A Set of Functional Brain Networks for the Comprehensive Evaluation of Human Characteristics.

PubMed

Sung, Yul-Wan; Kawachi, Yousuke; Choi, Uk-Su; Kang, Daehun; Abe, Chihiro; Otomo, Yuki; Ogawa, Seiji

2018-01-01

Many human characteristics must be evaluated to comprehensively understand an individual, and measurements of the corresponding cognition/behavior are required. Brain imaging by functional MRI (fMRI) has been widely used to examine brain function related to human cognition/behavior. However, few aspects of cognition/behavior of individuals or experimental groups can be examined through task-based fMRI. Recently, resting state fMRI (rs-fMRI) signals have been shown to represent functional infrastructure in the brain that is highly involved in processing information related to cognition/behavior. Using rs-fMRI may allow diverse information about the brain through a single MRI scan to be obtained, as rs-fMRI does not require stimulus tasks. In this study, we attempted to identify a set of functional networks representing cognition/behavior that are related to a wide variety of human characteristics and to evaluate these characteristics using rs-fMRI data. If possible, these findings would support the potential of rs-fMRI to provide diverse information about the brain. We used resting-state fMRI and a set of 130 psychometric parameters that cover most human characteristics, including those related to intelligence and emotional quotients and social ability/skill. We identified 163 brain regions by VBM analysis using regression analysis with 130 psychometric parameters. Next, using a 163 × 163 correlation matrix, we identified functional networks related to 111 of the 130 psychometric parameters. Finally, we made an 8-class support vector machine classifiers corresponding to these 111 functional networks. Our results demonstrate that rs-fMRI signals contain intrinsic information about brain function related to cognition/behaviors and that this set of 111 networks/classifiers can be used to comprehensively evaluate human characteristics.

Structural and Functional Correlates of Visual Field Asymmetry in the Human Brain by Diffusion Kurtosis MRI and Functional MRI

PubMed Central

O’Connell, Caitlin; Ho, Leon C.; Murphy, Matthew C.; Conner, Ian P.; Wollstein, Gadi; Cham, Rakie; Chan, Kevin C.

2016-01-01

Human visual performance has been observed to exhibit superiority in localized regions of the visual field across many classes of stimuli. However, the underlying neural mechanisms remain unclear. This study aims to determine if the visual information processing in the human brain is dependent on the location of stimuli in the visual field and the corresponding neuroarchitecture using blood-oxygenation-level-dependent functional MRI (fMRI) and diffusion kurtosis MRI (DKI), respectively in 15 healthy individuals at 3 Tesla. In fMRI, visual stimulation to the lower hemifield showed stronger brain responses and larger brain activation volumes than the upper hemifield, indicative of the differential sensitivity of the human brain across the visual field. In DKI, the brain regions mapping to the lower visual field exhibited higher mean kurtosis but not fractional anisotropy or mean diffusivity when compared to the upper visual field. These results suggested the different distributions of microstructural organization across visual field brain representations. There was also a strong positive relationship between diffusion kurtosis and fMRI responses in the lower field brain representations. In summary, this study suggested the structural and functional brain involvements in the asymmetry of visual field responses in humans, and is important to the neurophysiological and psychological understanding of human visual information processing. PMID:27631541

Accelerated recruitment of new brain development genes into the human genome.

PubMed

Zhang, Yong E; Landback, Patrick; Vibranovski, Maria D; Long, Manyuan

2011-10-01

How the human brain evolved has attracted tremendous interests for decades. Motivated by case studies of primate-specific genes implicated in brain function, we examined whether or not the young genes, those emerging genome-wide in the lineages specific to the primates or rodents, showed distinct spatial and temporal patterns of transcription compared to old genes, which had existed before primate and rodent split. We found consistent patterns across different sources of expression data: there is a significantly larger proportion of young genes expressed in the fetal or infant brain of humans than in mouse, and more young genes in humans have expression biased toward early developing brains than old genes. Most of these young genes are expressed in the evolutionarily newest part of human brain, the neocortex. Remarkably, we also identified a number of human-specific genes which are expressed in the prefrontal cortex, which is implicated in complex cognitive behaviors. The young genes upregulated in the early developing human brain play diverse functional roles, with a significant enrichment of transcription factors. Genes originating from different mechanisms show a similar expression bias in the developing brain. Moreover, we found that the young genes upregulated in early brain development showed rapid protein evolution compared to old genes also expressed in the fetal brain. Strikingly, genes expressed in the neocortex arose soon after its morphological origin. These four lines of evidence suggest that positive selection for brain function may have contributed to the origination of young genes expressed in the developing brain. These data demonstrate a striking recruitment of new genes into the early development of the human brain.

Brain/MINDS: brain-mapping project in Japan

PubMed Central

Okano, Hideyuki; Miyawaki, Atsushi; Kasai, Kiyoto

2015-01-01

There is an emerging interest in brain-mapping projects in countries across the world, including the USA, Europe, Australia and China. In 2014, Japan started a brain-mapping project called Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS). Brain/MINDS aims to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain, and takes advantage of a unique non-human primate animal model, the common marmoset (Callithrix jacchus). In Brain/MINDS, the RIKEN Brain Science Institute acts as a central institute. The objectives of Brain/MINDS can be categorized into the following three major subject areas: (i) structure and functional mapping of a non-human primate brain (the marmoset brain); (ii) development of innovative neurotechnologies for brain mapping; and (iii) human brain mapping; and clinical research. Brain/MINDS researchers are highly motivated to identify the neuronal circuits responsible for the phenotype of neurological and psychiatric disorders, and to understand the development of these devastating disorders through the integration of these three subject areas. PMID:25823872

Data-driven analysis of functional brain interactions during free listening to music and speech.

PubMed

Fang, Jun; Hu, Xintao; Han, Junwei; Jiang, Xi; Zhu, Dajiang; Guo, Lei; Liu, Tianming

2015-06-01

Natural stimulus functional magnetic resonance imaging (N-fMRI) such as fMRI acquired when participants were watching video streams or listening to audio streams has been increasingly used to investigate functional mechanisms of the human brain in recent years. One of the fundamental challenges in functional brain mapping based on N-fMRI is to model the brain's functional responses to continuous, naturalistic and dynamic natural stimuli. To address this challenge, in this paper we present a data-driven approach to exploring functional interactions in the human brain during free listening to music and speech streams. Specifically, we model the brain responses using N-fMRI by measuring the functional interactions on large-scale brain networks with intrinsically established structural correspondence, and perform music and speech classification tasks to guide the systematic identification of consistent and discriminative functional interactions when multiple subjects were listening music and speech in multiple categories. The underlying premise is that the functional interactions derived from N-fMRI data of multiple subjects should exhibit both consistency and discriminability. Our experimental results show that a variety of brain systems including attention, memory, auditory/language, emotion, and action networks are among the most relevant brain systems involved in classic music, pop music and speech differentiation. Our study provides an alternative approach to investigating the human brain's mechanism in comprehension of complex natural music and speech.

Driving and driven architectures of directed small-world human brain functional networks.

PubMed

Yan, Chaogan; He, Yong

2011-01-01

Recently, increasing attention has been focused on the investigation of the human brain connectome that describes the patterns of structural and functional connectivity networks of the human brain. Many studies of the human connectome have demonstrated that the brain network follows a small-world topology with an intrinsically cohesive modular structure and includes several network hubs in the medial parietal regions. However, most of these studies have only focused on undirected connections between regions in which the directions of information flow are not taken into account. How the brain regions causally influence each other and how the directed network of human brain is topologically organized remain largely unknown. Here, we applied linear multivariate Granger causality analysis (GCA) and graph theoretical approaches to a resting-state functional MRI dataset with a large cohort of young healthy participants (n = 86) to explore connectivity patterns of the population-based whole-brain functional directed network. This directed brain network exhibited prominent small-world properties, which obviously improved previous results of functional MRI studies showing weak small-world properties in the directed brain networks in terms of a kernel-based GCA and individual analysis. This brain network also showed significant modular structures associated with 5 well known subsystems: fronto-parietal, visual, paralimbic/limbic, subcortical and primary systems. Importantly, we identified several driving hubs predominantly located in the components of the attentional network (e.g., the inferior frontal gyrus, supplementary motor area, insula and fusiform gyrus) and several driven hubs predominantly located in the components of the default mode network (e.g., the precuneus, posterior cingulate gyrus, medial prefrontal cortex and inferior parietal lobule). Further split-half analyses indicated that our results were highly reproducible between two independent subgroups. The current study demonstrated the directions of spontaneous information flow and causal influences in the directed brain networks, thus providing new insights into our understanding of human brain functional connectome.

Segregated Systems of Human Brain Networks.

PubMed

Wig, Gagan S

2017-12-01

The organization of the brain network enables its function. Evaluation of this organization has revealed that large-scale brain networks consist of multiple segregated subnetworks of interacting brain areas. Descriptions of resting-state network architecture have provided clues for understanding the functional significance of these segregated subnetworks, many of which correspond to distinct brain systems. The present report synthesizes accumulating evidence to reveal how maintaining segregated brain systems renders the human brain network functionally specialized, adaptable to task demands, and largely resilient following focal brain damage. The organizational properties that support system segregation are harmonious with the properties that promote integration across the network, but confer unique and important features to the brain network that are central to its function and behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

What is feasible with imaging human brain function and connectivity using functional magnetic resonance imaging

PubMed Central

2016-01-01

When we consider all of the methods we employ to detect brain function, from electrophysiology to optical techniques to functional magnetic resonance imaging (fMRI), we do not really have a ‘golden technique’ that meets all of the needs for studying the brain. We have methods, each of which has significant limitations but provide often complimentary information. Clearly, there are many questions that need to be answered about fMRI, which unlike other methods, allows us to study the human brain. However, there are also extraordinary accomplishments or demonstration of the feasibility of reaching new and previously unexpected scales of function in the human brain. This article reviews some of the work we have pursued, often with extensive collaborations with other co-workers, towards understanding the underlying mechanisms of the methodology, defining its limitations, and developing solutions to advance it. No doubt, our knowledge of human brain function has vastly expanded since the introduction of fMRI. However, methods and instrumentation in this dynamic field have evolved to a state that discoveries about the human brain based on fMRI principles, together with information garnered at a much finer spatial and temporal scale through other methods, are poised to significantly accelerate in the next decade. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’. PMID:27574313

What is feasible with imaging human brain function and connectivity using functional magnetic resonance imaging.

PubMed

Ugurbil, Kamil

2016-10-05

When we consider all of the methods we employ to detect brain function, from electrophysiology to optical techniques to functional magnetic resonance imaging (fMRI), we do not really have a 'golden technique' that meets all of the needs for studying the brain. We have methods, each of which has significant limitations but provide often complimentary information. Clearly, there are many questions that need to be answered about fMRI, which unlike other methods, allows us to study the human brain. However, there are also extraordinary accomplishments or demonstration of the feasibility of reaching new and previously unexpected scales of function in the human brain. This article reviews some of the work we have pursued, often with extensive collaborations with other co-workers, towards understanding the underlying mechanisms of the methodology, defining its limitations, and developing solutions to advance it. No doubt, our knowledge of human brain function has vastly expanded since the introduction of fMRI. However, methods and instrumentation in this dynamic field have evolved to a state that discoveries about the human brain based on fMRI principles, together with information garnered at a much finer spatial and temporal scale through other methods, are poised to significantly accelerate in the next decade.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. © 2016 The Author(s).

Functional organization of the transcriptome in human brain

PubMed Central

Oldham, Michael C; Konopka, Genevieve; Iwamoto, Kazuya; Langfelder, Peter; Kato, Tadafumi; Horvath, Steve; Geschwind, Daniel H

2009-01-01

The enormous complexity of the human brain ultimately derives from a finite set of molecular instructions encoded in the human genome. These instructions can be directly studied by exploring the organization of the brain’s transcriptome through systematic analysis of gene coexpression relationships. We analyzed gene coexpression relationships in microarray data generated from specific human brain regions and identified modules of coexpressed genes that correspond to neurons, oligodendrocytes, astrocytes and microglia. These modules provide an initial description of the transcriptional programs that distinguish the major cell classes of the human brain and indicate that cell type–specific information can be obtained from whole brain tissue without isolating homogeneous populations of cells. Other modules corresponded to additional cell types, organelles, synaptic function, gender differences and the subventricular neurogenic niche. We found that subventricular zone astrocytes, which are thought to function as neural stem cells in adults, have a distinct gene expression pattern relative to protoplasmic astrocytes. Our findings provide a new foundation for neurogenetic inquiries by revealing a robust and previously unrecognized organization to the human brain transcriptome. PMID:18849986

[Is abortion murder?].

PubMed

Werning, C

1995-09-01

Discussions about Paragraph 218 of the German federal abortion law have spawned antithetical opinions: on the one hand, the full right of the mother or parents to decide about the incipient human life; and on the other hand, under the dogma of abortion is murder, providing abortion is rejected even when the pregnancy is the result of rape and it is unwanted. Two questions are closely related to this issue: 1) what makes human beings human and 2) when does human life begin. From a medical point of view the function of the brain is fundamentally linked to being human. The brain controls almost all functions of the body and determines its psychological makeup, such as intellect and, in a theological sense, the soul. Without the brain such functioning is not possible, since brain death means the death of human life. Children born with anencephaly and microencephaly can never live a human life. At the end of life various diseases (stroke, Alzheimer disease) can severely damage the brain. In these cases normal living is also no longer possible. Yet ethically it is untenable to actively kill these human beings. But when one considers that life-threatening diseases can require life-support intervention, then often the pragmatic intervention is not far removed from active euthanasia. The other question related to the beginning of human life is even more difficult to answer. It is the fertilization of the egg cells; but a conglomeration of cells in the early phase of pregnancy can hardly be characterized as a human person. The human identity, personality, and worth is associated with the functioning of the brain, so only when the brain is fully developed can there be any talk about an unborn human being.

Long-term neural and physiological phenotyping of a single human

PubMed Central

Poldrack, Russell A.; Laumann, Timothy O.; Koyejo, Oluwasanmi; Gregory, Brenda; Hover, Ashleigh; Chen, Mei-Yen; Gorgolewski, Krzysztof J.; Luci, Jeffrey; Joo, Sung Jun; Boyd, Ryan L.; Hunicke-Smith, Scott; Simpson, Zack Booth; Caven, Thomas; Sochat, Vanessa; Shine, James M.; Gordon, Evan; Snyder, Abraham Z.; Adeyemo, Babatunde; Petersen, Steven E.; Glahn, David C.; Reese Mckay, D.; Curran, Joanne E.; Göring, Harald H. H.; Carless, Melanie A.; Blangero, John; Dougherty, Robert; Leemans, Alexander; Handwerker, Daniel A.; Frick, Laurie; Marcotte, Edward M.; Mumford, Jeanette A.

2015-01-01

Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for results. We demonstrate dynamic changes in brain connectivity over the timescales of days to months, and relations between brain connectivity, gene expression and metabolites. This resource can serve as a testbed to study the joint dynamics of human brain and metabolic function over time, an approach that is critical for the development of precision medicine strategies for brain disorders. PMID:26648521

A Hybrid CPU-GPU Accelerated Framework for Fast Mapping of High-Resolution Human Brain Connectome

PubMed Central

Ren, Ling; Xu, Mo; Xie, Teng; Gong, Gaolang; Xu, Ningyi; Yang, Huazhong; He, Yong

2013-01-01

Recently, a combination of non-invasive neuroimaging techniques and graph theoretical approaches has provided a unique opportunity for understanding the patterns of the structural and functional connectivity of the human brain (referred to as the human brain connectome). Currently, there is a very large amount of brain imaging data that have been collected, and there are very high requirements for the computational capabilities that are used in high-resolution connectome research. In this paper, we propose a hybrid CPU-GPU framework to accelerate the computation of the human brain connectome. We applied this framework to a publicly available resting-state functional MRI dataset from 197 participants. For each subject, we first computed Pearson’s Correlation coefficient between any pairs of the time series of gray-matter voxels, and then we constructed unweighted undirected brain networks with 58 k nodes and a sparsity range from 0.02% to 0.17%. Next, graphic properties of the functional brain networks were quantified, analyzed and compared with those of 15 corresponding random networks. With our proposed accelerating framework, the above process for each network cost 80∼150 minutes, depending on the network sparsity. Further analyses revealed that high-resolution functional brain networks have efficient small-world properties, significant modular structure, a power law degree distribution and highly connected nodes in the medial frontal and parietal cortical regions. These results are largely compatible with previous human brain network studies. Taken together, our proposed framework can substantially enhance the applicability and efficacy of high-resolution (voxel-based) brain network analysis, and have the potential to accelerate the mapping of the human brain connectome in normal and disease states. PMID:23675425

Effect of cell therapy on recovery of cognitive functions in rats during the delayed period after brain injury.

PubMed

Roshal, L M; Tzyb, A F; Pavlova, L N; Soushkevitch, G N; Semenova, J B; Javoronkov, L P; Kolganova, O I; Konoplyannikov, A G; Shevchuk, A S; Yujakov, V V; Karaseva, O V; Ivanova, T F; Chernyshova, T A; Konoplyannikova, O A; Bandurko, L N; Marey, M V; Sukhikh, G T

2009-07-01

We studied the effect of systemic transplantation of human stem cells from various tissues on cognitive functions of the brain in rats during the delayed period after experimental brain injury. Stem cells were shown to increase the efficacy of medical treatment with metabolic and symptomatic drugs for recovery of cognitive functions. They accelerated the formation of the conditioned defense response. Fetal neural stem cells had a stronger effect on some parameters of cognitive function 2 months after brain injury. The efficacy of bone marrow mesenchymal stem cells from adult humans or fetuses was higher 3 months after brain injury.

Regional Homogeneity

PubMed Central

Jiang, Lili; Zuo, Xi-Nian

2015-01-01

Much effort has been made to understand the organizational principles of human brain function using functional magnetic resonance imaging (fMRI) methods, among which resting-state fMRI (rfMRI) is an increasingly recognized technique for measuring the intrinsic dynamics of the human brain. Functional connectivity (FC) with rfMRI is the most widely used method to describe remote or long-distance relationships in studies of cerebral cortex parcellation, interindividual variability, and brain disorders. In contrast, local or short-distance functional interactions, especially at a scale of millimeters, have rarely been investigated or systematically reviewed like remote FC, although some local FC algorithms have been developed and applied to the discovery of brain-based changes under neuropsychiatric conditions. To fill this gap between remote and local FC studies, this review will (1) briefly survey the history of studies on organizational principles of human brain function; (2) propose local functional homogeneity as a network centrality to characterize multimodal local features of the brain connectome; (3) render a neurobiological perspective on local functional homogeneity by linking its temporal, spatial, and individual variability to information processing, anatomical morphology, and brain development; and (4) discuss its role in performing connectome-wide association studies and identify relevant challenges, and recommend its use in future brain connectomics studies. PMID:26170004

Human sexual behavior related to pathology and activity of the brain.

PubMed

Komisaruk, Barry R; Rodriguez Del Cerro, Maria Cruz

2015-01-01

Reviewed in this chapter are: (1) correlations among human sexual behavior, brain pathology, and brain activity, including caveats regarding the interpretation of "cause and effect" among these factors, and the degree to which "hypersexuality" and reported changes in sexual orientation correlated with brain pathology are uniquely sexual or are attributable to a generalized disinhibition of brain function; (2) the effects, in some cases inhibitory, in others facilitatory, on sexual behavior and motivation, of stroke, epileptic seizures, traumatic brain injury, and brain surgery; and (3) insights into sexual motivation and behavior recently gained from functional brain imaging research and its interpretive limitations. We conclude from the reviewed research that the neural orchestra underlying the symphony of human sexuality comprises, rather than brain "centers," multiple integrated brain systems, and that there are more questions than answers in our understanding of the control of human sexual behavior by the brain - a level of understanding that is still in embryonic form. © 2015 Elsevier B.V. All rights reserved.

Mapping Prefrontal Cortex Functions in Human Infancy

ERIC Educational Resources Information Center

Grossmann, Tobias

2013-01-01

It has long been thought that the prefrontal cortex, as the seat of most higher brain functions, is functionally silent during most of infancy. This review highlights recent work concerned with the precise mapping (localization) of brain activation in human infants, providing evidence that prefrontal cortex exhibits functional activation much…

From Brain-Environment Connections to Temporal Dynamics and Social Interaction: Principles of Human Brain Function.

PubMed

Hari, Riitta

2017-06-07

Experimental data about brain function accumulate faster than does our understanding of how the brain works. To tackle some general principles at the grain level of behavior, I start from the omnipresent brain-environment connection that forces regularities of the physical world to shape the brain. Based on top-down processing, added by sparse sensory information, people are able to form individual "caricature worlds," which are similar enough to be shared among other people and which allow quick and purposeful reactions to abrupt changes. Temporal dynamics and social interaction in natural environments serve as further essential organizing principles of human brain function. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain and Cognitive Reserve: Translation via Network Control Theory

PubMed Central

Medaglia, John Dominic; Pasqualetti, Fabio; Hamilton, Roy H.; Thompson-Schill, Sharon L.; Bassett, Danielle S.

2017-01-01

Traditional approaches to understanding the brain’s resilience to neuropathology have identified neurophysiological variables, often described as brain or cognitive “reserve,” associated with better outcomes. However, mechanisms of function and resilience in large-scale brain networks remain poorly understood. Dynamic network theory may provide a basis for substantive advances in understanding functional resilience in the human brain. In this perspective, we describe recent theoretical approaches from network control theory as a framework for investigating network level mechanisms underlying cognitive function and the dynamics of neuroplasticity in the human brain. We describe the theoretical opportunities offered by the application of network control theory at the level of the human connectome to understand cognitive resilience and inform translational intervention. PMID:28104411

Elevated gene expression levels distinguish human from non-human primate brains

PubMed Central

Cáceres, Mario; Lachuer, Joel; Zapala, Matthew A.; Redmond, John C.; Kudo, Lili; Geschwind, Daniel H.; Lockhart, David J.; Preuss, Todd M.; Barlow, Carrolee

2003-01-01

Little is known about how the human brain differs from that of our closest relatives. To investigate the genetic basis of human specializations in brain organization and cognition, we compared gene expression profiles for the cerebral cortex of humans, chimpanzees, and rhesus macaques by using several independent techniques. We identified 169 genes that exhibited expression differences between human and chimpanzee cortex, and 91 were ascribed to the human lineage by using macaques as an outgroup. Surprisingly, most differences between the brains of humans and non-human primates involved up-regulation, with ≈90% of the genes being more highly expressed in humans. By contrast, in the comparison of human and chimpanzee heart and liver, the numbers of up- and down-regulated genes were nearly identical. Our results indicate that the human brain displays a distinctive pattern of gene expression relative to non-human primates, with higher expression levels for many genes belonging to a wide variety of functional classes. The increased expression of these genes could provide the basis for extensive modifications of cerebral physiology and function in humans and suggests that the human brain is characterized by elevated levels of neuronal activity. PMID:14557539

Growth and development of the brain and impact on cognitive outcomes.

PubMed

Hüppi, Petra S

2010-01-01

Understanding human brain development from the fetal life to adulthood is of great clinical importance as many neurological and neurobehavioral disorders have their origin in early structural and functional cerebral maturation. The developing brain is particularly prone to being affected by endogenous and exogenous events through the fetal and early postnatal life. The concept of 'developmental plasticity or disruption of the developmental program' summarizes these events. Increases in white matter, which speed up communication between brain cells, growing complexity of neuronal networks suggested by gray and white matter changes, and environmentally sensitive plasticity are all essential aspects in a child's ability to mentalize and maintain the adaptive flexibility necessary for achieving high sociocognitive functioning. Advancement in neuroimaging has opened up new ways for examining the developing human brain in vivo, the study of the effects of early antenatal, perinatal and neonatal events on later structural and functional brain development resulting in developmental disabilities or developmental resilience. In this review, methods of quantitative assessment of human brain development, such as 3D-MRI with image segmentation, diffusion tensor imaging to assess connectivity and functional MRI to visualize brain function will be presented. Copyright (c) 2010 S. Karger AG, Basel.

Eyes Open on Sleep and Wake: In Vivo to In Silico Neural Networks

PubMed Central

Vanvinckenroye, Amaury; Vandewalle, Gilles; Chellappa, Sarah L.

2016-01-01

Functional and effective connectivity of cortical areas are essential for normal brain function under different behavioral states. Appropriate cortical activity during sleep and wakefulness is ensured by the balanced activity of excitatory and inhibitory circuits. Ultimately, fast, millisecond cortical rhythmic oscillations shape cortical function in time and space. On a much longer time scale, brain function also depends on prior sleep-wake history and circadian processes. However, much remains to be established on how the brain operates at the neuronal level in humans during sleep and wakefulness. A key limitation of human neuroscience is the difficulty in isolating neuronal excitation/inhibition drive in vivo. Therefore, computational models are noninvasive approaches of choice to indirectly access hidden neuronal states. In this review, we present a physiologically driven in silico approach, Dynamic Causal Modelling (DCM), as a means to comprehend brain function under different experimental paradigms. Importantly, DCM has allowed for the understanding of how brain dynamics underscore brain plasticity, cognition, and different states of consciousness. In a broader perspective, noninvasive computational approaches, such as DCM, may help to puzzle out the spatial and temporal dynamics of human brain function at different behavioural states. PMID:26885400

Centrality of Social Interaction in Human Brain Function.

PubMed

Hari, Riitta; Henriksson, Linda; Malinen, Sanna; Parkkonen, Lauri

2015-10-07

People are embedded in social interaction that shapes their brains throughout lifetime. Instead of emerging from lower-level cognitive functions, social interaction could be the default mode via which humans communicate with their environment. Should this hypothesis be true, it would have profound implications on how we think about brain functions and how we dissect and simulate them. We suggest that the research on the brain basis of social cognition and interaction should move from passive spectator science to studies including engaged participants and simultaneous recordings from the brains of the interacting persons. Copyright © 2015 Elsevier Inc. All rights reserved.

Human brain networks function in connectome-specific harmonic waves.

PubMed

Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

2016-01-21

A key characteristic of human brain activity is coherent, spatially distributed oscillations forming behaviour-dependent brain networks. However, a fundamental principle underlying these networks remains unknown. Here we report that functional networks of the human brain are predicted by harmonic patterns, ubiquitous throughout nature, steered by the anatomy of the human cerebral cortex, the human connectome. We introduce a new technique extending the Fourier basis to the human connectome. In this new frequency-specific representation of cortical activity, that we call 'connectome harmonics', oscillatory networks of the human brain at rest match harmonic wave patterns of certain frequencies. We demonstrate a neural mechanism behind the self-organization of connectome harmonics with a continuous neural field model of excitatory-inhibitory interactions on the connectome. Remarkably, the critical relation between the neural field patterns and the delicate excitation-inhibition balance fits the neurophysiological changes observed during the loss and recovery of consciousness.

Dopaminergic Neurotransmission in the Human Brain: New Lessons from Perturbation and Imaging

PubMed Central

Ko, Ji Hyun; Strafella, Antonio P.

2012-01-01

Dopamine plays an important role in several brain functions and is involved in the pathogenesis of several psychiatric and neurological disorders. Neuroimaging techniques such as positron emission tomography allow us to quantify dopaminergic activity in the living human brain. Combining these with brain stimulation techniques offers us the unique opportunity to tackle questions regarding region-specific neurochemical activity. Such studies may aid clinicians and scientists to disentangle neural circuitries within the human brain and thereby help them to understand the underlying mechanisms of a given function in relation to brain diseases. Furthermore, it may also aid the development of alternative treatment approaches for various neurological and psychiatric conditions. PMID:21536838

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

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

Oxytocin, brain physiology, and functional connectivity: a review of intranasal oxytocin fMRI studies.

PubMed

Bethlehem, Richard A I; van Honk, Jack; Auyeung, Bonnie; Baron-Cohen, Simon

2013-07-01

In recent years the neuropeptide oxytocin (OT) has become one of the most studied peptides of the human neuroendocrine system. Research has shown widespread behavioural effects and numerous potential therapeutic benefits. However, little is known about how OT triggers these effects in the brain. Here, we discuss some of the physiological properties of OT in the human brain including the long half-life of neuropeptides, the diffuse projections of OT throughout the brain and interactions with other systems such as the dopaminergic system. These properties indicate that OT acts without clear spatial and temporal specificity. Therefore, it is likely to have widespread effects on the brain's intrinsic functioning. Additionally, we review studies that have used functional magnetic resonance imaging (fMRI) concurrently with OT administration. These studies reveal a specific set of 'social' brain regions that are likely to be the strongest targets for OT's potential to influence human behaviour. On the basis of the fMRI literature and the physiological properties of the neuropeptide, we argue that OT has the potential to not only modulate activity in a set of specific brain regions, but also the functional connectivity between these regions. In light of the increasing knowledge of the behavioural effects of OT in humans, studies of the effects of OT administration on brain function can contribute to our understanding of the neural networks in the social brain. Copyright © 2012 Elsevier Ltd. All rights reserved.

Multilayer modeling and analysis of human brain networks

PubMed Central

2017-01-01

Abstract Understanding how the human brain is structured, and how its architecture is related to function, is of paramount importance for a variety of applications, including but not limited to new ways to prevent, deal with, and cure brain diseases, such as Alzheimer’s or Parkinson’s, and psychiatric disorders, such as schizophrenia. The recent advances in structural and functional neuroimaging, together with the increasing attitude toward interdisciplinary approaches involving computer science, mathematics, and physics, are fostering interesting results from computational neuroscience that are quite often based on the analysis of complex network representation of the human brain. In recent years, this representation experienced a theoretical and computational revolution that is breaching neuroscience, allowing us to cope with the increasing complexity of the human brain across multiple scales and in multiple dimensions and to model structural and functional connectivity from new perspectives, often combined with each other. In this work, we will review the main achievements obtained from interdisciplinary research based on magnetic resonance imaging and establish de facto, the birth of multilayer network analysis and modeling of the human brain. PMID:28327916

Anatomical connectivity influences both intra- and inter-brain synchronizations.

PubMed

Dumas, Guillaume; Chavez, Mario; Nadel, Jacqueline; Martinerie, Jacques

2012-01-01

Recent development in diffusion spectrum brain imaging combined to functional simulation has the potential to further our understanding of how structure and dynamics are intertwined in the human brain. At the intra-individual scale, neurocomputational models have already started to uncover how the human connectome constrains the coordination of brain activity across distributed brain regions. In parallel, at the inter-individual scale, nascent social neuroscience provides a new dynamical vista of the coupling between two embodied cognitive agents. Using EEG hyperscanning to record simultaneously the brain activities of subjects during their ongoing interaction, we have previously demonstrated that behavioral synchrony correlates with the emergence of inter-brain synchronization. However, the functional meaning of such synchronization remains to be specified. Here, we use a biophysical model to quantify to what extent inter-brain synchronizations are related to the anatomical and functional similarity of the two brains in interaction. Pairs of interacting brains were numerically simulated and compared to real data. Results show a potential dynamical property of the human connectome to facilitate inter-individual synchronizations and thus may partly account for our propensity to generate dynamical couplings with others.

The development of Human Functional Brain Networks

PubMed Central

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

2010-01-01

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. PMID:20826306

Organization and hierarchy of the human functional brain network lead to a chain-like core.

PubMed

Mastrandrea, Rossana; Gabrielli, Andrea; Piras, Fabrizio; Spalletta, Gianfranco; Caldarelli, Guido; Gili, Tommaso

2017-07-07

The brain is a paradigmatic example of a complex system: its functionality emerges as a global property of local mesoscopic and microscopic interactions. Complex network theory allows to elicit the functional architecture of the brain in terms of links (correlations) between nodes (grey matter regions) and to extract information out of the noise. Here we present the analysis of functional magnetic resonance imaging data from forty healthy humans at rest for the investigation of the basal scaffold of the functional brain network organization. We show how brain regions tend to coordinate by forming a highly hierarchical chain-like structure of homogeneously clustered anatomical areas. A maximum spanning tree approach revealed the centrality of the occipital cortex and the peculiar aggregation of cerebellar regions to form a closed core. We also report the hierarchy of network segregation and the level of clusters integration as a function of the connectivity strength between brain regions.

The glia doctrine: addressing the role of glial cells in healthy brain ageing.

PubMed

Nagelhus, Erlend A; Amiry-Moghaddam, Mahmood; Bergersen, Linda H; Bjaalie, Jan G; Eriksson, Jens; Gundersen, Vidar; Leergaard, Trygve B; Morth, J Preben; Storm-Mathisen, Jon; Torp, Reidun; Walhovd, Kristine B; Tønjum, Tone

2013-10-01

Glial cells in their plurality pervade the human brain and impact on brain structure and function. A principal component of the emerging glial doctrine is the hypothesis that astrocytes, the most abundant type of glial cells, trigger major molecular processes leading to brain ageing. Astrocyte biology has been examined using molecular, biochemical and structural methods, as well as 3D brain imaging in live animals and humans. Exosomes are extracelluar membrane vesicles that facilitate communication between glia, and have significant potential for biomarker discovery and drug delivery. Polymorphisms in DNA repair genes may indirectly influence the structure and function of membrane proteins expressed in glial cells and predispose specific cell subgroups to degeneration. Physical exercise may reduce or retard age-related brain deterioration by a mechanism involving neuro-glial processes. It is most likely that additional information about the distribution, structure and function of glial cells will yield novel insight into human brain ageing. Systematic studies of glia and their functions are expected to eventually lead to earlier detection of ageing-related brain dysfunction and to interventions that could delay, reduce or prevent brain dysfunction. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain.

PubMed

Eide, Per Kristian; Ringstad, Geir

2015-11-01

Recently, the "glymphatic system" of the brain has been discovered in rodents, which is a paravascular, transparenchymal route for clearance of excess brain metabolites and distribution of compounds in the cerebrospinal fluid. It has already been demonstrated that intrathecally administered gadolinium (Gd) contrast medium distributes along this route in rats, but so far not in humans. A 27-year-old woman underwent magnetic resonance imaging (MRI) with intrathecal administration of gadobutrol, which distributed throughout her entire brain after 1 and 4.5 h. MRI with intrathecal Gd may become a tool to study glymphatic function in the human brain.

The effects of gut microbiota on CNS function in humans

PubMed Central

Tillisch, Kirsten

2014-01-01

The role of the gastrointestinal microbiota in human brain development and function is an area of increasing interest and research. Preclinical models suggest a role for the microbiota in broad aspects of human health, including mood, cognition, and chronic pain. Early human studies suggest that altering the microbiota with beneficial bacteria, or probiotics, can lead to changes in brain function, as well as subjective reports of mood. As the mechanisms of bidirectional communication between the brain and microbiota are better understood, it is expected that these pathways will be harnessed to provide novel methods to enhance health and treat disease. PMID:24838095

A pairwise maximum entropy model accurately describes resting-state human brain networks

PubMed Central

Watanabe, Takamitsu; Hirose, Satoshi; Wada, Hiroyuki; Imai, Yoshio; Machida, Toru; Shirouzu, Ichiro; Konishi, Seiki; Miyashita, Yasushi; Masuda, Naoki

2013-01-01

The resting-state human brain networks underlie fundamental cognitive functions and consist of complex interactions among brain regions. However, the level of complexity of the resting-state networks has not been quantified, which has prevented comprehensive descriptions of the brain activity as an integrative system. Here, we address this issue by demonstrating that a pairwise maximum entropy model, which takes into account region-specific activity rates and pairwise interactions, can be robustly and accurately fitted to resting-state human brain activities obtained by functional magnetic resonance imaging. Furthermore, to validate the approximation of the resting-state networks by the pairwise maximum entropy model, we show that the functional interactions estimated by the pairwise maximum entropy model reflect anatomical connexions more accurately than the conventional functional connectivity method. These findings indicate that a relatively simple statistical model not only captures the structure of the resting-state networks but also provides a possible method to derive physiological information about various large-scale brain networks. PMID:23340410

Human Brain Modeling with Its Anatomical Structure and Realistic Material Properties for Brain Injury Prediction.

PubMed

Atsumi, Noritoshi; Nakahira, Yuko; Tanaka, Eiichi; Iwamoto, Masami

2018-05-01

Impairments of executive brain function after traumatic brain injury (TBI) due to head impacts in traffic accidents need to be obviated. Finite element (FE) analyses with a human brain model facilitate understanding of the TBI mechanisms. However, conventional brain FE models do not suitably describe the anatomical structure in the deep brain, which is a critical region for executive brain function, and the material properties of brain parenchyma. In this study, for better TBI prediction, a novel brain FE model with anatomical structure in the deep brain was developed. The developed model comprises a constitutive model of brain parenchyma considering anisotropy and strain rate dependency. Validation was performed against postmortem human subject test data associated with brain deformation during head impact. Brain injury analyses were performed using head acceleration curves obtained from reconstruction analysis of rear-end collision with a human whole-body FE model. The difference in structure was found to affect the regions of strain concentration, while the difference in material model contributed to the peak strain value. The injury prediction result by the proposed model was consistent with the characteristics in the neuroimaging data of TBI patients due to traffic accidents.

Brain Imaging of Human Sexual Response: Recent Developments and Future Directions.

PubMed

Ruesink, Gerben B; Georgiadis, Janniko R

2017-01-01

The purpose of this study is to provide a comprehensive summary of the latest developments in the experimental brain study of human sexuality, focusing on brain connectivity during the sexual response. Stable patterns of brain activation have been established for different phases of the sexual response, especially with regard to the wanting phase, and changes in these patterns can be linked to sexual response variations, including sexual dysfunctions. From this solid basis, connectivity studies of the human sexual response have begun to add a deeper understanding of the brain network function and structure involved. The study of "sexual" brain connectivity is still very young. Yet, by approaching the brain as a connected organ, the essence of brain function is captured much more accurately, increasing the likelihood of finding useful biomarkers and targets for intervention in sexual dysfunction.

Human high intelligence is involved in spectral redshift of biophotonic activities in the brain

PubMed Central

Wang, Niting; Li, Zehua; Xiao, Fangyan; Dai, Jiapei

2016-01-01

Human beings hold higher intelligence than other animals on Earth; however, it is still unclear which brain properties might explain the underlying mechanisms. The brain is a major energy-consuming organ compared with other organs. Neural signal communications and information processing in neural circuits play an important role in the realization of various neural functions, whereas improvement in cognitive function is driven by the need for more effective communication that requires less energy. Combining the ultraweak biophoton imaging system (UBIS) with the biophoton spectral analysis device (BSAD), we found that glutamate-induced biophotonic activities and transmission in the brain, which has recently been demonstrated as a novel neural signal communication mechanism, present a spectral redshift from animals (in order of bullfrog, mouse, chicken, pig, and monkey) to humans, even up to a near-infrared wavelength (∼865 nm) in the human brain. This brain property may be a key biophysical basis for explaining high intelligence in humans because biophoton spectral redshift could be a more economical and effective measure of biophotonic signal communications and information processing in the human brain. PMID:27432962

Intraoperative Functional Ultrasound Imaging of Human Brain Activity.

PubMed

Imbault, Marion; Chauvet, Dorian; Gennisson, Jean-Luc; Capelle, Laurent; Tanter, Mickael

2017-08-04

The functional mapping of brain activity is essential to perform optimal glioma surgery and to minimize the risk of postoperative deficits. We introduce a new, portable neuroimaging modality of the human brain based on functional ultrasound (fUS) for deep functional cortical mapping. Using plane-wave transmissions at an ultrafast frame rate (1 kHz), fUS is performed during surgery to measure transient changes in cerebral blood volume with a high spatiotemporal resolution (250 µm, 1 ms). fUS identifies, maps and differentiates regions of brain activation during task-evoked cortical responses within the depth of a sulcus in both awake and anaesthetized patients.

Understanding How Cognitive Psychology Can Inform and Improve Spanish Vocabulary Acquisition in High School Classrooms

ERIC Educational Resources Information Center

Erbes, Stella; Folkerts, Michael; Gergis, Christina; Pederson, Sarah; Stivers, Holly

2010-01-01

Educators deal with the many dynamic functions and applications of the human brain on a daily basis. The theoretical research of the biology and functionality of the human brain is on the rise, and educational publishers continue to support books and scholarly articles that promote the notion that "brain research" can and should be applied to…

Multi-scale integration and predictability in resting state brain activity

PubMed Central

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

2014-01-01

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

Large-scale topology and the default mode network in the mouse connectome

PubMed Central

Stafford, James M.; Jarrett, Benjamin R.; Miranda-Dominguez, Oscar; Mills, Brian D.; Cain, Nicholas; Mihalas, Stefan; Lahvis, Garet P.; Lattal, K. Matthew; Mitchell, Suzanne H.; David, Stephen V.; Fryer, John D.; Nigg, Joel T.; Fair, Damien A.

2014-01-01

Noninvasive functional imaging holds great promise for serving as a translational bridge between human and animal models of various neurological and psychiatric disorders. However, despite a depth of knowledge of the cellular and molecular underpinnings of atypical processes in mouse models, little is known about the large-scale functional architecture measured by functional brain imaging, limiting translation to human conditions. Here, we provide a robust processing pipeline to generate high-resolution, whole-brain resting-state functional connectivity MRI (rs-fcMRI) images in the mouse. Using a mesoscale structural connectome (i.e., an anterograde tracer mapping of axonal projections across the mouse CNS), we show that rs-fcMRI in the mouse has strong structural underpinnings, validating our procedures. We next directly show that large-scale network properties previously identified in primates are present in rodents, although they differ in several ways. Last, we examine the existence of the so-called default mode network (DMN)—a distributed functional brain system identified in primates as being highly important for social cognition and overall brain function and atypically functionally connected across a multitude of disorders. We show the presence of a potential DMN in the mouse brain both structurally and functionally. Together, these studies confirm the presence of basic network properties and functional networks of high translational importance in structural and functional systems in the mouse brain. This work clears the way for an important bridge measurement between human and rodent models, enabling us to make stronger conclusions about how regionally specific cellular and molecular manipulations in mice relate back to humans. PMID:25512496

Cross-hemispheric functional connectivity in the human fetal brain.

PubMed

Thomason, Moriah E; Dassanayake, Maya T; Shen, Stephen; Katkuri, Yashwanth; Alexis, Mitchell; Anderson, Amy L; Yeo, Lami; Mody, Swati; Hernandez-Andrade, Edgar; Hassan, Sonia S; Studholme, Colin; Jeong, Jeong-Won; Romero, Roberto

2013-02-20

Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

PubMed

Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

2016-03-01

Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing.

[Introduction of neuroethics: out of clinic, beyond academia in human brain research].

PubMed

Fukushi, Tamami; Sakura, Osamu

2008-11-01

Higher cognitive function in human brain is one of well-developed fields of neuroscience research in the 21st century. Especially functional magnetic resonance imaging (fMRI) and near infrared recording system have brought so many non-clinical researchers whose background is such as cognitive psychology, economics, politics, pedagogy, and so on, to the human brain mapping study. Authors have introduced the ethical issues related to incidental findings during the fMRI recording for non-clinical purpose, which is a typical problem derived from such expanded human brain research under non clinical condition, that is, neuroethics. In the present article we would introduce neuroethical issues in contexts of "out of clinic" and "beyond academia".

MRI with intrathecal MRI gadolinium contrast medium administration: a possible method to assess glymphatic function in human brain

PubMed Central

Ringstad, Geir

2015-01-01

Recently, the “glymphatic system” of the brain has been discovered in rodents, which is a paravascular, transparenchymal route for clearance of excess brain metabolites and distribution of compounds in the cerebrospinal fluid. It has already been demonstrated that intrathecally administered gadolinium (Gd) contrast medium distributes along this route in rats, but so far not in humans. A 27-year-old woman underwent magnetic resonance imaging (MRI) with intrathecal administration of gadobutrol, which distributed throughout her entire brain after 1 and 4.5 h. MRI with intrathecal Gd may become a tool to study glymphatic function in the human brain. PMID:26634147

Phosphatidylserine and the human brain.

PubMed

Glade, Michael J; Smith, Kyl

2015-06-01

The aim of this study was to assess the roles and importance of phosphatidylserine (PS), an endogenous phospholipid and dietary nutrient, in human brain biochemistry, physiology, and function. A scientific literature search was conducted on MEDLINE for relevant articles regarding PS and the human brain published before June 2014. Additional publications were identified from references provided in original papers; 127 articles were selected for inclusion in this review. A large body of scientific evidence describes the interactions among PS, cognitive activity, cognitive aging, and retention of cognitive functioning ability. Phosphatidylserine is required for healthy nerve cell membranes and myelin. Aging of the human brain is associated with biochemical alterations and structural deterioration that impair neurotransmission. Exogenous PS (300-800 mg/d) is absorbed efficiently in humans, crosses the blood-brain barrier, and safely slows, halts, or reverses biochemical alterations and structural deterioration in nerve cells. It supports human cognitive functions, including the formation of short-term memory, the consolidation of long-term memory, the ability to create new memories, the ability to retrieve memories, the ability to learn and recall information, the ability to focus attention and concentrate, the ability to reason and solve problems, language skills, and the ability to communicate. It also supports locomotor functions, especially rapid reactions and reflexes. Copyright © 2015 Elsevier Inc. All rights reserved.

Relationship between concentrations of lutein and StARD3 among pediatric and geriatric human brain tissue

USDA-ARS?s Scientific Manuscript database

Lutein, a dietary carotenoid, selectively accumulates in human retina and brain. While many epidemiological studies show evidence of a relationship between lutein status and cognitive health, lutein's selective uptake in human brain tissue and its potential function in early neural development and c...

Dynamics of the brain: Mathematical models and non-invasive experimental studies

NASA Astrophysics Data System (ADS)

Toronov, V.; Myllylä, T.; Kiviniemi, V.; Tuchin, V. V.

2013-10-01

Dynamics is an essential aspect of the brain function. In this article we review theoretical models of neural and haemodynamic processes in the human brain and experimental non-invasive techniques developed to study brain functions and to measure dynamic characteristics, such as neurodynamics, neurovascular coupling, haemodynamic changes due to brain activity and autoregulation, and cerebral metabolic rate of oxygen. We focus on emerging theoretical biophysical models and experimental functional neuroimaging results, obtained mostly by functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS). We also included our current results on the effects of blood pressure variations on cerebral haemodynamics and simultaneous measurements of fast processes in the brain by near-infrared spectroscopy and a very novel functional MRI technique called magnetic resonance encephalography. Based on a rapid progress in theoretical and experimental techniques and due to the growing computational capacities and combined use of rapidly improving and emerging neuroimaging techniques we anticipate during next decade great achievements in the overall knowledge of the human brain.

Cell diversity and network dynamics in photosensitive human brain organoids

PubMed Central

Quadrato, Giorgia; Nguyen, Tuan; Macosko, Evan Z.; Sherwood, John L.; Yang, Sung Min; Berger, Daniel; Maria, Natalie; Scholvin, Jorg; Goldman, Melissa; Kinney, Justin; Boyden, Edward S.; Lichtman, Jeff; Williams, Ziv M.; McCarroll, Steven A.; Arlotta, Paola

2017-01-01

In vitro models of the developing brain such as 3D brain organoids offer an unprecedented opportunity to study aspects of human brain development and disease. However, it remains undefined what cells are generated within organoids and to what extent they recapitulate the regional complexity, cellular diversity, and circuit functionality of the brain. Here, we analyzed gene expression in over 80,000 individual cells isolated from 31 human brain organoids. We find that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina. Organoids could be developed over extended periods (over 9 months) enabling unprecedented levels of maturity including the formation of dendritic spines and of spontaneously-active neuronal networks. Finally, neuronal activity within organoids could be controlled using light stimulation of photoreceptor-like cells, which may offer ways to probe the functionality of human neuronal circuits using physiological sensory stimuli. PMID:28445462

Cell diversity and network dynamics in photosensitive human brain organoids.

PubMed

Quadrato, Giorgia; Nguyen, Tuan; Macosko, Evan Z; Sherwood, John L; Min Yang, Sung; Berger, Daniel R; Maria, Natalie; Scholvin, Jorg; Goldman, Melissa; Kinney, Justin P; Boyden, Edward S; Lichtman, Jeff W; Williams, Ziv M; McCarroll, Steven A; Arlotta, Paola

2017-05-04

In vitro models of the developing brain such as three-dimensional brain organoids offer an unprecedented opportunity to study aspects of human brain development and disease. However, the cells generated within organoids and the extent to which they recapitulate the regional complexity, cellular diversity and circuit functionality of the brain remain undefined. Here we analyse gene expression in over 80,000 individual cells isolated from 31 human brain organoids. We find that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina. Organoids could be developed over extended periods (more than 9 months), allowing for the establishment of relatively mature features, including the formation of dendritic spines and spontaneously active neuronal networks. Finally, neuronal activity within organoids could be controlled using light stimulation of photosensitive cells, which may offer a way to probe the functionality of human neuronal circuits using physiological sensory stimuli.

Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain

PubMed Central

2016-01-01

An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain. PMID:26982717

Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

PubMed

Li, Guangye; Zhang, Dingguo

2016-01-01

An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain.

Quantitative Imaging of Energy Expenditure in Human Brain

PubMed Central

Zhu, Xiao-Hong; Qiao, Hongyan; Du, Fei; Xiong, Qiang; Liu, Xiao; Zhang, Xiaoliang; Ugurbil, Kamil; Chen, Wei

2012-01-01

Despite the essential role of the brain energy generated from ATP hydrolysis in supporting cortical neuronal activity and brain function, it is challenging to noninvasively image and directly quantify the energy expenditure in the human brain. In this study, we applied an advanced in vivo 31P MRS imaging approach to obtain regional cerebral metabolic rates of high-energy phosphate reactions catalyzed by ATPase (CMRATPase) and creatine kinase (CMRCK), and to determine CMRATPase and CMRCK in pure grey mater (GM) and white mater (WM), respectively. It was found that both ATPase and CK rates are three times higher in GM than WM; and CMRCK is seven times higher than CMRATPase in GM and WM. Among the total brain ATP consumption in the human cortical GM and WM, 77% of them are used by GM in which approximately 96% is by neurons. A single cortical neuron utilizes approximately 4.7 billion ATPs per second in a resting human brain. This study demonstrates the unique utility of in vivo 31P MRS imaging modality for direct imaging of brain energy generated from ATP hydrolysis, and provides new insights into the human brain energetics and its role in supporting neuronal activity and brain function. PMID:22487547

Inter-species activity correlations reveal functional correspondences between monkey and human brain areas

PubMed Central

Mantini, Dante; Hasson, Uri; Betti, Viviana; Perrucci, Mauro G.; Romani, Gian Luca; Corbetta, Maurizio; Orban, Guy A.; Vanduffel, Wim

2012-01-01

Evolution-driven functional changes in the primate brain are typically assessed by aligning monkey and human activation maps using cortical surface expansion models. These models use putative homologous areas as registration landmarks, assuming they are functionally correspondent. In cases where functional changes have occurred in an area, this assumption prohibits to reveal whether other areas may have assumed lost functions. Here we describe a method to examine functional correspondences across species. Without making spatial assumptions, we assess similarities in sensory-driven functional magnetic resonance imaging responses between monkey (Macaca mulatta) and human brain areas by means of temporal correlation. Using natural vision data, we reveal regions for which functional processing has shifted to topologically divergent locations during evolution. We conclude that substantial evolution-driven functional reorganizations have occurred, not always consistent with cortical expansion processes. This novel framework for evaluating changes in functional architecture is crucial to building more accurate evolutionary models. PMID:22306809

Evolution of human brain functions: the functional structure of human consciousness.

PubMed

Cloninger, C Robert

2009-11-01

The functional structure of self-aware consciousness in human beings is described based on the evolution of human brain functions. Prior work on heritable temperament and character traits is extended to account for the quantum-like and holographic properties (i.e. parts elicit wholes) of self-aware consciousness. Cladistic analysis is used to identify the succession of ancestors leading to human beings. The functional capacities that emerge along this lineage of ancestors are described. The ecological context in which each cladogenesis occurred is described to illustrate the shifting balance of evolution as a complex adaptive system. Comparative neuroanatomy is reviewed to identify the brain structures and networks that emerged coincident with the emergent brain functions. Individual differences in human temperament traits were well developed in the common ancestor shared by reptiles and humans. Neocortical development in mammals proceeded in five major transitions: from early reptiles to early mammals, early primates, simians, early Homo, and modern Homo sapiens. These transitions provide the foundation for human self-awareness related to sexuality, materiality, emotionality, intellectuality, and spirituality, respectively. The functional structure of human self-aware consciousness is concerned with the regulation of five planes of being: sexuality, materiality, emotionality, intellectuality, and spirituality. Each plane elaborates neocortical functions organized around one of the five special senses. The interactions among these five planes gives rise to a 5 x 5 matrix of subplanes, which are functions that coarsely describe the focus of neocortical regulation. Each of these 25 neocortical functions regulates each of five basic motives or drives that can be measured as temperaments or basic emotions related to fear, anger, disgust, surprise, and happiness/sadness. The resulting 5 x 5 x 5 matrix of human characteristics provides a general and testable model of the functional structure of human consciousness that includes personality, physicality, emotionality, cognition, and spirituality in a unified developmental framework.

Selective Audiovisual Semantic Integration Enabled by Feature-Selective Attention.

PubMed

Li, Yuanqing; Long, Jinyi; Huang, Biao; Yu, Tianyou; Wu, Wei; Li, Peijun; Fang, Fang; Sun, Pei

2016-01-13

An audiovisual object may contain multiple semantic features, such as the gender and emotional features of the speaker. Feature-selective attention and audiovisual semantic integration are two brain functions involved in the recognition of audiovisual objects. Humans often selectively attend to one or several features while ignoring the other features of an audiovisual object. Meanwhile, the human brain integrates semantic information from the visual and auditory modalities. However, how these two brain functions correlate with each other remains to be elucidated. In this functional magnetic resonance imaging (fMRI) study, we explored the neural mechanism by which feature-selective attention modulates audiovisual semantic integration. During the fMRI experiment, the subjects were presented with visual-only, auditory-only, or audiovisual dynamical facial stimuli and performed several feature-selective attention tasks. Our results revealed that a distribution of areas, including heteromodal areas and brain areas encoding attended features, may be involved in audiovisual semantic integration. Through feature-selective attention, the human brain may selectively integrate audiovisual semantic information from attended features by enhancing functional connectivity and thus regulating information flows from heteromodal areas to brain areas encoding the attended features.

Sex differences in the brain-an interplay of sex steroid hormones and sex chromosomes.

PubMed

Grgurevic, Neza; Majdic, Gregor

2016-09-01

Although considerable progress has been made in our understanding of brain function, many questions remain unanswered. The ultimate goal of studying the brain is to understand the connection between brain structure and function and behavioural outcomes. Since sex differences in brain morphology were first observed, subsequent studies suggest different functional organization of the male and female brains in humans. Sex and gender have been identified as being a significant factor in understanding human physiology, health and disease, and the biological differences between the sexes is not limited to the gonads and secondary sexual characteristics, but also affects the structure and, more crucially, the function of the brain and other organs. Significant variability in brain structures between individuals, in addition to between the sexes, is factor that complicates the study of sex differences in the brain. In this review, we explore the current understanding of sex differences in the brain, mostly focusing on preclinical animal studies. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans

USDA-ARS?s Scientific Manuscript database

Objective: In animals, intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation. In humans, functional brain magnetic resonance imaging (fMRI) studies during carbohydrate ingestion suggest that glucose may regulate HT signaling but are potentially confoun...

Chapter 18: the origins of functional brain imaging in humans.

PubMed

Raichle, Marcus E

2010-01-01

Functional brain imaging in humans as we presently know it began when the experimental strategies of cognitive psychology were combined with modern brain imaging techniques, first positron emission tomography (PET) and then functional magnetic resonance imaging (fMRI), to examine how brain function supports mental activities. This marriage of disciplines and techniques galvanized the field of cognitive neuroscience, which has rapidly expanded to include a broad range of the social sciences as well as basic scientists interested in the neurophysiology, cell biology and genetics of the imaging signals. While much of this work has transpired over the past couple of decades, its roots can be traced back more than a century.

Symmetry and asymmetry in the human brain

NASA Astrophysics Data System (ADS)

Hugdahl, Kenneth

2005-10-01

Structural and functional asymmetry in the human brain and nervous system is reviewed in a historical perspective, focusing on the pioneering work of Broca, Wernicke, Sperry, and Geschwind. Structural and functional asymmetry is exemplified from work done in our laboratory on auditory laterality using an empirical procedure called dichotic listening. This also involves different ways of validating the dichotic listening procedure against both invasive and non-invasive techniques, including PET and fMRI blood flow recordings. A major argument is that the human brain shows a substantial interaction between structurally, or "bottom-up" asymmetry and cognitively, or "top-down" modulation, through a focus of attention to the right or left side in auditory space. These results open up a more dynamic and interactive view of functional brain asymmetry than the traditional static view that the brain is lateralized, or asymmetric, only for specific stimuli and stimulus properties.

Small-world human brain networks: Perspectives and challenges.

PubMed

Liao, Xuhong; Vasilakos, Athanasios V; He, Yong

2017-06-01

Modelling the human brain as a complex network has provided a powerful mathematical framework to characterize the structural and functional architectures of the brain. In the past decade, the combination of non-invasive neuroimaging techniques and graph theoretical approaches enable us to map human structural and functional connectivity patterns (i.e., connectome) at the macroscopic level. One of the most influential findings is that human brain networks exhibit prominent small-world organization. Such a network architecture in the human brain facilitates efficient information segregation and integration at low wiring and energy costs, which presumably results from natural selection under the pressure of a cost-efficiency balance. Moreover, the small-world organization undergoes continuous changes during normal development and ageing and exhibits dramatic alterations in neurological and psychiatric disorders. In this review, we survey recent advances regarding the small-world architecture in human brain networks and highlight the potential implications and applications in multidisciplinary fields, including cognitive neuroscience, medicine and engineering. Finally, we highlight several challenging issues and areas for future research in this rapidly growing field. Copyright © 2017 Elsevier Ltd. All rights reserved.

Individual differences in intrinsic brain connectivity predict decision strategy.

PubMed

Barnes, Kelly Anne; Anderson, Kevin M; Plitt, Mark; Martin, Alex

2014-10-15

When humans are provided with ample time to make a decision, individual differences in strategy emerge. Using an adaptation of a well-studied decision making paradigm, motion direction discrimination, we probed the neural basis of individual differences in strategy. We tested whether strategies emerged from moment-to-moment reconfiguration of functional brain networks involved in decision making with task-evoked functional MRI (fMRI) and whether intrinsic properties of functional brain networks, measured at rest with functional connectivity MRI (fcMRI), were associated with strategy use. We found that human participants reliably selected one of two strategies across 2 days of task performance, either continuously accumulating evidence or waiting for task difficulty to decrease. Individual differences in decision strategy were predicted both by the degree of task-evoked activation of decision-related brain regions and by the strength of pretask correlated spontaneous brain activity. These results suggest that spontaneous brain activity constrains strategy selection on perceptual decisions.

Energetic and nutritional constraints on infant brain development: implications for brain expansion during human evolution.

PubMed

Cunnane, Stephen C; Crawford, Michael A

2014-12-01

The human brain confronts two major challenges during its development: (i) meeting a very high energy requirement, and (ii) reliably accessing an adequate dietary source of specific brain selective nutrients needed for its structure and function. Implicitly, these energetic and nutritional constraints to normal brain development today would also have been constraints on human brain evolution. The energetic constraint was solved in large measure by the evolution in hominins of a unique and significant layer of body fat on the fetus starting during the third trimester of gestation. By providing fatty acids for ketone production that are needed as brain fuel, this fat layer supports the brain's high energy needs well into childhood. This fat layer also contains an important reserve of the brain selective omega-3 fatty acid, docosahexaenoic acid (DHA), not available in other primates. Foremost amongst the brain selective minerals are iodine and iron, with zinc, copper and selenium also being important. A shore-based diet, i.e., fish, molluscs, crustaceans, frogs, bird's eggs and aquatic plants, provides the richest known dietary sources of brain selective nutrients. Regular access to these foods by the early hominin lineage that evolved into humans would therefore have helped free the nutritional constraint on primate brain development and function. Inadequate dietary supply of brain selective nutrients still has a deleterious impact on human brain development on a global scale today, demonstrating the brain's ongoing vulnerability. The core of the shore-based paradigm of human brain evolution proposes that sustained access by certain groups of early Homo to freshwater and marine food resources would have helped surmount both the nutritional as well as the energetic constraints on mammalian brain development. Copyright © 2014 Elsevier Ltd. All rights reserved.

ABC transporters and cytochromes P450 in the human central nervous system: influence on brain pharmacokinetics and contribution to neurodegenerative disorders.

PubMed

Dutheil, Fabien; Jacob, Aude; Dauchy, Sandrine; Beaune, Philippe; Scherrmann, Jean-Michel; Declèves, Xavier; Loriot, Marie-Anne

2010-10-01

The identification of xenobiotic metabolizing enzymes (i.e., CYP) and transporters (i.e., ABC transporters) (XMET) in the human brain, including the BBB, raises the question whether these transporters and enzymes have specific functions in brain physiology, neuropharmacology and toxicology. Relevant literature was identified using PubMed search articles published up to March 2010. Search terms included 'ABC transporters and P450 or CYP', 'drug metabolism, effect and toxicity' and 'neurodegenerative disease (Alzheimer and Parkinson diseases)' restricted to the field of 'brain or human brain'. This review aims to provide a better understanding of XMET functions in the human brain and show their pharmacological importance for improving drug delivery and efficacy and also for managing their side effects. Finally, the impact of brain XMET activity during neurodegenerative processes is discussed, giving an opportunity to identify new markers of human brain diseases. During the last 2 decades, much evidence concerning the specific distribution patterns of XMET, their induction by xenobiotics and endobiotics and their genetic variations have made cerebral ABC transporters and CYP enzymes key elements in the way individual patients respond to centrally acting drugs.

Transgenic Mice Carrying GLUD2 as a Tool for Studying the Expressional and the Functional Adaptation of this Positive Selected Gene in Human Brain Evolution.

PubMed

Plaitakis, Andreas; Kotzamani, Dimitra; Petraki, Zoe; Delidaki, Maria; Rinotas, Vagelis; Zaganas, Ioannis; Douni, Eleni; Sidiropoulou, Kyriaki; Spanaki, Cleanthe

2018-05-18

Human evolution is characterized by brain expansion and up-regulation of genes involved in energy metabolism and synaptic transmission, including the glutamate signaling pathway. Glutamate is the excitatory transmitter of neural circuits sub-serving cognitive functions, with glutamate-modulation of synaptic plasticity being central to learning and memory. GLUD2 is a novel positively-selected human gene involved in glutamatergic transmission and energy metabolism that underwent rapid evolutionary adaptation concomitantly with prefrontal cortex enlargement. Two evolutionary replacements (Gly456Ala and Arg443Ser) made hGDH2 resistant to GTP inhibition and allowed distinct regulation, enabling enhanced enzyme function under high glutamatergic system demands. GLUD2 adaptation may have contributed to unique human traits, but evidence for this is lacking. GLUD2 arose through retro-positioning of a processed GLUD1 mRNA to the X chromosome, a DNA replication mechanism that typically generates pseudogenes. However, by finding a suitable promoter, GLUD2 is thought to have gained expression in nerve and other tissues, where it adapted to their particular needs. Here we generated GLUD2 transgenic (Tg) mice by inserting in their genome a segment of the human X chromosome, containing the GLUD2 gene and its putative promoter. Double IF studies of Tg mouse brain revealed that the human gene is expressed in the host mouse brain in a pattern similar to that observed in human brain, thus providing credence to the above hypothesis. This expressional adaptation may have conferred novel role(s) on GLUD2 in human brain. Previous observations, also in GLUD2 Tg mice, generated and studied independently, showed that the non-redundant function of hGDH2 is markedly activated during early post-natal brain development, contributing to developmental changes in prefrontal cortex similar to those attributed to human divergence. Hence, GLUD2 adaptation may have influenced the evolutionary course taken by the human brain, but understanding the mechanism(s) involved remains challenging.

Multilayer motif analysis of brain networks

NASA Astrophysics Data System (ADS)

Battiston, Federico; Nicosia, Vincenzo; Chavez, Mario; Latora, Vito

2017-04-01

In the last decade, network science has shed new light both on the structural (anatomical) and on the functional (correlations in the activity) connectivity among the different areas of the human brain. The analysis of brain networks has made possible to detect the central areas of a neural system and to identify its building blocks by looking at overabundant small subgraphs, known as motifs. However, network analysis of the brain has so far mainly focused on anatomical and functional networks as separate entities. The recently developed mathematical framework of multi-layer networks allows us to perform an analysis of the human brain where the structural and functional layers are considered together. In this work, we describe how to classify the subgraphs of a multiplex network, and we extend the motif analysis to networks with an arbitrary number of layers. We then extract multi-layer motifs in brain networks of healthy subjects by considering networks with two layers, anatomical and functional, respectively, obtained from diffusion and functional magnetic resonance imaging. Results indicate that subgraphs in which the presence of a physical connection between brain areas (links at the structural layer) coexists with a non-trivial positive correlation in their activities are statistically overabundant. Finally, we investigate the existence of a reinforcement mechanism between the two layers by looking at how the probability to find a link in one layer depends on the intensity of the connection in the other one. Showing that functional connectivity is non-trivially constrained by the underlying anatomical network, our work contributes to a better understanding of the interplay between the structure and function in the human brain.

Expression of functional neurotransmitter receptors in Xenopus oocytes after injection of human brain membranes

NASA Astrophysics Data System (ADS)

Miledi, Ricardo; Eusebi, Fabrizio; Martínez-Torres, Ataúlfo; Palma, Eleonora; Trettel, Flavia

2002-10-01

The Xenopus oocyte is a very powerful tool for studies of the structure and function of membrane proteins, e.g., messenger RNA extracted from the brain and injected into oocytes leads to the synthesis and membrane incorporation of many types of functional receptors and ion channels, and membrane vesicles from Torpedo electroplaques injected into oocytes fuse with the oocyte membrane and cause the appearance of functional Torpedo acetylcholine receptors and Cl channels. This approach was developed further to transplant already assembled neurotransmitter receptors from human brain cells to the plasma membrane of Xenopus oocytes. Membranes isolated from the temporal neocortex of a patient, operated for intractable epilepsy, were injected into oocytes and, within a few hours, the oocyte membrane acquired functional neurotransmitter receptors to -aminobutyric acid, -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, and glycine. These receptors were also expressed in the plasma membrane of oocytes injected with mRNA extracted from the temporal neocortex of the same patient. All of this makes the Xenopus oocyte a more useful model than it already is for studies of the structure and function of many human membrane proteins and opens the way to novel pathophysiological investigations of some human brain disorders.

Age-associated changes in rich-club organisation in autistic and neurotypical human brains

PubMed Central

Watanabe, Takamitsu; Rees, Geraint

2015-01-01

Macroscopic structural networks in the human brain have a rich-club architecture comprising both highly inter-connected central regions and sparsely connected peripheral regions. Recent studies show that disruption of this functionally efficient organisation is associated with several psychiatric disorders. However, despite increasing attention to this network property, whether age-associated changes in rich-club organisation occur during human adolescence remains unclear. Here, analysing a publicly shared diffusion tensor imaging dataset, we found that, during adolescence, brains of typically developing (TD) individuals showed increases in rich-club organisation and inferred network functionality, whereas individuals with autism spectrum disorders (ASD) did not. These differences between TD and ASD groups were statistically significant for both structural and functional properties. Moreover, this typical age-related changes in rich-club organisation were characterised by progressive involvement of the right anterior insula. In contrast, in ASD individuals, did not show typical increases in grey matter volume, and this relative anatomical immaturity was correlated with the severity of ASD social symptoms. These results provide evidence that rich-club architecture is one of the bases of functionally efficient brain networks underpinning complex cognitive functions in adult human brains. Furthermore, our findings suggest that immature rich-club organisation might be associated with some neurodevelopmental disorders. PMID:26537477

Asymmetry of Hemispheric Network Topology Reveals Dissociable Processes between Functional and Structural Brain Connectome in Community-Living Elders

PubMed Central

Sun, Yu; Li, Junhua; Suckling, John; Feng, Lei

2017-01-01

Human brain is structurally and functionally asymmetrical and the asymmetries of brain phenotypes have been shown to change in normal aging. Recent advances in graph theoretical analysis have showed topological lateralization between hemispheric networks in the human brain throughout the lifespan. Nevertheless, apparent discrepancies of hemispheric asymmetry were reported between the structural and functional brain networks, indicating the potentially complex asymmetry patterns between structural and functional networks in aging population. In this study, using multimodal neuroimaging (resting-state fMRI and structural diffusion tensor imaging), we investigated the characteristics of hemispheric network topology in 76 (male/female = 15/61, age = 70.08 ± 5.30 years) community-dwelling older adults. Hemispheric functional and structural brain networks were obtained for each participant. Graph theoretical approaches were then employed to estimate the hemispheric topological properties. We found that the optimal small-world properties were preserved in both structural and functional hemispheric networks in older adults. Moreover, a leftward asymmetry in both global and local levels were observed in structural brain networks in comparison with a symmetric pattern in functional brain network, suggesting a dissociable process of hemispheric asymmetry between structural and functional connectome in healthy older adults. Finally, the scores of hemispheric asymmetry in both structural and functional networks were associated with behavioral performance in various cognitive domains. Taken together, these findings provide new insights into the lateralized nature of multimodal brain connectivity, highlight the potentially complex relationship between structural and functional brain network alterations, and augment our understanding of asymmetric structural and functional specializations in normal aging. PMID:29209197

Docosahexaenoic acid and human brain development: evidence that a dietary supply is needed for optimal development.

PubMed

Brenna, J Thomas; Carlson, Susan E

2014-12-01

Humans evolved a uniquely large brain among terrestrial mammals. Brain and nervous tissue is rich in the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA). Docosahexaenoic acid is required for lower and high order functions in humans because of understood and emerging molecular mechanisms. Among brain components that depend on dietary components, DHA is limiting because its synthesis from terrestrial plant food precursors is low but its utilization when consumed in diet is very efficient. Negligible DHA is found in terrestrial plants, but in contrast, DHA is plentiful at the shoreline where it is made by single-celled organisms and plants, and in the seas supports development of very large marine mammal brains. Modern human brains accumulate DHA up to age 18, most aggressively from about half-way through gestation to about two years of age. Studies in modern humans and non-human primates show that modern infants consuming infant formulas that include only DHA precursors have lower DHA levels than for those with a source of preformed DHA. Functional measures show that infants consuming preformed DHA have improved visual and cognitive function. Dietary preformed DHA in the breast milk of modern mothers supports many-fold greater breast milk DHA than is found in the breast milk of vegans, a phenomenon linked to consumption of shore-based foods. Most current evidence suggests that the DHA-rich human brain required an ample and sustained source of dietary DHA to reach its full potential. Copyright © 2014 Elsevier Ltd. All rights reserved.

Resting State Network Topology of the Ferret Brain

PubMed Central

Zhou, Zhe Charles; Salzwedel, Andrew P.; Radtke-Schuller, Susanne; Li, Yuhui; Sellers, Kristin K.; Gilmore, John H.; Shih, Yen-Yu Ian; Fröhlich, Flavio; Gao, Wei

2016-01-01

Resting state functional magnetic resonance imaging (rsfMRI) has emerged as a versatile tool for non-invasive measurement of functional connectivity patterns in the brain. RsfMRI brain dynamics in rodents, non-human primates, and humans share similar properties; however, little is known about the resting state functional connectivity patterns in the ferret, an animal model with high potential for developmental and cognitive translational study. To address this knowledge-gap, we performed rsfMRI on anesthetized ferrets using a 9.4 tesla MRI scanner, and subsequently performed group-level independent component analysis (gICA) to identify functionally connected brain networks. Group-level ICA analysis revealed distributed sensory, motor, and higher-order networks in the ferret brain. Subsequent connectivity analysis showed interconnected higher-order networks that constituted a putative default mode network (DMN), a network that exhibits altered connectivity in neuropsychiatric disorders. Finally, we assessed ferret brain topological efficiency using graph theory analysis and found that the ferret brain exhibits small-world properties. Overall, these results provide additional evidence for pan-species resting-state networks, further supporting ferret-based studies of sensory and cognitive function. PMID:27596024

Stepwise Connectivity of the Modal Cortex Reveals the Multimodal Organization of the Human Brain

PubMed Central

Sepulcre, Jorge; Sabuncu, Mert R.; Yeo, Thomas B.; Liu, Hesheng; Johnson, Keith A.

2012-01-01

How human beings integrate information from external sources and internal cognition to produce a coherent experience is still not well understood. During the past decades, anatomical, neurophysiological and neuroimaging research in multimodal integration have stood out in the effort to understand the perceptual binding properties of the brain. Areas in the human lateral occipito-temporal, prefrontal and posterior parietal cortices have been associated with sensory multimodal processing. Even though this, rather patchy, organization of brain regions gives us a glimpse of the perceptual convergence, the articulation of the flow of information from modality-related to the more parallel cognitive processing systems remains elusive. Using a method called Stepwise Functional Connectivity analysis, the present study analyzes the functional connectome and transitions from primary sensory cortices to higher-order brain systems. We identify the large-scale multimodal integration network and essential connectivity axes for perceptual integration in the human brain. PMID:22855814

An Animal-to-Human Scaling Law for Blast-Induced Traumatic Brain Injury Risk Assessment

DTIC Science & Technology

2014-10-28

TERMS b. ABSTRACT 2. REPORT TYPE 17. LIMITATION OF ABSTRACT 15. NUMBER OF PAGES 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 5c...brain, as well as their acoustic impedance. Peak stresses transmitted to the brain tissue by the blast are then shown to be a power function of the...be a power function of the scaling parameter for a range of blast conditions relevant to TBI. In particu- lar, it is found that human brain

The Brain Prize 2014: complex human functions.

PubMed

Grigaityte, Kristina; Iacoboni, Marco

2014-11-01

Giacomo Rizzolatti, Stanislas Dehaene, and Trevor Robbins were recently awarded the 2014 Grete Lundbeck European Brain Research Prize for their 'pioneering research on higher brain mechanisms underpinning such complex human functions as literacy, numeracy, motivated behavior and social cognition, and for their effort to understand cognitive and behavioral disorders'. Why was their work highlighted? Is there anything that links together these seemingly disparate lines of research? Copyright © 2014 Elsevier Ltd. All rights reserved.

Sex Differences in the Brain.

ERIC Educational Resources Information Center

Kimura, Doreen

1992-01-01

Explores the neural and hormonal basis of human intellectual function that gives rise to sex differences in the brain. Discusses behavioral, neurological, endocrinological studies, and studies of the effects of hormones on brain functioning that show a relationship between cognitive variations and sex. (MCO)

Evidence of native α-synuclein conformers in the human brain.

PubMed

Gould, Neal; Mor, Danielle E; Lightfoot, Richard; Malkus, Kristen; Giasson, Benoit; Ischiropoulos, Harry

2014-03-14

α-Synuclein aggregation is central to the pathogenesis of several brain disorders. However, the native conformations and functions of this protein in the human brain are not precisely known. The native state of α-synuclein was probed by gel filtration coupled with native gradient gel separation, an array of antibodies with non-overlapping epitopes, and mass spectrometry. The existence of metastable conformers and stable monomer was revealed in the human brain.

Defining functional SMA and pre-SMA subregions in human MFC using resting state fMRI: functional connectivity-based parcellation method.

PubMed

Kim, Jae-Hun; Lee, Jong-Min; Jo, Hang Joon; Kim, Sook Hui; Lee, Jung Hee; Kim, Sung Tae; Seo, Sang Won; Cox, Robert W; Na, Duk L; Kim, Sun I; Saad, Ziad S

2010-02-01

Noninvasive parcellation of the human cerebral cortex is an important goal for understanding and examining brain functions. Recently, the patterns of anatomical connections using diffusion tensor imaging (DTI) have been used to parcellate brain regions. Here, we present a noninvasive parcellation approach that uses "functional fingerprints" obtained by correlation measures on resting state functional magnetic resonance imaging (fMRI) data to parcellate brain regions. In other terms, brain regions are parcellated based on the similarity of their connection--as reflected by correlation during resting state--to the whole brain. The proposed method was used to parcellate the medial frontal cortex (MFC) into supplementary motor areas (SMA) and pre-SMA subregions. In agreement with anatomical landmark-based parcellation, we find that functional fingerprint clustering of the MFC results in anterior and posterior clusters. The probabilistic maps from 12 subjects showed that the anterior cluster is mainly located rostral to the vertical commissure anterior (VCA) line, whereas the posterior cluster is mainly located caudal to VCA line, suggesting the homologues of pre-SMA and SMA. The functional connections from the putative pre-SMA cluster were connected to brain regions which are responsible for complex/cognitive motor control, whereas those from the putative SMA cluster were connected to brain regions which are related to the simple motor control. These findings demonstrate the feasibility of the functional connectivity-based parcellation of the human cerebral cortex using resting state fMRI. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Default mode network, motor network, dorsal and ventral basal ganglia networks in the rat brain: comparison to human networks using resting state-fMRI.

PubMed

Sierakowiak, Adam; Monnot, Cyril; Aski, Sahar Nikkhou; Uppman, Martin; Li, Tie-Qiang; Damberg, Peter; Brené, Stefan

2015-01-01

Rodent models are developed to enhance understanding of the underlying biology of different brain disorders. However, before interpreting findings from animal models in a translational aspect to understand human disease, a fundamental step is to first have knowledge of similarities and differences of the biological systems studied. In this study, we analyzed and verified four known networks termed: default mode network, motor network, dorsal basal ganglia network, and ventral basal ganglia network using resting state functional MRI (rsfMRI) in humans and rats. Our work supports the notion that humans and rats have common robust resting state brain networks and that rsfMRI can be used as a translational tool when validating animal models of brain disorders. In the future, rsfMRI may be used, in addition to short-term interventions, to characterize longitudinal effects on functional brain networks after long-term intervention in humans and rats.

Default Mode Network, Motor Network, Dorsal and Ventral Basal Ganglia Networks in the Rat Brain: Comparison to Human Networks Using Resting State-fMRI

PubMed Central

Sierakowiak, Adam; Monnot, Cyril; Aski, Sahar Nikkhou; Uppman, Martin; Li, Tie-Qiang; Damberg, Peter; Brené, Stefan

2015-01-01

Rodent models are developed to enhance understanding of the underlying biology of different brain disorders. However, before interpreting findings from animal models in a translational aspect to understand human disease, a fundamental step is to first have knowledge of similarities and differences of the biological systems studied. In this study, we analyzed and verified four known networks termed: default mode network, motor network, dorsal basal ganglia network, and ventral basal ganglia network using resting state functional MRI (rsfMRI) in humans and rats. Our work supports the notion that humans and rats have common robust resting state brain networks and that rsfMRI can be used as a translational tool when validating animal models of brain disorders. In the future, rsfMRI may be used, in addition to short-term interventions, to characterize longitudinal effects on functional brain networks after long-term intervention in humans and rats. PMID:25789862

The Right Brain: An Emerging Frontier in Education.

ERIC Educational Resources Information Center

Beals, Mark G.

The main thrust of American education has been cognitively oriented. Recent research on the human brain suggests that such orientation is a general function of only one hemisphere of the brain, the left. Because of the close relationships among speech, language, thinking, reasoning, and the higher mental functions, the left brain hemisphere…

Effects of Diet on Brain Plasticity in Animal and Human Studies: Mind the Gap

PubMed Central

Dias, Gisele Pereira

2014-01-01

Dietary interventions have emerged as effective environmental inducers of brain plasticity. Among these dietary interventions, we here highlight the impact of caloric restriction (CR: a consistent reduction of total daily food intake), intermittent fasting (IF, every-other-day feeding), and diet supplementation with polyphenols and polyunsaturated fatty acids (PUFAs) on markers of brain plasticity in animal studies. Moreover, we also discuss epidemiological and intervention studies reporting the effects of CR, IF and dietary polyphenols and PUFAs on learning, memory, and mood. In particular, we evaluate the gap in mechanistic understanding between recent findings from animal studies and those human studies reporting that these dietary factors can benefit cognition, mood, and anxiety, aging, and Alzheimer's disease—with focus on the enhancement of structural and functional plasticity markers in the hippocampus, such as increased expression of neurotrophic factors, synaptic function and adult neurogenesis. Lastly, we discuss some of the obstacles to harnessing the promising effects of diet on brain plasticity in animal studies into effective recommendations and interventions to promote healthy brain function in humans. Together, these data reinforce the important translational concept that diet, a modifiable lifestyle factor, holds the ability to modulate brain health and function. PMID:24900924

Selective Audiovisual Semantic Integration Enabled by Feature-Selective Attention

PubMed Central

Li, Yuanqing; Long, Jinyi; Huang, Biao; Yu, Tianyou; Wu, Wei; Li, Peijun; Fang, Fang; Sun, Pei

2016-01-01

An audiovisual object may contain multiple semantic features, such as the gender and emotional features of the speaker. Feature-selective attention and audiovisual semantic integration are two brain functions involved in the recognition of audiovisual objects. Humans often selectively attend to one or several features while ignoring the other features of an audiovisual object. Meanwhile, the human brain integrates semantic information from the visual and auditory modalities. However, how these two brain functions correlate with each other remains to be elucidated. In this functional magnetic resonance imaging (fMRI) study, we explored the neural mechanism by which feature-selective attention modulates audiovisual semantic integration. During the fMRI experiment, the subjects were presented with visual-only, auditory-only, or audiovisual dynamical facial stimuli and performed several feature-selective attention tasks. Our results revealed that a distribution of areas, including heteromodal areas and brain areas encoding attended features, may be involved in audiovisual semantic integration. Through feature-selective attention, the human brain may selectively integrate audiovisual semantic information from attended features by enhancing functional connectivity and thus regulating information flows from heteromodal areas to brain areas encoding the attended features. PMID:26759193

Primary Cortical Folding in the Human Newborn: An Early Marker of Later Functional Development

ERIC Educational Resources Information Center

Dubois, J.; Benders, M.; Borradori-Tolsa, C.; Cachia, A.; Lazeyras, F.; Leuchter, R. Ha-Vinh; Sizonenko, S. V.; Warfield, S. K.; Mangin, J. F.; Huppi, P. S.

2008-01-01

In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be…

How Language Learners Can Improve Their Emotional Functioning: Important Psychological and Psychospiritual Theories

ERIC Educational Resources Information Center

Oxford, Rebecca L.

2015-01-01

Emotion is "the primary human motive" (MacIntyre, 2002, p. 61). The human brain is an emotional brain, creating relationships among thought, emotion, and motivation in a complex dynamic system (Dörnyei, 2009). Emotion "functions as an amplifier, providing the intensity, urgency, and energy to propel our behavior" in…

High-field fMRI unveils orientation columns in humans.

PubMed

Yacoub, Essa; Harel, Noam; Ugurbil, Kâmil

2008-07-29

Functional (f)MRI has revolutionized the field of human brain research. fMRI can noninvasively map the spatial architecture of brain function via localized increases in blood flow after sensory or cognitive stimulation. Recent advances in fMRI have led to enhanced sensitivity and spatial accuracy of the measured signals, indicating the possibility of detecting small neuronal ensembles that constitute fundamental computational units in the brain, such as cortical columns. Orientation columns in visual cortex are perhaps the best known example of such a functional organization in the brain. They cannot be discerned via anatomical characteristics, as with ocular dominance columns. Instead, the elucidation of their organization requires functional imaging methods. However, because of insufficient sensitivity, spatial accuracy, and image resolution of the available mapping techniques, thus far, they have not been detected in humans. Here, we demonstrate, by using high-field (7-T) fMRI, the existence and spatial features of orientation- selective columns in humans. Striking similarities were found with the known spatial features of these columns in monkeys. In addition, we found that a larger number of orientation columns are devoted to processing orientations around 90 degrees (vertical stimuli with horizontal motion), whereas relatively similar fMRI signal changes were observed across any given active column. With the current proliferation of high-field MRI systems and constant evolution of fMRI techniques, this study heralds the exciting prospect of exploring unmapped and/or unknown columnar level functional organizations in the human brain.

Detecting activity-evoked pH changes in human brain

PubMed Central

Magnotta, Vincent A.; Heo, Hye-Young; Dlouhy, Brian J.; Dahdaleh, Nader S.; Follmer, Robin L.; Thedens, Daniel R.; Welsh, Michael J.; Wemmie, John A.

2012-01-01

Localized pH changes have been suggested to occur in the brain during normal function. However, the existence of such pH changes has also been questioned. Lack of methods for noninvasively measuring pH with high spatial and temporal resolution has limited insight into this issue. Here we report that a magnetic resonance imaging (MRI) strategy, T1 relaxation in the rotating frame (T1ρ), is sufficiently sensitive to detect widespread pH changes in the mouse and human brain evoked by systemically manipulating carbon dioxide or bicarbonate. Moreover, T1ρ detected a localized acidosis in the human visual cortex induced by a flashing checkerboard. Lactate measurements and pH-sensitive 31P spectroscopy at the same site also identified a localized acidosis. Consistent with the established role for pH in blood flow recruitment, T1ρ correlated with blood oxygenation level-dependent contrast commonly used in functional MRI. However, T1ρ was not directly sensitive to blood oxygen content. These observations indicate that localized pH fluctuations occur in the human brain during normal function. Furthermore, they suggest a unique functional imaging strategy based on pH that is independent of traditional functional MRI contrast mechanisms. PMID:22566645

Synaptogenesis and heritable aspects of executive attention.

PubMed

Fossella, John A; Sommer, Tobias; Fan, Jin; Pfaff, Don; Posner, Michael I

2003-01-01

In humans, changes in brain structure and function can be measured non-invasively during postnatal development. In animals, advanced optical imaging measures can track the formation of synapses during learning and behavior. With the recent progress in these technologies, it is appropriate to begin to assess how the physiological processes of synapse, circuit, and neural network formation relate to the process of cognitive development. Of particular interest is the development of executive function, which develops more gradually in humans. One approach that has shown promise is molecular genetics. The completion of the human genome project and the human genome diversity project make it straightforward to ask whether variation in a particular gene correlates with variation in behavior, brain structure, brain activity, or all of the above. Strategies that unify the wealth of biochemical knowledge pertaining to synapse formation with the functional measures of brain structure and activity may lead to new insights in developmental cognitive psychology. Copyright 2003 Wiley-Liss, Inc.

Resting-State Functional Connectivity in the Human Connectome Project: Current Status and Relevance to Understanding Psychopathology.

PubMed

Barch, Deanna M

A key tenet of modern psychiatry is that psychiatric disorders arise from abnormalities in brain circuits that support human behavior. Our ability to examine hypotheses around circuit-level abnormalities in psychiatric disorders has been made possible by advances in human neuroimaging technologies. These advances have provided the basis for recent efforts to develop a more complex understanding of the function of brain circuits in health and of their relationship to behavior-providing, in turn, a foundation for our understanding of how disruptions in such circuits contribute to the development of psychiatric disorders. This review focuses on the use of resting-state functional connectivity MRI to assess brain circuits, on the advances generated by the Human Connectome Project, and on how these advances potentially contribute to understanding neural circuit dysfunction in psychopathology. The review gives particular attention to the methods developed by the Human Connectome Project that may be especially relevant to studies of psychopathology; it outlines some of the key findings about what constitutes a brain region; and it highlights new information about the nature and stability of brain circuits. Some of the Human Connectome Project's new findings particularly relevant to psychopathology-about neural circuits and their relationships to behavior-are also presented. The review ends by discussing the extension of Human Connectome Project methods across the lifespan and into manifest illness. Potential treatment implications are also considered.

Design analysis of an MPI human functional brain scanner

PubMed Central

Mason, Erica E.; Cooley, Clarissa Z.; Cauley, Stephen F.; Griswold, Mark A.; Conolly, Steven M.; Wald, Lawrence L.

2017-01-01

MPI’s high sensitivity makes it a promising modality for imaging brain function. Functional contrast is proposed based on blood SPION concentration changes due to Cerebral Blood Volume (CBV) increases during activation, a mechanism utilized in fMRI studies. MPI offers the potential for a direct and more sensitive measure of SPION concentration, and thus CBV, than fMRI. As such, fMPI could surpass fMRI in sensitivity, enhancing the scientific and clinical value of functional imaging. As human-sized MPI systems have not been attempted, we assess the technical challenges of scaling MPI from rodent to human brain. We use a full-system MPI simulator to test arbitrary hardware designs and encoding practices, and we examine tradeoffs imposed by constraints that arise when scaling to human size as well as safety constraints (PNS and central nervous system stimulation) not considered in animal scanners, thereby estimating spatial resolutions and sensitivities achievable with current technology. Using a projection FFL MPI system, we examine coil hardware options and their implications for sensitivity and spatial resolution. We estimate that an fMPI brain scanner is feasible, although with reduced sensitivity (20×) and spatial resolution (5×) compared to existing rodent systems. Nonetheless, it retains sufficient sensitivity and spatial resolution to make it an attractive future instrument for studying the human brain; additional technical innovations can result in further improvements. PMID:28752130

Free-floating adult human brain-derived slice cultures as a model to study the neuronal impact of Alzheimer's disease-associated Aβ oligomers.

PubMed

Mendes, Niele D; Fernandes, Artur; Almeida, Glaucia M; Santos, Luis E; Selles, Maria Clara; Lyra-Silva, Natalia; Machado, Carla M; Horta-Júnior, José A C; Louzada, Paulo R; De Felice, Fernanda G; Alvez-Leon, Soniza; Marcondes, Jorge; Assirati, João Alberto; Matias, Caio M; Klein, William L; Garcia-Cairasco, Norberto; Ferreira, Sergio T; Neder, Luciano; Sebollela, Adriano

2018-05-31

Slice cultures have been prepared from several organs. With respect to the brain, advantages of slice cultures over dissociated cell cultures include maintenance of the cytoarchitecture and neuronal connectivity. Slice cultures from adult human brain have been reported and constitute a promising method to study neurological diseases. Despite this potential, few studies have characterized in detail cell survival and function along time in short-term, free-floating cultures. We used tissue from adult human brain cortex from patients undergoing temporal lobectomy to prepare 200 μm-thick slices. Along the period in culture, we evaluated neuronal survival, histological modifications, and neurotransmitter release. The toxicity of Alzheimer's-associated Aβ oligomers (AβOs) to cultured slices was also analyzed. Neurons in human brain slices remain viable and neurochemically active for at least four days in vitro, which allowed detection of binding of AβOs. We further found that slices exposed to AβOs presented elevated levels of hyperphosphorylated Tau, a hallmark of Alzheimer's disease. Although slice cultures from adult human brain have been previously prepared, this is the first report to analyze cell viability and neuronal activity in short-term free-floating cultures as a function of days in vitro. Once surgical tissue is available, the current protocol is easy to perform and produces functional slices from adult human brain. These slice cultures may represent a preferred model for translational studies of neurodegenerative disorders when long term culturing in not required, as in investigations on AβO neurotoxicity. Copyright © 2018 Elsevier B.V. All rights reserved.

Large-scale network integration in the human brain tracks temporal fluctuations in memory encoding performance.

PubMed

Keerativittayayut, Ruedeerat; Aoki, Ryuta; Sarabi, Mitra Taghizadeh; Jimura, Koji; Nakahara, Kiyoshi

2018-06-18

Although activation/deactivation of specific brain regions have been shown to be predictive of successful memory encoding, the relationship between time-varying large-scale brain networks and fluctuations of memory encoding performance remains unclear. Here we investigated time-varying functional connectivity patterns across the human brain in periods of 30-40 s, which have recently been implicated in various cognitive functions. During functional magnetic resonance imaging, participants performed a memory encoding task, and their performance was assessed with a subsequent surprise memory test. A graph analysis of functional connectivity patterns revealed that increased integration of the subcortical, default-mode, salience, and visual subnetworks with other subnetworks is a hallmark of successful memory encoding. Moreover, multivariate analysis using the graph metrics of integration reliably classified the brain network states into the period of high (vs. low) memory encoding performance. Our findings suggest that a diverse set of brain systems dynamically interact to support successful memory encoding. © 2018, Keerativittayayut et al.

Addressing Literacy through Neuroscience

ERIC Educational Resources Information Center

Miller, Steve; Tallal, Paula A.

2006-01-01

Brain is the source of all human thoughts, feelings and emotions. Now the mysteries of the human brain are rapidly being elucidated by neuroscience research. For more than 150 years, neuroscience has held that most of the brain's functionality develops during critical periods in early childhood and that once past these critical periods, the window…

Intranasal Neuropeptide Administration To Target the Human Brain in Health and Disease.

PubMed

Spetter, Maartje S; Hallschmid, Manfred

2015-08-03

Central nervous system control of metabolic function relies on the input of endocrine messengers from the periphery, including the pancreatic hormone insulin and the adipokine leptin. This concept primarily derives from experiments in animals where substances can be directly applied to the brain. A feasible approach to study the impact of peptidergic messengers on brain function in humans is the intranasal (IN) route of administration, which bypasses the blood-brain barrier and delivers neuropeptides to the brain compartment, but induces considerably less, if any, peripheral uptake than other administration modes. Experimental IN insulin administration has been extensively used to delineate the role of brain insulin signaling in the control of energy homeostasis, but also cognitive function in healthy humans. Clinical pilot studies have found beneficial effects of IN insulin in patients with memory deficits, suggesting that the IN delivery of this and other peptides bears some promise for new, selectively brain-targeted pharmaceutical approaches in the treatment of metabolic and cognitive disorders. More recently, experiments relying on the IN delivery of the hypothalamic hormone oxytocin, which is primarily known for its involvement in psychosocial processes, have provided evidence that oxytocin influences metabolic control in humans. The IN administration of leptin has been successfully tested in animal models but remains to be investigated in the human setting. We briefly summarize the literature on the IN administration of insulin, leptin, and oxytocin, with a particular focus on metabolic effects, and address limitations and perspectives of IN neuropeptide administration.

Hemisphere- and gender-related differences in small-world brain networks: a resting-state functional MRI study.

PubMed

Tian, Lixia; Wang, Jinhui; Yan, Chaogan; He, Yong

2011-01-01

We employed resting-state functional MRI (R-fMRI) to investigate hemisphere- and gender-related differences in the topological organization of human brain functional networks. Brain networks were first constructed by measuring inter-regional temporal correlations of R-fMRI data within each hemisphere in 86 young, healthy, right-handed adults (38 males and 48 females) followed by a graph-theory analysis. The hemispheric networks exhibit small-world attributes (high clustering and short paths) that are compatible with previous results in the whole-brain functional networks. Furthermore, we found that compared with females, males have a higher normalized clustering coefficient in the right hemispheric network but a lower clustering coefficient in the left hemispheric network, suggesting a gender-hemisphere interaction. Moreover, we observed significant hemisphere-related differences in the regional nodal characteristics in various brain regions, such as the frontal and occipital regions (leftward asymmetry) and the temporal regions (rightward asymmetry), findings that are consistent with previous studies of brain structural and functional asymmetries. Together, our results suggest that the topological organization of human brain functional networks is associated with gender and hemispheres, and they provide insights into the understanding of functional substrates underlying individual differences in behaviors and cognition. Copyright © 2010 Elsevier Inc. All rights reserved.

Canonical Genetic Signatures of the Adult Human Brain

PubMed Central

Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Jegga, Anil G.; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L.; Menche, Jörge; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A.; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R.; Jones, Allan; Van Essen, David C.; Koch, Christof; Lein, Ed

2015-01-01

The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological annotations, disease associations, drug targets, and literature citations. Using high DS genes we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components, and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely-patterned genes displayed dramatic shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

2015 Summer Series - Lee Stone - Brain Function Through the Eyes of the Beholder

NASA Image and Video Library

2015-06-09

The Visuomotor Control Laboratory (VCL) at NASA Ames conducts neuroscience research on the link between eye movements and brain function to provide an efficient and quantitative means of monitoring human perceptual performance. The VCL aims to make dramatic improvements in mission success through analysis, experimentation, and modeling of human performance and human-automation interaction. Dr. Lee Stone elaborates on how this research is conducted and how it contributes to NASA's mission and advances human-centered design and operations of complex aerospace systems.

Bridging animal and human models of exercise-induced brain plasticity

PubMed Central

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

2015-01-01

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

Increased Global Interaction Across Functional Brain Modules During Cognitive Emotion Regulation.

PubMed

Brandl, Felix; Mulej Bratec, Satja; Xie, Xiyao; Wohlschläger, Afra M; Riedl, Valentin; Meng, Chun; Sorg, Christian

2017-07-13

Cognitive emotion regulation (CER) enables humans to flexibly modulate their emotions. While local theories of CER neurobiology suggest interactions between specialized local brain circuits underlying CER, e.g., in subparts of amygdala and medial prefrontal cortices (mPFC), global theories hypothesize global interaction increases among larger functional brain modules comprising local circuits. We tested the global CER hypothesis using graph-based whole-brain network analysis of functional MRI data during aversive emotional processing with and without CER. During CER, global between-module interaction across stable functional network modules increased. Global interaction increase was particularly driven by subregions of amygdala and cuneus-nodes of highest nodal participation-that overlapped with CER-specific local activations, and by mPFC and posterior cingulate as relevant connector hubs. Results provide evidence for the global nature of human CER, complementing functional specialization of embedded local brain circuits during successful CER. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Toward a standardized structural-functional group connectome in MNI space.

PubMed

Horn, Andreas; Blankenburg, Felix

2016-01-01

The analysis of the structural architecture of the human brain in terms of connectivity between its subregions has provided profound insights into its underlying functional organization and has coined the concept of the "connectome", a structural description of the elements forming the human brain and the connections among them. Here, as a proof of concept, we introduce a novel group connectome in standard space based on a large sample of 169 subjects from the Enhanced Nathan Kline Institute-Rockland Sample (eNKI-RS). Whole brain structural connectomes of each subject were estimated with a global tracking approach, and the resulting fiber tracts were warped into standard stereotactic (MNI) space using DARTEL. Employing this group connectome, the results of published tracking studies (i.e., the JHU white matter and Oxford thalamic connectivity atlas) could be largely reproduced directly within MNI space. In a second analysis, a study that examined structural connectivity between regions of a functional network, namely the default mode network, was reproduced. Voxel-wise structural centrality was then calculated and compared to others' findings. Furthermore, including additional resting-state fMRI data from the same subjects, structural and functional connectivity matrices between approximately forty thousand nodes of the brain were calculated. This was done to estimate structure-function agreement indices of voxel-wise whole brain connectivity. Taken together, the combination of a novel whole brain fiber tracking approach and an advanced normalization method led to a group connectome that allowed (at least heuristically) performing fiber tracking directly within MNI space. Such an approach may be used for various purposes like the analysis of structural connectivity and modeling experiments that aim at studying the structure-function relationship of the human connectome. Moreover, it may even represent a first step toward a standard DTI template of the human brain in stereotactic space. The standardized group connectome might thus be a promising new resource to better understand and further analyze the anatomical architecture of the human brain on a population level. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain Evolution and Human Neuropsychology: The Inferential Brain Hypothesis

PubMed Central

Koscik, Timothy R.; Tranel, Daniel

2013-01-01

Collaboration between human neuropsychology and comparative neuroscience has generated invaluable contributions to our understanding of human brain evolution and function. Further cross-talk between these disciplines has the potential to continue to revolutionize these fields. Modern neuroimaging methods could be applied in a comparative context, yielding exciting new data with the potential of providing insight into brain evolution. Conversely, incorporating an evolutionary base into the theoretical perspectives from which we approach human neuropsychology could lead to novel hypotheses and testable predictions. In the spirit of these objectives, we present here a new theoretical proposal, the Inferential Brain Hypothesis, whereby the human brain is thought to be characterized by a shift from perceptual processing to inferential computation, particularly within the social realm. This shift is believed to be a driving force for the evolution of the large human cortex. PMID:22459075

'What' and 'where' in the human brain.

PubMed

Ungerleider, L G; Haxby, J V

1994-04-01

Multiple visual areas in the cortex of nonhuman primates are organized into two hierarchically organized and functionally specialized processing pathways, a 'ventral stream' for object vision and a 'dorsal stream' for spatial vision. Recent findings from positron emission tomography activation studies have localized these pathways within the human brain, yielding insights into cortical hierarchies, specialization of function, and attentional mechanisms.

Identification of the Transcriptional Targets of FOXP2, a Gene Linked to Speech and Language, in Developing Human Brain

PubMed Central

Spiteri, Elizabeth ; Konopka, Genevieve ; Coppola, Giovanni ; Bomar, Jamee ; Oldham, Michael ; Ou, Jing ; Vernes, Sonja C. ; Fisher, Simon E. ; Ren, Bing ; Geschwind, Daniel H. 

2007-01-01

Mutations in FOXP2, a member of the forkhead family of transcription factor genes, are the only known cause of developmental speech and language disorders in humans. To date, there are no known targets of human FOXP2 in the nervous system. The identification of FOXP2 targets in the developing human brain, therefore, provides a unique tool with which to explore the development of human language and speech. Here, we define FOXP2 targets in human basal ganglia (BG) and inferior frontal cortex (IFC) by use of chromatin immunoprecipitation followed by microarray analysis (ChIP-chip) and validate the functional regulation of targets in vitro. ChIP-chip identified 285 FOXP2 targets in fetal human brain; statistically significant overlap of targets in BG and IFC indicates a core set of 34 transcriptional targets of FOXP2. We identified targets specific to IFC or BG that were not observed in lung, suggesting important regional and tissue differences in FOXP2 activity. Many target genes are known to play critical roles in specific aspects of central nervous system patterning or development, such as neurite outgrowth, as well as plasticity. Subsets of the FOXP2 transcriptional targets are either under positive selection in humans or differentially expressed between human and chimpanzee brain. This is the first ChIP-chip study to use human brain tissue, making the FOXP2-target genes identified in these studies important to understanding the pathways regulating speech and language in the developing human brain. These data provide the first insight into the functional network of genes directly regulated by FOXP2 in human brain and by evolutionary comparisons, highlighting genes likely to be involved in the development of human higher-order cognitive processes. PMID:17999357

Neonatal brain resting-state functional connectivity imaging modalities.

PubMed

Mohammadi-Nejad, Ali-Reza; Mahmoudzadeh, Mahdi; Hassanpour, Mahlegha S; Wallois, Fabrice; Muzik, Otto; Papadelis, Christos; Hansen, Anne; Soltanian-Zadeh, Hamid; Gelovani, Juri; Nasiriavanaki, Mohammadreza

2018-06-01

Infancy is the most critical period in human brain development. Studies demonstrate that subtle brain abnormalities during this state of life may greatly affect the developmental processes of the newborn infants. One of the rapidly developing methods for early characterization of abnormal brain development is functional connectivity of the brain at rest. While the majority of resting-state studies have been conducted using magnetic resonance imaging (MRI), there is clear evidence that resting-state functional connectivity (rs-FC) can also be evaluated using other imaging modalities. The aim of this review is to compare the advantages and limitations of different modalities used for the mapping of infants' brain functional connectivity at rest. In addition, we introduce photoacoustic tomography, a novel functional neuroimaging modality, as a complementary modality for functional mapping of infants' brain.

Ad cerebrum per scientia: Ira Hirsh, psychoacoustics, and new approaches to understanding the human brain

NASA Astrophysics Data System (ADS)

Lauter, Judith

2002-05-01

As Research Director of CID, Ira emphasized the importance of combining information from biology with rigorous studies of behavior, such as psychophysics, to better understand how the brain and body accomplish the goals of everyday life. In line with this philosophy, my doctoral dissertation sought to explain brain functional asymmetries (studied with dichotic listening) in terms of the physical dimensions of a library of test sounds designed to represent a speech-music continuum. Results highlighted individual differences plus similarities in terms of patterns of relative ear advantages, suggesting an organizational basis for brain asymmetries depending on physical dimensions of stimulus and gesture with analogs in auditory, visual, somatosensory, and motor systems. My subsequent work has employed a number of noninvasive methods (OAEs, EPs, qEEG, PET, MRI) to explore the neurobiological bases of individual differences in general and functional asymmetries in particular. This research has led to (1) the AXS test battery for assessing the neurobiology of human sensory-motor function; (2) the handshaking model of brain function, describing dynamic relations along all three body/brain axes; (3) the four-domain EPIC model of functional asymmetries; and (4) the trimodal brain, a new model of individual differences based on psychoimmunoneuroendocrinology.

Resting state network topology of the ferret brain.

PubMed

Zhou, Zhe Charles; Salzwedel, Andrew P; Radtke-Schuller, Susanne; Li, Yuhui; Sellers, Kristin K; Gilmore, John H; Shih, Yen-Yu Ian; Fröhlich, Flavio; Gao, Wei

2016-12-01

Resting state functional magnetic resonance imaging (rsfMRI) has emerged as a versatile tool for non-invasive measurement of functional connectivity patterns in the brain. RsfMRI brain dynamics in rodents, non-human primates, and humans share similar properties; however, little is known about the resting state functional connectivity patterns in the ferret, an animal model with high potential for developmental and cognitive translational study. To address this knowledge-gap, we performed rsfMRI on anesthetized ferrets using a 9.4T MRI scanner, and subsequently performed group-level independent component analysis (gICA) to identify functionally connected brain networks. Group-level ICA analysis revealed distributed sensory, motor, and higher-order networks in the ferret brain. Subsequent connectivity analysis showed interconnected higher-order networks that constituted a putative default mode network (DMN), a network that exhibits altered connectivity in neuropsychiatric disorders. Finally, we assessed ferret brain topological efficiency using graph theory analysis and found that the ferret brain exhibits small-world properties. Overall, these results provide additional evidence for pan-species resting-state networks, further supporting ferret-based studies of sensory and cognitive function. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional Specialization in the Human Brain Estimated By Intrinsic Hemispheric Interaction

PubMed Central

Wang, Danhong; Buckner, Randy L.

2014-01-01

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

A Four-Dimensional Probabilistic Atlas of the Human Brain

PubMed Central

Mazziotta, John; Toga, Arthur; Evans, Alan; Fox, Peter; Lancaster, Jack; Zilles, Karl; Woods, Roger; Paus, Tomas; Simpson, Gregory; Pike, Bruce; Holmes, Colin; Collins, Louis; Thompson, Paul; MacDonald, David; Iacoboni, Marco; Schormann, Thorsten; Amunts, Katrin; Palomero-Gallagher, Nicola; Geyer, Stefan; Parsons, Larry; Narr, Katherine; Kabani, Noor; Le Goualher, Georges; Feidler, Jordan; Smith, Kenneth; Boomsma, Dorret; Pol, Hilleke Hulshoff; Cannon, Tyrone; Kawashima, Ryuta; Mazoyer, Bernard

2001-01-01

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype– phenotype–behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders. PMID:11522763

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

ERIC Educational Resources Information Center

Johnson, Mark H.; Grossmann, Tobias; Kadosh, Kathrin Cohen

2009-01-01

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…

Triadic (ecological, neural, cognitive) niche construction: a scenario of human brain evolution extrapolating tool use and language from the control of reaching actions

PubMed Central

Iriki, Atsushi; Taoka, Miki

2012-01-01

Hominin evolution has involved a continuous process of addition of new kinds of cognitive capacity, including those relating to manufacture and use of tools and to the establishment of linguistic faculties. The dramatic expansion of the brain that accompanied additions of new functional areas would have supported such continuous evolution. Extended brain functions would have driven rapid and drastic changes in the hominin ecological niche, which in turn demanded further brain resources to adapt to it. In this way, humans have constructed a novel niche in each of the ecological, cognitive and neural domains, whose interactions accelerated their individual evolution through a process of triadic niche construction. Human higher cognitive activity can therefore be viewed holistically as one component in a terrestrial ecosystem. The brain's functional characteristics seem to play a key role in this triadic interaction. We advance a speculative argument about the origins of its neurobiological mechanisms, as an extension (with wider scope) of the evolutionary principles of adaptive function in the animal nervous system. The brain mechanisms that subserve tool use may bridge the gap between gesture and language—the site of such integration seems to be the parietal and extending opercular cortices. PMID:22106423

Triadic (ecological, neural, cognitive) niche construction: a scenario of human brain evolution extrapolating tool use and language from the control of reaching actions.

PubMed

Iriki, Atsushi; Taoka, Miki

2012-01-12

Hominin evolution has involved a continuous process of addition of new kinds of cognitive capacity, including those relating to manufacture and use of tools and to the establishment of linguistic faculties. The dramatic expansion of the brain that accompanied additions of new functional areas would have supported such continuous evolution. Extended brain functions would have driven rapid and drastic changes in the hominin ecological niche, which in turn demanded further brain resources to adapt to it. In this way, humans have constructed a novel niche in each of the ecological, cognitive and neural domains, whose interactions accelerated their individual evolution through a process of triadic niche construction. Human higher cognitive activity can therefore be viewed holistically as one component in a terrestrial ecosystem. The brain's functional characteristics seem to play a key role in this triadic interaction. We advance a speculative argument about the origins of its neurobiological mechanisms, as an extension (with wider scope) of the evolutionary principles of adaptive function in the animal nervous system. The brain mechanisms that subserve tool use may bridge the gap between gesture and language--the site of such integration seems to be the parietal and extending opercular cortices.

Development of Human Brain Structural Networks Through Infancy and Childhood

PubMed Central

Huang, Hao; Shu, Ni; Mishra, Virendra; Jeon, Tina; Chalak, Lina; Wang, Zhiyue J.; Rollins, Nancy; Gong, Gaolang; Cheng, Hua; Peng, Yun; Dong, Qi; He, Yong

2015-01-01

During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers. PMID:24335033

Synaptic inputs from stroke-injured brain to grafted human stem cell-derived neurons activated by sensory stimuli.

PubMed

Tornero, Daniel; Tsupykov, Oleg; Granmo, Marcus; Rodriguez, Cristina; Grønning-Hansen, Marita; Thelin, Jonas; Smozhanik, Ekaterina; Laterza, Cecilia; Wattananit, Somsak; Ge, Ruimin; Tatarishvili, Jemal; Grealish, Shane; Brüstle, Oliver; Skibo, Galina; Parmar, Malin; Schouenborg, Jens; Lindvall, Olle; Kokaia, Zaal

2017-03-01

Transplanted neurons derived from stem cells have been proposed to improve function in animal models of human disease by various mechanisms such as neuronal replacement. However, whether the grafted neurons receive functional synaptic inputs from the recipient's brain and integrate into host neural circuitry is unknown. Here we studied the synaptic inputs from the host brain to grafted cortical neurons derived from human induced pluripotent stem cells after transplantation into stroke-injured rat cerebral cortex. Using the rabies virus-based trans-synaptic tracing method and immunoelectron microscopy, we demonstrate that the grafted neurons receive direct synaptic inputs from neurons in different host brain areas located in a pattern similar to that of neurons projecting to the corresponding endogenous cortical neurons in the intact brain. Electrophysiological in vivo recordings from the cortical implants show that physiological sensory stimuli, i.e. cutaneous stimulation of nose and paw, can activate or inhibit spontaneous activity in grafted neurons, indicating that at least some of the afferent inputs are functional. In agreement, we find using patch-clamp recordings that a portion of grafted neurons respond to photostimulation of virally transfected, channelrhodopsin-2-expressing thalamo-cortical axons in acute brain slices. The present study demonstrates, for the first time, that the host brain regulates the activity of grafted neurons, providing strong evidence that transplanted human induced pluripotent stem cell-derived cortical neurons can become incorporated into injured cortical circuitry. Our findings support the idea that these neurons could contribute to functional recovery in stroke and other conditions causing neuronal loss in cerebral cortex. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Perturbation of Brain Oscillations after Ischemic Stroke: A Potential Biomarker for Post-Stroke Function and Therapy

PubMed Central

Rabiller, Gratianne; He, Ji-Wei; Nishijima, Yasuo; Wong, Aaron; Liu, Jialing

2015-01-01

Brain waves resonate from the generators of electrical current and propagate across brain regions with oscillation frequencies ranging from 0.05 to 500 Hz. The commonly observed oscillatory waves recorded by an electroencephalogram (EEG) in normal adult humans can be grouped into five main categories according to the frequency and amplitude, namely δ (1–4 Hz, 20–200 μV), θ (4–8 Hz, 10 μV), α (8–12 Hz, 20–200 μV), β (12–30 Hz, 5–10 μV), and γ (30–80 Hz, low amplitude). Emerging evidence from experimental and human studies suggests that groups of function and behavior seem to be specifically associated with the presence of each oscillation band, although the complex relationship between oscillation frequency and function, as well as the interaction between brain oscillations, are far from clear. Changes of brain oscillation patterns have long been implicated in the diseases of the central nervous system including ischemic stroke, in which the reduction of cerebral blood flow as well as the progression of tissue damage have direct spatiotemporal effects on the power of several oscillatory bands and their interactions. This review summarizes the current knowledge in behavior and function associated with each brain oscillation, and also in the specific changes in brain electrical activities that correspond to the molecular events and functional alterations observed after experimental and human stroke. We provide the basis of the generations of brain oscillations and potential cellular and molecular mechanisms underlying stroke-induced perturbation. We will also discuss the implications of using brain oscillation patterns as biomarkers for the prediction of stroke outcome and therapeutic efficacy. PMID:26516838

Critical perspectives on causality and inference in brain networks: Allusions, illusions, solutions?. Comment on: "Foundational perspectives on causality in large-scale brain networks" by M. Mannino and S.L. Bressler

NASA Astrophysics Data System (ADS)

Diwadkar, Vaibhav A.

2015-12-01

The human brain is an impossibly difficult cartographic landscape to map out. Within it's convoluted and labyrinthine structure is folded a million years of phylogeny, somehow expressed in the ontogeny of the specific organism; an ontogeny that conceals idiosyncratic effects of countless genes, and then the (perhaps) countably infinite effects of processes of the organism's lifespan subsequently resulting in remarkable heterogeneity [1,2]. The physical brain itself is therefore a nearly un-decodable ;time machine; motivating more questions than frameworks for answering those questions: Why has evolution endowed it with the general structure that is possesses [3]; Is there regularity in macroscopic metrics of structure across species [4]; What are the most meaningful structural units in the brain: molecules, neurons, cortical columns or cortical maps [5]? Remarkably, understanding the intricacies of structure is perhaps not even the most difficult aspect of understanding the human brain. In fact, and as recently argued, a central issue lies in resolving the dialectic between structure and function: how does dynamic function arises from static (at least at the time scales at which human brain function is experimentally studied) brain structures [6]? In other words, if the mind is the brain ;in action;, how does it arise?

Brain-Congruent Instruction: Does the Computer Make It Feasible?

ERIC Educational Resources Information Center

Stewart, William J.

1984-01-01

Based on the premise that computers could translate brain research findings into classroom practice, this article presents discoveries concerning human brain development, organization, and operation, and describes brain activity monitoring devices, brain function and structure variables, and a procedure for monitoring and analyzing brain activity…

Connectivity profiles reveal the relationship between brain areas for social cognition in human and monkey temporoparietal cortex

PubMed Central

Mars, Rogier B.; Sallet, Jérôme; Neubert, Franz-Xaver; Rushworth, Matthew F. S.

2013-01-01

The human ability to infer the thoughts and beliefs of others, often referred to as “theory of mind,” as well as the predisposition to even consider others, are associated with activity in the temporoparietal junction (TPJ) area. Unlike the case of most human brain areas, we have little sense of whether or how TPJ is related to brain areas in other nonhuman primates. It is not possible to address this question by looking for similar task-related activations in nonhuman primates because there is no evidence that nonhuman primates engage in theory-of-mind tasks in the same manner as humans. Here, instead, we explore the relationship by searching for areas in the macaque brain that interact with other macaque brain regions in the same manner as human TPJ interacts with other human brain regions. In other words, we look for brain regions with similar positions within a distributed neural circuit in the two species. We exploited the fact that human TPJ has a unique functional connectivity profile with cortical areas with known homologs in the macaque. For each voxel in the macaque temporal and parietal cortex we evaluated the similarity of its functional connectivity profile to that of human TPJ. We found that areas in the middle part of the superior temporal cortex, often associated with the processing of faces and other social stimuli, have the most similar connectivity profile. These results suggest that macaque face processing areas and human mentalizing areas might have a similar precursor. PMID:23754406

Brain Activity and Human Unilateral Chewing

PubMed Central

Quintero, A.; Ichesco, E.; Myers, C.; Schutt, R.; Gerstner, G.E.

2012-01-01

Brain mechanisms underlying mastication have been studied in non-human mammals but less so in humans. We used functional magnetic resonance imaging (fMRI) to evaluate brain activity in humans during gum chewing. Chewing was associated with activations in the cerebellum, motor cortex and caudate, cingulate, and brainstem. We also divided the 25-second chew-blocks into 5 segments of equal 5-second durations and evaluated activations within and between each of the 5 segments. This analysis revealed activation clusters unique to the initial segment, which may indicate brain regions involved with initiating chewing. Several clusters were uniquely activated during the last segment as well, which may represent brain regions involved with anticipatory or motor events associated with the end of the chew-block. In conclusion, this study provided evidence for specific brain areas associated with chewing in humans and demonstrated that brain activation patterns may dynamically change over the course of chewing sequences. PMID:23103631

Understanding the Dorsal and Ventral Systems of the Human Cerebral Cortex: Beyond Dichotomies

ERIC Educational Resources Information Center

Borst, Gregoire; Thompson, William L.; Kosslyn, Stephen M.

2011-01-01

Traditionally, characterizations of the macrolevel functional organization of the human cerebral cortex have focused on the left and right cerebral hemispheres. However, the idea of left brain versus right brain functions has been shown to be an oversimplification. We argue here that a top-bottom divide, rather than a left-right divide, is a more…

The gravitational field and brain function.

PubMed

Mei, L; Zhou, C D; Lan, J Q; Wang, Z G; Wu, W C; Xue, X M

1983-01-01

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.

Correspondence of the brain's functional architecture during activation and rest.

PubMed

Smith, Stephen M; Fox, Peter T; Miller, Karla L; Glahn, David C; Fox, P Mickle; Mackay, Clare E; Filippini, Nicola; Watkins, Kate E; Toro, Roberto; Laird, Angela R; Beckmann, Christian F

2009-08-04

Neural connections, providing the substrate for functional networks, exist whether or not they are functionally active at any given moment. However, it is not known to what extent brain regions are continuously interacting when the brain is "at rest." In this work, we identify the major explicit activation networks by carrying out an image-based activation network analysis of thousands of separate activation maps derived from the BrainMap database of functional imaging studies, involving nearly 30,000 human subjects. Independently, we extract the major covarying networks in the resting brain, as imaged with functional magnetic resonance imaging in 36 subjects at rest. The sets of major brain networks, and their decompositions into subnetworks, show close correspondence between the independent analyses of resting and activation brain dynamics. We conclude that the full repertoire of functional networks utilized by the brain in action is continuously and dynamically "active" even when at "rest."

PET evaluation of the dopamine system of the human brain

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

Volkow, N.D.; Fowler, J.S.; Gatley, S.

1996-07-01

Dopamine plays a pivotal role in the regulation and control of movement, motivation and cognition. It also is closely linked to reward, reinforcement and addiction. Abnormalities in brain dopamine are associated with many neurological and psychiatric disorders including Parkinson`s disease, schizophrenia and substance abuse. This close association between dopamine and neurological and psychiatric diseases and with substance abuse make it an important topic in research in the neurosciences and an important molecular target in drug development. PET enables the direct measurement of components of the dopamine system in the living human brain. It relies on radiotracers which label dopamine receptors,more » dopamine transporters, precursors of dopamine or compounds which have specificity for the enzymes which degrade dopamine. Additionally, by using tracers that provide information on regional brain metabolism or blood flow as well as neurochemically specific pharmacological interventions, PET can be used to assess the functional consequences of change in brain dopamine activity. PET dopamine measurements have been used to investigate the normal human brain and its involvement in psychiatric and neurological diseases. It has also been used in psychopharmacological research to investigate dopamine drugs used in the treatment of Parkinson`s disease and of schizophrenia as well as to investigate the effects of drugs of abuse on the dopamine system. Since various functional and neurochemical parameters can be studied in the same subject, PET enables investigation of the functional integrity of the dopamine system in the human brain and investigation of the interactions of dopamine with other neurotransmitters. This paper summarizes the different tracers and experimental strategies developed to evaluate the various elements of the dopamine system in the human brain with PET and their applications to clinical research. 254 refs., 7 figs., 3 tabs.« less

Distributed Neural Activity Patterns during Human-to-Human Competition

PubMed Central

Piva, Matthew; Zhang, Xian; Noah, J. Adam; Chang, Steve W. C.; Hirsch, Joy

2017-01-01

Interpersonal interaction is the essence of human social behavior. However, conventional neuroimaging techniques have tended to focus on social cognition in single individuals rather than on dyads or groups. As a result, relatively little is understood about the neural events that underlie face-to-face interaction. We resolved some of the technical obstacles inherent in studying interaction using a novel imaging modality and aimed to identify neural mechanisms engaged both within and across brains in an ecologically valid instance of interpersonal competition. Functional near-infrared spectroscopy was utilized to simultaneously measure hemodynamic signals representing neural activity in pairs of subjects playing poker against each other (human–human condition) or against computer opponents (human–computer condition). Previous fMRI findings concerning single subjects confirm that neural areas recruited during social cognition paradigms are individually sensitive to human–human and human–computer conditions. However, it is not known whether face-to-face interactions between opponents can extend these findings. We hypothesize distributed effects due to live processing and specific variations in across-brain coherence not observable in single-subject paradigms. Angular gyrus (AG), a component of the temporal-parietal junction (TPJ) previously found to be sensitive to socially relevant cues, was selected as a seed to measure within-brain functional connectivity. Increased connectivity was confirmed between AG and bilateral dorsolateral prefrontal cortex (dlPFC) as well as a complex including the left subcentral area (SCA) and somatosensory cortex (SS) during interaction with a human opponent. These distributed findings were supported by contrast measures that indicated increased activity at the left dlPFC and frontopolar area that partially overlapped with the region showing increased functional connectivity with AG. Across-brain analyses of neural coherence between the players revealed synchrony between dlPFC and supramarginal gyrus (SMG) and SS in addition to synchrony between AG and the fusiform gyrus (FG) and SMG. These findings present the first evidence of a frontal-parietal neural complex including the TPJ, dlPFC, SCA, SS, and FG that is more active during human-to-human social cognition both within brains (functional connectivity) and across brains (across-brain coherence), supporting a model of functional integration of socially and strategically relevant information during live face-to-face competitive behaviors. PMID:29218005

Transcriptional Landscape of the Prenatal Human Brain

PubMed Central

Miller, Jeremy A.; Ding, Song-Lin; Sunkin, Susan M.; Smith, Kimberly A; Ng, Lydia; Szafer, Aaron; Ebbert, Amanda; Riley, Zackery L.; Aiona, Kaylynn; Arnold, James M.; Bennet, Crissa; Bertagnolli, Darren; Brouner, Krissy; Butler, Stephanie; Caldejon, Shiella; Carey, Anita; Cuhaciyan, Christine; Dalley, Rachel A.; Dee, Nick; Dolbeare, Tim A.; Facer, Benjamin A. C.; Feng, David; Fliss, Tim P.; Gee, Garrett; Goldy, Jeff; Gourley, Lindsey; Gregor, Benjamin W.; Gu, Guangyu; Howard, Robert E.; Jochim, Jayson M.; Kuan, Chihchau L.; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Lemon, Tracy A.; Lesnar, Phil; McMurray, Bergen; Mastan, Naveed; Mosqueda, Nerick F.; Naluai-Cecchini, Theresa; Ngo, Nhan-Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D.; Parry, Sheana E.; Player, Allison Stevens; Pletikos, Mihovil; Reding, Melissa; Royall, Joshua J.; Roll, Kate; Sandman, David; Sarreal, Melaine; Shapouri, Sheila; Shapovalova, Nadiya V.; Shen, Elaine H.; Sjoquist, Nathan; Slaughterbeck, Clifford R.; Smith, Michael; Sodt, Andy J.; Williams, Derric; Zöllei, Lilla; Fischl, Bruce; Gerstein, Mark B.; Geschwind, Daniel H.; Glass, Ian A.; Hawrylycz, Michael J.; Hevner, Robert F.; Huang, Hao; Jones, Allan R.; Knowles, James A.; Levitt, Pat; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Dang, Chinh; Bernard, Amy; Hohmann, John G.; Lein, Ed S.

2014-01-01

Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development. PMID:24695229

The Human Brain Uses Noise

NASA Astrophysics Data System (ADS)

Mori, Toshio; Kai, Shoichi

2003-05-01

We present the first observation of stochastic resonance (SR) in the human brain's visual processing area. The novel experimental protocol is to stimulate the right eye with a sub-threshold periodic optical signal and the left eye with a noisy one. The stimuli bypass sensory organs and are mixed in the visual cortex. With many noise sources present in the brain, higher brain functions, e.g. perception and cognition, may exploit SR.

Hemispheric Asymmetry of Human Brain Anatomical Network Revealed by Diffusion Tensor Tractography

PubMed Central

Liu, Yaou; Duan, Yunyun; Li, Kuncheng

2015-01-01

The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. However, few studies have investigated the hemispheric asymmetries of the human brain from the perspective of the network model, and little is known about the asymmetries of the connection patterns of brain regions, which may reflect the functional integration and interaction between different regions. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 72 right-handed healthy adult subjects. We established the existence of structural connections between any pair of the 90 cortical and subcortical regions using deterministic tractography. To investigate the hemispheric asymmetries of the brain, statistical analyses were performed to reveal the brain regions with significant differences between bilateral topological properties, such as degree of connectivity, characteristic path length, and betweenness centrality. Furthermore, local structural connections were also investigated to examine the local asymmetries of some specific white matter tracts. From the perspective of both the global and local connection patterns, we identified the brain regions with hemispheric asymmetries. Combined with the previous studies, we suggested that the topological asymmetries in the anatomical network may reflect the functional lateralization of the human brain. PMID:26539535

DUF1220 protein domains drive proliferation in human neural stem cells and are associated with increased cortical volume in anthropoid primates.

PubMed

Keeney, J G; Davis, J M; Siegenthaler, J; Post, M D; Nielsen, B S; Hopkins, W D; Sikela, J M

2015-09-01

Genome sequences encoding DUF1220 protein domains show a burst in copy number among anthropoid species and especially humans, where they have undergone the greatest human lineage-specific copy number expansion of any protein coding sequence in the genome. While DUF1220 copy number shows a dosage-related association with brain size in both normal populations and in 1q21.1-associated microcephaly and macrocephaly, a function for these domains has not yet been described. Here we provide multiple lines of evidence supporting the view that DUF1220 domains function as drivers of neural stem cell proliferation among anthropoid species including humans. First, we show that brain MRI data from 131 individuals across 7 anthropoid species shows a strong correlation between DUF1220 copy number and multiple brain size-related measures. Using in situ hybridization analyses of human fetal brain, we also show that DUF1220 domains are expressed in the ventricular zone and primarily during human cortical neurogenesis, and are therefore expressed at the right time and place to be affecting cortical brain development. Finally, we demonstrate that in vitro expression of DUF1220 sequences in neural stem cells strongly promotes proliferation. Taken together, these data provide the strongest evidence so far reported implicating DUF1220 dosage in anthropoid and human brain expansion through mechanisms involving increasing neural stem cell proliferation.

Prediction of individual brain maturity using fMRI.

PubMed

Dosenbach, Nico U F; Nardos, Binyam; Cohen, Alexander L; Fair, Damien A; Power, Jonathan D; Church, Jessica A; Nelson, Steven M; Wig, Gagan S; Vogel, Alecia C; Lessov-Schlaggar, Christina N; Barnes, Kelly Anne; Dubis, Joseph W; Feczko, Eric; Coalson, Rebecca S; Pruett, John R; Barch, Deanna M; Petersen, Steven E; Schlaggar, Bradley L

2010-09-10

Group functional connectivity magnetic resonance imaging (fcMRI) studies have documented reliable changes in human functional brain maturity over development. Here we show that support vector machine-based multivariate pattern analysis extracts sufficient information from fcMRI data to make accurate predictions about individuals' brain maturity across development. The use of only 5 minutes of resting-state fcMRI data from 238 scans of typically developing volunteers (ages 7 to 30 years) allowed prediction of individual brain maturity as a functional connectivity maturation index. The resultant functional maturation curve accounted for 55% of the sample variance and followed a nonlinear asymptotic growth curve shape. The greatest relative contribution to predicting individual brain maturity was made by the weakening of short-range functional connections between the adult brain's major functional networks.

Oligophrenin-1 (OPHN1), a Gene Involved in X-Linked Intellectual Disability, Undergoes RNA Editing and Alternative Splicing during Human Brain Development

PubMed Central

Athanasiadis, Alekos; Galeano, Federica; Locatelli, Franco; Bertini, Enrico; Zanni, Ginevra; Gallo, Angela

2014-01-01

Oligophrenin-1 (OPHN1) encodes for a Rho-GTPase-activating protein, important for dendritic morphogenesis and synaptic function. Mutations in this gene have been identified in patients with X-linked intellectual disability associated with cerebellar hypoplasia. ADAR enzymes are responsible for A-to-I RNA editing, an essential post-transcriptional RNA modification contributing to transcriptome and proteome diversification. Specifically, ADAR2 activity is essential for brain development and function. Herein, we show that the OPHN1 transcript undergoes post-transcriptional modifications such as A-to-I RNA editing and alternative splicing in human brain and other tissues. We found that OPHN1 editing is detectable already at the 18th week of gestation in human brain with a boost of editing at weeks 20 to 33, concomitantly with OPHN1 expression increase and the appearance of a novel OPHN1 splicing isoform. Our results demonstrate that multiple post-transcriptional events occur on OPHN1, a gene playing an important role in brain function and development. PMID:24637888

Oligophrenin-1 (OPHN1), a gene involved in X-linked intellectual disability, undergoes RNA editing and alternative splicing during human brain development.

PubMed

Barresi, Sabina; Tomaselli, Sara; Athanasiadis, Alekos; Galeano, Federica; Locatelli, Franco; Bertini, Enrico; Zanni, Ginevra; Gallo, Angela

2014-01-01

Oligophrenin-1 (OPHN1) encodes for a Rho-GTPase-activating protein, important for dendritic morphogenesis and synaptic function. Mutations in this gene have been identified in patients with X-linked intellectual disability associated with cerebellar hypoplasia. ADAR enzymes are responsible for A-to-I RNA editing, an essential post-transcriptional RNA modification contributing to transcriptome and proteome diversification. Specifically, ADAR2 activity is essential for brain development and function. Herein, we show that the OPHN1 transcript undergoes post-transcriptional modifications such as A-to-I RNA editing and alternative splicing in human brain and other tissues. We found that OPHN1 editing is detectable already at the 18th week of gestation in human brain with a boost of editing at weeks 20 to 33, concomitantly with OPHN1 expression increase and the appearance of a novel OPHN1 splicing isoform. Our results demonstrate that multiple post-transcriptional events occur on OPHN1, a gene playing an important role in brain function and development.

The brain-life theory: towards a consistent biological definition of humanness.

PubMed Central

Goldenring, J M

1985-01-01

This paper suggests that medically the term a 'human being' should be defined by the presence of an active human brain. The brain is the only unique and irreplaceable organ in the human body, as the orchestrator of all organ systems and the seat of personality. Thus, the presence or absence of brain life truly defines the presence or absence of human life in the medical sense. When viewed in this way, human life may be seen as a continuous spectrum between the onset of brain life in utero (eight weeks gestation), until the occurrence of brain death. At any point human tissue or organ systems may be present, but without the presence of a functional human brain, these do not constitute a 'human being', at least in a medical sense. The implications of this theory for various ethical concerns such as in vitro fertilisation and abortion are discussed. This theory is the most consistent possible for the definition of a human being with no contradictions inherent. However, having a good theory of definition of a 'human being' does not necessarily solve the ethical problems discussed herein. PMID:4078859

Use of Neuroimaging to Clarify How Human Brains Perform Mental Calculations

ERIC Educational Resources Information Center

Ortiz, Enrique

2010-01-01

The purpose of this study was to analyze participants' levels of hemoglobin as they performed arithmetic mental calculations using Optical Topography (OT, helmet type brain-scanning system, also known as Functional Near-Infrared Spectroscopy or fNIRS). A central issue in cognitive neuroscience involves the study of how the human brain encodes and…

From The Cover: Microtransplantation of functional receptors and channels from the Alzheimer's brain to frog oocytes

NASA Astrophysics Data System (ADS)

Miledi, R.; Dueñas, Z.; Martinez-Torres, A.; Kawas, C. H.; Eusebi, F.

2004-02-01

About a decade ago, cell membranes from the electric organ of Torpedo and from the rat brain were transplanted to frog oocytes, which thus acquired functional Torpedo and rat neurotransmitter receptors. Nevertheless, the great potential that this method has for studying human diseases has remained virtually untapped. Here, we show that cell membranes from the postmortem brains of humans that suffered Alzheimer's disease can be microtransplanted to the plasma membrane of Xenopus oocytes. We show also that these postmortem membranes carry neurotransmitter receptors and voltage-operated channels that are still functional, even after they have been kept frozen for many years. This method provides a new and powerful approach to study directly the functional characteristics and structure of receptors, channels, and other membrane proteins of the Alzheimer's brain. This knowledge may help in understanding the basis of Alzheimer's disease and also help in developing new treatments. -aminobutyric acid receptors | sodium channels | calcium channels | postmortem brain

Family-Based Training Program Improves Brain Function, Cognition, and Behavior in Lower Socioeconomic Status Preschoolers

ERIC Educational Resources Information Center

Pakulak, Eric; Stevens, Courtney; Bell, Theodore A.; Fanning, Jessica; Klein, Scott; Isbell, Elif; Neville, Helen

2013-01-01

Over the course of several years of research, the authors have employed psychophysics, electrophysiological (ERP) and magnetic resonance imaging (MRI) techniques to study the development and neuroplasticity of the human brain. During this time, they observed that different brain systems and related functions display markedly different degrees or…

Intrinsic and task-evoked network architectures of the human brain

PubMed Central

Cole, Michael W.; Bassett, Danielle S.; Power, Jonathan D.; Braver, Todd S.; Petersen, Steven E.

2014-01-01

Summary Many functional network properties of the human brain have been identified during rest and task states, yet it remains unclear how the two relate. We identified a whole-brain network architecture present across dozens of task states that was highly similar to the resting-state network architecture. The most frequent functional connectivity strengths across tasks closely matched the strengths observed at rest, suggesting this is an “intrinsic”, standard architecture of functional brain organization. Further, a set of small but consistent changes common across tasks suggests the existence of a task-general network architecture distinguishing task states from rest. These results indicate the brain’s functional network architecture during task performance is shaped primarily by an intrinsic network architecture that is also present during rest, and secondarily by evoked task-general and task-specific network changes. This establishes a strong relationship between resting-state functional connectivity and task-evoked functional connectivity – areas of neuroscientific inquiry typically considered separately. PMID:24991964

The role of symmetry in the regulation of brain dynamics

NASA Astrophysics Data System (ADS)

Tang, Evelyn; Giusti, Chad; Cieslak, Matthew; Grafton, Scott; Bassett, Danielle

Synchronous neural processes regulate a wide range of behaviors from attention to learning. Yet structural constraints on these processes are far from understood. We draw on new theoretical links between structural symmetries and the control of synchronous function, to offer a reconceptualization of the relationships between brain structure and function in human and non-human primates. By classifying 3-node motifs in macaque connectivity data, we find the most prevalent motifs can theoretically ensure a diversity of function including strict synchrony as well as control to arbitrary states. The least prevalent motifs are theoretically controllable to arbitrary states, which may not be desirable in a biological system. In humans, regions with high topological similarity of connections (a continuous notion related to symmetry) are most commonly found in fronto-parietal systems, which may account for their critical role in cognitive control. Collectively, our work underscores the role of symmetry and topological similarity in regulating dynamics of brain function.

Pushing spatial and temporal resolution for functional and diffusion MRI in the Human Connectome Project

PubMed Central

Uğurbil, Kamil; Xu, Junqian; Auerbach, Edward J.; Moeller, Steen; Vu, An; Duarte-Carvajalino, Julio M.; Lenglet, Christophe; Wu, Xiaoping; Schmitter, Sebastian; Van de Moortele, Pierre Francois; Strupp, John; Sapiro, Guillermo; De Martino, Federico; Wang, Dingxin; Harel, Noam; Garwood, Michael; Chen, Liyong; Feinberg, David A.; Smith, Stephen M.; Miller, Karla L.; Sotiropoulos, Stamatios N; Jbabdi, Saad; Andersson, Jesper L; Behrens, Timothy EJ; Glasser, Matthew F.; Van Essen, David; Yacoub, Essa

2013-01-01

The human connectome project (HCP) relies primarily on three complementary magnetic resonance (MR) methods. These are: 1) resting state functional MR imaging (rfMRI) which uses correlations in the temporal fluctuations in an fMRI time series to deduce ‘functional connectivity’; 2) diffusion imaging (dMRI), which provides the input for tractography algorithms used for the reconstruction of the complex axonal fiber architecture; and 3) task based fMRI (tfMRI), which is employed to identify functional parcellation in the human brain in order to assist analyses of data obtained with the first two methods. We describe technical improvements and optimization of these methods as well as instrumental choices that impact speed of acquisition of fMRI and dMRI images at 3 Tesla, leading to whole brain coverage with 2 mm isotropic resolution in 0.7 second for fMRI, and 1.25 mm isotropic resolution dMRI data for tractography analysis with three-fold reduction in total data acquisition time. Ongoing technical developments and optimization for acquisition of similar data at 7 Tesla magnetic field are also presented, targeting higher resolution, specificity of functional imaging signals, mitigation of the inhomogeneous radio frequency (RF) fields and power deposition. Results demonstrate that overall, these approaches represent a significant advance in MR imaging of the human brain to investigate brain function and structure. PMID:23702417

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

PubMed

Zaidel, Dahlia W

2010-02-01

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

Art and brain: insights from neuropsychology, biology and evolution

PubMed Central

Zaidel, Dahlia W

2010-01-01

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

A psychology of the human brain-gut-microbiome axis.

PubMed

Allen, Andrew P; Dinan, Timothy G; Clarke, Gerard; Cryan, John F

2017-04-01

In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain-gut-microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress-related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain-gut-microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain-gut-microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology.

Face Patch Resting State Networks Link Face Processing to Social Cognition

PubMed Central

Schwiedrzik, Caspar M.; Zarco, Wilbert; Everling, Stefan; Freiwald, Winrich A.

2015-01-01

Faces transmit a wealth of social information. How this information is exchanged between face-processing centers and brain areas supporting social cognition remains largely unclear. Here we identify these routes using resting state functional magnetic resonance imaging in macaque monkeys. We find that face areas functionally connect to specific regions within frontal, temporal, and parietal cortices, as well as subcortical structures supporting emotive, mnemonic, and cognitive functions. This establishes the existence of an extended face-recognition system in the macaque. Furthermore, the face patch resting state networks and the default mode network in monkeys show a pattern of overlap akin to that between the social brain and the default mode network in humans: this overlap specifically includes the posterior superior temporal sulcus, medial parietal, and dorsomedial prefrontal cortex, areas supporting high-level social cognition in humans. Together, these results reveal the embedding of face areas into larger brain networks and suggest that the resting state networks of the face patch system offer a new, easily accessible venue into the functional organization of the social brain and into the evolution of possibly uniquely human social skills. PMID:26348613

Kisspeptin modulates sexual and emotional brain processing in humans.

PubMed

Comninos, Alexander N; Wall, Matthew B; Demetriou, Lysia; Shah, Amar J; Clarke, Sophie A; Narayanaswamy, Shakunthala; Nesbitt, Alexander; Izzi-Engbeaya, Chioma; Prague, Julia K; Abbara, Ali; Ratnasabapathy, Risheka; Salem, Victoria; Nijher, Gurjinder M; Jayasena, Channa N; Tanner, Mark; Bassett, Paul; Mehta, Amrish; Rabiner, Eugenii A; Hönigsperger, Christoph; Silva, Meire Ribeiro; Brandtzaeg, Ole Kristian; Lundanes, Elsa; Wilson, Steven Ray; Brown, Rachel C; Thomas, Sarah A; Bloom, Stephen R; Dhillo, Waljit S

2017-02-01

Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin's enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC).

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

PubMed Central

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

2015-01-01

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

Structural architecture supports functional organization in the human aging brain at a regionwise and network level.

PubMed

Zimmermann, Joelle; Ritter, Petra; Shen, Kelly; Rothmeier, Simon; Schirner, Michael; McIntosh, Anthony R

2016-07-01

Functional interactions in the brain are constrained by the underlying anatomical architecture, and structural and functional networks share network features such as modularity. Accordingly, age-related changes of structural connectivity (SC) may be paralleled by changes in functional connectivity (FC). We provide a detailed qualitative and quantitative characterization of the SC-FC coupling in human aging as inferred from resting-state blood oxygen-level dependent functional magnetic resonance imaging and diffusion-weighted imaging in a sample of 47 adults with an age range of 18-82. We revealed that SC and FC decrease with age across most parts of the brain and there is a distinct age-dependency of regionwise SC-FC coupling and network-level SC-FC relations. A specific pattern of SC-FC coupling predicts age more reliably than does regionwise SC or FC alone (r = 0.73, 95% CI = [0.7093, 0.8522]). Hence, our data propose that regionwise SC-FC coupling can be used to characterize brain changes in aging. Hum Brain Mapp 37:2645-2661, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cerebral localization, then and now.

PubMed

Marshall, John C; Fink, Gereon R

2003-11-01

We review some of the progress made in understanding the nature of functional specialization in the human brain, beginning with the anatomical claim that all mental faculties have their own distinct material substrate in different regions of the brain and the psychological claim that each mental faculty is characterized by the content domain with which it deals. This conceptual framework led behavioral neurologists to show how discrete brain lesions provoked different types of language, praxic, gnostic, spatial, and memory disorders. The simplest way of interpreting these anatomoclinical associations was to conjecture that the normal function (now impaired by brain damage) was localized within that lesioned region. It was also realized that cognitive impairments could arise from lesions that spared the functional centers themselves but disconnected them from other centers. Nonetheless, many neuroscientists remained skeptical of the entire paradigm. Accordingly, in the late 19th century functional localization began to be studied in the intact human brain by such techniques as measuring the temperature of different brain regions when different cognitive tasks were performed. During the 20th century these crude techniques gave way to positron emission tomography, functional magnetic resonance imaging, and magnetoencephalography. The relatively precise spatial and temporal resolution of modern methods now raises a crucial question: Do the functional localizations obtained by the anatomoclinical method converge with those implied by the functional neuroimaging of cognition in healthy volunteers? We then conclude with some recent suggestions that functional specialization is not such a fixed property of brain regions as previously supposed.

The neurotechnological revolution: unlocking the brain's secrets to develop innovative technologies as well as treatments for neurological diseases.

PubMed

Banks, Jim

2015-01-01

The brain contains all that makes us human, but its complexity is the source of both inspiration and frailty. Aging population is increasingly in need of effective care and therapies for brain diseases, including stroke, Parkinson's disease and Alzheimer's disease. The world's scientific community working hard to unravel the secrets of the brain's computing power and to devise technologies that can heal it when it fails and restore critical functions to patients with neurological conditions. Neurotechnology is the emerging field that brings together the development of technologies to study the brain and devices that improve and repair brain function. What is certain is the momentum behind neurotechnological research is building, and whether through implants, BCIs, or innovative computational systems inspired by the human brain, more light will be shed on our most complex and most precious organ, which will no doubt lead to effective treatment for many neurological conditions.

Metabolic Brain Network Analysis of Hypothyroidism Symptom Based on [18F]FDG-PET of Rats.

PubMed

Wan, Hongkai; Tan, Ziyu; Zheng, Qiang; Yu, Jing

2018-03-12

Recent researches have demonstrated the value of using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) positron emission tomography (PET) imaging to reveal the hypothyroidism-related damages in local brain regions. However, the influence of hypothyroidism on the entire brain network is barely studied. This study focuses on the application of graph theory on analyzing functional brain networks of the hypothyroidism symptom. For both the hypothyroidism and the control groups of Wistar rats, the functional brain networks were constructed by thresholding the glucose metabolism correlation matrices of 58 brain regions. The network topological properties (including the small-world properties and the nodal centralities) were calculated and compared between the two groups. We found that the rat brains, like human brains, have typical properties of the small-world network in both the hypothyroidism and the control groups. However, the hypothyroidism group demonstrated lower global efficiency and decreased local cliquishness of the brain network, indicating hypothyroidism-related impairment to the brain network. The hypothyroidism group also has decreased nodal centrality in the left posterior hippocampus, the right hypothalamus, pituitary, pons, and medulla. This observation accorded with the hypothyroidism-related functional disorder of hypothalamus-pituitary-thyroid (HPT) feedback regulation mechanism. Our research quantitatively confirms that hypothyroidism hampers brain cognitive function by causing impairment to the brain network of glucose metabolism. This study reveals the feasibility and validity of applying graph theory method to preclinical [ 18 F]FDG-PET images and facilitates future study on human subjects.

Noise-Induced Entrainment and Stochastic Resonance in Human Brain Waves

NASA Astrophysics Data System (ADS)

Mori, Toshio; Kai, Shoichi

2002-05-01

We present the first observation of stochastic resonance (SR) in the human brain's visual processing area. The novel experimental protocol is to stimulate the right eye with a subthreshold periodic optical signal and the left eye with a noisy one. The stimuli bypass sensory organs and are mixed in the visual cortex. With many noise sources present in the brain, higher brain functions, e.g., perception and cognition, may exploit SR.

Non-invasive Brain Stimulation: A Paradigm Shift in Understanding Brain Oscillations.

PubMed

Vosskuhl, Johannes; Strüber, Daniel; Herrmann, Christoph S

2018-01-01

Cognitive neuroscience set out to understand the neural mechanisms underlying cognition. One central question is how oscillatory brain activity relates to cognitive processes. Up to now, most of the evidence supporting this relationship was correlative in nature. This situation changed dramatically with the recent development of non-invasive brain stimulation (NIBS) techniques, which open up new vistas for neuroscience by allowing researchers for the first time to validate their correlational theories by manipulating brain functioning directly. In this review, we focus on transcranial alternating current stimulation (tACS), an electrical brain stimulation method that applies sinusoidal currents to the intact scalp of human individuals to directly interfere with ongoing brain oscillations. We outline how tACS can impact human brain oscillations by employing different levels of observation from non-invasive tACS application in healthy volunteers and intracranial recordings in patients to animal studies demonstrating the effectiveness of alternating electric fields on neurons in vitro and in vivo . These findings likely translate to humans as comparable effects can be observed in human and animal studies. Neural entrainment and plasticity are suggested to mediate the behavioral effects of tACS. Furthermore, we focus on mechanistic theories about the relationship between certain cognitive functions and specific parameters of brain oscillaitons such as its amplitude, frequency, phase and phase coherence. For each of these parameters we present the current state of testing its functional relevance by means of tACS. Recent developments in the field of tACS are outlined which include the stimulation with physiologically inspired non-sinusoidal waveforms, stimulation protocols which allow for the observation of online-effects, and closed loop applications of tACS.

Broca's arrow: evolution, prediction, and language in the brain.

PubMed

Cooper, David L

2006-01-01

Brodmann's areas 44 and 45 in the human brain, also known as Broca's area, have long been associated with language functions, especially in the left hemisphere. However, the precise role Broca's area plays in human language has not been established with certainty. Broca's area has homologs in the great apes and in area F5 in monkeys, which suggests that its original function was not linguistic at all. In fact, great ape and hominid brains show very similar left-over-right asymmetries in Broca's area homologs as well as in other areas, such as homologs to Wernicke's area, that are normally associated with language in modern humans. Moreover, the so-called mirror neurons are located in Broca's area in great apes and area F5 in monkeys, which seem to provide a representation of cause and effect in a primate's environment, particularly its social environment. Humans appear to have these mirror neurons in Broca's area as well. Similarly, genetic evidence related to the FOXP2 gene implicates Broca's area in linguistic function and dysfunction, but the gene itself is a highly conserved developmental gene in vertebrates and is shared with only two or three differences between humans and great apes, five between humans and mice, and eight between humans and songbirds. Taking neurons and portions of the brain as discrete computational segments in the sense of constituting specific Turing machines, this evidence points to a predictive motor and conceptual function for Broca's area in primates, especially for social concepts. In human language, this is consistent with evidence from typological and cognitive linguistics. (c) 2006 Wiley-Liss, Inc.

Development of human brain structural networks through infancy and childhood.

PubMed

Huang, Hao; Shu, Ni; Mishra, Virendra; Jeon, Tina; Chalak, Lina; Wang, Zhiyue J; Rollins, Nancy; Gong, Gaolang; Cheng, Hua; Peng, Yun; Dong, Qi; He, Yong

2015-05-01

During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Tinnitus alters resting state functional connectivity (RSFC) in human auditory and non-auditory brain regions as measured by functional near-infrared spectroscopy (fNIRS)

PubMed Central

Hu, Xiao-Su; Issa, Mohamad; Bisconti, Silvia; Kovelman, Ioulia; Kileny, Paul; Basura, Gregory

2017-01-01

Tinnitus, or phantom sound perception, leads to increased spontaneous neural firing rates and enhanced synchrony in central auditory circuits in animal models. These putative physiologic correlates of tinnitus to date have not been well translated in the brain of the human tinnitus sufferer. Using functional near-infrared spectroscopy (fNIRS) we recently showed that tinnitus in humans leads to maintained hemodynamic activity in auditory and adjacent, non-auditory cortices. Here we used fNIRS technology to investigate changes in resting state functional connectivity between human auditory and non-auditory brain regions in normal-hearing, bilateral subjective tinnitus and controls before and after auditory stimulation. Hemodynamic activity was monitored over the region of interest (primary auditory cortex) and non-region of interest (adjacent non-auditory cortices) and functional brain connectivity was measured during a 60-second baseline/period of silence before and after a passive auditory challenge consisting of alternating pure tones (750 and 8000Hz), broadband noise and silence. Functional connectivity was measured between all channel-pairs. Prior to stimulation, connectivity of the region of interest to the temporal and fronto-temporal region was decreased in tinnitus participants compared to controls. Overall, connectivity in tinnitus was differentially altered as compared to controls following sound stimulation. Enhanced connectivity was seen in both auditory and non-auditory regions in the tinnitus brain, while controls showed a decrease in connectivity following sound stimulation. In tinnitus, the strength of connectivity was increased between auditory cortex and fronto-temporal, fronto-parietal, temporal, occipito-temporal and occipital cortices. Together these data suggest that central auditory and non-auditory brain regions are modified in tinnitus and that resting functional connectivity measured by fNIRS technology may contribute to conscious phantom sound perception and potentially serve as an objective measure of central neural pathology. PMID:28604786

Brain Structure and Function Associated with Younger Adults in Growth Hormone Receptor-Deficient Humans

PubMed Central

Nashiro, Kaoru; Braskie, Meredith N.; Velasco, Rico; Balasubramanian, Priya; Wei, Min; Thompson, Paul M.; Nelson, Marvin D.; Guevara, Alexandra

2017-01-01

Growth hormone receptor deficiency (GHRD) results in short stature, enhanced insulin sensitivity, and low circulating levels of insulin and insulin-like growth factor 1 (IGF-1). Previous studies in mice and humans suggested that GHRD has protective effects against age-related diseases, including cancer and diabetes. Whereas GHRD mice show improved age-dependent cognitive performance, the effect of GHRD on human cognition remains unknown. Using MRI, we compared brain structure, function, and connectivity between 13 people with GHRD and 12 unaffected relatives. We assessed differences in white matter microstructural integrity, hippocampal volume, subregional volumes, and cortical thickness and surface area of selected regions. We also evaluated brain activity at rest and during a hippocampal-dependent pattern separation task. The GHRD group had larger surface areas in several frontal and cingulate regions and showed trends toward larger dentate gyrus and CA1 regions of the hippocampus. They had lower mean diffusivity in the genu of the corpus callosum and the anterior thalamic tracts. The GHRD group showed enhanced cognitive performance and greater task-related activation in frontal, parietal, and hippocampal regions compared with controls. Furthermore, they had greater functional synchronicity of activity between the precuneus and the rest of the default mode network at rest. The results suggest that, compared with controls, GHRD subjects have brain structure and function that are more consistent with those observed in younger adults reported in previous studies. Further investigation may lead to improved understanding of underlying mechanisms and could contribute to the identification of treatments for age-related cognitive deficits. SIGNIFICANCE STATEMENT People and mice with growth hormone receptor deficiency (GHRD or Laron syndrome) are protected against age-related diseases including cancer and diabetes. However, in humans, it is unknown whether cognitive function and brain structure are affected by GHRD. Using MRI, we examined cognition in an Ecuadorian population with GHRD and their unaffected relatives. The GHRD group showed better memory performance than their relatives. The differences in brain structure and function that we saw between the two groups were not consistent with variations typically associated with brain deficits. This study contributes to our understanding of the connection between growth genes and brain aging in humans and provides data indicating that GHR inhibition has the potential to protect against age-dependent cognitive decline. PMID:28073935

Characterization of the resting-state brain network topology in the 6-hydroxydopamine rat model of Parkinson’s disease

PubMed Central

Simmons, Camilla; Mesquita, Michel B.; Wood, Tobias C.; Williams, Steve C. R.; Vernon, Anthony C.; Cash, Diana

2017-01-01

Resting-state functional MRI (rsfMRI) is an imaging technology that has recently gained attention for its ability to detect disruptions in functional brain networks in humans, including in patients with Parkinson’s disease (PD), revealing early and widespread brain network abnormalities. This methodology is now readily applicable to experimental animals offering new possibilities for cross-species translational imaging. In this context, we herein describe the application of rsfMRI to the unilaterally-lesioned 6-hydroxydopamine (6-OHDA) rat, a robust experimental model of the dopamine depletion implicated in PD. Using graph theory to analyse the rsfMRI data, we were able to provide meaningful and translatable measures of integrity, influence and segregation of the underlying functional brain architecture. Specifically, we confirm that rats share a similar functional brain network topology as observed in humans, characterised by small-worldness and modularity. Interestingly, we observed significantly reduced functional connectivity in the 6-OHDA rats, primarily in the ipsilateral (lesioned) hemisphere as evidenced by significantly lower node degree, local efficiency and clustering coefficient in the motor, orbital and sensorimotor cortices. In contrast, we found significantly, and bilaterally, increased thalamic functional connectivity in the lesioned rats. The unilateral deficits in the cortex are consistent with the unilateral nature of this model and further support the validity of the rsfMRI technique in rodents. We thereby provide a methodological framework for the investigation of brain networks in other rodent experimental models of PD, as well as of animal models in general, for cross-comparison with human data. PMID:28249008

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

ERIC Educational Resources Information Center

Kalbfleisch, M. Layne; Gillmarten, Charles

2013-01-01

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…

Midsagittal brain variation and MRI shape analysis of the precuneus in adult individuals.

PubMed

Bruner, Emiliano; Rangel de Lázaro, Gizéh; de la Cuétara, José Manuel; Martín-Loeches, Manuel; Colom, Roberto; Jacobs, Heidi I L

2014-04-01

Recent analyses indicate that the precuneus is one of the main centres of integration in terms of functional and structural processes within the human brain. This neuroanatomical element is formed by different subregions, involved in visuo-spatial integration, memory and self-awareness. We analysed the midsagittal brain shape in a sample of adult humans (n = 90) to evidence the patterns of variability and geometrical organization of this area. Interestingly, the major brain covariance pattern within adult humans is strictly associated with the relative proportions of the precuneus. Its morphology displays a marked individual variation, both in terms of geometry (mostly in its longitudinal dimensions) and anatomy (patterns of convolution). No patent differences are evident between males and females, and the allometric effect of size is minimal. However, in terms of morphology, the precuneus does not represent an individual module, being influenced by different neighbouring structures. Taking into consideration the apparent involvement of the precuneus in higher-order human brain functions and evolution, its wide variation further stresses the important role of these deep parietal areas in modern neuroanatomical organization. © 2014 Anatomical Society.

Prediction of human errors by maladaptive changes in event-related brain networks.

PubMed

Eichele, Tom; Debener, Stefan; Calhoun, Vince D; Specht, Karsten; Engel, Andreas K; Hugdahl, Kenneth; von Cramon, D Yves; Ullsperger, Markus

2008-04-22

Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional MRI and applying independent component analysis followed by deconvolution of hemodynamic responses, we studied error preceding brain activity on a trial-by-trial basis. We found a set of brain regions in which the temporal evolution of activation predicted performance errors. These maladaptive brain activity changes started to evolve approximately 30 sec before the error. In particular, a coincident decrease of deactivation in default mode regions of the brain, together with a decline of activation in regions associated with maintaining task effort, raised the probability of future errors. Our findings provide insights into the brain network dynamics preceding human performance errors and suggest that monitoring of the identified precursor states may help in avoiding human errors in critical real-world situations.

Prediction of human errors by maladaptive changes in event-related brain networks

PubMed Central

Eichele, Tom; Debener, Stefan; Calhoun, Vince D.; Specht, Karsten; Engel, Andreas K.; Hugdahl, Kenneth; von Cramon, D. Yves; Ullsperger, Markus

2008-01-01

Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional MRI and applying independent component analysis followed by deconvolution of hemodynamic responses, we studied error preceding brain activity on a trial-by-trial basis. We found a set of brain regions in which the temporal evolution of activation predicted performance errors. These maladaptive brain activity changes started to evolve ≈30 sec before the error. In particular, a coincident decrease of deactivation in default mode regions of the brain, together with a decline of activation in regions associated with maintaining task effort, raised the probability of future errors. Our findings provide insights into the brain network dynamics preceding human performance errors and suggest that monitoring of the identified precursor states may help in avoiding human errors in critical real-world situations. PMID:18427123

Brain shape in human microcephalics and Homo floresiensis.

PubMed

Falk, Dean; Hildebolt, Charles; Smith, Kirk; Morwood, M J; Sutikna, Thomas; Jatmiko; Saptomo, E Wayhu; Imhof, Herwig; Seidler, Horst; Prior, Fred

2007-02-13

Because the cranial capacity of LB1 (Homo floresiensis) is only 417 cm(3), some workers propose that it represents a microcephalic Homo sapiens rather than a new species. This hypothesis is difficult to assess, however, without a clear understanding of how brain shape of microcephalics compares with that of normal humans. We compare three-dimensional computed tomographic reconstructions of the internal braincases (virtual endocasts that reproduce details of external brain morphology, including cranial capacities and shape) from a sample of 9 microcephalic humans and 10 normal humans. Discriminant and canonical analyses are used to identify two variables that classify normal and microcephalic humans with 100% success. The classification functions classify the virtual endocast from LB1 with normal humans rather than microcephalics. On the other hand, our classification functions classify a pathological H. sapiens specimen that, like LB1, represents an approximately 3-foot-tall adult female and an adult Basuto microcephalic woman that is alleged to have an endocast similar to LB1's with the microcephalic humans. Although microcephaly is genetically and clinically variable, virtual endocasts from our highly heterogeneous sample share similarities in protruding and proportionately large cerebella and relatively narrow, flattened orbital surfaces compared with normal humans. These findings have relevance for hypotheses regarding the genetic substrates of hominin brain evolution and may have medical diagnostic value. Despite LB1's having brain shape features that sort it with normal humans rather than microcephalics, other shape features and its small brain size are consistent with its assignment to a separate species.

Selective Activation of Resting-State Networks following Focal Stimulation in a Connectome-Based Network Model of the Human Brain

PubMed Central

2016-01-01

Abstract When the brain is stimulated, for example, by sensory inputs or goal-oriented tasks, the brain initially responds with activities in specific areas. The subsequent pattern formation of functional networks is constrained by the structural connectivity (SC) of the brain. The extent to which information is processed over short- or long-range SC is unclear. Whole-brain models based on long-range axonal connections, for example, can partly describe measured functional connectivity dynamics at rest. Here, we study the effect of SC on the network response to stimulation. We use a human whole-brain network model comprising long- and short-range connections. We systematically activate each cortical or thalamic area, and investigate the network response as a function of its short- and long-range SC. We show that when the brain is operating at the edge of criticality, stimulation causes a cascade of network recruitments, collapsing onto a smaller space that is partly constrained by SC. We found both short- and long-range SC essential to reproduce experimental results. In particular, the stimulation of specific areas results in the activation of one or more resting-state networks. We suggest that the stimulus-induced brain activity, which may indicate information and cognitive processing, follows specific routes imposed by structural networks explaining the emergence of functional networks. We provide a lookup table linking stimulation targets and functional network activations, which potentially can be useful in diagnostics and treatments with brain stimulation. PMID:27752540

[Fractal characteristics of the functional state of the brain in patients with anxious phobic disorders].

PubMed

Dik, O E; Sviatogor, I A; Ishinova, V A; Nozdrachev, A D

2012-01-01

The task of estimation of the functional state of the human brain during psychotherapeutic treatment of psychogenic pain in patients with anxious phobic disorders is examined. For solving the task the methods of spectral and multifractal analyses of EEG fragments are applied during the perception of psychogenic pain and its removal by the psychorelaxation technique. Contrary to power spectra singularity spectra allow to distinguish EEGs quanitatively in the examined functional states of the human brain. The pain suppression in patients with anxious phobic disorders during psychorelaxation is accompanied by changing the width of the singularity spectrum and approximation of this multifractal partameter to the value corresponding to a healthy subject.

Developmental implications of children's brain networks and learning.

PubMed

Chan, John S Y; Wang, Yifeng; Yan, Jin H; Chen, Huafu

2016-10-01

The human brain works as a synergistic system where information exchanges between functional neuronal networks. Rudimentary networks are observed in the brain during infancy. In recent years, the question of how functional networks develop and mature in children has been a hotly discussed topic. In this review, we examined the developmental characteristics of functional networks and the impacts of skill training on children's brains. We first focused on the general rules of brain network development and on the typical and atypical development of children's brain networks. After that, we highlighted the essentials of neural plasticity and the effects of learning on brain network development. We also discussed two important theoretical and practical concerns in brain network training. Finally, we concluded by presenting the significance of network training in typically and atypically developed brains.

Plasticity following early-life brain injury: Insights from quantitative MRI.

PubMed

Fiori, Simona; Guzzetta, Andrea

2015-03-01

Over the last decade, the application of novel advanced neuroimaging techniques to study congenital brain damage has provided invaluable insights into the mechanisms underlying early neuroplasticity. The concept that is clearly emerging, both from human and nun-human studies, is that functional reorganization in the immature brain is substantially different from that of the more mature, developed brain. This applies to the reorganization of language, the sensorimotor system, and the visual system. The rapid implementation and development of higher order imaging methods will offer increased, currently unavailable knowledge about the specific mechanisms of cerebral plasticity in infancy, which is essential to support the development of early therapeutic interventions aimed at supporting and enhancing functional reorganization during a time of greatest potential brain plasticity. Copyright © 2015. Published by Elsevier Inc.

Solid lipid nanoparticles as a vehicle for brain-targeted drug delivery: two new strategies of functionalization with apolipoprotein E

NASA Astrophysics Data System (ADS)

Rute Neves, Ana; Fontes Queiroz, Joana; Weksler, Babette; Romero, Ignacio A.; Couraud, Pierre-Olivier; Reis, Salette

2015-12-01

Nanotechnology can be an important tool to improve the permeability of some drugs for the blood-brain barrier. In this work we created a new system to enter the brain by functionalizing solid lipid nanoparticles with apolipoprotein E, aiming to enhance their binding to low-density lipoprotein receptors on the blood-brain barrier endothelial cells. Solid lipid nanoparticles were successfully functionalized with apolipoprotein E using two distinct strategies that took advantage of the strong interaction between biotin and avidin. Transmission electron microscopy images revealed spherical nanoparticles, and dynamic light scattering gave a Z-average under 200 nm, a polydispersity index below 0.2, and a zeta potential between -10 mV and -15 mV. The functionalization of solid lipid nanoparticles with apolipoprotein E was demonstrated by infrared spectroscopy and fluorimetric assays. In vitro cytotoxic effects were evaluated by MTT and LDH assays in the human cerebral microvascular endothelial cells (hCMEC/D3) cell line, a human blood-brain barrier model, and revealed no toxicity up to 1.5 mg ml-1 over 4 h of incubation. The brain permeability was evaluated in transwell devices with hCMEC/D3 monolayers, and a 1.5-fold increment in barrier transit was verified for functionalized nanoparticles when compared with non-functionalized ones. The results suggested that these novel apolipoprotein E-functionalized nanoparticles resulted in dynamic stable systems capable of being used for an improved and specialized brain delivery of drugs through the blood-brain barrier.

Adult Human Neurogenesis: From Microscopy to Magnetic Resonance Imaging

PubMed Central

Sierra, Amanda; Encinas, Juan M.; Maletic-Savatic, Mirjana

2011-01-01

Neural stem cells reside in well-defined areas of the adult human brain and are capable of generating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases. PMID:21519376

Correspondence of the brain's functional architecture during activation and rest

PubMed Central

Smith, Stephen M.; Fox, Peter T.; Miller, Karla L.; Glahn, David C.; Fox, P. Mickle; Mackay, Clare E.; Filippini, Nicola; Watkins, Kate E.; Toro, Roberto; Laird, Angela R.; Beckmann, Christian F.

2009-01-01

Neural connections, providing the substrate for functional networks, exist whether or not they are functionally active at any given moment. However, it is not known to what extent brain regions are continuously interacting when the brain is “at rest.” In this work, we identify the major explicit activation networks by carrying out an image-based activation network analysis of thousands of separate activation maps derived from the BrainMap database of functional imaging studies, involving nearly 30,000 human subjects. Independently, we extract the major covarying networks in the resting brain, as imaged with functional magnetic resonance imaging in 36 subjects at rest. The sets of major brain networks, and their decompositions into subnetworks, show close correspondence between the independent analyses of resting and activation brain dynamics. We conclude that the full repertoire of functional networks utilized by the brain in action is continuously and dynamically “active” even when at “rest.” PMID:19620724

Graph Theoretical Analysis of BOLD Functional Connectivity during Human Sleep without EEG Monitoring.

PubMed

Lv, Jun; Liu, Dongdong; Ma, Jing; Wang, Xiaoying; Zhang, Jue

2015-01-01

Functional brain networks of human have been revealed to have small-world properties by both analyzing electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) time series. In our study, by using graph theoretical analysis, we attempted to investigate the changes of paralimbic-limbic cortex between wake and sleep states. Ten healthy young people were recruited to our experiment. Data from 2 subjects were excluded for the reason that they had not fallen asleep during the experiment. For each subject, blood oxygen level dependency (BOLD) images were acquired to analyze brain network, and peripheral pulse signals were obtained continuously to identify if the subject was in sleep periods. Results of fMRI showed that brain networks exhibited stronger small-world characteristics during sleep state as compared to wake state, which was in consistent with previous studies using EEG synchronization. Moreover, we observed that compared with wake state, paralimbic-limbic cortex had less connectivity with neocortical system and centrencephalic structure in sleep. In conclusion, this is the first study, to our knowledge, has observed that small-world properties of brain functional networks altered when human sleeps without EEG synchronization. Moreover, we speculate that paralimbic-limbic cortex organization owns an efficient defense mechanism responsible for suppressing the external environment interference when humans sleep, which is consistent with the hypothesis that the paralimbic-limbic cortex may be functionally disconnected from brain regions which directly mediate their interactions with the external environment. Our findings also provide a reasonable explanation why stable sleep exhibits homeostasis which is far less susceptible to outside world.

An Isozyme-specific Redox Switch in Human Brain Glycogen Phosphorylase Modulates Its Allosteric Activation by AMP.

PubMed

Mathieu, Cécile; Duval, Romain; Cocaign, Angélique; Petit, Emile; Bui, Linh-Chi; Haddad, Iman; Vinh, Joelle; Etchebest, Catherine; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

2016-11-11

Brain glycogen and its metabolism are increasingly recognized as major players in brain functions. Moreover, alteration of glycogen metabolism in the brain contributes to neurodegenerative processes. In the brain, both muscle and brain glycogen phosphorylase isozymes regulate glycogen mobilization. However, given their distinct regulatory features, these two isozymes could confer distinct metabolic functions of glycogen in brain. Interestingly, recent proteomics studies have identified isozyme-specific reactive cysteine residues in brain glycogen phosphorylase (bGP). In this study, we show that the activity of human bGP is redox-regulated through the formation of a disulfide bond involving a highly reactive cysteine unique to the bGP isozyme. We found that this disulfide bond acts as a redox switch that precludes the allosteric activation of the enzyme by AMP without affecting its activation by phosphorylation. This unique regulatory feature of bGP sheds new light on the isoform-specific regulation of glycogen phosphorylase and glycogen metabolism. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Sibling rivalry among paralogs promotes evolution of the human brain.

PubMed

Tyler-Smith, Chris; Xue, Yali

2012-05-11

Geneticists have long sought to identify the genetic changes that made us human, but pinpointing the functionally relevant changes has been challenging. Two papers in this issue suggest that partial duplication of SRGAP2, producing an incomplete protein that antagonizes the original, contributed to human brain evolution. Copyright © 2012 Elsevier Inc. All rights reserved.

The Human Thalamus Is an Integrative Hub for Functional Brain Networks

PubMed Central

Bertolero, Maxwell A.

2017-01-01

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

Algebraic Topology of Multi-Brain Connectivity Networks Reveals Dissimilarity in Functional Patterns during Spoken Communications

PubMed Central

Tadić, Bosiljka; Andjelković, Miroslav; Boshkoska, Biljana Mileva; Levnajić, Zoran

2016-01-01

Human behaviour in various circumstances mirrors the corresponding brain connectivity patterns, which are suitably represented by functional brain networks. While the objective analysis of these networks by graph theory tools deepened our understanding of brain functions, the multi-brain structures and connections underlying human social behaviour remain largely unexplored. In this study, we analyse the aggregate graph that maps coordination of EEG signals previously recorded during spoken communications in two groups of six listeners and two speakers. Applying an innovative approach based on the algebraic topology of graphs, we analyse higher-order topological complexes consisting of mutually interwoven cliques of a high order to which the identified functional connections organise. Our results reveal that the topological quantifiers provide new suitable measures for differences in the brain activity patterns and inter-brain synchronisation between speakers and listeners. Moreover, the higher topological complexity correlates with the listener’s concentration to the story, confirmed by self-rating, and closeness to the speaker’s brain activity pattern, which is measured by network-to-network distance. The connectivity structures of the frontal and parietal lobe consistently constitute distinct clusters, which extend across the listener’s group. Formally, the topology quantifiers of the multi-brain communities exceed the sum of those of the participating individuals and also reflect the listener’s rated attributes of the speaker and the narrated subject. In the broader context, the presented study exposes the relevance of higher topological structures (besides standard graph measures) for characterising functional brain networks under different stimuli. PMID:27880802

Transcriptional landscape of the prenatal human brain.

PubMed

Miller, Jeremy A; Ding, Song-Lin; Sunkin, Susan M; Smith, Kimberly A; Ng, Lydia; Szafer, Aaron; Ebbert, Amanda; Riley, Zackery L; Royall, Joshua J; Aiona, Kaylynn; Arnold, James M; Bennet, Crissa; Bertagnolli, Darren; Brouner, Krissy; Butler, Stephanie; Caldejon, Shiella; Carey, Anita; Cuhaciyan, Christine; Dalley, Rachel A; Dee, Nick; Dolbeare, Tim A; Facer, Benjamin A C; Feng, David; Fliss, Tim P; Gee, Garrett; Goldy, Jeff; Gourley, Lindsey; Gregor, Benjamin W; Gu, Guangyu; Howard, Robert E; Jochim, Jayson M; Kuan, Chihchau L; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Lemon, Tracy A; Lesnar, Phil; McMurray, Bergen; Mastan, Naveed; Mosqueda, Nerick; Naluai-Cecchini, Theresa; Ngo, Nhan-Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D; Parry, Sheana E; Stevens, Allison; Pletikos, Mihovil; Reding, Melissa; Roll, Kate; Sandman, David; Sarreal, Melaine; Shapouri, Sheila; Shapovalova, Nadiya V; Shen, Elaine H; Sjoquist, Nathan; Slaughterbeck, Clifford R; Smith, Michael; Sodt, Andy J; Williams, Derric; Zöllei, Lilla; Fischl, Bruce; Gerstein, Mark B; Geschwind, Daniel H; Glass, Ian A; Hawrylycz, Michael J; Hevner, Robert F; Huang, Hao; Jones, Allan R; Knowles, James A; Levitt, Pat; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Dang, Chinh; Bernard, Amy; Hohmann, John G; Lein, Ed S

2014-04-10

The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.

Does menaquinone participate in brain astrocyte electron transport?

PubMed

Lovern, Douglas; Marbois, Beth

2013-10-01

Quinone compounds act as membrane resident carriers of electrons between components of the electron transport chain in the periplasmic space of prokaryotes and in the mitochondria of eukaryotes. Vitamin K is a quinone compound in the human body in a storage form as menaquinone (MK); distribution includes regulated amounts in mitochondrial membranes. The human brain, which has low amounts of typical vitamin K dependent function (e.g., gamma carboxylase) has relatively high levels of MK, and different regions of brain have different amounts. Coenzyme Q (Q), is a quinone synthesized de novo, and the levels of synthesis decline with age. The levels of MK are dependent on dietary intake and generally increase with age. MK has a characterized role in the transfer of electrons to fumarate in prokaryotes. A newly recognized fumarate cycle has been identified in brain astrocytes. The MK precursor menadione has been shown to donate electrons directly to mitochondrial complex III. Vitamin K compounds function in the electron transport chain of human brain astrocytes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Proteomic and cellular localisation studies suggest non-tight junction cytoplasmic and nuclear roles for occludin in astrocytes.

PubMed

Morgan, Sarah V; Garwood, Claire J; Jennings, Luke; Simpson, Julie E; Castelli, Lydia M; Heath, Paul R; Mihaylov, Simeon R; Vaquéz-Villaseñor, Irina; Minshull, Thomas C; Ince, Paul G; Dickman, Mark J; Hautbergue, Guillaume M; Wharton, Stephen B

2018-05-08

Occludin is a component of tight junctions, which are essential structural components of the blood-brain barrier. However, occludin is expressed in cells without tight junctions, implying additional functions. We determined the expression and localisation of occludin in astrocytes in cell culture and in human brain tissue, and sought novel binding partners using a proteomic approach. Expression was investigated by immunocytochemistry and immunoblotting in the 1321N1 astrocytoma cell line and ScienCell human primary astrocytes, and by immunohistochemistry in human autopsy brain tissue. Recombinant N- and C-terminal occludin was used to pull-down proteins from 1321N1 cell lysates and protein-binding partners identified by mass spectrometry analysis. Occludin was expressed in both the cytoplasm and nucleus of astrocytes in vitro and in vivo. Mass spectrometry identified binding to nuclear and cytoplasmic proteins, particularly those related to RNA metabolism and nuclear function. Occludin is expressed in several subcellular compartments of brain cell-types that do not form tight junctions and the expression patterns in cell culture reflect those in human brain tissue, indicating they are suitable model systems. Proteomic analysis suggests that occludin has novel functions in neuroepithelial cells that are unrelated to tight junction formation. Further research will establish the roles of these functions in both cellular physiology and in disease states. © 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Differentiation and characterization of human pluripotent stem cell-derived brain microvascular endothelial cells.

PubMed

Stebbins, Matthew J; Wilson, Hannah K; Canfield, Scott G; Qian, Tongcheng; Palecek, Sean P; Shusta, Eric V

2016-05-15

The blood-brain barrier (BBB) is a critical component of the central nervous system (CNS) that regulates the flux of material between the blood and the brain. Because of its barrier properties, the BBB creates a bottleneck to CNS drug delivery. Human in vitro BBB models offer a potential tool to screen pharmaceutical libraries for CNS penetration as well as for BBB modulators in development and disease, yet primary and immortalized models respectively lack scalability and robust phenotypes. Recently, in vitro BBB models derived from human pluripotent stem cells (hPSCs) have helped overcome these challenges by providing a scalable and renewable source of human brain microvascular endothelial cells (BMECs). We have demonstrated that hPSC-derived BMECs exhibit robust structural and functional characteristics reminiscent of the in vivo BBB. Here, we provide a detailed description of the methods required to differentiate and functionally characterize hPSC-derived BMECs to facilitate their widespread use in downstream applications. Copyright © 2015 Elsevier Inc. All rights reserved.

Connectivity-based parcellation of human cingulate cortex and its relation to functional specialization.

PubMed

Beckmann, Matthias; Johansen-Berg, Heidi; Rushworth, Matthew F S

2009-01-28

Whole-brain neuroimaging studies have demonstrated regional variations in function within human cingulate cortex. At the same time, regional variations in cingulate anatomical connections have been found in animal models. It has, however, been difficult to estimate the relationship between connectivity and function throughout the whole cingulate cortex within the human brain. In this study, magnetic resonance diffusion tractography was used to investigate cingulate probabilistic connectivity in the human brain with two approaches. First, an algorithm was used to search for regional variations in the probabilistic connectivity profiles of all cingulate cortex voxels with the whole of the rest of the brain. Nine subregions with distinctive connectivity profiles were identified. It was possible to characterize several distinct areas in the dorsal cingulate sulcal region. Several distinct regions were also found in subgenual and perigenual cortex. Second, the probabilities of connection between cingulate cortex and 11 predefined target regions of interest were calculated. Cingulate voxels with a high probability of connection with the different targets formed separate clusters within cingulate cortex. Distinct connectivity fingerprints characterized the likelihood of connections between the extracingulate target regions and the nine cingulate subregions. Last, a meta-analysis of 171 functional studies reporting cingulate activation was performed. Seven different cognitive conditions were selected and peak activation coordinates were plotted to create maps of functional localization within the cingulate cortex. Regional functional specialization was found to be related to regional differences in probabilistic anatomical connectivity.

Unsupervised Decoding of Long-Term, Naturalistic Human Neural Recordings with Automated Video and Audio Annotations

PubMed Central

Wang, Nancy X. R.; Olson, Jared D.; Ojemann, Jeffrey G.; Rao, Rajesh P. N.; Brunton, Bingni W.

2016-01-01

Fully automated decoding of human activities and intentions from direct neural recordings is a tantalizing challenge in brain-computer interfacing. Implementing Brain Computer Interfaces (BCIs) outside carefully controlled experiments in laboratory settings requires adaptive and scalable strategies with minimal supervision. Here we describe an unsupervised approach to decoding neural states from naturalistic human brain recordings. We analyzed continuous, long-term electrocorticography (ECoG) data recorded over many days from the brain of subjects in a hospital room, with simultaneous audio and video recordings. We discovered coherent clusters in high-dimensional ECoG recordings using hierarchical clustering and automatically annotated them using speech and movement labels extracted from audio and video. To our knowledge, this represents the first time techniques from computer vision and speech processing have been used for natural ECoG decoding. Interpretable behaviors were decoded from ECoG data, including moving, speaking and resting; the results were assessed by comparison with manual annotation. Discovered clusters were projected back onto the brain revealing features consistent with known functional areas, opening the door to automated functional brain mapping in natural settings. PMID:27148018

Anatomical location of LPA1 activation and LPA phospholipid precursors in rodent and human brain.

PubMed

González de San Román, Estibaliz; Manuel, Iván; Giralt, María Teresa; Chun, Jerold; Estivill-Torrús, Guillermo; Rodríguez de Fonseca, Fernando; Santín, Luis Javier; Ferrer, Isidro; Rodríguez-Puertas, Rafael

2015-08-01

Lysophosphatidic acid (LPA) is a signaling molecule that binds to six known G protein-coupled receptors: LPA1 -LPA6 . LPA evokes several responses in the CNS, including cortical development and folding, growth of the axonal cone and its retraction process. Those cell processes involve survival, migration, adhesion proliferation, differentiation, and myelination. The anatomical localization of LPA1 is incompletely understood, particularly with regard to LPA binding. Therefore, we have used functional [(35) S]GTPγS autoradiography to verify the anatomical distribution of LPA1 binding sites in adult rodent and human brain. The greatest activity was observed in myelinated areas of the white matter such as corpus callosum, internal capsule and cerebellum. MaLPA1 -null mice (a variant of LPA1 -null) lack [(35) S]GTPγS basal binding in white matter areas, where the LPA1 receptor is expressed at high levels, suggesting a relevant role of the activity of this receptor in the most myelinated brain areas. In addition, phospholipid precursors of LPA were localized by MALDI-IMS in both rodent and human brain slices identifying numerous species of phosphatides and phosphatidylcholines. Both phosphatides and phosphatidylcholines species represent potential LPA precursors. The anatomical distribution of these precursors in rodent and human brain may indicate a metabolic relationship between LPA and LPA1 receptors. Lysophosphatidic acid (LPA) is a signaling molecule that binds to six known G protein-coupled receptors (GPCR), LPA1 to LPA6 . LPA evokes several responses in the central nervous system (CNS), including cortical development and folding, growth of the axonal cone and its retraction process. We used functional [(35) S]GTPγS autoradiography to verify the anatomical distribution of LPA1 -binding sites in adult rodent and human brain. The distribution of LPA1 receptors in rat, mouse and human brains show the highest activity in white matter myelinated areas. The basal and LPA-evoked activities are abolished in MaLPA1 -null mice. The phospholipid precursors of LPA are localized by MALDI-IMS. The anatomical distribution of LPA precursors in rodent and human brain suggests a relationship with functional LPA1 receptors. © 2015 International Society for Neurochemistry.

It's Never Too Late! What Neuroscience Has to Offer High Schools.

ERIC Educational Resources Information Center

Greenleaf, Robert K.

1999-01-01

Debunks brain/education myths. The term "brain-based education" is redundant; learning is the brain's function. More brain cell connections do not equal more learning. There is no "critical period" for developing human brain capacity. All learning is emotional, and learning never ends. Tips for high-school teachers are…

The Lateralizer: A Tool for Students to Explore the Divided Brain

ERIC Educational Resources Information Center

Motz, Benjamin A.; James, Karin H.; Busey, Thomas A.

2012-01-01

Despite a profusion of popular misinformation about the left brain and right brain, there are functional differences between the left and right cerebral hemispheres in humans. Evidence from split-brain patients, individuals with unilateral brain damage, and neuroimaging studies suggest that each hemisphere may be specialized for certain cognitive…

[Three Essential Shared Capabilities for Young Psychiatrists: Brain, Real-world, and Life-course Principles toward Values-based Psychiatry].

PubMed

Kasai, Kiyoto

2015-01-01

The discipline of psychiatry promotes well-being and recovery based on a comprehensive understanding of the patient from the perspectives of the brain, real-world, and life-course. Pursuant to efforts toward addressing social issues at a regional and national level, it is assumed that the psychiatrist can assist individuals based on an understanding of these three perspectives. This tripartite relationship goes beyond the history of extreme reductionism in neuroscience and the aftermath resulting from the anti-psychiatry movement to provide a foundation for the development of psychiatry and a theoretical groundwork for such basic psychiatric issues as what role pharmacotherapy plays in psychiatric treatment, just why the lives of people living in the community are thought to be important to an individual's well-being, and just what constitutes recovery. Humans have come to possess highly developed brain and mental functions as a result of the adaptation to the social environment that takes place as part of the evolutionary process. While mental functions are thus dictated in large part by evolution of the brain, they also consist of important features that are not attributable to reductionist models of the brain. That is, human mental functioning forms a foundation for metacognition and sophisticated language functions, and through interactions with others and society, one's mental functioning allows for further brain transformation and development (self-regulation of mental functions). Humans develop their own brain and mental functions through mutual exchanges with others, and their dealings with other people and society form their individual modes of living in the real-world. The human brain and mental functions have evolved in such a way as to provide for a better mode of living. Accordingly, for the individual, the makeup of his or her mode of living in the real-world is the source of the well-being that serves to support that individual's values. The scientific background that the human recovery process for those suffering from mental disease involves the combined support of work, school, marriage, and childrearing stems from this fact. Humans develop their own mental capital over their life-courses and utilize it in an effort to realize their well-beings. Humans utilize mental function self-regulation based on the emotional and interpersonal functions developed during childhood in order to formulate an image of themselves (the ego) as well as the type of person they want to become (values/needs). This is indeed the true essence of adolescence. The values that drive an individual's behavior by their very nature exist in the outside world and are shared by others as well as society. These are internalized as individual characteristics through the self-regulation process of adolescence. Regardless of life stage or type of mental illness, individual reflection, verbalization, and reorganization of adolescent ego and values formation are essential to the recovery process. Humans are born with both bodies and brains, and throughout the courses of their lives, they formulate and develop values. Based on an understanding of the tripartite relationship between the brain, real-world, and life courses, it can be argued that the supporting of individual values is the scientific basis for the so-called "patient-centered care" and "needs-based support" that serve as a psychiatrist's essential capabilities. Along with the patient's recovery, which is based on this values-based psychiatry, professional growth is the privilege enjoyed by those in the psychiatric field. Beginning with a foundation based on assisted recovery at the individual level, the psychiatrist can produce mental health changes at the regional level. The psychiatrist consequently possesses the national-level vision necessary to implement a community design model that combines mental health and preventive medicine.

Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer.

PubMed

Ngô, Huân M; Zhou, Ying; Lorenzi, Hernan; Wang, Kai; Kim, Taek-Kyun; Zhou, Yong; El Bissati, Kamal; Mui, Ernest; Fraczek, Laura; Rajagopala, Seesandra V; Roberts, Craig W; Henriquez, Fiona L; Montpetit, Alexandre; Blackwell, Jenefer M; Jamieson, Sarra E; Wheeler, Kelsey; Begeman, Ian J; Naranjo-Galvis, Carlos; Alliey-Rodriguez, Ney; Davis, Roderick G; Soroceanu, Liliana; Cobbs, Charles; Steindler, Dennis A; Boyer, Kenneth; Noble, A Gwendolyn; Swisher, Charles N; Heydemann, Peter T; Rabiah, Peter; Withers, Shawn; Soteropoulos, Patricia; Hood, Leroy; McLeod, Rima

2017-09-13

One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain. Transcriptomic and quantitative proteomic analyses of infected human, primary, neuronal stem and monocytic cells revealed effects on neurodevelopment and plasticity in neural, immune, and endocrine networks. These findings were supported by identification of protein and miRNA biomarkers in sera of ill children reflecting brain damage and T. gondii infection. These data were deconvoluted using three systems biology approaches: "Orbital-deconvolution" elucidated upstream, regulatory pathways interconnecting human susceptibility genes, biomarkers, proteomes, and transcriptomes. "Cluster-deconvolution" revealed visual protein-protein interaction clusters involved in processes affecting brain functions and circuitry, including lipid metabolism, leukocyte migration and olfaction. Finally, "disease-deconvolution" identified associations between the parasite-brain interactions and epilepsy, movement disorders, Alzheimer's disease, and cancer. This "reconstruction-deconvolution" logic provides templates of progenitor cells' potentiating effects, and components affecting human brain parasitism and diseases.

Effects of Physical Exercise Combined with Nutritional Supplements on Aging Brain Related Structures and Functions: A Systematic Review

PubMed Central

Schättin, Alexandra; Baur, Kilian; Stutz, Jan; Wolf, Peter; de Bruin, Eling D.

2016-01-01

Age-related decline in gray and white brain matter goes together with cognitive depletion. To influence cognitive functioning in elderly, several types of physical exercise and nutritional intervention have been performed. This paper systematically reviews the potential additive and complementary effects of nutrition/nutritional supplements and physical exercise on cognition. The search strategy was developed for EMBASE, Medline, PubMed, Cochrane, CINAHL, and PsycInfo databases and focused on the research question: “Is the combination of physical exercise with nutrition/nutritional supplementation more effective than nutrition/nutritional supplementation or physical exercise alone in effecting on brain structure, metabolism, and/or function?” Both mammalian and human studies were included. In humans, randomized controlled trials that evaluated the effects of nutrition/nutritional supplements and physical exercise on cognitive functioning and associated parameters in healthy elderly (>65 years) were included. The systematic search included English and German language literature without any limitation of publication date. The search strategy yielded a total of 3129 references of which 67 studies met the inclusion criteria; 43 human and 24 mammalian, mainly rodent, studies. Three out of 43 human studies investigated a nutrition/physical exercise combination and reported no additive effects. In rodent studies, additive effects were found for docosahexaenoic acid supplementation when combined with physical exercise. Although feasible combinations of physical exercise/nutritional supplements are available for influencing the brain, only a few studies evaluated which possible combinations of nutrition/nutritional supplementation and physical exercise might have an effect on brain structure, metabolism and/or function. The reason for no clear effects of combinatory approaches in humans might be explained by the misfit between the combinations of nutritional methods with the physical interventions in the sense that they were not selected on sharing of similar neuronal mechanisms. Based on the results from this systematic review, future human studies should focus on the combined effect of docosahexaenoic acid supplementation and physical exercise that contains elements of (motor) learning. PMID:27458371

Kisspeptin modulates sexual and emotional brain processing in humans

PubMed Central

Comninos, Alexander N.; Wall, Matthew B.; Demetriou, Lysia; Shah, Amar J.; Clarke, Sophie A.; Narayanaswamy, Shakunthala; Nesbitt, Alexander; Izzi-Engbeaya, Chioma; Prague, Julia K.; Abbara, Ali; Ratnasabapathy, Risheka; Salem, Victoria; Nijher, Gurjinder M.; Jayasena, Channa N.; Tanner, Mark; Bassett, Paul; Mehta, Amrish; Rabiner, Eugenii A.; Hönigsperger, Christoph; Silva, Meire Ribeiro; Brandtzaeg, Ole Kristian; Wilson, Steven Ray; Brown, Rachel C.; Thomas, Sarah A.; Bloom, Stephen R.; Dhillo, Waljit S.

2017-01-01

BACKGROUND. Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. METHODS. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. RESULTS. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin’s enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. CONCLUSIONS. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. FUNDING. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC). PMID:28112678

The Two Brains and the Education Process.

ERIC Educational Resources Information Center

Shook, Ronald

The human brain is lateralized, different functions being housed in each hemisphere. Several assumptions which are mistakenly considered fact by researchers include: (1) the left hemisphere is for rational functions, while the right is for intuitive functions; (2) the hemispheres do not interact as well with each other as they should; (3) the use…

Computational Neuroscience.

ERIC Educational Resources Information Center

Sejnowski, Terrence J.; And Others

1988-01-01

Describes the use of brain models to connect the microscopic level accessible by molecular and cellular techniques with the systems level accessible by the study of behavior. Discusses classes of brain models, and specific examples of such models. Evaluates the strengths and weaknesses of using brain modelling to understand human brain function.…

Automated voxel classification used with atlas-guided diffuse optical tomography for assessment of functional brain networks in young and older adults.

PubMed

Li, Lin; Cazzell, Mary; Babawale, Olajide; Liu, Hanli

2016-10-01

Atlas-guided diffuse optical tomography (atlas-DOT) is a computational means to image changes in cortical hemodynamic signals during human brain activities. Graph theory analysis (GTA) is a network analysis tool commonly used in functional neuroimaging to study brain networks. Atlas-DOT has not been analyzed with GTA to derive large-scale brain connectivity/networks based on near-infrared spectroscopy (NIRS) measurements. We introduced an automated voxel classification (AVC) method that facilitated the use of GTA with atlas-DOT images by grouping unequal-sized finite element voxels into anatomically meaningful regions of interest within the human brain. The overall approach included volume segmentation, AVC, and cross-correlation. To demonstrate the usefulness of AVC, we applied reproducibility analysis to resting-state functional connectivity measurements conducted from 15 young adults in a two-week period. We also quantified and compared changes in several brain network metrics between young and older adults, which were in agreement with those reported by a previous positron emission tomography study. Overall, this study demonstrated that AVC is a useful means for facilitating integration or combination of atlas-DOT with GTA and thus for quantifying NIRS-based, voxel-wise resting-state functional brain networks.

Chronnectome fingerprinting: Identifying individuals and predicting higher cognitive functions using dynamic brain connectivity patterns.

PubMed

Liu, Jin; Liao, Xuhong; Xia, Mingrui; He, Yong

2018-02-01

The human brain is a large, interacting dynamic network, and its architecture of coupling among brain regions varies across time (termed the "chronnectome"). However, very little is known about whether and how the dynamic properties of the chronnectome can characterize individual uniqueness, such as identifying individuals as a "fingerprint" of the brain. Here, we employed multiband resting-state functional magnetic resonance imaging data from the Human Connectome Project (N = 105) and a sliding time-window dynamic network analysis approach to systematically examine individual time-varying properties of the chronnectome. We revealed stable and remarkable individual variability in three dynamic characteristics of brain connectivity (i.e., strength, stability, and variability), which was mainly distributed in three higher order cognitive systems (i.e., default mode, dorsal attention, and fronto-parietal) and in two primary systems (i.e., visual and sensorimotor). Intriguingly, the spatial patterns of these dynamic characteristics of brain connectivity could successfully identify individuals with high accuracy and could further significantly predict individual higher cognitive performance (e.g., fluid intelligence and executive function), which was primarily contributed by the higher order cognitive systems. Together, our findings highlight that the chronnectome captures inherent functional dynamics of individual brain networks and provides implications for individualized characterization of health and disease. © 2017 Wiley Periodicals, Inc.

Hot heads and cold brains. Aristotle, Galen and the "radiator theory".

PubMed

Longo, O

1996-01-01

The Author examines two similar theories about the functioning of human brain as a refrigerator: Falk's and Fialkowski's (1990) and Aristotle's (IVth century b.C.). There are surprising, although fortuitous, convergences between the two, with the remarkable difference, however, that Artistotle's doctrine (later severely criticized by Galen) thinks of the brain merely as an organ for the cooling of the body's (the heart's) heat, while according to the modern radiator theory the human brain developed starting as a refrigerator of itself.

The gastrointestinal-brain axis in humans as an evolutionary advance of the root-leaf axis in plants: A hypothesis linking quantum effects of light on serotonin and auxin.

PubMed

Tonello, Lucio; Gashi, Bekim; Scuotto, Alessandro; Cappello, Glenda; Cocchi, Massimo; Gabrielli, Fabio; Tuszynski, Jack A

2018-01-01

Living organisms tend to find viable strategies under ambient conditions that optimize their search for, and utilization of, life-sustaining resources. For plants, a leading role in this process is performed by auxin, a plant hormone that drives morphological development, dynamics, and movement to optimize the absorption of light (through branches and leaves) and chemical "food" (through roots). Similarly to auxin in plants, serotonin seems to play an important role in higher animals, especially humans. Here, it is proposed that morphological and functional similarities between (i) plant leaves and the animal/human brain and (ii) plant roots and the animal/human gastro-intestinal tract have general features in common. Plants interact with light and use it for biological energy, whereas, neurons in the central nervous system seem to interact with bio-photons and use them for proper brain function. Further, as auxin drives roots "arborescence" within the soil, similarly serotonin seems to facilitate enteric nervous system connectivity within the human gastro-intestinal tract. This auxin/serotonin parallel suggests the root-branches axis in plants may be an evolutionary precursor to the gastro-intestinal-brain axis in humans. Finally, we hypothesize that light might be an important factor, both in gastro-intestinal dynamics and brain function. Such a comparison may indicate a key role for the interaction of light and serotonin in neuronal physiology (possibly in both the central nervous system and the enteric nervous system), and according to recent work, mind and consciousness.

In vivo functional neurochemistry of human cortical cholinergic function during visuospatial attention

PubMed Central

Lindner, Michael; Bell, Tiffany; Iqbal, Somya; Mullins, Paul Gerald

2017-01-01

Cortical acetylcholine is involved in key cognitive processes such as visuospatial attention. Dysfunction in the cholinergic system has been described in a number of neuropsychiatric disorders. Levels of brain acetylcholine can be pharmacologically manipulated, but it is not possible to directly measure it in vivo in humans. However, key parts of its biochemical cascade in neural tissue, such as choline, can be measured using magnetic resonance spectroscopy (MRS). There is evidence that levels of choline may be an indirect but proportional measure of acetylcholine availability in brain tissue. In this study, we measured relative choline levels in the parietal cortex using functional (event-related) MRS (fMRS) during performance of a visuospatial attention task, with a modelling approach verified using simulated data. We describe a task-driven interaction effect on choline concentration, specifically driven by contralateral attention shifts. Our results suggest that choline MRS has the potential to serve as a proxy of brain acetylcholine function in humans. PMID:28192451

Polyphenols and the human brain: plant “secondary metabolite” ecologic roles and endogenous signaling functions drive benefits.

PubMed

Kennedy, David O

2014-09-01

Flavonoids and other polyphenols are ubiquitous plant chemicals that fulfill a range of ecologic roles for their home plant, including protection from a range of biotic and abiotic stressors and a pivotal role in the management of pathogenic and symbiotic soil bacteria and fungi. They form a natural part of the human diet, and evidence suggests that their consumption is associated with the beneficial modulation of a number of health-related variables, including those related to cardiovascular and brain function. Over recent years, the consensus as to the mechanisms responsible for these effects in humans has shifted away from polyphenols having direct antioxidant effects and toward their modulation of cellular signal transduction pathways. To date, little consideration has been given to the question of why, rather than how, these plant-derived chemicals might exert these effects. Therefore, this review summarizes the evidence suggesting that polyphenols beneficially affect human brain function and describes the current mechanistic hypotheses explaining these effects. It then goes on to describe the ecologic roles and potential endogenous signaling functions that these ubiquitous phytochemicals play within their home plant and discusses whether these functions drive their beneficial effects in humans via a process of “cross-kingdom” signaling predicated on the many conserved similarities in plant, microbial, and human cellular signal transduction pathways.

Polyphenols and the Human Brain: Plant “Secondary Metabolite” Ecologic Roles and Endogenous Signaling Functions Drive Benefits12

PubMed Central

Kennedy, David O.

2014-01-01

Flavonoids and other polyphenols are ubiquitous plant chemicals that fulfill a range of ecologic roles for their home plant, including protection from a range of biotic and abiotic stressors and a pivotal role in the management of pathogenic and symbiotic soil bacteria and fungi. They form a natural part of the human diet, and evidence suggests that their consumption is associated with the beneficial modulation of a number of health-related variables, including those related to cardiovascular and brain function. Over recent years, the consensus as to the mechanisms responsible for these effects in humans has shifted away from polyphenols having direct antioxidant effects and toward their modulation of cellular signal transduction pathways. To date, little consideration has been given to the question of why, rather than how, these plant-derived chemicals might exert these effects. Therefore, this review summarizes the evidence suggesting that polyphenols beneficially affect human brain function and describes the current mechanistic hypotheses explaining these effects. It then goes on to describe the ecologic roles and potential endogenous signaling functions that these ubiquitous phytochemicals play within their home plant and discusses whether these functions drive their beneficial effects in humans via a process of “cross-kingdom” signaling predicated on the many conserved similarities in plant, microbial, and human cellular signal transduction pathways. PMID:25469384

Dynamic reconfiguration of frontal brain networks during executive cognition in humans

PubMed Central

Braun, Urs; Schäfer, Axel; Walter, Henrik; Erk, Susanne; Romanczuk-Seiferth, Nina; Haddad, Leila; Schweiger, Janina I.; Grimm, Oliver; Heinz, Andreas; Tost, Heike; Meyer-Lindenberg, Andreas; Bassett, Danielle S.

2015-01-01

The brain is an inherently dynamic system, and executive cognition requires dynamically reconfiguring, highly evolving networks of brain regions that interact in complex and transient communication patterns. However, a precise characterization of these reconfiguration processes during cognitive function in humans remains elusive. Here, we use a series of techniques developed in the field of “dynamic network neuroscience” to investigate the dynamics of functional brain networks in 344 healthy subjects during a working-memory challenge (the “n-back” task). In contrast to a control condition, in which dynamic changes in cortical networks were spread evenly across systems, the effortful working-memory condition was characterized by a reconfiguration of frontoparietal and frontotemporal networks. This reconfiguration, which characterizes “network flexibility,” employs transient and heterogeneous connectivity between frontal systems, which we refer to as “integration.” Frontal integration predicted neuropsychological measures requiring working memory and executive cognition, suggesting that dynamic network reconfiguration between frontal systems supports those functions. Our results characterize dynamic reconfiguration of large-scale distributed neural circuits during executive cognition in humans and have implications for understanding impaired cognitive function in disorders affecting connectivity, such as schizophrenia or dementia. PMID:26324898

Intrinsic connectivity of neural networks in the awake rabbit.

PubMed

Schroeder, Matthew P; Weiss, Craig; Procissi, Daniel; Disterhoft, John F; Wang, Lei

2016-04-01

The way in which the brain is functionally connected into different networks has emerged as an important research topic in order to understand normal neural processing and signaling. Since some experimental manipulations are difficult or unethical to perform in humans, animal models are better suited to investigate this topic. Rabbits are a species that can undergo MRI scanning in an awake and conscious state with minimal preparation and habituation. In this study, we characterized the intrinsic functional networks of the resting New Zealand White rabbit brain using BOLD fMRI data. Group independent component analysis revealed seven networks similar to those previously found in humans, non-human primates and/or rodents including the hippocampus, default mode, cerebellum, thalamus, and visual, somatosensory, and parietal cortices. For the first time, the intrinsic functional networks of the resting rabbit brain have been elucidated demonstrating the rabbit's applicability as a translational animal model. Without the confounding effects of anesthetics or sedatives, future experiments may employ rabbits to understand changes in neural connectivity and brain functioning as a result of experimental manipulation (e.g., temporary or permanent network disruption, learning-related changes, and drug administration). Copyright © 2016 Elsevier Inc. All rights reserved.

High-Speed and Scalable Whole-Brain Imaging in Rodents and Primates.

PubMed

Seiriki, Kaoru; Kasai, Atsushi; Hashimoto, Takeshi; Schulze, Wiebke; Niu, Misaki; Yamaguchi, Shun; Nakazawa, Takanobu; Inoue, Ken-Ichi; Uezono, Shiori; Takada, Masahiko; Naka, Yuichiro; Igarashi, Hisato; Tanuma, Masato; Waschek, James A; Ago, Yukio; Tanaka, Kenji F; Hayata-Takano, Atsuko; Nagayasu, Kazuki; Shintani, Norihito; Hashimoto, Ryota; Kunii, Yasuto; Hino, Mizuki; Matsumoto, Junya; Yabe, Hirooki; Nagai, Takeharu; Fujita, Katsumasa; Matsuda, Toshio; Takuma, Kazuhiro; Baba, Akemichi; Hashimoto, Hitoshi

2017-06-21

Subcellular resolution imaging of the whole brain and subsequent image analysis are prerequisites for understanding anatomical and functional brain networks. Here, we have developed a very high-speed serial-sectioning imaging system named FAST (block-face serial microscopy tomography), which acquires high-resolution images of a whole mouse brain in a speed range comparable to that of light-sheet fluorescence microscopy. FAST enables complete visualization of the brain at a resolution sufficient to resolve all cells and their subcellular structures. FAST renders unbiased quantitative group comparisons of normal and disease model brain cells for the whole brain at a high spatial resolution. Furthermore, FAST is highly scalable to non-human primate brains and human postmortem brain tissues, and can visualize neuronal projections in a whole adult marmoset brain. Thus, FAST provides new opportunities for global approaches that will allow for a better understanding of brain systems in multiple animal models and in human diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Overlapping regional distribution of CCK and TPPII mRNAs in Cynomolgus monkey brain and correlated levels in human cerebral cortex (BA 10).

PubMed

Radu, Diana; Tomkinson, Birgitta; Zachrisson, Olof; Weber, Günther; de Belleroche, Jacqueline; Hirsch, Steven; Lindefors, Nils

2006-08-09

Tripeptidyl peptidase II (TPPII) is a high molecular weight exopeptidase important in inactivating extracellular cholecystokinin (CCK). Our aims were to study the anatomical localization of TPPII and CCK mRNA in the Cynomolgus monkey brain as a basis for a possible functional anatomical connection between enzyme (TPPII) and substrate (CCK) and examine if indications of changes in substrate availability in the human brain might be reflected in changes of levels of TPPII mRNA. mRNA in situ hybridization on postmortem brain from patients having had a schizophrenia diagnosis as compared to controls and on monkey and rat brain slices. overlapping distribution patterns of mRNAs for TPPII and CCK in rat and monkey. High amounts of TPPII mRNA are seen in the neocortex, especially in the frontal region and the hippocampus. TPPII mRNA is also present in the basal ganglia and cerebellum where CCK immunoreactivity and/or CCK B receptors have been found in earlier studies, suggesting presence of CCK-ergic afferents from other brain regions. Levels of mRNAs for CCK and TPPII show a positive correlation in postmortem human cerebral cortex Brodmann area (BA) 10. TPPII mRNA might be affected following schizophrenia. overall TPPII and CCK mRNA show a similar distribution in rat and monkey brain, confirming and extending earlier studies in rodents. In addition, correlated levels of TPPII and CCK mRNA in human BA 10 corroborate a functional link between CCK and TPPII in the human brain.

Attentional performance is correlated with the local regional efficiency of intrinsic brain networks.

PubMed

Xu, Junhai; Yin, Xuntao; Ge, Haitao; Han, Yan; Pang, Zengchang; Tang, Yuchun; Liu, Baolin; Liu, Shuwei

2015-01-01

Attention is a crucial brain function for human beings. Using neuropsychological paradigms and task-based functional brain imaging, previous studies have indicated that widely distributed brain regions are engaged in three distinct attention subsystems: alerting, orienting and executive control (EC). Here, we explored the potential contribution of spontaneous brain activity to attention by examining whether resting-state activity could account for individual differences of the attentional performance in normal individuals. The resting-state functional images and behavioral data from attention network test (ANT) task were collected in 59 healthy subjects. Graph analysis was conducted to obtain the characteristics of functional brain networks and linear regression analyses were used to explore their relationships with behavioral performances of the three attentional components. We found that there was no significant relationship between the attentional performance and the global measures, while the attentional performance was associated with specific local regional efficiency. These regions related to the scores of alerting, orienting and EC largely overlapped with the regions activated in previous task-related functional imaging studies, and were consistent with the intrinsic dorsal and ventral attention networks (DAN/VAN). In addition, the strong associations between the attentional performance and specific regional efficiency suggested that there was a possible relationship between the DAN/VAN and task performances in the ANT. We concluded that the intrinsic activity of the human brain could reflect the processing efficiency of the attention system. Our findings revealed a robust evidence for the functional significance of the efficiently organized intrinsic brain network for highly productive cognitions and the hypothesized role of the DAN/VAN at rest.

Differentiating functional brain regions using optical coherence tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Gil, Daniel A.; Bow, Hansen C.; Shen, Jin-H.; Joos, Karen M.; Skala, Melissa C.

2017-02-01

The human brain is made up of functional regions governing movement, sensation, language, and cognition. Unintentional injury during neurosurgery can result in significant neurological deficits and morbidity. The current standard for localizing function to brain tissue during surgery, intraoperative electrical stimulation or recording, significantly increases the risk, time, and cost of the procedure. There is a need for a fast, cost-effective, and high-resolution intraoperative technique that can avoid damage to functional brain regions. We propose that optical coherence tomography (OCT) can fill this niche by imaging differences in the cellular composition and organization of functional brain areas. We hypothesized this would manifest as differences in the attenuation coefficient measured using OCT. Five functional regions (prefrontal, somatosensory, auditory, visual, and cerebellum) were imaged in ex vivo porcine brains (n=3), a model chosen due to a similar white/gray matter ratio as human brains. The attenuation coefficient was calculated using a depth-resolved model and quantitatively validated with Intralipid phantoms across a physiological range of attenuation coefficients (absolute difference < 0.1cm-1). Image analysis was performed on the attenuation coefficient images to derive quantitative endpoints. We observed a statistically significant difference among the median attenuation coefficients of these five regions (one-way ANOVA, p<0.05). Nissl-stained histology will be used to validate our results and correlate OCT-measured attenuation coefficients to neuronal density. Additional development and validation of OCT algorithms to discriminate brain regions are planned to improve the safety and efficacy of neurosurgical procedures such as biopsy, electrode placement, and tissue resection.

Structure-function relationships during segregated and integrated network states of human brain functional connectivity.

PubMed

Fukushima, Makoto; Betzel, Richard F; He, Ye; van den Heuvel, Martijn P; Zuo, Xi-Nian; Sporns, Olaf

2018-04-01

Structural white matter connections are thought to facilitate integration of neural information across functionally segregated systems. Recent studies have demonstrated that changes in the balance between segregation and integration in brain networks can be tracked by time-resolved functional connectivity derived from resting-state functional magnetic resonance imaging (rs-fMRI) data and that fluctuations between segregated and integrated network states are related to human behavior. However, how these network states relate to structural connectivity is largely unknown. To obtain a better understanding of structural substrates for these network states, we investigated how the relationship between structural connectivity, derived from diffusion tractography, and functional connectivity, as measured by rs-fMRI, changes with fluctuations between segregated and integrated states in the human brain. We found that the similarity of edge weights between structural and functional connectivity was greater in the integrated state, especially at edges connecting the default mode and the dorsal attention networks. We also demonstrated that the similarity of network partitions, evaluated between structural and functional connectivity, increased and the density of direct structural connections within modules in functional networks was elevated during the integrated state. These results suggest that, when functional connectivity exhibited an integrated network topology, structural connectivity and functional connectivity were more closely linked to each other and direct structural connections mediated a larger proportion of neural communication within functional modules. Our findings point out the possibility of significant contributions of structural connections to integrative neural processes underlying human behavior.

[Testosterone and psyche].

PubMed

Leiber, C; Wetterauer, U; Berner, M

2010-01-01

Testosterone, like other steroid hormones, crosses the blood-brain barrier, and the androgen receptor is present in most parts of the human brain. Therefore, testosterone has many effects on the psyche, mainly in men but also in women. Most often discussed is its influence on sexuality, especially on desire and sexual fantasies, spontaneous nighttime erections, sexual activity, and the number of orgasms and ejaculations. Mood and energy are also testosterone related. Testosterone deficiency in male patients can lead to depressive disorders. In the past, elevated testosterone levels were seen as responsible for strongly aggressive behaviour. Some cognitive functions (spatial and mathematical sense, verbal skills) are, at least to a certain point, testosterone related. Due to the extremely complex functioning of the human brain, a scientifically exact statement regarding the true relationship between testosterone and human behaviour is not possible. On the one hand, the cause is definitively multifactorial, but on the other, testosterone is metabolised in the brain, and the metabolites act by themselves. Furthermore, a bidirectional relationship exists between hormones and human behaviour: Human behaviour is influenced by hormones, and human behaviour also has a direct influence on the levels of many hormones in the human body. Finally, much data in this field are derived from animal studies; studies on humans cannot be conducted because of ethical reasons or scientific and technical problems.

Functional specificity in the human brain: A window into the functional architecture of the mind

PubMed Central

Kanwisher, Nancy

2010-01-01

Is the human mind/brain composed of a set of highly specialized components, each carrying out a specific aspect of human cognition, or is it more of a general-purpose device, in which each component participates in a wide variety of cognitive processes? For nearly two centuries, proponents of specialized organs or modules of the mind and brain—from the phrenologists to Broca to Chomsky and Fodor—have jousted with the proponents of distributed cognitive and neural processing—from Flourens to Lashley to McClelland and Rumelhart. I argue here that research using functional MRI is beginning to answer this long-standing question with new clarity and precision by indicating that at least a few specific aspects of cognition are implemented in brain regions that are highly specialized for that process alone. Cortical regions have been identified that are specialized not only for basic sensory and motor processes but also for the high-level perceptual analysis of faces, places, bodies, visually presented words, and even for the very abstract cognitive function of thinking about another person’s thoughts. I further consider the as-yet unanswered questions of how much of the mind and brain are made up of these functionally specialized components and how they arise developmentally. PMID:20484679

Recent Research into the Hemisphericity of the Human Brain and the Implications of Those Findings in the Teaching of Reading.

ERIC Educational Resources Information Center

McLendon, Gloria H.

Research data in neurosurgery, neuropsychology, and neurolinguistics indicate that the human brain is lateralized toward one of two methods of information processing, and that, in most humans, the language bias appears to be a left hemisphere function, while the visiospatial bias belongs to the right. Furthermore, the left hemisphere seems to…

Information flow between interacting human brains: Identification, validation, and relationship to social expertise.

PubMed

Bilek, Edda; Ruf, Matthias; Schäfer, Axel; Akdeniz, Ceren; Calhoun, Vince D; Schmahl, Christian; Demanuele, Charmaine; Tost, Heike; Kirsch, Peter; Meyer-Lindenberg, Andreas

2015-04-21

Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender's and receiver's temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions.

Biological and medical applications of a brain-on-a-chip

PubMed Central

2016-01-01

The desire to develop and evaluate drugs as potential countermeasures for biological and chemical threats requires test systems that can also substitute for the clinical trials normally crucial for drug development. Current animal models have limited predictivity for drug efficacy in humans as the large majority of drugs fails in clinical trials. We have limited understanding of the function of the central nervous system and the complexity of the brain, especially during development and neuronal plasticity. Simple in vitro systems do not represent physiology and function of the brain. Moreover, the difficulty of studying interactions between human genetics and environmental factors leads to lack of knowledge about the events that induce neurological diseases. Microphysiological systems (MPS) promise to generate more complex in vitro human models that better simulate the organ’s biology and function. MPS combine different cell types in a specific three-dimensional (3D) configuration to simulate organs with a concrete function. The final aim of these MPS is to combine different “organoids” to generate a human-on-a-chip, an approach that would allow studies of complex physiological organ interactions. The recent discovery of induced pluripotent stem cells (iPSCs) gives a range of possibilities allowing cellular studies of individuals with different genetic backgrounds (e.g., human disease models). Application of iPSCs from different donors in MPS gives the opportunity to better understand mechanisms of the disease and can be a novel tool in drug development, toxicology, and medicine. In order to generate a brain-on-a-chip, we have established a 3D model from human iPSCs based on our experience with a 3D rat primary aggregating brain model. After four weeks of differentiation, human 3D aggregates stain positive for different neuronal markers and show higher gene expression of various neuronal differentiation markers compared to 2D cultures. Here we present the applications and challenges of this emerging technology. PMID:24912505

A cellular perspective on brain energy metabolism and functional imaging.

PubMed

Magistretti, Pierre J; Allaman, Igor

2015-05-20

The energy demands of the brain are high: they account for at least 20% of the body's energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and point at a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales. Copyright © 2015 Elsevier Inc. All rights reserved.

Fluid and flexible minds: Intelligence reflects synchrony in the brain’s intrinsic network architecture

PubMed Central

Ferguson, Michael A.; Anderson, Jeffrey S.; Spreng, R. Nathan

2017-01-01

Human intelligence has been conceptualized as a complex system of dissociable cognitive processes, yet studies investigating the neural basis of intelligence have typically emphasized the contributions of discrete brain regions or, more recently, of specific networks of functionally connected regions. Here we take a broader, systems perspective in order to investigate whether intelligence is an emergent property of synchrony within the brain’s intrinsic network architecture. Using a large sample of resting-state fMRI and cognitive data (n = 830), we report that the synchrony of functional interactions within and across distributed brain networks reliably predicts fluid and flexible intellectual functioning. By adopting a whole-brain, systems-level approach, we were able to reliably predict individual differences in human intelligence by characterizing features of the brain’s intrinsic network architecture. These findings hold promise for the eventual development of neural markers to predict changes in intellectual function that are associated with neurodevelopment, normal aging, and brain disease.

Integration of fMRI, NIROT and ERP for studies of human brain function.

PubMed

Gore, John C; Horovitz, Silvina G; Cannistraci, Christopher J; Skudlarski, Pavel

2006-05-01

Different methods of assessing human brain function possess specific advantages and disadvantages compared to others, but it is believed that combining different approaches will provide greater information than can be obtained from each alone. For example, functional magnetic resonance imaging (fMRI) has good spatial resolution but poor temporal resolution, whereas the converse is true for electrophysiological recordings (event-related potentials or ERPs). In this review of recent work, we highlight a novel approach to combining these modalities in a manner designed to increase information on the origins and locations of the generators of specific ERPs and the relationship between fMRI and ERP signals. Near infrared imaging techniques have also been studied as alternatives to fMRI and can be readily integrated with simultaneous electrophysiological recordings. Each of these modalities may in principle be also used in so-called steady-state acquisitions in which the correlational structure of signals from the brain may be analyzed to provide new insights into brain function.

Nanotomography of brain networks

NASA Astrophysics Data System (ADS)

Saiga, Rino; Mizutani, Ryuta; Takekoshi, Susumu; Osawa, Motoki; Arai, Makoto; Takeuchi, Akihisa; Uesugi, Kentaro; Terada, Yasuko; Suzuki, Yoshio; de Andrade, Vincent; de Carlo, Francesco

The first step to understanding how the brain functions is to analyze its 3D network. The brain network consists of neurons having micrometer to nanometer sized structures. Therefore, 3D analysis of brain tissue at the relevant resolution is essential for elucidating brain's functional mechanisms. Here, we report 3D structures of human and fly brain networks revealed with synchrotron radiation nanotomography, or nano-CT. Neurons were stained with high-Z elements to visualize their structures with X-rays. Nano-CT experiments were then performed at the 32-ID beamline of the Advanced Photon Source, Argonne National Laboratory and at the BL37XU and BL47XU beamlines of SPring-8. Reconstructed 3D images illustrated precise structures of human neurons, including dendritic spines responsible for synaptic connections. The network of the fly brain hemisphere was traced to build a skeletonized wire model. An article reviewing our study appeared in MIT Technology Review. Movies of the obtained structures can be found in our YouTube channel.

Hemispherical map for the human brain cortex

NASA Astrophysics Data System (ADS)

Tosun, Duygu; Prince, Jerry L.

2001-07-01

Understanding the function of the human brain cortex is a primary goal in human brain mapping. Methods to unfold and flatten the cortical surface for visualization and measurement have been described in previous literature; but comparison across multiple subjects is still difficult because of the lack of a standard mapping technique. We describe a new approach that maps each hemisphere of the cortex to a portion of a sphere in a standard way, making comparison of anatomy and function across different subjects possible. Starting with a three-dimensional magnetic resonance image of the brain, the cortex is segmented and represented as a triangle mesh. Defining a cut around the corpus collosum identifies the left and right hemispheres. Together, the two hemispheres are mapped to the complex plane using a conformal mapping technique. A Mobius transformation, which is conformal, is used to transform the points on the complex plane so that a projective transformation maps each brain hemisphere onto a spherical segment comprising a sphere with a cap removed. We determined the best size of the spherical cap by minimizing the relative area distortion between hemispherical maps and original cortical surfaces. The relative area distortion between the hemispherical maps and the original cortical surfaces for fifteen human brains is analyzed.

The human sexual response cycle: brain imaging evidence linking sex to other pleasures.

PubMed

Georgiadis, J R; Kringelbach, M L

2012-07-01

Sexual behavior is critical to species survival, yet comparatively little is known about the neural mechanisms in the human brain. Here we systematically review the existing human brain imaging literature on sexual behavior and show that the functional neuroanatomy of sexual behavior is comparable to that involved in processing other rewarding stimuli. Sexual behavior clearly follows the established principles and phases for wanting, liking and satiety involved in the pleasure cycle of other rewards. The studies have uncovered the brain networks involved in sexual wanting or motivation/anticipation, as well as sexual liking or arousal/consummation, while there is very little data on sexual satiety or post-orgasmic refractory period. Human sexual behavior also interacts with other pleasures, most notably social interaction and high arousal states. We discuss the changes in the underlying brain networks supporting sexual behavior in the context of the pleasure cycle, the changes to this cycle over the individual's life-time and the interactions between them. Overall, it is clear from the data that the functional neuroanatomy of sex is very similar to that of other pleasures and that it is unlikely that there is anything special about the brain mechanisms and networks underlying sex. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hierarchical functional modularity in the resting-state human brain.

PubMed

Ferrarini, Luca; Veer, Ilya M; Baerends, Evelinda; van Tol, Marie-José; Renken, Remco J; van der Wee, Nic J A; Veltman, Dirk J; Aleman, André; Zitman, Frans G; Penninx, Brenda W J H; van Buchem, Mark A; Reiber, Johan H C; Rombouts, Serge A R B; Milles, Julien

2009-07-01

Functional magnetic resonance imaging (fMRI) studies have shown that anatomically distinct brain regions are functionally connected during the resting state. Basic topological properties in the brain functional connectivity (BFC) map have highlighted the BFC's small-world topology. Modularity, a more advanced topological property, has been hypothesized to be evolutionary advantageous, contributing to adaptive aspects of anatomical and functional brain connectivity. However, current definitions of modularity for complex networks focus on nonoverlapping clusters, and are seriously limited by disregarding inclusive relationships. Therefore, BFC's modularity has been mainly qualitatively investigated. Here, we introduce a new definition of modularity, based on a recently improved clustering measurement, which overcomes limitations of previous definitions, and apply it to the study of BFC in resting state fMRI of 53 healthy subjects. Results show hierarchical functional modularity in the brain. Copyright 2009 Wiley-Liss, Inc

The Brain's Versatile Toolbox.

ERIC Educational Resources Information Center

Pinker, Steven

1997-01-01

Considers the role of evolution and natural selection in the functioning of the modern human brain. Natural selection equipped humans with a mental toolbox of intuitive theories about the world which were used to master rocks, tools, plants, animals, and one another. The same toolbox is used today to master the intellectual challenges of modern…

Communication and the primate brain: insights from neuroimaging studies in humans, chimpanzees and macaques.

PubMed

Wilson, Benjamin; Petkov, Christopher I

2011-04-01

Considerable knowledge is available on the neural substrates for speech and language from brain-imaging studies in humans, but until recently there was a lack of data for comparison from other animal species on the evolutionarily conserved brain regions that process species-specific communication signals. To obtain new insights into the relationship of the substrates for communication in primates, we compared the results from several neuroimaging studies in humans with those that have recently been obtained from macaque monkeys and chimpanzees. The recent work in humans challenges the longstanding notion of highly localized speech areas. As a result, the brain regions that have been identified in humans for speech and nonlinguistic voice processing show a striking general correspondence to how the brains of other primates analyze species-specific vocalizations or information in the voice, such as voice identity. The comparative neuroimaging work has begun to clarify evolutionary relationships in brain function, supporting the notion that the brain regions that process communication signals in the human brain arose from a precursor network of regions that is present in nonhuman primates and is used for processing species-specific vocalizations. We conclude by considering how the stage now seems to be set for comparative neurobiology to characterize the ancestral state of the network that evolved in humans to support language.

Ascorbic acid, cognitive function, and Alzheimer’s disease: a current review and future direction

PubMed Central

Bowman, Gene L.

2013-01-01

This narrative review appraises the human and animal studies implicating ascorbic acid (AA) in normal cognitive function and Alzheimer’s disease. A research framework for how nutrition affects brain aging is proposed with emphasis on AA intake, status, metabolism, and transport into brain tissue. A final synopsis highlights areas for future research regarding AA nourishment and healthy brain aging. PMID:22419527

Left brain, right brain: facts and fantasies.

PubMed

Corballis, Michael C

2014-01-01

Handedness and brain asymmetry are widely regarded as unique to humans, and associated with complementary functions such as a left-brain specialization for language and logic and a right-brain specialization for creativity and intuition. In fact, asymmetries are widespread among animals, and support the gradual evolution of asymmetrical functions such as language and tool use. Handedness and brain asymmetry are inborn and under partial genetic control, although the gene or genes responsible are not well established. Cognitive and emotional difficulties are sometimes associated with departures from the "norm" of right-handedness and left-brain language dominance, more often with the absence of these asymmetries than their reversal.

Hemispheric Asymmetry of Visual Scene Processing in the Human Brain: Evidence from Repetition Priming and Intrinsic Activity

PubMed Central

Kahn, Itamar; Wig, Gagan S.; Schacter, Daniel L.

2012-01-01

Asymmetrical specialization of cognitive processes across the cerebral hemispheres is a hallmark of healthy brain development and an important evolutionary trait underlying higher cognition in humans. While previous research, including studies of priming, divided visual field presentation, and split-brain patients, demonstrates a general pattern of right/left asymmetry of form-specific versus form-abstract visual processing, little is known about brain organization underlying this dissociation. Here, using repetition priming of complex visual scenes and high-resolution functional magnetic resonance imaging (MRI), we demonstrate asymmetrical form specificity of visual processing between the right and left hemispheres within a region known to be critical for processing of visual spatial scenes (parahippocampal place area [PPA]). Next, we use resting-state functional connectivity MRI analyses to demonstrate that this functional asymmetry is associated with differential intrinsic activity correlations of the right versus left PPA with regions critically involved in perceptual versus conceptual processing, respectively. Our results demonstrate that the PPA comprises lateralized subregions across the cerebral hemispheres that are engaged in functionally dissociable yet complementary components of visual scene analysis. Furthermore, this functional asymmetry is associated with differential intrinsic functional connectivity of the PPA with distinct brain areas known to mediate dissociable cognitive processes. PMID:21968568

Hemispheric asymmetry of visual scene processing in the human brain: evidence from repetition priming and intrinsic activity.

PubMed

Stevens, W Dale; Kahn, Itamar; Wig, Gagan S; Schacter, Daniel L

2012-08-01

Asymmetrical specialization of cognitive processes across the cerebral hemispheres is a hallmark of healthy brain development and an important evolutionary trait underlying higher cognition in humans. While previous research, including studies of priming, divided visual field presentation, and split-brain patients, demonstrates a general pattern of right/left asymmetry of form-specific versus form-abstract visual processing, little is known about brain organization underlying this dissociation. Here, using repetition priming of complex visual scenes and high-resolution functional magnetic resonance imaging (MRI), we demonstrate asymmetrical form specificity of visual processing between the right and left hemispheres within a region known to be critical for processing of visual spatial scenes (parahippocampal place area [PPA]). Next, we use resting-state functional connectivity MRI analyses to demonstrate that this functional asymmetry is associated with differential intrinsic activity correlations of the right versus left PPA with regions critically involved in perceptual versus conceptual processing, respectively. Our results demonstrate that the PPA comprises lateralized subregions across the cerebral hemispheres that are engaged in functionally dissociable yet complementary components of visual scene analysis. Furthermore, this functional asymmetry is associated with differential intrinsic functional connectivity of the PPA with distinct brain areas known to mediate dissociable cognitive processes.

Neuronal Correlation Parameter and the Idea of Thermodynamic Entropy of an N-Body Gravitationally Bounded System.

PubMed

Haranas, Ioannis; Gkigkitzis, Ioannis; Kotsireas, Ilias; Austerlitz, Carlos

2017-01-01

Understanding how the brain encodes information and performs computation requires statistical and functional analysis. Given the complexity of the human brain, simple methods that facilitate the interpretation of statistical correlations among different brain regions can be very useful. In this report we introduce a numerical correlation measure that may serve the interpretation of correlational neuronal data, and may assist in the evaluation of different brain states. The description of the dynamical brain system, through a global numerical measure may indicate the presence of an action principle which may facilitate a application of physics principles in the study of the human brain and cognition.

Mapping the human brain during a specific Vojta's tactile input: the ipsilateral putamen's role.

PubMed

Sanz-Esteban, Ismael; Calvo-Lobo, Cesar; Ríos-Lago, Marcos; Álvarez-Linera, Juan; Muñoz-García, Daniel; Rodríguez-Sanz, David

2018-03-01

A century of research in human brain parcellation has demonstrated that different brain areas are associated with functional tasks. New neuroscientist perspectives to achieve the parcellation of the human brain have been developed to know the brain areas activation and its relationship with different stimuli. This descriptive study aimed to compare brain regions activation by specific tactile input (STI) stimuli according to the Vojta protocol (STI-group) to a non-STI stimulation (non-STI-group). An exploratory functional magnetic resonance imaging (fMRI) study was performed. The 2 groups of participants were passively stimulated by an expert physical therapist using the same paradigm structure, although differing in the place of stimulation. The stimulation was presented to participants using a block design in all cases. A sample of 16 healthy participants, 5 men and 11 women, with mean age 31.31 ± 8.13 years was recruited. Indeed, 12 participants were allocated in the STI-group and 4 participants in the non-STI-group. fMRI was used to map the human brain in vivo while these tactile stimuli were being applied. Data were analyzed using a general linear model in SPM12 implemented in MATLAB. Differences between groups showed a greater activation in the right cortical areas (temporal and frontal lobes), subcortical regions (thalamus, brainstem, and basal nuclei), and in the cerebellum (anterior lobe). STI-group had specific difference brain activation areas, such as the ipsilateral putamen. Future studies should study clinical implications in neurorehabilitation patients.

Researching and Reducing the Health Burden of Stroke

MedlinePlus

... the result of continuing research to map the brain and interface it with a computer to enable stroke patients to regain function. How important is the new effort to map the human brain? The brain is more complex than any computer ...

Two distinct forms of functional lateralization in the human brain

PubMed Central

Gotts, Stephen J.; Jo, Hang Joon; Wallace, Gregory L.; Saad, Ziad S.; Cox, Robert W.; Martin, Alex

2013-01-01

The hemispheric lateralization of certain faculties in the human brain has long been held to be beneficial for functioning. However, quantitative relationships between the degree of lateralization in particular brain regions and the level of functioning have yet to be established. Here we demonstrate that two distinct forms of functional lateralization are present in the left vs. the right cerebral hemisphere, with the left hemisphere showing a preference to interact more exclusively with itself, particularly for cortical regions involved in language and fine motor coordination. In contrast, right-hemisphere cortical regions involved in visuospatial and attentional processing interact in a more integrative fashion with both hemispheres. The degree of lateralization present in these distinct systems selectively predicted behavioral measures of verbal and visuospatial ability, providing direct evidence that lateralization is associated with enhanced cognitive ability. PMID:23959883

Functional acetylcholine muscarinic receptor subtypes in human brain microcirculation: identification and cellular localization.

PubMed

Elhusseiny, A; Cohen, Z; Olivier, A; Stanimirović, D B; Hamel, E

1999-07-01

Acetylcholine is an important regulator of local cerebral blood flow. There is, however, limited information available on the possible sites of action of this neurotransmitter on brain intraparenchymal microvessels. In this study, a combination of molecular and functional approaches was used to identify which of the five muscarinic acetylcholine receptors (mAChR) are present in human brain microvessels and their intimately associated astroglial cells. Microvessel and capillary fractions isolated from human cerebral cortex were found by reverse transcriptase-polymerase chain reaction to express m2, m3, and, occasionally, m1 and m5 receptor subtypes. To localize these receptors to a specific cellular compartment of the vessel wall, cultures of human brain microvascular endothelial and smooth muscle cells were used, together with cultured human brain astrocytes. Endothelial cells invariably expressed m2 and m5 receptors, and occasionally the m1 receptor; smooth muscle cells exhibited messages for all except the m4 mAChR subtypes, whereas messages for all five muscarinic receptors were identified in astrocytes. In all three cell types studied, acetylcholine induced a pirenzepine-sensitive increase (62% to 176%, P<0.05 to 0.01) in inositol trisphosphate, suggesting functional coupling of m1, m3, or m5 mAChR to a phospholipase C signaling cascade. Similarly, coupling of m2 or m4 mAChR to adenylate cyclase inhibition in endothelial cells and astrocytes, but not in smooth muscle cells, was demonstrated by the ability of carbachol to significantly reduce (44% to 50%, P<0.05 to 0.01) the forskolin-stimulated increase in cAMP levels. This effect was reversed by the mAChR antagonist AFDX 384. The results indicate that microvessels are able to respond to neurally released acetylcholine and that mAChR, distributed in different vascular and astroglial compartments, could regulate cortical perfusion and, possibly, blood-brain barrier permeability, functions that could become jeopardized in neurodegenerative disorders such as Alzheimer's disease.

Evidence for a double dissociation of articulatory rehearsal and non-articulatory maintenance of phonological information in human verbal working memory.

PubMed

Trost, Sarah; Gruber, Oliver

2012-01-01

Recent functional neuroimaging studies have provided evidence that human verbal working memory is represented by two complementary neural systems, a left lateralized premotor-parietal network implementing articulatory rehearsal and a presumably phylogenetically older bilateral anterior-prefrontal/inferior-parietal network subserving non-articulatory maintenance of phonological information. In order to corroborate these findings from functional neuroimaging, we performed a targeted behavioural study in patients with very selective and circumscribed brain lesions to key regions suggested to support these different subcomponents of human verbal working memory. Within a sample of over 500 neurological patients assessed with high-resolution structural magnetic resonance imaging, we identified 2 patients with corresponding brain lesions, one with an isolated lesion to Broca's area and the other with a selective lesion bilaterally to the anterior middle frontal gyrus. These 2 patients as well as groups of age-matched healthy controls performed two circuit-specific verbal working memory tasks. In this way, we systematically assessed the hypothesized selective behavioural effects of these brain lesions on the different subcomponents of verbal working memory in terms of a double dissociation. Confirming prior findings, the lesion to Broca's area led to reduced performance under articulatory rehearsal, whereas the non-articulatory maintenance of phonological information was unimpaired. Conversely, the bifrontopolar brain lesion was associated with impaired non-articulatory phonological working memory, whereas performance under articulatory rehearsal was unaffected. The present experimental neuropsychological study in patients with specific and circumscribed brain lesions confirms the hypothesized double dissociation of two complementary brain systems underlying verbal working memory in humans. In particular, the results demonstrate the functional relevance of the anterior prefrontal cortex for non-articulatory maintenance of phonological information and, in this way, provide further support for the evolutionary-based functional-neuroanatomical model of human working memory. Copyright © 2012 S. Karger AG, Basel.

Functional Neuroimaging Insights into the Physiology of Human Sleep

PubMed Central

Dang-Vu, Thien Thanh; Schabus, Manuel; Desseilles, Martin; Sterpenich, Virginie; Bonjean, Maxime; Maquet, Pierre

2010-01-01

Functional brain imaging has been used in humans to noninvasively investigate the neural mechanisms underlying the generation of sleep stages. On the one hand, REM sleep has been associated with the activation of the pons, thalamus, limbic areas, and temporo-occipital cortices, and the deactivation of prefrontal areas, in line with theories of REM sleep generation and dreaming properties. On the other hand, during non-REM (NREM) sleep, decreases in brain activity have been consistently found in the brainstem, thalamus, and in several cortical areas including the medial prefrontal cortex (MPFC), in agreement with a homeostatic need for brain energy recovery. Benefiting from a better temporal resolution, more recent studies have characterized the brain activations related to phasic events within specific sleep stages. In particular, they have demonstrated that NREM sleep oscillations (spindles and slow waves) are indeed associated with increases in brain activity in specific subcortical and cortical areas involved in the generation or modulation of these waves. These data highlight that, even during NREM sleep, brain activity is increased, yet regionally specific and transient. Besides refining the understanding of sleep mechanisms, functional brain imaging has also advanced the description of the functional properties of sleep. For instance, it has been shown that the sleeping brain is still able to process external information and even detect the pertinence of its content. The relationship between sleep and memory has also been refined using neuroimaging, demonstrating post-learning reactivation during sleep, as well as the reorganization of memory representation on the systems level, sometimes with long-lasting effects on subsequent memory performance. Further imaging studies should focus on clarifying the role of specific sleep patterns for the processing of external stimuli, as well as the consolidation of freshly encoded information during sleep. Citation: Dang-Vu TT; Schabus M; Desseilles M; Sterpenich V; Bonjean M; Maquet P. Functional neuroimaging insights into the physiology of human sleep. SLEEP 2010;33(12):1589-1603. PMID:21120121

Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons.

PubMed

Jo, Junghyun; Xiao, Yixin; Sun, Alfred Xuyang; Cukuroglu, Engin; Tran, Hoang-Dai; Göke, Jonathan; Tan, Zi Ying; Saw, Tzuen Yih; Tan, Cheng-Peow; Lokman, Hidayat; Lee, Younghwan; Kim, Donghoon; Ko, Han Seok; Kim, Seong-Oh; Park, Jae Hyeon; Cho, Nam-Joon; Hyde, Thomas M; Kleinman, Joel E; Shin, Joo Heon; Weinberger, Daniel R; Tan, Eng King; Je, Hyunsoo Shawn; Ng, Huck-Hui

2016-08-04

Recent advances in 3D culture systems have led to the generation of brain organoids that resemble different human brain regions; however, a 3D organoid model of the midbrain containing functional midbrain dopaminergic (mDA) neurons has not been reported. We developed a method to differentiate human pluripotent stem cells into a large multicellular organoid-like structure that contains distinct layers of neuronal cells expressing characteristic markers of human midbrain. Importantly, we detected electrically active and functionally mature mDA neurons and dopamine production in our 3D midbrain-like organoids (MLOs). In contrast to human mDA neurons generated using 2D methods or MLOs generated from mouse embryonic stem cells, our human MLOs produced neuromelanin-like granules that were structurally similar to those isolated from human substantia nigra tissues. Thus our MLOs bearing features of the human midbrain may provide a tractable in vitro system to study the human midbrain and its related diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Hyperspectral functional imaging of the human brain

NASA Astrophysics Data System (ADS)

Toronov, Vladislav; Schelkanova, Irina

2013-03-01

We performed the independent component analysis of the hyperspectral functional near-infrared data acquired on humans during exercise and rest. We found that the hyperspectral functional data acquired on the human brain requires only two physiologically meaningful components to cover more than 50% o the temporal variance in hundreds of wavelengths. The analysis of the spectra of independent components showed that these components could be interpreted as results of changes in the cerebral blood volume and blood flow. Also, we found significant contributions of water and cytochrome c oxydase into changes associated with the independent components. Another remarkable effect of ICA was its good performance in terms of the filtering of the data noise.

Linking brains and brawn: exercise and the evolution of human neurobiology.

PubMed

Raichlen, David A; Polk, John D

2013-01-07

The hunting and gathering lifestyle adopted by human ancestors around 2 Ma required a large increase in aerobic activity. High levels of physical activity altered the shape of the human body, enabling access to new food resources (e.g. animal protein) in a changing environment. Recent experimental work provides strong evidence that both acute bouts of exercise and long-term exercise training increase the size of brain components and improve cognitive performance in humans and other taxa. However, to date, researchers have not explored the possibility that the increases in aerobic capacity and physical activity that occurred during human evolution directly influenced the human brain. Here, we hypothesize that proximate mechanisms linking physical activity and neurobiology in living species may help to explain changes in brain size and cognitive function during human evolution. We review evidence that selection acting on endurance increased baseline neurotrophin and growth factor signalling (compounds responsible for both brain growth and for metabolic regulation during exercise) in some mammals, which in turn led to increased overall brain growth and development. This hypothesis suggests that a significant portion of human neurobiology evolved due to selection acting on features unrelated to cognitive performance.

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

PubMed

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

2018-01-01

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

[Factor structure of regional CBF and CMRglu values as a tool for the study of default mode of the brain].

PubMed

Kataev, G V; Korotkov, A D; Kireev, M V; Medvedev, S V

2013-01-01

In the present article it was shown that the functional connectivity of brain structures, revealed by factor analysis of resting PET CBF and rCMRglu data, is an adequate tool to study the default mode of the human brain. The identification of neuroanatomic systems of default mode (default mode network) during routine clinical PET investigations is important for further studying the functional organization of the normal brain and its reorganizations in pathological conditions.

Dynamic Multi-Coil Shimming of the Human Brain at 7 Tesla

PubMed Central

Juchem, Christoph; Nixon, Terence W.; McIntyre, Scott; Boer, Vincent O.; Rothman, Douglas L.; de Graaf, Robin A.

2011-01-01

High quality magnetic field homogenization of the human brain (i.e. shimming) for MR imaging and spectroscopy is a demanding task. The susceptibility differences between air and tissue are a longstanding problem as they induce complex field distortions in the prefrontal cortex and the temporal lobes. To date, the theoretical gains of high field MR have only been realized partially in the human brain due to limited magnetic field homogeneity. A novel shimming technique for the human brain is presented that is based on the combination of non-orthogonal basis fields from 48 individual, circular coils. Custom-built amplifier electronics enabled the dynamic application of the multi-coil shim fields in a slice-specific fashion. Dynamic multi-coil (DMC) shimming is shown to eliminate most of the magnetic field inhomogeneity apparent in the human brain at 7 Tesla and provided improved performance compared to state-of-the-art dynamic shim updating with zero through third order spherical harmonic functions. The novel technique paves the way for high field MR applications of the human brain for which excellent magnetic field homogeneity is a prerequisite. PMID:21824794

Disrupted Brain Functional Organization in Epilepsy Revealed by Graph Theory Analysis.

PubMed

Song, Jie; Nair, Veena A; Gaggl, Wolfgang; Prabhakaran, Vivek

2015-06-01

The human brain is a complex and dynamic system that can be modeled as a large-scale brain network to better understand the reorganizational changes secondary to epilepsy. In this study, we developed a brain functional network model using graph theory methods applied to resting-state fMRI data acquired from a group of epilepsy patients and age- and gender-matched healthy controls. A brain functional network model was constructed based on resting-state functional connectivity. A minimum spanning tree combined with proportional thresholding approach was used to obtain sparse connectivity matrices for each subject, which formed the basis of brain networks. We examined the brain reorganizational changes in epilepsy thoroughly at the level of the whole brain, the functional network, and individual brain regions. At the whole-brain level, local efficiency was significantly decreased in epilepsy patients compared with the healthy controls. However, global efficiency was significantly increased in epilepsy due to increased number of functional connections between networks (although weakly connected). At the functional network level, there were significant proportions of newly formed connections between the default mode network and other networks and between the subcortical network and other networks. There was a significant proportion of decreasing connections between the cingulo-opercular task control network and other networks. Individual brain regions from different functional networks, however, showed a distinct pattern of reorganizational changes in epilepsy. These findings suggest that epilepsy alters brain efficiency in a consistent pattern at the whole-brain level, yet alters brain functional networks and individual brain regions differently.

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

PubMed

Glorioso, Christin; Sibille, Etienne

2011-02-01

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

Distinct Neurocognitive Strategies for Comprehensions of Human and Artificial Intelligence

PubMed Central

Ge, Jianqiao; Han, Shihui

2008-01-01

Although humans have inevitably interacted with both human and artificial intelligence in real life situations, it is unknown whether the human brain engages homologous neurocognitive strategies to cope with both forms of intelligence. To investigate this, we scanned subjects, using functional MRI, while they inferred the reasoning processes conducted by human agents or by computers. We found that the inference of reasoning processes conducted by human agents but not by computers induced increased activity in the precuneus but decreased activity in the ventral medial prefrontal cortex and enhanced functional connectivity between the two brain areas. The findings provide evidence for distinct neurocognitive strategies of taking others' perspective and inhibiting the process referenced to the self that are specific to the comprehension of human intelligence. PMID:18665211

Determination of Death: A Scientific Perspective on Biological Integration

PubMed Central

Condic, Maureen L.

2016-01-01

Human life is operationally defined by the onset and cessation of organismal function. At postnatal stages of life, organismal integration critically and uniquely requires a functioning brain. In this article, a distinction is drawn between integrated and coordinated biologic activities. While communication between cells can provide a coordinated biologic response to specific signals, it does not support the integrated function that is characteristic of a living human being. Determining the loss of integrated function can be complicated by medical interventions (i.e., “life support”) that uncouple elements of the natural biologic hierarchy underlying our intuitive understanding of death. Such medical interventions can allow living human beings who are no longer able to function in an integrated manner to be maintained in a living state. In contrast, medical intervention can also allow the cells and tissues of an individual who has died to be maintained in a living state. To distinguish between a living human being and living human cells, two criteria are proposed: either the persistence of any form of brain function or the persistence of autonomous integration of vital functions. Either of these criteria is sufficient to determine a human being is alive. PMID:27075193

Non-coding-regulatory regions of human brain genes delineated by bacterial artificial chromosome knock-in mice.

PubMed

Schmouth, Jean-François; Castellarin, Mauro; Laprise, Stéphanie; Banks, Kathleen G; Bonaguro, Russell J; McInerny, Simone C; Borretta, Lisa; Amirabbasi, Mahsa; Korecki, Andrea J; Portales-Casamar, Elodie; Wilson, Gary; Dreolini, Lisa; Jones, Steven J M; Wasserman, Wyeth W; Goldowitz, Daniel; Holt, Robert A; Simpson, Elizabeth M

2013-10-14

The next big challenge in human genetics is understanding the 98% of the genome that comprises non-coding DNA. Hidden in this DNA are sequences critical for gene regulation, and new experimental strategies are needed to understand the functional role of gene-regulation sequences in health and disease. In this study, we build upon our HuGX ('high-throughput human genes on the X chromosome') strategy to expand our understanding of human gene regulation in vivo. In all, ten human genes known to express in therapeutically important brain regions were chosen for study. For eight of these genes, human bacterial artificial chromosome clones were identified, retrofitted with a reporter, knocked single-copy into the Hprt locus in mouse embryonic stem cells, and mouse strains derived. Five of these human genes expressed in mouse, and all expressed in the adult brain region for which they were chosen. This defined the boundaries of the genomic DNA sufficient for brain expression, and refined our knowledge regarding the complexity of gene regulation. We also characterized for the first time the expression of human MAOA and NR2F2, two genes for which the mouse homologs have been extensively studied in the central nervous system (CNS), and AMOTL1 and NOV, for which roles in CNS have been unclear. We have demonstrated the use of the HuGX strategy to functionally delineate non-coding-regulatory regions of therapeutically important human brain genes. Our results also show that a careful investigation, using publicly available resources and bioinformatics, can lead to accurate predictions of gene expression.

Brain Entropy Mapping Using fMRI

PubMed Central

Wang, Ze; Li, Yin; Childress, Anna Rose; Detre, John A.

2014-01-01

Entropy is an important trait for life as well as the human brain. Characterizing brain entropy (BEN) may provide an informative tool to assess brain states and brain functions. Yet little is known about the distribution and regional organization of BEN in normal brain. The purpose of this study was to examine the whole brain entropy patterns using a large cohort of normal subjects. A series of experiments were first performed to validate an approximate entropy measure regarding its sensitivity, specificity, and reliability using synthetic data and fMRI data. Resting state fMRI data from a large cohort of normal subjects (n = 1049) from multi-sites were then used to derive a 3-dimensional BEN map, showing a sharp low-high entropy contrast between the neocortex and the rest of brain. The spatial heterogeneity of resting BEN was further studied using a data-driven clustering method, and the entire brain was found to be organized into 7 hierarchical regional BEN networks that are consistent with known structural and functional brain parcellations. These findings suggest BEN mapping as a physiologically and functionally meaningful measure for studying brain functions. PMID:24657999

Drugs, Biogenic Amine Targets and the Developing Brain

PubMed Central

Frederick, Aliya L.; Stanwood, Gregg D.

2009-01-01

Defects in the development of the brain have profound impacts on mature brain functions and underlie psychopathology. Classical neurotransmitters and neuromodulators, such as dopamine, serotonin, norepinephrine, acetycholine, glutamate and GABA, have pleiotropic effects during brain development. In other words, these molecules produce multiple, diverse effects to serve as regulators of distinct cellular functions at different times in neurodevelopment. These systems are impacted upon by a variety of illicit drugs of abuse, neurotherapeutics, and environmental contaminants. In this review, we describe the impact of drugs and chemicals on brain formation and function in animal models and in human populations, highlighting sensitive periods and effects that may not emerge until later in life. PMID:19372683

Carbohydrates as a cerebral metabolic fuel.

PubMed

Evans, M; Amiel, S A

1998-03-01

The human brain is an extremely active metabolic organ with little endogenous stores of energy. It is thus dependent on circulating glucose to fuel metabolism and support cognitive functioning. However there is growing evidence that the human brain is able to utilise other non-glucose fuels during times of glucose lack. We review the evidence for the potential of the human brain to use the alternate fuels lactate and beta-hydroxybutyrate, and some recent studies examining the ability of regions of brain to use non-glucose lipid fuels. The human brain does not seem to have the ability to use the gluconeogenic precursor alanine to any significant degree. Regionality within the brain can be examined in vivo by the use of positron emission tomography, which offers the exciting prospect of studying human brain metabolism in vivo using a simple and non-interventional technique. Increased understanding of the brain's metabolism, the way in which hypoglycaemia is recognised and the manner in which this can be altered in the syndrome of hypoglycaemia unawareness and deficient counterregulation will help develop further strategies to prevent the clinical problems associated with hypoglycaemia in insulin-dependent diabetic adults and children.

Probabilistic map of critical functional regions of the human cerebral cortex: Broca's area revisited.

PubMed

Tate, Matthew C; Herbet, Guillaume; Moritz-Gasser, Sylvie; Tate, Joseph E; Duffau, Hugues

2014-10-01

The organization of basic functions of the human brain, particularly in the right hemisphere, remains poorly understood. Recent advances in functional neuroimaging have improved our understanding of cortical organization but do not allow for direct interrogation or determination of essential (versus participatory) cortical regions. Direct cortical stimulation represents a unique opportunity to provide novel insights into the functional distribution of critical epicentres. Direct cortical stimulation (bipolar, 60 Hz, 1-ms pulse) was performed in 165 consecutive patients undergoing awake mapping for resection of low-grade gliomas. Tasks included motor, sensory, counting, and picture naming. Stimulation sites eliciting positive (sensory/motor) or negative (speech arrest, dysarthria, anomia, phonological and semantic paraphasias) findings were recorded and mapped onto a standard Montreal Neurological Institute brain atlas. Montreal Neurological Institute-space functional data were subjected to cluster analysis algorithms (K-means, partition around medioids, hierarchical Ward) to elucidate crucial network epicentres. Sensorimotor function was observed in the pre/post-central gyri as expected. Articulation epicentres were also found within the pre/post-central gyri. However, speech arrest localized to ventral premotor cortex, not the classical Broca's area. Anomia/paraphasia data demonstrated foci not only within classical Wernicke's area but also within the middle and inferior frontal gyri. We report the first bilateral probabilistic map for crucial cortical epicentres of human brain functions in the right and left hemispheres, including sensory, motor, and language (speech, articulation, phonology and semantics). These data challenge classical theories of brain organization (e.g. Broca's area as speech output region) and provide a distributed framework for future studies of neural networks. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mapping the functional connectome traits of levels of consciousness.

PubMed

Amico, Enrico; Marinazzo, Daniele; Di Perri, Carol; Heine, Lizette; Annen, Jitka; Martial, Charlotte; Dzemidzic, Mario; Kirsch, Murielle; Bonhomme, Vincent; Laureys, Steven; Goñi, Joaquín

2017-03-01

Examining task-free functional connectivity (FC) in the human brain offers insights on how spontaneous integration and segregation of information relate to human cognition, and how this organization may be altered in different conditions, and neurological disorders. This is particularly relevant for patients in disorders of consciousness (DOC) following severe acquired brain damage and coma, one of the most devastating conditions in modern medical care. We present a novel data-driven methodology, connICA, which implements Independent Component Analysis (ICA) for the extraction of robust independent FC patterns (FC-traits) from a set of individual functional connectomes, without imposing any a priori data stratification into groups. We here apply connICA to investigate associations between network traits derived from task-free FC and cognitive/clinical features that define levels of consciousness. Three main independent FC-traits were identified and linked to consciousness-related clinical features. The first one represents the functional configuration of a "resting" human brain, and it is associated to a sedative (sevoflurane), the overall effect of the pathology and the level of arousal. The second FC-trait reflects the disconnection of the visual and sensory-motor connectivity patterns. It also relates to the time since the insult and to the ability of communicating with the external environment. The third FC-trait isolates the connectivity pattern encompassing the fronto-parietal and the default-mode network areas as well as the interaction between left and right hemispheres, which are also associated to the awareness of the self and its surroundings. Each FC-trait represents a distinct functional process with a role in the degradation of conscious states of functional brain networks, shedding further light on the functional sub-circuits that get disrupted in severe brain-damage. Copyright © 2017. Published by Elsevier Inc.

Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain

PubMed Central

Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

2013-01-01

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain. PMID:23440889

Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain.

PubMed

Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

2013-01-01

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain.

Insights into Human Behavior from Lesions to the Prefrontal Cortex

PubMed Central

Szczepanski, Sara M.; Knight, Robert T.

2014-01-01

SUMMARY The prefrontal cortex (PFC), a cortical region that was once thought to be functionally insignificant, is now known to play an essential role in the organization and control of goal-directed thought and behavior. Neuroimaging, neurophysiological, and modeling techniques have lead to tremendous advances in our understanding of PFC functions over the last few decades. It should be noted, however, that neurological, neuropathological, and neuropsychological studies have contributed some of the most essential, historical, and often prescient, conclusions regarding the functions of this region. Importantly, examination of patients with brain damage allows one to draw conclusions about whether a brain area is necessary for a particular function. Here, we provide a broad overview of PFC functions based upon behavioral and neural changes resulting from damage to PFC in both human patients and non-human primates. PMID:25175878

The Human BNST: Functional Role in Anxiety and Addiction

PubMed Central

Avery, S N; Clauss, J A; Blackford, J U

2016-01-01

The consequences of chronic stress on brain structure and function are far reaching. Whereas stress can produce short-term adaptive changes in the brain, chronic stress leads to long-term maladaptive changes that increase vulnerability to psychiatric disorders, such as anxiety and addiction. These two disorders are the most prevalent psychiatric disorders in the United States, and are typically chronic, disabling, and highly comorbid. Emerging evidence implicates a tiny brain region—the bed nucleus of the stria terminalis (BNST)—in the body's stress response and in anxiety and addiction. Rodent studies provide compelling evidence that the BNST plays a central role in sustained threat monitoring, a form of adaptive anxiety, and in the withdrawal and relapse stages of addiction; however, little is known about the role of BNST in humans. Here, we review current evidence for BNST function in humans, including evidence for a role in the production of both adaptive and maladaptive anxiety. We also review preliminary evidence of the role of BNST in addiction in humans. Together, these studies provide a foundation of knowledge about the role of BNST in adaptive anxiety and stress-related disorders. Although the field is in its infancy, future investigations of human BNST function have tremendous potential to illuminate mechanisms underlying stress-related disorders and identify novel neural targets for treatment. PMID:26105138

The Human BNST: Functional Role in Anxiety and Addiction.

PubMed

Avery, S N; Clauss, J A; Blackford, J U

2016-01-01

The consequences of chronic stress on brain structure and function are far reaching. Whereas stress can produce short-term adaptive changes in the brain, chronic stress leads to long-term maladaptive changes that increase vulnerability to psychiatric disorders, such as anxiety and addiction. These two disorders are the most prevalent psychiatric disorders in the United States, and are typically chronic, disabling, and highly comorbid. Emerging evidence implicates a tiny brain region-the bed nucleus of the stria terminalis (BNST)-in the body's stress response and in anxiety and addiction. Rodent studies provide compelling evidence that the BNST plays a central role in sustained threat monitoring, a form of adaptive anxiety, and in the withdrawal and relapse stages of addiction; however, little is known about the role of BNST in humans. Here, we review current evidence for BNST function in humans, including evidence for a role in the production of both adaptive and maladaptive anxiety. We also review preliminary evidence of the role of BNST in addiction in humans. Together, these studies provide a foundation of knowledge about the role of BNST in adaptive anxiety and stress-related disorders. Although the field is in its infancy, future investigations of human BNST function have tremendous potential to illuminate mechanisms underlying stress-related disorders and identify novel neural targets for treatment.

Prefrontal Brain Activity Predicts Temporally Extended Decision-Making Behavior

ERIC Educational Resources Information Center

Yarkoni, Tal; Braver, Todd S.; Gray, Jeremy R.; Green, Leonard

2005-01-01

Although functional neuroimaging studies of human decision-making processes are increasingly common, most of the research in this area has relied on passive tasks that generate little individual variability. Relatively little attention has been paid to the ability of brain activity to predict overt behavior. Using functional magnetic resonance…

Function and regulation of AUTS2, a gene implicated in autism and human evolution.

PubMed

Oksenberg, Nir; Stevison, Laurie; Wall, Jeffrey D; Ahituv, Nadav

2013-01-01

Nucleotide changes in the AUTS2 locus, some of which affect only noncoding regions, are associated with autism and other neurological disorders, including attention deficit hyperactivity disorder, epilepsy, dyslexia, motor delay, language delay, visual impairment, microcephaly, and alcohol consumption. In addition, AUTS2 contains the most significantly accelerated genomic region differentiating humans from Neanderthals, which is primarily composed of noncoding variants. However, the function and regulation of this gene remain largely unknown. To characterize auts2 function, we knocked it down in zebrafish, leading to a smaller head size, neuronal reduction, and decreased mobility. To characterize AUTS2 regulatory elements, we tested sequences for enhancer activity in zebrafish and mice. We identified 23 functional zebrafish enhancers, 10 of which were active in the brain. Our mouse enhancer assays characterized three mouse brain enhancers that overlap an ASD-associated deletion and four mouse enhancers that reside in regions implicated in human evolution, two of which are active in the brain. Combined, our results show that AUTS2 is important for neurodevelopment and expose candidate enhancer sequences in which nucleotide variation could lead to neurological disease and human-specific traits.

An Adaptive Complex Network Model for Brain Functional Networks

PubMed Central

Gomez Portillo, Ignacio J.; Gleiser, Pablo M.

2009-01-01

Brain functional networks are graph representations of activity in the brain, where the vertices represent anatomical regions and the edges their functional connectivity. These networks present a robust small world topological structure, characterized by highly integrated modules connected sparsely by long range links. Recent studies showed that other topological properties such as the degree distribution and the presence (or absence) of a hierarchical structure are not robust, and show different intriguing behaviors. In order to understand the basic ingredients necessary for the emergence of these complex network structures we present an adaptive complex network model for human brain functional networks. The microscopic units of the model are dynamical nodes that represent active regions of the brain, whose interaction gives rise to complex network structures. The links between the nodes are chosen following an adaptive algorithm that establishes connections between dynamical elements with similar internal states. We show that the model is able to describe topological characteristics of human brain networks obtained from functional magnetic resonance imaging studies. In particular, when the dynamical rules of the model allow for integrated processing over the entire network scale-free non-hierarchical networks with well defined communities emerge. On the other hand, when the dynamical rules restrict the information to a local neighborhood, communities cluster together into larger ones, giving rise to a hierarchical structure, with a truncated power law degree distribution. PMID:19738902

At least eighty percent of brain grey matter is modifiable by physical activity: A review study.

PubMed

Batouli, Seyed Amir Hossein; Saba, Valiallah

2017-08-14

The human brain is plastic, i.e. it can show structural changes in response to the altered environment. Physical activity (PA) is a lifestyle factor which has significant associations with the structural and functional aspects of the human brain, as well as with the mind and body health. Many studies have reported regional/global brain volume increments due to exercising; however, a map which shows the overall extent of the influences of PAs on brain structure is not available. In this study, we collected all the reports on brain structural alterations in association with PA in healthy humans, and next, a brain map of the extent of these effects is provided. The results of this study showed that a large network of brain areas, equal to 82% of the total grey matter volume, were associated with PA. This finding has important implications in utilizing PA as a mediator factor for educational purposes in children, rehabilitation applications in patients, improving the cognitive abilities of the human brain such as in learning or memory, and preventing age-related brain deteriorations. Copyright © 2017 Elsevier B.V. All rights reserved.

Neurological impressions on the organization of language networks in the human brain.

PubMed

Oliveira, Fabricio Ferreira de; Marin, Sheilla de Medeiros Correia; Bertolucci, Paulo Henrique Ferreira

2017-01-01

More than 95% of right-handed individuals, as well as almost 80% of left-handed individuals, have left hemisphere dominance for language. The perisylvian networks of the dominant hemisphere tend to be the most important language systems in human brains, usually connected by bidirectional fibres originated from the superior longitudinal fascicle/arcuate fascicle system and potentially modifiable by learning. Neuroplasticity mechanisms take place to preserve neural functions after brain injuries. Language is dependent on a hierarchical interlinkage of serial and parallel processing areas in distinct brain regions considered to be elementary processing units. Whereas aphasic syndromes typically result from injuries to the dominant hemisphere, the extent of the distribution of language functions seems to be variable for each individual. Review of the literature Results: Several theories try to explain the organization of language networks in the human brain from a point of view that involves either modular or distributed processing or sometimes both. The most important evidence for each approach is discussed under the light of modern theories of organization of neural networks. Understanding the connectivity patterns of language networks may provide deeper insights into language functions, supporting evidence-based rehabilitation strategies that focus on the enhancement of language organization for patients with aphasic syndromes.

Relationship of Topology, Multiscale Phase Synchronization, and State Transitions in Human Brain Networks

PubMed Central

Kim, Minkyung; Kim, Seunghwan; Mashour, George A.; Lee, UnCheol

2017-01-01

How the brain reconstitutes consciousness and cognition after a major perturbation like general anesthesia is an important question with significant neuroscientific and clinical implications. Recent empirical studies in animals and humans suggest that the recovery of consciousness after anesthesia is not random but ordered. Emergence patterns have been classified as progressive and abrupt transitions from anesthesia to consciousness, with associated differences in duration and electroencephalogram (EEG) properties. We hypothesized that the progressive and abrupt emergence patterns from the unconscious state are associated with, respectively, continuous and discontinuous synchronization transitions in functional brain networks. The discontinuous transition is explainable with the concept of explosive synchronization, which has been studied almost exclusively in network science. We used the Kuramato model, a simple oscillatory network model, to simulate progressive and abrupt transitions in anatomical human brain networks acquired from diffusion tensor imaging (DTI) of 82 brain regions. To facilitate explosive synchronization, distinct frequencies for hub nodes with a large frequency disassortativity (i.e., higher frequency nodes linking with lower frequency nodes, or vice versa) were applied to the brain network. In this simulation study, we demonstrated that both progressive and abrupt transitions follow distinct synchronization processes at the individual node, cluster, and global network levels. The characteristic synchronization patterns of brain regions that are “progressive and earlier” or “abrupt but delayed” account for previously reported behavioral responses of gradual and abrupt emergence from the unconscious state. The characteristic network synchronization processes observed at different scales provide new insights into how regional brain functions are reconstituted during progressive and abrupt emergence from the unconscious state. This theoretical approach also offers a principled explanation of how the brain reconstitutes consciousness and cognitive functions after physiologic (sleep), pharmacologic (anesthesia), and pathologic (coma) perturbations. PMID:28713258

Relationship of Topology, Multiscale Phase Synchronization, and State Transitions in Human Brain Networks.

PubMed

Kim, Minkyung; Kim, Seunghwan; Mashour, George A; Lee, UnCheol

2017-01-01

How the brain reconstitutes consciousness and cognition after a major perturbation like general anesthesia is an important question with significant neuroscientific and clinical implications. Recent empirical studies in animals and humans suggest that the recovery of consciousness after anesthesia is not random but ordered. Emergence patterns have been classified as progressive and abrupt transitions from anesthesia to consciousness, with associated differences in duration and electroencephalogram (EEG) properties. We hypothesized that the progressive and abrupt emergence patterns from the unconscious state are associated with, respectively, continuous and discontinuous synchronization transitions in functional brain networks. The discontinuous transition is explainable with the concept of explosive synchronization, which has been studied almost exclusively in network science. We used the Kuramato model, a simple oscillatory network model, to simulate progressive and abrupt transitions in anatomical human brain networks acquired from diffusion tensor imaging (DTI) of 82 brain regions. To facilitate explosive synchronization, distinct frequencies for hub nodes with a large frequency disassortativity (i.e., higher frequency nodes linking with lower frequency nodes, or vice versa) were applied to the brain network. In this simulation study, we demonstrated that both progressive and abrupt transitions follow distinct synchronization processes at the individual node, cluster, and global network levels. The characteristic synchronization patterns of brain regions that are "progressive and earlier" or "abrupt but delayed" account for previously reported behavioral responses of gradual and abrupt emergence from the unconscious state. The characteristic network synchronization processes observed at different scales provide new insights into how regional brain functions are reconstituted during progressive and abrupt emergence from the unconscious state. This theoretical approach also offers a principled explanation of how the brain reconstitutes consciousness and cognitive functions after physiologic (sleep), pharmacologic (anesthesia), and pathologic (coma) perturbations.

Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain

PubMed Central

Lieblein-Boff, Jacqueline C.; Johnson, Elizabeth J.; Kennedy, Adam D.; Lai, Chron-Si; Kuchan, Matthew J.

2015-01-01

Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510) were excluded. In addition, moderate correlations with xenobiotic relationships (2) or those driven by single outliers (3) were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region—specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development. PMID:26317757

Noninvasive near-infrared topography of human brain activity using intensity modulation spectroscopy

NASA Astrophysics Data System (ADS)

Yamashita, Yuichi; Maki, Atsushi; Ito, Yoshitoshi; Watanabe, Eiju; Mayanagi, Yoshiaki; Koizumi, Hideaki

1996-04-01

We describe the functional topography of human brain activity due to motor stimulation by using near-infrared spectroscopy. Finger motion by each hand was used as the motor stimulation, and activity in the left fronto-central region of the brain was measured. A greater change in oxyhemoglobin concentration due to brain activity during the stimulation was obtained for the right hand than for the left hand. Localization of the activity was obtained by topographically mapping the measured changes for ten positions within the region.

Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants

USDA-ARS?s Scientific Manuscript database

In rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown. The objective of this study is to compare BDNF concentrations of subjects wi...

Hypothesis on two different functionalities co-existing in frontal lobe of human brains.

PubMed

Wang, Jue

2013-09-01

Human frontal lobe is a key area from where our cognition, memory and emotion display or function. In medical case study, there are patients with social dysfunctions, lack of passion or emotion as result of their frontal lobe damage caused by pathological changes, traumatic damage, and brain tumor remove operations. The syndrome of frontal lobe damage remains at large unanswered medically. From early stage of pregnancy, there exists lobe layers, nerve combine, and neurons synaptic, indicating a completion of growth of functionality inside frontal lobe. However, this completion of growth does not match the growth of human intelligence. Human infants only start and complete their cognition and memory functionality one full year after their birth which is marked by huge amount of neurons synaptic inside their frontal lobe, which is not part of a continual growth of originally developed functions. By reasoning on pathological changes of frontal lobe, a hypothesis was established that two individually functional mechanisms co-existed inside one frontal lobe. This neuron system is particularly for human beings. Copyright © 2013 Elsevier Ltd. All rights reserved.

Language systems in normal and aphasic human subjects: functional imaging studies and inferences from animal studies.

PubMed

Wise, Richard J S

2003-01-01

The old neurological model of language, based on the writings of Broca, Wernicke and Lichtheim in the 19th century, is now undergoing major modifications. Observations on the anatomy and physiology of auditory processing in non-human primates are giving strong indicators as to how speech perception is organised in the human brain. In the light of this knowledge, functional activation studies with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are achieving a new level of precision in the investigation of language organisation in the human brain, in a manner not possible with observations on patients with aphasic stroke. Although the use of functional imaging to inform methods of improving aphasia rehabilitation remains underdeveloped, there are strong indicators that this methodology will provide the means to research a very imperfectly developed area of therapy.

Gene expression links functional networks across cortex and striatum.

PubMed

Anderson, Kevin M; Krienen, Fenna M; Choi, Eun Young; Reinen, Jenna M; Yeo, B T Thomas; Holmes, Avram J

2018-04-12

The human brain is comprised of a complex web of functional networks that link anatomically distinct regions. However, the biological mechanisms supporting network organization remain elusive, particularly across cortical and subcortical territories with vastly divergent cellular and molecular properties. Here, using human and primate brain transcriptional atlases, we demonstrate that spatial patterns of gene expression show strong correspondence with limbic and somato/motor cortico-striatal functional networks. Network-associated expression is consistent across independent human datasets and evolutionarily conserved in non-human primates. Genes preferentially expressed within the limbic network (encompassing nucleus accumbens, orbital/ventromedial prefrontal cortex, and temporal pole) relate to risk for psychiatric illness, chloride channel complexes, and markers of somatostatin neurons. Somato/motor associated genes are enriched for oligodendrocytes and markers of parvalbumin neurons. These analyses indicate that parallel cortico-striatal processing channels possess dissociable genetic signatures that recapitulate distributed functional networks, and nominate molecular mechanisms supporting cortico-striatal circuitry in health and disease.

Possible psycho-physiological consequences of human long-term space missions

NASA Astrophysics Data System (ADS)

Belisheva, N. K.; Lammer, H.; Biernat, H. K.; Kachanova, T. L.; Kalashnikova, I. V.

Experiments carried out on the Earth s surface during different years and under contrast periods of solar activity have shown that the functional state of biosystems including the human organisms are controlled by global and local geocosmical agents Our finding have a close relation to space research because they demonstrate the reactions of biosystems on variations of global and local geocosmical agents and the mechanisms of modulations of biosystems state by geocosmical agents We revealed the role of variations of the geomagnetic field for the stimulation of immune systems functional state of peripheral blood human brain growth of microflora skin covers and pathogenic microorganisms The study of the psycho-physiological state of the human organism has demonstrated that an increase of the neutron intensity near the Earth s surface is associated with anxiety decrease of normal and increase of paradox reactions of examinees The analysis of the human brain functional state in dependent on the geomagnetic variation structure dose under exposure to the variations of geomagnetic field in a certain amplitude-frequency range and also the intensity of the nucleon component of secondary cosmic rays showed that the stable and unstable states of the human brain are determined by geomagnetic field variations and the intensity of the nucleon component The stable state of the brain manifested under the periodic oscillations of the geomagnetic field in a certain amplitude-frequency range The low level of geomagnetic activity associated with an

Individual differences and time-varying features of modular brain architecture.

PubMed

Liao, Xuhong; Cao, Miao; Xia, Mingrui; He, Yong

2017-05-15

Recent studies have suggested that human brain functional networks are topologically organized into functionally specialized but inter-connected modules to facilitate efficient information processing and highly flexible cognitive function. However, these studies have mainly focused on group-level network modularity analyses using "static" functional connectivity approaches. How these extraordinary modular brain structures vary across individuals and spontaneously reconfigure over time remain largely unknown. Here, we employed multiband resting-state functional MRI data (N=105) from the Human Connectome Project and a graph-based modularity analysis to systematically investigate individual variability and dynamic properties in modular brain networks. We showed that the modular structures of brain networks dramatically vary across individuals, with higher modular variability primarily in the association cortex (e.g., fronto-parietal and attention systems) and lower variability in the primary systems. Moreover, brain regions spontaneously changed their module affiliations on a temporal scale of seconds, which cannot be simply attributable to head motion and sampling error. Interestingly, the spatial pattern of intra-subject dynamic modular variability largely overlapped with that of inter-subject modular variability, both of which were highly reproducible across repeated scanning sessions. Finally, the regions with remarkable individual/temporal modular variability were closely associated with network connectors and the number of cognitive components, suggesting a potential contribution to information integration and flexible cognitive function. Collectively, our findings highlight individual modular variability and the notable dynamic characteristics in large-scale brain networks, which enhance our understanding of the neural substrates underlying individual differences in a variety of cognition and behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

Discovering transnosological molecular basis of human brain diseases using biclustering analysis of integrated gene expression data.

PubMed

Cha, Kihoon; Hwang, Taeho; Oh, Kimin; Yi, Gwan-Su

2015-01-01

It has been reported that several brain diseases can be treated as transnosological manner implicating possible common molecular basis under those diseases. However, molecular level commonality among those brain diseases has been largely unexplored. Gene expression analyses of human brain have been used to find genes associated with brain diseases but most of those studies were restricted either to an individual disease or to a couple of diseases. In addition, identifying significant genes in such brain diseases mostly failed when it used typical methods depending on differentially expressed genes. In this study, we used a correlation-based biclustering approach to find coexpressed gene sets in five neurodegenerative diseases and three psychiatric disorders. By using biclustering analysis, we could efficiently and fairly identified various gene sets expressed specifically in both single and multiple brain diseases. We could find 4,307 gene sets correlatively expressed in multiple brain diseases and 3,409 gene sets exclusively specified in individual brain diseases. The function enrichment analysis of those gene sets showed many new possible functional bases as well as neurological processes that are common or specific for those eight diseases. This study introduces possible common molecular bases for several brain diseases, which open the opportunity to clarify the transnosological perspective assumed in brain diseases. It also showed the advantages of correlation-based biclustering analysis and accompanying function enrichment analysis for gene expression data in this type of investigation.

Discovering transnosological molecular basis of human brain diseases using biclustering analysis of integrated gene expression data

PubMed Central

2015-01-01

Background It has been reported that several brain diseases can be treated as transnosological manner implicating possible common molecular basis under those diseases. However, molecular level commonality among those brain diseases has been largely unexplored. Gene expression analyses of human brain have been used to find genes associated with brain diseases but most of those studies were restricted either to an individual disease or to a couple of diseases. In addition, identifying significant genes in such brain diseases mostly failed when it used typical methods depending on differentially expressed genes. Results In this study, we used a correlation-based biclustering approach to find coexpressed gene sets in five neurodegenerative diseases and three psychiatric disorders. By using biclustering analysis, we could efficiently and fairly identified various gene sets expressed specifically in both single and multiple brain diseases. We could find 4,307 gene sets correlatively expressed in multiple brain diseases and 3,409 gene sets exclusively specified in individual brain diseases. The function enrichment analysis of those gene sets showed many new possible functional bases as well as neurological processes that are common or specific for those eight diseases. Conclusions This study introduces possible common molecular bases for several brain diseases, which open the opportunity to clarify the transnosological perspective assumed in brain diseases. It also showed the advantages of correlation-based biclustering analysis and accompanying function enrichment analysis for gene expression data in this type of investigation. PMID:26043779

Functional specificity for high-level linguistic processing in the human brain.

PubMed

Fedorenko, Evelina; Behr, Michael K; Kanwisher, Nancy

2011-09-27

Neuroscientists have debated for centuries whether some regions of the human brain are selectively engaged in specific high-level mental functions or whether, instead, cognition is implemented in multifunctional brain regions. For the critical case of language, conflicting answers arise from the neuropsychological literature, which features striking dissociations between deficits in linguistic and nonlinguistic abilities, vs. the neuroimaging literature, which has argued for overlap between activations for linguistic and nonlinguistic processes, including arithmetic, domain general abilities like cognitive control, and music. Here, we use functional MRI to define classic language regions functionally in each subject individually and then examine the response of these regions to the nonlinguistic functions most commonly argued to engage these regions: arithmetic, working memory, cognitive control, and music. We find little or no response in language regions to these nonlinguistic functions. These data support a clear distinction between language and other cognitive processes, resolving the prior conflict between the neuropsychological and neuroimaging literatures.

Fitted hyperelastic parameters for Human brain tissue from reported tension, compression, and shear tests.

PubMed

Moran, Richard; Smith, Joshua H; García, José J

2014-11-28

The mechanical properties of human brain tissue are the subject of interest because of their use in understanding brain trauma and in developing therapeutic treatments and procedures. To represent the behavior of the tissue, we have developed hyperelastic mechanical models whose parameters are fitted in accordance with experimental test results. However, most studies available in the literature have fitted parameters with data of a single type of loading, such as tension, compression, or shear. Recently, Jin et al. (Journal of Biomechanics 46:2795-2801, 2013) reported data from ex vivo tests of human brain tissue under tension, compression, and shear loading using four strain rates and four different brain regions. However, they do not report parameters of energy functions that can be readily used in finite element simulations. To represent the tissue behavior for the quasi-static loading conditions, we aimed to determine the best fit of the hyperelastic parameters of the hyperfoam, Ogden, and polynomial strain energy functions available in ABAQUS for the low strain rate data, while simultaneously considering all three loading modes. We used an optimization process conducted in MATLAB, calling iteratively three finite element models developed in ABAQUS that represent the three loadings. Results showed a relatively good fit to experimental data in all loading modes using two terms in the energy functions. Values for the shear modulus obtained in this analysis (897-1653Pa) are in the range of those presented in other studies. These energy-function parameters can be used in brain tissue simulations using finite element models. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inferential stereomorphology of human brain lesions

NASA Astrophysics Data System (ADS)

Gedye, John L.

1980-07-01

I very much appreciated the invitation to contribute a paper to this Symposium on Applications of Human Biostereometrics, as it provides a valuable opportunity for me to take a fresh look at a problemâ€""the cerebral localisation of psychological function"â€"in which I have been interested for many years. This interest grew out of considerations of the clinically important problem of how we should go about the task of relating the form of the changes in human behavior consequent upon damage to the human brain following, say, head injury, to the form of the changes in brain morphology which constitute that damage, and related issues.

BECon: a tool for interpreting DNA methylation findings from blood in the context of brain.

PubMed

Edgar, R D; Jones, M J; Meaney, M J; Turecki, G; Kobor, M S

2017-08-01

Tissue differences are one of the largest contributors to variability in the human DNA methylome. Despite the tissue-specific nature of DNA methylation, the inaccessibility of human brain samples necessitates the frequent use of surrogate tissues such as blood, in studies of associations between DNA methylation and brain function and health. Results from studies of surrogate tissues in humans are difficult to interpret in this context, as the connection between blood-brain DNA methylation is tenuous and not well-documented. Here, we aimed to provide a resource to the community to aid interpretation of blood-based DNA methylation results in the context of brain tissue. We used paired samples from 16 individuals from three brain regions and whole blood, run on the Illumina 450 K Human Methylation Array to quantify the concordance of DNA methylation between tissues. From these data, we have made available metrics on: the variability of cytosine-phosphate-guanine dinucleotides (CpGs) in our blood and brain samples, the concordance of CpGs between blood and brain, and estimations of how strongly a CpG is affected by cell composition in both blood and brain through the web application BECon (Blood-Brain Epigenetic Concordance; https://redgar598.shinyapps.io/BECon/). We anticipate that BECon will enable biological interpretation of blood-based human DNA methylation results, in the context of brain.

Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species

PubMed Central

Semple, Bridgette D.; Blomgren, Klas; Gimlin, Kayleen; Ferriero, Donna M.; Noble-Haeusslein, Linda J.

2013-01-01

Hypoxic-ischemic and traumatic brain injuries are leading causes of long-term mortality and disability in infants and children. Although several preclinical models using rodents of different ages have been developed, species differences in the timing of key brain maturation events can render comparisons of vulnerability and regenerative capacities difficult to interpret. Traditional models of developmental brain injury have utilized rodents at postnatal day 7–10 as being roughly equivalent to a term human infant, based historically on the measurement of post-mortem brain weights during the 1970s. Here we will examine fundamental brain development processes that occur in both rodents and humans, to delineate a comparable time course of postnatal brain development across species. We consider the timing of neurogenesis, synaptogenesis, gliogenesis, oligodendrocyte maturation and age-dependent behaviors that coincide with developmentally regulated molecular and biochemical changes. In general, while the time scale is considerably different, the sequence of key events in brain maturation is largely consistent between humans and rodents. Further, there are distinct parallels in regional vulnerability as well as functional consequences in response to brain injuries. With a focus on developmental hypoxicischemic encephalopathy and traumatic brain injury, this review offers guidelines for researchers when considering the most appropriate rodent age for the developmental stage or process of interest to approximate human brain development. PMID:23583307

The Use of Functional MRI to Study Appetite Control in the CNS

PubMed Central

De Silva, Akila; Salem, Victoria; Matthews, Paul M.; Dhillo, Waljit S.

2012-01-01

Functional magnetic resonance imaging (fMRI) has provided the opportunity to safely investigate the workings of the human brain. This paper focuses on its use in the field of human appetitive behaviour and its impact in obesity research. In the present absence of any safe or effective centrally acting appetite suppressants, a better understanding of how appetite is controlled is vital for the development of new antiobesity pharmacotherapies. Early functional imaging techniques revealed an attenuation of brain reward area activity in response to visual food stimuli when humans are fed—in other words, the physiological state of hunger somehow increases the appeal value of food. Later studies have investigated the action of appetite modulating hormones on the fMRI signal, showing how the attenuation of brain reward region activity that follows feeding can be recreated in the fasted state by the administration of anorectic gut hormones. Furthermore, differences in brain activity between obese and lean individuals have provided clues about the possible aetiology of overeating. The hypothalamus acts as a central gateway modulating homeostatic and nonhomeostatic drives to eat. As fMRI techniques constantly improve, functional data regarding the role of this small but hugely important structure in appetite control is emerging. PMID:22719753

A functional architecture of the human brain: Emerging insights from the science of emotion

PubMed Central

Lindquist, Kristen A.; Barrett, Lisa Feldman

2012-01-01

The ‘faculty psychology’ approach to the mind, which attempts to explain mental function in terms of categories that reflect modular ‘faculties’, such as emotions, cognitions, and perceptions, has dominated research into the mind and its physical correlates. In this paper, we argue that brain organization does not respect the commonsense categories belonging to the faculty psychology approach. We review recent research from the science of emotion demonstrating that the human brain contains broadly distributed functional networks that can each be re-described as basic psychological operations that interact to produce a range of mental states, including, but not limited to, anger, sadness, fear, disgust, and so on. When compared to the faculty psychology approach, this ‘constructionist’ approach provides an alternative functional architecture to guide the design and interpretation of experiments in cognitive neuroscience. PMID:23036719

Transcallosal transfer of information and functional asymmetry of the human brain.

PubMed

Nowicka, Anna; Tacikowski, Pawel

2011-01-01

The corpus callosum is the largest commissure in the brain and acts as a "bridge" of nerve fibres connecting the two cerebral hemispheres. It plays a crucial role in interhemispheric integration and is responsible for normal communication and cooperation between the two hemispheres. Evolutionary pressures guiding brain size are accompanied by reduced interhemispheric and enhanced intrahemispheric connectivity. Some lines of evidence suggest that the speed of transcallosal conduction is limited in large brains (e.g., in humans), thus favouring intrahemispheric processing and brain lateralisation. Patterns of directional symmetry/asymmetry of transcallosal transfer time may be related to the degree of brain lateralisation. Neural network modelling and electrophysiological studies on interhemispheric transmission provide data supporting this supposition.

Can a few non‐coding mutations make a human brain?

PubMed Central

Franchini, Lucía F.

2015-01-01

The recent finding that the human version of a neurodevelopmental enhancer of the Wnt receptor Frizzled 8 (FZD8) gene alters neural progenitor cell cycle timing and brain size is a step forward to understanding human brain evolution. The human brain is distinctive in terms of its cognitive abilities as well as its susceptibility to neurological disease. Identifying which of the millions of genomic changes that occurred during human evolution led to these and other uniquely human traits is extremely challenging. Recent studies have demonstrated that many of the fastest evolving regions of the human genome function as gene regulatory enhancers during embryonic development and that the human‐specific mutations in them might alter expression patterns. However, elucidating molecular and cellular effects of sequence or expression pattern changes is a major obstacle to discovering the genetic bases of the evolution of our species. There is much work to do before human‐specific genetic and genomic changes are linked to complex human traits. Also watch the Video Abstract. PMID:26350501

Neuronal glycogen synthesis contributes to physiological aging

PubMed Central

Sinadinos, Christopher; Valles-Ortega, Jordi; Boulan, Laura; Solsona, Estel; Tevy, Maria F; Marquez, Mercedes; Duran, Jordi; Lopez-Iglesias, Carmen; Calbó, Joaquim; Blasco, Ester; Pumarola, Marti; Milán, Marco; Guinovart, Joan J

2014-01-01

Glycogen is a branched polymer of glucose and the carbohydrate energy store for animal cells. In the brain, it is essentially found in glial cells, although it is also present in minute amounts in neurons. In humans, loss-of-function mutations in laforin and malin, proteins involved in suppressing glycogen synthesis, induce the presence of high numbers of insoluble polyglucosan bodies in neuronal cells. Known as Lafora bodies (LBs), these deposits result in the aggressive neurodegeneration seen in Lafora’s disease. Polysaccharide-based aggregates, called corpora amylacea (CA), are also present in the neurons of aged human brains. Despite the similarity of CA to LBs, the mechanisms and functional consequences of CA formation are yet unknown. Here, we show that wild-type laboratory mice also accumulate glycogen-based aggregates in the brain as they age. These structures are immunopositive for an array of metabolic and stress-response proteins, some of which were previously shown to aggregate in correlation with age in the human brain and are also present in LBs. Remarkably, these structures and their associated protein aggregates are not present in the aged mouse brain upon genetic ablation of glycogen synthase. Similar genetic intervention in Drosophila prevents the accumulation of glycogen clusters in the neuronal processes of aged flies. Most interestingly, targeted reduction of Drosophila glycogen synthase in neurons improves neurological function with age and extends lifespan. These results demonstrate that neuronal glycogen accumulation contributes to physiological aging and may therefore constitute a key factor regulating age-related neurological decline in humans. PMID:25059425

Toward a cross-species neuroscientific understanding of the affective mind: do animals have emotional feelings?

PubMed

Panksepp, Jaak

2011-06-01

Do we need to consider mental processes in our analysis of brain functions in other animals? Obviously we do, if such BrainMind functions exist in the animals we wish to understand. If so, how do we proceed, while still retaining materialistic-mechanistic perspectives? This essay outlines the historical forces that led to emotional feelings in animals being marginalized in behavioristic scientific discussions of why animals behave the way they do, and why mental constructs are generally disregarded in modern neuroscientific analyses. The roots of this problem go back to Cartesian dualism and the attempt of 19th century physician-scientists to ground a new type of medical curriculum on a completely materialistic approach to body functions. Thereby all vitalistic principles were discarded from the lexicon of science, and subjective experience in animals was put in that category and discarded as an invalid approach to animal behavior. This led to forms of rigid operationalism during the era of behaviorism and subsequently ruthless reductionism in brain research, leaving little room for mentalistic concepts such as emotional feelings in animal research. However, modern studies of the brain clearly indicate that artificially induced arousals of emotional networks, as with localized electrical and chemical brain stimulation, can serve as "rewards" and "punishments" in various learning tasks. This strongly indicates that animal brains elaborate various experienced states, with those having affective contents being easiest to study rigorously. However, in approaching emotional feelings empirically we must pay special attention to the difficulties and vagaries of human language and evolutionary levels of control in the brain. We need distinct nomenclatures from primary (unconditioned phenomenal experiences) to tertiary (reflective) levels of mind. The scientific pursuit of affective brain processes in other mammals can now reveal general BrainMind principles that also apply to human feelings, as with neurochemical predictions from preclinical animal models to self-reports of corresponding human experiences. In short, brain research has now repeatedly verified the existence of affective experience-various reward and punishment functions-during artificial arousal of emotional networks in our fellow animals. The implications for new conceptual schema for understanding human/primate affective feelings and how such knowledge can impact scientific advances in biological psychiatry are also addressed. © 2011 Wiley-Liss, Inc.

APPswe/PS1dE9 mice with cortical amyloid pathology show a reduced NAA/Cr ratio without apparent brain atrophy: A MRS and MRI study.

PubMed

Kuhla, Angela; Rühlmann, Claire; Lindner, Tobias; Polei, Stefan; Hadlich, Stefan; Krause, Bernd J; Vollmar, Brigitte; Teipel, Stefan J

2017-01-01

Transgenic animal models of Aβ pathology provide mechanistic insight into some aspects of Alzheimer disease (AD) pathology related to Aβ accumulation. Quantitative neuroimaging is a possible aid to improve translation of mechanistic findings in transgenic models to human end phenotypes of brain morphology or function. Therefore, we combined MRI-based morphometry, MRS-based NAA-assessment and quantitative histology of neurons and amyloid plaque load in the APPswe/PS1dE9 mouse model to determine the interrelationship between morphological changes, changes in neuron numbers and amyloid plaque load with reductions of NAA levels as marker of neuronal functional viability. The APPswe/PS1dE9 mouse showed an increase of Aβ plaques, loss of neurons and an impairment of NAA/Cr ratio, which however was not accompanied with brain atrophy. As brain atrophy is one main characteristic in human AD, conclusions from murine to human AD pathology should be drawn with caution.

Building a neuroscience of pleasure and well-being

PubMed Central

Berridge, Kent C; Kringelbach, Morten L

2012-01-01

Background How is happiness generated via brain function in lucky individuals who have the good fortune to be happy? Conceptually, well-being or happiness has long been viewed as requiring at least two crucial ingredients: positive affect or pleasure (hedonia) and a sense of meaningfulness or engagement in life (eudaimonia). Science has recently made progress in relating hedonic pleasure to brain function, and so here we survey new insights into how brains generate the hedonic ingredient of sustained or frequent pleasure. We also briefly discuss how brains might connect hedonia states of pleasure to eudaimonia assessments of meaningfulness, and so create balanced states of positive well-being. Results Notable progress has been made in understanding brain bases of hedonic processing, producing insights into that brain systems that cause and/or code sensory pleasures. Progress has been facilitated by the recognition that hedonic brain mechanisms are largely shared between humans and other mammals, allowing application of conclusions from animal studies to a better understanding of human pleasures. In the past few years, evidence has also grown to indicate that for humans, brain mechanisms of higher abstract pleasures strongly overlap with more basic sensory pleasures. This overlap may provide a window into underlying brain circuitry that generates all pleasures, including even the hedonic quality of pervasive well-being that detaches from any particular sensation to apply to daily life in a more sustained or frequent fashion. Conclusions Hedonic insights are applied to understanding human well-being here. Our strategy combines new findings on brain mediators that generate the pleasure of sensations with evidence that human brains use many of the same hedonic circuits from sensory pleasures to create the higher pleasures. This in turn may be linked to how hedonic systems interact with other brain systems relevant to self-understanding and the meaning components of eudaimonic happiness. Finally, we speculate a bit about how brains that generate hedonia states might link to eudaimonia assessments to create properly balanced states of positive well-being that approach true happiness. PMID:22328976

Slice-to-Volume Nonrigid Registration of Histological Sections to MR Images of the Human Brain

PubMed Central

Osechinskiy, Sergey; Kruggel, Frithjof

2011-01-01

Registration of histological images to three-dimensional imaging modalities is an important step in quantitative analysis of brain structure, in architectonic mapping of the brain, and in investigation of the pathology of a brain disease. Reconstruction of histology volume from serial sections is a well-established procedure, but it does not address registration of individual slices from sparse sections, which is the aim of the slice-to-volume approach. This study presents a flexible framework for intensity-based slice-to-volume nonrigid registration algorithms with a geometric transformation deformation field parametrized by various classes of spline functions: thin-plate splines (TPS), Gaussian elastic body splines (GEBS), or cubic B-splines. Algorithms are applied to cross-modality registration of histological and magnetic resonance images of the human brain. Registration performance is evaluated across a range of optimization algorithms and intensity-based cost functions. For a particular case of histological data, best results are obtained with a TPS three-dimensional (3D) warp, a new unconstrained optimization algorithm (NEWUOA), and a correlation-coefficient-based cost function. PMID:22567290

Cerebral cartography and connectomics

PubMed Central

Sporns, Olaf

2015-01-01

Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics. PMID:25823870

Myelination, oligodendrocytes, and serious mental illness.

PubMed

Haroutunian, V; Katsel, P; Roussos, P; Davis, K L; Altshuler, L L; Bartzokis, G

2014-11-01

Historically, the human brain has been conceptually segregated from the periphery and further dichotomized into gray matter (GM) and white matter (WM) based on the whitish appearance of the exceptionally high lipid content of the myelin sheaths encasing neuronal axons. These simplistic dichotomies were unfortunately extended to conceptually segregate neurons from glia, cognition from behavior, and have been codified in the separation of clinical and scientific fields into medicine, psychiatry, neurology, pathology, etc. The discrete classifications have helped obscure the importance of continual dynamic communication between all brain cell types (neurons, astrocytes, microglia, oligodendrocytes, and precursor (NG2) cells) as well as between brain and periphery through multiple signaling systems. The signaling systems range from neurotransmitters to insulin, angiotensin, and multiple kinases such a glycogen synthase kinase 3 (GSK-3) that together help integrate metabolism, inflammation, and myelination processes and orchestrate the development, plasticity, maintenance, and repair that continually optimize function of neural networks. A more comprehensive, evolution-based, systems biology approach that integrates brain, body, and environmental interactions may ultimately prove more fruitful in elucidating the complexities of human brain function. The historic focus on neurons/GM is rebalanced herein by highlighting the importance of a systems-level understanding of the interdependent age-related shifts in both central and peripheral homeostatic mechanisms that can lead to remarkably prevalent and devastating neuropsychiatric diseases. Herein we highlight the role of glia, especially the most recently evolved oligodendrocytes and the myelin they produce, in achieving and maintaining optimal brain function. The human brain undergoes exceptionally protracted and pervasive myelination (even throughout its GM) and can thus achieve and maintain the rapid conduction and synchronous timing of neural networks on which optimal function depends. The continuum of increasing myelin vulnerability resulting from the human brain's protracted myelination underlies underappreciated communalities between different disease phenotypes ranging from developmental ones such as schizophrenia (SZ) and bipolar disorder (BD) to degenerative ones such as Alzheimer's disease (AD). These shared vulnerabilities also expose significant yet underexplored opportunities for novel treatment and prevention approaches that have the potential to considerably reduce the tremendous burden of neuropsychiatric disease. © 2014 Wiley Periodicals, Inc.

Brain and Social Networks: Fundamental Building Blocks of Human Experience.

PubMed

Falk, Emily B; Bassett, Danielle S

2017-09-01

How do brains shape social networks, and how do social ties shape the brain? Social networks are complex webs by which ideas spread among people. Brains comprise webs by which information is processed and transmitted among neural units. While brain activity and structure offer biological mechanisms for human behaviors, social networks offer external inducers or modulators of those behaviors. Together, these two axes represent fundamental contributors to human experience. Integrating foundational knowledge from social and developmental psychology and sociology on how individuals function within dyads, groups, and societies with recent advances in network neuroscience can offer new insights into both domains. Here, we use the example of how ideas and behaviors spread to illustrate the potential of multilayer network models. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional network organization of the human brain

PubMed Central

Power, Jonathan D; Cohen, Alexander L; Nelson, Steven M; Wig, Gagan S; Barnes, Kelly Anne; Church, Jessica A; Vogel, Alecia C; Laumann, Timothy O; Miezin, Fran M; Schlaggar, Bradley L; Petersen, Steven E

2011-01-01

Summary Real-world complex systems may be mathematically modeled as graphs, revealing properties of the system. Here we study graphs of functional brain organization in healthy adults using resting state functional connectivity MRI. We propose two novel brain-wide graphs, one of 264 putative functional areas, the other a modification of voxelwise networks that eliminates potentially artificial short-distance relationships. These graphs contain many subgraphs in good agreement with known functional brain systems. Other subgraphs lack established functional identities; we suggest possible functional characteristics for these subgraphs. Further, graph measures of the areal network indicate that the default mode subgraph shares network properties with sensory and motor subgraphs: it is internally integrated but isolated from other subgraphs, much like a “processing” system. The modified voxelwise graph also reveals spatial motifs in the patterning of systems across the cortex. PMID:22099467

Systemic Analysis of Brain Mechanisms Underlying Learning Disabilities: An Introduction to the Brain Behavior Relationship.

ERIC Educational Resources Information Center

Scaramella-Nowinski, Valerie L.

The paper presents a discussion of human mental processes as they relate to learning disabilities. Pathognomonic symptoms associated with disturbances to brain areas or functional systems are discussed, as well as treatment procedures. This brain behavior relationship is offered as a basis for a classification system that is seen to more clearly…

How Children's Brains Think: Not Left or Right but Both Together

ERIC Educational Resources Information Center

Geake, John

2004-01-01

The burgeoning interest over recent decades about the human brain, and possible implications for education, has, perhaps not surprisingly, fostered a suite of urban myths about brain functioning. The prize for the barmiest goes to the one about using only 10% of the brain, but there are plenty more that deserve dishonourable mention. The most…

Exercise and the brain: something to chew on

PubMed Central

van Praag, Henriette

2009-01-01

Evidence is accumulating that exercise has profound benefits for brain function. Physical activity improves learning and memory in humans and animals. Moreover, an active lifestyle might prevent or delay loss of cognitive function with aging or neurodegenerative disease. Recent research indicates that the effects of exercise on the brain can be enhanced by concurrent consumption of natural products such as omega fatty acids or plant polyphenols. The potential synergy between diet and exercise could involve common cellular pathways important for neurogenesis, cell survival, synaptic plasticity and vascular function. Optimal maintenance of brain health might depend on exercise and intake of natural products. PMID:19349082

Mapping the human brain during a specific Vojta's tactile input: the ipsilateral putamen's role

PubMed Central

Sanz-Esteban, Ismael; Calvo-Lobo, Cesar; Ríos-Lago, Marcos; Álvarez-Linera, Juan; Muñoz-García, Daniel; Rodríguez-Sanz, David

2018-01-01

Abstract A century of research in human brain parcellation has demonstrated that different brain areas are associated with functional tasks. New neuroscientist perspectives to achieve the parcellation of the human brain have been developed to know the brain areas activation and its relationship with different stimuli. This descriptive study aimed to compare brain regions activation by specific tactile input (STI) stimuli according to the Vojta protocol (STI-group) to a non-STI stimulation (non-STI-group). An exploratory functional magnetic resonance imaging (fMRI) study was performed. The 2 groups of participants were passively stimulated by an expert physical therapist using the same paradigm structure, although differing in the place of stimulation. The stimulation was presented to participants using a block design in all cases. A sample of 16 healthy participants, 5 men and 11 women, with mean age 31.31 ± 8.13 years was recruited. Indeed, 12 participants were allocated in the STI-group and 4 participants in the non-STI-group. fMRI was used to map the human brain in vivo while these tactile stimuli were being applied. Data were analyzed using a general linear model in SPM12 implemented in MATLAB. Differences between groups showed a greater activation in the right cortical areas (temporal and frontal lobes), subcortical regions (thalamus, brainstem, and basal nuclei), and in the cerebellum (anterior lobe). STI-group had specific difference brain activation areas, such as the ipsilateral putamen. Future studies should study clinical implications in neurorehabilitation patients. PMID:29595683

Simultaneous measurement of glucose transport and utilization in the human brain

PubMed Central

Shestov, Alexander A.; Emir, Uzay E.; Kumar, Anjali; Henry, Pierre-Gilles; Seaquist, Elizabeth R.

2011-01-01

Glucose is the primary fuel for brain function, and determining the kinetics of cerebral glucose transport and utilization is critical for quantifying cerebral energy metabolism. The kinetic parameters of cerebral glucose transport, KMt and Vmaxt, in humans have so far been obtained by measuring steady-state brain glucose levels by proton (1H) NMR as a function of plasma glucose levels and fitting steady-state models to these data. Extraction of the kinetic parameters for cerebral glucose transport necessitated assuming a constant cerebral metabolic rate of glucose (CMRglc) obtained from other tracer studies, such as 13C NMR. Here we present new methodology to simultaneously obtain kinetic parameters for glucose transport and utilization in the human brain by fitting both dynamic and steady-state 1H NMR data with a reversible, non-steady-state Michaelis-Menten model. Dynamic data were obtained by measuring brain and plasma glucose time courses during glucose infusions to raise and maintain plasma concentration at ∼17 mmol/l for ∼2 h in five healthy volunteers. Steady-state brain vs. plasma glucose concentrations were taken from literature and the steady-state portions of data from the five volunteers. In addition to providing simultaneous measurements of glucose transport and utilization and obviating assumptions for constant CMRglc, this methodology does not necessitate infusions of expensive or radioactive tracers. Using this new methodology, we found that the maximum transport capacity for glucose through the blood-brain barrier was nearly twofold higher than maximum cerebral glucose utilization. The glucose transport and utilization parameters were consistent with previously published values for human brain. PMID:21791622

Evolution of Osteocrin as an activity-regulated factor in the primate brain

PubMed Central

Ataman, Bulent; Boulting, Gabriella L.; Harmin, David A.; Yang, Marty G.; Baker-Salisbury, Mollie; Yap, Ee-Lynn; Malik, Athar N.; Mei, Kevin; Rubin, Alex A.; Spiegel, Ivo; Durresi, Ershela; Sharma, Nikhil; Hu, Linda S.; Pletikos, Mihovil; Griffith, Eric C.; Partlow, Jennifer N.; Stevens, Christine R.; Adli, Mazhar; Chahrour, Maria; Sestan, Nenad; Walsh, Christopher A.; Berezovskii, Vladimir K.; Livingstone, Margaret S.; Greenberg, Michael E.

2017-01-01

Sensory stimuli drive the maturation and function of the mammalian nervous system in part through the activation of gene expression networks that regulate synapse development and plasticity. These networks have primarily been studied in mice, and it is not known whether there are species- or clade-specific activity-regulated genes that control features of brain development and function. Here we use transcriptional profiling of human fetal brain cultures to identify an activity-dependent secreted factor, Osteocrin (OSTN), that is induced by membrane depolarization of human but not mouse neurons. We find that OSTN has been repurposed in primates through the evolutionary acquisition of DNA regulatory elements that bind the activity-regulated transcription factor MEF2. In addition, we demonstrate that OSTN is expressed in primate neocortex and restricts activity-dependent dendritic growth in human neurons. These findings suggest that, in response to sensory input, OSTN regulates features of neuronal structure and function that are unique to primates. PMID:27830782

Genetic Causes of Microcephaly and Lessons for Neuronal Development

PubMed Central

Gilmore, Edward C.; Walsh, Christopher A.

2012-01-01

The study of human developmental microcephaly is providing important insights into brain development. It has become clear that developmental microcephalies are associated with abnormalities in cellular production, and that the pathophysiology of microcephaly provides remarkable insights into how the brain generates the proper number of neurons that determine brain size. Most of the genetic causes of ‘primary’ developmental microcephaly (i.e., not associated with other syndromic features) are associated with centrosomal abnormalities. In addition to other functions, centrosomal proteins control the mitotic spindle, which is essential for normal cell proliferation during mitosis. However, the brain is often uniquely affected when microcephaly genes are mutated implying special centrosomal related functions in neuronal production. Although models explaining how this could occur have some compelling data, they are not without controversy. Interestingly, some of the microcephaly genes show evidence that they were targets of evolutionary selection in primates and human ancestors, suggesting potential evolutionary roles in controlling neuronal number and brain volume across species. Mutations in DNA repair pathway genes also lead to microcephaly. Double stranded DNA breaks appear to be a prominent type of damage that needs to be repaired during brain development, yet why defects in DNA repair affect the brain preferentially and if DNA repair relates to centrosome function, are not clearly understood. PMID:24014418

Age-related changes in the ease of dynamical transitions in human brain activity.

PubMed

Ezaki, Takahiro; Sakaki, Michiko; Watanabe, Takamitsu; Masuda, Naoki

2018-06-01

Executive functions, a set of cognitive processes that enable flexible behavioral control, are known to decay with aging. Because such complex mental functions are considered to rely on the dynamic coordination of functionally different neural systems, the age-related decline in executive functions should be underpinned by alteration of large-scale neural dynamics. However, the effects of age on brain dynamics have not been firmly formulated. Here, we investigate such age-related changes in brain dynamics by applying "energy landscape analysis" to publicly available functional magnetic resonance imaging data from healthy younger and older human adults. We quantified the ease of dynamical transitions between different major patterns of brain activity, and estimated it for the default mode network (DMN) and the cingulo-opercular network (CON) separately. We found that the two age groups shared qualitatively the same trajectories of brain dynamics in both the DMN and CON. However, in both of networks, the ease of transitions was significantly smaller in the older than the younger group. Moreover, the ease of transitions was associated with the performance in executive function tasks in a doubly dissociated manner: for the younger adults, the ability of executive functions was mainly correlated with the ease of transitions in the CON, whereas that for the older adults was specifically associated with the ease of transitions in the DMN. These results provide direct biological evidence for age-related changes in macroscopic brain dynamics and suggest that such neural dynamics play key roles when individuals carry out cognitively demanding tasks. © 2018 Wiley Periodicals, Inc.

Efficiency of weak brain connections support general cognitive functioning.

PubMed

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

2014-09-01

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. Copyright © 2014 Wiley Periodicals, Inc.

Identification of prefrontal cortex (BA10) activation while performing Stroop test using diffuse optical tomography

NASA Astrophysics Data System (ADS)

Khadka, Sabin; Chityala, Srujan R.; Tian, Fenghua; Liu, Hanli

2011-03-01

Stroop test is commonly used as a behavior-testing tool for psychological examinations that are related to attention and cognitive control of the human brain. Studies have shown activations in Broadmann area 10 (BA10) of prefrontal cortex (PFC) during attention and cognitive process. The use of diffuse optical tomography (DOT) for human brain mapping is becoming more prevalent. In this study we expect to find neural correlates between the performed cognitive tasks and hemodynamic signals detected by a DOT system. Our initial observation showed activation of oxy-hemoglobin concentration in BA 10, which is consistent with some results seen by positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Our study demonstrates the possibility of combining DOT with Stroop test to quantitatively investigate cognitive functions of the human brain at the prefrontal cortex.

The role of sleep in human declarative memory consolidation.

PubMed

Alger, Sara E; Chambers, Alexis M; Cunningham, Tony; Payne, Jessica D

2015-01-01

Through a variety of methods, researchers have begun unraveling the mystery of why humans spend one-third of their lives asleep. Though sleep likely serves multiple functions, it has become clear that the sleeping brain offers an ideal environment for solidifying newly learned information in the brain. Sleep , which comprises a complex collection of brain states, supports the consolidation of many different types of information. It not only promotes learning and memory stabilization, but also memory reorganization that can lead to various forms of insightful behavior. As this chapter will describe, research provides ample support for these crucial cognitive functions of sleep . Focusing on the declarative memory system in humans, we review the literature regarding the benefits of sleep for both neutral and emotionally salient declarative memory. Finally, we discuss the literature regarding the impact of sleep on emotion regulation.

Autism as an adaptive common variant pathway for human brain development.

PubMed

Johnson, Mark H

2017-06-01

While research on focal perinatal lesions has provided evidence for recovery of function, much less is known about processes of brain adaptation resulting from mild but widespread disturbances to neural processing over the early years (such as alterations in synaptic efficiency). Rather than being viewed as a direct behavioral consequence of life-long neural dysfunction, I propose that autism is best viewed as the end result of engaging adaptive processes during a sensitive period. From this perspective, autism is not appropriately described as a disorder of neurodevelopment, but rather as an adaptive common variant pathway of human functional brain development. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

Information flow between interacting human brains: Identification, validation, and relationship to social expertise

PubMed Central

Bilek, Edda; Ruf, Matthias; Schäfer, Axel; Akdeniz, Ceren; Calhoun, Vince D.; Schmahl, Christian; Demanuele, Charmaine; Tost, Heike; Kirsch, Peter; Meyer-Lindenberg, Andreas

2015-01-01

Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender’s and receiver’s temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions. PMID:25848050

A Child's Brain: Part III.

ERIC Educational Resources Information Center

Sylwester, Robert

1982-01-01

This article, the last in a series about the human brain, focuses on the skin and its importance for the brain. Physiological functions of the skin, concerning touch and body protection, are explained, as well as its social role in nonverbal communication. Suggestions for student discussions are given. (PP)

The Anatomy of Memory.

ERIC Educational Resources Information Center

Cave, Sitara; Schwartzenberg, Susan

1998-01-01

Fleeting electrochemical connections made between brain cells help people remember the thoughts, skills, experiences, and knowledge that make them unique. Presents the dissection of the brain of a sheep, an animal in which brain structure and function are similar to that in humans, to demonstrate where these processes take place. (PVD)

A balanced view of the cerebrospinal fluid composition and functions: Focus on adult humans.

PubMed

Spector, Reynold; Robert Snodgrass, S; Johanson, Conrad E

2015-11-01

In this review, a companion piece to our recent examination of choroid plexus (CP), the organ that secretes the cerebrospinal fluid (CSF), we focus on recent information in the context of reliable older data concerning the composition and functions of adult human CSF. To accomplish this, we define CSF, examine the methodology employed in studying the CSF focusing on ideal or near ideal experiments and discuss the pros and cons of several widely used analogical descriptions of the CSF including: the CSF as the "third circulation," the CSF as a "nourishing liquor," the similarities of the CSF/choroid plexus to the glomerular filtrate/kidney and finally the CSF circulation as part of the "glymphatic system." We also consider the close interrelationship between the CSF and extracellular space of brain through gap junctions and the paucity of data suggesting that the cerebral capillaries secrete a CSF-like fluid. Recently human CSF has been shown to be in dynamic flux with heart-beat, posture and especially respiration. Functionally, the CSF provides buoyancy, nourishment (e.g., vitamins) and endogenous waste product removal for the brain by bulk flow into the venous (arachnoid villi and nerve roots) and lymphatic (nasal) systems, and by carrier-mediated reabsorptive transport systems in CP. The CSF also presents many exogenous compounds to CP for metabolism or removal, indirectly cleansing the extracellular space of brain (e.g., of xenobiotics like penicillin). The CSF also carries hormones (e.g., leptin) from blood via CP or synthesized in CP (e.g., IGF-2) to the brain. In summary the CP/CSF, the third circulation, performs many functions comparable to the kidney including nourishing the brain and contributing to a stable internal milieu for the brain. These tasks are essential to normal adult brain functioning. Copyright © 2015. Published by Elsevier Inc.

Coherent activity between brain regions that code for value is linked to the malleability of human behavior

PubMed Central

Cooper, Nicole; Bassett, Danielle S.; Falk, Emily B.

2017-01-01

Brain activity in medial prefrontal cortex (MPFC) during exposure to persuasive messages can predict health behavior change. This brain-behavior relationship has been linked to areas of MPFC previously associated with self-related processing; however, the mechanism underlying this relationship is unclear. We explore two components of self-related processing – self-reflection and subjective valuation – and examine coherent activity between relevant networks of brain regions during exposure to health messages encouraging exercise and discouraging sedentary behaviors. We find that objectively logged reductions in sedentary behavior in the following month are linked to functional connectivity within brain regions associated with positive valuation, but not within regions associated with self-reflection on personality traits. Furthermore, functional connectivity between valuation regions contributes additional information compared to average brain activation within single brain regions. These data support an account in which MPFC integrates the value of messages to the self during persuasive health messaging and speak to broader questions of how humans make decisions about how to behave. PMID:28240271

Anti-correlated cortical networks of intrinsic connectivity in the rat brain.

PubMed

Schwarz, Adam J; Gass, Natalia; Sartorius, Alexander; Risterucci, Celine; Spedding, Michael; Schenker, Esther; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang

2013-01-01

In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline "DMN-like" network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans.

Anti-Correlated Cortical Networks of Intrinsic Connectivity in the Rat Brain

PubMed Central

Gass, Natalia; Sartorius, Alexander; Risterucci, Celine; Spedding, Michael; Schenker, Esther; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang

2013-01-01

Abstract In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline “DMN-like” network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans. PMID:23919836

Human hippocampus associates information in memory

PubMed Central

Henke, Katharina; Weber, Bruno; Kneifel, Stefan; Wieser, Heinz Gregor; Buck, Alfred

1999-01-01

The hippocampal formation, one of the most complex and vulnerable brain structures, is recognized as a crucial brain area subserving human long-term memory. Yet, its specific functions in memory are controversial. Recent experimental results suggest that the hippocampal contribution to human memory is limited to episodic memory, novelty detection, semantic (deep) processing of information, and spatial memory. We measured the regional cerebral blood flow by positron-emission tomography while healthy volunteers learned pairs of words with different learning strategies. These led to different forms of learning, allowing us to test the degree to which they challenge hippocampal function. Neither novelty detection nor depth of processing activated the hippocampal formation as much as semantically associating the primarily unrelated words in memory. This is compelling evidence for another function of the human hippocampal formation in memory: establishing semantic associations. PMID:10318979

Developmental Differences in Error-Related ERPs in Middle- to Late-Adolescent Males

ERIC Educational Resources Information Center

Santesso, Diane L.; Segalowitz, Sidney J.

2008-01-01

Although there are some studies documenting structural brain changes during late adolescence, there are few showing functional brain changes over this period in humans. Of special interest would be functional changes in the medial frontal cortex that reflect response monitoring. In order to examine such age-related differences, the authors…

Human Cells Display Reduced Apoptotic Function Relative to Chimpanzee Cells

PubMed Central

McDonald, John F.

2012-01-01

Previously published gene expression analyses suggested that apoptotic function may be reduced in humans relative to chimpanzees and led to the hypothesis that this difference may contribute to the relatively larger size of the human brain and the increased propensity of humans to develop cancer. In this study, we sought to further test the hypothesis that humans maintain a reduced apoptotic function relative to chimpanzees by conducting a series of apoptotic function assays on human, chimpanzee and macaque primary fibroblastic cells. Human cells consistently displayed significantly reduced apoptotic function relative to the chimpanzee and macaque cells. These results are consistent with earlier findings indicating that apoptotic function is reduced in humans relative to chimpanzees. PMID:23029431

Structured Illumination Diffuse Optical Tomography for Mouse Brain Imaging

NASA Astrophysics Data System (ADS)

Reisman, Matthew David

As advances in functional magnetic resonance imaging (fMRI) have transformed the study of human brain function, they have also widened the divide between standard research techniques used in humans and those used in mice, where high quality images are difficult to obtain using fMRI given the small volume of the mouse brain. Optical imaging techniques have been developed to study mouse brain networks, which are highly valuable given the ability to study brain disease treatments or development in a controlled environment. A planar imaging technique known as optical intrinsic signal (OIS) imaging has been a powerful tool for capturing functional brain hemodynamics in rodents. Recent wide field-of-view implementations of OIS have provided efficient maps of functional connectivity from spontaneous brain activity in mice. However, OIS requires scalp retraction and is limited to imaging a 2-dimensional view of superficial cortical tissues. Diffuse optical tomography (DOT) is a non-invasive, volumetric neuroimaging technique that has been valuable for bedside imaging of patients in the clinic, but previous DOT systems for rodent neuroimaging have been limited by either sparse spatial sampling or by slow speed. My research has been to develop diffuse optical tomography for whole brain mouse neuroimaging by expanding previous techniques to achieve high spatial sampling using multiple camera views for detection and high speed using structured illumination sources. I have shown the feasibility of this method to perform non-invasive functional neuroimaging in mice and its capabilities of imaging the entire volume of the brain. Additionally, the system has been built with a custom, flexible framework to accommodate the expansion to imaging multiple dynamic contrasts in the brain and populations that were previously difficult or impossible to image, such as infant mice and awake mice. I have contributed to preliminary feasibility studies of these more advanced techniques using OIS, which can now be carried out using the structured illumination diffuse optical tomography technique to perform longitudinal, non-invasive studies of the whole volume of the mouse brain.

The Conundrum of Functional Brain Networks: Small-World Efficiency or Fractal Modularity

PubMed Central

Gallos, Lazaros K.; Sigman, Mariano; Makse, Hernán A.

2012-01-01

The human brain has been studied at multiple scales, from neurons, circuits, areas with well-defined anatomical and functional boundaries, to large-scale functional networks which mediate coherent cognition. In a recent work, we addressed the problem of the hierarchical organization in the brain through network analysis. Our analysis identified functional brain modules of fractal structure that were inter-connected in a small-world topology. Here, we provide more details on the use of network science tools to elaborate on this behavior. We indicate the importance of using percolation theory to highlight the modular character of the functional brain network. These modules present a fractal, self-similar topology, identified through fractal network methods. When we lower the threshold of correlations to include weaker ties, the network as a whole assumes a small-world character. These weak ties are organized precisely as predicted by theory maximizing information transfer with minimal wiring costs. PMID:22586406

Relationship between diet, the gut microbiota, and brain function.

PubMed

Tengeler, Anouk C; Kozicz, Tamas; Kiliaan, Amanda J

2018-04-28

The human intestinal microbiota, comprising trillions of microorganisms, exerts a substantial effect on the host. The microbiota plays essential roles in the function and development of several physiological processes, including those in the brain. A disruption in the microbial composition of the gut has been associated with many metabolic, inflammatory, neurodevelopmental, and neurodegenerative disorders. Nutrition is one of several key factors that shape the microbial composition during infancy and throughout life, thereby affecting brain structure and function. This review examines the effect of the gut microbiota on brain function. The ability of external factors, such as diet, to influence the microbial composition implies a certain vulnerability of the gut microbiota. However, it also offers a potential therapeutic strategy for ameliorating symptoms of mental and physical disorders. Therefore, this review examines the potential effect of nutritional components on gut microbial composition and brain function.

White matter changes linked to visual recovery after nerve decompression

PubMed Central

Paul, David A.; Gaffin-Cahn, Elon; Hintz, Eric B.; Adeclat, Giscard J.; Zhu, Tong; Williams, Zoë R.; Vates, G. Edward; Mahon, Bradford Z.

2015-01-01

The relationship between the integrity of white matter tracts and cortical function in the human brain remains poorly understood. Here we use a model of reversible white matter injury, compression of the optic chiasm by tumors of the pituitary gland, to study the structural and functional changes that attend spontaneous recovery of cortical function and visual abilities after surgical tumor removal and subsequent decompression of the nerves. We show that compression of the optic chiasm leads to demyelination of the optic tracts, which reverses as quickly as 4 weeks after nerve decompression. Furthermore, variability across patients in the severity of demyelination in the optic tracts predicts visual ability and functional activity in early cortical visual areas, and pre-operative measurements of myelination in the optic tracts predicts the magnitude of visual recovery after surgery. These data indicate that rapid regeneration of myelin in the human brain is a significant component of the normalization of cortical activity, and ultimately the recovery of sensory and cognitive function, after nerve decompression. More generally, our findings demonstrate the utility of diffusion tensor imaging as an in vivo measure of myelination in the human brain. PMID:25504884

Different impressions of other agents obtained through social interaction uniquely modulate dorsal and ventral pathway activities in the social human brain.

PubMed

Takahashi, Hideyuki; Terada, Kazunori; Morita, Tomoyo; Suzuki, Shinsuke; Haji, Tomoki; Kozima, Hideki; Yoshikawa, Masahiro; Matsumoto, Yoshio; Omori, Takashi; Asada, Minoru; Naito, Eiichi

2014-09-01

Internal (neuronal) representations in the brain are modified by our experiences, and this phenomenon is not unique to sensory and motor systems. Here, we show that different impressions obtained through social interaction with a variety of agents uniquely modulate activity of dorsal and ventral pathways of the brain network that mediates human social behavior. We scanned brain activity with functional magnetic resonance imaging (fMRI) in 16 healthy volunteers when they performed a simple matching-pennies game with a human, human-like android, mechanical robot, interactive robot, and a computer. Before playing this game in the scanner, participants experienced social interactions with each opponent separately and scored their initial impressions using two questionnaires. We found that the participants perceived opponents in two mental dimensions: one represented "mind-holderness" in which participants attributed anthropomorphic impressions to some of the opponents that had mental functions, while the other dimension represented "mind-readerness" in which participants characterized opponents as intelligent. Interestingly, this "mind-readerness" dimension correlated to participants frequently changing their game tactic to prevent opponents from envisioning their strategy, and this was corroborated by increased entropy during the game. We also found that the two factors separately modulated activity in distinct social brain regions. Specifically, mind-holderness modulated activity in the dorsal aspect of the temporoparietal junction (TPJ) and medial prefrontal and posterior paracingulate cortices, while mind-readerness modulated activity in the ventral aspect of TPJ and the temporal pole. These results clearly demonstrate that activity in social brain networks is modulated through pre-scanning experiences of social interaction with a variety of agents. Furthermore, our findings elucidated the existence of two distinct functional networks in the social human brain. Social interaction with anthropomorphic or intelligent-looking agents may distinctly shape the internal representation of our social brain, which may in turn determine how we behave for various agents that we encounter in our society. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

A Putative Multiple-Demand System in the Macaque Brain.

PubMed

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

2016-08-17

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

Perceived quality of maternal care in childhood and structure and function of mothers’ brain

PubMed Central

Kim, Pilyoung; Leckman, James F.; Mayes, Linda C.; Newman, Michal-Ann; Feldman, Ruth; Swain, James E.

2014-01-01

Animal studies indicate that early maternal care has long-term effects on brain areas related to social attachment and parenting, whereas neglectful mothering is linked with heightened stress reactivity in the hippocampus across the lifespan. The present study explores the possibility, using magnetic resonance imaging, that perceived quality of maternal care in childhood is associated with brain structure and functional responses to salient infant stimuli among human mothers in the first postpartum month. Mothers who reported higher maternal care in childhood showed larger grey matter volumes in the superior and middle frontal gyri, orbital gyrus, superior temporal gyrus and fusiform gyrus. In response to infant cries, these mothers exhibited higher activations in the middle frontal gyrus, superior temporal gyrus and fusiform gyrus, whereas mothers reporting lower maternal care showed increased hippocampal activations. These findings suggest that maternal care in childhood may be associated with anatomy and functions in brain regions implicated in appropriate responsivity to infant stimuli in human mothers. PMID:20590729

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

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

EEG classification of emotions using emotion-specific brain functional network.

PubMed

Gonuguntla, V; Shafiq, G; Wang, Y; Veluvolu, K C

2015-08-01

The brain functional network perspective forms the basis to relate mechanisms of brain functions. This work analyzes the network mechanisms related to human emotion based on synchronization measure - phase-locking value in EEG to formulate the emotion specific brain functional network. Based on network dissimilarities between emotion and rest tasks, most reactive channel pairs and the reactive band corresponding to emotions are identified. With the identified most reactive pairs, the subject-specific functional network is formed. The identified subject-specific and emotion-specific dynamic network pattern show significant synchrony variation in line with the experiment protocol. The same network pattern are then employed for classification of emotions. With the study conducted on the 4 subjects, an average classification accuracy of 62 % was obtained with the proposed technique.

Dissociable Changes of Frontal and Parietal Cortices in Inherent Functional Flexibility across the Human Life Span.

PubMed

Yin, Dazhi; Liu, Wenjing; Zeljic, Kristina; Wang, Zhiwei; Lv, Qian; Fan, Mingxia; Cheng, Wenhong; Wang, Zheng

2016-09-28

Extensive evidence suggests that frontoparietal regions can dynamically update their pattern of functional connectivity, supporting cognitive control and adaptive implementation of task demands. However, it is largely unknown whether this flexibly functional reconfiguration is intrinsic and occurs even in the absence of overt tasks. Based on recent advances in dynamics of resting-state functional resonance imaging (fMRI), we propose a probabilistic framework in which dynamic reconfiguration of intrinsic functional connectivity between each brain region and others can be represented as a probability distribution. A complexity measurement (i.e., entropy) was used to quantify functional flexibility, which characterizes heterogeneous connectivity between a particular region and others over time. Following this framework, we identified both functionally flexible and specialized regions over the human life span (112 healthy subjects from 13 to 76 years old). Across brainwide regions, we found regions showing high flexibility mainly in the higher-order association cortex, such as the lateral prefrontal cortex (LPFC), lateral parietal cortex, and lateral temporal lobules. In contrast, visual, auditory, and sensory areas exhibited low flexibility. Furthermore, we observed that flexibility of the right LPFC improved during maturation and reduced due to normal aging, with the opposite occurring for the left lateral parietal cortex. Our findings reveal dissociable changes of frontal and parietal cortices over the life span in terms of inherent functional flexibility. This study not only provides a new framework to quantify the spatiotemporal behavior of spontaneous brain activity, but also sheds light on the organizational principle behind changes in brain function across the human life span. Recent neuroscientific research has demonstrated that the human capability of adaptive task control is primarily the result of the flexible operation of frontal brain networks. However, it remains unclear whether this flexibly functional reconfiguration is intrinsic and occurs in the absence of an overt task. In this study, we propose a probabilistic framework to quantify the functional flexibility of each brain region using resting-state fMRI. We identify regions showing high flexibility mainly in the higher-order association cortex. In contrast, primary and unimodal visual and sensory areas show low flexibility. On the other hand, our findings reveal dissociable changes of frontal and parietal cortices in terms of inherent functional flexibility over the life span. Copyright © 2016 the authors 0270-6474/16/3610060-15$15.00/0.

Not single brain areas but a network is involved in language: Applications in presurgical planning.

PubMed

Alemi, Razieh; Batouli, Seyed Amir Hossein; Behzad, Ebrahim; Ebrahimpoor, Mitra; Oghabian, Mohammad Ali

2018-02-01

Language is an important human function, and is a determinant of the quality of life. In conditions such as brain lesions, disruption of the language function may occur, and lesion resection is a solution for that. Presurgical planning to determine the language-related brain areas would enhance the chances of language preservation after the operation; however, availability of a normative language template is essential. In this study, using data from 60 young individuals who were meticulously checked for mental and physical health, and using fMRI and robust imaging and data analysis methods, functional brain maps for the language production, perception and semantic were produced. The obtained templates showed that the language function should be considered as the product of the collaboration of a network of brain regions, instead of considering only few brain areas to be involved in that. This study has important clinical applications, and extends our knowledge on the neuroanatomy of the language function. Copyright © 2018 Elsevier B.V. All rights reserved.

Advantages in functional imaging of the brain.

PubMed

Mier, Walter; Mier, Daniela

2015-01-01

As neuronal pathologies cause only minor morphological alterations, molecular imaging techniques are a prerequisite for the study of diseases of the brain. The development of molecular probes that specifically bind biochemical markers and the advances of instrumentation have revolutionized the possibilities to gain insight into the human brain organization and beyond this-visualize structure-function and brain-behavior relationships. The review describes the development and current applications of functional brain imaging techniques with a focus on applications in psychiatry. A historical overview of the development of functional imaging is followed by the portrayal of the principles and applications of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), two key molecular imaging techniques that have revolutionized the ability to image molecular processes in the brain. We conclude that the juxtaposition of PET and fMRI in hybrid PET/MRI scanners enhances the significance of both modalities for research in neurology and psychiatry and might pave the way for a new area of personalized medicine.

Neural Signatures of Trust During Human-Automation Interactions

DTIC Science & Technology

2016-04-01

magnetic resonance imaging by manipulating the reliability of advice from a human or automated luggage inspector framed as experts. HAT and HHT were...human-human trust, human-automation trust, brain, functional magnetic resonance imaging 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18...behavioral X-ray luggage-screening task with functional magnetic resonance imaging (fMRI) and manipulated reliabilities of advice (unknown to the

Functional brain networks reconstruction using group sparsity-regularized learning.

PubMed

Zhao, Qinghua; Li, Will X Y; Jiang, Xi; Lv, Jinglei; Lu, Jianfeng; Liu, Tianming

2018-06-01

Investigating functional brain networks and patterns using sparse representation of fMRI data has received significant interests in the neuroimaging community. It has been reported that sparse representation is effective in reconstructing concurrent and interactive functional brain networks. To date, most of data-driven network reconstruction approaches rarely take consideration of anatomical structures, which are the substrate of brain function. Furthermore, it has been rarely explored whether structured sparse representation with anatomical guidance could facilitate functional networks reconstruction. To address this problem, in this paper, we propose to reconstruct brain networks utilizing the structure guided group sparse regression (S2GSR) in which 116 anatomical regions from the AAL template, as prior knowledge, are employed to guide the network reconstruction when performing sparse representation of whole-brain fMRI data. Specifically, we extract fMRI signals from standard space aligned with the AAL template. Then by learning a global over-complete dictionary, with the learned dictionary as a set of features (regressors), the group structured regression employs anatomical structures as group information to regress whole brain signals. Finally, the decomposition coefficients matrix is mapped back to the brain volume to represent functional brain networks and patterns. We use the publicly available Human Connectome Project (HCP) Q1 dataset as the test bed, and the experimental results indicate that the proposed anatomically guided structure sparse representation is effective in reconstructing concurrent functional brain networks.

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

PubMed

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

2016-08-01

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

Novel transcriptional networks regulated by CLOCK in human neurons.

PubMed

Fontenot, Miles R; Berto, Stefano; Liu, Yuxiang; Werthmann, Gordon; Douglas, Connor; Usui, Noriyoshi; Gleason, Kelly; Tamminga, Carol A; Takahashi, Joseph S; Konopka, Genevieve

2017-11-01

The molecular mechanisms underlying human brain evolution are not fully understood; however, previous work suggested that expression of the transcription factor CLOCK in the human cortex might be relevant to human cognition and disease. In this study, we investigated this novel transcriptional role for CLOCK in human neurons by performing chromatin immunoprecipitation sequencing for endogenous CLOCK in adult neocortices and RNA sequencing following CLOCK knockdown in differentiated human neurons in vitro. These data suggested that CLOCK regulates the expression of genes involved in neuronal migration, and a functional assay showed that CLOCK knockdown increased neuronal migratory distance. Furthermore, dysregulation of CLOCK disrupts coexpressed networks of genes implicated in neuropsychiatric disorders, and the expression of these networks is driven by hub genes with human-specific patterns of expression. These data support a role for CLOCK-regulated transcriptional cascades involved in human brain evolution and function. © 2017 Fontenot et al.; Published by Cold Spring Harbor Laboratory Press.

A chronological expression profile of gene activity during embryonic mouse brain development.

PubMed

Goggolidou, P; Soneji, S; Powles-Glover, N; Williams, D; Sethi, S; Baban, D; Simon, M M; Ragoussis, I; Norris, D P

2013-12-01

The brain is a functionally complex organ, the patterning and development of which are key to adult health. To help elucidate the genetic networks underlying mammalian brain patterning, we conducted detailed transcriptional profiling during embryonic development of the mouse brain. A total of 2,400 genes were identified as showing differential expression between three developmental stages. Analysis of the data identified nine gene clusters to demonstrate analogous expression profiles. A significant group of novel genes of as yet undiscovered biological function were detected as being potentially relevant to brain development and function, in addition to genes that have previously identified roles in the brain. Furthermore, analysis for genes that display asymmetric expression between the left and right brain hemispheres during development revealed 35 genes as putatively asymmetric from a combined data set. Our data constitute a valuable new resource for neuroscience and neurodevelopment, exposing possible functional associations between genes, including novel loci, and encouraging their further investigation in human neurological and behavioural disorders.

Atlas-guided volumetric diffuse optical tomography enhanced by generalized linear model analysis to image risk decision-making responses in young adults.

PubMed

Lin, Zi-Jing; Li, Lin; Cazzell, Mary; Liu, Hanli

2014-08-01

Diffuse optical tomography (DOT) is a variant of functional near infrared spectroscopy and has the capability of mapping or reconstructing three dimensional (3D) hemodynamic changes due to brain activity. Common methods used in DOT image analysis to define brain activation have limitations because the selection of activation period is relatively subjective. General linear model (GLM)-based analysis can overcome this limitation. In this study, we combine the atlas-guided 3D DOT image reconstruction with GLM-based analysis (i.e., voxel-wise GLM analysis) to investigate the brain activity that is associated with risk decision-making processes. Risk decision-making is an important cognitive process and thus is an essential topic in the field of neuroscience. The Balloon Analog Risk Task (BART) is a valid experimental model and has been commonly used to assess human risk-taking actions and tendencies while facing risks. We have used the BART paradigm with a blocked design to investigate brain activations in the prefrontal and frontal cortical areas during decision-making from 37 human participants (22 males and 15 females). Voxel-wise GLM analysis was performed after a human brain atlas template and a depth compensation algorithm were combined to form atlas-guided DOT images. In this work, we wish to demonstrate the excellence of using voxel-wise GLM analysis with DOT to image and study cognitive functions in response to risk decision-making. Results have shown significant hemodynamic changes in the dorsal lateral prefrontal cortex (DLPFC) during the active-choice mode and a different activation pattern between genders; these findings correlate well with published literature in functional magnetic resonance imaging (fMRI) and fNIRS studies. Copyright © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.

Annual Research Review: Parenting and Children's Brain Development--The End of the Beginning

ERIC Educational Resources Information Center

Belsky, Jay; de Haan, Michelle

2011-01-01

After questioning the practical significance of evidence that parenting influences brain development--while highlighting the scientific importance of such work for understanding "how" family experience shapes human development--this paper reviews evidence suggesting that brain structure and function are "chiselled" by parenting. Although the…

With Boys and Girls in Mind

ERIC Educational Resources Information Center

Gurian, Michael; Stevens, Kathy

2004-01-01

New positron emission tomography (PET) and MRI technologies, which allow looking inside the brains, show that the brains of boys and girls differ both structurally and functionally that profoundly affect the human learning. These gender differences in the brain are corroborated in males and females throughout the world and do not differ…

An anatomical and functional topography of human auditory cortical areas

PubMed Central

Moerel, Michelle; De Martino, Federico; Formisano, Elia

2014-01-01

While advances in magnetic resonance imaging (MRI) throughout the last decades have enabled the detailed anatomical and functional inspection of the human brain non-invasively, to date there is no consensus regarding the precise subdivision and topography of the areas forming the human auditory cortex. Here, we propose a topography of the human auditory areas based on insights on the anatomical and functional properties of human auditory areas as revealed by studies of cyto- and myelo-architecture and fMRI investigations at ultra-high magnetic field (7 Tesla). Importantly, we illustrate that—whereas a group-based approach to analyze functional (tonotopic) maps is appropriate to highlight the main tonotopic axis—the examination of tonotopic maps at single subject level is required to detail the topography of primary and non-primary areas that may be more variable across subjects. Furthermore, we show that considering multiple maps indicative of anatomical (i.e., myelination) as well as of functional properties (e.g., broadness of frequency tuning) is helpful in identifying auditory cortical areas in individual human brains. We propose and discuss a topography of areas that is consistent with old and recent anatomical post-mortem characterizations of the human auditory cortex and that may serve as a working model for neuroscience studies of auditory functions. PMID:25120426

Influence of Fragrances on Human Psychophysiological Activity: With Special Reference to Human Electroencephalographic Response

PubMed Central

Sowndhararajan, Kandhasamy; Kim, Songmun

2016-01-01

The influence of fragrances such as perfumes and room fresheners on the psychophysiological activities of humans has been known for a long time, and its significance is gradually increasing in the medicinal and cosmetic industries. A fragrance consists of volatile chemicals with a molecular weight of less than 300 Da that humans perceive through the olfactory system. In humans, about 300 active olfactory receptor genes are devoted to detecting thousands of different fragrance molecules through a large family of olfactory receptors of a diverse protein sequence. The sense of smell plays an important role in the physiological effects of mood, stress, and working capacity. Electrophysiological studies have revealed that various fragrances affected spontaneous brain activities and cognitive functions, which are measured by an electroencephalograph (EEG). The EEG is a good temporal measure of responses in the central nervous system and it provides information about the physiological state of the brain both in health and disease. The EEG power spectrum is classified into different frequency bands such as delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (13–30 Hz) and gamma (30–50 Hz), and each band is correlated with different features of brain states. A quantitative EEG uses computer software to provide the topographic mapping of the brain activity in frontal, temporal, parietal and occipital brain regions. It is well known that decreases of alpha and beta activities and increases of delta and theta activities are associated with brain pathology and general cognitive decline. In the last few decades, many scientific studies were conducted to investigate the effect of inhalation of aroma on human brain functions. The studies have suggested a significant role for olfactory stimulation in the alteration of cognition, mood, and social behavior. This review aims to evaluate the available literature regarding the influence of fragrances on the psychophysiological activities of humans with special reference to EEG changes. PMID:27916830

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: A review of human brain oscillations as effective endophenotypes

PubMed Central

Rangaswamy, Madhavi; Porjesz, Bernice

2010-01-01

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders. PMID:18634760

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: a review of human brain oscillations as effective endophenotypes.

PubMed

Rangaswamy, Madhavi; Porjesz, Bernice

2008-10-15

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders.

The brain-tumor related protein podoplanin regulates synaptic plasticity and hippocampus-dependent learning and memory.

PubMed

Cicvaric, Ana; Yang, Jiaye; Krieger, Sigurd; Khan, Deeba; Kim, Eun-Jung; Dominguez-Rodriguez, Manuel; Cabatic, Maureen; Molz, Barbara; Acevedo Aguilar, Juan Pablo; Milicevic, Radoslav; Smani, Tarik; Breuss, Johannes M; Kerjaschki, Dontscho; Pollak, Daniela D; Uhrin, Pavel; Monje, Francisco J

2016-12-01

Podoplanin is a cell-surface glycoprotein constitutively expressed in the brain and implicated in human brain tumorigenesis. The intrinsic function of podoplanin in brain neurons remains however uncharacterized. Using an established podoplanin-knockout mouse model and electrophysiological, biochemical, and behavioral approaches, we investigated the brain neuronal role of podoplanin. Ex-vivo electrophysiology showed that podoplanin deletion impairs dentate gyrus synaptic strengthening. In vivo, podoplanin deletion selectively impaired hippocampus-dependent spatial learning and memory without affecting amygdala-dependent cued fear conditioning. In vitro, neuronal overexpression of podoplanin promoted synaptic activity and neuritic outgrowth whereas podoplanin-deficient neurons exhibited stunted outgrowth and lower levels of p-Ezrin, TrkA, and CREB in response to nerve growth factor (NGF). Surface Plasmon Resonance data further indicated a physical interaction between podoplanin and NGF. This work proposes podoplanin as a novel component of the neuronal machinery underlying neuritogenesis, synaptic plasticity, and hippocampus-dependent memory functions. The existence of a relevant cross-talk between podoplanin and the NGF/TrkA signaling pathway is also for the first time proposed here, thus providing a novel molecular complex as a target for future multidisciplinary studies of the brain function in the physiology and the pathology. Key messages Podoplanin, a protein linked to the promotion of human brain tumors, is required in vivo for proper hippocampus-dependent learning and memory functions. Deletion of podoplanin selectively impairs activity-dependent synaptic strengthening at the neurogenic dentate-gyrus and hampers neuritogenesis and phospho Ezrin, TrkA and CREB protein levels upon NGF stimulation. Surface plasmon resonance data indicates a physical interaction between podoplanin and NGF. On these grounds, a relevant cross-talk between podoplanin and NGF as well as a role for podoplanin in plasticity-related brain neuronal functions is here proposed.

[Evolution of human brain and intelligence].

PubMed

Lakatos, László; Janka, Zoltán

2008-07-30

The biological evolution, including human evolution is mainly driven by environmental changes. Accidental genetic modifications and their innovative results make the successful adaptation possible. As we know the human evolution started 7-8 million years ago in the African savannah, where upright position and bipedalism were significantly advantageous. The main drive of improving manual actions and tool making could be to obtain more food. Our ancestor got more meat due to more successful hunting, resulting in more caloric intake, more protein and essential fatty acid in the meal. The nervous system uses disproportionally high level of energy, so better quality of food was a basic condition for the evolution of huge human brain. The size of human brain was tripled during 3.5 million years, it increased from the average of 450 cm3 of Australopithecinae to the average of 1350 cm3 of Homo sapiens. A genetic change in the system controlling gene expression could happen about 200 000 years ago, which influenced the development of nervous system, the sensorimotor function and learning ability for motor processes. The appearance and stabilisation of FOXP2 gene structure as feature of modern man coincided with the first presence and quick spread of Homo sapiens on the whole Earth. This genetic modification made opportunity for human language, as the basis of abrupt evolution of human intelligence. The brain region being responsible for human language is the left planum temporale, which is much larger in left hemisphere. This shows the most typical human brain asymmetry. In this case the anatomical asymmetry means a clearly defined functional asymmetry as well, where the brain hemispheres act differently. The preference in using hands, the lateralised using of tools resulted in the brain asymmetry, which is the precondition of human language and intelligence. However, it cannot be held anymore, that only humans make tools, because our closest relatives, the chimpanzees are able not only to use, but also to make tools, and they can be taught how to produce quite difficult ones. Some brain characteristics connected to human consciousness and intelligence, like brain asymmetry, the "consciousness" or "theory of mind" based on mirror neurons are surprisingly present in monkeys. Nevertheless, the human intelligence is extremely flexible and different, while the animal intelligence is specialised, producing one thing at high level. Based on recent knowledge the level of intelligence is related anatomically to the number of cortical neurons and physiologically to the speed of conductivity of neural pathways, the latter being dependent on the degree of myelinisation. The improvement of cognitive functions including language is driver by the need of more effective communication requiring less energy, the need of social dominance, the competitive advantages within smaller groups and species or against other species, which improves the opportunity for obtaining food. Better mental skills give also sexual dominance, which is beneficial for stabilising "cleverness" genes. The evolutionary history of human consciousness emphasises its adaptive survival helping nature. The evolution of language was the basic condition of conscious thinking as a qualitative change, which fundamentally differentiate us from all other creatures.

Human immunodeficiency virus-infected macrophages produce soluble factors that cause histological and neurochemical alterations in cultured human brains.

PubMed Central

Pulliam, L; Herndier, B G; Tang, N M; McGrath, M S

1991-01-01

We wanted to establish an in vitro human model for AIDS-associated dementia and pursue the hypothesis that this disease process may be a result of soluble factors produced by HIV-infected macrophages. Human brain aggregates were prepared from nine different brain specimens, and were treated with supernatants from in vitro HIV-infected macrophages (SI), uninfected macrophages (SU), infected T cells, or macrophage-conditioned media from four AIDS patients. Seven of nine treated brains exposed to SI showed peripheral rarefaction after 1 wk of incubation that by ultrastructural analysis showed cytoplasmic vacuolation. Aggregates from two of three brain cultures treated with SI for 3 wk became smaller, an approximately 50% decrease in size. The degree of apparent toxicity in brains exposed to patient-derived macrophage supernatants paralleled the proportion of macrophages found to be expressing HIV p24. Ultrastructural abnormalities were not observed in brains treated with supernatants from HIV-infected T cells, uninfected macrophages, or LPS-activated macrophages. Levels of five neurotransmitter amino acids were decreased in comparison to the structural amino acid leucine. These findings suggest that HIV-infected macrophages, infected both in vitro as well as derived from AIDS patients' peripheral blood, produce factors that cause reproducible histochemical, ultrastructural, and functional abnormalities in human brain aggregates. Images PMID:1671392

A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

PubMed

Cecchelli, Romeo; Aday, Sezin; Sevin, Emmanuel; Almeida, Catarina; Culot, Maxime; Dehouck, Lucie; Coisne, Caroline; Engelhardt, Britta; Dehouck, Marie-Pierre; Ferreira, Lino

2014-01-01

The human blood brain barrier (BBB) is a selective barrier formed by human brain endothelial cells (hBECs), which is important to ensure adequate neuronal function and protect the central nervous system (CNS) from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs) express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

Making Sense in the Edge of Chaos: A Framework for Effective Initial Response Efforts to Large-Scale Incidents

DTIC Science & Technology

2010-09-01

working with equally experienced partners who can, cumulatively, help each other make sense of chaotic situations. “Human brains collect, organize...but a process reinforced by years of Fire Department training. No matter what we do, even an optimally functioning human brain will prepare for...trick or reorganize the brain of those who will be first responding incident commanders to an edge-of-chaos event into creatively making sense of

Neuroticism modulates brain visuo-vestibular and anxiety systems during a virtual rollercoaster task.

PubMed

Riccelli, Roberta; Indovina, Iole; Staab, Jeffrey P; Nigro, Salvatore; Augimeri, Antonio; Lacquaniti, Francesco; Passamonti, Luca

2017-02-01

Different lines of research suggest that anxiety-related personality traits may influence the visual and vestibular control of balance, although the brain mechanisms underlying this effect remain unclear. To our knowledge, this is the first functional magnetic resonance imaging (fMRI) study that investigates how individual differences in neuroticism and introversion, two key personality traits linked to anxiety, modulate brain regional responses and functional connectivity patterns during a fMRI task simulating self-motion. Twenty-four healthy individuals with variable levels of neuroticism and introversion underwent fMRI while performing a virtual reality rollercoaster task that included two main types of trials: (1) trials simulating downward or upward self-motion (vertical motion), and (2) trials simulating self-motion in horizontal planes (horizontal motion). Regional brain activity and functional connectivity patterns when comparing vertical versus horizontal motion trials were correlated with personality traits of the Five Factor Model (i.e., neuroticism, extraversion-introversion, openness, agreeableness, and conscientiousness). When comparing vertical to horizontal motion trials, we found a positive correlation between neuroticism scores and regional activity in the left parieto-insular vestibular cortex (PIVC). For the same contrast, increased functional connectivity between the left PIVC and right amygdala was also detected as a function of higher neuroticism scores. Together, these findings provide new evidence that individual differences in personality traits linked to anxiety are significantly associated with changes in the activity and functional connectivity patterns within visuo-vestibular and anxiety-related systems during simulated vertical self-motion. Hum Brain Mapp 38:715-726, 2017. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Toward Developmental Connectomics of the Human Brain

PubMed Central

Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

2016-01-01

Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood, and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and developmental dyslexia). Collectively, we showed that delineation of the brain network from a connectomics perspective offers a unique and refreshing view of both normal development and neuropsychiatric disorders. PMID:27064378

Evidence for hubs in human functional brain networks

PubMed Central

Power, Jonathan D; Schlaggar, Bradley L; Lessov-Schlaggar, Christina N; Petersen, Steven E

2013-01-01

Summary Hubs integrate and distribute information in powerful ways due to the number and positioning of their contacts in a network. Several resting state functional connectivity MRI reports have implicated regions of the default mode system as brain hubs; we demonstrate that previous degree-based approaches to hub identification may have identified portions of large brain systems rather than critical nodes of brain networks. We utilize two methods to identify hub-like brain regions: 1) finding network nodes that participate in multiple sub-networks of the brain, and 2) finding spatial locations where several systems are represented within a small volume. These methods converge on a distributed set of regions that differ from previous reports on hubs. This work identifies regions that support multiple systems, leading to spatially constrained predictions about brain function that may be tested in terms of lesions, evoked responses, and dynamic patterns of activity. PMID:23972601

Proteomics analyses for the global proteins in the brain tissues of different human prion diseases.

PubMed

Shi, Qi; Chen, Li-Na; Zhang, Bao-Yun; Xiao, Kang; Zhou, Wei; Chen, Cao; Zhang, Xiao-Mei; Tian, Chan; Gao, Chen; Wang, Jing; Han, Jun; Dong, Xiao-Ping

2015-04-01

Proteomics changes of brain tissues have been described in different neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the brain proteomics of human prion disease remains less understood. In the study, the proteomics patterns of cortex and cerebellum of brain tissues of sporadic Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD were analyzed with isobaric tags for relative and absolute quantitation combined with multidimensional liquid chromatography and MS analysis, with the brains from three normal individuals as controls. Global protein profiling, significant pathway, and functional categories were analyzed. In total, 2287 proteins were identified with quantitative information both in cortex and cerebellum regions. Cerebellum tissues appeared to contain more up- and down-regulated proteins (727 proteins) than cortex regions (312 proteins) of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD. Viral myocarditis, Parkinson's disease, Alzheimer's disease, lysosome, oxidative phosphorylation, protein export, and drug metabolism-cytochrome P450 were the most commonly affected pathways of the three kinds of diseases. Almost coincident biological functions were identified in the brain tissues of the three diseases. In all, data here demonstrate that the brain tissues of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD have obvious proteomics changes at their terminal stages, which show the similarities not only among human prion diseases but also with other neurodegeneration diseases. This is the first study to provide a reference proteome map for human prion diseases and will be helpful for future studies focused on potential biomarkers for the diagnosis and therapy of human prion diseases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Evidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primates

PubMed Central

Harrison, Peter W.; Caravas, Jason A.; Raghanti, Mary Ann; Phillips, Kimberley A.; Mundy, Nicholas I.

2017-01-01

The adaptive significance of human brain evolution has been frequently studied through comparisons with other primates. However, the evolution of increased brain size is not restricted to the human lineage but is a general characteristic of primate evolution. Whether or not these independent episodes of increased brain size share a common genetic basis is unclear. We sequenced and de novo assembled the transcriptome from the neocortical tissue of the most highly encephalized nonhuman primate, the tufted capuchin monkey (Cebus apella). Using this novel data set, we conducted a genome-wide analysis of orthologous brain-expressed protein coding genes to identify evidence of conserved gene–phenotype associations and species-specific adaptations during three independent episodes of brain size increase. We identify a greater number of genes associated with either total brain mass or relative brain size across these six species than show species-specific accelerated rates of evolution in individual large-brained lineages. We test the robustness of these associations in an expanded data set of 13 species, through permutation tests and by analyzing how genome-wide patterns of substitution co-vary with brain size. Many of the genes targeted by selection during brain expansion have glutamatergic functions or roles in cell cycle dynamics. We also identify accelerated evolution in a number of individual capuchin genes whose human orthologs are associated with human neuropsychiatric disorders. These findings demonstrate the value of phenotypically informed genome analyses, and suggest at least some aspects of human brain evolution have occurred through conserved gene–phenotype associations. Understanding these commonalities is essential for distinguishing human-specific selection events from general trends in brain evolution. PMID:28391320

Impact of Zika Virus on adult human brain structure and functional organization.

PubMed

Bido-Medina, Richard; Wirsich, Jonathan; Rodríguez, Minelly; Oviedo, Jairo; Miches, Isidro; Bido, Pamela; Tusen, Luis; Stoeter, Peter; Sadaghiani, Sepideh

2018-06-01

To determine the impact of Zika virus (ZIKV) infection on brain structure and functional organization of severely affected adult patients with neurological complications that extend beyond Guillain-Barré Syndrome (GBS)-like manifestations and include symptoms of the central nervous system (CNS). In this first case-control neuroimaging study, we obtained structural and functional magnetic resonance images in nine rare adult patients in the subacute phase, and healthy age- and sex-matched controls. ZIKV patients showed atypical descending and rapidly progressing peripheral nervous system (PNS) manifestations, and importantly, additional CNS presentations such as perceptual deficits. Voxel-based morphometry was utilized to evaluate gray matter volume, and resting state functional connectivity and Network Based Statistics were applied to assess the functional organization of the brain. Gray matter volume was decreased bilaterally in motor areas (supplementary motor cortex, specifically Frontal Eye Fields) and beyond (left inferior frontal sulcus). Additionally, gray matter volume increased in right middle frontal gyrus. Functional connectivity increased in a widespread network within and across temporal lobes. We provide preliminary evidence for a link between ZIKV neurological complications and changes in adult human brain structure and functional organization, comprising both motor-related regions potentially secondary to prolonged PNS weakness, and nonsomatomotor regions indicative of PNS-independent alternations. The latter included the temporal lobes, particularly vulnerable in a range of neurological conditions. While future studies into the ZIKV-related neuroinflammatory mechanisms in adults are urgently needed, this study indicates that ZIKV infection can lead to an impact on the brain.

An animal-to-human scaling law for blast-induced traumatic brain injury risk assessment.

PubMed

Jean, Aurélie; Nyein, Michelle K; Zheng, James Q; Moore, David F; Joannopoulos, John D; Radovitzky, Raúl

2014-10-28

Despite recent efforts to understand blast effects on the human brain, there are still no widely accepted injury criteria for humans. Recent animal studies have resulted in important advances in the understanding of brain injury due to intense dynamic loads. However, the applicability of animal brain injury results to humans remains uncertain. Here, we use advanced computational models to derive a scaling law relating blast wave intensity to the mechanical response of brain tissue across species. Detailed simulations of blast effects on the brain are conducted for different mammals using image-based biofidelic models. The intensity of the stress waves computed for different external blast conditions is compared across species. It is found that mass scaling, which successfully estimates blast tolerance of the thorax, fails to capture the brain mechanical response to blast across mammals. Instead, we show that an appropriate scaling variable must account for the mass of protective tissues relative to the brain, as well as their acoustic impedance. Peak stresses transmitted to the brain tissue by the blast are then shown to be a power function of the scaling parameter for a range of blast conditions relevant to TBI. In particular, it is found that human brain vulnerability to blast is higher than for any other mammalian species, which is in distinct contrast to previously proposed scaling laws based on body or brain mass. An application of the scaling law to recent experiments on rabbits furnishes the first physics-based injury estimate for blast-induced TBI in humans.

Neuroimaging in human MDMA (Ecstasy) users: A cortical model

PubMed Central

Cowan, Ronald L; Roberts, Deanne M; Joers, James M

2009-01-01

MDMA (3,4 methylenedioxymethamphetamine) has been used by millions of people worldwide as a recreational drug. MDMA and Ecstasy are often used synonymously but it is important to note that the purity of Ecstasy sold as MDMA is not certain. MDMA use is of public health concern, not so much because MDMA produces a common or severe dependence syndrome, but rather because rodent and non-human primate studies have indicated that MDMA (when administered at certain dosages and intervals) can cause long-lasting reductions in markers of brain serotonin (5-HT) that appear specific to fine diameter axons arising largely from the dorsal raphe nucleus (DR). Given the popularity of MDMA, the potential for the drug to produce long-lasting or permanent 5-HT axon damage or loss, and the widespread role of 5-HT function in the brain, there is a great need for a better understanding of brain function in human users of this drug. To this end, neuropsychological, neuroendocrine, and neuroimaging studies have all suggested that human MDMA users may have long-lasting changes in brain function consistent with 5-HT toxicity. Data from animal models leads to testable hypotheses regarding MDMA effects on the human brain. Because neuropsychological and neuroimaging findings have focused on the neocortex, a cortical model is developed to provide context for designing and interpreting neuroimaging studies in MDMA users. Aspects of the model are supported by the available neuroimaging data but there are controversial findings in some areas and most findings have not been replicated across different laboratories and using different modalities. This paper reviews existing findings in the context of a cortical model and suggests directions for future research. PMID:18991874

The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by beta-amyloid peptide.

PubMed

Kurz, C; Ungerer, I; Lipka, U; Kirr, S; Schütt, T; Eckert, A; Leuner, K; Müller, W E

2010-05-01

beta-Amyloid peptide (Abeta) is implicated in the pathogenesis of Alzheimer's disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally induced oxidative stress. We used cell lines (PC12 and HEK cells) and murine dissociated brain cells. The protective effects of piracetam in vitro and ex vivo on Abeta-induced impairment of mitochondrial function (as mitochondrial membrane potential and ATP production), on secretion of soluble Abeta and on neurite outgrowth in PC12 cells were investigated. Piracetam improves mitochondrial function of PC12 cells and acutely dissociated brain cells from young NMRI mice following exposure to extracellular Abeta(1-42). Similar protective effects against Abeta(1-42) were observed in dissociated brain cells from aged NMRI mice, or mice transgenic for mutant human amyloid precursor protein (APP) treated with piracetam for 14 days. Soluble Abeta load was markedly diminished in the brain of those animals after treatment with piracetam. Abeta production by HEK cells stably transfected with mutant human APP was elevated by oxidative stress and this was reduced by piracetam. Impairment of neuritogenesis is an important consequence of Abeta-induced mitochondrial dysfunction and Abeta-induced reduction of neurite growth in PC12 cells was substantially improved by piracetam. Our findings strongly support the concept of improving mitochondrial function as an approach to ameliorate the detrimental effects of Abeta on brain function.

Finer parcellation reveals detailed correlational structure of resting-state fMRI signals.

PubMed

Dornas, João V; Braun, Jochen

2018-01-15

Even in resting state, the human brain generates functional signals (fMRI) with complex correlational structure. To simplify this structure, it is common to parcellate a standard brain into coarse chunks. Finer parcellations are considered less reproducible and informative, due to anatomical and functional variability of individual brains. Grouping signals with similar local correlation profiles, restricted to each anatomical region (Tzourio-Mazoyer et al., 2002), we divide a standard brain into 758 'functional clusters' averaging 1.7cm 3 gray matter volume ('MD758' parcellation). We compare 758 'spatial clusters' of similar size ('S758'). 'Functional clusters' are spatially contiguous and cluster quality (integration and segregation of temporal variance) is far superior to 'spatial clusters', comparable to multi-modal parcellations of half the resolution (Craddock et al., 2012; Glasser et al., 2016). Moreover, 'functional clusters' capture many long-range functional correlations, with O(10 5 ) reproducibly correlated cluster pairs in different anatomical regions. The pattern of functional correlations closely mirrors long-range anatomical connectivity established by fibre tracking. MD758 is comparable to coarser parcellations (Craddock et al., 2012; Glasser et al., 2016) in terms of cluster quality, correlational structure (54% relative mutual entropy vs 60% and 61%), and sparseness (35% significant pairwise correlations vs 36% and 44%). We describe and evaluate a simple path to finer functional parcellations of the human brain. Detailed correlational structure is surprisingly consistent between individuals, opening new possibilities for comparing functional correlations between cognitive conditions, states of health, or pharmacological interventions. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Testosterone affects language areas of the adult human brain.

PubMed

Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

2016-05-01

Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Maintaining brain health by monitoring inflammatory processes: a mechanism to promote successful aging.

PubMed

Rosano, Caterina; Marsland, Anna L; Gianaros, Peter J

2012-02-01

Maintaining brain health promotes successful aging. The main determinants of brain health are the preservation of cognitive function and remaining free from structural and metabolic abnormalities, including loss of neuronal synapses, atrophy, small vessel disease and focal amyloid deposits visible by neuroimaging. Promising studies indicate that these determinants are to some extent modifiable, even among adults seventy years and older. Converging animal and human evidence further suggests that inflammation is a shared mechanism, contributing to both cognitive decline and abnormalities in brain structure and metabolism. Thus, inflammation may provide a target for intervention. Specifically, circulating inflammatory markers have been associated with declines in cognitive function and worsening of brain structural and metabolic characteristics. Additionally, it has been proposed that older brains are characterized by a sensitization to neuroinflammatory responses, even in the absence of overt disease. This increased propensity to central inflammation may contribute to poor brain health and premature brain aging. Still unknown is whether and how peripheral inflammatory factors directly contribute to decline of brain health. Human research is limited by the challenges of directly measuring neuroinflammation in vivo. This review assesses the role that inflammation may play in the brain changes that often accompany aging, focusing on relationships between peripheral inflammatory markers and brain health among well-functioning, community-dwelling adults seventy years and older. We propose that monitoring and maintaining lower levels of systemic and central inflammation among older adults could help preserve brain health and support successful aging. Hence, we also identify plausible ways and novel experimental study designs of maintaining brain health late in age through interventions that target the immune system.

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

PubMed

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

2013-06-01

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

Insights into Brain Glycogen Metabolism: THE STRUCTURE OF HUMAN BRAIN GLYCOGEN PHOSPHORYLASE.

PubMed

Mathieu, Cécile; Li de la Sierra-Gallay, Ines; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

2016-08-26

Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Derivation of Functional Human Astrocytes from Cerebral Organoids

PubMed Central

Dezonne, Rômulo Sperduto; Sartore, Rafaela Costa; Nascimento, Juliana Minardi; Saia-Cereda, Verônica M.; Romão, Luciana Ferreira; Alves-Leon, Soniza Vieira; de Souza, Jorge Marcondes; Martins-de-Souza, Daniel; Rehen, Stevens Kastrup; Gomes, Flávia Carvalho Alcantara

2017-01-01

Astrocytes play a critical role in the development and homeostasis of the central nervous system (CNS). Astrocyte dysfunction results in several neurological and degenerative diseases. However, a major challenge to our understanding of astrocyte physiology and pathology is the restriction of studies to animal models, human post-mortem brain tissues, or samples obtained from invasive surgical procedures. Here, we report a protocol to generate human functional astrocytes from cerebral organoids derived from human pluripotent stem cells. The cellular isolation of cerebral organoids yielded cells that were morphologically and functionally like astrocytes. Immunolabelling and proteomic assays revealed that human organoid-derived astrocytes express the main astrocytic molecular markers, including glutamate transporters, specific enzymes and cytoskeletal proteins. We found that organoid-derived astrocytes strongly supported neuronal survival and neurite outgrowth and responded to ATP through transient calcium wave elevations, which are hallmarks of astrocyte physiology. Additionally, these astrocytes presented similar functional pathways to those isolated from adult human cortex by surgical procedures. This is the first study to provide proteomic and functional analyses of astrocytes isolated from human cerebral organoids. The isolation of these astrocytes holds great potential for the investigation of developmental and evolutionary features of the human brain and provides a useful approach to drug screening and neurodegenerative disease modelling. PMID:28345587

Metabolic constraint imposes tradeoff between body size and number of brain neurons in human evolution

PubMed Central

Fonseca-Azevedo, Karina; Herculano-Houzel, Suzana

2012-01-01

Despite a general trend for larger mammals to have larger brains, humans are the primates with the largest brain and number of neurons, but not the largest body mass. Why are great apes, the largest primates, not also those endowed with the largest brains? Recently, we showed that the energetic cost of the brain is a linear function of its numbers of neurons. Here we show that metabolic limitations that result from the number of hours available for feeding and the low caloric yield of raw foods impose a tradeoff between body size and number of brain neurons, which explains the small brain size of great apes compared with their large body size. This limitation was probably overcome in Homo erectus with the shift to a cooked diet. Absent the requirement to spend most available hours of the day feeding, the combination of newly freed time and a large number of brain neurons affordable on a cooked diet may thus have been a major positive driving force to the rapid increased in brain size in human evolution. PMID:23090991

Metabolic constraint imposes tradeoff between body size and number of brain neurons in human evolution.

PubMed

Fonseca-Azevedo, Karina; Herculano-Houzel, Suzana

2012-11-06

Despite a general trend for larger mammals to have larger brains, humans are the primates with the largest brain and number of neurons, but not the largest body mass. Why are great apes, the largest primates, not also those endowed with the largest brains? Recently, we showed that the energetic cost of the brain is a linear function of its numbers of neurons. Here we show that metabolic limitations that result from the number of hours available for feeding and the low caloric yield of raw foods impose a tradeoff between body size and number of brain neurons, which explains the small brain size of great apes compared with their large body size. This limitation was probably overcome in Homo erectus with the shift to a cooked diet. Absent the requirement to spend most available hours of the day feeding, the combination of newly freed time and a large number of brain neurons affordable on a cooked diet may thus have been a major positive driving force to the rapid increased in brain size in human evolution.

Control-related systems in the human brain

PubMed Central

Power, Jonathan D; Petersen, Steven E

2013-01-01

A fundamental question in cognitive neuroscience is how the human brain self-organizes to perform tasks. Multiple accounts of this self-organization are currently influential and in this article we survey one of these accounts. We begin by introducing a psychological model of task control and several neuroimaging signals it predicts. We then discuss where such signals are found across tasks with emphasis on brain regions where multiple control signals are present. We then present results derived from spontaneous task-free functional connectivity between control-related regions that dovetail with distinctions made by control signals present in these regions, leading to a proposal that there are at least two task control systems in the brain. This prompts consideration of whether and how such control systems distinguish themselves from other brain regions in a whole-brain context. We present evidence from whole-brain networks that such distinctions do occur and that control systems comprise some of the basic system-level organizational elements of the human brain. We close with observations from the whole-brain networks that may suggest parsimony between multiple accounts of cognitive control. PMID:23347645

Human brain mapping: A systematic comparison of parcellation methods for the human cerebral cortex.

PubMed

Arslan, Salim; Ktena, Sofia Ira; Makropoulos, Antonios; Robinson, Emma C; Rueckert, Daniel; Parisot, Sarah

2018-04-15

The macro-connectome elucidates the pathways through which brain regions are structurally connected or functionally coupled to perform a specific cognitive task. It embodies the notion of representing and understanding all connections within the brain as a network, while the subdivision of the brain into interacting functional units is inherent in its architecture. As a result, the definition of network nodes is one of the most critical steps in connectivity network analysis. Although brain atlases obtained from cytoarchitecture or anatomy have long been used for this task, connectivity-driven methods have arisen only recently, aiming to delineate more homogeneous and functionally coherent regions. This study provides a systematic comparison between anatomical, connectivity-driven and random parcellation methods proposed in the thriving field of brain parcellation. Using resting-state functional MRI data from the Human Connectome Project and a plethora of quantitative evaluation techniques investigated in the literature, we evaluate 10 subject-level and 24 groupwise parcellation methods at different resolutions. We assess the accuracy of parcellations from four different aspects: (1) reproducibility across different acquisitions and groups, (2) fidelity to the underlying connectivity data, (3) agreement with fMRI task activation, myelin maps, and cytoarchitectural areas, and (4) network analysis. This extensive evaluation of different parcellations generated at the subject and group level highlights the strengths and shortcomings of the various methods and aims to provide a guideline for the choice of parcellation technique and resolution according to the task at hand. The results obtained in this study suggest that there is no optimal method able to address all the challenges faced in this endeavour simultaneously. Copyright © 2017 Elsevier Inc. All rights reserved.

In vivo functional connectome of human brainstem nuclei of the ascending arousal, autonomic, and motor systems by high spatial resolution 7-Tesla fMRI.

PubMed

Bianciardi, Marta; Toschi, Nicola; Eichner, Cornelius; Polimeni, Jonathan R; Setsompop, Kawin; Brown, Emery N; Hämäläinen, Matti S; Rosen, Bruce R; Wald, Lawrence L

2016-06-01

Our aim was to map the in vivo human functional connectivity of several brainstem nuclei with the rest of the brain by using seed-based correlation of ultra-high magnetic field functional magnetic resonance imaging (fMRI) data. We used the recently developed template of 11 brainstem nuclei derived from multi-contrast structural MRI at 7 Tesla as seed regions to determine their connectivity to the rest of the brain. To achieve this, we used the increased contrast-to-noise ratio of 7-Tesla fMRI compared with 3 Tesla and time-efficient simultaneous multi-slice imaging to cover the brain with high spatial resolution (1.1-mm isotropic nominal resolution) while maintaining a short repetition time (2.5 s). The delineated Pearson's correlation-based functional connectivity diagrams (connectomes) of 11 brainstem nuclei of the ascending arousal, motor, and autonomic systems from 12 controls are presented and discussed in the context of existing histology and animal work. Considering that the investigated brainstem nuclei play a crucial role in several vital functions, the delineated preliminary connectomes might prove useful for future in vivo research and clinical studies of human brainstem function and pathology, including disorders of consciousness, sleep disorders, autonomic disorders, Parkinson's disease, and other motor disorders.

Constructing fine-granularity functional brain network atlases via deep convolutional autoencoder.

PubMed

Zhao, Yu; Dong, Qinglin; Chen, Hanbo; Iraji, Armin; Li, Yujie; Makkie, Milad; Kou, Zhifeng; Liu, Tianming

2017-12-01

State-of-the-art functional brain network reconstruction methods such as independent component analysis (ICA) or sparse coding of whole-brain fMRI data can effectively infer many thousands of volumetric brain network maps from a large number of human brains. However, due to the variability of individual brain networks and the large scale of such networks needed for statistically meaningful group-level analysis, it is still a challenging and open problem to derive group-wise common networks as network atlases. Inspired by the superior spatial pattern description ability of the deep convolutional neural networks (CNNs), a novel deep 3D convolutional autoencoder (CAE) network is designed here to extract spatial brain network features effectively, based on which an Apache Spark enabled computational framework is developed for fast clustering of larger number of network maps into fine-granularity atlases. To evaluate this framework, 10 resting state networks (RSNs) were manually labeled from the sparsely decomposed networks of Human Connectome Project (HCP) fMRI data and 5275 network training samples were obtained, in total. Then the deep CAE models are trained by these functional networks' spatial maps, and the learned features are used to refine the original 10 RSNs into 17 network atlases that possess fine-granularity functional network patterns. Interestingly, it turned out that some manually mislabeled outliers in training networks can be corrected by the deep CAE derived features. More importantly, fine granularities of networks can be identified and they reveal unique network patterns specific to different brain task states. By further applying this method to a dataset of mild traumatic brain injury study, it shows that the technique can effectively identify abnormal small networks in brain injury patients in comparison with controls. In general, our work presents a promising deep learning and big data analysis solution for modeling functional connectomes, with fine granularities, based on fMRI data. Copyright © 2017 Elsevier B.V. All rights reserved.

Brain Imaging and Human Nutrition: Which Measures to Use in Intervention Studies?12

PubMed Central

Sizonenko, Stéphane V.; Babiloni, Claudio; Sijben, John W.; Walhovd, Kristine B.

2013-01-01

Throughout the life span, the brain is a metabolically highly active organ that uses a large proportion of total nutrient and energy intake. Furthermore, the development and repair of neural tissue depend on the proper intake of essential structural nutrients, minerals, and vitamins. Therefore, what we eat, or refrain from eating, may have an important impact on our cognitive ability and mental performance. Two of the key areas in which diet is thought to play an important role are in optimizing neurodevelopment in children and in preventing neurodegeneration and cognitive decline during aging. From early development to aging, brain imaging can detect structural, functional, and metabolic changes in humans and modifications due to altered nutrition or to additional nutritional supplementation. Inclusion of imaging measures in clinical studies can increase understanding with regard to the modification of brain structure, metabolism, and functional endpoints and may provide early sensitive measures of long-term effects. In this symposium, the utility of existing brain imaging technologies to assess the effects of nutritional intervention in humans is described. Examples of current research showing the utility of these markers are reviewed. PMID:24038255

An anatomically comprehensive atlas of the adult human brain transcriptome

PubMed Central

Guillozet-Bongaarts, Angela L.; Shen, Elaine H.; Ng, Lydia; Miller, Jeremy A.; van de Lagemaat, Louie N.; Smith, Kimberly A.; Ebbert, Amanda; Riley, Zackery L.; Abajian, Chris; Beckmann, Christian F.; Bernard, Amy; Bertagnolli, Darren; Boe, Andrew F.; Cartagena, Preston M.; Chakravarty, M. Mallar; Chapin, Mike; Chong, Jimmy; Dalley, Rachel A.; David Daly, Barry; Dang, Chinh; Datta, Suvro; Dee, Nick; Dolbeare, Tim A.; Faber, Vance; Feng, David; Fowler, David R.; Goldy, Jeff; Gregor, Benjamin W.; Haradon, Zeb; Haynor, David R.; Hohmann, John G.; Horvath, Steve; Howard, Robert E.; Jeromin, Andreas; Jochim, Jayson M.; Kinnunen, Marty; Lau, Christopher; Lazarz, Evan T.; Lee, Changkyu; Lemon, Tracy A.; Li, Ling; Li, Yang; Morris, John A.; Overly, Caroline C.; Parker, Patrick D.; Parry, Sheana E.; Reding, Melissa; Royall, Joshua J.; Schulkin, Jay; Sequeira, Pedro Adolfo; Slaughterbeck, Clifford R.; Smith, Simon C.; Sodt, Andy J.; Sunkin, Susan M.; Swanson, Beryl E.; Vawter, Marquis P.; Williams, Derric; Wohnoutka, Paul; Zielke, H. Ronald; Geschwind, Daniel H.; Hof, Patrick R.; Smith, Stephen M.; Koch, Christof; Grant, Seth G. N.; Jones, Allan R.

2014-01-01

Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ~900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography— the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function. PMID:22996553

Distributed affective space represents multiple emotion categories across the human brain

PubMed Central

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

2018-01-01

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

Integrating Retinoic Acid Signaling with Brain Function

ERIC Educational Resources Information Center

Luo, Tuanlian; Wagner, Elisabeth; Drager, Ursula C.

2009-01-01

The vitamin A derivative retinoic acid (RA) regulates the transcription of about a 6th of the human genome. Compelling evidence indicates a role of RA in cognitive activities, but its integration with the molecular mechanisms of higher brain functions is not known. Here we describe the properties of RA signaling in the mouse, which point to…

Individual Brain Charting, a high-resolution fMRI dataset for cognitive mapping.

PubMed

Pinho, Ana Luísa; Amadon, Alexis; Ruest, Torsten; Fabre, Murielle; Dohmatob, Elvis; Denghien, Isabelle; Ginisty, Chantal; Becuwe-Desmidt, Séverine; Roger, Séverine; Laurier, Laurence; Joly-Testault, Véronique; Médiouni-Cloarec, Gaëlle; Doublé, Christine; Martins, Bernadette; Pinel, Philippe; Eger, Evelyn; Varoquaux, Gaël; Pallier, Christophe; Dehaene, Stanislas; Hertz-Pannier, Lucie; Thirion, Bertrand

2018-06-12

Functional Magnetic Resonance Imaging (fMRI) has furthered brain mapping on perceptual, motor, as well as higher-level cognitive functions. However, to date, no data collection has systematically addressed the functional mapping of cognitive mechanisms at a fine spatial scale. The Individual Brain Charting (IBC) project stands for a high-resolution multi-task fMRI dataset that intends to provide the objective basis toward a comprehensive functional atlas of the human brain. The data refer to a cohort of 12 participants performing many different tasks. The large amount of task-fMRI data on the same subjects yields a precise mapping of the underlying functions, free from both inter-subject and inter-site variability. The present article gives a detailed description of the first release of the IBC dataset. It comprises a dozen of tasks, addressing both low- and high- level cognitive functions. This openly available dataset is thus intended to become a reference for cognitive brain mapping.

Comparison Between Folic Acid and gH625 Peptide-Based Functionalization of Fe3O4 Magnetic Nanoparticles for Enhanced Cell Internalization

NASA Astrophysics Data System (ADS)

Tudisco, C.; Cambria, M. T.; Giuffrida, A. E.; Sinatra, F.; Anfuso, C. D.; Lupo, G.; Caporarello, N.; Falanga, A.; Galdiero, S.; Oliveri, V.; Satriano, C.; Condorelli, G. G.

2018-02-01

A versatile synthetic route based on magnetic Fe3O4 nanoparticle (MNP) prefunctionalization with a phosphonic acid monolayer has been used to covalently bind the gH625 peptide on the nanoparticle surface. gH625 is a membranotropic peptide capable of easily crossing the membranes of various cells including the typical human blood-brain barrier components. A similar synthetic route was used to prepare another class of MNPs having a functional coating based on PEG, rhodamine, and folic acid, a well-known target molecule, to compare the performance of the two cell-penetrating systems (i.e., gH625 and folic acid). Our results demonstrate that the uptake of gH625-decorated MNPs in immortalized human brain microvascular endothelial cells after 24 h is more evident compared to folic acid-functionalized MNPs as evidenced by confocal laser scanning microscopy. On the other hand, both functionalized systems proved capable of being internalized in a brain tumor cell line (i.e., glioblastoma A-172). These findings indicate that the functionalization of MNPs with gH625 improves their endothelial cell internalization, suggesting a viable strategy in designing functional nanostructures capable of first crossing the BBB and, then, of reaching specific tumor brain cells.

Studying variability in human brain aging in a population-based German cohort-rationale and design of 1000BRAINS.

PubMed

Caspers, Svenja; Moebus, Susanne; Lux, Silke; Pundt, Noreen; Schütz, Holger; Mühleisen, Thomas W; Gras, Vincent; Eickhoff, Simon B; Romanzetti, Sandro; Stöcker, Tony; Stirnberg, Rüdiger; Kirlangic, Mehmet E; Minnerop, Martina; Pieperhoff, Peter; Mödder, Ulrich; Das, Samir; Evans, Alan C; Jöckel, Karl-Heinz; Erbel, Raimund; Cichon, Sven; Nöthen, Markus M; Sturma, Dieter; Bauer, Andreas; Jon Shah, N; Zilles, Karl; Amunts, Katrin

2014-01-01

The ongoing 1000 brains study (1000BRAINS) is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR) Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45-75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions and language; examination of motor skills; ratings of personality, life quality, mood and daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3 Tesla) of the brain. The latter includes (i) 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii) three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fiber tracking and for diffusion kurtosis imaging; (iii) resting-state and task-based functional MRI; and (iv) fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i) comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii) identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates.

Cortical Plasticity and Olfactory Function in Early Blindness

PubMed Central

Araneda, Rodrigo; Renier, Laurent A.; Rombaux, Philippe; Cuevas, Isabel; De Volder, Anne G.

2016-01-01

Over the last decade, functional brain imaging has provided insight to the maturation processes and has helped elucidate the pathophysiological mechanisms involved in brain plasticity in the absence of vision. In case of congenital blindness, drastic changes occur within the deafferented “visual” cortex that starts receiving and processing non visual inputs, including olfactory stimuli. This functional reorganization of the occipital cortex gives rise to compensatory perceptual and cognitive mechanisms that help blind persons achieve perceptual tasks, leading to superior olfactory abilities in these subjects. This view receives support from psychophysical testing, volumetric measurements and functional brain imaging studies in humans, which are presented here. PMID:27625596

Imaging deductive reasoning and the new paradigm

PubMed Central

Oaksford, Mike

2015-01-01

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

Novel Antitransferrin Receptor Antibodies Improve the Blood-Brain Barrier Crossing Efficacy of Immunoliposomes.

PubMed

Gregori, Maria; Orlando, Antonina; Re, Francesca; Sesana, Silvia; Nardo, Luca; Salerno, Domenico; Mantegazza, Francesco; Salvati, Elisa; Zito, Andrea; Malavasi, Fabio; Masserini, Massimo; Cazzaniga, Emanuela

2016-01-01

Surface functionalization with antitransferrin receptor (TfR) mAbs has been suggested as the strategy to enhance the transfer of nanoparticles (NPs) across the blood-brain barrier (BBB) and to carry nonpermeant drugs from the blood into the brain. However, the efficiency of BBB crossing is currently too poor to be used in vivo. In the present investigation, we compared 6 different murine mAbs specific for different epitopes of the human TfR to identify the best performing one for the functionalization of NPs. For this purpose, we compared the ability of mAbs to cross an in vitro BBB model made of human brain capillary endothelial cells (hCMEC/D3). Liposomes functionalized with the best performing mAb (MYBE/4C1) were uptaken, crossed the BBB in vitro, and facilitated the BBB in vitro passage of doxorubicin, an anticancer drug, 3.9 folds more than liposomes functionalized with a nonspecific IgG, as assessed by confocal microscopy, radiochemical techniques, and fluorescence, and did not modify the cell monolayer structural or functional properties. These results show that MYBE/4C1 antihuman TfR mAb is a powerful resource for the enhancement of BBB crossing of NPs and is therefore potentially useful in the treatment of neurologic diseases and disorders including brain carcinomas. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Genetic enhancement of cognition in a kindred with cone–rod dystrophy due to RIMS1 mutation

PubMed Central

Sisodiya, Sanjay M; Thompson, Pamela J; Need, Anna; Harris, Sarah E; Weale, Michael E; Wilkie, Susan E; Michaelides, Michel; Free, Samantha L; Walley, Nicole; Gumbs, Curtis; Gerrelli, Dianne; Ruddle, Piers; Whalley, Lawrence J; Starr, John M; Hunt, David M; Goldstein, David B; Deary, Ian J; Moore, Anthony T

2007-01-01

Background The genetic basis of variation in human cognitive abilities is poorly understood. RIMS1 encodes a synapse active‐zone protein with important roles in the maintenance of normal synaptic function: mice lacking this protein have greatly reduced learning ability and memory function. Objective An established paradigm examining the structural and functional effects of mutations in genes expressed in the eye and the brain was used to study a kindred with an inherited retinal dystrophy due to RIMS1 mutation. Materials and methods Neuropsychological tests and high‐resolution MRI brain scanning were undertaken in the kindred. In a population cohort, neuropsychological scores were associated with common variation in RIMS1. Additionally, RIMS1 was sequenced in top‐scoring individuals. Evolution of RIMS1 was assessed, and its expression in developing human brain was studied. Results Affected individuals showed significantly enhanced cognitive abilities across a range of domains. Analysis suggests that factors other than RIMS1 mutation were unlikely to explain enhanced cognition. No association with common variation and verbal IQ was found in the population cohort, and no other mutations in RIMS1 were detected in the highest scoring individuals from this cohort. RIMS1 protein is expressed in developing human brain, but RIMS1 does not seem to have been subjected to accelerated evolution in man. Conclusions A possible role for RIMS1 in the enhancement of cognitive function at least in this kindred is suggested. Although further work is clearly required to explore these findings before a role for RIMS1 in human cognition can be formally accepted, the findings suggest that genetic mutation may enhance human cognition in some cases. PMID:17237123

Neuronal glycogen synthesis contributes to physiological aging.

PubMed

Sinadinos, Christopher; Valles-Ortega, Jordi; Boulan, Laura; Solsona, Estel; Tevy, Maria F; Marquez, Mercedes; Duran, Jordi; Lopez-Iglesias, Carmen; Calbó, Joaquim; Blasco, Ester; Pumarola, Marti; Milán, Marco; Guinovart, Joan J

2014-10-01

Glycogen is a branched polymer of glucose and the carbohydrate energy store for animal cells. In the brain, it is essentially found in glial cells, although it is also present in minute amounts in neurons. In humans, loss-of-function mutations in laforin and malin, proteins involved in suppressing glycogen synthesis, induce the presence of high numbers of insoluble polyglucosan bodies in neuronal cells. Known as Lafora bodies (LBs), these deposits result in the aggressive neurodegeneration seen in Lafora's disease. Polysaccharide-based aggregates, called corpora amylacea (CA), are also present in the neurons of aged human brains. Despite the similarity of CA to LBs, the mechanisms and functional consequences of CA formation are yet unknown. Here, we show that wild-type laboratory mice also accumulate glycogen-based aggregates in the brain as they age. These structures are immunopositive for an array of metabolic and stress-response proteins, some of which were previously shown to aggregate in correlation with age in the human brain and are also present in LBs. Remarkably, these structures and their associated protein aggregates are not present in the aged mouse brain upon genetic ablation of glycogen synthase. Similar genetic intervention in Drosophila prevents the accumulation of glycogen clusters in the neuronal processes of aged flies. Most interestingly, targeted reduction of Drosophila glycogen synthase in neurons improves neurological function with age and extends lifespan. These results demonstrate that neuronal glycogen accumulation contributes to physiological aging and may therefore constitute a key factor regulating age-related neurological decline in humans. © 2014 The Authors. Aging cell published by the Anatomical Society and John Wiley & Sons Ltd.

Midsagittal Brain Variation among Non-Human Primates: Insights into Evolutionary Expansion of the Human Precuneus.

PubMed

Pereira-Pedro, Ana Sofia; Rilling, James K; Chen, Xu; Preuss, Todd M; Bruner, Emiliano

2017-01-01

The precuneus is a major element of the superior parietal lobule, positioned on the medial side of the hemisphere and reaching the dorsal surface of the brain. It is a crucial functional region for visuospatial integration, visual imagery, and body coordination. Previously, we argued that the precuneus expanded in recent human evolution, based on a combination of paleontological, comparative, and intraspecific evidence from fossil and modern human endocasts as well as from human and chimpanzee brains. The longitudinal proportions of this region are a major source of anatomical variation among adult humans and, being much larger in Homo sapiens, is the main characteristic differentiating human midsagittal brain morphology from that of our closest living primate relative, the chimpanzee. In the current shape analysis, we examine precuneus variation in non-human primates through landmark-based models, to evaluate the general pattern of variability in non-human primates, and to test whether precuneus proportions are influenced by allometric effects of brain size. Results show that precuneus proportions do not covary with brain size, and that the main difference between monkeys and apes involves a vertical expansion of the frontal and occipital regions in apes. Such differences might reflect differences in brain proportions or differences in cranial architecture. In this sample, precuneus variation is apparently not influenced by phylogenetic or allometric factors, but does vary consistently within species, at least in chimpanzees and macaques. This result further supports the hypothesis that precuneus expansion in modern humans is not merely a consequence of increasing brain size or of allometric scaling, but rather represents a species-specific morphological change in our lineage. © 2017 S. Karger AG, Basel.

Development of large-scale functional brain networks in children.

PubMed

Supekar, Kaustubh; Musen, Mark; Menon, Vinod

2009-07-01

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 have similar "small-world" organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism.

Development of Large-Scale Functional Brain Networks in Children

PubMed Central

Supekar, Kaustubh; Musen, Mark; Menon, Vinod

2009-01-01

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 have similar “small-world” organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism. PMID:19621066

A neurologist looks at mind and brain: "the enchanted loom".

PubMed

Hansotia, Phiroze

2003-10-01

For a long time, before we developed an appreciation of the neuroanatomy and neurophysiology of the brain, there was uncertainty as to the nature and source of the human mind. Philosophers linked the mind to mythical "humors" that controlled the human body, and others speculated that the mind was associated with "life-force" or soul. Few felt that there was a relation between the human mind and brain, but they had to wait for the Age of Enlightenment and scientific discovery in the 18th and 19th centuries to establish a clear association between the two. Three centuries ago Rene Descartes described the mind as an extracorporeal entity that was expressed through the pineal gland. Descartes was wrong about the pineal, but the debate he set off regarding the relationship between mind and brain rages on. This review looks at the history of speculation on the mind and the development of ideas that have led to our present understanding of this phenomenon. The basic anatomy and physiology of the brain is reviewed to help us understand the brain's association with the complex function we call mind. This is followed by a look at some syndromes that may result when part of the brain is damaged-the parietal lobe is arbitrarily selected as an example-and the resulting effect on the subject's mind. This assists us in understanding the association of mind and brain, and also to better understanding its components, behavior, function and dysfunction.

The Brain’s Default Network and its Adaptive Role in Internal Mentation

PubMed Central

Andrews-Hanna, Jessica R.

2013-01-01

During the many idle moments that comprise daily life, the human brain increases its activity across a set of midline and lateral cortical brain regions known as the “default network.” Despite the robustness with which the brain defaults to this pattern of activity, surprisingly little is known about the network’s precise anatomical organization and adaptive functions. To provide insight into these questions, this article synthesizes recent literature from structural and functional imaging with a growing behavioral literature on mind wandering. Results characterize the default network as a set of interacting hubs and subsystems that play an important role in “internal mentation” – the introspective and adaptive mental activities in which humans spontaneously and deliberately engage in everyday. . PMID:21677128

The effect of alcohol use on human adolescent brain structures and systems.

PubMed

Squeglia, Lindsay M; Jacobus, Joanna; Tapert, Susan F

2014-01-01

This article reviews the neurocognitive and neuroimaging literature regarding the effect of alcohol use on human adolescent brain structure and function. Adolescents who engage in heavy alcohol use, even at subdiagnostic levels, show differences in brain structure, function, and behavior when compared with non-drinking controls. Preliminary longitudinal studies have helped disentangle premorbid factors from consequences associated with drinking. Neural abnormalities and cognitive disadvantages both appear to predate drinking, particularly in youth who have a family history of alcoholism, and are directly related to the neurotoxic effect of alcohol use. Binge drinking and withdrawal and hangover symptoms have been associated with the greatest neural abnormalities during adolescence, particularly in frontal, parietal, and temporal regions. © 2014 Elsevier B.V. All rights reserved.

Simultaneous measurement of glucose transport and utilization in the human brain.

PubMed

Shestov, Alexander A; Emir, Uzay E; Kumar, Anjali; Henry, Pierre-Gilles; Seaquist, Elizabeth R; Öz, Gülin

2011-11-01

Glucose is the primary fuel for brain function, and determining the kinetics of cerebral glucose transport and utilization is critical for quantifying cerebral energy metabolism. The kinetic parameters of cerebral glucose transport, K(M)(t) and V(max)(t), in humans have so far been obtained by measuring steady-state brain glucose levels by proton ((1)H) NMR as a function of plasma glucose levels and fitting steady-state models to these data. Extraction of the kinetic parameters for cerebral glucose transport necessitated assuming a constant cerebral metabolic rate of glucose (CMR(glc)) obtained from other tracer studies, such as (13)C NMR. Here we present new methodology to simultaneously obtain kinetic parameters for glucose transport and utilization in the human brain by fitting both dynamic and steady-state (1)H NMR data with a reversible, non-steady-state Michaelis-Menten model. Dynamic data were obtained by measuring brain and plasma glucose time courses during glucose infusions to raise and maintain plasma concentration at ∼17 mmol/l for ∼2 h in five healthy volunteers. Steady-state brain vs. plasma glucose concentrations were taken from literature and the steady-state portions of data from the five volunteers. In addition to providing simultaneous measurements of glucose transport and utilization and obviating assumptions for constant CMR(glc), this methodology does not necessitate infusions of expensive or radioactive tracers. Using this new methodology, we found that the maximum transport capacity for glucose through the blood-brain barrier was nearly twofold higher than maximum cerebral glucose utilization. The glucose transport and utilization parameters were consistent with previously published values for human brain.

White Matter Connectivity of the Thalamus Delineates the Functional Architecture of Competing Thalamocortical Systems

PubMed Central

O'Muircheartaigh, Jonathan; Keller, Simon S.; Barker, Gareth J.; Richardson, Mark P.

2015-01-01

There is an increasing awareness of the involvement of thalamic connectivity on higher level cortical functioning in the human brain. This is reflected by the influence of thalamic stimulation on cortical activity and behavior as well as apparently cortical lesion syndromes occurring as a function of small thalamic insults. Here, we attempt to noninvasively test the correspondence of structural and functional connectivity of the human thalamus using diffusion-weighted and resting-state functional MRI. Using a large sample of 102 adults, we apply tensor independent component analysis to diffusion MRI tractography data to blindly parcellate bilateral thalamus according to diffusion tractography-defined structural connectivity. Using resting-state functional MRI collected in the same subjects, we show that the resulting structurally defined thalamic regions map to spatially distinct, and anatomically predictable, whole-brain functional networks in the same subjects. Although there was significant variability in the functional connectivity patterns, the resulting 51 structural and functional patterns could broadly be reduced to a subset of 7 similar core network types. These networks were distinct from typical cortical resting-state networks. Importantly, these networks were distributed across the brain and, in a subset, map extremely well to known thalamocortico-basal-ganglial loops. PMID:25899706

Gender similarities and differences in brain activation strategies: Voxel-based meta-analysis on fMRI studies.

PubMed

AlRyalat, Saif Aldeen

2017-01-01

Gender similarities and differences have long been a matter of debate in almost all human research, especially upon reaching the discussion about brain functions. This large scale meta-analysis was performed on functional MRI studies. It included more than 700 active brain foci from more than 70 different experiments to study gender related similarities and differences in brain activation strategies for three of the main brain functions: Visual-spatial cognition, memory, and emotion. Areas that are significantly activated by both genders (i.e. core areas) for the tested brain function are mentioned, whereas those areas significantly activated exclusively in one gender are the gender specific areas. During visual-spatial cognition task, and in addition to the core areas, males significantly activated their left superior frontal gyrus, compared with left superior parietal lobule in females. For memory tasks, several different brain areas activated by each gender, but females significantly activated two areas from the limbic system during memory retrieval tasks. For emotional task, males tend to recruit their bilateral prefrontal regions, whereas females tend to recruit their bilateral amygdalae. This meta-analysis provides an overview based on functional MRI studies on how males and females use their brain.

Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.

PubMed

Bardy, Cedric; van den Hurk, Mark; Eames, Tameji; Marchand, Cynthia; Hernandez, Ruben V; Kellogg, Mariko; Gorris, Mark; Galet, Ben; Palomares, Vanessa; Brown, Joshua; Bang, Anne G; Mertens, Jerome; Böhnke, Lena; Boyer, Leah; Simon, Suzanne; Gage, Fred H

2015-05-19

Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro.

Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro

PubMed Central

Bardy, Cedric; van den Hurk, Mark; Eames, Tameji; Marchand, Cynthia; Hernandez, Ruben V.; Kellogg, Mariko; Gorris, Mark; Galet, Ben; Palomares, Vanessa; Brown, Joshua; Bang, Anne G.; Mertens, Jerome; Böhnke, Lena; Boyer, Leah; Simon, Suzanne; Gage, Fred H.

2015-01-01

Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro. PMID:25870293

Interpreting and Utilising Intersubject Variability in Brain Function.

PubMed

Seghier, Mohamed L; Price, Cathy J

2018-06-01

We consider between-subject variance in brain function as data rather than noise. We describe variability as a natural output of a noisy plastic system (the brain) where each subject embodies a particular parameterisation of that system. In this context, variability becomes an opportunity to: (i) better characterise typical versus atypical brain functions; (ii) reveal the different cognitive strategies and processing networks that can sustain similar tasks; and (iii) predict recovery capacity after brain damage by taking into account both damaged and spared processing pathways. This has many ramifications for understanding individual learning preferences and explaining the wide differences in human abilities and disabilities. Understanding variability boosts the translational potential of neuroimaging findings, in particular in clinical and educational neuroscience. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Developmental imaging genetics: linking dopamine function to adolescent behavior.

PubMed

Padmanabhan, Aarthi; Luna, Beatriz

2014-08-01

Adolescence is a period of development characterized by numerous neurobiological changes that significantly influence behavior and brain function. Adolescence is of particular interest due to the alarming statistics indicating that mortality rates increase two to three-fold during this time compared to childhood, due largely to a peak in risk-taking behaviors resulting from increased impulsivity and sensation seeking. Furthermore, there exists large unexplained variability in these behaviors that are in part mediated by biological factors. Recent advances in molecular genetics and functional neuroimaging have provided a unique and exciting opportunity to non-invasively study the influence of genetic factors on brain function in humans. While genes do not code for specific behaviors, they do determine the structure and function of proteins that are essential to the neuronal processes that underlie behavior. Therefore, studying the interaction of genotype with measures of brain function over development could shed light on critical time points when biologically mediated individual differences in complex behaviors emerge. Here we review animal and human literature examining the neurobiological basis of adolescent development related to dopamine neurotransmission. Dopamine is of critical importance because of (1) its role in cognitive and affective behaviors, (2) its role in the pathogenesis of major psychopathology, and (3) the protracted development of dopamine signaling pathways over adolescence. We will then focus on current research examining the role of dopamine-related genes on brain function. We propose the use of imaging genetics to examine the influence of genetically mediated dopamine variability on brain function during adolescence, keeping in mind the limitations of this approach. Copyright © 2014 Elsevier Inc. All rights reserved.

Sex Differences and Brain Development: A Bibliography.

ERIC Educational Resources Information Center

Motomatsu, Nancy; Patterson, Bobbie

This bibliography cites references dealing with background material on the functions of the human brain and current research on sex differences in brain development. A list of 10 books published since 1974 is followed by a more extensive annotated bibliography of 29 articles, and a bibliography of 19 reports, complete with ERIC reference numbers…

Sex Differences in the Effects of Unilateral Brain Damage on Intelligence

NASA Astrophysics Data System (ADS)

Inglis, James; Lawson, J. S.

1981-05-01

A sexual dimorphism in the functional asymmetry of the damaged human brain is reflected in a test-specific laterality effect in male but not in female patients. This sex difference explains some contradictions concerning the effects of unilateral brain damage on intelligence in studies in which the influence of sex was overlooked.

Contrasting Acute and Slow-Growing Lesions: A New Door to Brain Plasticity

ERIC Educational Resources Information Center

Desmurget, Michel; Bonnetblanc, FranCois; Duffau, Hugues

2007-01-01

The concept of plasticity describes the mechanisms that rearrange cerebral organization following a brain injury. During the last century, plasticity has been mainly investigated in humans with acute strokes. It was then shown: (i) that the brain is organized into highly specialized functional areas, often designated "eloquent" areas and (ii) that…

Aggression, the Prequel: Preventing the Need

ERIC Educational Resources Information Center

Gartrell, Dan

2011-01-01

An authority on neuroscience (the study of the structure and functioning of the brain) and human relationships, Daniel Siegel (2001) begins his classic work, "The Developing Mind: How Relationships and the Brain Interact to Shape Who We Are," with a basic concept: the brain is an open system that physically changes throughout life in response to…

The self-regulating brain and neurofeedback: Experimental science and clinical promise.

PubMed

Thibault, Robert T; Lifshitz, Michael; Raz, Amir

2016-01-01

Neurofeedback, one of the primary examples of self-regulation, designates a collection of techniques that train the brain and help to improve its function. Since coming on the scene in the 1960s, electroencephalography-neurofeedback has become a treatment vehicle for a host of mental disorders; however, its clinical effectiveness remains controversial. Modern imaging technologies of the living human brain (e.g., real-time functional magnetic resonance imaging) and increasingly rigorous research protocols that utilize such methodologies begin to shed light on the underlying mechanisms that may facilitate more effective clinical applications. In this paper we focus on recent technological advances in the field of human brain imaging and discuss how these modern methods may influence the field of neurofeedback. Toward this end, we outline the state of the evidence and sketch out future directions to further explore the potential merits of this contentious therapeutic prospect. Copyright © 2015 Elsevier Ltd. All rights reserved.

Addition of visual noise boosts evoked potential-based brain-computer interface.

PubMed

Xie, Jun; Xu, Guanghua; Wang, Jing; Zhang, Sicong; Zhang, Feng; Li, Yeping; Han, Chengcheng; Li, Lili

2014-05-14

Although noise has a proven beneficial role in brain functions, there have not been any attempts on the dedication of stochastic resonance effect in neural engineering applications, especially in researches of brain-computer interfaces (BCIs). In our study, a steady-state motion visual evoked potential (SSMVEP)-based BCI with periodic visual stimulation plus moderate spatiotemporal noise can achieve better offline and online performance due to enhancement of periodic components in brain responses, which was accompanied by suppression of high harmonics. Offline results behaved with a bell-shaped resonance-like functionality and 7-36% online performance improvements can be achieved when identical visual noise was adopted for different stimulation frequencies. Using neural encoding modeling, these phenomena can be explained as noise-induced input-output synchronization in human sensory systems which commonly possess a low-pass property. Our work demonstrated that noise could boost BCIs in addressing human needs.

Neuroelectrical Decomposition of Spontaneous Brain Activity Measured with Functional Magnetic Resonance Imaging

PubMed Central

Liu, Zhongming; de Zwart, Jacco A.; Chang, Catie; Duan, Qi; van Gelderen, Peter; Duyn, Jeff H.

2014-01-01

Spontaneous activity in the human brain occurs in complex spatiotemporal patterns that may reflect functionally specialized neural networks. Here, we propose a subspace analysis method to elucidate large-scale networks by the joint analysis of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data. The new approach is based on the notion that the neuroelectrical activity underlying the fMRI signal may have EEG spectral features that report on regional neuronal dynamics and interregional interactions. Applying this approach to resting healthy adults, we indeed found characteristic spectral signatures in the EEG correlates of spontaneous fMRI signals at individual brain regions as well as the temporal synchronization among widely distributed regions. These spectral signatures not only allowed us to parcel the brain into clusters that resembled the brain's established functional subdivision, but also offered important clues for disentangling the involvement of individual regions in fMRI network activity. PMID:23796947

Breaking the Blood-Brain Barrier With Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain.

PubMed

Tajiri, Naoki; Lee, Jea Young; Acosta, Sandra; Sanberg, Paul R; Borlongan, Cesar V

2016-01-01

Blood-brain barrier (BBB) permeabilizers, such as mannitol, can facilitate peripherally delivered stem cells to exert therapeutic benefits on the stroke brain. Although this BBB permeation-aided stem cell therapy has been demonstrated in the acute stage of stroke, such BBB permeation in the chronic stage of the disease remains to be examined. Adult Sprague-Dawley rats initially received sham surgery or experimental stroke via the 1-h middle cerebral artery occlusion (MCAo) model. At 1 month after the MCAo surgery, stroke animals were randomly assigned to receive human umbilical cord stem cells only (2 million viable cells), mannitol only (1.1 mol/L mannitol at 4°C), combined human umbilical cord stem cells (200,000 viable cells) and mannitol (1.1 mol/L mannitol at 4°C), and vehicle (phosphate-buffered saline) only. Stroke animals that received human umbilical cord blood cells alone or combined human umbilical cord stem cells and mannitol exhibited significantly improved motor performance and significantly better brain cell survival in the peri-infarct area compared to stroke animals that received vehicle or mannitol alone, with mannitol treatment reducing the stem cell dose necessary to afford functional outcomes. Enhanced neurogenesis in the subventricular zone accompanied the combined treatment of human umbilical cord stem cells and mannitol. We showed that BBB permeation facilitates the therapeutic effects of a low dose of peripherally transplanted stem cells to effectively cause functional improvement and increase neurogenesis in chronic stroke.

Lifelong Brain Health is a Lifelong Challenge: From Evolutionary Principles to Empirical Evidence

PubMed Central

Mattson, Mark P.

2015-01-01

Although the human brain is exceptional in size and information processing capabilities, it is similar to other mammals with regards to the factors that promote its optimal performance. Three such factors are the challenges of physical exercise, food deprivation/fasting, and social/intellectual engagement. Because it evolved, in part, for success in seeking and acquiring food, the brain functions best when the individual is hungry and physically active, as typified by the hungry lion stalking and chasing its prey. Indeed, studies of animal models and human subjects demonstrate robust beneficial effects of regular exercise and intermittent energy restriction/fasting on cognitive function and mood, particularly in the contexts of aging and associated neurodegenerative disorders. Unfortunately, the agricultural revolution and the invention of effort-sparing technologies have resulted in a dramatic reduction or elimination of vigorous exercise and fasting, leaving only intellectual challenges to bolster brain function. In addition to disengaging beneficial adaptive responses in the brain, sedentary overindulgent lifestyles promote obesity, diabetes and cardiovascular disease, all of which may increase the risk of cognitive impairment and Alzheimer’s disease. It is therefore important to embrace the reality of the requirements for exercise, intermittent fasting and critical thinking for optimal brain health throughout life, and to recognize the dire consequences for our aging population of failing to implement such brain-healthy lifestyles. PMID:25576651

Lifelong brain health is a lifelong challenge: from evolutionary principles to empirical evidence.

PubMed

Mattson, Mark P

2015-03-01

Although the human brain is exceptional in size and information processing capabilities, it is similar to other mammals with regard to the factors that promote its optimal performance. Three such factors are the challenges of physical exercise, food deprivation/fasting, and social/intellectual engagement. Because it evolved, in part, for success in seeking and acquiring food, the brain functions best when the individual is hungry and physically active, as typified by the hungry lion stalking and chasing its prey. Indeed, studies of animal models and human subjects demonstrate robust beneficial effects of regular exercise and intermittent energy restriction/fasting on cognitive function and mood, particularly in the contexts of aging and associated neurodegenerative disorders. Unfortunately, the agricultural revolution and the invention of effort-sparing technologies have resulted in a dramatic reduction or elimination of vigorous exercise and fasting, leaving only intellectual challenges to bolster brain function. In addition to disengaging beneficial adaptive responses in the brain, sedentary overindulgent lifestyles promote obesity, diabetes and cardiovascular disease, all of which may increase the risk of cognitive impairment and Alzheimer's disease. It is therefore important to embrace the reality of the requirements for exercise, intermittent fasting and critical thinking for optimal brain health throughout life, and to recognize the dire consequences for our aging population of failing to implement such brain-healthy lifestyles. Published by Elsevier B.V.

Application of Functional Near-Infrared Spectroscopy to the Study of Brain Function in Humans and Animal Models

PubMed Central

Kim, Hak Yeong; Seo, Kain; Jeon, Hong Jin; Lee, Unjoo; Lee, Hyosang

2017-01-01

Functional near-infrared spectroscopy (fNIRS) is a noninvasive optical imaging technique that indirectly assesses neuronal activity by measuring changes in oxygenated and deoxygenated hemoglobin in tissues using near-infrared light. fNIRS has been used not only to investigate cortical activity in healthy human subjects and animals but also to reveal abnormalities in brain function in patients suffering from neurological and psychiatric disorders and in animals that exhibit disease conditions. Because of its safety, quietness, resistance to motion artifacts, and portability, fNIRS has become a tool to complement conventional imaging techniques in measuring hemodynamic responses while a subject performs diverse cognitive and behavioral tasks in test settings that are more ecologically relevant and involve social interaction. In this review, we introduce the basic principles of fNIRS and discuss the application of this technique in human and animal studies. PMID:28835022

Forging our understanding of lncRNAs in the brain.

PubMed

Andersen, Rebecca E; Lim, Daniel A

2018-01-01

During both development and adulthood, the human brain expresses many thousands of long noncoding RNAs (lncRNAs), and aberrant lncRNA expression has been associated with a wide range of neurological diseases. Although the biological significance of most lncRNAs remains to be discovered, it is now clear that certain lncRNAs carry out important functions in neurodevelopment, neural cell function, and perhaps even diseases of the human brain. Given the relatively inclusive definition of lncRNAs-transcripts longer than 200 nucleotides with essentially no protein coding potential-this class of noncoding transcript is both large and very diverse. Furthermore, emerging data indicate that lncRNA genes can act via multiple, non-mutually exclusive molecular mechanisms, and specific functions are difficult to predict from lncRNA expression or sequence alone. Thus, the different experimental approaches used to explore the role of a lncRNA might each shed light upon distinct facets of its overall molecular mechanism, and combining multiple approaches may be necessary to fully illuminate the function of any particular lncRNA. To understand how lncRNAs affect brain development and neurological disease, in vivo studies of lncRNA function are required. Thus, in this review, we focus our discussion upon a small set of neural lncRNAs that have been experimentally manipulated in mice. Together, these examples illustrate how studies of individual lncRNAs using multiple experimental approaches can help reveal the richness and complexity of lncRNA function in both neurodevelopment and diseases of the brain.

Preserved speech abilities and compensation following prefrontal damage.

PubMed

Buckner, R L; Corbetta, M; Schatz, J; Raichle, M E; Petersen, S E

1996-02-06

Lesions to left frontal cortex in humans produce speech production impairments (nonfluent aphasia). These impairments vary from subject to subject and performance on certain speech production tasks can be relatively preserved in some patients. A possible explanation for preservation of function under these circumstances is that areas outside left prefrontal cortex are used to compensate for the injured brain area. We report here a direct demonstration of preserved language function in a stroke patient (LF1) apparently due to the activation of a compensatory brain pathway. We used functional brain imaging with positron emission tomography (PET) as a basis for this study.

Study of the functional hyperconnectivity between couples of pilots during flight simulation: an EEG hyperscanning study.

PubMed

Astolfi, L; Toppi, J; Borghini, G; Vecchiato, G; Isabella, R; De Vico Fallani, F; Cincotti, F; Salinari, S; Mattia, D; He, B; Caltagirone, C; Babiloni, F

2011-01-01

Brain Hyperscanning, i.e. the simultaneous recording of the cerebral activity of different human subjects involved in interaction tasks, is a very recent field of Neuroscience aiming at understanding the cerebral processes generating and generated by social interactions. This approach allows the observation and modeling of the neural signature specifically dependent on the interaction between subjects, and, even more interestingly, of the functional links existing between the activities in the brains of the subjects interacting together. In this EEG hyperscanning study we explored the functional hyperconnectivity between the activity in different scalp sites of couples of Civil Aviation Pilots during different phases of a flight reproduced in a flight simulator. Results shown a dense network of connections between the two brains in the takeoff and landing phases, when the cooperation between them is maximal, in contrast with phases during which the activity of the two pilots was independent, when no or quite few links were shown. These results confirms that the study of the brain connectivity between the activity simultaneously acquired in human brains during interaction tasks can provide important information about the neural basis of the "spirit of the group".

Continuous monitoring of brain dynamics with functional near infrared spectroscopy as a tool for neuroergonomic research: empirical examples and a technological development

PubMed Central

Ayaz, Hasan; Onaral, Banu; Izzetoglu, Kurtulus; Shewokis, Patricia A.; McKendrick, Ryan; Parasuraman, Raja

2013-01-01

Functional near infrared spectroscopy (fNIRS) is a non-invasive, safe, and portable optical neuroimaging method that can be used to assess brain dynamics during skill acquisition and performance of complex work and everyday tasks. In this paper we describe neuroergonomic studies that illustrate the use of fNIRS in the examination of training-related brain dynamics and human performance assessment. We describe results of studies investigating cognitive workload in air traffic controllers, acquisition of dual verbal-spatial working memory skill, and development of expertise in piloting unmanned vehicles. These studies used conventional fNIRS devices in which the participants were tethered to the device while seated at a workstation. Consistent with the aims of mobile brain imaging (MoBI), we also describe a compact and battery-operated wireless fNIRS system that performs with similar accuracy as other established fNIRS devices. Our results indicate that both wired and wireless fNIRS systems allow for the examination of brain function in naturalistic settings, and thus are suitable for reliable human performance monitoring and training assessment. PMID:24385959

Cerebral cartography and connectomics.

PubMed

Sporns, Olaf

2015-05-19

Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

The Neuropathology of Obesity: Insights from Human Disease

PubMed Central

Lee, Edward B.; Mattson, Mark P.

2013-01-01

Obesity, a pathologic state defined by excess adipose tissue, is a significant public health problem as it affects a large proportion of individuals and is linked with increased risk for numerous chronic diseases. Obesity is the result of fundamental changes associated with modern society including overnutrition and sedentary lifestyles. Proper energy homeostasis is dependent on normal brain function as the master metabolic regulator which integrates peripheral signals, modulates autonomic outflow and controls feeding behavior. Therefore, many human brain diseases are associated with obesity. This review explores the neuropathology of obesity by examining brain diseases which either cause or are influenced by obesity. First, several genetic and acquired brain diseases are discussed as a means to understand the central regulation of peripheral metabolism. These diseases range from monogenetic causes of obesity (leptin deficiency, MC4R deficiency, Bardet-Biedl syndrome and others) to complex neurodevelopmental disorders (Prader-Willi syndrome and Sim1 deficiency) and neurodegenerative conditions (frontotemporal dementia and Gourmand’s syndrome) and serve to highlight the central regulatory mechanisms which have evolved to maintain energy homeostasis. Next, to examine the effect of obesity on the brain, chronic neuropathologic conditions (epilepsy, multiple sclerosis and Alzheimer’s disease) are discussed as examples of obesity leading to maladaptive processes which exacerbate chronic disease. Thus obesity is associated with multiple pathways including abnormal metabolism, altered hormonal signaling and increased inflammation which act in concert to promote downstream neuropathology. Finally, the effect of anti-obesity interventions is discussed in terms of brain structure and function. Together, understanding human diseases and anti-obesity interventions leads to insights into the bidirectional interaction between peripheral metabolism and central brain function, highlighting the need for continued clinicopathologic and mechanistic studies of the neuropathology of obesity. PMID:24096619

The role of physical exercise in cognitive recovery after traumatic brain injury: A systematic review.

PubMed

Morris, Timothy; Gomes Osman, Joyce; Tormos Muñoz, Jose Maria; Costa Miserachs, David; Pascual Leone, Alvaro

2016-11-22

There is a growing body of evidence revealing exercise-induced effects on brain structure and cognitive function across the lifespan. Animal models of traumatic brain injury also suggest exercise is capable of modulating not only the pathophysiological changes following trauma but also the associated cognitive deficits. To evaluate the effect of physical exercise on cognitive impairment following traumatic brain injury in humans. A systematic search of the PubMed database was performed using the search terms "cognition" and "executive function, memory or attention", "traumatic brain injury" and "physical exercise". Adult human traumatic brain injury studies that assessed cognitive function as an outcome measure (primary or secondary) and used physical exercise as a treatment (single or combined) were assessed by two independent reviewers. Data was extracted under the guidance of the population intervention comparison outcome framework wherein, characteristics of included studies (exercise duration, intensity, combined or single intervention, control groups and cognitive measures) were collected, after which, methodological quality (Cochrane criteria) was assessed. A total of 240 citations were identified, but only 6 met our inclusion criteria (3 from search records, 3 from reference lists. Only a small number of studies have evaluated the effect of exercise on cognition following traumatic brain injury in humans, and of those, assessment of efficacy is difficult due to low methodological strength and a high risk of different types of bias. Evidence of an effect of physical exercise on cognitive recovery suggests further studies should explore this treatment option with greater methodological approaches. Recommendations to reduce risk of bias and methodological shortfalls are discussed and include stricter inclusion criteria to create homogenous groups and larger patient pools, more rigorous cognitive assessments and the study and reporting of additional and combined rehabilitation techniques.

Asymmetries of the human social brain in the visual, auditory and chemical modalities.

PubMed

Brancucci, Alfredo; Lucci, Giuliana; Mazzatenta, Andrea; Tommasi, Luca

2009-04-12

Structural and functional asymmetries are present in many regions of the human brain responsible for motor control, sensory and cognitive functions and communication. Here, we focus on hemispheric asymmetries underlying the domain of social perception, broadly conceived as the analysis of information about other individuals based on acoustic, visual and chemical signals. By means of these cues the brain establishes the border between 'self' and 'other', and interprets the surrounding social world in terms of the physical and behavioural characteristics of conspecifics essential for impression formation and for creating bonds and relationships. We show that, considered from the standpoint of single- and multi-modal sensory analysis, the neural substrates of the perception of voices, faces, gestures, smells and pheromones, as evidenced by modern neuroimaging techniques, are characterized by a general pattern of right-hemispheric functional asymmetry that might benefit from other aspects of hemispheric lateralization rather than constituting a true specialization for social information.

Altered resting-state whole-brain functional networks of neonates with intrauterine growth restriction.

PubMed

Batalle, Dafnis; Muñoz-Moreno, Emma; Tornador, Cristian; Bargallo, Nuria; Deco, Gustavo; Eixarch, Elisenda; Gratacos, Eduard

2016-04-01

The feasibility to use functional MRI (fMRI) during natural sleep to assess low-frequency basal brain activity fluctuations in human neonates has been demonstrated, although its potential to characterise pathologies of prenatal origin has not yet been exploited. In the present study, we used intrauterine growth restriction (IUGR) as a model of altered neurodevelopment due to prenatal condition to show the suitability of brain networks to characterise functional brain organisation at neonatal age. Particularly, we analysed resting-state fMRI signal of 20 neonates with IUGR and 13 controls, obtaining whole-brain functional networks based on correlations of blood oxygen level-dependent (BOLD) signal in 90 grey matter regions of an anatomical atlas (AAL). Characterisation of the networks obtained with graph theoretical features showed increased network infrastructure and raw efficiencies but reduced efficiency after normalisation, demonstrating hyper-connected but sub-optimally organised IUGR functional brain networks. Significant association of network features with neurobehavioral scores was also found. Further assessment of spatiotemporal dynamics displayed alterations into features associated to frontal, cingulate and lingual cortices. These findings show the capacity of functional brain networks to characterise brain reorganisation from an early age, and their potential to develop biomarkers of altered neurodevelopment. Copyright © 2016 Elsevier Ltd. All rights reserved.

From motor cortex to visual cortex: the application of noninvasive brain stimulation to amblyopia.

PubMed

Thompson, Benjamin; Mansouri, Behzad; Koski, Lisa; Hess, Robert F

2012-04-01

Noninvasive brain stimulation is a technique for inducing changes in the excitability of discrete neural populations in the human brain. A current model of the underlying pathological processes contributing to the loss of motor function after stroke has motivated a number of research groups to investigate the potential therapeutic application of brain stimulation to stroke rehabilitation. The loss of motor function is modeled as resulting from a combination of reduced excitability in the lesioned motor cortex and an increased inhibitory drive from the nonlesioned hemisphere over the lesioned hemisphere. This combination of impaired neural function and pathological suppression resonates with current views on the cause of the visual impairment in amblyopia. Here, we discuss how the rationale for using noninvasive brain stimulation in stroke rehabilitation can be applied to amblyopia, review a proof-of-principle study demonstrating that brain stimulation can temporarily improve amblyopic eye function, and propose future research avenues. Copyright © 2010 Wiley Periodicals, Inc.

Multivariate Heteroscedasticity Models for Functional Brain Connectivity.

PubMed

Seiler, Christof; Holmes, Susan

2017-01-01

Functional brain connectivity is the co-occurrence of brain activity in different areas during resting and while doing tasks. The data of interest are multivariate timeseries measured simultaneously across brain parcels using resting-state fMRI (rfMRI). We analyze functional connectivity using two heteroscedasticity models. Our first model is low-dimensional and scales linearly in the number of brain parcels. Our second model scales quadratically. We apply both models to data from the Human Connectome Project (HCP) comparing connectivity between short and conventional sleepers. We find stronger functional connectivity in short than conventional sleepers in brain areas consistent with previous findings. This might be due to subjects falling asleep in the scanner. Consequently, we recommend the inclusion of average sleep duration as a covariate to remove unwanted variation in rfMRI studies. A power analysis using the HCP data shows that a sample size of 40 detects 50% of the connectivity at a false discovery rate of 20%. We provide implementations using R and the probabilistic programming language Stan.

Selectively altering belief formation in the human brain

PubMed Central

Sharot, Tali; Kanai, Ryota; Marston, David; Korn, Christoph W.; Rees, Geraint; Dolan, Raymond J.

2012-01-01

Humans form beliefs asymmetrically; we tend to discount bad news but embrace good news. This reduced impact of unfavorable information on belief updating may have important societal implications, including the generation of financial market bubbles, ill preparedness in the face of natural disasters, and overly aggressive medical decisions. Here, we selectively improved people’s tendency to incorporate bad news into their beliefs by disrupting the function of the left (but not right) inferior frontal gyrus using transcranial magnetic stimulation, thereby eliminating the engrained “good news/bad news effect.” Our results provide an instance of how selective disruption of regional human brain function paradoxically enhances the ability to incorporate unfavorable information into beliefs of vulnerability. PMID:23011798

The effect of claustrum lesions on human consciousness and recovery of function.

PubMed

Chau, Aileen; Salazar, Andres M; Krueger, Frank; Cristofori, Irene; Grafman, Jordan

2015-11-01

Crick and Koch proposed that the claustrum plays a crucial role in consciousness. Their proposal was based on the structure and connectivity of the claustrum that suggested it had a role in coordinating a set of diverse brain functions. Given the few human studies investigating this claim, we decided to study the effects of claustrum lesions on consciousness in 171 combat veterans with penetrating traumatic brain injuries. Additionally, we studied the effects of claustrum lesions and loss of consciousness on long-term cognitive abilities. Claustrum damage was associated with the duration, but not frequency, of loss of consciousness, indicating that the claustrum may have an important role in regaining, but not maintaining, consciousness. Total brain volume loss, but not claustrum lesions, was associated with long-term recovery of neurobehavioral functions. Our findings constrain the current understanding of the neurobehavioral functions of the claustrum and its role in maintaining and regaining consciousness. Copyright © 2015 Elsevier Inc. All rights reserved.

Individual Functional ROI Optimization via Maximization of Group-wise Consistency of Structural and Functional Profiles

PubMed Central

Li, Kaiming; Guo, Lei; Zhu, Dajiang; Hu, Xintao; Han, Junwei; Liu, Tianming

2013-01-01

Studying connectivities among functional brain regions and the functional dynamics on brain networks has drawn increasing interest. A fundamental issue that affects functional connectivity and dynamics studies is how to determine the best possible functional brain regions or ROIs (regions of interest) for a group of individuals, since the connectivity measurements are heavily dependent on ROI locations. Essentially, identification of accurate, reliable and consistent corresponding ROIs is challenging due to the unclear boundaries between brain regions, variability across individuals, and nonlinearity of the ROIs. In response to these challenges, this paper presents a novel methodology to computationally optimize ROIs locations derived from task-based fMRI data for individuals so that the optimized ROIs are more consistent, reproducible and predictable across brains. Our computational strategy is to formulate the individual ROI location optimization as a group variance minimization problem, in which group-wise consistencies in functional/structural connectivity patterns and anatomic profiles are defined as optimization constraints. Our experimental results from multimodal fMRI and DTI data show that the optimized ROIs have significantly improved consistency in structural and functional profiles across individuals. These improved functional ROIs with better consistency could contribute to further study of functional interaction and dynamics in the human brain. PMID:22281931

Artistic creativity, style and brain disorders.

PubMed

Bogousslavsky, Julien

2005-01-01

The production of novel, motivated or useful material defines creativity, which appears to be one of the higher, specific, human brain functions. While creativity can express itself in virtually any domain, art might particularly well illustrate how creativity may be modulated by the normal or pathological brain. Evidence emphasizes global brain functioning in artistic creativity and output, but critical steps which link perception processing to execution of a work, such as extraction-abstraction, as well as major developments of non-esthetic values attached to art also underline complex activation and inhibition processes mainly localized in the frontal lobe. Neurological diseases in artists provide a unique opportunity to study brain-creativity relationships, in particular through the stylistic changes which may develop after brain lesion. (c) 2005 S. Karger AG, Basel

Role of maternal thyroid hormones in the developing neocortex and during human evolution

PubMed Central

Stenzel, Denise; Huttner, Wieland B.

2013-01-01

The importance of thyroid hormones during brain development has been appreciated for many decades. In humans, low levels of circulating maternal thyroid hormones, e.g., caused by maternal hypothyroidism or lack of iodine in diet, results in a wide spectrum of severe neurological defects, including neurological cretinism characterized by profound neurologic impairment and mental retardation, underlining the importance of the maternal thyroid hormone contribution. In fact, iodine intake, which is essential for thyroid hormone production in the thyroid gland, has been related to the expansion of the brain, associated with the increased cognitive capacities during human evolution. Because thyroid hormones regulate transcriptional activity of target genes via their nuclear thyroid hormone receptors (THRs), even mild and transient changes in maternal thyroid hormone levels can directly affect and alter the gene expression profile, and thus disturb fetal brain development. Here we summarize how thyroid hormones may have influenced human brain evolution through the adaptation to new habitats, concomitant with changes in diet and, therefore, iodine intake. Further, we review the current picture we gained from experimental studies in rodents on the function of maternal thyroid hormones during developmental neurogenesis. We aim to evaluate the effects of maternal thyroid hormone deficiency as well as lack of THRs and transporters on brain development and function, shedding light on the cellular behavior conducted by thyroid hormones. PMID:23882187

Functional and Topological Conditions for Explosive Synchronization Develop in Human Brain Networks with the Onset of Anesthetic-Induced Unconsciousness

PubMed Central

Kim, Minkyung; Mashour, George A.; Moraes, Stefanie-Blain; Vanini, Giancarlo; Tarnal, Vijay; Janke, Ellen; Hudetz, Anthony G.; Lee, Uncheol

2016-01-01

Sleep, anesthesia, and coma share a number of neural features but the recovery profiles are radically different. To understand the mechanisms of reversibility of unconsciousness at the network level, we studied the conditions for gradual and abrupt transitions in conscious and anesthetized states. We hypothesized that the conditions for explosive synchronization (ES) in human brain networks would be present in the anesthetized brain just over the threshold of unconsciousness. To test this hypothesis, functional brain networks were constructed from multi-channel electroencephalogram (EEG) recordings in seven healthy subjects across conscious, unconscious, and recovery states. We analyzed four variables that are involved in facilitating ES in generic, non-biological networks: (1) correlation between node degree and frequency, (2) disassortativity (i.e., the tendency of highly-connected nodes to link with less-connected nodes, or vice versa), (3) frequency difference of coupled nodes, and (4) an inequality relationship between local and global network properties, which is referred to as the suppressive rule. We observed that the four network conditions for ES were satisfied in the unconscious state. Conditions for ES in the human brain suggest a potential mechanism for rapid recovery from the lightly-anesthetized state. This study demonstrates for the first time that the network conditions for ES, formerly shown in generic networks only, are present in empirically-derived functional brain networks. Further investigations with deep anesthesia, sleep, and coma could provide insight into the underlying causes of variability in recovery profiles of these unconscious states. PMID:26834616

Haptic contents of a movie dynamically engage the spectator's sensorimotor cortex.

PubMed

Lankinen, Kaisu; Smeds, Eero; Tikka, Pia; Pihko, Elina; Hari, Riitta; Koskinen, Miika

2016-11-01

Observation of another person's actions and feelings activates brain areas that support similar functions in the observer, thereby facilitating inferences about the other's mental and bodily states. In real life, events eliciting this kind of vicarious brain activations are intermingled with other complex, ever-changing stimuli in the environment. One practical approach to study the neural underpinnings of real-life vicarious perception is to image brain activity during movie viewing. Here the goal was to find out how observed haptic events in a silent movie would affect the spectator's sensorimotor cortex. The functional state of the sensorimotor cortex was monitored by analyzing, in 16 healthy subjects, magnetoencephalographic (MEG) responses to tactile finger stimuli that were presented once per second throughout the session. Using canonical correlation analysis and spatial filtering, consistent single-trial responses across subjects were uncovered, and their waveform changes throughout the movie were quantified. The long-latency (85-175 ms) parts of the responses were modulated in concordance with the participants' average moment-by-moment ratings of own engagement in the haptic content of the movie (correlation r = 0.49; ratings collected after the MEG session). The results, obtained by using novel signal-analysis approaches, demonstrate that the functional state of the human sensorimotor cortex fluctuates in a fine-grained manner even during passive observation of temporally varying haptic events. Hum Brain Mapp 37:4061-4068, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Short desynchronization episodes prevail in synchronous dynamics of human brain rhythms.

PubMed

Ahn, Sungwoo; Rubchinsky, Leonid L

2013-03-01

Neural synchronization is believed to be critical for many brain functions. It frequently exhibits temporal variability, but it is not known if this variability has a specific temporal patterning. This study explores these synchronization/desynchronization patterns. We employ recently developed techniques to analyze the fine temporal structure of phase-locking to study the temporal patterning of synchrony of the human brain rhythms. We study neural oscillations recorded by electroencephalograms in α and β frequency bands in healthy human subjects at rest and during the execution of a task. While the phase-locking strength depends on many factors, dynamics of synchrony has a very specific temporal pattern: synchronous states are interrupted by frequent, but short desynchronization episodes. The probability for a desynchronization episode to occur decreased with its duration. The transition matrix between synchronized and desynchronized states has eigenvalues close to 0 and 1 where eigenvalue 1 has multiplicity 1, and therefore if the stationary distribution between these states is perturbed, the system converges back to the stationary distribution very fast. The qualitative similarity of this patterning across different subjects, brain states and electrode locations suggests that this may be a general type of dynamics for the brain. Earlier studies indicate that not all oscillatory networks have this kind of patterning of synchronization/desynchronization dynamics. Thus, the observed prevalence of short (but potentially frequent) desynchronization events (length of one cycle of oscillations) may have important functional implications for the brain. Numerous short desynchronizations (as opposed to infrequent, but long desynchronizations) may allow for a quick and efficient formation and break-up of functionally significant neuronal assemblies.

Functional and Topological Conditions for Explosive Synchronization Develop in Human Brain Networks with the Onset of Anesthetic-Induced Unconsciousness.

PubMed

Kim, Minkyung; Mashour, George A; Moraes, Stefanie-Blain; Vanini, Giancarlo; Tarnal, Vijay; Janke, Ellen; Hudetz, Anthony G; Lee, Uncheol

2016-01-01

Sleep, anesthesia, and coma share a number of neural features but the recovery profiles are radically different. To understand the mechanisms of reversibility of unconsciousness at the network level, we studied the conditions for gradual and abrupt transitions in conscious and anesthetized states. We hypothesized that the conditions for explosive synchronization (ES) in human brain networks would be present in the anesthetized brain just over the threshold of unconsciousness. To test this hypothesis, functional brain networks were constructed from multi-channel electroencephalogram (EEG) recordings in seven healthy subjects across conscious, unconscious, and recovery states. We analyzed four variables that are involved in facilitating ES in generic, non-biological networks: (1) correlation between node degree and frequency, (2) disassortativity (i.e., the tendency of highly-connected nodes to link with less-connected nodes, or vice versa), (3) frequency difference of coupled nodes, and (4) an inequality relationship between local and global network properties, which is referred to as the suppressive rule. We observed that the four network conditions for ES were satisfied in the unconscious state. Conditions for ES in the human brain suggest a potential mechanism for rapid recovery from the lightly-anesthetized state. This study demonstrates for the first time that the network conditions for ES, formerly shown in generic networks only, are present in empirically-derived functional brain networks. Further investigations with deep anesthesia, sleep, and coma could provide insight into the underlying causes of variability in recovery profiles of these unconscious states.

Short desynchronization episodes prevail in synchronous dynamics of human brain rhythms

NASA Astrophysics Data System (ADS)

Ahn, Sungwoo; Rubchinsky, Leonid L.

2013-03-01

Neural synchronization is believed to be critical for many brain functions. It frequently exhibits temporal variability, but it is not known if this variability has a specific temporal patterning. This study explores these synchronization/desynchronization patterns. We employ recently developed techniques to analyze the fine temporal structure of phase-locking to study the temporal patterning of synchrony of the human brain rhythms. We study neural oscillations recorded by electroencephalograms in α and β frequency bands in healthy human subjects at rest and during the execution of a task. While the phase-locking strength depends on many factors, dynamics of synchrony has a very specific temporal pattern: synchronous states are interrupted by frequent, but short desynchronization episodes. The probability for a desynchronization episode to occur decreased with its duration. The transition matrix between synchronized and desynchronized states has eigenvalues close to 0 and 1 where eigenvalue 1 has multiplicity 1, and therefore if the stationary distribution between these states is perturbed, the system converges back to the stationary distribution very fast. The qualitative similarity of this patterning across different subjects, brain states and electrode locations suggests that this may be a general type of dynamics for the brain. Earlier studies indicate that not all oscillatory networks have this kind of patterning of synchronization/desynchronization dynamics. Thus, the observed prevalence of short (but potentially frequent) desynchronization events (length of one cycle of oscillations) may have important functional implications for the brain. Numerous short desynchronizations (as opposed to infrequent, but long desynchronizations) may allow for a quick and efficient formation and break-up of functionally significant neuronal assemblies.

Do anesthetics harm the developing human brain? An integrative analysis of animal and human studies.

PubMed

Lin, Erica P; Lee, Jeong-Rim; Lee, Christopher S; Deng, Meng; Loepke, Andreas W

Anesthetics that permit surgical procedures and stressful interventions have been found to cause structural brain abnormalities and functional impairment in immature animals, generating extensive concerns among clinicians, parents, and government regulators regarding the safe use of these drugs in young children. Critically important questions remain, such as the exact age at which the developing brain is most vulnerable to the effects of anesthetic exposure, whether a particular age exists beyond which anesthetics are devoid of long-term effects on the brain, and whether any specific exposure duration exists that does not lead to deleterious effects. Accordingly, the present analysis attempts to put the growing body of animal studies, which we identified to include >440 laboratory studies to date, into a translational context, by integrating the preclinical data on brain structure and function with clinical results attained from human neurocognitive studies, which currently exceed 30 studies. Our analysis demonstrated no clear exposure duration threshold below which no structural injury or subsequent cognitive abnormalities occurred. Animal data did not clearly identify a specific age beyond which anesthetic exposure did not cause any structural or functional abnormalities. Several potential mitigating strategies were found, however, no general anesthetic was identified that consistently lacked neurodegenerative properties and could be recommended over other anesthetics. It therefore is imperative, to expand efforts to devise safer anesthetic techniques and mitigating strategies, even before long-term alterations in brain development are unequivocally confirmed to occur in millions of young children undergoing anesthesia every year. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of omega-3 polyunsaturated fatty acids on human brain morphology and function: What is the evidence?

PubMed

Bos, Dienke J; van Montfort, Simone J T; Oranje, Bob; Durston, Sarah; Smeets, Paul A M

2016-03-01

Public opinion and media coverage suggest that there are benefits of long-chain ω-3 polyunsaturated fatty acid (LC-PUFA) intake on brain functioning. However, it is an open question whether this is indeed the case. Therefore, we reviewed the evidence for effects of ω-3 LC-PUFA on human brain morphology and function. We included studies on (1) naturalistic long-term ω-3 LC-PUFA intake during life (2) the effects of short-term ω-3 LC-PUFA supplementation in healthy subjects and (3) the effects of ω-3 LC-PUFA supplementation as alternative or add-on treatment for psychiatric or neurological disorders. To date, 24 studies have been published on the effect of ω-3 LC-PUFA on brain function and structure. Findings from naturalistic studies and clinical trials in healthy individuals indicate that ω-3 LC-PUFA intake may be associated with increased functional activation of the prefrontal cortex in children, and greater gray matter volume and white matter integrity during aging. However, most naturalistic studies were cross-sectional or did not find any effect on cognition. As such, it is hard to estimate the magnitude of any beneficial effects. Furthermore, there is only limited evidence to support that ω-3 LC-PUFA supplementation is beneficial in brain disorders, such as Alzheimer's Disease, Attention Deficit/Hyperactivity Disorder, Major Depressive Disorder and schizophrenia. Overall, the literature suggests that sensitivity to supplementation may vary over development, and as a consequence of brain disorders. The biological mechanisms underlying any (beneficial) effects ω-3 LC-PUFAs on the brain are currently unknown and need to be investigated. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

What We Know About the Brain Structure-Function Relationship.

PubMed

Batista-García-Ramó, Karla; Fernández-Verdecia, Caridad Ivette

2018-04-18

How the human brain works is still a question, as is its implication with brain architecture: the non-trivial structure–function relationship. The main hypothesis is that the anatomic architecture conditions, but does not determine, the neural network dynamic. The functional connectivity cannot be explained only considering the anatomical substrate. This involves complex and controversial aspects of the neuroscience field and that the methods and methodologies to obtain structural and functional connectivity are not always rigorously applied. The goal of the present article is to discuss about the progress made to elucidate the structure–function relationship of the Central Nervous System, particularly at the brain level, based on results from human and animal studies. The current novel systems and neuroimaging techniques with high resolutive physio-structural capacity have brought about the development of an integral framework of different structural and morphometric tools such as image processing, computational modeling and graph theory. Different laboratories have contributed with in vivo, in vitro and computational/mathematical models to study the intrinsic neural activity patterns based on anatomical connections. We conclude that multi-modal techniques of neuroimaging are required such as an improvement on methodologies for obtaining structural and functional connectivity. Even though simulations of the intrinsic neural activity based on anatomical connectivity can reproduce much of the observed patterns of empirical functional connectivity, future models should be multifactorial to elucidate multi-scale relationships and to infer disorder mechanisms.

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

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

Spatial Mapping of Structural and Connectional Imaging Data for the Developing Human Brain with Diffusion Tensor Imaging

PubMed Central

Ouyang, Austin; Jeon, Tina; Sunkin, Susan M.; Pletikos, Mihovil; Sedmak, Goran; Sestan, Nenad; Lein, Ed S.; Huang, Hao

2014-01-01

During human brain development from fetal stage to adulthood, the white matter (WM) tracts undergo dramatic changes. Diffusion tensor imaging (DTI), a widely used magnetic resonance imaging (MRI) modality, offers insight into the dynamic changes of WM fibers as these fibers can be noninvasively traced and three-dimensionally (3D) reconstructed with DTI tractography. The DTI and conventional T1 weighted MRI images also provide sufficient cortical anatomical details for mapping the cortical regions of interests (ROIs). In this paper, we described basic concepts and methods of DTI techniques that can be used to trace major WM tracts noninvasively from fetal brain of 14 postconceptional weeks (pcw) to adult brain. We applied these techniques to acquire DTI data and trace, reconstruct and visualize major WM tracts during development. After categorizing major WM fiber bundles into five unique functional tract groups, namely limbic, brain stem, projection, commissural and association tracts, we revealed formation and maturation of these 3D reconstructed WM tracts of the developing human brain. The structural and connectional imaging data offered by DTI provides the anatomical backbone of transcriptional atlas of the developing human brain. PMID:25448302

In vivo studies of brain development by magnetic resonance techniques.

PubMed

Inder, T E; Huppi, P S

2000-01-01

Understanding of the morphological development of the human brain has largely come from neuropathological studies obtained postmortem. Magnetic resonance (MR) techniques have recently allowed the provision of detailed structural, metabolic, and functional information in vivo on the human brain. These techniques have been utilized in studies from premature infants to adults and have provided invaluable data on the sequence of normal human brain development. This article will focus on MR techniques including conventional structural MR imaging techniques, quantitative morphometric MR techniques, diffusion weighted MR techniques, and MR spectroscopy. In order to understand the potential applications and limitations of MR techniques, relevant physical and biological principles for each of the MR techniques are first reviewed. This is followed by a review of the understanding of the sequence of normal brain development utilizing these techniques. MRDD Research Reviews 6:59-67, 2000. Copyright 2000 Wiley-Liss, Inc.

Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan.

PubMed

Nomi, Jason S; Bolt, Taylor S; Ezie, C E Chiemeka; Uddin, Lucina Q; Heller, Aaron S

2017-05-31

Variability of neuronal responses is thought to underlie flexible and optimal brain function. Because previous work investigating BOLD signal variability has been conducted within task-based fMRI contexts on adults and older individuals, very little is currently known regarding regional changes in spontaneous BOLD signal variability in the human brain across the lifespan. The current study used resting-state fMRI data from a large sample of male and female human participants covering a wide age range (6-85 years) across two different fMRI acquisition parameters (TR = 0.645 and 1.4 s). Variability in brain regions including a key node of the salience network (anterior insula) increased linearly across the lifespan across datasets. In contrast, variability in most other large-scale networks decreased linearly over the lifespan. These results demonstrate unique lifespan trajectories of BOLD variability related to specific regions of the brain and add to a growing literature demonstrating the importance of identifying normative trajectories of functional brain maturation. SIGNIFICANCE STATEMENT Although brain signal variability has traditionally been considered a source of unwanted noise, recent work demonstrates that variability in brain signals during task performance is related to brain maturation in old age as well as individual differences in behavioral performance. The current results demonstrate that intrinsic fluctuations in resting-state variability exhibit unique maturation trajectories in specific brain regions and systems, particularly those supporting salience detection. These results have implications for investigations of brain development and aging, as well as interpretations of brain function underlying behavioral changes across the lifespan. Copyright © 2017 the authors 0270-6474/17/375539-10$15.00/0.

Network science and the human brain: Using graph theory to understand the brain and one of its hubs, the amygdala, in health and disease.

PubMed

Mears, David; Pollard, Harvey B

2016-06-01

Over the past 15 years, the emerging field of network science has revealed the key features of brain networks, which include small-world topology, the presence of highly connected hubs, and hierarchical modularity. The value of network studies of the brain is underscored by the range of network alterations that have been identified in neurological and psychiatric disorders, including epilepsy, depression, Alzheimer's disease, schizophrenia, and many others. Here we briefly summarize the concepts of graph theory that are used to quantify network properties and describe common experimental approaches for analysis of brain networks of structural and functional connectivity. These range from tract tracing to functional magnetic resonance imaging, diffusion tensor imaging, electroencephalography, and magnetoencephalography. We then summarize the major findings from the application of graph theory to nervous systems ranging from Caenorhabditis elegans to more complex primate brains, including man. Focusing, then, on studies involving the amygdala, a brain region that has attracted intense interest as a center for emotional processing, fear, and motivation, we discuss the features of the amygdala in brain networks for fear conditioning and emotional perception. Finally, to highlight the utility of graph theory for studying dysfunction of the amygdala in mental illness, we review data with regard to changes in the hub properties of the amygdala in brain networks of patients with depression. We suggest that network studies of the human brain may serve to focus attention on regions and connections that act as principal drivers and controllers of brain function in health and disease. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Exploratory metabolomic analyses reveal compounds correlated with lutein concentration in frontal cortex, hippocampus, and occipital cortex of human infant brain

USDA-ARS?s Scientific Manuscript database

Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with...

Residual effects of cannabis use in adolescent and adult brains - A meta-analysis of fMRI studies.

PubMed

Blest-Hopley, Grace; Giampietro, Vincent; Bhattacharyya, Sagnik

2018-05-01

While numerous studies have investigated the residual effects of cannabis use on human brain function, results of these studies have been inconsistent. Using meta-analytic approaches we summarize the effects of prolonged cannabis exposure on human brain function as measured using task-based functional MRI (fMRI) across studies employing a range of cognitive activation tasks comparing regular cannabis users with non-users. Separate meta-analyses were carried out for studies investigating adult and adolescent cannabis users. Systematic literature search identified 20 manuscripts (13 adult and 7 adolescent studies) meeting study inclusion criteria. Adult analyses compared 530 cannabis users to 580 healthy controls while adolescent analyses compared 219 cannabis users to 224 healthy controls. In adult cannabis users brain activation was increased in the superior and posterior transverse temporal and inferior frontal gyri and decreased in the striate area, insula and middle temporal gyrus. In adolescent cannabis users, activation was increased in the inferior parietal gyrus and putamen compared to healthy controls. Functional alteration in these areas may reflect compensatory neuroadaptive changes in cannabis users. Copyright © 2018 Elsevier Ltd. All rights reserved.

DICCCOL: Dense Individualized and Common Connectivity-Based Cortical Landmarks

PubMed Central

Zhu, Dajiang; Guo, Lei; Jiang, Xi; Zhang, Tuo; Zhang, Degang; Chen, Hanbo; Deng, Fan; Faraco, Carlos; Jin, Changfeng; Wee, Chong-Yaw; Yuan, Yixuan; Lv, Peili; Yin, Yan; Hu, Xiaolei; Duan, Lian; Hu, Xintao; Han, Junwei; Wang, Lihong; Shen, Dinggang; Miller, L Stephen

2013-01-01

Is there a common structural and functional cortical architecture that can be quantitatively encoded and precisely reproduced across individuals and populations? This question is still largely unanswered due to the vast complexity, variability, and nonlinearity of the cerebral cortex. Here, we hypothesize that the common cortical architecture can be effectively represented by group-wise consistent structural fiber connections and take a novel data-driven approach to explore the cortical architecture. We report a dense and consistent map of 358 cortical landmarks, named Dense Individualized and Common Connectivity–based Cortical Landmarks (DICCCOLs). Each DICCCOL is defined by group-wise consistent white-matter fiber connection patterns derived from diffusion tensor imaging (DTI) data. Our results have shown that these 358 landmarks are remarkably reproducible over more than one hundred human brains and possess accurate intrinsically established structural and functional cross-subject correspondences validated by large-scale functional magnetic resonance imaging data. In particular, these 358 cortical landmarks can be accurately and efficiently predicted in a new single brain with DTI data. Thus, this set of 358 DICCCOL landmarks comprehensively encodes the common structural and functional cortical architectures, providing opportunities for many applications in brain science including mapping human brain connectomes, as demonstrated in this work. PMID:22490548

A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra.

PubMed

Rae, Caroline D

2014-01-01

The current knowledge of the normal biochemistry of compounds that give rise to resonances in human brain proton magnetic resonance spectra measureable at readily available field strengths (i.e. ≤3 T) is reviewed. Molecules covered include myo- and scyllo-inositol, glycerophospho- and phospho-choline and choline, creatine and phosphocreatine, N-acetylaspartate, N-acetylaspartylglutamate, glutamate, glutamine, γ-aminobutyrate, glucose, glutathione and lactate. The factors which influence changes in the levels of these compounds are discussed. As most proton resonances in the brain at low field are derived from a combination of moieties whose biochemistry is complex and interrelated, an understanding of the mechanisms underlying why these species change is crucial to meaningful interpretation of human brain spectra.

Intraoperative intrinsic optical imaging of human somatosensory cortex during neurosurgical operations.

PubMed

Sato, Katsushige; Nariai, Tadashi; Momose-Sato, Yoko; Kamino, Kohtaro

2017-07-01

Intrinsic optical imaging as developed by Grinvald et al. is a powerful technique for monitoring neural function in the in vivo central nervous system. The advent of this dye-free imaging has also enabled us to monitor human brain function during neurosurgical operations. We briefly describe our own experience in functional mapping of the human somatosensory cortex, carried out using intraoperative optical imaging. The maps obtained demonstrate new additional evidence of a hierarchy for sensory response patterns in the human primary somatosensory cortex.

BrainNet Viewer: a network visualization tool for human brain connectomics.

PubMed

Xia, Mingrui; Wang, Jinhui; He, Yong

2013-01-01

The human brain is a complex system whose topological organization can be represented using connectomics. Recent studies have shown that human connectomes can be constructed using various neuroimaging technologies and further characterized using sophisticated analytic strategies, such as graph theory. These methods reveal the intriguing topological architectures of human brain networks in healthy populations and explore the changes throughout normal development and aging and under various pathological conditions. However, given the huge complexity of this methodology, toolboxes for graph-based network visualization are still lacking. Here, using MATLAB with a graphical user interface (GUI), we developed a graph-theoretical network visualization toolbox, called BrainNet Viewer, to illustrate human connectomes as ball-and-stick models. Within this toolbox, several combinations of defined files with connectome information can be loaded to display different combinations of brain surface, nodes and edges. In addition, display properties, such as the color and size of network elements or the layout of the figure, can be adjusted within a comprehensive but easy-to-use settings panel. Moreover, BrainNet Viewer draws the brain surface, nodes and edges in sequence and displays brain networks in multiple views, as required by the user. The figure can be manipulated with certain interaction functions to display more detailed information. Furthermore, the figures can be exported as commonly used image file formats or demonstration video for further use. BrainNet Viewer helps researchers to visualize brain networks in an easy, flexible and quick manner, and this software is freely available on the NITRC website (www.nitrc.org/projects/bnv/).

Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease

PubMed Central

Horowitz, Alana M.; Villeda, Saul A.

2017-01-01

Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans. PMID:28815019

Reconstruction of human brain spontaneous activity based on frequency-pattern analysis of magnetoencephalography data

PubMed Central

Llinás, Rodolfo R.; Ustinin, Mikhail N.; Rykunov, Stanislav D.; Boyko, Anna I.; Sychev, Vyacheslav V.; Walton, Kerry D.; Rabello, Guilherme M.; Garcia, John

2015-01-01

A new method for the analysis and localization of brain activity has been developed, based on multichannel magnetic field recordings, over minutes, superimposed on the MRI of the individual. Here, a high resolution Fourier Transform is obtained over the entire recording period, leading to a detailed multi-frequency spectrum. Further analysis implements a total decomposition of the frequency components into functionally invariant entities, each having an invariant field pattern localizable in recording space. The method, addressed as functional tomography, makes it possible to find the distribution of magnetic field sources in space. Here, the method is applied to the analysis of simulated data, to oscillating signals activating a physical current dipoles phantom, and to recordings of spontaneous brain activity in 10 healthy adults. In the analysis of simulated data, 61 dipoles are localized with 0.7 mm precision. Concerning the physical phantom the method is able to localize three simultaneously activated current dipoles with 1 mm precision. Spatial resolution 3 mm was attained when localizing spontaneous alpha rhythm activity in 10 healthy adults, where the alpha peak was specified for each subject individually. Co-registration of the functional tomograms with each subject's head MRI localized alpha range activity to the occipital and/or posterior parietal brain region. This is the first application of this new functional tomography to human brain activity. The method successfully provides an overall view of brain electrical activity, a detailed spectral description and, combined with MRI, the localization of sources in anatomical brain space. PMID:26528119

Imaging brain development: the adolescent brain.

PubMed

Blakemore, Sarah-Jayne

2012-06-01

The past 15 years have seen a rapid expansion in the number of studies using neuroimaging techniques to investigate maturational changes in the human brain. In this paper, I review MRI studies on structural changes in the developing brain, and fMRI studies on functional changes in the social brain during adolescence. Both MRI and fMRI studies point to adolescence as a period of continued neural development. In the final section, I discuss a number of areas of research that are just beginning and may be the subject of developmental neuroimaging in the next twenty years. Future studies might focus on complex questions including the development of functional connectivity; how gender and puberty influence adolescent brain development; the effects of genes, environment and culture on the adolescent brain; development of the atypical adolescent brain; and implications for policy of the study of the adolescent brain. Copyright © 2011 Elsevier Inc. All rights reserved.

Non-invasive Brain Stimulation: Probing Intracortical Circuits and Improving Cognition in the Aging Brain

PubMed Central

Gomes-Osman, Joyce; Indahlastari, Aprinda; Fried, Peter J.; Cabral, Danylo L. F.; Rice, Jordyn; Nissim, Nicole R.; Aksu, Serkan; McLaren, Molly E.; Woods, Adam J.

2018-01-01

The impact of cognitive aging on brain function and structure is complex, and the relationship between aging-related structural changes and cognitive function are not fully understood. Physiological and pathological changes to the aging brain are highly variable, making it difficult to estimate a cognitive trajectory with which to monitor the conversion to cognitive decline. Beyond the information on the structural and functional consequences of cognitive aging gained from brain imaging and neuropsychological studies, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can enable stimulation of the human brain in vivo, offering useful insights into the functional integrity of intracortical circuits using electrophysiology and neuromodulation. TMS measurements can be used to identify and monitor changes in cortical reactivity, the integrity of inhibitory and excitatory intracortical circuits, the mechanisms of long-term potentiation (LTP)/depression-like plasticity and central cholinergic function. Repetitive TMS and tDCS can be used to modulate neuronal excitability and enhance cortical function, and thus offer a potential means to slow or reverse cognitive decline. This review will summarize and critically appraise relevant literature regarding the use of TMS and tDCS to probe cortical areas affected by the aging brain, and as potential therapeutic tools to improve cognitive function in the aging population. Challenges arising from intra-individual differences, limited reproducibility, and methodological differences will be discussed.

Functional neuroimaging insights into the physiology of human sleep.

PubMed

Dang-Vu, Thien Thanh; Schabus, Manuel; Desseilles, Martin; Sterpenich, Virginie; Bonjean, Maxime; Maquet, Pierre

2010-12-01

Functional brain imaging has been used in humans to noninvasively investigate the neural mechanisms underlying the generation of sleep stages. On the one hand, REM sleep has been associated with the activation of the pons, thalamus, limbic areas, and temporo-occipital cortices, and the deactivation of prefrontal areas, in line with theories of REM sleep generation and dreaming properties. On the other hand, during non-REM (NREM) sleep, decreases in brain activity have been consistently found in the brainstem, thalamus, and in several cortical areas including the medial prefrontal cortex (MPFC), in agreement with a homeostatic need for brain energy recovery. Benefiting from a better temporal resolution, more recent studies have characterized the brain activations related to phasic events within specific sleep stages. In particular, they have demonstrated that NREM sleep oscillations (spindles and slow waves) are indeed associated with increases in brain activity in specific subcortical and cortical areas involved in the generation or modulation of these waves. These data highlight that, even during NREM sleep, brain activity is increased, yet regionally specific and transient. Besides refining the understanding of sleep mechanisms, functional brain imaging has also advanced the description of the functional properties of sleep. For instance, it has been shown that the sleeping brain is still able to process external information and even detect the pertinence of its content. The relationship between sleep and memory has also been refined using neuroimaging, demonstrating post-learning reactivation during sleep, as well as the reorganization of memory representation on the systems level, sometimes with long-lasting effects on subsequent memory performance. Further imaging studies should focus on clarifying the role of specific sleep patterns for the processing of external stimuli, as well as the consolidation of freshly encoded information during sleep.

Docosahexaenoic acid (DHA), a fundamental fatty acid for the brain: New dietary sources.

PubMed

Echeverría, Francisca; Valenzuela, Rodrigo; Catalina Hernandez-Rodas, María; Valenzuela, Alfonso

2017-09-01

Docosahexaenoic acid (C22: 6n-3, DHA) is a long-chain polyunsaturated fatty acid of marine origin fundamental for the formation and function of the nervous system, particularly the brain and the retina of humans. It has been proposed a remarkable role of DHA during human evolution, mainly on the growth and development of the brain. Currently, DHA is considered a critical nutrient during pregnancy and breastfeeding due their active participation in the development of the nervous system in early life. DHA and specifically one of its derivatives known as neuroprotectin D-1 (NPD-1), has neuroprotective properties against brain aging, neurodegenerative diseases and injury caused after brain ischemia-reperfusion episodes. This paper discusses the importance of DHA in the human brain given its relevance in the development of the tissue and as neuroprotective agent. It is also included a critical view about the ways to supply this noble fatty acid to the population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intranasal insulin enhances brain functional connectivity mediating the relationship between adiposity and subjective feeling of hunger.

PubMed

Kullmann, Stephanie; Heni, Martin; Veit, Ralf; Scheffler, Klaus; Machann, Jürgen; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

2017-05-09

Brain insulin sensitivity is an important link between metabolism and cognitive dysfunction. Intranasal insulin is a promising tool to investigate central insulin action in humans. We evaluated the acute effects of 160 U intranasal insulin on resting-state brain functional connectivity in healthy young adults. Twenty-five lean and twenty-two overweight and obese participants underwent functional magnetic resonance imaging, on two separate days, before and after intranasal insulin or placebo application. Insulin compared to placebo administration resulted in increased functional connectivity between the prefrontal regions of the default-mode network and the hippocampus as well as the hypothalamus. The change in hippocampal functional connectivity significantly correlated with visceral adipose tissue and the change in subjective feeling of hunger after intranasal insulin. Mediation analysis revealed that the intranasal insulin induced hippocampal functional connectivity increase served as a mediator, suppressing the relationship between visceral adipose tissue and hunger. The insulin-induced hypothalamic functional connectivity change showed a significant interaction with peripheral insulin sensitivity. Only participants with high peripheral insulin sensitivity showed a boost in hypothalamic functional connectivity. Hence, brain insulin action may regulate eating behavior and facilitate weight loss by modifying brain functional connectivity within and between cognitive and homeostatic brain regions.

Resolving rates of mutation in the brain using single-neuron genomics

PubMed Central

Evrony, Gilad D; Lee, Eunjung; Park, Peter J; Walsh, Christopher A

2016-01-01

Whether somatic mutations contribute functional diversity to brain cells is a long-standing question. Single-neuron genomics enables direct measurement of somatic mutation rates in human brain and promises to answer this question. A recent study (Upton et al., 2015) reported high rates of somatic LINE-1 element (L1) retrotransposition in the hippocampus and cerebral cortex that would have major implications for normal brain function, and suggested that these events preferentially impact genes important for neuronal function. We identify aspects of the single-cell sequencing approach, bioinformatic analysis, and validation methods that led to thousands of artifacts being interpreted as somatic mutation events. Our reanalysis supports a mutation frequency of approximately 0.2 events per cell, which is about fifty-fold lower than reported, confirming that L1 elements mobilize in some human neurons but indicating that L1 mosaicism is not ubiquitous. Through consideration of the challenges identified, we provide a foundation and framework for designing single-cell genomics studies. DOI: http://dx.doi.org/10.7554/eLife.12966.001 PMID:26901440

Functional Brain Organization for Number Processing in Pre-Verbal Infants

ERIC Educational Resources Information Center

Edwards, Laura A.; Wagner, Jennifer B.; Simon, Charline E.; Hyde, Daniel C.

2016-01-01

Humans are born with the ability to mentally represent the approximate numerosity of a set of objects, but little is known about the brain systems that sub-serve this ability early in life and their relation to the brain systems underlying symbolic number and mathematics later in development. Here we investigate processing of numerical magnitudes…

Searching for Factors Underlying Cerebral Plasticity in the Normal and Injured Brain

ERIC Educational Resources Information Center

Kolb, Bryan; Muhammad, Arif; Gibb, Robbin

2011-01-01

Brain plasticity refers to the capacity of the nervous system to change its structure and ultimately its function over a lifetime. There have been major advances in our understanding of the principles of brain plasticity and behavior in laboratory animals and humans. Over the past decade there have been advances in the application of these…

Microglial Dynamics During Human Brain Development

PubMed Central

Menassa, David A.; Gomez-Nicola, Diego

2018-01-01

Microglial cells are thought to colonize the human cerebrum between the 4th and 24th gestational weeks. Rodent studies have demonstrated that these cells originate from yolk sac progenitors though it is not clear whether this directly pertains to human development. Our understanding of microglial cell dynamics in the developing human brain comes mostly from postmortem studies demonstrating that the beginning of microglial colonization precedes the appearance of the vasculature, the blood–brain barrier, astrogliogenesis, oligodendrogenesis, neurogenesis, migration, and myelination of the various brain areas. Furthermore, migrating microglial populations cluster by morphology and express differential markers within the developing brain and according to developmental age. With the advent of novel technologies such as RNA-sequencing in fresh human tissue, we are beginning to identify the molecular features of the adult microglial signature. However, this is may not extend to the much more dynamic and rapidly changing antenatal microglial population and this is further complicated by the scarcity of tissue resources. In this brief review, we first describe the various historic schools of thought that had debated the origin of microglial cells while examining the evidence supporting the various theories. We then proceed to examine the evidence we have accumulated on microglial dynamics in the developing human brain, present evidence from rodent studies on the functional role of microglia during development and finally identify limitations for the used approaches in human studies and highlight under investigated questions. PMID:29881376

The Vertebrate Brain, Evidence of Its Modular Organization and Operating System: Insights into the Brain's Basic Units of Structure, Function, and Operation and How They Influence Neuronal Signaling and Behavior.

PubMed

Baslow, Morris H

2011-01-01

The human brain is a complex organ made up of neurons and several other cell types, and whose role is processing information for use in eliciting behaviors. However, the composition of its repeating cellular units for both structure and function are unresolved. Based on recent descriptions of the brain's physiological "operating system", a function of the tri-cellular metabolism of N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) for supply of energy, and on the nature of "neuronal words and languages" for intercellular communication, insights into the brain's modular structural and functional units have been gained. In this article, it is proposed that the basic structural unit in brain is defined by its physiological operating system, and that it consists of a single neuron, and one or more astrocytes, oligodendrocytes, and vascular system endothelial cells. It is also proposed that the basic functional unit in the brain is defined by how neurons communicate, and consists of two neurons and their interconnecting dendritic-synaptic-dendritic field. Since a functional unit is composed of two neurons, it requires two structural units to form a functional unit. Thus, the brain can be envisioned as being made up of the three-dimensional stacking and intertwining of myriad structural units which results not only in its gross structure, but also in producing a uniform distribution of binary functional units. Since the physiological NAA-NAAG operating system for supply of energy is repeated in every structural unit, it is positioned to control global brain function.

Functional connectome fingerprinting: identifying individuals using patterns of brain connectivity.

PubMed

Finn, Emily S; Shen, Xilin; Scheinost, Dustin; Rosenberg, Monica D; Huang, Jessica; Chun, Marvin M; Papademetris, Xenophon; Constable, R Todd

2015-11-01

Functional magnetic resonance imaging (fMRI) studies typically collapse data from many subjects, but brain functional organization varies between individuals. Here we establish that this individual variability is both robust and reliable, using data from the Human Connectome Project to demonstrate that functional connectivity profiles act as a 'fingerprint' that can accurately identify subjects from a large group. Identification was successful across scan sessions and even between task and rest conditions, indicating that an individual's connectivity profile is intrinsic, and can be used to distinguish that individual regardless of how the brain is engaged during imaging. Characteristic connectivity patterns were distributed throughout the brain, but the frontoparietal network emerged as most distinctive. Furthermore, we show that connectivity profiles predict levels of fluid intelligence: the same networks that were most discriminating of individuals were also most predictive of cognitive behavior. Results indicate the potential to draw inferences about single subjects on the basis of functional connectivity fMRI.

Future developments in brain-machine interface research.

PubMed

Lebedev, Mikhail A; Tate, Andrew J; Hanson, Timothy L; Li, Zheng; O'Doherty, Joseph E; Winans, Jesse A; Ifft, Peter J; Zhuang, Katie Z; Fitzsimmons, Nathan A; Schwarz, David A; Fuller, Andrew M; An, Je Hi; Nicolelis, Miguel A L

2011-01-01

Neuroprosthetic devices based on brain-machine interface technology hold promise for the restoration of body mobility in patients suffering from devastating motor deficits caused by brain injury, neurologic diseases and limb loss. During the last decade, considerable progress has been achieved in this multidisciplinary research, mainly in the brain-machine interface that enacts upper-limb functionality. However, a considerable number of problems need to be resolved before fully functional limb neuroprostheses can be built. To move towards developing neuroprosthetic devices for humans, brain-machine interface research has to address a number of issues related to improving the quality of neuronal recordings, achieving stable, long-term performance, and extending the brain-machine interface approach to a broad range of motor and sensory functions. Here, we review the future steps that are part of the strategic plan of the Duke University Center for Neuroengineering, and its partners, the Brazilian National Institute of Brain-Machine Interfaces and the École Polytechnique Fédérale de Lausanne (EPFL) Center for Neuroprosthetics, to bring this new technology to clinical fruition.

Human Cerebral Function at High Altitude.

DTIC Science & Technology

1983-08-01

known acute organic brain syndrome (10). How do increasing degrees of oxygen deprivation, together with extreme climatic conditions, produce the...these, half experienced symptoms similar to an acute organic brain syndrome ; "for several weeks after the expedition they continued to feel poorly

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

PubMed Central

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

2013-01-01

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. PMID:23359801

Resting-State fMRI Functional Connectivity Is Associated with Sleepiness, Imagery, and Discontinuity of Mind

PubMed Central

Chen, Gang; den Braber, Anouk; van ‘t Ent, Dennis; Boomsma, Dorret I.; Mansvelder, Huibert D.; de Geus, Eco; Van Someren, Eus J. W.; Linkenkaer-Hansen, Klaus

2015-01-01

Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to investigate the functional architecture of the healthy human brain and how it is affected by learning, lifelong development, brain disorders or pharmacological intervention. Non-sensory experiences are prevalent during rest and must arise from ongoing brain activity, yet little is known about this relationship. Here, we used two runs of rs-fMRI both immediately followed by the Amsterdam Resting-State Questionnaire (ARSQ) to investigate the relationship between functional connectivity within ten large-scale functional brain networks and ten dimensions of thoughts and feelings experienced during the scan in 106 healthy participants. We identified 11 positive associations between brain-network functional connectivity and ARSQ dimensions. ‘Sleepiness’ exhibited significant associations with functional connectivity within Visual, Sensorimotor and Default Mode networks. Similar associations were observed for ‘Visual Thought’ and ‘Discontinuity of Mind’, which may relate to variation in imagery and thought control mediated by arousal fluctuations. Our findings show that self-reports of thoughts and feelings experienced during a rs-fMRI scan help understand the functional significance of variations in functional connectivity, which should be of special relevance to clinical studies. PMID:26540239

Neuroimaging in human MDMA (Ecstasy) users.

PubMed

Cowan, Ronald L; Roberts, Deanne M; Joers, James M

2008-10-01

MDMA (3,4 methylenedioxymethamphetamine) has been used by millions of people worldwide as a recreational drug. The terms "MDMA" and "Ecstasy" are often used synonymously, but it is important to note that the purity of Ecstasy sold as MDMA is not certain. MDMA use is of public health concern, not so much because MDMA produces a common or severe dependence syndrome, but rather because rodent and nonhuman primate studies have indicated that MDMA (when administered at certain dosages and intervals) can cause long-lasting reductions in markers of brain serotonin (5-HT) that appear specific to fine-diameter axons arising largely from the dorsal raphe nucleus (DR). Given the popularity of MDMA, the potential for the drug to produce long-lasting or permanent 5-HT axon damage or loss, and the widespread role of 5-HT function in the brain, there is a great need for a better understanding of brain function in human users of this drug. To this end, neuropsychological, neuroendocrine, and neuroimaging studies have all suggested that human MDMA users may have long-lasting changes in brain function consistent with 5-HT toxicity. Data from animal models leads to testable hypotheses regarding MDMA's effects on the human brain. Because neuropsychological and neuroimaging findings have focused on the neocortex, a cortical model is developed to provide a context for designing and interpreting neuroimaging studies in MDMA users. Aspects of the model are supported by the available neuroimaging data, but there are controversial findings in some areas and most findings have not been replicated across different laboratories and using different modalities. This paper reviews existing findings in the context of a cortical model and suggests directions for future research.

Towards ultrahigh resting-state functional connectivity in the mouse brain using photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Hariri, Ali; Bely, Nicholas; Chen, Chen; Nasiriavanaki, Mohammadreza

2016-03-01

The increasing use of mouse models for human brain disease studies, coupled with the fact that existing high-resolution functional imaging modalities cannot be easily applied to mice, presents an emerging need for a new functional imaging modality. Utilizing both mechanical and optical scanning in the photoacoustic microscopy, we can image spontaneous cerebral hemodynamic fluctuations and their associated functional connections in the mouse brain. The images is going to be acquired noninvasively with a fast frame rate, a large field of view, and a high spatial resolution. We developed an optical resolution photoacoustic microscopy (OR-PAM) with diode laser. Laser light was raster scanned due to XY-stage movement. Images from ultra-high OR-PAM can then be used to study brain disorders such as stroke, Alzheimer's, schizophrenia, multiple sclerosis, autism, and epilepsy.

Inferring Selective Constraint from Population Genomic Data Suggests Recent Regulatory Turnover in the Human Brain

PubMed Central

Schrider, Daniel R.; Kern, Andrew D.

2015-01-01

The comparative genomics revolution of the past decade has enabled the discovery of functional elements in the human genome via sequence comparison. While that is so, an important class of elements, those specific to humans, is entirely missed by searching for sequence conservation across species. Here we present an analysis based on variation data among human genomes that utilizes a supervised machine learning approach for the identification of human-specific purifying selection in the genome. Using only allele frequency information from the complete low-coverage 1000 Genomes Project data set in conjunction with a support vector machine trained from known functional and nonfunctional portions of the genome, we are able to accurately identify portions of the genome constrained by purifying selection. Our method identifies previously known human-specific gains or losses of function and uncovers many novel candidates. Candidate targets for gain and loss of function along the human lineage include numerous putative regulatory regions of genes essential for normal development of the central nervous system, including a significant enrichment of gain of function events near neurotransmitter receptor genes. These results are consistent with regulatory turnover being a key mechanism in the evolution of human-specific characteristics of brain development. Finally, we show that the majority of the genome is unconstrained by natural selection currently, in agreement with what has been estimated from phylogenetic methods but in sharp contrast to estimates based on transcriptomics or other high-throughput functional methods. PMID:26590212

Copine1 regulates neural stem cell functions during brain development.

PubMed

Kim, Tae Hwan; Sung, Soo-Eun; Cheal Yoo, Jae; Park, Jae-Yong; Yi, Gwan-Su; Heo, Jun Young; Lee, Jae-Ran; Kim, Nam-Soon; Lee, Da Yong

2018-01-01

Copine 1 (CPNE1) is a well-known phospholipid binding protein in plasma membrane of various cell types. In brain cells, CPNE1 is closely associated with AKT signaling pathway, which is important for neural stem cell (NSC) functions during brain development. Here, we investigated the role of CPNE1 in the regulation of brain NSC functions during brain development and determined its underlying mechanism. In this study, abundant expression of CPNE1 was observed in neural lineage cells including NSCs and immature neurons in human. With mouse brain tissues in various developmental stages, we found that CPNE1 expression was higher at early embryonic stages compared to postnatal and adult stages. To model developing brain in vitro, we used primary NSCs derived from mouse embryonic hippocampus. Our in vitro study shows decreased proliferation and multi-lineage differentiation potential in CPNE1 deficient NSCs. Finally, we found that the deficiency of CPNE1 downregulated mTOR signaling in embryonic NSCs. These data demonstrate that CPNE1 plays a key role in the regulation of NSC functions through the activation of AKT-mTOR signaling pathway during brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

EEG-based research on brain functional networks in cognition.

PubMed

Wang, Niannian; Zhang, Li; Liu, Guozhong

2015-01-01

Recently, exploring the cognitive functions of the brain by establishing a network model to understand the working mechanism of the brain has become a popular research topic in the field of neuroscience. In this study, electroencephalography (EEG) was used to collect data from subjects given four different mathematical cognitive tasks: recite numbers clockwise and counter-clockwise, and letters clockwise and counter-clockwise to build a complex brain function network (BFN). By studying the connectivity features and parameters of those brain functional networks, it was found that the average clustering coefficient is much larger than its corresponding random network and the average shortest path length is similar to the corresponding random networks, which clearly shows the characteristics of the small-world network. The brain regions stimulated during the experiment are consistent with traditional cognitive science regarding learning, memory, comprehension, and other rational judgment results. The new method of complex networking involves studying the mathematical cognitive process of reciting, providing an effective research foundation for exploring the relationship between brain cognition and human learning skills and memory. This could help detect memory deficits early in young and mentally handicapped children, and help scientists understand the causes of cognitive brain disorders.

When Neuroscience 'Touches' Architecture: From Hapticity to a Supramodal Functioning of the Human Brain.

PubMed

Papale, Paolo; Chiesi, Leonardo; Rampinini, Alessandra C; Pietrini, Pietro; Ricciardi, Emiliano

2016-01-01

In the last decades, the rapid growth of functional brain imaging methodologies allowed cognitive neuroscience to address open questions in philosophy and social sciences. At the same time, novel insights from cognitive neuroscience research have begun to influence various disciplines, leading to a turn to cognition and emotion in the fields of planning and architectural design. Since 2003, the Academy of Neuroscience for Architecture has been supporting 'neuro-architecture' as a way to connect neuroscience and the study of behavioral responses to the built environment. Among the many topics related to multisensory perceptual integration and embodiment, the concept of hapticity was recently introduced, suggesting a pivotal role of tactile perception and haptic imagery in architectural appraisal. Arguments have thus risen in favor of the existence of shared cognitive foundations between hapticity and the supramodal functional architecture of the human brain. Precisely, supramodality refers to the functional feature of defined brain regions to process and represent specific information content in a more abstract way, independently of the sensory modality conveying such information to the brain. Here, we highlight some commonalities and differences between the concepts of hapticity and supramodality according to the distinctive perspectives of architecture and cognitive neuroscience. This comparison and connection between these two different approaches may lead to novel observations in regard to people-environment relationships, and even provide empirical foundations for a renewed evidence-based design theory.

Early Development of Functional Network Segregation Revealed by Connectomic Analysis of the Preterm Human Brain.

PubMed

Cao, Miao; He, Yong; Dai, Zhengjia; Liao, Xuhong; Jeon, Tina; Ouyang, Minhui; Chalak, Lina; Bi, Yanchao; Rollins, Nancy; Dong, Qi; Huang, Hao

2017-03-01

Human brain functional networks are topologically organized with nontrivial connectivity characteristics such as small-worldness and densely linked hubs to support highly segregated and integrated information processing. However, how they emerge and change at very early developmental phases remains poorly understood. Here, we used resting-state functional MRI and voxel-based graph theory analysis to systematically investigate the topological organization of whole-brain networks in 40 infants aged around 31 to 42 postmenstrual weeks. The functional connectivity strength and heterogeneity increased significantly in primary motor, somatosensory, visual, and auditory regions, but much less in high-order default-mode and executive-control regions. The hub and rich-club structures in primary regions were already present at around 31 postmenstrual weeks and exhibited remarkable expansions with age, accompanied by increased local clustering and shortest path length, indicating a transition from a relatively random to a more organized configuration. Moreover, multivariate pattern analysis using support vector regression revealed that individual brain maturity of preterm babies could be predicted by the network connectivity patterns. Collectively, we highlighted a gradually enhanced functional network segregation manner in the third trimester, which is primarily driven by the rapid increases of functional connectivity of the primary regions, providing crucial insights into the topological development patterns prior to birth. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Novel Human Body Area Network for Brain Diseases Analysis.

PubMed

Lin, Kai; Xu, Tianlang

2016-10-01

Development of wireless sensor and mobile communication technology provide an unprecedented opportunity for realizing smart and interactive healthcare systems. Designing such systems aims to remotely monitor the health and diagnose the diseases for users. In this paper, we design a novel human body area network for brain diseases analysis, which is named BABDA. Considering the brain is one of the most complex organs in the human body, the BABDA system provides four function modules to ensure the high quality of the analysis result, which includes initial data collection, data correction, data transmission and comprehensive data analysis. The performance evaluation conducted in a realistic environment with several criteria shows the availability and practicability of the BABDA system.

Inferring consistent functional interaction patterns from natural stimulus FMRI data

PubMed Central

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

2014-01-01

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

Training the Brain: Practical Applications of Neural Plasticity From the Intersection of Cognitive Neuroscience, Developmental Psychology, and Prevention Science

PubMed Central

Bryck, Richard L.; Fisher, Philip A.

2012-01-01

Prior researchers have shown that the brain has a remarkable ability for adapting to environmental changes. The positive effects of such neural plasticity include enhanced functioning in specific cognitive domains and shifts in cortical representation following naturally occurring cases of sensory deprivation; however, maladaptive changes in brain function and development owing to early developmental adversity and stress have also been well documented. Researchers examining enriched rearing environments in animals have revealed the potential for inducing positive brain plasticity effects and have helped to popularize methods for training the brain to reverse early brain deficits or to boost normal cognitive functioning. In this paper, two classes of empirically based methods of brain training in children are reviewed and critiqued: laboratory-based, mental process training paradigms and ecological interventions based upon neurocognitive conceptual models. Given the susceptibility of executive function disruption, special attention is paid to training programs that emphasize executive function enhancement. In addition, a third approach to brain training, aimed at tapping into compensatory processes, is postulated. Study results showing the effectiveness of this strategy in the field of neurorehabilitation and in terms of naturally occurring compensatory processing in human aging lend credence to the potential of this approach. PMID:21787037

Training the brain: practical applications of neural plasticity from the intersection of cognitive neuroscience, developmental psychology, and prevention science.

PubMed

Bryck, Richard L; Fisher, Philip A

2012-01-01

Prior researchers have shown that the brain has a remarkable ability for adapting to environmental changes. The positive effects of such neural plasticity include enhanced functioning in specific cognitive domains and shifts in cortical representation following naturally occurring cases of sensory deprivation; however, maladaptive changes in brain function and development owing to early developmental adversity and stress have also been well documented. Researchers examining enriched rearing environments in animals have revealed the potential for inducing positive brain plasticity effects and have helped to popularize methods for training the brain to reverse early brain deficits or to boost normal cognitive functioning. In this article, two classes of empirically based methods of brain training in children are reviewed and critiqued: laboratory-based, mental process training paradigms and ecological interventions based upon neurocognitive conceptual models. Given the susceptibility of executive function disruption, special attention is paid to training programs that emphasize executive function enhancement. In addition, a third approach to brain training, aimed at tapping into compensatory processes, is postulated. Study results showing the effectiveness of this strategy in the field of neurorehabilitation and in terms of naturally occurring compensatory processing in human aging lend credence to the potential of this approach. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

INVESTIGATING DIFFERENCES IN BRAIN FUNCTIONAL NETWORKS USING HIERARCHICAL COVARIATE-ADJUSTED INDEPENDENT COMPONENT ANALYSIS.

PubMed

Shi, Ran; Guo, Ying

2016-12-01

Human brains perform tasks via complex functional networks consisting of separated brain regions. A popular approach to characterize brain functional networks in fMRI studies is independent component analysis (ICA), which is a powerful method to reconstruct latent source signals from their linear mixtures. In many fMRI studies, an important goal is to investigate how brain functional networks change according to specific clinical and demographic variabilities. Existing ICA methods, however, cannot directly incorporate covariate effects in ICA decomposition. Heuristic post-ICA analysis to address this need can be inaccurate and inefficient. In this paper, we propose a hierarchical covariate-adjusted ICA (hc-ICA) model that provides a formal statistical framework for estimating covariate effects and testing differences between brain functional networks. Our method provides a more reliable and powerful statistical tool for evaluating group differences in brain functional networks while appropriately controlling for potential confounding factors. We present an analytically tractable EM algorithm to obtain maximum likelihood estimates of our model. We also develop a subspace-based approximate EM that runs significantly faster while retaining high accuracy. To test the differences in functional networks, we introduce a voxel-wise approximate inference procedure which eliminates the need of computationally expensive covariance matrix estimation and inversion. We demonstrate the advantages of our methods over the existing method via simulation studies. We apply our method to an fMRI study to investigate differences in brain functional networks associated with post-traumatic stress disorder (PTSD).

Default network connectivity decodes brain states with simulated microgravity.

PubMed

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

2016-04-01

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

Neuropsychology and cognitive neuroscience in the fMRI era: A recapitulation of localizationist and connectionist views.

PubMed

Sutterer, Matthew J; Tranel, Daniel

2017-11-01

We highlight the past 25 years of cognitive neuroscience and neuropsychology, focusing on the impact to the field of the introduction in 1992 of functional MRI (fMRI). We reviewed the past 25 years of literature in cognitive neuroscience and neuropsychology, focusing on the relation and interplay of fMRI studies and studies utilizing the "lesion method" in human participants with focal brain damage. Our review highlights the state of localist/connectionist research debates in cognitive neuroscience and neuropsychology circa 1992, and details how the introduction of fMRI into the field at that time catalyzed a new wave of efforts to map complex human behavior to specific brain regions. This, in turn, eventually evolved into many studies that focused on networks and connections between brain areas, culminating in recent years with large-scale investigations such as the Human Connectome Project. We argue that throughout the past 25 years, neuropsychology-and more precisely, the "lesion method" in humans-has continued to play a critical role in arbitrating conclusions and theories derived from inferred patterns of local brain activity or wide-spread connectivity from functional imaging approaches. We conclude by highlighting the future for neuropsychology in the context of an increasingly complex methodological armamentarium. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Ghrelin modulates encoding-related brain function without enhancing memory formation in humans.

PubMed

Kunath, N; Müller, N C J; Tonon, M; Konrad, B N; Pawlowski, M; Kopczak, A; Elbau, I; Uhr, M; Kühn, S; Repantis, D; Ohla, K; Müller, T D; Fernández, G; Tschöp, M; Czisch, M; Steiger, A; Dresler, M

2016-11-15

Ghrelin regulates energy homeostasis in various species and enhances memory in rodent models. In humans, the role of ghrelin in cognitive processes has yet to be characterized. Here we show in a double-blind randomized crossover design that acute administration of ghrelin alters encoding-related brain activity, however does not enhance memory formation in humans. Twenty-one healthy young male participants had to memorize food- and non-food-related words presented on a background of a virtual navigational route while undergoing fMRI recordings. After acute ghrelin administration, we observed decreased post-encoding resting state fMRI connectivity between the caudate nucleus and the insula, amygdala, and orbitofrontal cortex. In addition, brain activity related to subsequent memory performance was modulated by ghrelin. On the next day, however, no differences were found in free word recall or cued location-word association recall between conditions; and ghrelin's effects on brain activity or functional connectivity were unrelated to memory performance. Further, ghrelin had no effect on a cognitive test battery comprising tests for working memory, fluid reasoning, creativity, mental speed, and attention. In conclusion, in contrast to studies with animal models, we did not find any evidence for the potential of ghrelin acting as a short-term cognitive enhancer in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

T cell–derived interleukin (IL)-21 promotes brain injury following stroke in mice

PubMed Central

Clarkson, Benjamin D.S.; Ling, Changying; Shi, Yejie; Harris, Melissa G.; Rayasam, Aditya; Sun, Dandan; Salamat, M. Shahriar; Kuchroo, Vijay; Lambris, John D.; Sandor, Matyas

2014-01-01

T lymphocytes are key contributors to the acute phase of cerebral ischemia reperfusion injury, but the relevant T cell–derived mediators of tissue injury remain unknown. Using a mouse model of transient focal brain ischemia, we report that IL-21 is highly up-regulated in the injured mouse brain after cerebral ischemia. IL-21–deficient mice have smaller infarcts, improved neurological function, and reduced lymphocyte accumulation in the brain within 24 h of reperfusion. Intracellular cytokine staining and adoptive transfer experiments revealed that brain-infiltrating CD4+ T cells are the predominant IL-21 source. Mice treated with decoy IL-21 receptor Fc fusion protein are protected from reperfusion injury. In postmortem human brain tissue, IL-21 localized to perivascular CD4+ T cells in the area surrounding acute stroke lesions, suggesting that IL-21–mediated brain injury may be relevant to human stroke. PMID:24616379

Foxp2 Regulates Gene Networks Implicated in Neurite Outgrowth in the Developing Brain

PubMed Central

Vernes, Sonja C.; Oliver, Peter L.; Spiteri, Elizabeth; Lockstone, Helen E.; Puliyadi, Rathi; Taylor, Jennifer M.; Ho, Joses; Mombereau, Cedric; Brewer, Ariel; Lowy, Ernesto; Nicod, Jérôme; Groszer, Matthias; Baban, Dilair; Sahgal, Natasha; Cazier, Jean-Baptiste; Ragoussis, Jiannis; Davies, Kay E.; Geschwind, Daniel H.; Fisher, Simon E.

2011-01-01

Forkhead-box protein P2 is a transcription factor that has been associated with intriguing aspects of cognitive function in humans, non-human mammals, and song-learning birds. Heterozygous mutations of the human FOXP2 gene cause a monogenic speech and language disorder. Reduced functional dosage of the mouse version (Foxp2) causes deficient cortico-striatal synaptic plasticity and impairs motor-skill learning. Moreover, the songbird orthologue appears critically important for vocal learning. Across diverse vertebrate species, this well-conserved transcription factor is highly expressed in the developing and adult central nervous system. Very little is known about the mechanisms regulated by Foxp2 during brain development. We used an integrated functional genomics strategy to robustly define Foxp2-dependent pathways, both direct and indirect targets, in the embryonic brain. Specifically, we performed genome-wide in vivo ChIP–chip screens for Foxp2-binding and thereby identified a set of 264 high-confidence neural targets under strict, empirically derived significance thresholds. The findings, coupled to expression profiling and in situ hybridization of brain tissue from wild-type and mutant mouse embryos, strongly highlighted gene networks linked to neurite development. We followed up our genomics data with functional experiments, showing that Foxp2 impacts on neurite outgrowth in primary neurons and in neuronal cell models. Our data indicate that Foxp2 modulates neuronal network formation, by directly and indirectly regulating mRNAs involved in the development and plasticity of neuronal connections. PMID:21765815

Foxp2 regulates gene networks implicated in neurite outgrowth in the developing brain.

PubMed

Vernes, Sonja C; Oliver, Peter L; Spiteri, Elizabeth; Lockstone, Helen E; Puliyadi, Rathi; Taylor, Jennifer M; Ho, Joses; Mombereau, Cedric; Brewer, Ariel; Lowy, Ernesto; Nicod, Jérôme; Groszer, Matthias; Baban, Dilair; Sahgal, Natasha; Cazier, Jean-Baptiste; Ragoussis, Jiannis; Davies, Kay E; Geschwind, Daniel H; Fisher, Simon E

2011-07-01

Forkhead-box protein P2 is a transcription factor that has been associated with intriguing aspects of cognitive function in humans, non-human mammals, and song-learning birds. Heterozygous mutations of the human FOXP2 gene cause a monogenic speech and language disorder. Reduced functional dosage of the mouse version (Foxp2) causes deficient cortico-striatal synaptic plasticity and impairs motor-skill learning. Moreover, the songbird orthologue appears critically important for vocal learning. Across diverse vertebrate species, this well-conserved transcription factor is highly expressed in the developing and adult central nervous system. Very little is known about the mechanisms regulated by Foxp2 during brain development. We used an integrated functional genomics strategy to robustly define Foxp2-dependent pathways, both direct and indirect targets, in the embryonic brain. Specifically, we performed genome-wide in vivo ChIP-chip screens for Foxp2-binding and thereby identified a set of 264 high-confidence neural targets under strict, empirically derived significance thresholds. The findings, coupled to expression profiling and in situ hybridization of brain tissue from wild-type and mutant mouse embryos, strongly highlighted gene networks linked to neurite development. We followed up our genomics data with functional experiments, showing that Foxp2 impacts on neurite outgrowth in primary neurons and in neuronal cell models. Our data indicate that Foxp2 modulates neuronal network formation, by directly and indirectly regulating mRNAs involved in the development and plasticity of neuronal connections.

Comparative Analysis of Human and Rodent Brain Primary Neuronal Culture Spontaneous Activity Using Micro-Electrode Array Technology.

PubMed

Napoli, Alessandro; Obeid, Iyad

2016-03-01

Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. © 2015 Wiley Periodicals, Inc.

Species-Specific 5 mC and 5 hmC Genomic Landscapes Indicate Epigenetic Contribution to Human Brain Evolution

PubMed Central

Madrid, Andy; Chopra, Pankaj; Alisch, Reid S.

2018-01-01

Human evolution from non-human primates has seen substantial change in the central nervous system, with the molecular mechanisms underlying human brain evolution remaining largely unknown. Methylation of cytosine at the fifth carbon (5-methylcytosine; 5 mC) is an essential epigenetic mark linked to neurodevelopment, as well as neurological disease. The emergence of another modified form of cytosine (5-hydroxymethylcytosine; 5 hmC) that is enriched in the brain further substantiates a role for these epigenetic marks in neurodevelopment, yet little is known about the evolutionary importance of these marks in brain development. Here, human and monkey brain tissue were profiled, identifying 5,516 and 4,070 loci that were differentially methylated and hydroxymethylated, respectively, between the species. Annotation of these loci to the human genome revealed genes critical for the development of the nervous system and that are associated with intelligence and higher cognitive functioning, such as RELN and GNAS. Moreover, ontological analyses of these differentially methylated and hydroxymethylated genes revealed a significant enrichment of neuronal/immunological–related processes, including neurogenesis and axon development. Finally, the sequences flanking the differentially methylated/hydroxymethylated loci contained a significant enrichment of binding sites for neurodevelopmentally important transcription factors (e.g., OTX1 and PITX1), suggesting that DNA methylation may regulate gene expression by mediating transcription factor binding on these transcripts. Together, these data support dynamic species-specific epigenetic contributions in the evolution and development of the human brain from non-human primates. PMID:29491831

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

PubMed Central

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

1995-01-01

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

Effects of geomagnetic activity variations on the physiological and psychological state of functionally healthy humans: Some results of Azerbaijani studies

NASA Astrophysics Data System (ADS)

Babayev, Elchin S.; Allahverdiyeva, Aysel A.

There are collaborative and cross-disciplinary space weather studies in the Azerbaijan National Academy of Sciences conducted with purposes of revealing possible effects of solar, geomagnetic and cosmic ray variability on certain technological, biological and ecological systems. This paper describes some results of the experimental studies of influence of the periodical and aperiodical changes of geomagnetic activity upon human brain, human health and psycho-emotional state. It also covers the conclusions of studies on influence of violent solar events and severe geomagnetic storms of the solar cycle 23 on the mentioned systems in middle-latitude location. It is experimentally established that weak and moderate geomagnetic storms do not cause significant changes in the brain's bioelectrical activity and exert only stimulating influence while severe disturbances of geomagnetic conditions cause negative influence, seriously disintegrate brain's functionality, activate braking processes and amplify the negative emotional background of an individual. It is concluded that geomagnetic disturbances affect mainly emotional and vegetative spheres of human beings while characteristics reflecting personality properties do not undergo significant changes.

Multichannel optical mapping: investigation of depth information

NASA Astrophysics Data System (ADS)

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

2001-06-01

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

Modeling Pediatric Brain Trauma: Piglet Model of Controlled Cortical Impact.

PubMed

Pareja, Jennifer C Munoz; Keeley, Kristen; Duhaime, Ann-Christine; Dodge, Carter P

2016-01-01

The brain has different responses to traumatic injury as a function of its developmental stage. As a model of injury to the immature brain, the piglet shares numerous similarities in regards to morphology and neurodevelopmental sequence compared to humans. This chapter describes a piglet scaled focal contusion model of traumatic brain injury that accounts for the changes in mass and morphology of the brain as it matures, facilitating the study of age-dependent differences in response to a comparable mechanical trauma.

Low calorie sweeteners: Evidence remains lacking for effects on human gut function.

PubMed

Bryant, Charlotte; Mclaughlin, John

2016-10-01

The importance of nutrient induced gut-brain signalling in the regulation of human food intake has become an increasing focus of research. Much of the caloric excess consumed comes from dietary sugars, but our knowledge about the mechanisms mediating the physiological and appetitive effects of sweet tastants in the human gut and gut-brain axis is far from complete. The comparative effects of natural sugars vs low calorie sweeteners are also poorly understood. Research in animal and cellular models has suggested a key functional role in gut endocrine cells for the sweet taste receptors previously well described in oral taste. However human studies to date have very consistently failed to show that activation of the sweet taste receptor by low calorie sweeteners placed in the human gut fails to replicate any of the effects on gastric motility, gut hormones or appetitive responses evoked by caloric sugars. Copyright © 2016. Published by Elsevier Inc.

Brain regions with mirror properties: a meta-analysis of 125 human fMRI studies.

PubMed

Molenberghs, Pascal; Cunnington, Ross; Mattingley, Jason B

2012-01-01

Mirror neurons in macaque area F5 fire when an animal performs an action, such as a mouth or limb movement, and also when the animal passively observes an identical or similar action performed by another individual. Brain-imaging studies in humans conducted over the last 20 years have repeatedly attempted to reveal analogous brain regions with mirror properties in humans, with broad and often speculative claims about their functional significance across a range of cognitive domains, from language to social cognition. Despite such concerted efforts, the likely neural substrates of these mirror regions have remained controversial, and indeed the very existence of a distinct subcategory of human neurons with mirroring properties has been questioned. Here we used activation likelihood estimation (ALE), to provide a quantitative index of the consistency of patterns of fMRI activity measured in human studies of action observation and action execution. From an initial sample of more than 300 published works, data from 125 papers met our strict inclusion and exclusion criteria. The analysis revealed 14 separate clusters in which activation has been consistently attributed to brain regions with mirror properties, encompassing 9 different Brodmann areas. These clusters were located in areas purported to show mirroring properties in the macaque, such as the inferior parietal lobule, inferior frontal gyrus and the adjacent ventral premotor cortex, but surprisingly also in regions such as the primary visual cortex, cerebellum and parts of the limbic system. Our findings suggest a core network of human brain regions that possess mirror properties associated with action observation and execution, with additional areas recruited during tasks that engage non-motor functions, such as auditory, somatosensory and affective components. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Methodological Problems on the Way to Integrative Human Neuroscience.

PubMed

Kotchoubey, Boris; Tretter, Felix; Braun, Hans A; Buchheim, Thomas; Draguhn, Andreas; Fuchs, Thomas; Hasler, Felix; Hastedt, Heiner; Hinterberger, Thilo; Northoff, Georg; Rentschler, Ingo; Schleim, Stephan; Sellmaier, Stephan; Tebartz Van Elst, Ludger; Tschacher, Wolfgang

2016-01-01

Neuroscience is a multidisciplinary effort to understand the structures and functions of the brain and brain-mind relations. This effort results in an increasing amount of data, generated by sophisticated technologies. However, these data enhance our descriptive knowledge , rather than improve our understanding of brain functions. This is caused by methodological gaps both within and between subdisciplines constituting neuroscience, and the atomistic approach that limits the study of macro- and mesoscopic issues. Whole-brain measurement technologies do not resolve these issues, but rather aggravate them by the complexity problem. The present article is devoted to methodological and epistemic problems that obstruct the development of human neuroscience. We neither discuss ontological questions (e.g., the nature of the mind) nor review data, except when it is necessary to demonstrate a methodological issue. As regards intradisciplinary methodological problems, we concentrate on those within neurobiology (e.g., the gap between electrical and chemical approaches to neurophysiological processes) and psychology (missing theoretical concepts). As regards interdisciplinary problems, we suggest that core disciplines of neuroscience can be integrated using systemic concepts that also entail human-environment relations. We emphasize the necessity of a meta-discussion that should entail a closer cooperation with philosophy as a discipline of systematic reflection. The atomistic reduction should be complemented by the explicit consideration of the embodiedness of the brain and the embeddedness of humans. The discussion is aimed at the development of an explicit methodology of integrative human neuroscience , which will not only link different fields and levels, but also help in understanding clinical phenomena.

Methodological Problems on the Way to Integrative Human Neuroscience

PubMed Central

Kotchoubey, Boris; Tretter, Felix; Braun, Hans A.; Buchheim, Thomas; Draguhn, Andreas; Fuchs, Thomas; Hasler, Felix; Hastedt, Heiner; Hinterberger, Thilo; Northoff, Georg; Rentschler, Ingo; Schleim, Stephan; Sellmaier, Stephan; Tebartz Van Elst, Ludger; Tschacher, Wolfgang

2016-01-01

Neuroscience is a multidisciplinary effort to understand the structures and functions of the brain and brain-mind relations. This effort results in an increasing amount of data, generated by sophisticated technologies. However, these data enhance our descriptive knowledge, rather than improve our understanding of brain functions. This is caused by methodological gaps both within and between subdisciplines constituting neuroscience, and the atomistic approach that limits the study of macro- and mesoscopic issues. Whole-brain measurement technologies do not resolve these issues, but rather aggravate them by the complexity problem. The present article is devoted to methodological and epistemic problems that obstruct the development of human neuroscience. We neither discuss ontological questions (e.g., the nature of the mind) nor review data, except when it is necessary to demonstrate a methodological issue. As regards intradisciplinary methodological problems, we concentrate on those within neurobiology (e.g., the gap between electrical and chemical approaches to neurophysiological processes) and psychology (missing theoretical concepts). As regards interdisciplinary problems, we suggest that core disciplines of neuroscience can be integrated using systemic concepts that also entail human-environment relations. We emphasize the necessity of a meta-discussion that should entail a closer cooperation with philosophy as a discipline of systematic reflection. The atomistic reduction should be complemented by the explicit consideration of the embodiedness of the brain and the embeddedness of humans. The discussion is aimed at the development of an explicit methodology of integrative human neuroscience, which will not only link different fields and levels, but also help in understanding clinical phenomena. PMID:27965548

Language Impairments in ASD Resulting from a Failed Domestication of the Human Brain

PubMed Central

Benítez-Burraco, Antonio; Lattanzi, Wanda; Murphy, Elliot

2016-01-01

Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders entailing social and cognitive deficits, including marked problems with language. Numerous genes have been associated with ASD, but it is unclear how language deficits arise from gene mutation or dysregulation. It is also unclear why ASD shows such high prevalence within human populations. Interestingly, the emergence of a modern faculty of language has been hypothesized to be linked to changes in the human brain/skull, but also to the process of self-domestication of the human species. It is our intention to show that people with ASD exhibit less marked domesticated traits at the morphological, physiological, and behavioral levels. We also discuss many ASD candidates represented among the genes known to be involved in the “domestication syndrome” (the constellation of traits exhibited by domesticated mammals, which seemingly results from the hypofunction of the neural crest) and among the set of genes involved in language function closely connected to them. Moreover, many of these genes show altered expression profiles in the brain of autists. In addition, some candidates for domestication and language-readiness show the same expression profile in people with ASD and chimps in different brain areas involved in language processing. Similarities regarding the brain oscillatory behavior of these areas can be expected too. We conclude that ASD may represent an abnormal ontogenetic itinerary for the human faculty of language resulting in part from changes in genes important for the “domestication syndrome” and, ultimately, from the normal functioning of the neural crest. PMID:27621700

Effect of Mobile Phone-Induced Electromagnetic Field on Brain Hemodynamics and Human Stem Cell Functioning: Possible Mechanistic Link to Cancer Risk and Early Diagnostic Value of Electronphotonic Imaging.

PubMed

Bhargav, Hemant; Srinivasan, T M; Varambally, S; Gangadhar, B N; Koka, Prasad

2015-01-01

The mobile phones (MP) are low power radio devices which work on electromagnetic fields (EMFs), in the frequency range of 900-1800 MHz. Exposure to MPEMFs may affect brain physiology and lead to various health hazards including brain tumors. Earlier studies with positron emission tomography (PET) have found alterations in cerebral blood flow (CBF) after acute exposure to MPEMFs. It is widely accepted that DNA double-strand breaks (DSBs) and their misrepair in stem cells are critical events in the multistage origination of various leukemia and tumors, including brain tumors such as gliomas. Both significant misbalance in DSB repair and severe stress response have been triggered by MPEMFs and EMFs from cell towers. It has been shown that stem cells are most sensitive to microwave exposure and react to more frequencies than do differentiated cells. This may be important for cancer risk assessment and indicates that stem cells are the most relevant cellular model for validating safe mobile communication signals. Recently developed technology for recording the human bio-electromagnetic (BEM) field using Electron photonic Imaging (EPI) or Gas Discharge Visualisation (GDV) technique provides useful information about the human BEM. Studies have recorded acute effects of Mobile Phone Electromagnetic Fields (MPEMFs) using EPI and found quantifiable effects on human BEM field. Present manuscript reviews evidences of altered brain physiology and stem cell functioning due to mobile phone/cell tower radiations, its association with increased cancer risk and explores early diagnostic value of EPI imaging in detecting EMF induced changes on human BEM.

Comparison of NREM sleep and intravenous sedation through local information processing and whole brain network to explore the mechanism of general anesthesia.

PubMed

Li, Yun; Wang, Shengpei; Pan, Chuxiong; Xue, Fushan; Xian, Junfang; Huang, Yaqi; Wang, Xiaoyi; Li, Tianzuo; He, Huiguang

2018-01-01

The mechanism of general anesthesia (GA) has been explored for hundreds of years, but unclear. Previous studies indicated a possible correlation between NREM sleep and GA. The purpose of this study is to compare them by in vivo human brain function to probe the neuromechanism of consciousness, so as to find out a clue to GA mechanism. 24 healthy participants were equally assigned to sleep or propofol sedation group by sleeping ability. EEG and Ramsay Sedation Scale were applied to determine sleep stage and sedation depth respectively. Resting-state functional magnetic resonance imaging (RS-fMRI) was acquired at each status. Regional homogeneity (ReHo) and seed-based whole brain functional connectivity maps (WB-FC maps) were compared. During sleep, ReHo primarily weakened on frontal lobe (especially preoptic area), but strengthened on brainstem. While during sedation, ReHo changed in various brain areas, including cingulate, precuneus, thalamus and cerebellum. Cingulate, fusiform and insula were concomitance of sleep and sedation. Comparing to sleep, FCs between the cortex and subcortical centers (centralized in cerebellum) were significantly attenuated under sedation. As sedation deepening, cerebellum-based FC maps were diminished, while thalamus- and brainstem-based FC maps were increased. There're huge distinctions in human brain function between sleep and GA. Sleep mainly rely on brainstem and frontal lobe function, while sedation is prone to affect widespread functional network. The most significant differences exist in the precuneus and cingulate, which may play important roles in mechanisms of inducing unconciousness by anesthetics. Institutional Review Board (IRB) ChiCTR-IOC-15007454.

Toward reliable characterization of functional homogeneity in the human brain: Preprocessing, scan duration, imaging resolution and computational space

PubMed Central

Zuo, Xi-Nian; Xu, Ting; Jiang, Lili; Yang, Zhi; Cao, Xiao-Yan; He, Yong; Zang, Yu-Feng; Castellanos, F. Xavier; Milham, Michael P.

2013-01-01

While researchers have extensively characterized functional connectivity between brain regions, the characterization of functional homogeneity within a region of the brain connectome is in early stages of development. Several functional homogeneity measures were proposed previously, among which regional homogeneity (ReHo) was most widely used as a measure to characterize functional homogeneity of resting state fMRI (R-fMRI) signals within a small region (Zang et al., 2004). Despite a burgeoning literature on ReHo in the field of neuroimaging brain disorders, its test–retest (TRT) reliability remains unestablished. Using two sets of public R-fMRI TRT data, we systematically evaluated the ReHo’s TRT reliability and further investigated the various factors influencing its reliability and found: 1) nuisance (head motion, white matter, and cerebrospinal fluid) correction of R-fMRI time series can significantly improve the TRT reliability of ReHo while additional removal of global brain signal reduces its reliability, 2) spatial smoothing of R-fMRI time series artificially enhances ReHo intensity and influences its reliability, 3) surface-based R-fMRI computation largely improves the TRT reliability of ReHo, 4) a scan duration of 5 min can achieve reliable estimates of ReHo, and 5) fast sampling rates of R-fMRI dramatically increase the reliability of ReHo. Inspired by these findings and seeking a highly reliable approach to exploratory analysis of the human functional connectome, we established an R-fMRI pipeline to conduct ReHo computations in both 3-dimensions (volume) and 2-dimensions (surface). PMID:23085497

Introducing graph theory to track for neuroplastic alterations in the resting human brain: a transcranial direct current stimulation study.

PubMed

Polanía, Rafael; Paulus, Walter; Antal, Andrea; Nitsche, Michael A

2011-02-01

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability and activity in a polarity-dependent way. Stimulation for a few minutes has been shown to induce plastic alterations of cortical excitability and to improve cognitive performance. These effects might be related to stimulation-induced alterations of functional cortical network connectivity. We aimed to investigate the impact of tDCS on cortical network function by functional connectivity and graph theoretical analysis of the BOLD fMRI spontaneous activity. fMRI resting-state datasets were acquired immediately before and after 10-min bipolar tDCS during rest, with the anode placed over the left primary motor cortex (M1) and the cathode over the contralateral frontopolar cortex. For each dataset, grey matter voxel-based synchronization matrices were calculated and thresholded to construct undirected graphs. Nodal connectivity degree and minimum path length maps were calculated and compared before and after tDCS. Nodal minimum path lengths significantly increased in the left somatomotor (SM1) cortex after anodal tDCS, which means that the number of direct functional connections from the left SM1 to topologically distant grey matter voxels significantly decreased. In contrast, functional coupling between premotor and superior parietal areas with the left SM1 significantly increased. Additionally, the nodal connectivity degree in the left posterior cingulate cortex (PCC) area as well as in the right dorsolateral prefrontal cortex (right DLPFC) significantly increased. In summary, we provide initial support that tDCS-induced neuroplastic alterations might be related to functional connectivity changes in the human brain. Additionally, we propose our approach as a powerful method to track for neuroplastic changes in the human brain. Copyright © 2010 Elsevier Inc. All rights reserved.

The brain-tumor related protein podoplanin regulates synaptic plasticity and hippocampus-dependent learning and memory

PubMed Central

Cicvaric, Ana; Yang, Jiaye; Krieger, Sigurd; Khan, Deeba; Kim, Eun-Jung; Dominguez-Rodriguez, Manuel; Cabatic, Maureen; Molz, Barbara; Acevedo Aguilar, Juan Pablo; Milicevic, Radoslav; Smani, Tarik; Breuss, Johannes M.; Kerjaschki, Dontscho; Pollak, Daniela D.; Uhrin, Pavel; Monje, Francisco J.

2016-01-01

Abstract Introduction: Podoplanin is a cell-surface glycoprotein constitutively expressed in the brain and implicated in human brain tumorigenesis. The intrinsic function of podoplanin in brain neurons remains however uncharacterized. Materials and methods: Using an established podoplanin-knockout mouse model and electrophysiological, biochemical, and behavioral approaches, we investigated the brain neuronal role of podoplanin. Results: Ex-vivo electrophysiology showed that podoplanin deletion impairs dentate gyrus synaptic strengthening. In vivo, podoplanin deletion selectively impaired hippocampus-dependent spatial learning and memory without affecting amygdala-dependent cued fear conditioning. In vitro, neuronal overexpression of podoplanin promoted synaptic activity and neuritic outgrowth whereas podoplanin-deficient neurons exhibited stunted outgrowth and lower levels of p-Ezrin, TrkA, and CREB in response to nerve growth factor (NGF). Surface Plasmon Resonance data further indicated a physical interaction between podoplanin and NGF. Discussion: This work proposes podoplanin as a novel component of the neuronal machinery underlying neuritogenesis, synaptic plasticity, and hippocampus-dependent memory functions. The existence of a relevant cross-talk between podoplanin and the NGF/TrkA signaling pathway is also for the first time proposed here, thus providing a novel molecular complex as a target for future multidisciplinary studies of the brain function in the physiology and the pathology.Key messagesPodoplanin, a protein linked to the promotion of human brain tumors, is required in vivo for proper hippocampus-dependent learning and memory functions.Deletion of podoplanin selectively impairs activity-dependent synaptic strengthening at the neurogenic dentate-gyrus and hampers neuritogenesis and phospho Ezrin, TrkA and CREB protein levels upon NGF stimulation.Surface plasmon resonance data indicates a physical interaction between podoplanin and NGF. On these grounds, a relevant cross-talk between podoplanin and NGF as well as a role for podoplanin in plasticity-related brain neuronal functions is here proposed. PMID:27558977

A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System.

PubMed

Beliveau, Vincent; Ganz, Melanie; Feng, Ling; Ozenne, Brice; Højgaard, Liselotte; Fisher, Patrick M; Svarer, Claus; Greve, Douglas N; Knudsen, Gitte M

2017-01-04

The serotonin (5-hydroxytryptamine, 5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. Here, we present a high-resolution, multidimensional, in vivo atlas of four of the human brain's 5-HT receptors (5-HT 1A , 5-HT 1B , 5-HT 2A , and 5-HT 4 ) and the 5-HT transporter (5-HTT). The atlas is created from molecular and structural high-resolution neuroimaging data consisting of positron emission tomography (PET) and magnetic resonance imaging (MRI) scans acquired in a total of 210 healthy individuals. Comparison of the regional PET binding measures with postmortem human brain autoradiography outcomes showed a high correlation for the five 5-HT targets and this enabled us to transform the atlas to represent protein densities (in picomoles per milliliter). We also assessed the regional association between protein concentration and mRNA expression in the human brain by comparing the 5-HT density across the atlas with data from the Allen Human Brain atlas and identified receptor- and transporter-specific associations that show the regional relation between the two measures. Together, these data provide unparalleled insight into the serotonin system of the human brain. We present a high-resolution positron emission tomography (PET)- and magnetic resonance imaging-based human brain atlas of important serotonin receptors and the transporter. The regional PET-derived binding measures correlate strongly with the corresponding autoradiography protein levels. The strong correlation enables the transformation of the PET-derived human brain atlas into a protein density map of the serotonin (5-hydroxytryptamine, 5-HT) system. Next, we compared the regional receptor/transporter protein densities with mRNA levels and uncovered unique associations between protein expression and density at high detail. This new in vivo neuroimaging atlas of the 5-HT system not only provides insight in the human brain's regional protein synthesis, transport, and density, but also represents a valuable source of information for the neuroscience community as a comparative instrument to assess brain disorders. Copyright © 2017 the authors 0270-6474/17/370120-09$15.00/0.

Mapping the Alzheimer’s Brain with Connectomics

PubMed Central

Xie, Teng; He, Yong

2012-01-01

Alzheimer’s disease (AD) is the most common form of dementia. As an incurable, progressive, and neurodegenerative disease, it causes cognitive and memory deficits. However, the biological mechanisms underlying the disease are not thoroughly understood. In recent years, non-invasive neuroimaging and neurophysiological techniques [e.g., structural magnetic resonance imaging (MRI), diffusion MRI, functional MRI, and EEG/MEG] and graph theory based network analysis have provided a new perspective on structural and functional connectivity patterns of the human brain (i.e., the human connectome) in health and disease. Using these powerful approaches, several recent studies of patients with AD exhibited abnormal topological organization in both global and regional properties of neuronal networks, indicating that AD not only affects specific brain regions, but also alters the structural and functional associations between distinct brain regions. Specifically, disruptive organization in the whole-brain networks in AD is involved in the loss of small-world characters and the re-organization of hub distributions. These aberrant neuronal connectivity patterns were associated with cognitive deficits in patients with AD, even with genetic factors in healthy aging. These studies provide empirical evidence to support the existence of an aberrant connectome of AD. In this review we will summarize recent advances discovered in large-scale brain network studies of AD, mainly focusing on graph theoretical analysis of brain connectivity abnormalities. These studies provide novel insights into the pathophysiological mechanisms of AD and could be helpful in developing imaging biomarkers for disease diagnosis and monitoring. PMID:22291664

Anesthesia, brain changes, and behavior: Insights from neural systems biology.

PubMed

Colon, Elisabeth; Bittner, Edward A; Kussman, Barry; McCann, Mary Ellen; Soriano, Sulpicio; Borsook, David

2017-06-01

Long-term consequences of anesthetic exposure in humans are not well understood. It is possible that alterations in brain function occur beyond the initial anesthetic administration. Research in children and adults has reported cognitive and/or behavioral changes after surgery and general anesthesia that may be short lived in some patients, while in others, such changes may persist. The changes observed in humans are corroborated by a large body of evidence from animal studies that support a role for alterations in neuronal survival (neuroapoptosis) or structure (altered dendritic and glial morphology) and later behavioral deficits at older age after exposure to various anesthetic agents during fetal or early life. The potential of anesthetics to induce long-term alterations in brain function, particularly in vulnerable populations, warrants investigation. In this review, we critically evaluate the available preclinical and clinical data on the developing and aging brain, and in known vulnerable populations to provide insights into potential changes that may affect the general population of patients in a more, subtle manner. In addition this review summarizes underlying processes of how general anesthetics produce changes in the brain at the cellular and systems level and the current understanding underlying mechanisms of anesthetics agents on brain systems. Finally, we present how neuroimaging techniques currently emerge as promising approaches to evaluate and define changes in brain function resulting from anesthesia, both in the short and the long-term. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aging Brain, Aging Mind.

ERIC Educational Resources Information Center

Selkoe, Dennis J.

1992-01-01

Discusses the aging process related to physical changes of the human neural structure involved in learning, memory, and reasoning. Presents evidence that indicates such alterations do not necessarily signal the decline in cognitive function. Vignettes provide images of brain structures involved in learning, memory, and reasoning; hippocampal…

Evaluation of molecular brain changes associated with environmental stress in rodent models compared to human major depressive disorder: A proteomic systems approach.

PubMed

Cox, David Alan; Gottschalk, Michael Gerd; Stelzhammer, Viktoria; Wesseling, Hendrik; Cooper, Jason David; Bahn, Sabine

2016-11-25

Rodent models of major depressive disorder (MDD) are indispensable when screening for novel treatments, but assessing their translational relevance with human brain pathology has proved difficult. Using a novel systems approach, proteomics data obtained from post-mortem MDD anterior prefrontal cortex tissue (n = 12) and matched controls (n = 23) were compared with equivalent data from three commonly used preclinical models exposed to environmental stressors (chronic mild stress, prenatal stress and social defeat). Functional pathophysiological features associated with depression-like behaviour were identified in these models through enrichment of protein-protein interaction networks. A cross-species comparison evaluated which model(s) represent human MDD pathology most closely. Seven functional domains associated with MDD and represented across at least two models such as "carbohydrate metabolism and cellular respiration" were identified. Through statistical evaluation using kernel-based machine learning techniques, the social defeat model was found to represent MDD brain changes most closely for four of the seven domains. This is the first study to apply a method for directly evaluating the relevance of the molecular pathology of multiple animal models to human MDD on the functional level. The methodology and findings outlined here could help to overcome translational obstacles of preclinical psychiatric research.