support vector machine, we have achieved a cross-validated classification accuracy of 83.9% (specificity: 82.5%; sensitivity: 85%) across individuals from a large dataset consisting of 180 healthy controls and epileptic patients. We identified significantly changed functional pathways and subnetworks in epileptic patients that underlie the pathophysiological mechanism of the impaired cognitive functions. Specifically, we find that the asymmetry of brain operation for epileptic patients is markedly enhanced in temporal lobe and limbic system, in comparison with healthy individuals. The present study indicates that with specifically designed informative neuroimaging markers, resting-state fMRI can serve as a most promising tool for clinical diagnosis, and also shed light onto the physiology behind complex neuropsychiatric disorders. The systematic approaches we present here are expected to have wider applications in general neuropsychiatric disorders.

Zhang, ZhiQiang; Lu, WenLian; Lu, GuangMing; Feng, Jianfeng

2012-01-01

171

Cell type-specific genes show striking and distinct patterns of spatial expression in the mouse brain  

PubMed Central

To characterize gene expression patterns in the regional subdivisions of the mammalian brain, we integrated spatial gene expression patterns from the Allen Brain Atlas for the adult mouse with panels of cell type-specific genes for neurons, astrocytes, and oligodendrocytes from previously published transcriptome profiling experiments. We found that the combined spatial expression patterns of 170 neuron-specific transcripts revealed strikingly clear and symmetrical signatures for most of the brain’s major subdivisions. Moreover, the brain expression spatial signatures correspond to anatomical structures and may even reflect developmental ontogeny. Spatial expression profiles of astrocyte- and oligodendrocyte-specific genes also revealed regional differences; these defined fewer regions and were less distinct but still symmetrical in the coronal plane. Follow-up analysis suggested that region-based clustering of neuron-specific genes was related to (i) a combination of individual genes with restricted expression patterns, (ii) region-specific differences in the relative expression of functional groups of genes, and (iii) regional differences in neuronal density. Products from some of these neuron-specific genes are present in peripheral blood, raising the possibility that they could reflect the activities of disease- or injury-perturbed networks and collectively function as biomarkers for clinical disease diagnostics.

Ko, Younhee; Ament, Seth A.; Eddy, James A.; Caballero, Juan; Earls, John C.; Hood, Leroy; Price, Nathan D.

2013-01-01

172

Predicting regional neurodegeneration from the healthy brain functional connectome  

PubMed Central

Summary Neurodegenerative diseases target large-scale neural networks. Four competing mechanistic hypotheses have been proposed to explain network-based disease patterning: nodal stress, transneuronal spread, trophic failure, and shared vulnerability. Here, we used task-free fMRI to derive the healthy intrinsic connectivity patterns seeded by brain regions vulnerable to any of five distinct neurodegenerative diseases. These data enabled us to investigate how intrinsic connectivity in health predicts region-by-region vulnerability to disease. For each illness, specific regions emerged as critical network “epicenters” whose normal connectivity profiles most resembled the disease-associated atrophy pattern. Graph theoretical analyses in healthy subjects revealed that regions with higher total connectional flow and, more consistently, shorter functional paths to the epicenters, showed greater disease-related vulnerability. These findings best fit a transneuronal spread model of network-based vulnerability. Molecular pathological approaches may help clarify what makes each epicenter vulnerable to its targeting disease and how toxic protein species travel between networked brain structures.

Zhou, Juan; Gennatas, Efstathios D.; Kramer, Joel H.; Miller, Bruce L.; Seeley, William W.

2012-01-01

173

Memory Networks in Tinnitus: A Functional Brain Image Study  

PubMed Central

Tinnitus is characterized by the perception of sound in the absence of an external auditory stimulus. The network connectivity of auditory and non-auditory brain structures associated with emotion, memory and attention are functionally altered in debilitating tinnitus. Current studies suggest that tinnitus results from neuroplastic changes in the frontal and limbic temporal regions. The objective of this study was to use Single-Photon Emission Computed Tomography (SPECT) to evaluate changes in the cerebral blood flow in tinnitus patients with normal hearing compared with healthy controls. Methods: Twenty tinnitus patients with normal hearing and 17 healthy controls, matched for sex, age and years of education, were subjected to Single Photon Emission Computed Tomography using the radiotracer ethylenedicysteine diethyl ester, labeled with Technetium 99 m (99 mTc-ECD SPECT). The severity of tinnitus was assessed using the “Tinnitus Handicap Inventory” (THI). The images were processed and analyzed using “Statistical Parametric Mapping” (SPM8). Results: A significant increase in cerebral perfusion in the left parahippocampal gyrus (pFWE <0.05) was observed in patients with tinnitus compared with healthy controls. The average total THI score was 50.8+18.24, classified as moderate tinnitus. Conclusion: It was possible to identify significant changes in the limbic system of the brain perfusion in tinnitus patients with normal hearing, suggesting that central mechanisms, not specific to the auditory pathway, are involved in the pathophysiology of symptoms, even in the absence of clinically diagnosed peripheral changes.

Laureano, Maura Regina; Onishi, Ektor Tsuneo; Bressan, Rodrigo Affonseca; Castiglioni, Mario Luiz Vieira; Batista, Ilza Rosa; Reis, Marilia Alves; Garcia, Michele Vargas; de Andrade, Adriana Neves; de Almeida, Roberta Ribeiro; Garrido, Griselda J.; Jackowski, Andrea Parolin

2014-01-01

174

Selectionist and evolutionary approaches to brain function: a critical appraisal.  

PubMed

We consider approaches to brain dynamics and function that have been claimed to be Darwinian. These include Edelman's theory of neuronal group selection, Changeux's theory of synaptic selection and selective stabilization of pre-representations, Seung's Darwinian synapse, Loewenstein's synaptic melioration, Adam's selfish synapse, and Calvin's replicating activity patterns. Except for the last two, the proposed mechanisms are selectionist but not truly Darwinian, because no replicators with information transfer to copies and hereditary variation can be identified in them. All of them fit, however, a generalized selectionist framework conforming to the picture of Price's covariance formulation, which deliberately was not specific even to selection in biology, and therefore does not imply an algorithmic picture of biological evolution. Bayesian models and reinforcement learning are formally in agreement with selection dynamics. A classification of search algorithms is shown to include Darwinian replicators (evolutionary units with multiplication, heredity, and variability) as the most powerful mechanism for search in a sparsely occupied search space. Examples are given of cases where parallel competitive search with information transfer among the units is more efficient than search without information transfer between units. Finally, we review our recent attempts to construct and analyze simple models of true Darwinian evolutionary units in the brain in terms of connectivity and activity copying of neuronal groups. Although none of the proposed neuronal replicators include miraculous mechanisms, their identification remains a challenge but also a great promise. PMID:22557963

Fernando, Chrisantha; Szathmáry, Eörs; Husbands, Phil

2012-01-01

175

Human Brain Language Areas Identified by Functional Magnetic Resonance Imaging  

Microsoft Academic Search

Functional magnetic resonance imaging (FMRI) was used to identify candidate language processing areas in the intact hu- man brain. Language was defined broadly to include both phonological and lexical-semantic functions and to exclude sensory, motor, and general executive functions. The language activation task required phonetic and semantic analysis of aurally presented words and was compared with a control task involving

Jeffrey R. Binder; Julie A. Frost; Thomas A. Hammeke; Robert W. Cox; Stephen M. Rao; Thomas Prieto

1997-01-01

176

Quetiapine modulates functional connectivity in brain aggression networks.  

PubMed

Aggressive behavior is associated with dysfunctions in an affective regulation network encompassing amygdala and prefrontal areas such as orbitofrontal (OFC), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC). In particular, prefrontal regions have been postulated to control amygdala activity by inhibitory projections, and this process may be disrupted in aggressive individuals. The atypical antipsychotic quetiapine successfully attenuates aggressive behavior in various disorders; the underlying neural processes, however, are unknown. A strengthened functional coupling in the prefrontal-amygdala system may account for these anti-aggressive effects. An inhibition of this network has been reported for virtual aggression in violent video games as well. However, there have been so far no in-vivo observations of pharmacological influences on corticolimbic projections during human aggressive behavior. In a double-blind, placebo-controlled study, quetiapine and placebo were administered for three successive days prior to an fMRI experiment. In this experiment, functional brain connectivity was assessed during virtual aggressive behavior in a violent video game and an aggression-free control task in a non-violent modification. Quetiapine increased the functional connectivity of ACC and DLPFC with the amygdala during virtual aggression, whereas OFC-amygdala coupling was attenuated. These effects were observed neither for placebo nor for the non-violent control. These results demonstrate for the first time a pharmacological modification of aggression-related human brain networks in a naturalistic setting. The violence-specific modulation of prefrontal-amygdala networks appears to control aggressive behavior and provides a neurobiological model for the anti-aggressive effects of quetiapine. PMID:23501053

Klasen, Martin; Zvyagintsev, Mikhail; Schwenzer, Michael; Mathiak, Krystyna A; Sarkheil, Pegah; Weber, René; Mathiak, Klaus

2013-07-15

177

Functional Geometry Alignment and Localization of Brain Areas  

PubMed Central

Matching functional brain regions across individuals is a challenging task, largely due to the variability in their location and extent. It is particularly difficult, but highly relevant, for patients with pathologies such as brain tumors, which can cause substantial reorganization of functional systems. In such cases spatial registration based on anatomical data is only of limited value if the goal is to establish correspondences of functional areas among different individuals, or to localize potentially displaced active regions. Rather than rely on spatial alignment, we propose to perform registration in an alternative space whose geometry is governed by the functional interaction patterns in the brain. We first embed each brain into a functional map that reflects connectivity patterns during a fMRI experiment. The resulting functional maps are then registered, and the obtained correspondences are propagated back to the two brains. In application to a language fMRI experiment, our preliminary results suggest that the proposed method yields improved functional correspondences across subjects. This advantage is pronounced for subjects with tumors that affect the language areas and thus cause spatial reorganization of the functional regions.

Langs, Georg; Golland, Polina; Tie, Yanmei; Rigolo, Laura; Golby, Alexandra J.

2011-01-01

178

Magnetic Resonance Imaging Mapping of Brain Function Human Visual Cortex  

PubMed Central

Belliveau JW, Kwong KK, Kennedy DN, Baker JR, Stern CE, Benson R, Chesler DA, Weisskoff RM, Cohen MS, Tootell RBH, Fox PT, Brady TJ, Rosen BR. Magnetic resonance imaging mapping of brain function: human visual cortex. Invest Radiol 1992;27:SS9–S65. Magnetic resonance imaging (MRI) studies of human brain activity are described. Task-induced changes in brain cognitive state were measured using high-speed MRI techniques sensitive to changes in cerebral blood volume (CBV), blood flow (CBF), and blood oxygenation. These techniques were used to generate the first functional MRI maps of human task activation, by using a visual stimulus paradigm. The methodology of MRI brain mapping and results from the investigation of the functional organization and frequency response of human primary visual cortex (Vl) are presented.

BELLIVEAU, J.W.; KWONG, K.K.; KENNEDY, D.N.; BAKER, J.R.; STERN, C.E.; BENSON, R.; CHESLER, D.A.; WEISSKOFF, R.M.; COHEN, M.S.; TOOTELL, R.B.H.; FOX, P.T.; BRADY, T.J.; ROSEN, B.R.

2014-01-01

179

Brain function decoding process and system  

US Patent & Trademark Office Database

A method of interpreting cognitive response to a stimulus is disclosed. The method includes collecting baseline neural activity data from a subject absent a stimulus. Neural activity data is collected while the subject is being stimulated through exposure to a stimulus. A unique three-dimensional cognitive engram is then plotted representative of cerebral regions of stimulated neural activity caused by the stimulus. A novel graphical representation is plotted in three dimensions to indicate the brain region response unique to that stimulus.

2009-12-01

180

Hormones, Brain Plasticity and Reproductive Functions  

Microsoft Academic Search

The magnocellular oxytocin system of the hypothalamus illustrates remarkably well activity-dependent structural plasticity\\u000a in the adult brain. Its neurons secrete the neurohormone oxytocin, which plays a key role in the initiation of parturition\\u000a and maintenance of lactation. The somata and dendrites of oxytocin neurons accumulate in the supraoptic and paraventricular\\u000a nuclei of the hypothalamus whereas their axons project to the

Dionysia T. Theodosis

181

Region-specific protein abundance changes in the brain of MPTP-induced Parkinson's disease mouse model.  

PubMed

Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration in the nigrostriatal region of the brain; however, the neurodegeneration extends well beyond dopaminergic neurons. To gain a better understanding of the molecular changes relevant to PD, we applied two-dimensional LC-MS/MS to comparatively analyze the proteome changes in four brain regions (striatum, cerebellum, cortex, and the rest of brain) using a MPTP-induced PD mouse model with the objective to identify potential nigrostriatal-specific and other region-specific protein abundance changes. The combined analyses resulted in the identification of 4,895 nonredundant proteins with at least two unique peptides per protein. The relative abundance changes in each analyzed brain region were estimated based on the spectral count information. A total of 518 proteins were observed with substantial MPTP-induced abundance changes across different brain regions. A total of 270 of these proteins were observed with specific changes occurring either only in the striatum and/or in the rest of the brain region that contains substantia nigra, suggesting that these proteins are associated with the underlying nigrostriatal pathways. Many of the proteins that exhibit changes were associated with dopamine signaling, mitochondrial dysfunction, the ubiquitin system, calcium signaling, the oxidative stress response, and apoptosis. A set of proteins with either consistent change across all brain regions or with changes specific to the cortex and cerebellum regions were also detected. Ubiquitin specific protease (USP9X), a deubiquination enzyme involved in the protection of proteins from degradation and promotion of the TGF-beta pathway, exhibited altered abundance in all brain regions. Western blot validation showed similar spatial changes, suggesting that USP9X is potentially associated with neurodegeneration. Together, this study for the first time presents an overall picture of proteome changes underlying both nigrostriatal pathways and other brain regions potentially involved in MPTP-induced neurodegeneration. The observed molecular changes provide a valuable reference resource for future hypothesis-driven functional studies of PD. PMID:20155936

Zhang, Xu; Zhou, Jian-Ying; Chin, Mark H; Schepmoes, Athena A; Petyuk, Vladislav A; Weitz, Karl K; Petritis, Brianne O; Monroe, Matthew E; Camp, David G; Wood, Stephen A; Melega, William P; Bigelow, Diana J; Smith, Desmond J; Qian, Wei-Jun; Smith, Richard D

2010-03-01

182

Changes in functional brain organization and behavioral correlations after rehabilitative therapy using a brain-computer interface  

PubMed Central

This study aims to examine the changes in task-related brain activity induced by rehabilitative therapy using brain-computer interface (BCI) technologies and whether these changes are relevant to functional gains achieved through the use of these therapies. Stroke patients with persistent upper-extremity motor deficits received interventional rehabilitation therapy using a closed-loop neurofeedback BCI device (n = 8) or no therapy (n = 6). Behavioral assessments using the Stroke Impact Scale, the Action Research Arm Test (ARAT), and the Nine-Hole Peg Test (9-HPT) as well as task-based fMRI scans were conducted before, during, after, and 1 month after therapy administration or at analogous intervals in the absence of therapy. Laterality Index (LI) values during finger tapping of each hand were calculated for each time point and assessed for correlation with behavioral outcomes. Brain activity during finger tapping of each hand shifted over the course of BCI therapy, but not in the absence of therapy, to greater involvement of the non-lesioned hemisphere (and lesser involvement of the stroke-lesioned hemisphere) as measured by LI. Moreover, changes from baseline LI values during finger tapping of the impaired hand were correlated with gains in both objective and subjective behavioral measures. These findings suggest that the administration of interventional BCI therapy can induce differential changes in brain activity patterns between the lesioned and non-lesioned hemispheres and that these brain changes are associated with changes in specific motor functions.

Young, Brittany M.; Nigogosyan, Zack; Walton, Leo M.; Song, Jie; Nair, Veena A.; Grogan, Scott W.; Tyler, Mitchell E.; Edwards, Dorothy F.; Caldera, Kristin; Sattin, Justin A.; Williams, Justin C.; Prabhakaran, Vivek

2014-01-01

183

Functional abnormalities in normally appearing athletes following mild traumatic brain injury: a functional MRI study  

PubMed Central

Memory problems are one of the most common symptoms of sport-related mild traumatic brain injury (MTBI), known as concussion. Surprisingly, little research has examined spatial memory in concussed athletes given its importance in athletic environments. Here, we combine functional magnetic resonance imaging (fMRI) with a virtual reality (VR) paradigm designed to investigate the possibility of residual functional deficits in recently concussed but asymptomatic individuals. Specifically, we report performance of spatial memory navigation tasks in a VR environment and fMRI data in 15 athletes suffering from MTBI and 15 neurologically normal, athletically active age matched controls. No differences in performance were observed between these two groups of subjects in terms of success rate (94 and 92%) and time to complete the spatial memory navigation tasks (mean = 19.5 and 19.7 s). Whole brain analysis revealed that similar brain activation patterns were observed during both encoding and retrieval among the groups. However, concussed athletes showed larger cortical networks with additional increases in activity outside of the shared region of interest (ROI) during encoding. Quantitative analysis of blood oxygen level dependent (BOLD) signal revealed that concussed individuals had a significantly larger cluster size during encoding at parietal cortex, right dorsolateral prefrontal cortex, and right hippocampus. In addition, there was a significantly larger BOLD signal percent change at the right hippocampus. Neither cluster size nor BOLD signal percent change at shared ROIs was different between groups during retrieval. These major findings are discussed with respect to current hypotheses regarding the neural mechanism responsible for alteration of brain functions in a clinical setting.

Slobounov, Semyon M.; Zhang, K.; Pennell, D.; Ray, W.; Johnson, B.; Sebastianelli, W.

2010-01-01

184

Repetitive Transcranial Magnetic Stimulation Activates Specific Regions in Rat Brain  

Microsoft Academic Search

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS

Ru-Rong Ji; Carlos D. Aizenman; Charles M. Epstein; Dike Qiu; Justin C. Huang; Fabio Rupp

1998-01-01

185

ABCD: a functional database for the avian brain.  

PubMed

Here we present the first database developed for storing, retrieving and cross-referencing neuroscience information about the connectivity of the avian brain. The Avian Brain Circuitry Database (ABCD) contains entries about the new and old terminology of the areas and their hierarchy, data on connections between brain regions, as well as a functional keyword system linked to brain regions and connections. Data were collected from the primary literature and textbooks, and an online submission system was developed to facilitate further data collection directly from researchers. The database aims to help spread the results of avian connectivity studies, the recently revised nomenclature and also to provide data for brain network research. ABCD is freely available at http://www.behav.org/abcd. PMID:17889371

Schrott, Aniko; Kabai, Peter

2008-01-30

186

Human brain functional MRI and DTI visualization with virtual reality.  

PubMed

Magnetic resonance diffusion tensor imaging (DTI) and functional MRI (fMRI) are two active research areas in neuroimaging. DTI is sensitive to the anisotropic diffusion of water exerted by its macromolecular environment and has been shown useful in characterizing structures of ordered tissues such as the brain white matter, myocardium, and cartilage. The diffusion tensor provides two new types of information of water diffusion: the magnitude and the spatial orientation of water diffusivity inside the tissue. This information has been used for white matter fiber tracking to review physical neuronal pathways inside the brain. Functional MRI measures brain activations using the hemodynamic response. The statistically derived activation map corresponds to human brain functional activities caused by neuronal activities. The combination of these two methods provides a new way to understand human brain from the anatomical neuronal fiber connectivity to functional activities between different brain regions. In this study, virtual reality (VR) based MR DTI and fMRI visualization with high resolution anatomical image segmentation and registration, ROI definition and neuronal white matter fiber tractography visualization and fMRI activation map integration is proposed. Rationale and methods for producing and distributing stereoscopic videos are also discussed. PMID:23256049

Chen, Bin; Moreland, John; Zhang, Jingyu

2011-12-01

187

Final Report on LDRD Project 130784: Functional Brain Imaging by Tunable Multi-Spectral Event-Related Optical Signal (EROS).  

National Technical Information Service (NTIS)

Functional brain imaging is of great interest for understanding correlations between specific cognitive processes and underlying neural activity. This understanding can provide the foundation for developing enhanced human-machine interfaces, decision aide...

A. E. Speed A. Y. C. Hsu O. B. Spahn

2009-01-01

188

Glucocorticoid-induction of hypothalamic aromatase via its brain-specific promoter  

PubMed Central

In the brain, a 36-kb distal promoter (I.f) regulates the Cyp19a1 gene that encodes aromatase, the key enzyme for estrogen biosynthesis. Local estrogen production in the brain regulates critical functions such as gonadotropin secretion and sexual behavior. The mechanisms that control brain aromatase production are not well understood. Here we show that the glucocorticoid dexamethasone robustly increases aromatase mRNA and protein by up to 98-fold in mouse hypothalamic cell lines in a dose- and time-dependent fashion. Using deletion mutants of the brain-specific promoter I.f and chromatin immunoprecipitation-PCR, we isolated a distinct region (?500/?200bp) which becomes enriched in bound glucocorticoid receptor upon dexamethasone stimulation. A glucocorticoid antagonist or siRNA based knockdown of glucocorticoid receptor ablated dexamethasone stimulation of aromatase expression. Our findings demonstrate how glucocorticoids alter aromatase expression in the hypothalamus and might indicate a mechanism whereby glucocorticoid action modifies gonadotropin pulses and the menstrual cycle.

Brooks, DC; Zhao, H; Yilmaz, B; Coon, VJS; Bulun, SE

2012-01-01

189

Functional community analysis of brain: A new approach for EEG-based investigation of the brain pathology  

Microsoft Academic Search

Analysis of structure of the brain functional connectivity (SBFC) is a fundamental issue for understanding of the brain cognition as well as the pathology of brain disorders. Analysis of communities among sub-parts of a system is increasingly used for social, ecological, and other networks. This paper presents a new methodology for investigation of the SBFC and understanding of the brain

Mehran Ahmadlou; Hojjat Adeli

2011-01-01

190

Magnetic resonance and the human brain: anatomy, function and metabolism.  

PubMed

The introduction and development, over the last three decades, of magnetic resonance (MR) imaging and MR spectroscopy technology for in vivo studies of the human brain represents a truly remarkable achievement, with enormous scientific and clinical ramifications. These effectively non-invasive techniques allow for studies of the anatomy, the function and the metabolism of the living human brain. They have allowed for new understandings of how the healthy brain works and have provided insights into the mechanisms underlying multiple disease processes which affect the brain. Different MR techniques have been developed for studying anatomy, function and metabolism. The primary focus of this review is to describe these different methodologies and to briefly review how they are being employed to more fully appreciate the intricacies associated with the organ, which most distinctly differentiates the human species from the other animal forms on earth. PMID:16568243

Talos, I-F; Mian, A Z; Zou, K H; Hsu, L; Goldberg-Zimring, D; Haker, S; Bhagwat, J G; Mulkern, R V

2006-05-01

191

Structural and functional organization of a developing brain and formation of cognitive functions in child ontogeny  

Microsoft Academic Search

Results of multidisciplinary studies, including neuromorphological, neurophysiological, neuropsychological, and psychphysiological\\u000a studies, are reviewed. They allow the brain mechanisms of cognition formation and development during maturation to be identified.\\u000a The role of regulatory (modulatory) brain systems in forming the cognitive function in the child is demonstrated. Data on\\u000a considerable changes in the brain systems responsible for the development of cognitive functions

M. M. Bezrukikh; R. I. Machinskaya; D. A. Farber

2009-01-01

192

Integrating the roles of long and small non-coding RNA in brain function and disease.  

PubMed

Regulatory RNA is emerging as the major architect of cognitive evolution and innovation in the mammalian brain. While the protein machinery has remained largely constant throughout animal evolution, the non protein-coding transcriptome has expanded considerably to provide essential and widespread cellular regulation, partly through directing generic protein function. Both long (long non-coding RNA) and small non-coding RNAs (for example, microRNA) have been demonstrated to be essential for brain development and higher cognitive abilities, and to be involved in psychiatric disease. Long non-coding RNAs, highly expressed in the brain and expanded in mammalian genomes, provide tissue- and activity-specific epigenetic and transcriptional regulation, partly through functional control of evolutionary conserved effector small RNA activity. However, increased cognitive sophistication has likely introduced concomitant psychiatric vulnerabilities, predisposing to conditions such as autism and schizophrenia, and cooperation between regulatory and effector RNAs may underlie neural complexity and concomitant fragility in the human brain. PMID:24468823

Barry, G

2014-04-01

193

Transforming Growth Factor-? in Brain Functions and Dysfunctions  

Microsoft Academic Search

Transforming growth factor-?s (TGF-?s) belong to a superfamily of related peptides that play pivotal roles in intercellular\\u000a communication. Among these biological agents, TGF-?1 has been involved in a number of brain functions and dysfunctions throughout\\u000a life, ranging from neurogenesis to neurodegeneration. Animal models mimicking some aspects of human brain pathologies have\\u000a led to the idea that TGF-? may be a

Denis Vivien; Karim Benchenane; Carine Ali

194

Investigating brain dynamics and connectivity with functional MRI  

Microsoft Academic Search

Functional magnetic resonance imaging (fMRI) scans provide a record of ongoing neural processing through the measurement of changes in regional levels of blood oxygenation. While subjects are resting, fMRI has revealed networks of brain regions exhibiting synchronised 0.02-0.12 Hz fluctuations in spontaneous, low frequency brain activity. The physiology underlying these 'resting state' fluctuations is poorly understood. Our current research investigates

Eugene Duff; Gary Egan; Ross Cunnington; Iven Mareels; Binquan Wang; Peter Fox; Jinhu Xiong

2004-01-01

195

The adolescent brain: Insights from functional neuroimaging research  

PubMed Central

With the development of functional neuroimaging tools, the past two decades have witnessed an explosion of work examining functional brain maps, mostly in the adult brain. Against this backdrop of work in adults, developmental research begins to gather a substantial body of knowledge about brain maturation. The purpose of this review is to present some of these findings from the perspective of functional neuroimaging. First, a brief survey of available neuroimaging techniques (i.e., fMRI, MRS, MEG, PET, SPECT, and infrared techniques) is provided. Next, the key cognitive, emotional, and social changes taking place during adolescence are outlined. The third section gives examples of how these behavioral changes can be understood from a neuroscience perspective. The conclusion places this functional neuroimaging research in relation to clinical and molecular work, and shows how answers will ultimately come from the combined efforts of these disciplines.

Ernst, M.; Mueller, S.C.

2009-01-01

196

Functional Connectivity between Brain Areas Estimated by Analysis of Gamma Waves  

PubMed Central

The goal of this study is to investigate functional connectivity between different brain regions by analyzing the temporal relationship of the maxima of gamma waves recorded in multiple brain areas. Local field potentials were recorded from motor cortex, hippocampus, entorhinal cortex and piriform cortex of rats. Gamma activity was filtered and separated into two bands; high (65–90Hz) and low (30–55Hz) gamma. Maxima for gamma activity waves were detected and functional connectivity between different brain regions was determined using Shannon entropy for perievent histograms for each pair channels. Significant Shannon entropy values were reported as connectivity factors. We defined a connectivity matrix based the connectivity factors between different regions. We found that maxima of low and high frequency gamma occur in strong temporal relationship between some brain areas, indicating the existence of functional connections between these areas. The spatial pattern of functional connections between brain areas was different for slow wave sleep and waking states. However for each behavioral state in the same animal the pattern of functional connections was stable over time within 30 minutes of continuous analysis and over a 5 day period. With the same electrode montage the pattern of functional connectivity varied from one subject to another. Analysis of the temporal relationship of maxima of gamma waves between various brain areas could be a useful tool for investigation of functional connections between these brain areas. This approach could be applied for analysis of functional alterations occurring in these connections during different behavioral tasks and during processes related to learning and memory. The specificity in the connectivity pattern from one subject to another can be explained by the existence of unique functional networks for each subject.

Kheiri, Farshad; Bragin, Anatol; Engel, Jerome

2013-01-01

197

Functional brain connectivity using fMRI in aging and Alzheimer's disease.  

PubMed

Normal aging and Alzheimer's disease (AD) cause profound changes in the brain's structure and function. AD in particular is accompanied by widespread cortical neuronal loss, and loss of connections between brain systems. This degeneration of neural pathways disrupts the functional coherence of brain activation. Recent innovations in brain imaging have detected characteristic disruptions in functional networks. Here we review studies examining changes in functional connectivity, measured through fMRI (functional magnetic resonance imaging), starting with healthy aging and then Alzheimer's disease. We cover studies that employ the three primary methods to analyze functional connectivity--seed-based, ICA (independent components analysis), and graph theory. At the end we include a brief discussion of other methodologies, such as EEG (electroencephalography), MEG (magnetoencephalography), and PET (positron emission tomography). We also describe multi-modal studies that combine rsfMRI (resting state fMRI) with PET imaging, as well as studies examining the effects of medications. Overall, connectivity and network integrity appear to decrease in healthy aging, but this decrease is accelerated in AD, with specific systems hit hardest, such as the default mode network (DMN). Functional connectivity is a relatively new topic of research, but it holds great promise in revealing how brain network dynamics change across the lifespan and in disease. PMID:24562737

Dennis, Emily L; Thompson, Paul M

2014-03-01

198

On imputing function to structure from the behavioural effects of brain lesions.  

PubMed Central

What is the link, if any, between the patterns of connections in the brain and the behavioural effects of localized brain lesions? We explored this question in four related ways. First, we investigated the distribution of activity decrements that followed simulated damage to elements of the thalamocortical network, using integrative mechanisms that have recently been used to successfully relate connection data to information on the spread of activation, and to account simultaneously for a variety of lesion effects. Second, we examined the consequences of the patterns of decrement seen in the simulation for each type of inference that has been employed to impute function to structure on the basis of the effects of brain lesions. Every variety of conventional inference, including double dissociation, readily misattributed function to structure. Third, we tried to derive a more reliable framework of inference for imputing function to structure, by clarifying concepts of function, and exploring a more formal framework, in which knowledge of connectivity is necessary but insufficient, based on concepts capable of mathematical specification. Fourth, we applied this framework to inferences about function relating to a simple network that reproduces intact, lesioned and paradoxically restored orientating behaviour. Lesion effects could be used to recover detailed and reliable information on which structures contributed to particular functions in this simple network. Finally, we explored how the effects of brain lesions and this formal approach could be used in conjunction with information from multiple neuroscience methodologies to develop a practical and reliable approach to inferring the functional roles of brain structures.

Young, M P; Hilgetag, C C; Scannell, J W

2000-01-01

199

Functional magnetic resonance imaging (FMRI) of the human brain  

Microsoft Academic Search

Functional magnetic resonance imaging (FMRI) can provide detailed images of human brain that reflect localized changes in cerebral blood flow and oxygenation induced by sensory, motor, or cognitive tasks. This review presents methods for gradient-recalled echo-planar functional magnetic resonance imaging (FMRI). Also included is a discussion of the hypothesized basis of FMRI, imaging hardware, a unique visual stimulation apparatus, image

Edgar A. DeYoe; Peter Bandettini; Jay Neitz; David Miller; Paula Winans

1994-01-01

200

Resting-State Brain Organization Revealed by Functional Covariance Networks  

PubMed Central

Background Brain network studies using techniques of intrinsic connectivity network based on fMRI time series (TS-ICN) and structural covariance network (SCN) have mapped out functional and structural organization of human brain at respective time scales. However, there lacks a meso-time-scale network to bridge the ICN and SCN and get insights of brain functional organization. Methodology and Principal Findings We proposed a functional covariance network (FCN) method by measuring the covariance of amplitude of low-frequency fluctuations (ALFF) in BOLD signals across subjects, and compared the patterns of ALFF-FCNs with the TS-ICNs and SCNs by mapping the brain networks of default network, task-positive network and sensory networks. We demonstrated large overlap among FCNs, ICNs and SCNs and modular nature in FCNs and ICNs by using conjunctional analysis. Most interestingly, FCN analysis showed a network dichotomy consisting of anti-correlated high-level cognitive system and low-level perceptive system, which is a novel finding different from the ICN dichotomy consisting of the default-mode network and the task-positive network. Conclusion The current study proposed an ALFF-FCN approach to measure the interregional correlation of brain activity responding to short periods of state, and revealed novel organization patterns of resting-state brain activity from an intermediate time scale.

Wang, Zhengge; Yuan, Cuiping; Jiao, Qing; Chen, Huafu; Biswal, Bharat B.; Lu, Guangming; Liu, Yijun

2011-01-01

201

Functional imaging of dolphin brain metabolism and blood flow.  

PubMed

This report documents the first use of magnetic resonance images (MRIs) of living dolphins to register functional brain scans, allowing for the exploration of potential mechanisms of unihemispheric sleep. Diazepam has been shown to induce unihemispheric slow waves (USW), therefore we used functional imaging of dolphins with and without diazepam to observe hemispheric differences in brain metabolism and blood flow. MRIs were used to register functional brain scans with single photon emission computed tomography (SPECT) and positron emission tomography (PET) in trained dolphins. Scans using SPECT revealed unihemispheric blood flow reduction following diazepam doses greater than 0.55 mg kg(-1) for these 180-200 kg animals. Scans using PET revealed hemispheric differences in brain glucose consumption when scans with and without diazepam were compared. The findings suggest that unihemispheric reduction in blood flow and glucose metabolism in the hemisphere showing USW are important features of unihemispheric sleep. Functional scans may also help to elucidate the degree of hemispheric laterality of sensory and motor systems as well as in neurotransmitter or molecular mechanisms of unihemispheric sleep in delphinoid cetaceans. The findings also demonstrate the potential value of functional scans to explore other aspects of dolphin brain physiology as well as pathology. PMID:16857874

Ridgway, Sam; Houser, Dorian; Finneran, James; Carder, Don; Keogh, Mandy; Van Bonn, William; Smith, Cynthia; Scadeng, Miriam; Dubowitz, David; Mattrey, Robert; Hoh, Carl

2006-08-01

202

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

PubMed Central

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

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

2014-01-01

203

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

PubMed

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

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

2014-01-01

204

Functional MRI study of brain function under resting and activated states  

Microsoft Academic Search

Numerous magnetic resonance imaging (MRI) techniques have been developed with various imaging contrasts, which can be tightly linked to brain functions, electrophysiology and diseases. Recent MRI technology developments have resulted in several important functional MRI (fMRI) methods based on the blood oxygenation level dependent (BOLD) contrast. These fMRI methods have been applied to mapping brain activation in laminar level as

Wei Chen; Xiao Liu; Xiao-Hong Zhu; Nanyin Zhang

2009-01-01

205

Control of a specific motor program by a small brain area in zebrafish  

PubMed Central

Complex motor behaviors are thought to be coordinated by networks of brain nuclei that may control different elementary motor programs. Transparent zebrafish larvae offer the opportunity to analyze the functional organization of motor control networks by optical manipulations of neuronal activity during behavior. We examined motor behavior in transgenic larvae expressing channelrhodopsin-2 throughout many neurons in the brain. Wide-field optical stimulation triggered backward and rotating movements caused by the repeated execution of J-turns, a specific motor program that normally occurs during prey capture. Although optically-evoked activity was widespread, behavioral responses were highly coordinated and lateralized. 3-D mapping of behavioral responses to local optical stimuli revealed that J-turns can be triggered specifically in the anterior-ventral optic tectum (avOT) and/or the adjacent pretectum. These results suggest that the execution of J-turns is controlled by a small group of neurons in the midbrain that may act as a command center. The identification of a brain area controlling a defined motor program involved in prey capture is a step toward a comprehensive analysis of neuronal circuits mediating sensorimotor behaviors of zebrafish.

Fajardo, Otto; Zhu, Peixin; Friedrich, Rainer W.

2013-01-01

206

Altered host behaviour and brain serotonergic activity caused by acanthocephalans: evidence for specificity  

PubMed Central

Manipulative parasites can alter the phenotype of intermediate hosts in various ways. However, it is unclear whether such changes are just by-products of infection or adaptive and enhance transmission to the final host. Here, we show that the alteration of serotonergic activity is functionally linked to the alteration of specific behaviour in the amphipod Gammarus pulex infected with acanthocephalan parasites. Pomphorhynchus laevis and, to a lesser extent, Pomphorhynchus tereticollis altered phototactism, but not geotactism, in G. pulex, whereas the reverse was true for Polymorphus minutus. Serotonin (5-hydroxytryptamine, 5-HT) injected to uninfected G. pulex mimicked the altered phototactism, but had no effect on geotactism. Photophilic G. pulex infected with P. laevis or P. tereticollis showed a 40% increase in brain 5-HT immunoreactivity compared to photophobic, uninfected individuals. In contrast, brain 5-HT immunoreactivity did not differ between P. minutus-infected and uninfected G. pulex. Finally, brain 5-HT immunoreactivity differed significantly among P. tereticollis-infected individuals in accordance with their degree of manipulation. Our results demonstrate that altered 5-HT activity is not the mere consequence of infection by acanthocephalans but is specifically linked to the disruption of host photophobic behaviour, whereas the alteration of other behaviours such as geotactism may rely on distinct physiological routes.

Tain, Luke; Perrot-Minnot, Marie-Jeanne; Cezilly, Frank

2006-01-01

207

Inhaled anesthetics elicit region-specific changes in protein expression in mammalian brain.  

PubMed

Inhaled anesthetics bind specifically to many proteins in the mammalian brain. Within the subgroup of proteins whose activity is substantially modulated by anesthetic binding, it is reasonable to expect anesthetic-induced alterations in host expression level. Thus, in an attempt to define the group of functional targets for these commonly used drugs, we examined changes in protein expression after anesthetic exposure in both intact rodent brains and in neuronal cell culture. Differential in-gel electrophoresis was used to minimize variance, in order to detect small changes. Quantitative analysis shows that 5 h exposures to 1 minimum alveolar concentration (1 MAC) halothane caused changes in the expression of approximately 2% of detectable proteins, but only at 2-24 h after awakening, and only in the cortex. An equipotent concentration of isoflurane altered the expression of only approximately 1% of detectable proteins, and only in the hippocampus. Primary cortical neurons were exposed to three-fold higher concentrations of anesthetics with no evidence of cytotoxicity. Small changes in protein expression were elicited by both drugs. Despite the fact that anesthetics produce profound changes in neurobiology and behavior, we found only minor changes in brain protein expression. A pronounced degree of regional selectivity was noted, indicating an under appreciated degree of specificity for these promiscuous drugs. PMID:18655074

Pan, Jonathan Z; Xi, Jin; Eckenhoff, Maryellen F; Eckenhoff, Roderic G

2008-07-01

208

Stereotactic PET atlas of the human brain: Aid for visual interpretation of functional brain images  

SciTech Connect

In the routine analysis of functional brain images obtained by PET, subjective visual interpretation is often used for anatomic localization. To enhance the accuracy and consistency of the anatomic interpretation, a PET stereotactic atlas and localization approach was designed for functional brain images. The PET atlas was constructed from a high-resolution [{sup 18}F]fluorodeoxyglucose (FDG) image set of a normal volunteer (a 41-yr-ld woman). The image set was reoriented stereotactically, according to the intercommissural (anterior and posterior commissures) line and transformed to the standard stereotactic atlas coordinates. Cerebral structures were annotated on the transaxial planes using a proportional grid system and surface-rendered images. The stereotactic localization technique was applied to image sets from patients with Alzheimer`s disease, and areas of functional alteration were localized visually by referring to the PET atlas. Major brain structures were identified on both transaxial planes and surface-rendered images. In the stereotactic system, anatomic correspondence between the PET atlas and stereotactically reoriented individual image sets of patients with Alzheimer`s disease facilitated both indirect and direct localization of the cerebral structures. Because rapid stereotactic alignment methods for PET images are now available for routine use, the PET atlas will serve as an aid for visual interpretation of functional brain images in the stereotactic system. Widespread application of stereotactic localization may be used in functional brain images, not only in the research setting, but also in routine clinical situations. 41 refs., 3 figs.

Minoshima, S.; Koeppe, R.A.; Frey, A.; Ishihara, M.; Kuhl, D.E. [Univ. of Michigan, Ann Arbor, MI (United States)

1994-06-01

209

Democratic reinforcement: A principle for brain function  

SciTech Connect

We introduce a simple ``toy`` brain model. The model consists of a set of randomly connected, or layered integrate-and-fire neurons. Inputs to and outputs from the environment are connected randomly to subsets of neurons. The connections between firing neurons are strengthened or weakened according to whether the action was successful or not. Unlike previous reinforcement learning algorithms, the feedback from the environment is democratic: it affects all neurons in the same way, irrespective of their position in the network and independent of the output signal. Thus no unrealistic back propagation or other external computation is needed. This is accomplished by a global threshold regulation which allows the system to self-organize into a highly susceptible, possibly ``critical`` state with low activity and sparse connections between firing neurons. The low activity permits memory in quiescent areas to be conserved since only firing neurons are modified when new information is being taught.

Stassinopoulos, D.; Bak, P. [Brookhaven National Laboratory, Upton, New York 11973 (United States)] [Brookhaven National Laboratory, Upton, New York 11973 (United States)

1995-05-01

210

Functional Imaging of the Brain with exp 18 F-Fluorodeoxyglucose.  

National Technical Information Service (NTIS)

A techniques is reported by which it is possible to determine which regions of the human brain become functionally active in response to a specific stimulus. The method utilizes exp 18 F-2-fluoro-2-deoxyglucose (( exp 18 F)-FDG) administered as a bolus. (...

M. Reivich J. Greenberg A. Alavi P. Hand W. Rintelmann

1980-01-01

211

Brain region-specific expression of MeCP2 isoforms correlates with DNA methylation within Mecp2 regulatory elements.  

PubMed

MeCP2 is a critical epigenetic regulator in brain and its abnormal expression or compromised function leads to a spectrum of neurological disorders including Rett Syndrome and autism. Altered expression of the two MeCP2 isoforms, MeCP2E1 and MeCP2E2 has been implicated in neurological complications. However, expression, regulation and functions of the two isoforms are largely uncharacterized. Previously, we showed the role of MeCP2E1 in neuronal maturation and reported MeCP2E1 as the major protein isoform in the adult mouse brain, embryonic neurons and astrocytes. Recently, we showed that DNA methylation at the regulatory elements (REs) within the Mecp2 promoter and intron 1 impact the expression of Mecp2 isoforms in differentiating neural stem cells. This current study is aimed for a comparative analysis of temporal, regional and cell type-specific expression of MeCP2 isoforms in the developing and adult mouse brain. MeCP2E2 displayed a later expression onset than MeCP2E1 during mouse brain development. In the adult female and male brain hippocampus, both MeCP2 isoforms were detected in neurons, astrocytes and oligodendrocytes. Furthermore, MeCP2E1 expression was relatively uniform in different brain regions (olfactory bulb, striatum, cortex, hippocampus, thalamus, brainstem and cerebellum), whereas MeCP2E2 showed differential enrichment in these brain regions. Both MeCP2 isoforms showed relatively similar distribution in these brain regions, except for cerebellum. Lastly, a preferential correlation was observed between DNA methylation at specific CpG dinucleotides within the REs and Mecp2 isoform-specific expression in these brain regions. Taken together, we show that MeCP2 isoforms display differential expression patterns during brain development and in adult mouse brain regions. DNA methylation patterns at the Mecp2 REs may impact this differential expression of Mecp2/MeCP2 isoforms in brain regions. Our results significantly contribute towards characterizing the expression profiles of Mecp2/MeCP2 isoforms and thereby provide insights on the potential role of MeCP2 isoforms in the developing and adult brain. PMID:24594659

Olson, Carl O; Zachariah, Robby M; Ezeonwuka, Chinelo D; Liyanage, Vichithra R B; Rastegar, Mojgan

2014-01-01

212

Brain Region-Specific Expression of MeCP2 Isoforms Correlates with DNA Methylation within Mecp2 Regulatory Elements  

PubMed Central

MeCP2 is a critical epigenetic regulator in brain and its abnormal expression or compromised function leads to a spectrum of neurological disorders including Rett Syndrome and autism. Altered expression of the two MeCP2 isoforms, MeCP2E1 and MeCP2E2 has been implicated in neurological complications. However, expression, regulation and functions of the two isoforms are largely uncharacterized. Previously, we showed the role of MeCP2E1 in neuronal maturation and reported MeCP2E1 as the major protein isoform in the adult mouse brain, embryonic neurons and astrocytes. Recently, we showed that DNA methylation at the regulatory elements (REs) within the Mecp2 promoter and intron 1 impact the expression of Mecp2 isoforms in differentiating neural stem cells. This current study is aimed for a comparative analysis of temporal, regional and cell type-specific expression of MeCP2 isoforms in the developing and adult mouse brain. MeCP2E2 displayed a later expression onset than MeCP2E1 during mouse brain development. In the adult female and male brain hippocampus, both MeCP2 isoforms were detected in neurons, astrocytes and oligodendrocytes. Furthermore, MeCP2E1 expression was relatively uniform in different brain regions (olfactory bulb, striatum, cortex, hippocampus, thalamus, brainstem and cerebellum), whereas MeCP2E2 showed differential enrichment in these brain regions. Both MeCP2 isoforms showed relatively similar distribution in these brain regions, except for cerebellum. Lastly, a preferential correlation was observed between DNA methylation at specific CpG dinucleotides within the REs and Mecp2 isoform-specific expression in these brain regions. Taken together, we show that MeCP2 isoforms display differential expression patterns during brain development and in adult mouse brain regions. DNA methylation patterns at the Mecp2 REs may impact this differential expression of Mecp2/MeCP2 isoforms in brain regions. Our results significantly contribute towards characterizing the expression profiles of Mecp2/MeCP2 isoforms and thereby provide insights on the potential role of MeCP2 isoforms in the developing and adult brain.

Liyanage, Vichithra R. B.; Rastegar, Mojgan

2014-01-01

213

Rehabilitation of Executive Functioning in Patients with Frontal Lobe Brain Damage with Goal Management Training  

PubMed Central

Executive functioning deficits due to brain disease affecting frontal lobe functions cause significant real-life disability, yet solid evidence in support of executive functioning interventions is lacking. Goal Management Training (GMT), an executive functioning intervention that draws upon theories concerning goal processing and sustained attention, has received empirical support in studies of patients with traumatic brain injury, normal aging, and case studies. GMT promotes a mindful approach to complex real-life tasks that pose problems for patients with executive functioning deficits, with a main goal of periodically stopping ongoing behavior to monitor and adjust goals. In this controlled trial, an expanded version of GMT was compared to an alternative intervention, Brain Health Workshop that was matched to GMT on non-specific characteristics that can affect intervention outcome. Participants included 19 individuals in the chronic phase of recovery from brain disease (predominantly stroke) affecting frontal lobe function. Outcome data indicated specific effects of GMT on the Sustained Attention to Response Task as well as the Tower Test, a visuospatial problem-solving measure that reflected far transfer of training effects. There were no significant effects on self-report questionnaires, likely owing to the complexity of these measures in this heterogeneous patient sample. Overall, these data support the efficacy of GMT in the rehabilitation of executive functioning deficits.

Levine, Brian; Schweizer, Tom A.; O'Connor, Charlene; Turner, Gary; Gillingham, Susan; Stuss, Donald T.; Manly, Tom; Robertson, Ian H.

2011-01-01

214

Resting state magnetoencephalography functional connectivity in traumatic brain injury  

PubMed Central

Object Traumatic brain injury (TBI) is one of the leading causes of morbidity worldwide. One mechanism by which blunt head trauma may disrupt normal cognition and behavior is through alteration of functional connectivity between brain regions. In this pilot study, the authors applied a rapid automated resting state magnetoencephalography (MEG) imaging technique suitable for routine clinical use to test the hypothesis that there is decreased functional connectivity in patients with TBI compared with matched controls, even in cases of mild TBI. Furthermore, they posit that these abnormal reductions in MEG functional connectivity can be detected even in TBI patients without specific evidence of traumatic lesions on 3-T MR images. Finally, they hypothesize that the reductions of functional connectivity can improve over time across serial MEG scans during recovery from TBI. Methods Magnetoencephalography maps of functional connectivity in the alpha (8- to 12-Hz) band from 21 patients who sustained a TBI were compared with those from 18 age- and sex-matched controls. Regions of altered functional connectivity in each patient were detected in automated fashion through atlas-based registration to the control database. The extent of reduced functional connectivity in the patient group was tested for correlations with clinical characteristics of the injury as well as with findings on 3-T MRI. Finally, the authors compared initial connectivity maps with 2-year follow-up functional connectivity in a subgroup of 5 patients with TBI. Results Fourteen male and 7 female patients (17–53 years old, median 29 years) were enrolled. By Glasgow Coma Scale (GCS) criteria, 11 patients had mild, 1 had moderate, and 3 had severe TBI, and 6 had no GCS score recorded. On 3-T MRI, 16 patients had abnormal findings attributable to the trauma and 5 had findings in the normal range. As a group, the patients with TBI had significantly lower functional connectivity than controls (p < 0.01). Three of the 5 patients with normal findings on 3-T MRI showed regions of abnormally reduced MEG functional connectivity. No significant correlations were seen between extent of functional disconnection and injury severity or posttraumatic symptoms (p > 0.05). In the subgroup undergoing 2-year follow-up, the second MEG scan demonstrated a significantly lower percentage of voxels with decreased connectivity (p < 0.05) than the initial MEG scan. Conclusions A rapid automated resting-state MEG imaging technique demonstrates abnormally decreased functional connectivity that may persist for years after TBI, including cases classified as “mild” by GCS criteria. Disrupted MEG connectivity can be detected even in some patients with normal findings on 3-T MRI. Analysis of follow-up MEG scans in a subgroup of patients shows that, over time, the abnormally reduced connectivity can improve, suggesting neuroplasticity during the recovery from TBI. Resting state MEG deserves further investigation as a prognostic and predictive biomarker for TBI.

Tarapore, Phiroz E.; Findlay, Anne M.; LaHue, Sara C.; Lee, Hana; Honma, Susanne M.; Mizuiri, Danielle; Luks, Tracy L.; Manley, Geoffrey T.; Nagarajan, Srikantan S.; Mukherjee, Pratik

2014-01-01

215

Local sleep homeostasis in the avian brain: convergence of sleep function in mammals and birds?  

PubMed Central

The function of the brain activity that defines slow wave sleep (SWS) and rapid eye movement (REM) sleep in mammals is unknown. During SWS, the level of electroencephalogram slow wave activity (SWA or 0.5–4.5 Hz power density) increases and decreases as a function of prior time spent awake and asleep, respectively. Such dynamics occur in response to waking brain use, as SWA increases locally in brain regions used more extensively during prior wakefulness. Thus, SWA is thought to reflect homeostatically regulated processes potentially tied to maintaining optimal brain functioning. Interestingly, birds also engage in SWS and REM sleep, a similarity that arose via convergent evolution, as sleeping reptiles and amphibians do not show similar brain activity. Although birds deprived of sleep show global increases in SWA during subsequent sleep, it is unclear whether avian sleep is likewise regulated locally. Here, we provide, to our knowledge, the first electrophysiological evidence for local sleep homeostasis in the avian brain. After staying awake watching David Attenborough's The Life of Birds with only one eye, SWA and the slope of slow waves (a purported marker of synaptic strength) increased only in the hyperpallium—a primary visual processing region—neurologically connected to the stimulated eye. Asymmetries were specific to the hyperpallium, as the non-visual mesopallium showed a symmetric increase in SWA and wave slope. Thus, hypotheses for the function of mammalian SWS that rely on local sleep homeostasis may apply also to birds.

Lesku, John A.; Vyssotski, Alexei L.; Martinez-Gonzalez, Dolores; Wilzeck, Christiane; Rattenborg, Niels C.

2011-01-01

216

Decreased Functional Brain Connectivity in Adolescents with Internet Addiction  

PubMed Central

Background Internet addiction has become increasingly recognized as a mental disorder, though its neurobiological basis is unknown. This study used functional neuroimaging to investigate whole-brain functional connectivity in adolescents diagnosed with internet addiction. Based on neurobiological changes seen in other addiction related disorders, it was predicted that connectivity disruptions in adolescents with internet addiction would be most prominent in cortico-striatal circuitry. Methods Participants were 12 adolescents diagnosed with internet addiction and 11 healthy comparison subjects. Resting-state functional magnetic resonance images were acquired, and group differences in brain functional connectivity were analyzed using the network-based statistic. We also analyzed network topology, testing for between-group differences in key graph-based network measures. Results Adolescents with internet addiction showed reduced functional connectivity spanning a distributed network. The majority of impaired connections involved cortico-subcortical circuits (?24% with prefrontal and ?27% with parietal cortex). Bilateral putamen was the most extensively involved subcortical brain region. No between-group difference was observed in network topological measures, including the clustering coefficient, characteristic path length, or the small-worldness ratio. Conclusions Internet addiction is associated with a widespread and significant decrease of functional connectivity in cortico-striatal circuits, in the absence of global changes in brain functional network topology.

Hong, Soon-Beom; Zalesky, Andrew; Cocchi, Luca; Fornito, Alex; Choi, Eun-Jung; Kim, Ho-Hyun; Suh, Jeong-Eun; Kim, Chang-Dai; Kim, Jae-Won; Yi, Soon-Hyung

2013-01-01

217

Cellular mechanisms of brain energy metabolism and their relevance to functional brain imaging.  

PubMed Central

Despite striking advances in functional brain imaging, the cellular and molecular mechanisms that underlie the signals detected by these techniques are still largely unknown. The basic physiological principle of functional imaging is represented by the tight coupling existing between neuronal activity and the associated local increase in both blood flow and energy metabolism. Positron emission tomography (PET) signals detect blood flow, oxygen consumption and glucose use associated with neuronal activity; the degree of blood oxygenation is currently thought to contribute to the signal detected with functional magnetic resonance imaging, while magnetic resonance spectroscopy (MRS) identifies the spatio-temporal pattern of the activity-dependent appearance of certain metabolic intermediates such as glucose or lactate. Recent studies, including those of neurotransmitter-regulated metabolic fluxes in purified preparations and analyses of the cellular localization of enzymes and transporters involved in energy metabolism, as well as in vivo microdialysis and MRS approaches have identified the neurotransmitter glutamate and astrocytes, a specific type of glial cell, as pivotal elements in the coupling of synaptic activity with energy metabolism. Astrocytes are ideally positioned to sense increases in synaptic activity and to couple them with energy metabolism. Indeed they possess specialized processes that cover the surface of intraparenchymal capillaries, suggesting that astrocytes may be a likely site of prevalent glucose uptake. Other astrocyte processes are wrapped around synaptic contacts which possess receptors and reuptake sites for neurotransmitters. Glutamate stimulates glucose uptake into astrocytes. This effect is mediated by specific glutamate transporters present on these cells. The activity of these transporters, which is tightly coupled to the synaptic release of glutamate and operates the clearance of glutamate from the extracellular space, is driven by the electrochemical gradient of Na+. This Na(+)-dependent uptake of glutamate into astrocytes triggers a cascade of molecular events involving the Na+/K(+)-ATPase leading to the glycolytic processing of glucose and the release of lactate by astrocytes. The stoichiometry of this process is such that for one glutamate molecule taken up with three Na+ ions, one glucose molecule enters an astrocyte, two ATP molecules are produced through aerobic glycolysis and two lactate molecules are released. Within the astrocyte, one ATP molecule fuels one 'turn of the pump' while the other provides the energy needed to convert glutamate to glutamine by glutamine synthase. Evidence has been accumulated from structural as well as functional studies indicating that, under aerobic conditions, lactate may be the preferred energy substrate of activated neurons. Indeed, in the presence of oxygen, lactate is converted to pyruvate, which can be processed through the tricarboxylic acid cycle and the associated oxidative phosphorylation, to yield 17 ATP molecules per lactate molecule. These data suggest that during activation the brain may transiently resort to aerobic glycolysis occurring in astrocytes, followed by the oxidation of lactate by neurons. The proposed model provides a direct mechanism to couple synaptic activity with glucose use and is consistent with the notion that the signals detected during physiological activation with 18F-deoxyglucose (DG)-PET may reflect predominantly uptake of the tracer into astrocytes. This conclusion does not question the validity of the 2-DG-based techniques, rather it provides a cellular and molecular basis for these functional brain imaging techniques.

Magistretti, P J; Pellerin, L

1999-01-01

218

The Mouse Blood-Brain Barrier Transcriptome: A New Resource for Understanding the Development and Function of Brain Endothelial Cells  

PubMed Central

The blood-brain barrier (BBB) maintains brain homeostasis and limits the entry of toxins and pathogens into the brain. Despite its importance, little is known about the molecular mechanisms regulating the development and function of this crucial barrier. In this study we have developed methods to highly purify and gene profile endothelial cells from different tissues, and by comparing the transcriptional profile of brain endothelial cells with those purified from the liver and lung, we have generated a comprehensive resource of transcripts that are enriched in the BBB forming endothelial cells of the brain. Through this comparison we have identified novel tight junction proteins, transporters, metabolic enzymes, signaling components, and unknown transcripts whose expression is enriched in central nervous system (CNS) endothelial cells. This analysis has identified that RXRalpha signaling cascade is specifically enriched at the BBB, implicating this pathway in regulating this vital barrier. This dataset provides a resource for understanding CNS endothelial cells and their interaction with neural and hematogenous cells.

Daneman, Richard; Zhou, Lu; Agalliu, Dritan; Cahoy, John D.; Kaushal, Amit; Barres, Ben A.

2010-01-01

219

Reorganization of functional brain networks during the recovery of stroke: a functional MRI study.  

PubMed

Studies have demonstrated that reorganization of the cortex after stroke contributed to the recovery of motor function. However, these studies paid much more attention to the reorganization of motor-related brain regions and motor executive network which only contained tens of brain regions, ignoring the change in brain-wide network during the restoration of motor function. Based on this consideration, this paper investigated the functional reorganization of brain-wide network during the recovery after stroke from the perspective of graph theory. At four time points (less than 10 days, around 2 weeks, 1 month and 3 months) after stroke onset, we obtained the functional MRI (fMRI) data of stroke patients when they were doing finger tapping task. Based on the fMRI data, we constructed the brain-wide functional network which consisted of 264 putative functional areas for each subject at each time point. Then the topological parameters (e.g., characteristic path length and cluster coefficient) of these brain networks were examined. Results showed that the brain networks shifted towards a non-optimal topological configuration with low small-worldness during the process of recovery. And this finding may broaden our knowledge about the reorganization of brain function during recovery after stroke. PMID:23366837

Cheng, Lin; Wu, Zhiyuan; Fu, Yi; Miao, Fei; Sun, Junfeng; Tong, Shanbao

2012-01-01

220

Quantitative Expression Profile of Distinct Functional Regions in the Adult Mouse Brain  

PubMed Central

The adult mammalian brain is composed of distinct regions with specialized roles including regulation of circadian clocks, feeding, sleep/awake, and seasonal rhythms. To find quantitative differences of expression among such various brain regions, we conducted the BrainStars (B*) project, in which we profiled the genome-wide expression of ?50 small brain regions, including sensory centers, and centers for motion, time, memory, fear, and feeding. To avoid confounds from temporal differences in gene expression, we sampled each region every 4 hours for 24 hours, and pooled the samples for DNA-microarray assays. Therefore, we focused on spatial differences in gene expression. We used informatics to identify candidate genes with expression changes showing high or low expression in specific regions. We also identified candidate genes with stable expression across brain regions that can be used as new internal control genes, and ligand-receptor interactions of neurohormones and neurotransmitters. Through these analyses, we found 8,159 multi-state genes, 2,212 regional marker gene candidates for 44 small brain regions, 915 internal control gene candidates, and 23,864 inferred ligand-receptor interactions. We also found that these sets include well-known genes as well as novel candidate genes that might be related to specific functions in brain regions. We used our findings to develop an integrated database (http://brainstars.org/) for exploring genome-wide expression in the adult mouse brain, and have made this database openly accessible. These new resources will help accelerate the functional analysis of the mammalian brain and the elucidation of its regulatory network systems.

Nagano, Mamoru; Uno, Kenichiro D.; Tsujino, Kaori; Hanashima, Carina; Shigeyoshi, Yasufumi; Ueda, Hiroki R.

2011-01-01

221

Neurocognitive Function of Patients with Brain Metastasis Who Received Either Whole Brain Radiotherapy Plus Stereotactic Radiosurgery or Radiosurgery Alone  

Microsoft Academic Search

Purpose: To determine how the omission of whole brain radiotherapy (WBRT) affects the neurocognitive function of patients with one to four brain metastases who have been treated with stereotactic radiosurgery (SRS). Methods and Materials: In a prospective randomized trial between WBRT+SRS and SRS alone for patients with one to four brain metastases, we assessed the neurocognitive function using the Mini-Mental

Hidefumi. Aoyama; Masao Tago; Norio Kato; Tatsuya Toyoda; Masahiro Kenjyo; Saeko Hirota; Hiroki Shioura; Taisuke Inomata; Etsuo Kunieda; Kazushige Hayakawa; Keiichi Nakagawa; Gen Kobashi; Hiroki Shirato

2007-01-01

222

Functional Representation of Enzymes by Specific Peptides  

PubMed Central

Predicting the function of a protein from its sequence is a long-standing goal of bioinformatic research. While sequence similarity is the most popular tool used for this purpose, sequence motifs may also subserve this goal. Here we develop a motif-based method consisting of applying an unsupervised motif extraction algorithm (MEX) to all enzyme sequences, and filtering the results by the four-level classification hierarchy of the Enzyme Commission (EC). The resulting motifs serve as specific peptides (SPs), appearing on single branches of the EC. In contrast to previous motif-based methods, the new method does not require any preprocessing by multiple sequence alignment, nor does it rely on over-representation of motifs within EC branches. The SPs obtained comprise on average 8.4 ± 4.5 amino acids, and specify the functions of 93% of all enzymes, which is much higher than the coverage of 63% provided by ProSite motifs. The SP classification thus compares favorably with previous function annotation methods and successfully demonstrates an added value in extreme cases where sequence similarity fails. Interestingly, SPs cover most of the annotated active and binding site amino acids, and occur in active-site neighboring 3-D pockets in a highly statistically significant manner. The latter are assumed to have strong biological relevance to the activity of the enzyme. Further filtering of SPs by biological functional annotations results in reduced small subsets of SPs that possess very large enzyme coverage. Overall, SPs both form a very useful tool for enzyme functional classification and bear responsibility for the catalytic biological function carried out by enzymes.

Kunik, Vered; Meroz, Yasmine; Solan, Zach; Sandbank, Ben; Weingart, Uri; Ruppin, Eytan; Horn, David

2007-01-01

223

Neurosteroid Biosynthesis and Function in the Brain of Domestic Birds  

PubMed Central

It is now established that the brain and other nervous systems have the capability of forming steroids de novo, the so-called “neurosteroids.” The pioneering discovery of Baulieu and his colleagues, using rodents, has opened the door to a new research field of “neurosteroids.” In contrast to mammalian vertebrates, little has been known regarding de novo neurosteroidogenesis in the brain of birds. We therefore investigated neurosteroid formation and metabolism in the brain of quail, a domestic bird. Our studies over the past two decades demonstrated that the quail brain possesses cytochrome P450 side-chain cleavage enzyme (P450scc), 3?-hydroxysteroid dehydrogenase/?5-?4-isomerase (3?-HSD), 5?-reductase, cytochrome P450 17?-hydroxylase/c17,20-lyase (P45017?,lyase), 17?-HSD, etc., and produces pregnenolone, progesterone, 5?-dihydroprogesterone (5?-DHP), 3?, 5?-tetrahydroprogesterone (3?, 5?-THP), androstenedione, testosterone, and estradiol from cholesterol. Independently, Schlinger’s laboratory demonstrated that the brain of zebra finch, a songbird, also produces various neurosteroids. Thus, the formation and metabolism of neurosteroids from cholesterol is now known to occur in the brain of birds. In addition, we recently found that the quail brain expresses cytochrome P4507? and produces 7?- and 7?-hydroxypregnenolone, previously undescribed avian neurosteroids, from pregnenolone. This paper summarizes the advances made in our understanding of neurosteroid formation and metabolism in the brain of domestic birds. This paper also describes what are currently known about physiological changes in neurosteroid formation and biological functions of neurosteroids in the brain of domestic and other birds.

Tsutsui, Kazuyoshi

2011-01-01

224

MiR-92b and miR-9/9* Are Specifically Expressed in Brain Primary Tumors and Can Be Used to Differentiate Primary from Metastatic Brain Tumors  

PubMed Central

A recurring challenge for brain pathologists is to diagnose whether a brain malignancy is a primary tumor or a metastasis from some other tissue. The accurate diagnosis of brain malignancies is essential for selection of proper treatment. MicroRNAs are a class of small non-coding RNA species that regulate gene expression; many exhibit tissue-specific expression and are misregulated in cancer. Using microRNA expression profiling, we found that hsa-miR-92b and hsa-miR-9/hsa-miR-9* are over-expressed, specifically in brain primary tumors, as compared to primary tumors from other tissues and their metastases to the brain. By considering the expression of only these two microRNAs, it is possible to distinguish between primary and metastatic brain tumors with very high accuracy. These microRNAs thus represent excellent biomarkers for brain primary tumors. Previous reports have found that hsa-miR-92b and hsa-miR-9/hsa-miR-9* are expressed more strongly in developing neurons and brain than in adult brain. Thus, their specific over-expression in brain primary tumors supports a functional role for these microRNAs or a link between neuronal stem cells and brain tumorigenesis.

Nass, Dvora; Rosenwald, Shai; Meiri, Eti; Gilad, Shlomit; Tabibian-Keissar, Hilla; Schlosberg, Anat; Kuker, Hagit; Sion-Vardy, Netta; Tobar, Ana; Kharenko, Oleg; Sitbon, Einat; Yanai, Gila Lithwick; Elyakim, Eran; Cholakh, Hila; Gibori, Hadas; Spector, Yael; Bentwich, Zvi; Barshack, Iris; Rosenfeld, Nitzan

2009-01-01

225

Allelic specificity of Ube3a Expression In The Mouse Brain During Postnatal Development.  

PubMed

Genetic alterations of the maternal UBE3A allele result in Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe developmental delay, lack of speech, and difficulty with movement and balance. The combined effects of maternal UBE3A mutation and cell type-specific epigenetic silencing of paternal UBE3A are hypothesized to result in a complete loss of functional UBE3A protein in neurons. However, the allelic specificity of UBE3A expression in neurons and other cell types in the brain has yet to be characterized throughout development, including the early postnatal period when AS phenotypes emerge. Here we define maternal and paternal allele-specific Ube3a protein expression throughout postnatal brain development in the mouse, a species that exhibits orthologous epigenetic silencing of paternal Ube3a in neurons and AS-like behavioral phenotypes subsequent to maternal Ube3a deletion. We find that neurons downregulate paternal Ube3a protein expression as they mature and, with the exception of neurons born from postnatal stem cell niches, do not express detectable paternal Ube3a beyond the first postnatal week. By contrast, neurons express maternal Ube3a throughout postnatal development, during which time localization of the protein becomes increasingly nuclear. Unlike neurons, astrocytes and oligodendrotyes biallelically express Ube3a. Notably, mature oligodendrocytes emerge as the predominant Ube3a-expressing glial cell type in the cortex and white matter tracts during postnatal development. These findings demonstrate the spatiotemporal characteristics of allele-specific Ube3a expression in key brain cell types, thereby improving our understanding of the developmental parameters of paternal Ube3a silencing and the cellular basis of AS. J. Comp. Neurol. 522:1874-1896, 2014. © 2013 Wiley Periodicals, Inc. PMID:24254964

Judson, Matthew C; Sosa-Pagan, Jason O; Del Cid, Wilmer A; Han, Ji Eun; Philpot, Benjamin D

2014-06-01

226

PET scans relate clinical picture to more specific nerve function  

SciTech Connect

This article describes the historical development of the use of positron emission tomography in studies of brain chemistry and the specific pathways associated with specific disease states. Fluorine-18 is used to label dopa since dopa can cross the blood-brain barrier. This radiopharmaceutical has been used to study the role of dopamine in Parkinson's disease and other motor disorders. The new PET technologies may also allow insight into the cause of variable responses to levo-dopa therapy.

Ziporyn, T.

1985-02-15

227

From the connectome to brain function.  

PubMed

In this Historical Perspective, we ask what information is needed beyond connectivity diagrams to understand the function of nervous systems. Informed by invertebrate circuits whose connectivities are known, we highlight the importance of neuronal dynamics and neuromodulation, and the existence of parallel circuits. The vertebrate retina has these features in common with invertebrate circuits, suggesting that they are general across animals. Comparisons across these systems suggest approaches to study the functional organization of large circuits based on existing knowledge of small circuits. PMID:23866325

Bargmann, Cornelia I; Marder, Eve

2013-06-01

228

Linking human brain local activity fluctuations to structural and functional network architectures  

PubMed Central

Activity of cortical local neuronal populations fluctuates continuously, and a large proportion of these fluctuations are shared across populations of neurons. Here we seek organizational rules that link these two phenomena. Using neuronal activity, as identified by functional MRI (fMRI) and for a given voxel or brain region, we derive a single measure of full bandwidth brain-oxygenation-level-dependent (BOLD) fluctuations by calculating the slope, ?, for the log-linear power spectrum. For the same voxel or region, we also measure the temporal coherence of its fluctuations to other voxels or regions, based on exceeding a given threshold, ?, for zero lag correlation, establishing functional connectivity between pairs of neuronal populations. From resting state fMRI, we calculated whole-brain group-averaged maps for ? and for functional connectivity. Both maps showed similar spatial organization, with a correlation coefficient of 0.75 between the two parameters across all brain voxels, as well as variability with hodology. A computational model replicated the main results, suggesting that synaptic low-pass filtering can account for these interrelationships. We also investigated the relationship between ? and structural connectivity, as determined by diffusion tensor imaging-based tractography. We observe that the correlation between ? and connectivity depends on attentional state; specifically, ? correlated more highly to structural connectivity during rest than while attending to a task. Overall, these results provide global rules for the dynamics between frequency characteristics of local brain activity and the architecture of underlying brain networks.

Baria, A.T.; Mansour, A.; Huang, L.; Baliki, M.N.; Cecchi, G.A.; Mesulam, M.M.; Apkarian, A.V.

2013-01-01

229

Metabolism of exogenous sex steroids and effect on brain functions with a focus on tibolone  

Microsoft Academic Search

Around the menopause, changes in ovarian secretion of steroids result in changes in brain function: hot flushes and sweating later followed by changes in mood, libido and cognition. The relationship between sex steroids and brain functions are reviewed, with focus on hormonal treatments, in particular tibolone, on the postmenopausal brain and on associations between tissue levels and brain functions. Data

H. A. M. Verheul; H. J. Kloosterboer

2006-01-01

230

Brain tissue segmentation of neonatal MR images using a longitudinal subject-specific probabilistic atlas  

NASA Astrophysics Data System (ADS)

Brain tissue segmentation of neonate MR images is a challenging task in study of early brain development, due to low signal contrast among brain tissues and high intensity variability especially in white matter. Among various brain tissue segmentation algorithms, the atlas-based segmentation techniques can potentially produce reasonable segmentation results on neonatal brain images. However, their performance on the population-based atlas is still limited due to the high variability of brain structures across different individuals. Moreover, it may be impossible to generate a reasonable probabilistic atlas for neonates without tissue segmentation samples. To overcome these limitations, we present a neonatal brain tissue segmentation method by taking advantage of the longitudinal data available in our study to establish a subject-specific probabilistic atlas. In particular, tissue segmentation of the neonatal brain is formulated as two iterative steps of bias correction and probabilistic atlas based tissue segmentation, along with the guidance of brain tissue segmentation resulted from the later time images of the same subject which serve as a subject-specific probabilistic atlas. The proposed method has been evaluated qualitatively through visual inspection and quantitatively by comparing with manual delineation results. Experimental results show that the utilization of a subject-specific probabilistic atlas can substantially improve tissue segmentation of neonatal brain images.

Shi, Feng; Fan, Yong; Tang, Songyuan; Gilmore, John; Lin, Weili; Shen, Dinggang

2009-02-01

231

Structural and functional rich club organization of the brain in children and adults.  

PubMed

Recent studies using Magnetic Resonance Imaging (MRI) have proposed that the brain's white matter is organized as a rich club, whereby the most highly connected regions of the brain are also highly connected to each other. Here we use both functional and diffusion-weighted MRI in the human brain to investigate whether the rich club phenomena is present with functional connectivity, and how this organization relates to the structural phenomena. We also examine whether rich club regions serve to integrate information between distinct brain systems, and conclude with a brief investigation of the developmental trajectory of rich-club phenomena. In agreement with prior work, both adults and children showed robust structural rich club organization, comprising regions of the superior medial frontal/dACC, medial parietal/PCC, insula, and inferior temporal cortex. We also show that these regions were highly integrated across the brain's major networks. Functional brain networks were found to have rich club phenomena in a similar spatial layout, but a high level of segregation between systems. While no significant differences between adults and children were found structurally, adults showed significantly greater functional rich club organization. This difference appeared to be driven by a specific set of connections between superior parietal, insula, and supramarginal cortex. In sum, this work highlights the existence of both a structural and functional rich club in adult and child populations with some functional changes over development. It also offers a potential target in examining atypical network organization in common developmental brain disorders, such as ADHD and Autism. PMID:24505468

Grayson, David S; Ray, Siddharth; Carpenter, Samuel; Iyer, Swathi; Dias, Taciana G Costa; Stevens, Corinne; Nigg, Joel T; Fair, Damien A

2014-01-01

232

Ubiquity and specificity of reinforcement signals throughout the human brain.  

PubMed

Reinforcements and punishments facilitate adaptive behavior in diverse domains ranging from perception to social interactions. A conventional approach to understanding the corresponding neural substrates focuses on the basal ganglia and its dopaminergic projections. Here, we show that reinforcement and punishment signals are surprisingly ubiquitous in the gray matter of nearly every subdivision of the human brain. Humans played either matching-pennies or rock-paper-scissors games against computerized opponents while being scanned using fMRI. Multivoxel pattern analysis was used to decode previous choices and their outcomes, and to predict upcoming choices. Whereas choices were decodable from a confined set of brain structures, their outcomes were decodable from nearly all cortical and subcortical structures. In addition, signals related to both reinforcements and punishments were recovered reliably in many areas and displayed patterns not consistent with salience-based explanations. Thus, reinforcement and punishment might play global modulatory roles in the entire brain. PMID:21982377

Vickery, Timothy J; Chun, Marvin M; Lee, Daeyeol

2011-10-01

233

Regional and cell-type specific distribution of HDAC2 in the adult mouse brain.  

PubMed

The effects of epigenetics on brain functions are not completely understood, but histone deacetylases (HDACs) are known to affect brain function and dysfunction by mediating the acetylation status of target proteins, thereby affecting gene expression. The current study used immunochemistry to illuminate the regional distribution of one member of the HDAC family, HDAC2, in the C57BL/6J mouse brain. Our data show that HDAC2 is ubiquitously expressed throughout the mouse brain and is localized primarily within the cell nucleus. Using double-immunofluorescence, we demonstrated HDAC2 expression in neuronal cells, including cholinergic, serotonergic and catecholaminergic neurons, as well as postsynaptic glutamatergic and GABAergic neurons. HDAC2 was also observed in oligodendrocytes, but not in astrocytes or microglia. These detailed immunological studies illuminate the distribution of HDAC2 throughout the mouse brain and will facilitate investigation of the roles of HDAC2 in brain function and neurological disorders. PMID:22532304

Yao, Zhi-Gang; Zhang, Ling; Huang, Lan; Zhu, Hua; Liu, Ying; Ma, Chun-Mei; Sheng, Shu-Li; Qin, Chuan

2013-03-01

234

Functional specificity of local synaptic connections in neocortical networks  

PubMed Central

Neuronal connectivity is fundamental to information processing in the brain. Understanding the mechanisms of sensory processing, therefore, requires uncovering how connection patterns between neurons relate to their function. On a coarse scale long range projections can preferentially link cortical regions with similar responses to sensory stimuli1-4. But on the local scale, where dendrites and axons overlap substantially, the functional specificity of connections remains unknown. Here we determine synaptic connectivity between nearby layer 2/3 pyramidal neurons in vitro whose response properties were first characterized in mouse visual cortex in vivo. We found that connection probability was related to the similarity of visually driven neuronal activity. Neurons with the same preference for oriented stimuli connected at twice the rate of neurons with orthogonal orientation preferences. Neurons responding similarly to naturalistic stimuli formed connections at much higher rates than those with uncorrelated responses. Bidirectional synaptic connections were found more frequently between neuronal pairs with strongly correlated visual responses. Our results reveal the deg of functional specificity of local synaptic connections in visual cortex, and point to the existence of fine-scale subnetworks dedicated to processing related sensory information.

Ko, Ho; Hofer, Sonja B.; Pichler, Bruno; Buchanan, Kate; Sjostrom, P. Jesper; Mrsic-Flogel, Thomas D.

2011-01-01

235

DNA microarray analysis of functionally discrete human brain regions reveals divergent transcriptional profiles  

PubMed Central

Transcriptional profiles within discrete human brain regions are likely to reflect structural and functional specialization. Using DNA microarray technology, this study investigates differences in transcriptional profiles of highly divergent brain regions (the cerebellar cortex and the cerebral cortex) as well as differences between two closely related brain structures (the anterior cingulate cortex and the dorsolateral prefrontal cortex). Replication of this study across three independent laboratories, to address false-positive and false-negative results using microarray technology, is also discussed. We find greater than a thousand transcripts to be differentially expressed between cerebellum and cerebral cortex and very few transcripts to be differentially expressed between the two neocortical regions. We further characterized transcripts that were found to be specifically expressed within brain regions being compared and found that ontological classes representing signal transduction machinery, neurogenesis, synaptic transmission, and transcription factors were most highly represented.

Evans, S.J.; Choudary, P.V.; Vawter, M.P.; Li, J.; Meador-Woodruff, J.H.; Lopez, J.F.; Burke, S.M.; Thompson, R.C.; Myers, R.M.; Jones, E.G.; Bunney, W.E.; Watson, S.J.; Akil, H.

2010-01-01

236

Automated identification of cell-type-specific genes in the mouse brain by image computing of expression patterns  

PubMed Central

Background Differential gene expression patterns in cells of the mammalian brain result in the morphological, connectional, and functional diversity of cells. A wide variety of studies have shown that certain genes are expressed only in specific cell-types. Analysis of cell-type-specific gene expression patterns can provide insights into the relationship between genes, connectivity, brain regions, and cell-types. However, automated methods for identifying cell-type-specific genes are lacking to date. Results Here, we describe a set of computational methods for identifying cell-type-specific genes in the mouse brain by automated image computing of in situ hybridization (ISH) expression patterns. We applied invariant image feature descriptors to capture local gene expression information from cellular-resolution ISH images. We then built image-level representations by applying vector quantization on the image descriptors. We employed regularized learning methods for classifying genes specifically expressed in different brain cell-types. These methods can also rank image features based on their discriminative power. We used a data set of 2,872 genes from the Allen Brain Atlas in the experiments. Results showed that our methods are predictive of cell-type-specificity of genes. Our classifiers achieved AUC values of approximately 87% when the enrichment level is set to 20. In addition, we showed that the highly-ranked image features captured the relationship between cell-types. Conclusions Overall, our results showed that automated image computing methods could potentially be used to identify cell-type-specific genes in the mouse brain.

2014-01-01

237

The Role of Noise in Brain Function  

NASA Astrophysics Data System (ADS)

Noise plays a fundamental role in all living organisms from the earliest prokaryotes to advanced mammalian forms, such as ourselves. In the context of living organisms, the term 'noise' usually refers to the variance amongst measurements obtained from repeated identical experimental conditions, or from output signals from these systems. It is noteworthy that both these conditions are universally characterized by the presence of background fluctuations. In non-biological systems, such as electronics or in communications sciences, where the aim is to send error-free messages, noise was generally regarded as a problem. The discovery of Stochastic Resonances (SR) in non-linear dynamics brought a shift of perception where noise, rather than representing a problem, became fundamental to system function, especially so in biology. The question now is: to what extent is biological function dependent on random noise. Indeed, it seems feasible that noise also plays an important role in neuronal communication and oscillatory synchronization. Given this approach, it follows that determining Fisher information content could be relevant in neuronal communication. It also seems possible that the principle of least time, and that of the sum over histories, could be important basic principles in understanding the coherence dynamics responsible for action and perception. Ultimately, external noise cancellation combined with intrinsic noise signal embedding and, the use of the principle of least time may be considered an essential step in the organization of central nervous system (CNS) function.

Roy, S.; Llinás, R.

2012-12-01

238

Identification of subject specific and functional consistent ROIs using semi-supervised learning  

NASA Astrophysics Data System (ADS)

Regions of interests (ROIs) for defining nodes of brain network are of great importance in brain network analysis of fMRI data. The ROIs are typically identified using prior anatomical information, seed region based correlation analysis, clustering analysis, region growing or ICA based methods. In this paper, we propose a novel method to identify subject specific and functional consistent ROIs for brain network analysis using semi-supervised learning. Specifically, a graph theory based semi-supervised learning method is adopted to optimize ROIs defined using prior knowledge with a constraint of local and global functional consistency, yielding subject specific ROIs with enhanced functional connectivity. Experiments using simulated fMRI data have demonstrated that functional consistent ROIs can be identified effectively from data with different signal to noise ratios (SNRs). Experiments using resting state fMRI data of 25 normal subjects for identifying ROIs of the default mode network have demonstrated that the proposed method is capable of identifying subject specific ROIs with stronger functional connectivity and higher consistency across subjects than existing alternative techniques, indicating that the proposed method can better identify brain network ROIs with intrinsic functional connectivity.

Du, Yuhui; Li, Hongming; Wu, Hong; Fan, Yong

2012-02-01

239

Nuclear magnetic resonance imaging and spectroscopy of human brain function.  

PubMed Central

The techniques of in vivo magnetic resonance (MR) imaging and spectroscopy have been established over the past two decades. Recent applications of these methods to study human brain function have become a rapidly growing area of research. The development of methods using standard MR contrast agents within the cerebral vasculature has allowed measurements of regional cerebral blood volume (rCBV), which are activity dependent. Subsequent investigations linked the MR relaxation properties of brain tissue to blood oxygenation levels which are also modulated by consumption and blood flow (rCBF). These methods have allowed mapping of brain activity in human visual and motor cortex as well as in areas of the frontal lobe involved in language. The methods have high enough spatial and temporal sensitivity to be used in individual subjects. MR spectroscopy of proton and carbon-13 nuclei has been used to measure rates of glucose transport and metabolism in the human brain. The steady-state measurements of brain glucose concentrations can be used to monitor the glycolytic flux, whereas subsequent glucose metabolism--i.e., the flux into the cerebral glutamate pool--can be used to measure tricarboxylic acid cycle flux. Under visual stimulation the concentration of lactate in the visual cortex has been shown to increase by MR spectroscopy. This increase is compatible with an increase of anaerobic glycolysis under these conditions as earlier proposed from positron emission tomography studies. It is shown how MR spectroscopy can extend this understanding of brain metabolism. Images Fig. 1 Fig. 2 Fig. 3

Shulman, R G; Blamire, A M; Rothman, D L; McCarthy, G

1993-01-01

240

Fine-grained mapping of mouse brain functional connectivity with resting-state fMRI.  

PubMed

Understanding the intrinsic circuit-level functional organization of the brain has benefited tremendously from the advent of resting-state fMRI (rsfMRI). In humans, resting-state functional network has been consistently mapped and its alterations have been shown to correlate with symptomatology of various neurological or psychiatric disorders. To date, deciphering the mouse brain functional connectivity (MBFC) with rsfMRI remains a largely underexplored research area, despite the plethora of human brain disorders that can be modeled in this specie. To pave the way from pre-clinical to clinical investigations we characterized here the intrinsic architecture of mouse brain functional circuitry, based on rsfMRI data acquired at 7T using the Cryoprobe technology. High-dimensional spatial group independent component analysis demonstrated fine-grained segregation of cortical and subcortical networks into functional clusters, overlapping with high specificity onto anatomical structures, down to single gray matter nuclei. These clusters, showing a high level of stability and reliability in their patterning, formed the input elements for computing the MBFC network using partial correlation and graph theory. Its topological architecture conserved the fundamental characteristics described for the human and rat brain, such as small-worldness and partitioning into functional modules. Our results additionally showed inter-modular interactions via "network hubs". Each major functional system (motor, somatosensory, limbic, visual, autonomic) was found to have representative hubs that might play an important input/output role and form a functional core for information integration. Moreover, the rostro-dorsal hippocampus formed the highest number of relevant connections with other brain areas, highlighting its importance as core structure for MBFC. PMID:24718287

Mechling, Anna E; Hübner, Neele S; Lee, Hsu-Lei; Hennig, Jürgen; von Elverfeldt, Dominik; Harsan, Laura-Adela

2014-08-01

241

HIV and Aging Independently Affect Brain Function as Measured by Functional Magnetic Resonance Imaging  

PubMed Central

We investigated interactions between HIV and aging on brain function demands using functional magnetic resonance imaging (fMRI). A multiple regression model studied the association and interaction between fMRI measures, HIV serostatus, and age for 26 HIV infected (HIV+) and 25 seronegative (HIV?) subjects. While HIV serostatus and age independently affected fMRI measures, no interaction occurred. Functional brain demands in HIV+ subjects were equivalent to ~15–20 year older HIV? subjects. Frailty parallels between HIV and aging could result from continued immunological challenges depleting resources and triggering increased metabolic demands. fMRI could be a non-invasive biomarker to assess HIV in the brain.

Ances, Beau M.; Vaida, Florin; Yeh, Melinda J.; Liang, Christine L.; Buxton, Richard B.; Letendre, Scott; McCutchan, J. Allen; Ellis, Ronald J.

2009-01-01

242

Disease-specific, neurosphere-derived cells as models for brain disorders.  

PubMed

There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson's disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson's disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery. PMID:20699480

Matigian, Nicholas; Abrahamsen, Greger; Sutharsan, Ratneswary; Cook, Anthony L; Vitale, Alejandra M; Nouwens, Amanda; Bellette, Bernadette; An, Jiyuan; Anderson, Matthew; Beckhouse, Anthony G; Bennebroek, Maikel; Cecil, Rowena; Chalk, Alistair M; Cochrane, Julie; Fan, Yongjun; Féron, François; McCurdy, Richard; McGrath, John J; Murrell, Wayne; Perry, Chris; Raju, Jyothy; Ravishankar, Sugandha; Silburn, Peter A; Sutherland, Greg T; Mahler, Stephen; Mellick, George D; Wood, Stephen A; Sue, Carolyn M; Wells, Christine A; Mackay-Sim, Alan

2010-01-01

243

Surface mapping brain function on 3D models  

Microsoft Academic Search

A flexible graphics system for displaying functional and anatomic data on arbitrary collections of surfaces on or within the brain is presented. The system makes it possible to show complex, convoluted surfaces with the shading cues necessary to understand their shapes; to vary viewpoint, object position, illumination, and perspective easily; to show multiple-objects in one view, with or without transparency,

Bradley A. Payne; Arthur W. Toga

1990-01-01

244

Functional craniology and brain evolution: from paleontology to biomedicine  

PubMed Central

Anatomical systems are organized through a network of structural and functional relationships among their elements. This network of relationships is the result of evolution, it represents the actual target of selection, and it generates the set of rules orienting and constraining the morphogenetic processes. Understanding the relationship among cranial and cerebral components is necessary to investigate the factors that have influenced and characterized our neuroanatomy, and possible drawbacks associated with the evolution of large brains. The study of the spatial relationships between skull and brain in the human genus has direct relevance in cranial surgery. Geometrical modeling can provide functional perspectives in evolution and brain physiology, like in simulations to investigate metabolic heat production and dissipation in the endocranial form. Analysis of the evolutionary constraints between facial and neural blocks can provide new information on visual impairment. The study of brain form variation in fossil humans can supply a different perspective for interpreting the processes behind neurodegeneration and Alzheimer’s disease. Following these examples, it is apparent that paleontology and biomedicine can exchange relevant information and contribute at the same time to the development of robust evolutionary hypotheses on brain evolution, while offering more comprehensive biological perspectives with regard to the interpretation of pathological processes.

Bruner, Emiliano; de la Cuetara, Jose Manuel; Masters, Michael; Amano, Hideki; Ogihara, Naomichi

2014-01-01

245

Distribution and Function of Melanocortin Receptors within the Brain  

Microsoft Academic Search

\\u000a \\u000a Biological responses to pro-opiomelanocortin (POMC)-derived peptides administered in the brain were documented in the 1950s\\u000a but their molecular mechanisms of action only began to be resolved with the mapping of melanocortin receptor subtypes to specific\\u000a brain regions in the 1990s. Out of the five melanocortin receptor subtypes, MC3R and MC4R are widely recognised as ‘neural’\\u000a melanocortin receptors. In situ hybridization

Kathleen G. Mountjoy

246

Repetitive Transcranial Magnetic Stimulation Activates Specific Regions in Rat Brain  

NASA Astrophysics Data System (ADS)

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

Ji, Ru-Rong; Schlaepfer, Thomas E.; Aizenman, Carlos D.; Epstein, Charles M.; Qiu, Dike; Huang, Justin C.; Rupp, Fabio

1998-12-01

247

Left Brain vs. Right Brain: Findings on Visual Spatial Capacities and the Functional Neurology of Giftedness  

ERIC Educational Resources Information Center

As neuroimaging technologies increase their sensitivity to assess the function of the human brain and results from these studies draw the attention of educators, it becomes paramount to identify misconceptions about what these data illustrate and how these findings might be applied to educational contexts. Some of these "neuromyths" have…

Kalbfleisch, M. Layne; Gillmarten, Charles

2013-01-01

248

Abnormal Brain Functional Connectivity of the Hypothalamus in Cluster Headaches  

PubMed Central

The aim of this study was to detect the abnormality of the brain functional connectivity of the hypothalamus during acute spontaneous cluster headache (CH) attacks (‘in attack’) and headache-free intervals (‘out of attack’) using resting-state functional magnetic resonance imaging (RS-fMRI) technique. The RS-fMRI data from twelve male CH patients during ‘in attack’ and ‘out of attack’ periods and twelve age- and sex-matched normal controls were analyzed by the region-of-interest -based functional connectivity method using SPM5 software. Abnormal brain functional connectivity of the hypothalamus is present in CH, which is located mainly in the pain system during the spontaneous CH attacks. It extends beyond the pain system during CH attack intervals.

Qiu, Enchao; Wang, Yan; Ma, Lin; Tian, Lixia; Liu, Ruozhuo; Dong, Zhao; Xu, Xian; Zou, Zhitong; Yu, Shengyuan

2013-01-01

249

Brain miner: a 3D visual interface for the investigation of functional relationships in the brain  

NASA Astrophysics Data System (ADS)

Brain imaging methods used in experimental brain research such as Positron Emission Tomography (PET) and Functional Magnetic Resonance (fMRI) require the analysis of large amounts of data. Statistical methods are necessary to obtain a reliable measure of a given effect. Typically, researchers report their findings by listing those regions which show significant statistical activity in a group of subjects under some experimental condition or task. A number of methods create statistical parametric maps (SPMs) of the brain on a voxel- basis. However, a major limitation of the voxel-based technique is the inaccuracy of the transformation into a stereotaxic space (e.g., Talairach-Tournoux) given the wide variability in human brain structure. In order to account for this, researchers have turned to computing the statistics not on individual voxels but on predefined anatomical regions-of- interest (ROIs). A correlation coefficient is used to quantify similarity in response for various regions during an experimental setting. Since the functional inter-relationships can become rather complex, they are best understood in the context of the underlying 3-D brain anatomy. In this paper, we present a novel 3-D interface that allows the interactive exploration of the correlation datasets within a common stereotaxic atlas.

Welsh, Tom F.; Mueller, Klaus D.; Zhu, Wei; Meade, Jeffrey R.; Volkow, Nora

2001-05-01

250

MMPI2 validity scales versus domain specific measures in detection of factitious traumatic brain injury  

Microsoft Academic Search

A known group methodology was used to compare the predictive accuracies of MMPI-2 validity scales and malingered amnesia measures in the detection of real versus feigned traumatic brain-injury. The domain specific compliance measures were consistently more accurate in the separation of factitious brain-injury patients (n = 68) from severe brain-injury patients (N = 56). Among MMPI-2 measures, only scale Sc

Manfred F. Greiffenstein; Thomas Gola; W. John Baker

1995-01-01

251

Human brain somatic representation: a functional magnetic resonance mapping  

NASA Astrophysics Data System (ADS)

Central nervous system studies of injury and plasticity for the reorganization in the phantom limb sensation area presented. In particular functional magnetic resonance imaging (fMRI) mapping of the somatic and motor cortex of amputee patients, in the case of referred sensations. Using fMRI we can show the correlation between structure and functional field and study the reorganization due to plasticity in the brain. .

Romero-Romo, Juan; Rojas, Rafael; Salgado, Perla; Sánchez-Cortázar, Julián; Vazquez-Vela, Arturo; Barrios, Fernando A.

2001-10-01

252

Anatomical and functional assemblies of brain BOLD oscillations  

PubMed Central

Brain oscillatory activity has long been thought to have spatial properties, the details of which are unresolved. Here we examine spatial organizational rules for the human brain oscillatory activity as measured by blood oxygen level-dependent (BOLD). Resting state BOLD signal was transformed into frequency space (Welch’s method), averaged across subjects, and its spatial distribution studied as a function of four frequency bands, spanning the full bandwidth of BOLD. The brain showed anatomically constrained distribution of power for each frequency band. This result was replicated on a repository dataset of 195 subjects. Next, we examined larger-scale organization by parceling the neocortex into regions approximating Brodmann Areas (BAs). This indicated that BAs of simple function/connectivity (unimodal), vs. complex properties (transmodal), are dominated by low frequency BOLD oscillations, and within the visual ventral stream we observe a graded shift of power to higher frequency bands for BAs further removed from the primary visual cortex (increased complexity), linking frequency properties of BOLD to hodology. Additionally, BOLD oscillation properties for the default mode network demonstrated that it is composed of distinct frequency dependent regions. When the same analysis was performed on a visual-motor task, frequency-dependent global and voxel-wise shifts in BOLD oscillations could be detected at brain sites mostly outside those identified with general linear modeling. Thus, analysis of BOLD oscillations in full bandwidth uncovers novel brain organizational rules, linking anatomical structures and functional networks to characteristic BOLD oscillations. The approach also identifies changes in brain intrinsic properties in relation to responses to external inputs.

Baria, Alexis T.; Baliki, Marwan N.; Parrish, Todd; Apkarian, A. Vania

2011-01-01

253

Structure, Expression, and Functional Analysis of a Na^+Dependent Glutamate\\/Aspartate Transporter from Rat Brain  

Microsoft Academic Search

Transport systems specific for L-glutamate and L-aspartate play an important role in the termination of neurotransmitter signals at excitatory synapses. We describe here the structure and function of a 66-kDa glycoprotein that was purified from rat brain and identified as an L-glutamate\\/L-aspartate transporter (GLAST). A GLAST-specific cDNA clone was isolated from a rat brain cDNA library. The cDNA insert encodes

Thorsten Storck; Stefan Schulte; Kay Hofmann; Wilhelm Stoffel

1992-01-01

254

Reconceptualizing functional brain connectivity in autism from a developmental perspective  

PubMed Central

While there is almost universal agreement amongst researchers that autism is associated with alterations in brain connectivity, the precise nature of these alterations continues to be debated. Theoretical and empirical work is beginning to reveal that autism is associated with a complex functional phenotype characterized by both hypo- and hyper-connectivity of large-scale brain systems. It is not yet understood why such conflicting patterns of brain connectivity are observed across different studies, and the factors contributing to these heterogeneous findings have not been identified. Developmental changes in functional connectivity have received inadequate attention to date. We propose that discrepancies between findings of autism related hypo-connectivity and hyper-connectivity might be reconciled by taking developmental changes into account. We review neuroimaging studies of autism, with an emphasis on functional magnetic resonance imaging studies of intrinsic functional connectivity in children, adolescents and adults. The consistent pattern emerging across several studies is that while intrinsic functional connectivity in adolescents and adults with autism is generally reduced compared with age-matched controls, functional connectivity in younger children with the disorder appears to be increased. We suggest that by placing recent empirical findings within a developmental framework, and explicitly characterizing age and pubertal stage in future work, it may be possible to resolve conflicting findings of hypo- and hyper-connectivity in the extant literature and arrive at a more comprehensive understanding of the neurobiology of autism.

Uddin, Lucina Q.; Supekar, Kaustubh; Menon, Vinod

2013-01-01

255

Phospholipase D in brain function and Alzheimer's disease  

PubMed Central

Alzheimer’s disease is the most common neurodegenerative disorder. Although lipids are major constituents of brain, their role in Alzheimer’s disease pathogenesis is poorly understood. Much attention has been given to cholesterol, but growing evidence suggests that other lipids, such as phospholipids, might play an important role in this disorder. In this review, we will summarize the evidence linking phospholipase D, a phosphatidic acid-synthesizing enzyme, to multiple aspects of normal brain function and to Alzheimer’s disease. The role of phospholipase D in signaling mechanisms downstream of beta-amyloid as well as in the trafficking and processing of amyloid precursor protein will be emphasized.

Oliveira, Tiago Gil; Di Paolo, Gilbert

2012-01-01

256

Reentry: a key mechanism for integration of brain function  

PubMed Central

Reentry in nervous systems is the ongoing bidirectional exchange of signals along reciprocal axonal fibers linking two or more brain areas. The hypothesis that reentrant signaling serves as a general mechanism to couple the functioning of multiple areas of the cerebral cortex and thalamus was first proposed in 1977 and 1978 (Edelman, 1978). A review of the amount and diversity of supporting experimental evidence accumulated since then suggests that reentry is among the most important integrative mechanisms in vertebrate brains (Edelman, 1993). Moreover, these data prompt testable hypotheses regarding mechanisms that favor the development and evolution of reentrant neural architectures.

Edelman, Gerald M.; Gally, Joseph A.

2013-01-01

257

Restoration of function after brain damage using a neural prosthesis.  

PubMed

Neural interface systems are becoming increasingly more feasible for brain repair strategies. This paper tests the hypothesis that recovery after brain injury can be facilitated by a neural prosthesis serving as a communication link between distant locations in the cerebral cortex. The primary motor area in the cerebral cortex was injured in a rat model of focal brain injury, disrupting communication between motor and somatosensory areas and resulting in impaired reaching and grasping abilities. After implantation of microelectrodes in cerebral cortex, a neural prosthesis discriminated action potentials (spikes) in premotor cortex that triggered electrical stimulation in somatosensory cortex continuously over subsequent weeks. Within 1 wk, while receiving spike-triggered stimulation, rats showed substantially improved reaching and grasping functions that were indistinguishable from prelesion levels by 2 wk. Post hoc analysis of the spikes evoked by the stimulation provides compelling evidence that the neural prosthesis enhanced functional connectivity between the two target areas. This proof-of-concept study demonstrates that neural interface systems can be used effectively to bridge damaged neural pathways functionally and promote recovery after brain injury. PMID:24324155

Guggenmos, David J; Azin, Meysam; Barbay, Scott; Mahnken, Jonathan D; Dunham, Caleb; Mohseni, Pedram; Nudo, Randolph J

2013-12-24

258

Cloning and localization of the cGMP-specific phosphodiesterase type 9 in the rat brain.  

PubMed

In this study, we report the cloning of the rat cGMP-specific phosphodiesterase type 9 (PDE9A) and its localization in rat and mouse brain by non-radioactive in situ hybridization. Rat PDE9A was 97.6% identical to mouse PDE9A1 and showed 92.1% similarity on the amino acid level to the human homologue. PDE9A mRNA was widely distributed throughout the rat and mouse brain, with the highest expression observed in cerebellar Purkinje cells. Furthermore, strong staining was detected in areas such as cortical layer V, olfactory tubercle, caudate putamen and hippocampal pyramidal and granule cells. Comparison of PDE9A mRNA expression by double staining with the cellular markers NeuN and glial fibrillary acidic protein demonstrated that PDE9A expression was mainly detected in neurons and in a subpopulation of astrocytes. Using cGMP-immunocytochemistry, the localization of cGMP was investigated in the cerebellum in which the highest PDE9 expression was demonstrated. Strong cGMP immunoreactivity was detected in the molecular layer in the presence of the non-selective PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX). After treatment with soluble guanylyl cyclase activators the granular layer also showed cGMP staining, whereas no clear immunostaining was detected in Purkinje cells under all conditions investigated, which might be due to the presence of the IBMX-insensitive PDE9A in these cells. The present findings indicate that PDE9A is highly conserved between species and is widely distributed throughout the rodent brain. PDE9A is probably involved in maintenance of low cGMP levels in cells and might play an important role in a variety of brain functions involving cGMP-mediated signal transduction. PMID:14501210

van Staveren, W C G; Glick, J; Markerink-van Ittersum, M; Shimizu, M; Beavo, J A; Steinbusch, H W M; de Vente, J

2002-01-01

259

Functional Brain Image Analysis Using Joint Function-Structure Priors  

PubMed Central

We propose a new method for context-driven analysis of functional magnetic resonance images (fMRI) that incorporates spatial relationships between functional parameter clusters and anatomical structure directly for the first time. We design a parametric scheme that relates functional and structural spatially-compact regions in a single unified manner. Our method is motivated by the fact that the fMRI and anatomical MRI (aMRI) have consistent relations that provide configurations and context that aid in fMRI analysis. We develop a statistical decision-making strategy to estimate new fMRI parameter images (based on a General Linear Model-GLM) and spatially-clustered zones within these images. The analysis is based on the time-series data and contextual information related to appropriate spatial grouping of parameters in the functional data and the relationship of this grouping to relevant gray matter structure from the anatomical data. We introduce a representation for the joint prior of the functional and structural information, and define a joint probability distribution over the variations of functional clusters and the related structure contained in a set of training images. We estimate the Maximum A Posteriori (MAP) functional parameters, formulating the function-structure model in terms of level set functions. Results from 3D fMRI and aMRI show that this context-driven analysis potentially extracts more meaningful information than the standard GLM approach.

Yang, Jing; Papademetris, Xenophon; Staib, Lawrence H.; Schultz, Robert T.; Duncan, James S.

2010-01-01

260

Identification of brain- and bone-specific breast cancer metastasis genes  

Microsoft Academic Search

In breast cancer, metastases are relatively widely distributed, with the most common sites being bone, regional lymph nodes, lung, liver, and brain. The detailed mechanism of organ-specific metastasis is poorly understood. In this study, we initiated a search for genes that are implicated in brain or bone metastasis of primary human breast cancer. We generated gene expression profiles of 18

Andreas Klein; Christian Olendrowitz; Rita Schmutzler; Juergen Hampl; Peter M. Schlag; Nicolai Maass; Norbert Arnold; Ralf Wessel; Juliane Ramser; Alfons Meindl; Siegfried Scherneck; Susanne Seitz

2009-01-01

261

Covert brand recognition engages emotion-specific brain networks.  

PubMed

Consumer goods' brands have become a major driver of consumers' choice: they have got symbolic, relational and even social properties that add substantial cultural and affective value to goods and services. Therefore, measuring the role of brands in consumers' cognitive and affective processes would be very helpful to better understand economic decision making. This work aimed at finding the neural correlates of automatic, spontaneous emotional response to brands, showing how deeply integrated are consumption symbols within the cognitive and affective processes of individuals. Functional magnetic resonance imaging (fMRI) was measured during a visual oddball paradigm consisting in the presentation of scrambled pictures as frequent stimuli, colored squares as targets, and brands and emotional pictures (selected from the International Affective Picture System [IAPS]) as emotionally-salient distractors. Affective rating of brands was assessed individually after scanning by a validated questionnaire. Results showed that, similarly to IAPS pictures, brands activated a well-defined emotional network, including amygdala and dorsolateral prefrontal cortex, highly specific of affective valence. In conclusion, this work identified the neural correlates of brands within cognitive and affective processes of consumers. PMID:23479459

Casarotto, Silvia; Ricciardi, Emiliano; Romani, Simona; Dalli, Daniele; Pietrini, Pietro

2012-12-01

262

Partial sleep in the context of augmentation of brain function  

PubMed Central

Inability to solve complex problems or errors in decision making is often attributed to poor brain processing, and raises the issue of brain augmentation. Investigation of neuronal activity in the cerebral cortex in the sleep-wake cycle offers insights into the mechanisms underlying the reduction in mental abilities for complex problem solving. Some cortical areas may transit into a sleep state while an organism is still awake. Such local sleep would reduce behavioral ability in the tasks for which the sleeping areas are crucial. The studies of this phenomenon have indicated that local sleep develops in high order cortical areas. This is why complex problem solving is mostly affected by local sleep, and prevention of local sleep might be a potential way of augmentation of brain function. For this approach to brain augmentation not to entail negative consequences for the organism, it is necessary to understand the functional role of sleep. Our studies have given an unexpected answer to this question. It was shown that cortical areas that process signals from extero- and proprioreceptors during wakefulness, switch to the processing of interoceptive information during sleep. It became clear that during sleep all “computational power” of the brain is directed to the restoration of the vital functions of internal organs. These results explain the logic behind the initiation of total and local sleep. Indeed, a mismatch between the current parameters of any visceral system and the genetically determined normal range would provide the feeling of tiredness, or sleep pressure. If an environmental situation allows falling asleep, the organism would transit to a normal total sleep in all cortical areas. However, if it is impossible to go to sleep immediately, partial sleep may develop in some cortical areas in the still behaviorally awake organism. This local sleep may reduce both the “intellectual power” and the restorative function of sleep for visceral organs.

Pigarev, Ivan N.; Pigareva, Marina L.

2014-01-01

263

Individual Variability in Functional Connectivity Architecture of the Human Brain  

PubMed Central

Summary The fact that people think or behave differently from one another is rooted in individual differences in brain anatomy and connectivity. Here we used repeated-measurement resting-state functional MRI to explore inter-subject variability in connectivity. Individual differences in functional connectivity were heterogeneous across the cortex, with significantly higher variability in heteromodal association cortex and lower variability in unimodal cortices. Inter-subject variability in connectivity was significantly correlated with the degree of evolutionary cortical expansion, suggesting a potential evolutionary root of functional variability. The connectivity variability was also related to variability in sulcal depth but not cortical thickness, positively correlated with the degree of long-range connectivity but negatively correlated with local connectivity. A meta-analysis further revealed that regions predicting individual differences in cognitive domains are predominantly located in regions of high connectivity variability. Our findings have potential implications for understanding brain evolution and development, guiding intervention, and interpreting statistical maps in neuroimaging.

Mueller, Sophia; Wang, Danhong; Fox, Michael D.; Thomas Yeo, B. T.; Sepulcre, Jorge; Sabuncu, Mert R.; Shafee, Rebecca; Lu, Jie; Liu, Hesheng

2013-01-01

264

The functional neuroanatomy of working memory: Contributions of human brain lesion studies  

Microsoft Academic Search

Studies of patients with focal brain lesions remain critical components of research programs attempting to understand human brain function. Whereas functional imaging typically reveals activity in distributed brain regions that are involved in a task, lesion studies can define which of these brain regions are necessary for a cognitive process. Further, lesion studies are less critical regarding the selection of

N. G. Müller; R. T. Knight

2006-01-01

265

Identification of brain-specific angiogenesis inhibitor 2 as an interaction partner of glutaminase interacting protein  

SciTech Connect

Highlights: {yields} Brain-specific angiogenesis inhibitor 2 (BAI2) is a new partner protein for GIP. {yields} BAI2 interaction with GIP was revealed by yeast two-hybrid assay. {yields} Binding of BAI2 to GIP was characterized by NMR, CD and fluorescence. {yields} BAI2 and GIP binding was mediated through the C-terminus of BAI2. -- Abstract: The vast majority of physiological processes in living cells are mediated by protein-protein interactions often specified by particular protein sequence motifs. PDZ domains, composed of 80-100 amino acid residues, are an important class of interaction motif. Among the PDZ-containing proteins, glutaminase interacting protein (GIP), also known as Tax Interacting Protein TIP-1, is unique in being composed almost exclusively of a single PDZ domain. GIP has important roles in cellular signaling, protein scaffolding and modulation of tumor growth and interacts with a number of physiological partner proteins, including Glutaminase L, {beta}-Catenin, FAS, HTLV-1 Tax, HPV16 E6, Rhotekin and Kir 2.3. To identify the network of proteins that interact with GIP, a human fetal brain cDNA library was screened using a yeast two-hybrid assay with GIP as bait. We identified brain-specific angiogenesis inhibitor 2 (BAI2), a member of the adhesion-G protein-coupled receptors (GPCRs), as a new partner of GIP. BAI2 is expressed primarily in neurons, further expanding GIP cellular functions. The interaction between GIP and the carboxy-terminus of BAI2 was characterized using fluorescence, circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy assays. These biophysical analyses support the interaction identified in the yeast two-hybrid assay. This is the first study reporting BAI2 as an interaction partner of GIP.

Zencir, Sevil [Department of Biochemistry, Faculty of Science, Ege University, Izmir 35100 (Turkey)] [Department of Biochemistry, Faculty of Science, Ege University, Izmir 35100 (Turkey); Ovee, Mohiuddin [Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849 (United States)] [Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849 (United States); Dobson, Melanie J. [Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada B3H 4R2 (Canada)] [Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada B3H 4R2 (Canada); Banerjee, Monimoy [Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849 (United States)] [Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849 (United States); Topcu, Zeki, E-mail: zeki.topcu@ege.edu.tr [Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Ege University, Izmir 35100 (Turkey)] [Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Ege University, Izmir 35100 (Turkey); Mohanty, Smita, E-mail: mohansm@auburn.edu [Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849 (United States)] [Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849 (United States)

2011-08-12

266

Monoamines tissue content analysis reveals restricted and site-specific correlations in brain regions involved in cognition.  

PubMed

The dopamine (DA), noradrenalin (NA) and serotonin (5-HT) monoaminergic systems are deeply involved in cognitive processes via their influence on cortical and subcortical regions. The widespread distribution of these monoaminergic networks is one of the main difficulties in analyzing their functions and interactions. To address this complexity, we assessed whether inter-individual differences in monoamine tissue contents of various brain areas could provide information about their functional relationships. We used a sensitive biochemical approach to map endogenous monoamine tissue content in 20 rat brain areas involved in cognition, including 10 cortical areas and examined correlations within and between the monoaminergic systems. Whereas DA content and its respective metabolite largely varied across brain regions, the NA and 5-HT contents were relatively homogenous. As expected, the tissue content varied among individuals. Our analyses revealed a few specific relationships (10%) between the tissue content of each monoamine in paired brain regions and even between monoamines in paired brain regions. The tissue contents of NA, 5-HT and DA were inter-correlated with a high incidence when looking at a specific brain region. Most correlations found between cortical areas were positive while some cortico-subcortical relationships regarding the DA, NA and 5-HT tissue contents were negative, in particular for DA content. In conclusion, this work provides a useful database of the monoamine tissue content in numerous brain regions. It suggests that the regulation of these neuromodulatory systems is achieved mainly at the terminals, and that each of these systems contributes to the regulation of the other two. PMID:24120557

Fitoussi, A; Dellu-Hagedorn, F; De Deurwaerdère, P

2013-12-26

267

The Change of Functional Connectivity Specificity in Rats Under Various Anesthesia Levels and its Neural Origin  

PubMed Central

Spatiotemporal correlations of spontaneous blood oxygenation level dependent (BOLD) signals measured in the resting brain have been found to imply many resting-state coherent networks under both awake/conscious and anesthetized/unconscious conditions. To understand the resting-state brain networks in the unconscious state, spontaneous BOLD signals from the rat sensorimotor cortex were studied across a wide range of anesthesia levels induced by isoflurane. Distinct resting-state networks covering functionally specific sub-regions of the sensorimotor system were observed under light anesthesia with 1.0 % isoflurane; however, they gradually merged into a highly synchronized and spatially less-specific network under deep anesthesia with 1.8 % isoflurane. The EEG power correlations recorded using three electrodes from a separate group of rats showed similar dependency on anesthesia depth, suggesting the neural origin of the change in functional connectivity specificity. The specific-to-less-specific transition of resting-state networks may reflect a functional reorganization of the brain at different anesthesia levels or brain states.

Liu, Xiao; Zhu, Xiao-Hong; Zhang, Yi

2012-01-01

268

The change of functional connectivity specificity in rats under various anesthesia levels and its neural origin.  

PubMed

Spatiotemporal correlations of spontaneous blood oxygenation level dependent (BOLD) signals measured in the resting brain have been found to imply many resting-state coherent networks under both awake/conscious and anesthetized/unconscious conditions. To understand the resting-state brain networks in the unconscious state, spontaneous BOLD signals from the rat sensorimotor cortex were studied across a wide range of anesthesia levels induced by isoflurane. Distinct resting-state networks covering functionally specific sub-regions of the sensorimotor system were observed under light anesthesia with 1.0% isoflurane; however, they gradually merged into a highly synchronized and spatially less-specific network under deep anesthesia with 1.8% isoflurane. The EEG power correlations recorded using three electrodes from a separate group of rats showed similar dependency on anesthesia depth, suggesting the neural origin of the change in functional connectivity specificity. The specific-to-less-specific transition of resting-state networks may reflect a functional reorganization of the brain at different anesthesia levels or brain states. PMID:23208517

Liu, Xiao; Zhu, Xiao-Hong; Zhang, Yi; Chen, Wei

2013-07-01

269

Intestinal barrier function and the brain-gut axis.  

PubMed

The luminal-mucosal interface of the intestinal tract is the first relevant location where microorganism-derived antigens and all other potentially immunogenic particles face the scrutiny of the powerful mammalian immune system. Upon regular functioning conditions, the intestinal barrier is able to effectively prevent most environmental and external antigens to interact openly with the numerous and versatile elements that compose the mucosal-associated immune system. This evolutionary super system is capable of processing an astonishing amount of antigens and non-immunogenic particles, approximately 100 tons in one individual lifetime, only considering food-derived components. Most important, to develop oral tolerance and proper active immune responses needed to prevent disease and inflammation, this giant immunogenic load has to be managed in a way that physiological inflammatory balance is constantly preserved. Adequate functioning of the intestinal barrier involves local and distant regulatory networks integrating the so-called brain-gut axis. Along this complex axis both brain and gut structures participate in the processing and execution of response signals to external and internal changes coming from the digestive tract, using multidirectional pathways to communicate. Dysfunction of brain-gut axis facilitates malfunctioning of the intestinal barrier, and vice versa, increasing the risk of uncontrolled immunological reactions that may trigger mucosal and brain low-grade inflammation, a putative first step to the initiation of more permanent gut disorders. In this chapter, we describe the structure, function and interactions of intestinal barrier, microbiota and brain-gut axis in both healthy and pathological conditions. PMID:24997030

Alonso, Carmen; Vicario, María; Pigrau, Marc; Lobo, Beatriz; Santos, Javier

2014-01-01

270

Whole brain functional connectivity using phase locking measures of resting state magnetoencephalography  

PubMed Central

The analysis of spontaneous functional connectivity (sFC) reveals the statistical connections between regions of the brain consistent with underlying functional communication networks within the brain. In this work, we describe the implementation of a complete all-to-all network analysis of resting state neuronal activity from magnetoencephalography (MEG). Using graph theory to define networks at the dipole level, we established functionally defined regions by k-means clustering cortical surface locations using Eigenvector centrality (EVC) scores from the all-to-all adjacency model. Permutation testing was used to estimate regions with statistically significant connections compared to empty room data, which adjusts for spatial dependencies introduced by the MEG inverse problem. In order to test this model, we performed a series of numerical simulations investigating the effects of the MEG reconstruction on connectivity estimates. We subsequently applied the approach to subject data to investigate the effectiveness of our method in obtaining whole brain networks. Our findings indicated that our model provides statistically robust estimates of functional region networks. Application of our phase locking network methodology to real data produced networks with similar connectivity to previously published findings, specifically, we found connections between contralateral areas of the arcuate fasciculus that have been previously investigated. The use of data-driven methods for neuroscientific investigations provides a new tool for researchers in identifying and characterizing whole brain functional connectivity networks.

Schmidt, Benjamin T.; Ghuman, Avniel S.; Huppert, Theodore J.

2014-01-01

271

Nanoparticle-Mediated Brain-Specific Drug Delivery, Imaging, and Diagnosis  

Microsoft Academic Search

Central nervous system (CNS) diseases represent the largest and fastest-growing area of unmet medical need. Nanotechnology\\u000a plays a unique instrumental role in the revolutionary development of brain-specific drug delivery, imaging, and diagnosis.\\u000a With the aid of nanoparticles of high specificity and multifunctionality, such as dendrimers and quantum dots, therapeutics,\\u000a imaging agents, and diagnostic molecules can be delivered to the brain

Hu Yang

2010-01-01

272

Developmental changes in brain activation and functional connectivity during response inhibition in the early childhood brain.  

PubMed

Response inhibition is an attention function which develops relatively early during childhood. Behavioral data suggest that by the age of 3, children master the basic task requirements for the assessment of response inhibition but performance improves substantially until the age of 7. The neuronal mechanisms underlying these developmental processes, however, are not well understood. In this study, we examined brain activation patterns and behavioral performance of children aged between 4 and 6 years compared to adults by applying a go/no-go paradigm during near-infrared spectroscopy (NIRS) brain imaging. We furthermore applied task-independent functional connectivity measures to the imaging data to identify maturation of intrinsic neural functional networks. We found a significant group×condition related interaction in terms of inhibition-related reduced right fronto-parietal activation in children compared to adults. In contrast, motor-related activation did not differ between age groups. Functional connectivity analysis revealed that in the children's group, short-range coherence within frontal areas was stronger, and long-range coherence between frontal and parietal areas was weaker, compared to adults. Our findings show that in children aged from 4 to 6 years fronto-parietal brain maturation plays a crucial part in the cognitive development of response inhibition. PMID:23265620

Mehnert, Jan; Akhrif, Atae; Telkemeyer, Silke; Rossi, Sonja; Schmitz, Christoph H; Steinbrink, Jens; Wartenburger, Isabell; Obrig, Hellmuth; Neufang, Susanne

2013-11-01

273

Resting-state functional brain connectivity: lessons from functional near-infrared spectroscopy.  

PubMed

Resting-state functional near-infrared spectroscopy (R-fNIRS) is an active area of interest and is currently attracting considerable attention as a new imaging tool for the study of resting-state brain function. Using variations in hemodynamic concentration signals, R-fNIRS measures the brain's low-frequency spontaneous neural activity, combining the advantages of portability, low-cost, high temporal sampling rate and less physical burden to participants. The temporal synchronization of spontaneous neuronal activity in anatomically separated regions is referred to as resting-state functional connectivity (RSFC). In the past several years, an increasing body of R-fNIRS RSFC studies has led to many important findings about functional integration among local or whole-brain regions by measuring inter-regional temporal synchronization. Here, we summarize recent advances made in the R-fNIRS RSFC methodologies, from the detection of RSFC (e.g., seed-based correlation analysis, independent component analysis, whole-brain correlation analysis, and graph-theoretical topological analysis), to the assessment of RSFC performance (e.g., reliability, repeatability, and validity), to the application of RSFC in studying normal development and brain disorders. The literature reviewed here suggests that RSFC analyses based on R-fNIRS data are valid and reliable for the study of brain function in healthy and diseased populations, thus providing a promising imaging tool for cognitive science and clinics. PMID:24022325

Niu, Haijing; He, Yong

2014-04-01

274

An antigen-specific pathway for CD8 T cells across the blood-brain barrier  

PubMed Central

CD8 T cells are nature's foremost defense in encephalitis and brain tumors. Antigen-specific CD8 T cells need to enter the brain to exert their beneficial effects. On the other hand, traffic of CD8 T cells specific for neural antigen may trigger autoimmune diseases like multiple sclerosis. T cell traffic into the central nervous system is thought to occur when activated T cells cross the blood-brain barrier (BBB) regardless of their antigen specificity, but studies have focused on CD4 T cells. Here, we show that selective traffic of antigen-specific CD8 T cells into the brain occurs in vivo and is dependent on luminal expression of major histocompatibility complex (MHC) class I by cerebral endothelium. After intracerebral antigen injection, using a minimally invasive technique, transgenic CD8 T cells only infiltrated the brain when and where their cognate antigen was present. This was independent of antigen presentation by perivascular macrophages. Marked reduction of antigen-specific CD8 T cell infiltration was observed after intravenous injection of blocking anti–MHC class I antibody. These results expose a hitherto unappreciated route by which CD8 T cells home onto their cognate antigen behind the BBB: luminal MHC class I antigen presentation by cerebral endothelium to circulating CD8 T cells. This has implications for a variety of diseases in which antigen-specific CD8 T cell traffic into the brain is a beneficial or deleterious feature.

Galea, Ian; Bernardes-Silva, Martine; Forse, Penny A.; van Rooijen, Nico; Liblau, Roland S.; Perry, V. Hugh

2007-01-01

275

Region-Specific Protein Abundance Changes in the Brain of MPTP-induced Parkinson’s Disease Mouse Model  

SciTech Connect

Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration in the nigrostriatal region of the brain; however, the neurodegeneration extends well beyond dopaminergic neurons. To gain a better understanding of the molecular changes relevant to PD, we applied two-dimensional LC-MS/MS to comparatively analyze the proteome changes in four brain regions (striatum, cerebellum, cortex, and the rest of brain) using a MPTP-induced PD mouse model with the objective to identify nigrostriatal-specific and other region-specific protein abundance changes. The combined analyses resulted in the identification of 4,895 non-redundant proteins with at least two unique peptides per protein. The relative abundance changes in each analyzed brain region were estimated based on the spectral count information. A total of 518 proteins were observed with significant MPTP-induced changes across different brain regions. 270 of these proteins were observed with specific changes occurring either only in the striatum and/or in the rest of the brain region that contains substantia nigra, suggesting that these proteins are associated with the underlying nigrostriatal pathways. Many of the proteins that exhibit significant abundance changes were associated with dopamine signaling, mitochondrial dysfunction, the ubiquitin system, calcium signaling, the oxidative stress response, and apoptosis. A set of proteins with either consistent change across all brain regions or with changes specific to the cortex and cerebellum regions were also detected. One of the interesting proteins is ubiquitin specific protease (USP9X), a deubiquination enzyme involved in the protection of proteins from degradation and promotion of the TGF-? pathway, which exhibited altered abundances in all brain regions. Western blot validation showed similar spatial changes, suggesting that USP9X is potentially associated with neurodegeneration. Together, this study for the first time presents an overall picture of proteome changes underlying both nigrostriatal pathways and other brain regions potentially involved in MPTP-induced neurodegeneration. The observed molecular changes provide a valuable reference resource for future hypothesis-driven functional studies of PD.

Zhang, Xu; Zhou, Jianying; Chin, Mark H.; Schepmoes, Athena A.; Petyuk, Vladislav A.; Weitz, Karl K.; Petritis, Brianne O.; Monroe, Matthew E.; Camp, David G.; Wood, Stephen A.; Melega, William P.; Bigelow, Diana J.; Smith, Desmond J.; Qian, Weijun; Smith, Richard D.

2010-02-15

276

Beta-amyloid, blood vessels and brain function  

PubMed Central

Cerebrovascular disease and Alzheimer’s disease are common diseases of aging and frequently co-exist in the same brain. Accumulating evidence suggests that the presence of brain infarction, including silent infarction, influences the course of Alzheimer’s disease. Conversely, there is evidence that beta-amyloid can impair blood vessel function. Vascular beta-amyloid deposition, also known as cerebral amyloid angiopathy, is associated with vascular dysfunction in animal and human studies. Alzheimer’s disease is associated with morphological changes in capillary networks, and soluble beta-amyloid produces abnormal vascular responses to physiologic and pharmacologic stimuli. In this review we discuss current evidence linking beta-amyloid metabolism with vascular function and morphological changes in animals and humans.

Smith, Eric E.; Greenberg, Steven M.

2009-01-01

277

Revealing Topological Organization of Human Brain Functional Networks with Resting-State Functional near Infrared Spectroscopy  

PubMed Central

Background The human brain is a highly complex system that can be represented as a structurally interconnected and functionally synchronized network, which assures both the segregation and integration of information processing. Recent studies have demonstrated that a variety of neuroimaging and neurophysiological techniques such as functional magnetic resonance imaging (MRI), diffusion MRI and electroencephalography/magnetoencephalography can be employed to explore the topological organization of human brain networks. However, little is known about whether functional near infrared spectroscopy (fNIRS), a relatively new optical imaging technology, can be used to map functional connectome of the human brain and reveal meaningful and reproducible topological characteristics. Results We utilized resting-state fNIRS (R-fNIRS) to investigate the topological organization of human brain functional networks in 15 healthy adults. Brain networks were constructed by thresholding the temporal correlation matrices of 46 channels and analyzed using graph-theory approaches. We found that the functional brain network derived from R-fNIRS data had efficient small-world properties, significant hierarchical modular structure and highly connected hubs. These results were highly reproducible both across participants and over time and were consistent with previous findings based on other functional imaging techniques. Conclusions Our results confirmed the feasibility and validity of using graph-theory approaches in conjunction with optical imaging techniques to explore the topological organization of human brain networks. These results may expand a methodological framework for utilizing fNIRS to study functional network changes that occur in association with development, aging and neurological and psychiatric disorders.

Zhao, Tengda; Shu, Ni; He, Yong

2012-01-01

278

Molecular Diversity of Glutamate Receptors and Implications for Brain Function  

Microsoft Academic Search

The glutamate receptors mediate excitatory neurotransmission in the brain and are important in memory acquisition, learning, and some neurodegenerative disorders. This receptor family is classified in three groups: the N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-kainate, and metabotropic receptors. Recent molecular studies have shown that many receptor subtypes exist in all three groups of the receptors and exhibit heterogeneity in function and expression

Shigetada Nakanishi

1992-01-01

279

Exploiting Temporal Information in Functional Magnetic Resonance Imaging Brain Data  

Microsoft Academic Search

Functional Magnetic Resonance Imaging(fMRI) has enabled scientists to look into the active human brain, leading to a flood of new data, thus encouraging the development of new data analysis methods. In this paper, we contribute a comprehensive framework for spatial and tem- poral exploration of fMRI data, and apply it to a challenging case study: separating drug addicted subjects from

Lei Zhang; Dimitris Samaras; Dardo Tomasi; Nelly Alia-klein; Lisa Cottone; Andreana Leskovjan; Nora D. Volkow; Rita Goldstein

2005-01-01

280

Disrutpted resting-state functional architecture of the brain after 45-day simulated microgravity  

PubMed Central

Long-term spaceflight induces both physiological and psychological changes in astronauts. To understand the neural mechanisms underlying these physiological and psychological changes, it is critical to investigate the effects of microgravity on the functional architecture of the brain. In this study, we used resting-state functional MRI (rs-fMRI) to study whether the functional architecture of the brain is altered after 45 days of ?6° head-down tilt (HDT) bed rest, which is a reliable model for the simulation of microgravity. Sixteen healthy male volunteers underwent rs-fMRI scans before and after 45 days of ?6° HDT bed rest. Specifically, we used a commonly employed graph-based measure of network organization, i.e., degree centrality (DC), to perform a full-brain exploration of the regions that were influenced by simulated microgravity. We subsequently examined the functional connectivities of these regions using a seed-based resting-state functional connectivity (RSFC) analysis. We found decreased DC in two regions, the left anterior insula (aINS) and the anterior part of the middle cingulate cortex (MCC; also called the dorsal anterior cingulate cortex in many studies), in the male volunteers after 45 days of ?6° HDT bed rest. Furthermore, seed-based RSFC analyses revealed that a functional network anchored in the aINS and MCC was particularly influenced by simulated microgravity. These results provide evidence that simulated microgravity alters the resting-state functional architecture of the brains of males and suggest that the processing of salience information, which is primarily subserved by the aINS–MCC functional network, is particularly influenced by spaceflight. The current findings provide a new perspective for understanding the relationships between microgravity, cognitive function, autonomic neural function, and central neural activity.

Zhou, Yuan; Wang, Yun; Rao, Li-Lin; Liang, Zhu-Yuan; Chen, Xiao-Ping; Zheng, Dang; Tan, Cheng; Tian, Zhi-Qiang; Wang, Chun-Hui; Bai, Yan-Qiang; Chen, Shan-Guang; Li, Shu

2014-01-01

281

Phosphodiesterase isoform-specific expression induced by traumatic brain injury.  

PubMed

Traumatic brain injury (TBI) results in significant inflammation which contributes to the evolving pathology. Previously, we have demonstrated that cyclic AMP (cAMP), a molecule involved in inflammation, is down-regulated after TBI. To determine the mechanism by which cAMP is down-regulated after TBI, we determined whether TBI induces changes in phosphodiesterase (PDE) expression. Adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury (FPI) or sham injury, and the ipsilateral, parietal cortex was analyzed by western blotting. In the ipsilateral parietal cortex, expression of PDE1A, PDE4B2, and PDE4D2, significantly increased from 30 min to 24 h post-injury. PDE10A significantly increased at 6 and 24 h after TBI. Phosphorylation of PDE4A significantly increased from 6 h to 7 days post-injury. In contrast, PDE1B, PD4A5, and PDE4A8 significantly decreased after TBI. No changes were observed with PDE1C, PDE3A, PDE4B1/3, PDE4B4, PDE4D3, PDE4D4, PDE8A, or PDE8B. Co-localization studies showed that PDE1A, PDE4B2, and phospho-PDE4A were neuronally expressed, whereas PDE4D2 was expressed in neither neurons nor glia. These findings suggest that therapies to reduce inflammation after TBI could be facilitated with targeted therapies, in particular for PDE1A, PDE4B2, PDE4D2, or PDE10A. PMID:23057870

Oliva, Anthony A; Kang, Yuan; Furones, Concepcion; Alonso, Ofelia F; Bruno, Olga; Dietrich, W Dalton; Atkins, Coleen M

2012-12-01

282

Analysis of the Role of Lead Resistivity in Specific Absorption Rate for Deep Brain Stimulator Leads at 3T MRI  

Microsoft Academic Search

Magnetic resonance imaging (MRI) on patients with implanted deep brain stimulators (DBSs) can be hazardous because of the antenna-effect of leads exposed to the incident radio-frequency field. This study evaluated electromagnetic field and specific absorption rate (SAR) changes as a function of lead resistivity on an anatomically precise head model in a 3T system. The anatomical accuracy of our head

Leonardo M. Angelone; Jyrki Ahveninen; John W. Belliveau; Giorgio Bonmassar

2010-01-01

283

Region-specific differences in brain melanocortin receptors in rats of the lean phenotype.  

PubMed

The brain melanocortin (MC) system is one of numerous overlapping systems regulating energy balance; it consists of peptides including ?-melanocyte-stimulating hormone that act through melanocortin receptors (MCRs). Mutations and polymorphisms in MC3R and MC4R have been identified as one of the most common genetic contributors to obesity in human studies. Brain MC3R and MC4R are known to modulate energy expenditure (EE) and food intake, but much less is known regarding brain MC5R. To test the hypothesis that brain MC modulates physical activity (PA) and EE, we compared brain MCR profiles in rats that consistently show high versus low levels of 'spontaneous' daily PA. Compared with low-activity rats, high-activity rats show enhanced mRNA expression of MCRs in the brain, specifically of MC3R in the paraventricular nucleus (PVN), and MC4R and MC5R in the perifornical lateral hypothalamus. Next, we microinjected the MCR agonist melanotan II into the PVN region and measured PA and EE. Intra-PVN melanotan II induced a dose-dependent increase in PA and this effect was greater in high-activity rats compared with low-activity rats. These results indicate region-specific brain MCR expression in the heightened PA seen in association with high endurance capacity and identify promising targets in the brain MC system that may contribute to interindividual variability in energy balance. PMID:22643233

Shukla, Charu; Britton, Steven L; Koch, Lauren G; Novak, Colleen M

2012-07-11

284

Region-Specific Differences in Brain Melanocortin Receptors in Rats of the Lean Phenotype  

PubMed Central

The brain melanocortin (MC) system is one of numerous overlapping systems regulating energy balance; it consists of peptides including ?-MSH that act via MC receptors (MCR). Mutations and polymorphisms in MC3R and MC4R have been identified as one of the most common genetic contributors to obesity in human studies. Brain MC3R and MC4R are known to modulate energy expenditure (EE) and food intake, but much less is known regarding brain MC5R. To test the hypothesis that brain MC modulates physical activity (PA) and EE, we compared brain MCR profiles in rats that consistently show high vs. low levels of “spontaneous” daily PA. Compared to low-activity rats, high-activity rats show enhanced mRNA expression of MC receptors in the brain, specifically of MC3R in the paraventricular nucleus (PVN), and MC4R and MC5R in the perifornical lateral hypothalamus (PeFLH). Next, we microinjected the MCR agonist MTII into the PVN region and measured PA and EE. Intra-PVN MTII caused a dose-dependent increase in PA and this effect was greater in high-activity compared to low-activity rats. These results implicate region-specific brain MC receptor expression in the heightened PA seen in association with high endurance capacity and identify promising targets in the brain MC system that may contribute to inter-individual variability in energy balance.

Shukla, Charu; Britton, Steven L; Koch, Lauren G; Novak, Colleen M

2013-01-01

285

Brain Oscillations and Functional Connectivity during Overt Language Production  

PubMed Central

In the present study we investigate the communication of different large scale brain sites during an overt language production task with state of the art methods for the estimation of EEG functional connectivity. Participants performed a semantic blocking task in which objects were named in semantically homogeneous blocks of trials consisting of members of a semantic category (e.g., all objects are tools) or in heterogeneous blocks, consisting of unrelated objects. The classic pattern of slower naming times in the homogeneous relative to heterogeneous blocks is assumed to reflect the duration of lexical selection. For the collected data in the homogeneous and heterogeneous conditions the imaginary part of coherency (ImC) was evaluated at different frequencies. The ImC is a measure for detecting the coupling of different brain sites acting on sensor level. Most importantly, the ImC is robust to the artifact of volume conduction. We analyzed the ImC at all pairs of 56 EEG channels across all frequencies. Contrasting the two experimental conditions we found pronounced differences in the theta band at 7?Hz and estimated the most dominant underlying brain sources via a minimum norm inverse solution based on the ImC. As a result of the source localization, we observed connectivity between occipito-temporal and frontal areas, which are well-known to play a major role in lexical-semantic language processes. Our findings demonstrate the feasibility of investigating interactive brain activity during overt language production.

Ewald, Arne; Aristei, Sabrina; Nolte, Guido; Rahman, Rasha Abdel

2012-01-01

286

Neurobehavioral abnormalities in a brain-specific NADPH-cytochrome P450 reductase knockout mouse model  

PubMed Central

The aim of the present study was to test a new hypothesis that brain cytochrome P450 reductase (CPR) and CPR-dependent enzymes play important roles in behavioral performance. A mouse model with brain neuron-specific deletion of the Cpr gene (brain-Cpr-null) was recently generated. Brain-Cpr-null mice and wild-type (WT) littermates were compared in a variety of behavioral assays. Notable differences were found in the exploratory behavior assay: for both males and females, activity in the center of the chamber was significantly higher for brain-Cpr-null than for WT mice on days 2 and 3 of the assay, although no significant difference was found between the two groups in anxiety-like behavior in the elevated zero maze. Furthermore, in the fear-conditioning assay, brain-Cpr-null mice exhibited significantly less activity suppression than did WT controls. This deficit in activity suppression was not accompanied by any difference between WT and brain-Cpr-null mice in nociceptive responses to foot shocks. Abnormal activity suppression was also observed in both male and female brain-Cpr-null mice during the contextual memory test. However, in the Morris water maze assay, the brain-Cpr-null and WT mice were indistinguishable, indicating normal spatial memory in the mutant mice. These data collectively indicate a novel role of the Cpr gene in fear conditioning and memory.

Fang, Cheng; Bolivar, Valerie J.; Gu, Jun; Yang, Weizhu; Zeitlin, Scott O.; Ding, Xinxin

2012-01-01

287

Topological correlations of structural and functional networks in patients with traumatic brain injury  

PubMed Central

Despite an increasing amount of specific correlation studies between structural and functional connectivity, there is still a need for combined studies, especially in pathological conditions. Impairments of brain white matter (WM) and diffuse axonal injuries are commonly suspected to be responsible for the disconnection hypothesis in traumatic brain injury (TBI) patients. Moreover, our previous research on TBI patients shows a strong relationship between abnormalities in topological organization of brain networks and behavioral deficits. In this study, we combined task-related functional connectivity (using event-related fMRI) with structural connectivity (derived from fiber tractography using diffusion MRI data) estimates in the same participants (17 adults with TBI and 16 controls), allowing for direct comparison between graph metrics of the different imaging modalities. Connectivity matrices were computed covering the switching motor network, which includes the basal ganglia, anterior cingulate cortex/supplementary motor area, and anterior insula/inferior frontal gyrus. The edges constituting this network consisted of the partial correlations between the fMRI time series from each node of the switching motor network. The interregional anatomical connections between the switching-related areas were determined using the fiber tractography results. We found that graph metrics and hubs obtained showed no agreement in both groups. The topological properties of brain functional networks could not be solely accounted for by the properties of the underlying structural networks. However, combining complementary information from both imaging modalities could improve accuracy in prediction of switching performance. Direct comparison between functional task-related and anatomical structural connectivity, presented here for the first time in TBI patients, links two powerful approaches to map the patterns of brain connectivity that may underlie behavioral deficits in brain-injured patients.

Caeyenberghs, Karen; Leemans, Alexander; Leunissen, Inge; Michiels, Karla; Swinnen, Stephan P.

2013-01-01

288

Functional magnetic resonance imaging reflects changes in brain functioning with sedation.  

PubMed

Functional magnetic resonance imaging (fMRI) studies have demonstrated localized brain activation during cognitive tasks. Brain activation increases with task complexity and decreases with familiarity. This study investigates how sleepiness alters the relationship between brain activation and task familiarity. We hypothesize that sleepiness prevents the reduction in activation associated with practice. Twenty-nine individuals rated their sleepiness using the Stanford Sleepiness Scale before fMRI. During imaging, subjects performed the Paced Auditory Serial Addition Test, a continuous mental arithmetic task. A positive correlation was observed between self-rated sleepiness and frontal brain activation. Fourteen subjects participated in phase 2. Sleepiness was induced by evening dosing with chlorpheniramine (CP) (8 mg or 12 mg) and terfenadine (60 mg) in the morning for 3 days before the second fMRI scan. The Multiple Sleep Latency Test (MSLT) was also performed. Results revealed a significant increase in fMRI activation in proportion to the dose of CP. In contrast, for all subjects receiving placebo there was a reduction in brain activation. MSLT revealed significant daytime sleepiness for subjects receiving CP. These findings suggest that sleepiness interferes with efficiency of brain functioning. The sleepy or sedated brain shows increased oxygen utilization during performance of a familiar cognitive task. Thus, the beneficial effect of prior task exposure is lost under conditions of sedation. Copyright 2000 John Wiley & Sons, Ltd. PMID:12404614

Starbuck, Victoria N; Kay, Gary G; Platenberg, R. Craig; Lin, Chin-Shoou; Zielinski, Brandon A

2000-12-01

289

Altered functional brain networks in Prader-Willi syndrome  

PubMed Central

Prader–Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous functional neuroimaging studies used visual stimuli to examine abnormal activities in the eating-related neural circuitry of patients with PWS. It was found that patients with PWS exhibited both excessive hunger and hyperphagia consistently, even in situations without any food stimulation. In the present study, we employed resting-state functional MRI techniques to investigate abnormal brain networks related to eating disorders in children with PWS. First, we applied amplitude of low-frequency fluctuation analysis to define the regions of interest that showed significant alterations in resting-state brain activity levels in patients compared with their sibling control group. We then applied a functional connectivity (FC) analysis to these regions of interest in order to characterize interactions among the brain regions. Our results demonstrated that patients with PWS showed decreased FC strength in the medial prefrontal cortex (MPFC)/inferior parietal lobe (IPL), MPFC/precuneus, IPL/precuneus and IPL/hippocampus in the default mode network; decreased FC strength in the pre-/postcentral gyri and dorsolateral prefrontal cortex (DLPFC)/orbitofrontal cortex (OFC) in the motor sensory network and prefrontal cortex network, respectively; and increased FC strength in the anterior cingulate cortex/insula, ventrolateral prefrontal cortex (VLPFC)/OFC and DLPFC/VLPFC in the core network and prefrontal cortex network, respectively. These findings indicate that there are FC alterations among the brain regions implicated in eating as well as rewarding, even during the resting state, which may provide further evidence supporting the use of PWS as a model to study obesity and to provide information on potential neural targets for the medical treatment of overeating.

Zhang, Yi; Zhao, Heng; Qiu, Siyou; Tian, Jie; Wen, Xiaotong; Miller, Jennifer L.; von Deneen, Karen M.; Zhou, Zhenyu; Gold, Mark S.; Liu, Yijun

2013-01-01

290

Multifaceted genomic risk for brain function in schizophrenia.  

PubMed

Recently, deriving candidate endophenotypes from brain imaging data has become a valuable approach to study genetic influences on schizophrenia (SZ), whose pathophysiology remains unclear. In this work we utilized a multivariate approach, parallel independent component analysis, to identify genomic risk components associated with brain function abnormalities in SZ. 5157 candidate single nucleotide polymorphisms (SNPs) were derived from genome-wide array based on their possible connections with SZ and further investigated for their associations with brain activations captured with functional magnetic resonance imaging (fMRI) during a sensorimotor task. Using data from 92 SZ patients and 116 healthy controls, we detected a significant correlation (r=0.29; p=2.41 × 10(-5)) between one fMRI component and one SNP component, both of which significantly differentiated patients from controls. The fMRI component mainly consisted of precentral and postcentral gyri, the major activated regions in the motor task. On average, higher activation in these regions was observed in participants with higher loadings of the linked SNP component, predominantly contributed to by 253 SNPs. 138 identified SNPs were from known coding regions of 100 unique genes. 31 identified SNPs did not differ between groups, but moderately correlated with some other group-discriminating SNPs, indicating interactions among alleles contributing toward elevated SZ susceptibility. The genes associated with the identified SNPs participated in four neurotransmitter pathways: GABA receptor signaling, dopamine receptor signaling, neuregulin signaling and glutamate receptor signaling. In summary, our work provides further evidence for the complexity of genomic risk to the functional brain abnormality in SZ and suggests a pathological role of interactions between SNPs, genes and multiple neurotransmitter pathways. PMID:22440650

Chen, Jiayu; Calhoun, Vince D; Pearlson, Godfrey D; Ehrlich, Stefan; Turner, Jessica A; Ho, Beng-Choon; Wassink, Thomas H; Michael, Andrew M; Liu, Jingyu

2012-07-16

291

Dynamic representations and generative models of brain function.  

PubMed

The main point made in this article is that the representational capacity and inherent function of any neuron, neuronal population or cortical area is dynamic and context-sensitive. This adaptive and contextual specialisation is mediated by functional integration or interactions among brain systems with a special emphasis on backwards or top-down connections. The critical notion is that neuronal responses, in any given cortical area, can represent different things at different times. Our argument is developed under the perspective of generative models of functional brain architectures, where higher-level systems provide a prediction of the inputs to lower-level regions. Conflict between the two is resolved by changes in the higher-level representations, driven by the resulting error in lower regions, until the mismatch is 'cancelled'. In this model the specialisation of any region is determined both by bottom-up driving inputs and by top-down predictions. Specialisation is therefore not an intrinsic property of any region but depends on both forward and backward connections with other areas. Because these other areas have access to the context in which the inputs are generated they are in a position to modulate the selectivity or specialisation of lower areas. The implications for 'classical' models (e.g., classical receptive fields in electrophysiology, classical specialisation in neuroimaging and connectionism in cognitive models) are severe and suggest these models provide incomplete accounts of real brain architectures. Generative models represent a far more plausible framework for understanding selective neurophysiological responses and how representations are constructed in the brain. PMID:11287132

Friston, K J; Price, C J

2001-02-01

292

Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases  

PubMed Central

Background Primary and secondary brain cancers are highly treatment resistant, and their marked angiogenesis attracts interest as a potential therapeutic target. Recent observations reveal that the microvascular endothelium of primary high-grade gliomas expresses prostate specific membrane antigen (PSMA). Breast cancers express PSMA and they frequently form secondary brain tumors. Hence we report here our pilot study addressing the feasibility of PSMA targeting in brain and metastatic breast tumors, by examining PSMA levels in all glioma grades (19 patients) and in breast cancer brain metastases (5 patients). Methods Tumor specimens were acquired from archival material and normal brain tissues from autopsies. Tissue were stained and probed for PSMA, and the expression levels imaged and quantified using automated hardware and software. PSMA staining intensities of glioma subtypes, breast tumors, and breast tumor brain metastases were compared statistically versus normals. Results Normal brain microvessels (4 autopsies) did not stain for PSMA, while a small proportion (<5%) of healthy neurons stained, and were surrounded by an intact blood brain barrier. Tumor microvessels of the highly angiogenic grade IV gliomas showed intense PSMA staining which varied between patients and was significantly higher (p?brain. Grade I gliomas showed moderate vessel staining, while grade II and III gliomas had no vessel staining, but a few (<2%) of the tumor cells stained. Both primary breast cancer tissues and the associated brain metastases exhibited vascular PSMA staining, although the intensity of staining was generally less for the metastatic lesions. Conclusions Our results align with and extend previous data showing PSMA expression in blood vessels of gliomas and breast cancer brain metastases. These results provide a rationale for more comprehensive studies to explore PSMA targeted agents for treating secondary brain tumors with PSMA expressing vasculature. Moreover, given that PSMA participates in angiogenesis, cell signaling, tumor survival, and invasion, characterizing its expression may help guide later investigations of the poorly understood process of low grade glioma progression to glioblastoma.

2014-01-01

293

Neural Darwinism: selection and reentrant signaling in higher brain function.  

PubMed

Variation and selection within neural populations play key roles in the development and function of the brain. In this article, I review a population theory of the nervous system aimed at understanding the significance of these processes. Since its original formulation in 1978, considerable evidence has accumulated to support this theory of neuronal group selection. Extensive neural modeling based on the theory has provided useful insights into several outstanding neurobiological problems including those concerned with integration of cortical function, sensorimotor control, and perceptually based behavior. PMID:8094962

Edelman, G M

1993-02-01

294

[The effect of Piracetam on adolescent brain function].  

PubMed

A report on investigations with Piracetam, recently introduced into therapy, is given. Piracetam is mainly characterized by cerebral metabolic effects, leading to an activation of cerebral functions as well as to brain protection. Experimental studies showed the highly selective activity of Piracetam on cerebral cortex, which is responsible for higher mental functions as consciousness, vigilance and memory. Therapeutic results in 48 adolescents with poor school results are reported. These patients were treated with Piracetam for a continuous period up to 14 months. The therapy lead to convincing improvements in terms of school results. PMID:1213644

Fiegel, G

1975-09-11

295

Brain region specific mitophagy capacity could contribute to selective neuronal vulnerability in Parkinson's disease  

PubMed Central

Parkinson's disease (PD) is histologically well defined by its characteristic degeneration of dopaminergic neurons in the substantia nigra pars compacta. Remarkably, divergent PD-related mutations can generate comparable brain region specific pathologies. This indicates that some intrinsic region-specificity respecting differential neuron vulnerability exists, which codetermines the disease progression. To gain insight into the pathomechanism of PD, we investigated protein expression and protein oxidation patterns of three different brain regions in a PD mouse model, the PINK1 knockout mice (PINK1-KO), in comparison to wild type control mice. The dysfunction of PINK1 presumably affects mitochondrial turnover by disturbing mitochondrial autophagic pathways. The three brain regions investigated are the midbrain, which is the location of substantia nigra; striatum, the major efferent region of substantia nigra; and cerebral cortex, which is more distal to PD pathology. In all three regions, mitochondrial proteins responsible for energy metabolism and membrane potential were significantly altered in the PINK1-KO mice, but with very different region specific accents in terms of up/down-regulations. This suggests that disturbed mitophagy presumably induced by PINK1 knockout has heterogeneous impacts on different brain regions. Specifically, the midbrain tissue seems to be most severely hit by defective mitochondrial turnover, whereas cortex and striatum could compensate for mitophagy nonfunction by feedback stimulation of other catabolic programs. In addition, cerebral cortex tissues showed the mildest level of protein oxidation in both PINK1-KO and wild type mice, indicating either a better oxidative protection or less reactive oxygen species (ROS) pressure in this brain region. Ultra-structural histological examination in normal mouse brain revealed higher incidences of mitophagy vacuoles in cerebral cortex than in striatum and substantia nigra. Taken together, the delicate balance between oxidative protection and mitophagy capacity in different brain regions could contribute to brain region-specific pathological patterns in PD.

2011-01-01

296

Heritability of human brain functioning as assessed by electroencephalography.  

PubMed Central

To study the genetic and environmental contributions to individual differences in CNS functioning, the electroencephalogram (EEG) was measured in 213 twin pairs age 16 years. EEG was measured in 91 MZ and 122 DZ twins. To quantify sex differences in the genetic architecture, EEG was measured in female and male same-sex twins and in opposite-sex twins. EEG was recorded on 14 scalp positions during quiet resting with eyes closed. Spectral powers were calculated for four frequency bands: delta, theta, alpha, and beta. Twin correlations pointed toward high genetic influences for all these powers and scalp locations. Model fitting confirmed these findings; the largest part of the variance of the EEG is explained by additive genetic factors. The averaged heritabilites for the delta, theta, alpha and beta frequencies was 76%, 89%, 89%, and 86%, respectively. Multivariate analyses suggested that the same genes for EEG alpha rhythm were expressed in different brain areas in the left and right hemisphere. This study shows that brain functioning, as indexed by rhythmic brain-electrical activity, is one of the most heritable characteristics in humans.

van Beijsterveldt, C. E.; Molenaar, P. C.; de Geus, E. J.; Boomsma, D. I.

1996-01-01

297

Roles of Brain Angiotensin II in Cognitive Function and Dementia  

PubMed Central

The brain renin-angiotensin system (RAS) has been highlighted as having a pathological role in stroke, dementia, and neurodegenerative disease. Particularly, in dementia, epidemiological studies indicate a preventive effect of RAS blockade on cognitive impairment in Alzheimer disease (AD). Moreover, basic experiments suggest a role of brain angiotensin II in neural injury, neuroinflammation, and cognitive function and that RAS blockade attenuates cognitive impairment in rodent dementia models of AD. Therefore, RAS regulation is expected to have therapeutic potential for AD. Here, we discuss the role of angiotensin II in cognitive impairment and AD. Angiotensin II binds to the type 2 receptor (AT2) and works mainly by binding with the type 1 receptor (AT1). AT2 receptor signaling plays a role in protection against multiple-organ damage. A direct AT2 receptor agonist is now available and is expected to reduce inflammation and oxidative stress and enhance cell differentiation. We and other groups reported that AT2 receptor activation enhances neuronal differentiation and neurite outgrowth in the brain. Here, we also review the effect of the AT2 receptor on cognitive function. RAS modulation may be a new therapeutic option for dementia including AD in the future.

Mogi, Masaki; Iwanami, Jun; Horiuchi, Masatsugu

2012-01-01

298

Lateralization of Cognitive Functions in Aphasia after Right Brain Damage  

PubMed Central

Purpose The lateralization of cognitive functions in crossed aphasia in dextrals (CAD) has been explored and compared mainly with cases of aphasia with left hemisphere damage. However, comparing the neuropsychological aspects of CAD and aphasia after right brain damage in left-handers (ARL) could potentially provide more insights into the effect of a shift in the laterality of handedness or language on other cognitive organization. Thus, this case study compared two cases of CAD and one case of ARL. Materials and Methods The following neuropsychological measures were obtained from three aphasic patients with right brain damage (two cases of CAD and one case of ARL); language, oral and limb praxis, and nonverbal cognitive functions (visuospatial neglect and visuospatial construction). Results All three patients showed impaired visuoconstructional abilities, whereas each patient showed a different level of performances for oral and limb praxis, and visuospatial neglect. Conclusion Based on the analysis of these three aphasic patients' performances, we highlighted the lateralization of language, handedness, oral and limb praxis, visuospatial neglect and visuospatial constructive ability in aphasic patients with right brain damage.

Ha, Ji-Wan; Hwang, Yu Mi; Sim, Hyunsub

2012-01-01

299

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

ERIC Educational Resources Information Center

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…

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

300

CD36 expression and brain function: does CD36 deficiency impact learning ability?  

Microsoft Academic Search

This article first presents an overview of published literature documenting the role of the scavenger receptor CD36 in activation of brain microglia with reference to brain pathologies such as Alzheimer's and malaria. Second, the possibility that CD36 may play a role in brain FA metabolism is discussed. Long-chain polyunsaturated fatty acids (PUFAs) are important for brain function and are mostly

Nada A. Abumrad; Mohammad Ajmal; Kostas Pothakos; John K. Robinson

2005-01-01

301

Brain-specific deletion of neuropathy target esterase/swisscheese results in neurodegeneration  

PubMed Central

Neuropathy target esterase (NTE) is a neuronal membrane protein originally identified for its property to be modified by organo-phosphates (OPs), which in humans cause neuropathy characterized by axonal degeneration. Drosophila mutants for the homolog gene of NTE, swisscheese (sws), indicated a possible involvement of sws in the regulation of axon-glial cell interaction during glial wrapping. However, the role of NTE/sws in mammalian brain pathophysiology remains unknown. To investigate NTE function in vivo, we used the cre/loxP site-specific recombination strategy to generate mice with a specific deletion of NTE in neuronal tissues. Here we show that loss of NTE leads to prominent neuronal pathology in the hippocampus and thalamus and also defects in the cerebellum. Absence of NTE resulted in disruption of the endoplasmic reticulum, vacuolation of nerve cell bodies, and abnormal reticular aggregates. Thus, these results identify a physiological role for NTE in the nervous system and indicate that a loss-of-function mechanism may contribute to neurodegenerative diseases characterized by vacuolation and neuronal loss.

Akassoglou, Katerina; Malester, Brian; Xu, Jixiang; Tessarollo, Lino; Rosenbluth, Jack; Chao, Moses V.

2004-01-01

302

Effect of disease and recovery on functional anatomy in brain tumor patients: insights from functional MRI and diffusion tensor imaging  

PubMed Central

Patients with brain tumors provide a unique opportunity to understand functional brain plasticity. Using advanced imaging techniques, such as functional MRI and diffusion tensor imaging, we have gained tremendous knowledge of brain tumor behavior, transformation, infiltration and destruction of nearby structures. Using these advanced techniques as an adjunct with more proven techniques, such as direct cortical stimulation, intraoperative navigation and advanced microsurgical techniques, we now are able to better formulate safer resection trajectories, perform larger resections at reduced risk and better counsel patients and their families about possible complications. Brain mapping in patients with brain tumors and other lesions has shown us that the old idea of fixed function of the adult cerebral cortex is not entirely true. Improving care for patients with brain lesions in the future will depend on better understanding of the functional organization and plasticity of the adult brain. Advanced noninvasive brain imaging will undoubtedly play a role in advancing this understanding.

Abd-El-Barr, Muhammad M; Saleh, Emam; Huang, Raymond Y; Golby, Alexandra J

2014-01-01

303

Strengthened functional connectivity in the brain during muscle fatigue.  

PubMed

Fatigue caused by sustaining submaximal-intensity muscle contraction(s) involves increased activation in the brain such as primary motor cortex (M1), primary sensory cortex (S1), premotor and supplementary motor area (PM&SMA) and prefrontal cortex (PFC). The synchronized increases in activation level in these cortical areas suggest fatigue-related strengthening of functional coupling within the motor control network. In the present study, this hypothesis was tested using the cross-correlation based functional connectivity (FC) analysis method. Ten subjects performed a 20-minute intermittent (3.5s ON/6.5s OFF, 120 trials total) handgrip task using the right hand at 50% maximal voluntary contraction (MVC) force level while their brain was scanned by a 3 T Siemens Trio scanner using echo planar imaging (EPI) sequence. A representative signal time course of the left M1 was extracted by averaging the time course data of a 2-mm cluster of neighboring voxels of local maximal activation foci, which was identified by a general linear model. Two FC activation maps were created for each subject by cross-correlating the time course data of the minimal (the first 10 trials) and significant (the last 10 trials) fatigue stages across all the voxels in the brain to the corresponding representative time course. Histogram and quantile regression analysis were used to compare the FC between the minimal and significant fatigue stages and the results showed a significant increase in FC among multiple cortical regions, including right M1 and bilateral PM&SMA, S1 and PFC. This strengthened FC indicates that when muscle fatigue worsens, many brain regions increase their coupling with the left M1, the primary motor output control center for the right handgrip, to compensate for diminished force generating capability of the muscle in a coordinated fashion by enhancing the descending command for greater muscle recruitment to maintain the same force. PMID:22197785

Jiang, Zhiguo; Wang, Xiao-Feng; Kisiel-Sajewicz, Katarzyna; Yan, Jin H; Yue, Guang H

2012-03-01

304

[Localisation of brain function, 125 years after the thesis of Aletta Jacobs, the first Dutch female physician].  

PubMed

Aletta H. Jacobs was the first female physician in the Netherlands. In 1879, she defended her thesis which addressed the subject of localising brain functions. In it she described three neurological patients using systematic conventions highly resembling those in use today. Moreover, she discussed whether or not functions were regionally represented. Her discussion concluded in favour of localisation. These days, the concept of distributed networks goes beyond simple topographical representation. This is illustrated in the cerebral organisation of vision. It is possible to discern visual centres that are specialised in processing specific qualities such as colour or visual motion. An additional feature of such segregated processing streams is the presence of underlying connections to specific brain areas at a distance. Functioning as a node in multiple networks, one single brain region may potentially be involved in multiple functions. This depends on the interactions with other regions and on the actual dominance of information processing within such networks. PMID:15771345

de Jong, B M

2005-02-26

305

PROTEIN III, A NEURON-SPECIFIC PHOSPHOPROTEIN: VARIANT FORMS FOUND IN HUMAN BRAIN  

EPA Science Inventory

Recent work in the laboratory has shown the presence of many neuron-specific phosphoproteins in the mammalian nervous system. Two of these proteins, Protein III and Synapsin I, are specifically associated with synaptic vesicles in neurons throughout the brain. Protein III consist...

306

Atypical Brain Responses to Sounds in Children with Specific Language and Reading Impairments  

ERIC Educational Resources Information Center

This study tested if children with specific language impairment (SLI) or children with specific reading disability (SRD) have abnormal brain responses to sounds. We tested 6- to 12-year-old children with SLI (N = 19), children with SRD (N = 55), and age-matched controls (N = 36) for their passive auditory event-related potentials (ERPs) to tones,…

McArthur, Genevieve; Atkinson, Carmen; Ellis, Danielle

2009-01-01

307

Functional brain networks and cognitive deficits in Parkinson's disease.  

PubMed

Graph-theoretical analyses of functional networks obtained with resting-state functional magnetic resonance imaging (fMRI) have recently proven to be a useful approach for the study of the substrates underlying cognitive deficits in different diseases. We used this technique to investigate whether cognitive deficits in Parkinson's disease (PD) are associated with changes in global and local network measures. Thirty-six healthy controls (HC) and 66 PD patients matched for age, sex, and education were classified as having mild cognitive impairment (MCI) or not based on performance in the three mainly affected cognitive domains in PD: attention/executive, visuospatial/visuoperceptual (VS/VP), and declarative memory. Resting-state fMRI and graph theory analyses were used to evaluate network measures. We have found that patients with MCI had connectivity reductions predominantly affecting long-range connections as well as increased local interconnectedness manifested as higher measures of clustering, small-worldness, and modularity. The latter measures also tended to correlate negatively with cognitive performance in VS/VP and memory functions. Hub structure was also reorganized: normal hubs displayed reduced centrality and degree in MCI PD patients. Our study indicates that the topological properties of brain networks are changed in PD patients with cognitive deficits. Our findings provide novel data regarding the functional substrate of cognitive impairment in PD, which may prove to have value as a prognostic marker. Hum Brain Mapp 35:4620-4634, 2014. © 2014 Wiley Periodicals, Inc. PMID:24639411

Baggio, Hugo-Cesar; Sala-Llonch, Roser; Segura, Bàrbara; Marti, Maria-José; Valldeoriola, Francesc; Compta, Yaroslau; Tolosa, Eduardo; Junqué, Carme

2014-09-01

308

Neurophysiological architecture of functional magnetic resonance images of human brain.  

PubMed

We investigated large-scale systems organization of the whole human brain using functional magnetic resonance imaging (fMRI) data acquired from healthy volunteers in a no-task or 'resting' state. Images were parcellated using a prior anatomical template, yielding regional mean time series for each of 90 regions (major cortical gyri and subcortical nuclei) in each subject. Significant pairwise functional connections, defined by the group mean inter-regional partial correlation matrix, were mostly either local and intrahemispheric or symmetrically interhemispheric. Low-frequency components in the time series subtended stronger inter-regional correlations than high-frequency components. Intrahemispheric connectivity was generally related to anatomical distance by an inverse square law; many symmetrical interhemispheric connections were stronger than predicted by the anatomical distance between bilaterally homologous regions. Strong interhemispheric connectivity was notably absent in data acquired from a single patient, minimally conscious following a brainstem lesion. Multivariate analysis by hierarchical clustering and multidimensional scaling consistently defined six major systems in healthy volunteers-- corresponding approximately to four neocortical lobes, medial temporal lobe and subcortical nuclei- - that could be further decomposed into anatomically and functionally plausible subsystems, e.g. dorsal and ventral divisions of occipital cortex. An undirected graph derived by thresholding the healthy group mean partial correlation matrix demonstrated local clustering or cliquishness of connectivity and short mean path length compatible with prior data on small world characteristics of non-human cortical anatomy. Functional MRI demonstrates a neurophysiological architecture of the normal human brain that is anatomically sensible, strongly symmetrical, disrupted by acute brain injury, subtended predominantly by low frequencies and consistent with a small world network topology. PMID:15635061

Salvador, Raymond; Suckling, John; Coleman, Martin R; Pickard, John D; Menon, David; Bullmore, Ed

2005-09-01

309

Constructing Patient Specific Models for Correcting Intraoperative Brain Deformation  

Microsoft Academic Search

In this work we present a Mesh Warping technique for the construction of patient-specific Finite Element Method models from\\u000a patient MRI images, and demonstrate how simulated surgical loading can be applied to these models. We compare the results\\u000a of this simulation with observed deformation during surgery, and show that our model matches well with the observed degree\\u000a of deformation.

Andy D. Castellano-smith; Thomas Hartkens; Julia A. Schnabel; D. Rodney Hose; Haiying Liu; Walter A. Hall; Charles L. Truwit; David J. Hawkes; Derek L. G. Hill

2001-01-01

310

Brain region-specific altered expression and association of mitochondria-related genes in autism  

PubMed Central

Background Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most of the previous studies of MtD in autism have been restricted to the biomarkers of energy metabolism, while most of the genetic studies have been based on mutations in the mitochondrial DNA (mtDNA). Despite the mtDNA, most of the proteins essential for mitochondrial replication and function are encoded by the genomic DNA; so far, there have been very few studies of those genes. Therefore, we carried out a detailed study involving gene expression and genetic association studies of genes related to diverse mitochondrial functions. Methods For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus (ACG), motor cortex (MC) and thalamus (THL)) from autism patients (n=8) and controls (n=10) were obtained from the Autism Tissue Program (Princeton, NJ, USA). Quantitative real-time PCR arrays were used to quantify the expression of 84 genes related to diverse functions of mitochondria, including biogenesis, transport, translocation and apoptosis. We used the delta delta Ct (??Ct) method for quantification of gene expression. DNA samples from 841 Caucasian and 188 Japanese families were used in the association study of genes selected from the gene expression analysis. FBAT was used to examine genetic association with autism. Results Several genes showed brain region-specific expression alterations in autism patients compared to controls. Metaxin 2 (MTX2), neurofilament, light polypeptide (NEFL) and solute carrier family 25, member 27 (SLC25A27) showed consistently reduced expression in the ACG, MC and THL of autism patients. NEFL (P = 0.038; Z-score 2.066) and SLC25A27 (P = 0.046; Z-score 1.990) showed genetic association with autism in Caucasian and Japanese samples, respectively. The expression of DNAJC19, DNM1L, LRPPRC, SLC25A12, SLC25A14, SLC25A24 and TOMM20 were reduced in at least two of the brain regions of autism patients. Conclusions Our study, though preliminary, brings to light some new genes associated with MtD in autism. If MtD is detected in early stages, treatment strategies aimed at reducing its impact may be adopted.

2012-01-01

311

A New Type of Neuron-specific Aminopeptidase NAP-2 in Rat Brain Synaptosomes  

PubMed Central

A novel neutral aminopeptidase (NAP-2)1 was found exclusively in the rat central nervous system (CNS). It was separated from the ubiquitous puromycin-sensitive aminopeptidase (PSA) and the neuron-specific aminopeptidase (NAP) by an automated FPLC-aminopeptidase analyzer. The activity of the neuronal aminopeptidase enriched in the synaptosomes is different from NAP and PSA in distribution and during brain development. The enzyme was purified 2,230-fold to apparent homogeneity from rat brain cytosol with 4% recovery by ammonium sulfate fractionation, followed by column chromatography successively on Phenyl-Sepharose, Q-Sepharose, Sephadex G-200, and Mono Q. The single-chain enzyme with a molecular mass of 110 kDa has an optimal pH of 7.0 and a pI of 5.6. It splits ?-naphthylamides of amino acid with aliphatic, polar uncharged, positively charged, and aromatic side chain. Leucyl ?-naphthylamide (Leu ?NA) is the best substrate with the highest hydrolytic coefficiency followed by Met ?NA = Arg ?NA = Lys ?NA > Ala ?NA > Tyr ?NA > Phe ?NA. The cysteine-, metallo-, glyco-aminopeptidase releases the N-terminal Tyr from Leu-enkephalin with a Km 82 ?M and a kcat of 1.08 s?1, and Met-enkephalin with a Km of 106 ?M and a kcat of 2.6 s?1. The puromycin-sensitive enzyme is most susceptible to amastatin with an IC50 of 0.05 ?M. The data indicate that the enzyme is a new type of neuron-specific aminopeptidase found in rodent. Its possible function in neuron growth, neurodegeneration, and carcinomas is discussed.

Hui, Maria; Hui, Koon-Sea

2008-01-01

312

Brain Gut Microbiome Interactions and Functional Bowel Disorders  

PubMed Central

Alterations in the bidirectional interactions between the gut and the nervous system play an important role in IBS pathophysiology and symptom generation. A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. Characterizations of alterations of gut microbiota in unselected IBS patients, and assessment of changes in subjective symptoms associated with manipulations of the gut microbiota with prebiotics, probiotics and antibiotics support a small, but poorly defined role of dybiosis in overall IBS symptoms. It remains to be determined if the observed abnormalities are a consequence of altered top down signaling from the brain to the gut and microbiota, if they are secondary to a primary perturbation of the microbiota, and if they play a role in the development of altered brain gut interactions early in life. Different mechanisms may play role in subsets of patients. Characterization of gut microbiome alterations in large cohorts of well phenotyped patients as well as evidence correlating gut metabolites with specific abnormalities in the gut brain axis are required to answer these questions.

Mayer, Emeran A.; Savidge, Tor; Shulman, Robert J.

2014-01-01

313

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

PubMed

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

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

2009-05-01

314

Detecting brain state changes via fiber-centered functional connectivity analysis.  

PubMed

Diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) have been widely used to study structural and functional brain connectivity in recent years. A common assumption used in many previous functional brain connectivity studies is the temporal stationarity. However, accumulating literature evidence has suggested that functional brain connectivity is under temporal dynamic changes in different time scales. In this paper, a novel and intuitive approach is proposed to model and detect dynamic changes of functional brain states based on multimodal fMRI/DTI data. The basic idea is that functional connectivity patterns of all fiber-connected cortical voxels are concatenated into a descriptive functional feature vector to represent the brain's state, and the temporal change points of brain states are decided by detecting the abrupt changes of the functional vector patterns via the sliding window approach. Our extensive experimental results have shown that meaningful brain state change points can be detected in task-based fMRI/DTI, resting state fMRI/DTI, and natural stimulus fMRI/DTI data sets. Particularly, the detected change points of functional brain states in task-based fMRI corresponded well to the external stimulus paradigm administered to the participating subjects, thus partially validating the proposed brain state change detection approach. The work in this paper provides novel perspective on the dynamic behaviors of functional brain connectivity and offers a starting point for future elucidation of the complex patterns of functional brain interactions and dynamics. PMID:22941508

Li, Xiang; Lim, Chulwoo; Li, Kaiming; Guo, Lei; Liu, Tianming

2013-04-01

315

The novel brain-specific tryptophan hydroxylase-2 gene in panic disorder.  

PubMed

Panic disorder is a common psychiatric disorder characterized by recurrent anxiety attacks and anticipatory anxiety. Due to the severity of the symptoms of the panic attacks and the frequent additional occurrence of agoraphobia, panic disorder is an often debilitating disease. Elevation of central serotonin levels by drugs such as clomipramine represents one of the most effective treatment options for panic disorder. This points to an important role of dysregulation of the serotonergic system in the genetic etiology of panic disorder. The novel brain-specific 5-HT synthesizing enzyme, tryptophan hydroxylase-2 (TPH2), which represents the rate-limiting enzyme of 5-HT production in the brain, may therefore be of particular importance in panic disorder. We focused on the putative transcriptional control region of TPH2 and identified two novel common single nucleotide polymorphisms (SNPs) of TPH2 in and close to this region. Moreover, a recently described loss-of-function mutation of TPH2 which results in an 80% reduction of serotonin production, was assessed. In an analysis of the putative transcriptional control region SNPs in a sample of panic disorder patients and controls no association of the disorder with the TPH2 SNPs or haplotypes was found. Moreover, the loss-of-function R441H mutation of TPH2 was not present in the panic disorder patients. The results of this first study of TPH2 in panic disorder argue against an importance of allelic variation of TPH2 in the pathogenesis of panic disorder with or without agoraphobia. PMID:16401665

Mössner, Rainald; Freitag, Christine M; Gutknecht, Lise; Reif, Andreas; Tauber, Ralf; Franke, Petra; Fritze, Jürgen; Wagner, Gerd; Peikert, Gregor; Wenda, Berit; Sand, Philipp; Rietschel, Marcella; Garritsen, Henk; Jacob, Christian; Lesch, K Peter; Deckert, Jürgen

2006-07-01

316

Age-Specific Effects of Voluntary Exercise on Memory and the Older Brain  

PubMed Central

Background Physical exercise in early adulthood and mid-life improves cognitive function and enhances brain plasticity, but the effects of commencing exercise in late adulthood are not well-understood. Method We investigated the effects of voluntary exercise in the restoration of place recognition memory in aged rats and examined hippocampal changes of synaptic density and neurogenesis. Results We found a highly selective age-related deficit in place recognition memory that is stable across retest sessions and correlates strongly with loss of hippocampal synapses. Additionally, 12 weeks of voluntary running at 20 months of age removed the deficit in the hippocampally dependent place recognition memory. Voluntary running restored presynaptic density in the dentate gyrus and CA3 hippocampal subregions in aged rats to levels beyond those observed in younger animals, in which exercise had no functional or synaptic effects. By contrast, hippocampal neurogenesis, a possible memory-related mechanism, increased in both young and aged rats after physical exercise but was not linked with performance in the place recognition task. We used graph-based network analysis based on synaptic covariance patterns to characterize efficient intrahippocampal connectivity. This analysis revealed that voluntary running completely reverses the profound degradation of hippocampal network efficiency that accompanies sedentary aging. Furthermore, at an individual animal level, both overall hippocampal presynaptic density and subregional connectivity independently contribute to prediction of successful place recognition memory performance. Conclusions Our findings emphasize the unique synaptic effects of exercise on the aged brain and their specific relevance to a hippocampally based memory system for place recognition.

Siette, Joyce; Westbrook, R. Frederick; Cotman, Carl; Sidhu, Kuldip; Zhu, Wanlin; Sachdev, Perminder; Valenzuela, Michael J.

2014-01-01

317

Using computational models to relate structural and functional brain connectivity  

PubMed Central

Modern imaging methods allow a non-invasive assessment of both structural and functional brain connectivity. This has lead to the identification of disease-related alterations affecting functional connectivity. The mechanism of how such alterations in functional connectivity arise in a structured network of interacting neural populations is as yet poorly understood. Here we use a modeling approach to explore the way in which this can arise and to highlight the important role that local population dynamics can have in shaping emergent spatial functional connectivity patterns. The local dynamics for a neural population is taken to be of the Wilson–Cowan type, whilst the structural connectivity patterns used, describing long-range anatomical connections, cover both realistic scenarios (from the CoComac database) and idealized ones that allow for more detailed theoretical study. We have calculated graph–theoretic measures of functional network topology from numerical simulations of model networks. The effect of the form of local dynamics on the observed network state is quantified by examining the correlation between structural and functional connectivity. We document a profound and systematic dependence of the simulated functional connectivity patterns on the parameters controlling the dynamics. Importantly, we show that a weakly coupled oscillator theory explaining these correlations and their variation across parameter space can be developed. This theoretical development provides a novel way to characterize the mechanisms for the breakdown of functional connectivity in diseases through changes in local dynamics.

Hlinka, Jaroslav; Coombes, Stephen

2012-01-01

318

Task-specific deactivation patterns in functional magnetic resonance imaging  

Microsoft Academic Search

In general, image analysis of cognitive experiments using functional magnetic resonance imaging techniques has emphasized those regions of the brain where increases in signal intensity, with regard to the reference state, are associated with activation. Nevertheless, a number of recent papers have shown that there are areas of deactivation as well. In this study, we have used a univariate analysis

M Hutchinson; W Schiffer; S Joseffer; A Liu; R Schlosser; S Dikshit; E Goldberg; J. D Brodie

1999-01-01

319

Epigenetic Regulation of a Brain-specific Glycosyltransferase N-Acetylglucosaminyltransferase-IX (GnT-IX) by Specific Chromatin Modifiers.  

PubMed

Expression of glycosyltransferase genes is essential for glycosylation. However, the detailed mechanisms of how glycosyltransferase gene expression is regulated in a specific tissue or during disease progression are poorly understood. In particular, epigenetic studies of glycosyltransferase genes are limited, although epigenetic mechanisms, such as histone and DNA modifications, are central to establish tissue-specific gene expression. We previously found that epigenetic histone activation is essential for brain-specific expression of N-acetylglucosaminyltransferase-IX (GnT-IX, also designated GnT-Vb), but the mechanism of brain-specific chromatin activation around GnT-IX gene (Mgat5b) has not been clarified. To reveal the mechanisms regulating the chromatin surrounding GnT-IX, we have investigated the epigenetic factors that are specifically involved with the mouse GnT-IX locus by comparing their involvement with other glycosyltransferase loci. We first found that a histone deacetylase (HDAC) inhibitor enhanced the expression of GnT-IX but not of other glycosyltransferases tested. By overexpression and knockdown of a series of HDACs, we found that HDAC11 silenced GnT-IX. We also identified the O-GlcNAc transferase (OGT) and ten-eleven translocation-3 (TET3) complex as a specific chromatin activator of GnT-IX gene. Moreover, chromatin immunoprecipitation (ChIP) analysis in combination with OGT or TET3 knockdown showed that this OGT-TET3 complex facilitates the binding of a potent transactivator, NeuroD1, to the GnT-IX promoter, suggesting that epigenetic chromatin activation by the OGT-TET3 complex is a prerequisite for the efficient binding of NeuroD1. These results reveal a new epigenetic mechanism of brain-specific GnT-IX expression regulated by defined chromatin modifiers, providing new insights into the tissue-specific expression of glycosyltransferases. PMID:24619417

Kizuka, Yasuhiko; Kitazume, Shinobu; Okahara, Kyohei; Villagra, Alejandro; Sotomayor, Eduardo M; Taniguchi, Naoyuki

2014-04-18

320

Prepubertal stress and hippocampal function: Sex-specific effects.  

PubMed

The chances of developing psychiatric disorders in adulthood are increased when stress is experienced early in life. In particular, stress experienced in the childhood or 'prepubertal' phase is associated with the later development of disorders such as depression, anxiety, post-traumatic stress disorder, and psychosis. Relatively little is known about the biological basis of this effect, but one hypothesis is that prepubertal stress produces long-lasting changes in brain development, particularly in stress sensitive regions such as the hippocampus, leaving an individual vulnerable to disorders in adulthood. In this study, we used an animal model of prepubertal stress to investigate the hypothesis that prepubertal stress induces alterations in hippocampal function in adulthood. Male and female rats were exposed to a brief, variable prepubertal stress protocol (postnatal days 25-27), and their performance in two distinct hippocampal-dependent tasks (contextual fear and spatial navigation) was compared with controls in adulthood. Prepubertal stress significantly impaired contextual fear responses in males and enhanced performance in spatial navigation in females. These results demonstrate that exposure to a brief period of stress in the prepubertal phase alters hippocampal-dependent behaviors in adulthood in a sex-specific manner. © 2014 Wiley Periodicals, Inc. PMID:24677338

Brydges, Nichola M; Wood, Emma R; Holmes, Megan C; Hall, Jeremy

2014-06-01

321

Affect and the Brain's Functional Organization: A Resting-State Connectivity Approach  

PubMed Central

The question of how affective processing is organized in the brain is still a matter of controversial discussions. Based on previous initial evidence, several suggestions have been put forward regarding the involved brain areas: (a) right-lateralized dominance in emotional processing, (b) hemispheric dominance according to positive or negative valence, (c) one network for all emotional processing and (d) region-specific discrete emotion matching. We examined these hypotheses by investigating intrinsic functional connectivity patterns that covary with results of the Positive and Negative Affective Schedule (PANAS) from 65 participants. This approach has the advantage of being able to test connectivity rather than activation, and not requiring a potentially confounding task. Voxelwise functional connectivity from 200 regions-of-interest covering the whole brain was assessed. Positive and negative affect covaried with functional connectivity involving a shared set of regions, including the medial prefrontal cortex, the anterior cingulate, the visual cortex and the cerebellum. In addition, each affective domain had unique connectivity patterns, and the lateralization index showed a right hemispheric dominance for negative affect. Therefore, our results suggest a predominantly right-hemispheric network with affect-specific elements as the underlying organization of emotional processes.

Rohr, Christiane S.; Okon-Singer, Hadas; Craddock, R. Cameron; Villringer, Arno; Margulies, Daniel S.

2013-01-01

322

Distinct Functions of Glial and Neuronal Dystroglycan in the Developing and Adult Mouse Brain  

PubMed Central

SUMMARY Cobblestone (type II) lissencephaly and mental retardation are characteristic features of a subset of congenital muscular dystrophies that include Walker-Warburg Syndrome, Muscle-Eye-Brain disease, and Fukuyama-type congenital muscular dystrophy. Although the majority of clinical cases are genetically undefined, several causative genes have been identified that encode known or putative glycosyltransferases in the biosynthetic pathway of dystroglycan. Here we test the effects of brain-specific deletion of dystroglycan, and show distinct functions for neuronal and glial dystroglycan. Deletion of dystroglycan in the whole brain produced glial/neuronal heterotopia resembling the cerebral cortex malformation in cobblestone lissencephaly. In wild-type mice, dystroglycan stabilizes the basement membrane of the glia limitans, thereby supporting the cortical infrastructure necessary for neuronal migration. This function depends on extracellular dystroglycan interactions, since the cerebral cortex developed normally in transgenic mice that lack the dystroglycan intracellular domain. Also, forebrain histogenesis was preserved in mice with neuron-specific deletion of dystroglycan, but hippocampal long-term potentiation was blunted, as is also the case in the Largemyd mouse, in which dystroglycan glycosylation is disrupted. Our findings provide genetic evidence that neuronal dystroglycan plays a role in synaptic plasticity and that glial dystroglycan is involved in forebrain development. Differences in dystroglycan glycosylation in distinct cell types of the CNS may therefore contribute to the diversity of dystroglycan function in the CNS, as well as to the broad clinical spectrum of type II lissencephalies.

Satz, Jakob S.; Ostendorf, Adam P.; Hou, Shangwei; Turner, Amy; Kusano, Hajime; Lee, Jane C.; Turk, Rolf; Nguyen, Huy; Ross-Barta, Susan E.; Westra, Steve; Hoshi, Toshinori; Moore, Steven A.; Campbell, Kevin P.

2010-01-01

323

Mitochondrial activity and brain functions during cortical depolarization  

NASA Astrophysics Data System (ADS)

Cortical depolarization (CD) of the cerebral cortex could be developed under various pathophysiological conditions. In animal models, CD was recorded under partial or complete ischemia as well as when cortical spreading depression (SD) was induced externally or by internal stimulus. The development of CD in patients and the changes in various metabolic parameters, during CD, was rarely reported. Brain metabolic, hemodynamic, ionic and electrical responses to the CD event are dependent upon the O2 balance in the tissue. When the O2 balance is negative (i.e. ischemia), the CD process will be developed due to mitochondrial dysfunction, lack of energy and the inhibition of Na+-K+-ATPase. In contradiction, when oxygen is available (i.e. normoxia) the development of CD after induction of SD will accelerate mitochondrial respiration for retaining ionic homeostasis and normal brain functions. We used the multiparametric monitoring approach that enable real time monitoring of mitochondrial NADH redox state, microcirculatory blood flow and oxygenation, extracellular K+, Ca2+, H+ levels, DC steady potential and electrocorticogram (ECoG). This monitoring approach, provide a unique tool that has a significant value in analyzing the pathophysiology of the brain when SD developed under normoxia, ischemia, or hypoxia. We applied the same monitoring approach to patients suffered from severe head injury or exposed to neurosurgical procedures.

Mayevsky, Avraham; Sonn, Judith

2008-12-01

324

Imaging the ADHD brain: disorder-specificity, medication effects and clinical translation.  

PubMed

A plethora of magnetic resonance imaging studies have shown that ADHD is characterized by multiple functional and structural neural network abnormalities beyond the classical fronto-striatal model, including fronto-parieto-temporal, fronto-cerebellar and even fronto-limbic networks. There is evidence for a maturational delay in brain structure development which likely extends to brain function and structural and functional connectivity, but this needs corroboration by longitudinal imaging studies. Dysfunction of the ventrolateral prefrontal cortex seems to be more pronounced relative to other pediatric disorders and is also the most consistent target of acute psychostimulant medication. Future studies are likely to focus on using neuroimaging for clinical translation such as for individual diagnostic and prognostic classification and as a neurotherapy to reverse brain function abnormalities. PMID:24738703

Rubia, Katya; Alegria, Analucia; Brinson, Helen

2014-05-01

325

Longitudinal assessment of default-mode brain function in aging.  

PubMed

Age-related changes in the default-mode network (DMN) have been identified in prior cross-sectional functional magnetic resonance imaging studies. Here, we investigated longitudinal change in DMN activity and connectivity. Cognitively intact participants (aged 49-79 years at baseline) were scanned twice, with a 6-year interval, while performing an episodic memory task interleaved with a passive control condition. Longitudinal analyses showed that the DMN (control condition > memory task) could be reliably identified at both baseline and follow-up. Differences in the magnitude of task-induced deactivation in posterior DMN regions were observed between baseline and follow-up indicating reduced deactivation in these regions with increasing age. Although no overall longitudinal changes in within-network connectivity were found across the whole sample, individual differences in memory change correlated with change in connectivity. Thus, our results show stability of whole-brain DMN topology and functional connectivity over time in healthy older adults, whereas within-region DMN analyses show reduced deactivation between baseline and follow-up. The current findings provide novel insights into DMN functioning that may assist in identifying brain changes in patient populations, as well as characterizing factors that distinguish between normal and pathologic aging. PMID:24767950

Persson, Jonas; Pudas, Sara; Nilsson, Lars-Göran; Nyberg, Lars

2014-09-01

326

Support vector machine classification and characterization of age-related reorganization of functional brain networks.  

PubMed

Most of what is known about the reorganization of functional brain networks that accompanies normal aging is based on neuroimaging studies in which participants perform specific tasks. In these studies, reorganization is defined by the differences in task activation between young and old adults. However, task activation differences could be the result of differences in task performance, strategy, or motivation, and not necessarily reflect reorganization. Resting-state fMRI provides a method of investigating functional brain networks without such confounds. Here, a support vector machine (SVM) classifier was used in an attempt to differentiate older adults from younger adults based on their resting-state functional connectivity. In addition, the information used by the SVM was investigated to see what functional connections best differentiated younger adult brains from older adult brains. Three separate resting-state scans from 26 younger adults (18-35 yrs) and 26 older adults (55-85) were obtained from the International Consortium for Brain Mapping (ICBM) dataset made publically available in the 1000 Functional Connectomes project www.nitrc.org/projects/fcon_1000. 100 seed-regions from four functional networks with 5mm(3) radius were defined based on a recent study using machine learning classifiers on adolescent brains. Time-series for every seed-region were averaged and three matrices of z-transformed correlation coefficients were created for each subject corresponding to each individual's three resting-state scans. SVM was then applied using leave-one-out cross-validation. The SVM classifier was 84% accurate in classifying older and younger adult brains. The majority of the connections used by the classifier to distinguish subjects by age came from seed-regions belonging to the sensorimotor and cingulo-opercular networks. These results suggest that age-related decreases in positive correlations within the cingulo-opercular and default networks, and decreases in negative correlations between the default and sensorimotor networks, are the distinguishing characteristics of age-related reorganization. PMID:22227886

Meier, Timothy B; Desphande, Alok S; Vergun, Svyatoslav; Nair, Veena A; Song, Jie; Biswal, Bharat B; Meyerand, Mary E; Birn, Rasmus M; Prabhakaran, Vivek

2012-03-01

327

Brain Structure and Executive Functions in Children with Cerebral Palsy: A Systematic Review  

ERIC Educational Resources Information Center

This systematic review aimed to establish the current knowledge about brain structure and executive function (EF) in children with cerebral palsy (CP). Five databases were searched (up till July 2012). Six articles met the inclusion criteria, all included structural brain imaging though no functional brain imaging. Study quality was assessed using…

Weierink, Lonneke; Vermeulen, R. Jeroen; Boyd, Roslyn N.

2013-01-01

328

Correlation between structural and functional changes in brain in an idiopathic headache syndrome  

Microsoft Academic Search

Fundamental to the concept of idiopathic or primary headache, including migraine, tension-type headache and cluster headache, is the currently accepted view that these conditions are due to abnormal brain function with completely normal brain structure. Cluster headache is one such idiopathic headache with many similarities to migraine, including normal brain structure on magnetic resonance imaging and abnormal function in the

A. May; J. Ashburner; C. Büchel; D. J. McGonigle; K. J. Friston; R. S. J. Frackowiak; P. J. Goadsby

1999-01-01

329

Some Problems for Representations of Brain Organization Based on Activation in Functional Imaging  

ERIC Educational Resources Information Center

Functional brain imaging has overshadowed traditional lesion studies in becoming the dominant approach to the study of brain-behavior relationships. The proponents of functional imaging studies frequently argue that this approach provides an advantage over lesion studies by observing normal brain activity in vivo without the disruptive effects of…

Sidtis, John J.

2007-01-01

330

Preinjury emotional and family functioning in caregivers of persons with traumatic brain injury  

Microsoft Academic Search

Sander AM, Sherer M, Malec JF, High WM Jr, Thompson RN, Moessner AM, Josey J. Preinjury emotional and family functioning in caregivers of persons with traumatic brain injury. 2003;84:197-203. Objective: To characterize the preinjury family functioning, emotional distress, and social support of caregivers of persons with traumatic brain injury (TBI). Design: Inception cohort. Setting: Three Traumatic Brain Injury Model Systems

Angelle M. Sander; Mark Sherer; James F. Malec; Walter M. High; Risa Nakase Thompson; Anne M. Moessner; Jennifer Josey

2003-01-01

331

Functional Interactions as Big Data in the Human Brain  

PubMed Central

Noninvasive studies of human brain function hold great potential to unlock mysteries of the human mind. The complexity of data generated by such studies, however, has prompted various simplifying assumptions during analysis. Although this has enabled considerable progress, our current understanding is partly contingent upon these assumptions. An emerging approach embraces the complexity, accounting for the fact that neural representations are widely distributed, neural processes involve interactions between regions, interactions vary by cognitive state, and the space of interactions is massive. Because what you see depends on how you look, such unbiased approaches provide the greatest flexibility for discovery.

Turk-Browne, Nicholas B.

2014-01-01

332

Alcohol: Effects on Neurobehavioral Functions and the Brain  

PubMed Central

Alcoholism results from an interplay between genetic and environmental factors, and is linked to brain defects and associated cognitive, emotional, and behavioral impairments. A confluence of findings from neuroimaging, physiological, neuropathological, and neuropsychological studies of alcoholics indicate that the frontal lobes, limbic system, and cerebellum are particularly vulnerable to damage and dysfunction. An integrative approach employing a variety of neuroscientific technologies is essential for recognizing the interconnectivity of the different functional systems affected by alcoholism. In that way, relevant experimental techniques can be applied to assist in determining the degree to which abstinence and treatment contribute to the reversal of atrophy and dysfunction.

Oscar-Berman, Marlene; Marinkovic, Ksenija

2014-01-01

333

Multisensory Interplay Reveals Crossmodal Influences on 'Sensory-Specific' Brain Regions, Neural Responses, and Judgments  

PubMed Central

Although much traditional sensory research has studied each sensory modality in isolation, there has been a recent explosion of interest in causal interplay between different senses. Various techniques have now identified numerous multisensory convergence zones in the brain. Some convergence may arise surprisingly close to low-level sensory-specific cortex, and some direct connections may exist even between primary sensory cortices. A variety of multisensory phenomena have now been reported in which sensory-specific brain responses and perceptual judgments concerning one sense can be affected by relations with other senses. We survey recent progress in this multisensory field, foregrounding human studies against the background of invasive animal work and highlighting possible underlying mechanisms. These include rapid feedforward integration, possible thalamic influences, and/or feedback from multisensory regions to sensory-specific brain areas. Multisensory interplay is more prevalent than classic modular approaches assumed, and new methods are now available to determine the underlying circuits.

Driver, Jon; Noesselt, Toemme

2008-01-01

334

Expression and function of AGAT, GAMT and CT1 in the mammalian brain.  

PubMed

In mammals, creatine is taken up from the diet and can be synthesized endogenously by a two-step mechanism involving the enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT). Creatine (Cr) is taken up by cells through a specific transporter, CT1. While the major part of endogenous synthesis of Cr is thought to occur in kidney, pancreas and liver, the brain widely expresses AGAT, GAMT and CT1, both during development and in adulthood. The adult central nervous system (CNS) has a limited capacity to take up Cr from periphery, and seems to rely more on its endogenous Cr synthesis. In contrast, the embryonic CNS might be more dependent on Cr supply from periphery than on endogenous synthesis. This review will focus on the expression and function of AGAT, GAMT and CT1 in the mammalian CNS, both during development and in adulthood. Emphasis will also be placed on their specific roles in the different cell types of the brain, to analyze which brain cells are responsible for the CNS capacity of (i) endogenous Cr synthesis and (ii) Cr uptake from the periphery, and which brain cells are the main Cr consumers. The potential role of CT1 as guanidinoacetate transporter between "AGAT-only" and "GAMT-only" expressing cells will also be explored. PMID:18652072

Braissant, Olivier; Bachmann, Claude; Henry, Hugues

2007-01-01

335

Other minds in the brain: a functional imaging study of "theory of mind" in story comprehension.  

PubMed

The ability of normal children and adults to attribute independent mental states to self and others in order to explain and predict behaviour ("theory of mind") has been a focus of much recent research. Autism is a biologically based disorder which appears to be characterised by a specific impairment in this "mentalising" process. The present paper reports a functional neuroimaging study with positron emission tomography in which we studied brain activity in normal volunteers while they performed story comprehension tasks necessitating the attribution of mental states. The resultant brain activity was compared with that measured in two control tasks: "physical" stories which did not require this mental attribution, and passages of unlinked sentences. Both story conditions, when compared to the unlinked sentences, showed significantly increased regional cerebral blood flow in the following regions: the temporal poles bilaterally, the left superior temporal gyrus and the posterior cingulate cortex. Comparison of the "theory of mind" stories with "physical" stores revealed a specific pattern of activation associated with mental state attribution: it was only this task which produced activation in the medial frontal gyrus on the left (Brodmann's area 8). This comparison also showed significant activation in the posterior cingulate cortex. These surprisingly clear-cut findings are discussed in relation to previous studies of brain activation during story comprehension. The localisation of brain regions involved in normal attribution of mental states and contextual problem solving is feasible and may have implication for the neural basis of autism. PMID:8556839

Fletcher, P C; Happé, F; Frith, U; Baker, S C; Dolan, R J; Frackowiak, R S; Frith, C D

1995-11-01

336

Neural stem cells encapsulated in a functionalized self-assembling peptide hydrogel for brain tissue engineering.  

PubMed

Brain injury is almost irreparable due to the poor regenerative capability of neural tissue. Nowadays, new therapeutic strategies have been focused on stem cell therapy and supplying an appropriate three dimensional (3D) matrix for the repair of injured brain tissue. In this study, we specifically linked laminin-derived IKVAV motif on the C-terminal to enrich self-assembling peptide RADA(16) as a functional peptide-based scaffold. Our purpose is providing a functional self-assembling peptide 3D hydrogel with encapsulated neural stem cells to enhance the reconstruction of the injured brain. The physiochemical properties reported that RADA(16)-IKVAV can self-assemble into nanofibrous morphology with bilayer ?-sheet structure and become gelationed hydrogel with mechanical stiffness similar to brain tissue. The in vitro results showed that the extended IKVAV sequence can serve as a signal or guiding cue to direct the encapsulated neural stem cells (NSCs) adhesion and then towards neuronal differentiation. Animal study was conducted in a rat brain surgery model to demonstrate the damage in cerebral neocortex/neopallium loss. The results showed that the injected peptide solution immediately in situ formed the 3D hydrogel filling up the cavity and bridging the gaps. The histological analyses revealed the RADA(16)-IKVAV self-assembling peptide hydrogel not only enhanced survival of encapsulated NSCs but also reduced the formation of glial astrocytes. The peptide hydrogel with IKVAV extended motifs also showed the support of encapsulated NSCs in neuronal differentiation and the improvement in brain tissue regeneration after 6 weeks post-transplantation. PMID:23237515

Cheng, Tzu-Yun; Chen, Ming-Hong; Chang, Wen-Han; Huang, Ming-Yuan; Wang, Tzu-Wei

2013-03-01

337

Mushroom bodies of the honeybee brain show cell population-specific plasticity in expression of amine-receptor genes.  

PubMed

Dopamine and octopamine released in the mushroom bodies of the insect brain play a critical role in the formation of aversive and appetitive memories, respectively. As recent evidence suggests a complex relationship between the effects of these two amines on the output of mushroom body circuits, we compared the expression of dopamine- and octopamine-receptor genes in three major subpopulations of mushroom body intrinsic neurons (Kenyon cells). Using the brain of the honeybee, Apis mellifera, we found that expression of amine-receptor genes differs markedly across Kenyon cell subpopulations. We found, in addition, that levels of expression of these genes change dramatically during the lifetime of the bee and that shifts in expression are cell population-specific. Differential expression of amine-receptor genes in mushroom body neurons and the plasticity that exists at this level are features largely ignored in current models of mushroom body function. However, our results are consistent with the growing body of evidence that short- and long-term olfactory memories form in different regions of the mushroom bodies of the brain and that there is functional compartmentalization of the modulatory inputs to this multifunctional brain center. PMID:22411422

McQuillan, H James; Nakagawa, Shinichi; Mercer, Alison R

2012-04-01

338

The Angiotensin II Type 2 Receptor in Brain Functions: An Update  

PubMed Central

Angiotensin II (Ang II) is the main active product of the renin-angiotensin system (RAS), mediating its action via two major receptors, namely, the Ang II type 1 (AT1) receptor and the type 2 (AT2) receptor. Recent results also implicate several other members of the renin-angiotensin system in various aspects of brain functions. The first aim of this paper is to summarize the current state of knowledge regarding the properties and signaling of the AT2 receptor, its expression in the brain, and its well-established effects. Secondly, we will highlight the potential role of the AT2 receptor in cognitive function, neurological disorders and in the regulation of appetite and the possible link with development of metabolic disorders. The potential utility of novel nonpeptide selective AT2 receptor ligands in clarifying potential roles of this receptor in physiology will also be discussed. If confirmed, these new pharmacological tools should help to improve impaired cognitive performance, not only through its action on brain microcirculation and inflammation, but also through more specific effects on neurons. However, the overall physiological relevance of the AT2 receptor in the brain must also consider the Ang IV/AT4 receptor.

Guimond, Marie-Odile; Gallo-Payet, Nicole

2012-01-01

339

Nuclear lamins in the brain--new insights into function and regulation  

PubMed Central

The nuclear lamina is an intermediate filament meshwork composed largely of four nuclear lamins—lamins A and C (A-type lamins) and lamins B1 and B2 (B-type lamins). Located immediately adjacent to the inner nuclear membrane, the nuclear lamina provides a structural scaffolding for the cell nucleus. It also interacts with both nuclear membrane proteins and the chromatin and is thought to participate in many important functions within the cell nucleus. Defects in A-type lamins cause cardiomyopathy, muscular dystrophy, peripheral neuropathy, lipodystrophy, and progeroid disorders. In contrast, the only bona fide link between the B-type lamins and human disease is a rare demyelinating disease of the central nervous system—adult-onset autosomal-dominant leukoencephalopathy, caused by a duplication of the gene for lamin B1. However, this leukoencephalopathy is not the only association between the brain and B-type nuclear lamins. Studies of conventional and tissue-specific knockout mice have demonstrated that B-type lamins play essential roles in neuronal migration in the developing brain and in neuronal survival. The importance of A-type lamin expression in the brain is unclear, but it is intriguing that the adult brain preferentially expresses lamin C rather than lamin A, very likely due to microRNA-mediated removal of prelamin A transcripts. Here, we review recent studies on nuclear lamins, focusing on the function and regulation of the nuclear lamins in the central nervous system.

Jung, Hea-Jin; Lee, John M.; Yang, Shao H.; Young, Stephen G.; Fong, Loren G.

2012-01-01

340

Relating structural and functional anomalous connectivity in the aging brain via neural mass modeling.  

PubMed

The structural changes that arise as the brain ages influence its functionality. In many cases, the anatomical degradation simply leads to normal aging. In others, the neurodegeneration is large enough to cause neurological disorders (e.g. Alzheimer's disease). Structure and function can be both currently measured using noninvasive techniques, such as magnetic resonance imaging (MRI) and electroencephalography (EEG) respectively. However, a full theoretical scheme linking structural and functional degradation is still lacking. Here we present a neural mass model that aims to bridge both levels of description and that reproduces experimentally observed multichannel EEG recordings of alpha rhythm in young subjects, healthy elderly subjects, and patients with mild cognitive impairment. We focus our attention in the dominant frequency of the signals at different electrodes and in the correlation between specific electrode pairs, measured via the phase-lag index. Our model allows us to study the influence of different structural connectivity pathways, independently of each other, on the normal and aberrantly aging brain. In particular, we study in detail the effect of the thalamic input on specific cortical regions, the long-range connectivity between cortical regions, and the short-range coupling within the same cortical area. Once the influence of each type of connectivity is determined, we characterize the regions of parameter space compatible with the EEG recordings of the populations under study. Our results show that the different types of connectivity must be fine-tuned to maintain the brain in a healthy functioning state independently of its age and brain condition. PMID:20056154

Pons, A J; Cantero, Jose L; Atienza, Mercedes; Garcia-Ojalvo, Jordi

2010-09-01

341

EEG Combined with MEG and TMS in Studies of Human Brain Function.  

National Technical Information Service (NTIS)

This thesis deals with the recording of the brain's electrophysiological responses either to sensory stimuli or to direct magnetic stimulation of the cortex. In order to develop novel tools for experimental brain research, two combinations of functional b...

J. Virtanen

1998-01-01

342

Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia  

PubMed Central

Objective: We aimed to investigate whether cognitive deficits and structural and functional connectivity changes can be detected before symptom onset in a large cohort of carriers of microtubule-associated protein tau and progranulin mutations. Methods: In this case-control study, 75 healthy individuals (aged 20–70 years) with 50% risk for frontotemporal dementia (FTD) underwent DNA screening, neuropsychological assessment, and structural and functional MRI. We used voxel-based morphometry and tract-based spatial statistics for voxelwise analyses of gray matter volume and diffusion tensor imaging measures. Using resting-state fMRI scans, we assessed whole-brain functional connectivity to frontoinsula, anterior midcingulate cortex (aMCC), and posterior cingulate cortex. Results: Although carriers (n = 37) and noncarriers (n = 38) had similar neuropsychological performance, worse performance on Stroop III, Ekman faces, and Happé cartoons correlated with higher age in carriers, but not controls. Reduced fractional anisotropy and increased radial diffusivity throughout frontotemporal white matter tracts were found in carriers and correlated with higher age. Reductions in functional aMCC connectivity were found in carriers compared with controls, and connectivity between frontoinsula and aMCC seeds and several brain regions significantly decreased with higher age in carriers but not controls. We found no significant differences or age correlations in posterior cingulate cortex connectivity. No differences in regional gray matter volume were found. Conclusions: This study convincingly demonstrates that alterations in structural and functional connectivity develop before the first symptoms of FTD arise. These findings suggest that diffusion tensor imaging and resting-state fMRI may have the potential to become sensitive biomarkers for early FTD in future clinical trials.

Dopper, Elise G.P.; Rombouts, Serge A.R.B.; Jiskoot, Lize C.; den Heijer, Tom; de Graaf, J. Roos A.; de Koning, Inge; Hammerschlag, Anke R.; Seelaar, Harro; Seeley, William W.; Veer, Ilya M.; van Buchem, Mark A.; Rizzu, Patrizia

2013-01-01

343

Formal Specification of Bounded Buffer using Stream Functions  

Microsoft Academic Search

Formal specifications of software components are critical to software development. Several types of formal or semi-formal methods are commonly used for software specification, such as specification languages, graphic diagrams, algebraic descriptions, and stream functions. Each of these methods addresses the specification problem from a different view point and has its own strengthens and weaknesses. In this paper, we use the

Gongzhu Hu; Mount Pleasant

2009-01-01

344

Constraints-Based Specification and Synthesis of Functional Analog Modules.  

National Technical Information Service (NTIS)

This paper describes a new methodology for synthesizing analog circuits based on declarative behavioral specifications. Behavioral specifications are translated into a convex energy function. Analog circuitry is used for the realtime search for a solution...

J. Maitan

1989-01-01

345

Functional Brain Mapping in Freely Moving Rats During Treadmill Walking  

PubMed Central

Summary A dilemma in functional neuroimaging is that immobilization of the subject, necessary to avoid movement artifact, extinguishes all but the simplest behaviors. Recently, we developed an implantable microbolus infusion pump (MIP) that allows bolus injection of radiotracers by remote activation in freely moving, nontethered animals. The MIP is examined as a tool for brain mapping in rats during a locomotor task. Cerebral blood flow–related tissue radioactivity (CBF-TR) was measured using [14C]-iodoantipyrine with an indicator-fractionation method, followed by autoradiography. Rats exposed to walking on a treadmill, compared to quiescent controls, showed increases in CBF-TR in motor circuits (primary motor cortex, dorsolateral striatum, ventrolateral thalamus, midline cerebellum, copula pyramis, paramedian lobule), in primary somatosensory cortex mapping the forelimbs, hindlimbs and trunk, as well as in secondary visual cortex. These results support the use of implantable pumps as adjunct tools for functional neuroimaging of behaviors that cannot be elicited in restrained or tethered animals.

Holschneider, D. P.; Maarek, J.-M. I.; Yang, J.; Harimoto, J.; Scremin, O. U.

2014-01-01

346

Long-Term Enhancement of Brain Function and Cognition Using Cognitive Training and Brain Stimulation  

PubMed Central

Summary Noninvasive brain stimulation has shown considerable promise for enhancing cognitive functions by the long-term manipulation of neuroplasticity [1–3]. However, the observation of such improvements has been focused at the behavioral level, and enhancements largely restricted to the performance of basic tasks. Here, we investigate whether transcranial random noise stimulation (TRNS) can improve learning and subsequent performance on complex arithmetic tasks. TRNS of the bilateral dorsolateral prefrontal cortex (DLPFC), a key area in arithmetic [4, 5], was uniquely coupled with near-infrared spectroscopy (NIRS) to measure online hemodynamic responses within the prefrontal cortex. Five consecutive days of TRNS-accompanied cognitive training enhanced the speed of both calculation- and memory-recall-based arithmetic learning. These behavioral improvements were associated with defined hemodynamic responses consistent with more efficient neurovascular coupling within the left DLPFC. Testing 6 months after training revealed long-lasting behavioral and physiological modifications in the stimulated group relative to sham controls for trained and nontrained calculation material. These results demonstrate that, depending on the learning regime, TRNS can induce long-term enhancement of cognitive and brain functions. Such findings have significant implications for basic and translational neuroscience, highlighting TRNS as a viable approach to enhancing learning and high-level cognition by the long-term modulation of neuroplasticity.

Snowball, Albert; Tachtsidis, Ilias; Popescu, Tudor; Thompson, Jacqueline; Delazer, Margarete; Zamarian, Laura; Zhu, Tingting; Cohen Kadosh, Roi

2013-01-01

347

Immobilization method to preserve enzyme specificity in biosensors: consequences for brain glutamate detection.  

PubMed

Microelectrode biosensors are a promising technique to probe the brain interstitial fluid and estimate the extracellular concentration of neurotransmitters like glutamate. Their selectivity is largely based on maintaining high substrate specificity for the enzymes immobilized on microelectrodes. However, the effect of enzyme immobilization on substrate specificity is poorly understood. Furthermore, the accuracy of biosensor measurements for brain biological extracts has not been reliably established in comparison with conventional analytical techniques. In this study, microelectrode biosensors were prepared using different enzyme immobilization methods, including glutaraldehyde, a conventional cross-linker, and poly(ethylene glycol) diglycidyl ether (PEGDE), a milder immobilization reagent. Glutaraldehyde, but not PEGDE, significantly decreased the apparent substrate specificity of glutamate and glucose oxidase. For glutaraldehyde prepared biosensors, detection of secondary substrates by glutamate oxidase increased, resulting in a significant overestimate of glutamate levels. This effect was not observed with PEGDE-based biosensors, and when brain microdialysates were analyzed, the levels of glutamate detected by biosensors were consistent with those detected by capillary electrophoresis. In addition, basal concentrations of glutamate detected in vivo were approximately 10-fold lower than the levels detected with glutaraldehyde-based biosensors (e.g., 1.2 ?M vs 16 ?M, respectively). Overall, enzyme immobilization can significantly impact substrate specificity, and PEGDE is well-suited for the preparation of stable and selective biosensors. This development questions some of the previous biosensor studies aimed at detecting glutamate in the brain and opens new possibilities for specific neurotransmitter detection. PMID:23358125

Vasylieva, Natalia; Maucler, Caroline; Meiller, Anne; Viscogliosi, Henry; Lieutaud, Thomas; Barbier, Daniel; Marinesco, Stéphane

2013-02-19

348

A systematic review of the evidence that brain structure is related to muscle structure and their relationship to brain and muscle function in humans over the lifecourse  

PubMed Central

Background An association between cognition and physical function has been shown to exist but the roles of muscle and brain structure in this relationship are not fully understood. A greater understanding of these relationships may lead to identification of the underlying mechanisms in this important area of research. This systematic review examines the evidence for whether: a) brain structure is related to muscle structure; b) brain structure is related to muscle function; and c) brain function is related to muscle structure in healthy children and adults. Methods Medline, Embase, CINAHL and PsycINFO were searched on March 6th 2014. A grey literature search was performed using Google and Google Scholar. Hand searching through citations and references of relevant articles was also undertaken. Results 53 articles were included in the review; mean age of the subjects ranged from 8.8 to 85.5 years old. There is evidence of a positive association between both whole brain volume and white matter (WM) volume and muscle size. Total grey matter (GM) volume was not associated with muscle size but some areas of regional GM volume were associated with muscle size (right temporal pole and bilateral ventromedial prefrontal cortex). No evidence was found of a relationship between grip strength and whole brain volume however there was some evidence of a positive association with WM volume. Conversely, there is evidence that gait speed is positively associated with whole brain volume; this relationship may be driven by total WM volume or regional GM volumes, specifically the hippocampus. Markers of brain ageing, that is brain atrophy and greater accumulation of white matter hyperintensities (WMH), were associated with grip strength and gait speed. The location of WMH is important for gait speed; periventricular hyperintensities and brainstem WMH are associated with gait speed but subcortical WMH play less of a role. Cognitive function does not appear to be associated with muscle size. Conclusion There is evidence that brain structure is associated with muscle structure and function. Future studies need to follow these interactions longitudinally to understand potential causal relationships.

2014-01-01

349

Zinc homeostasis and functions of zinc in the brain  

Microsoft Academic Search

The brain barrier system, i.e., the blood-brain and blood-cerebrospinal fluid barriers, is important for zinc homeostasis in the brain. Zinc is supplied to the brain via both barriers. A large portion of zinc serves as zinc metalloproteins in neurons and glial cells. Approximately 10% of the total zinc in the brain, probably ionic zinc, exists in the synaptic vesicles, and

Atsushi Takeda

2001-01-01

350

CEEG Dynamic Brain Mapping, a New Method to Evaluate Brain Function in Different Psychological and Drug Conditions.  

National Technical Information Service (NTIS)

The electroencephalogram (EEG), discovered more than half a century ago, is still the only non-invasive, simple and objective method to continuously and repetitively study brain function, and has recently gained new significance since quantification by mi...

T. M. Itil K. Z. Itil E. Eralp A. Akman A. Manco

1988-01-01

351

Nanoparticle-mediated Brain-Specific Drug Delivery, Imaging, and Diagnosis  

PubMed Central

Central nervous system (CNS) diseases represent the largest and fastest growing area of unmet medical need. Nanotechnology plays a unique instrumental role in the revolutionary development of brain-specific drug delivery, imaging, and diagnosis. With the aid of nanoparticles of high specificity and multifunctionality, such as dendrimers and quantum dots, therapeutics, imaging agents, and diagnostic molecules can be delivered to the brain across the blood-brain barrier (BBB), enabling considerable progress in the understanding, diagnosis, and treatment of CNS diseases. Nanoparticles used in the CNS for drug delivery, imaging, and diagnosis are reviewed, as well as their administration routes, toxicity, and routes to cross the BBB. Future directions and major challenges are outlined.

Yang, Hu

2010-01-01

352

Functional Causal Mediation Analysis With an Application to Brain Connectivity  

PubMed Central

Mediation analysis is often used in the behavioral sciences to investigate the role of intermediate variables that lie on the causal path between a randomized treatment and an outcome variable. Typically, mediation is assessed using structural equation models (SEMs), with model coefficients interpreted as causal effects. In this article, we present an extension of SEMs to the functional data analysis (FDA) setting that allows the mediating variable to be a continuous function rather than a single scalar measure, thus providing the opportunity to study the functional effects of the mediator on the outcome. We provide sufficient conditions for identifying the average causal effects of the functional mediators using the extended SEM, as well as weaker conditions under which an instrumental variable estimand may be interpreted as an effect. The method is applied to data from a functional magnetic resonance imaging (fMRI) study of thermal pain that sought to determine whether activation in certain brain regions mediated the effect of applied temperature on self-reported pain. Our approach provides valuable information about the timing of the mediating effect that is not readily available when using the standard nonfunctional approach. To the best of our knowledge, this work provides the first application of causal inference to the FDA framework.

Lindquist, Martin A.

2014-01-01

353

Accurately Assessing the Risk of Schizophrenia Conferred by Rare Copy-Number Variation Affecting Genes with Brain Function  

PubMed Central

Investigators have linked rare copy number variation (CNVs) to neuropsychiatric diseases, such as schizophrenia. One hypothesis is that CNV events cause disease by affecting genes with specific brain functions. Under these circumstances, we expect that CNV events in cases should impact brain-function genes more frequently than those events in controls. Previous publications have applied “pathway” analyses to genes within neuropsychiatric case CNVs to show enrichment for brain-functions. While such analyses have been suggestive, they often have not rigorously compared the rates of CNVs impacting genes with brain function in cases to controls, and therefore do not address important confounders such as the large size of brain genes and overall differences in rates and sizes of CNVs. To demonstrate the potential impact of confounders, we genotyped rare CNV events in 2,415 unaffected controls with Affymetrix 6.0; we then applied standard pathway analyses using four sets of brain-function genes and observed an apparently highly significant enrichment for each set. The enrichment is simply driven by the large size of brain-function genes. Instead, we propose a case-control statistical test, cnv-enrichment-test, to compare the rate of CNVs impacting specific gene sets in cases versus controls. With simulations, we demonstrate that cnv-enrichment-test is robust to case-control differences in CNV size, CNV rate, and systematic differences in gene size. Finally, we apply cnv-enrichment-test to rare CNV events published by the International Schizophrenia Consortium (ISC). This approach reveals nominal evidence of case-association in neuronal-activity and the learning gene sets, but not the other two examined gene sets. The neuronal-activity genes have been associated in a separate set of schizophrenia cases and controls; however, testing in independent samples is necessary to definitively confirm this association. Our method is implemented in the PLINK software package.

Raychaudhuri, Soumya; Korn, Joshua M.; McCarroll, Steven A.; Altshuler, David; Sklar, Pamela; Purcell, Shaun; Daly, Mark J.

2010-01-01

354

Using local anaesthetics to block neuronal activity and map specific learning tasks to the mushroom bodies of an insect brain  

Microsoft Academic Search

The formation of a stable olfactory memory requires activity within several brain regions. The honeybee provides a valuable model to map complex olfactory learning tasks onto certain brain areas. To this end, we used injections of the local anaesthetic procaine to reversibly block spike activity in a specific brain region, the mushroom body (MB). We first investigated the physiological effects

Jean-Marc Devaud; Aline Blunk; Jasmin Podufall; Martin Giurfa; Bernd Grünewald

2007-01-01

355

ORIGINAL RESEARCH Restored Activation of Primary Motor Area from Motor Reorganization and Improved Motor Function after Brain Tumor Resection  

Microsoft Academic Search

BACKGROUND AND PURPOSE: Reorganization of brain function may result in preservation of motor function in patients with brain tumors. The goal of the present study was to investigate whether function of the primary motor area (M1) was restored and whether motor function improved after brain tumor resection. METHODS: Five patients with metastatic brain tumors located within or near M1 underwent

N. Shinoura; Y. Suzuki; R. Yamada; T. Kodama; M. Takahashi; K. Yagi

356

Larger Brains in Medication Naive High-Functioning Subjects with Pervasive Developmental Disorder  

ERIC Educational Resources Information Center

Background: Are brain volumes of individuals with Pervasive Developmental Disorder (PDD) still enlarged in adolescence and adulthood, and if so, is this enlargement confined to the gray and/or the white matter and is it global or more prominent in specific brain regions. Methods: Brain MRI scans were made of 21 adolescents with PDD and 21 closely…

Palmen, Saskia J. M. C.; Pol, Hilleke E. Hulshoff; Kemner, Chantal; Schnack, Hugo G.; Janssen, Joost; Kahn, Rene S.; van Engeland, Herman

2004-01-01

357

Evidence for a gender-specific protective role of innate immune receptors in a model of perinatal brain injury.  

PubMed

Hypoxia-ischemia is a common cause of neurological impairments in newborns, but little is known about how neuroinflammation contributes to the long-term outcome after a perinatal brain injury. In this study, we investigated the role of the fractalkine receptor chemokine CX3C motif receptor 1 (CX3CR1) and of toll-like receptor (TLR) signaling after a neonatal hypoxic-ischemic brain injury. Mice deficient in the TLR adaptor proteins Toll/interleukin-1 receptor-domain-containing adaptor protein inducing interferon ? (TRIF) or myeloid differentiation factor-88 (MyD88) and CX3CR1 knock-out (KO) mice were subjected to hypoxia-ischemia at postnatal day 3. In situ hybridization was used to evaluate the expression of TLRs during brain development and after hypoxic-ischemic insults. Behavioral deficits, hippocampal damage, reactive microgliosis, and subplate injury were compared among the groups. Although MyD88 KO mice exhibited no differences from wild-type animals in long-term structural and functional outcomes, TRIF KO mice presented a worse outcome, as evidenced by increased hippocampal CA3 atrophy in males and by the development of learning and motor deficits in females. CX3CR1-deficient female mice showed a marked increase in brain damage and long-lasting learning deficits, whereas CX3CR1 KO male animals did not exhibit more brain injury than wild-type mice. These data reveal a novel, gender-specific protective role of TRIF and CX3CR1 signaling in a mouse model of neonatal hypoxic-ischemic brain injury. These findings suggest that future studies seeking immunomodulatory therapies for preterm infants should consider gender as a critical variable and should be cautious not to abrogate the protective role of neuroinflammation. PMID:23843525

Pimentel-Coelho, Pedro M; Michaud, Jean-Philippe; Rivest, Serge

2013-07-10

358

California Verbal Learning Test Indicators of Malingered Neurocognitive Dysfunction: Sensitivity and Specificity in Traumatic Brain Injury  

ERIC Educational Resources Information Center

The present study used well-defined traumatic brain injury (TBI) and mixed neurological (other than TBI) and psychiatric samples to examine the specificity and sensitivity to Malingered Neurocognitive Dysfunction (MND) of four individual California Verbal Learning Test (CVLT) variables and eight composite CVLT malingering indicators. Participants…

Curtis, Kelly L.; Greve, Kevin W.; Bianchini, Kevin J.; Brennan, Adrianne

2006-01-01

359

Correlation between the Effects of Acupuncture at Taichong (LR3) and Functional Brain Areas: A Resting-State Functional Magnetic Resonance Imaging Study Using True versus Sham Acupuncture  

PubMed Central

Functional magnetic resonance imaging (fMRI) has been shown to detect the specificity of acupuncture points, as proved by numerous studies. In this study, resting-state fMRI was used to observe brain areas activated by acupuncture at the Taichong (LR3) acupoint. A total of 15 healthy subjects received brain resting-state fMRI before acupuncture and after sham and true acupuncture, respectively, at LR3. Image data processing was performed using Data Processing Assistant for Resting-State fMRI and REST software. The combination of amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) was used to analyze the changes in brain function during sham and true acupuncture. Acupuncture at LR3 can specifically activate or deactivate brain areas related to vision, movement, sensation, emotion, and analgesia. The specific alterations in the anterior cingulate gyrus, thalamus, and cerebellar posterior lobe have a crucial effect and provide a valuable reference. Sham acupuncture has a certain effect on psychological processes and does not affect brain areas related to function.

Qu, Shanshan; Zhang, Jiping; Chen, Junqi; Zhang, Shaoqun; Li, Zhipeng; Chen, Jiarong; Ouyang, Huailiang; Huang, Yong; Tang, Chunzhi

2014-01-01

360

Imaging brain neuronal activity using functionalized magnetonanoparticles and MRI.  

PubMed

This study explored the use of non-radioactive 2-deoxy glucose (2DG)-labeled magnetonanoparticles (MNP) and magnetic resonance imaging (MRI) to detect functional activity during rest, peripheral stimulation, and epileptic seizures, in animal models. Non-radioactive 2DG was covalently attached to magnetonanoparticles composed of iron oxide and dextran and intravenous (tail) injections were performed. 2DG-MNP was injected in resting and stimulated naïve rodents and the subsequent MRI was compared to published (14)C-2DG autoradiography data. Reproducibility and statistical significance was established in one studied model. Negative contrast enhancement (NCE) in acute seizures and chronic models of epilepsy were investigated. MRI NCE due to 2DG-MNP particles was compared to that of plain (unconjugated) MNP in one animal. NCE due to 2DG-MNP particles at 3 T, which is approved for human use, was also investigated. Histology showed presence of MNP (following intravenous injection) in the brain tissues of resting naïve animal. 2DG-MNP intraparenchymal uptake was visible on MRI and histology. The locations of NCE agreed with published results of 2DG autoradiography in resting and stimulated animals and epileptic rats. Localization of epileptogenicity was confirmed by subsequent depth-electrode EEG (iEEG). Non-radioactive 2DG-MNP can cross the blood-brain barrier (BBB) and may accurately localize areas of increased activity. Although, this proof-of-principle study involves only a limited number of animals, and much more research and quantification are necessary to demonstrate that 2DG-MNP, or MNPs conjugated with other ligands, could eventually be used to image localized cerebral function with MRI in humans, this MNP-MRI approach is potentially applicable to the use of many bioactive molecules as ligands for imaging normal and abnormal localized cerebral functions. PMID:22622772

Akhtari, Massoud; Bragin, Anatol; Moats, Rex; Frew, Andrew; Mandelkern, Mark

2012-10-01

361

Alterations in brain structure and functional connectivity in prescription opioid-dependent patients  

PubMed Central

A dramatic increase in the use and dependence of prescription opioids has occurred within the last 10 years. The consequences of long-term prescription opioid use and dependence on the brain are largely unknown, and any speculation is inferred from heroin and methadone studies. Thus, no data have directly demonstrated the effects of prescription opioid use on brain structure and function in humans. To pursue this issue, we used structural magnetic resonance imaging, diffusion tensor imaging and resting-state functional magnetic resonance imaging in a highly enriched group of prescription opioid-dependent patients [(n?=??10); from a larger study on prescription opioid dependent patients (n?=??133)] and matched healthy individuals (n?=??10) to characterize possible brain alterations that may be caused by long-term prescription opioid use. Criteria for patient selection included: (i) no dependence on alcohol or other drugs; (ii) no comorbid psychiatric or neurological disease; and (iii) no medical conditions, including pain. In comparison to control subjects, individuals with opioid dependence displayed bilateral volumetric loss in the amygdala. Prescription opioid-dependent subjects had significantly decreased anisotropy in axonal pathways specific to the amygdala (i.e. stria terminalis, ventral amygdalofugal pathway and uncinate fasciculus) as well as the internal and external capsules. In the patient group, significant decreases in functional connectivity were observed for seed regions that included the anterior insula, nucleus accumbens and amygdala subdivisions. Correlation analyses revealed that longer duration of prescription opioid exposure was associated with greater changes in functional connectivity. Finally, changes in amygdala functional connectivity were observed to have a significant dependence on amygdala volume and white matter anisotropy of efferent and afferent pathways of the amygdala. These findings suggest that prescription opioid dependence is associated with structural and functional changes in brain regions implicated in the regulation of affect and impulse control, as well as in reward and motivational functions. These results may have important clinical implications for uncovering the effects of long-term prescription opioid use on brain structure and function.

Upadhyay, Jaymin; Maleki, Nasim; Potter, Jennifer; Elman, Igor; Rudrauf, David; Knudsen, Jaime; Wallin, Diana; Pendse, Gautam; McDonald, Leah; Griffin, Margaret; Anderson, Julie; Nutile, Lauren; Renshaw, Perry; Weiss, Roger; Becerra, Lino

2010-01-01

362

Self-similar correlation function in brain resting-state functional magnetic resonance imaging  

PubMed Central

Adaptive behaviour, cognition and emotion are the result of a bewildering variety of brain spatio-temporal activity patterns. An important problem in neuroscience is to understand the mechanism by which the human brain's 100 billion neurons and 100 trillion synapses manage to produce this large repertoire of cortical configurations in a flexible manner. In addition, it is recognized that temporal correlations across such configurations cannot be arbitrary, but they need to meet two conflicting demands: while diverse cortical areas should remain functionally segregated from each other, they must still perform as a collective, i.e. they are functionally integrated. Here, we investigate these large-scale dynamical properties by inspecting the character of the spatio-temporal correlations of brain resting-state activity. In physical systems, these correlations in space and time are captured by measuring the correlation coefficient between a signal recorded at two different points in space at two different times. We show that this two-point correlation function extracted from resting-state functional magnetic resonance imaging data exhibits self-similarity in space and time. In space, self-similarity is revealed by considering three successive spatial coarse-graining steps while in time it is revealed by the 1/f frequency behaviour of the power spectrum. The uncovered dynamical self-similarity implies that the brain is spontaneously at a continuously changing (in space and time) intermediate state between two extremes, one of excessive cortical integration and the other of complete segregation. This dynamical property may be seen as an important marker of brain well-being in both health and disease.

Expert, Paul; Lambiotte, Renaud; Chialvo, Dante R.; Christensen, Kim; Jensen, Henrik Jeldtoft; Sharp, David J.; Turkheimer, Federico

2011-01-01

363

Brain site-specific proteome changes in aging-related dementia.  

PubMed

This study is aimed at gaining insights into the brain site-specific proteomic senescence signature while comparing physiologically aged brains with aging-related dementia brains (for example, Alzheimer's disease (AD)). Our study of proteomic differences within the hippocampus (Hp), parietal cortex (pCx) and cerebellum (Cb) could provide conceptual insights into the molecular mechanisms involved in aging-related neurodegeneration. Using an isobaric tag for relative and absolute quantitation (iTRAQ)-based two-dimensional liquid chromatography coupled with tandem mass spectrometry (2D-LC-MS/MS) brain site-specific proteomic strategy, we identified 950 proteins in the Hp, pCx and Cb of AD brains. Of these proteins, 31 were significantly altered. Most of the differentially regulated proteins are involved in molecular transport, nervous system development, synaptic plasticity and apoptosis. Particularly, proteins such as Gelsolin (GSN), Tenascin-R (TNR) and AHNAK could potentially act as novel biomarkers of aging-related neurodegeneration. Importantly, our Ingenuity Pathway Analysis (IPA)-based network analysis further revealed ubiquitin C (UBC) as a pivotal protein to interact with diverse AD-associated pathophysiological molecular factors and suggests the reduced ubiquitin proteasome degradation system (UPS) as one of the causative factors of AD. PMID:24008896

Manavalan, Arulmani; Mishra, Manisha; Feng, Lin; Sze, Siu Kwan; Akatsu, Hiroyasu; Heese, Klaus

2013-01-01

364

Cognitive and sexual functions in patients with traumatic brain injury  

PubMed Central

Background: Traumatic brain injury (TBI) has an immense psychosocial impact on an individual as well as on the close relatives. Sexuality is one among the functions which are usually found compromised post injury. The aim of present study was to examine cognitive and sexual functions post TBI. The objective of the study was to explore these domains and their relationship with each other. Tools: The tools used were sociodemographics record sheet, Edinburg handedness inventory, brief sexual function inventory, depression anxiety stress scales-21 and NIMHANS head injury battery. The sample consisted of 30 patients with mild-to-moderate TBI. All the subjects were tested individually in their regional language. Results: On cognitive domain, patients performed inadequately on all the tests; however, the percentage was higher in mental speed (43.3%), sustained attention (26.7%), verbal working memory (30%), response inhibition (36.7%), verbal memory (immediate and delayed) (43%) and visual (immediate, 23.3% and delayed, 26.7%). On the domain of sexual functions, all the four domains (sexual drive, erection, ejaculation and problem assessment) were affected however overall satisfaction (93.3%) was adequate. Among the four domains higher percentage of involvement was noted on problem assessment (70%), ejaculation (56.7%), and erection (46.7%). Significant correlation was found between mental speed, verbal working memory, planning, and visual memory with sexual drive, erection, ejaculation and overall satisfaction domains of sexual functioning. Negative correlation was found between motor speed and sustained attention with sexual drive, erection and ejaculation. Conclusion: Both cognitive and sexual functioning were found effected post TBI. However less emphasis is given to sexual functioning by the professionals. Educational intervention is needed to sensitize professional about this area and to include this area for better management.

War, Firdous A.; Jamuna, R.; Arivazhagan, A.

2014-01-01

365

Significance of vitamin A to brain function, behavior and learning  

PubMed Central

Retinoid acid, the bioactive metabolite of vitamin A, is a potent signaling molecule in the brains of growing and adult animals, regulates numerous gene products, and modulates neurogenesis, neuronal survival and synaptic plasticity. Vitamin A deficiency (VAD) is a global health problem, yet our knowledge of its effects on behavior and learning is still emerging. Here we review studies that have implicated retinoids in learning and memory deficits of post-embryonic and adult rodent and songbird models. Dietary vitamin A supplementation improves learning and memory in VAD rodents and can ameliorate cognitive declines associated with normal aging. Songbird studies examine the effects of retinoid signaling on vocal/auditory learning and are uniquely suited to study the behavioral effects of VAD because the neural circuitry of the song system is discrete and well understood. Similar to human speech acquisition, avian vocal learning proceeds in well-defined stages of template acquisition, rendition and maturation. Local blockade of retinoic acid production in the brain or excess dietary retinoic acid results in the failure of song maturation, yet does not affect prior song acquisition. Together these results yield significant insights into the role of vitamin A in maintaining neuronal plasticity and cognitive function in adulthood.

Olson, Christopher R.; Mello, Claudio V.

2011-01-01

366

Compelling Evidence that Exposure Therapy for PTSD Normalizes Brain Function.  

PubMed

Functional magnetic resonance imaging (fMRI) is helping us better understand the neurologic pathways involved in posttraumatic stress disorder (PTSD). We previously reported that military service members with PTSD after deployment to Iraq or Afghanistan demonstrated significant improvement, or normalization, in the fMRI-measured activation of the amygdala, prefrontal cortex and anterior cingulate gyrus following exposure therapy for PTSD. However, our original study design did not include repeat scans of control participants, rendering it difficult to discern how much of the observed normalization in brain activity is attributable to treatment, rather than merely a practice effect. Using the same Affective Stroop task paradigm, we now report on a larger sample of PTSD-positive combat veterans that we treated with exposure therapy, as well as a combat-exposed control group of service members who completed repeat scans at 3-4 month intervals. Findings from the treatment group are similar to our prior report. Combat controls showed no significant change on repeat scanning, indicating that the observed differences in the intervention group were in fact due to treatment. We continue to scan additional study participants, in order to determine whether virtual reality exposure therapy has a different impact on regional brain activation than other therapies for PTSD. PMID:24875691

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

2014-01-01

367

Eye and visual function in traumatic brain injury.  

PubMed

Combat blast is an important cause of traumatic brain injury (TBI) in the Department of Veterans Affairs polytrauma population, whereas common causes of TBI in the civilian sector include motor vehicle accidents and falls. Known visual consequences of civilian TBI include compromised visual acuity, visual fields, and oculomotor function. The visual consequences of TBI related to blast remain largely unknown. Blast injury may include open globe (eye) injury, which is usually detected and managed early in the rehabilitation journey. The incidence, locations, and types of ocular damage in eyes without open globe injury after exposure to powerful blast have not been systematically studied. Initial reports and preliminary data suggest that binocular function, visual fields, and other aspects of visual function may be impaired after blast-related TBI, despite relatively normal visual acuity. Damage to the ocular tissues may occur from blunt trauma without rupture or penetration (closed globe injury). Possible areas for research are development of common taxonomy and assessment tools across services, surgical management, and outcomes for blast-related eye injury; the incidence, locations, and natural history of closed globe injury; binocular and visual function impairment; quality of life in affected service members; pharmacological and visual therapies; and practice patterns for screening, management, and rehabilitation. PMID:20104404

Cockerham, Glenn C; Goodrich, Gregory L; Weichel, Eric D; Orcutt, James C; Rizzo, Joseph F; Bower, Kraig S; Schuchard, Ronald A

2009-01-01

368

One Decade Later: What has Gene Expression Profiling Told us About Neuronal Cell Types, Brain Function and Disease?  

PubMed Central

The many diverse functions executed by the central nervous system (CNS) are mirrored in the diverse shapes, connections, and firing patterns of its individual neuronal cell types. Furthermore, distinct neurological diseases are the result of defects in specific neuronal cell types. However, despite the significance of this cellular diversity underlying brain function and disease, we know relatively little about the genes that contribute to purposeful differences among regions and cell types within the brain. A major challenge in this endeavor is the paucity of markers that define the many regions and cell types thought to exist. Cataloging the neuronal cell types and cell- and region-specific marker genes requires novel avenues that enable researchers to define gene expression profiles of brain regions and individual neurons and to apply this information to understand functional and structural properties in the normal and diseased brain. Functional genomic approaches such as gene expression profiling offers the exclusive opportunity to glimpse the detailed inner workings of distinct neuronal cell types. Recent studies have applied microarray technology in unique and novel ways to understand the molecular mechanisms that underlie such neuronal diversity and their potential role in brain diseases.

Diaz, Elva

2009-01-01

369

Adaptive reconfiguration of fractal small-world human brain functional networks  

PubMed Central

Brain function depends on adaptive self-organization of large-scale neural assemblies, but little is known about quantitative network parameters governing these processes in humans. Here, we describe the topology and synchronizability of frequency-specific brain functional networks using wavelet decomposition of magnetoencephalographic time series, followed by construction and analysis of undirected graphs. Magnetoencephalographic data were acquired from 22 subjects, half of whom performed a finger-tapping task, whereas the other half were studied at rest. We found that brain functional networks were characterized by small-world properties at all six wavelet scales considered, corresponding approximately to classical ? (low and high), ?, ?, ?, and ? frequency bands. Global topological parameters (path length, clustering) were conserved across scales, most consistently in the frequency range 2–37 Hz, implying a scale-invariant or fractal small-world organization. Dynamical analysis showed that networks were located close to the threshold of order/disorder transition in all frequency bands. The highest-frequency ? network had greater synchronizability, greater clustering of connections, and shorter path length than networks in the scaling regime of (lower) frequencies. Behavioral state did not strongly influence global topology or synchronizability; however, motor task performance was associated with emergence of long-range connections in both ? and ? networks. Long-range connectivity, e.g., between frontal and parietal cortex, at high frequencies during a motor task may facilitate sensorimotor binding. Human brain functional networks demonstrate a fractal small-world architecture that supports critical dynamics and task-related spatial reconfiguration while preserving global topological parameters.

Bassett, Danielle S.; Meyer-Lindenberg, Andreas; Achard, Sophie; Duke, Thomas; Bullmore, Edward

2006-01-01

370

Methamphetamine disrupts blood brain barrier function by induction of oxidative stress in brain endothelial cells  

PubMed Central

Methamphetamine (METH), a potent stimulant with strong euphoric properties, has a high abuse liability and long-lasting neurotoxic effects. Recent studies in animal models have indicated that METH can induce impairment of the blood brain barrier (BBB), thus suggesting that some of the neurotoxic effects resulting from METH abuse could be the outcome of barrier disruption. Here we provide evidence that METH alters BBB function via direct effects on endothelial cells and explore possible underlying mechanisms leading to endothelial injury. We report that METH increases BBB permeability in vivo, and exposure of primary human microvascular endothelial cells (BMVEC) to METH diminishes tightness of BMVEC monolayers in a dose- and time-dependent manner by decreasing expression of cell membrane associated tight junction (TJ) proteins. These changes were accompanied by enhanced production of reactive oxygen species, increased monocyte migration across METH-treated endothelial monolayers, and activation of myosin light chain kinase (MLCK) in BMVEC. Anti-oxidant treatment attenuated or completely reversed all tested aspects of METH induced BBB dysfunction. Our data suggest that BBB injury is caused by METH-mediated oxidative stress, which activates MLCK and negatively affects the TJ complex. These observations provide a basis for antioxidant protection against brain endothelial injury caused by METH exposure.

Ramirez, Servio H.; Potula, Raghava; Fan, Shongshan; Eidem, Tess; Papugani, Anil; Reichenbach, Nancy; Dykstra, Holly; Weksler, Babette B.; Romero, Ignacio A.; Couraud, Pierre O.; Persidsky, Yuri

2012-01-01

371

Function and dysfunction of prefrontal brain circuitry in alcoholic Korsakoff's syndrome.  

PubMed

The signature symptom of alcohol-induced persisting amnestic disorder, more commonly referred to as alcoholic Korsakoff's syndrome (KS), is anterograde amnesia, or memory loss for recent events, and until the mid 20th Century, the putative brain damage was considered to be in diencephalic and medial temporal lobe structures. Overall intelligence, as measured by standardized IQ tests, usually remains intact. Preservation of IQ occurs because memories formed before the onset of prolonged heavy drinking--the types of information and abilities tapped by intelligence tests--remain relatively well preserved compared with memories recently acquired. However, clinical and experimental evidence has shown that neurobehavioral dysfunction in alcoholic patients with KS does include nonmnemonic abilities, and further brain damage involves extensive frontal and limbic circuitries. Among the abnormalities are confabulation, disruption of elements of executive functioning and cognitive control, and emotional impairments. Here, we discuss the relationship between neurobehavioral impairments in KS and alcoholism-related brain damage. More specifically, we examine the role of damage to prefrontal brain systems in the neuropsychological profile of alcoholic KS. PMID:22538385

Oscar-Berman, Marlene

2012-06-01

372

Dual-functional nanoparticles targeting amyloid plaques in the brains of Alzheimer's disease mice.  

PubMed

Alzheimer's disease (AD) is a common neurodegenerative disorder with few treatments. The limitations imposed by the blood-brain barrier (BBB) and the non-selective distribution of drugs in the brain have hindered the effective treatment of AD and may result in severe side effects on the normal brains. We developed a dual-functional nanoparticle drug delivery system based on a PEGylated poly (lactic acid) (PLA) polymer. Two targeting peptides that were screened by phage display, TGN and QSH, were conjugated to the surface of the nanoparticles. TGN specifically targets ligands at the BBB, while QSH has good affinity with A?(1-42), which is the main component of amyloid plaque. Tests probing the bEnd.3 cell uptake and in vivo imaging were conducted to determine the best density of TGN on the nanoparticles' surfaces. The optimal amount of QSH was studied using a Thioflavin T (ThT) binding assay and surface plasmon resonance (SPR) experiments. The optimal maleimide/peptide molar ratio was 3 for both TGN and QSH on the surface of the nanoparticles (T3Q3-NP), and these nanoparticles achieved enhanced and precise targeted delivery to amyloid plaque in the brains of AD model mice. A MTT assay also validated the safety of this dual-targeted delivery system; little cytotoxicity was demonstrated with both bEnd.3 and PC 12 cells. In conclusion, the T3Q3-NP might be a valuable targeting system for AD diagnosis and therapy. PMID:24099709

Zhang, Chi; Wan, Xu; Zheng, Xiaoyao; Shao, Xiayan; Liu, Qingfeng; Zhang, Qizhi; Qian, Yong

2014-01-01

373

Therapy insight: the impact of type 1 diabetes on brain development and function.  

PubMed

The CNS is one of the main organ systems that is affected in type 1 diabetes, as both cerebral glucose and insulin levels are frequently abnormal, even when the diabetes is well-controlled. Literature is emerging that documents pathophysiological CNS changes and neurocognitive deficits in both adults and children with type 1 diabetes, but empirical findings to date have often been inconsistent and difficult to interpret. This article provides a comprehensive review of current knowledge about the impact of type 1 diabetes on brain development and function, focusing particularly on the evidence for specific illness-related risk factors for CNS sequelae. We argue that clinical management of young patients with type 1 diabetes should take into account current knowledge of the relative risks of hypoglycemia and hyperglycemia to the developing brain. PMID:16932529

Northam, Elisabeth A; Rankins, Debbie; Cameron, Fergus J

2006-02-01