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

A Celebration of Neurons: An Educator's Guide to the Human Brain.

ERIC Educational Resources Information Center

Sylwester, Robert

This book provides an introduction to the current scientific understanding of the human brain and its processes. Chapter 1, "At the Edge of a Major Transformation," is an introduction to the field. Chapter 2, "How Our Brain Organizes Itself on the Cellular and Systems Levels," covers what body/brain cellular systems do, how…

Brains, genes, and primates.

PubMed

Izpisua Belmonte, Juan Carlos; Callaway, Edward M; Caddick, Sarah J; Churchland, Patricia; Feng, Guoping; Homanics, Gregg E; Lee, Kuo-Fen; Leopold, David A; Miller, Cory T; Mitchell, Jude F; Mitalipov, Shoukhrat; Moutri, Alysson R; Movshon, J Anthony; Okano, Hideyuki; Reynolds, John H; Ringach, Dario; Sejnowski, Terrence J; Silva, Afonso C; Strick, Peter L; Wu, Jun; Zhang, Feng

2015-05-06

One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators, and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive, and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward. Copyright © 2015 Elsevier Inc. All rights reserved.

Brains, Genes and Primates

PubMed Central

Belmonte, Juan Carlos Izpisua; Callaway, Edward M.; Churchland, Patricia; Caddick, Sarah J.; Feng, Guoping; Homanics, Gregg E.; Lee, Kuo-Fen; Leopold, David A.; Miller, Cory T.; Mitchell, Jude F.; Mitalipov, Shoukhrat; Moutri, Alysson R.; Movshon, J. Anthony; Okano, Hideyuki; Reynolds, John H.; Ringach, Dario; Sejnowski, Terrence J.; Silva, Afonso C.; Strick, Peter L.; Wu, Jun; Zhang, Feng

2015-01-01

One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward. PMID:25950631

We’re All in This Together | NIH MedlinePlus the Magazine

MedlinePlus

... research has been done on animals or from human autopsies. Live humans are needed to study the brain over time, ... and updating information, participants help researchers understand the human brain as it ages. Here’s how to register: ...

Avian Models for Human Cognitive Neuroscience: A Proposal.

PubMed

Clayton, Nicola S; Emery, Nathan J

2015-06-17

Research on avian cognitive neuroscience over the past two decades has revealed the avian brain to be a better model for understanding human cognition than previously thought, despite differences in the neuroarchitecture of avian and mammalian brains. The brain, behavior, and cognition of songbirds have provided an excellent model of human cognition in one domain, namely learning human language and the production of speech. There are other important behavioral candidates of avian cognition, however, notably the capacity of corvids to remember the past and plan for the future, as well as their ability to think about another's perspective, and physical reasoning. We review this work and assess the evidence that the corvid brain can support such a cognitive architecture. We propose potential applications of these behavioral paradigms for cognitive neuroscience, including recent work on single-cell recordings and neuroimaging in corvids. Finally, we discuss their impact on understanding human developmental cognition. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

A case for human systems neuroscience.

PubMed

Gardner, J L

2015-06-18

Can the human brain itself serve as a model for a systems neuroscience approach to understanding the human brain? After all, how the brain is able to create the richness and complexity of human behavior is still largely mysterious. What better choice to study that complexity than to study it in humans? However, measurements of brain activity typically need to be made non-invasively which puts severe constraints on what can be learned about the internal workings of the brain. Our approach has been to use a combination of psychophysics in which we can use human behavioral flexibility to make quantitative measurements of behavior and link those through computational models to measurements of cortical activity through magnetic resonance imaging. In particular, we have tested various computational hypotheses about what neural mechanisms could account for behavioral enhancement with spatial attention (Pestilli et al., 2011). Resting both on quantitative measurements and considerations of what is known through animal models, we concluded that weighting of sensory signals by the magnitude of their response is a neural mechanism for efficient selection of sensory signals and consequent improvements in behavioral performance with attention. While animal models have many technical advantages over studying the brain in humans, we believe that human systems neuroscience should endeavor to validate, replicate and extend basic knowledge learned from animal model systems and thus form a bridge to understanding how the brain creates the complex and rich cognitive capacities of humans. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

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.

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 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

78 FR 66611 - National Alzheimer's Disease Awareness Month, 2013

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-05

... Proclamation Alzheimer's disease is an irreversible and progressive brain disease that slowly erodes precious... year, I proposed the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, which aims to revolutionize our understanding of the human brain. By mapping the brain, we hope to...

Localization of migraine susceptibility genes in human brain by single-cell RNA sequencing.

PubMed

Renthal, William

2018-01-01

Background Migraine is a debilitating disorder characterized by severe headaches and associated neurological symptoms. A key challenge to understanding migraine has been the cellular complexity of the human brain and the multiple cell types implicated in its pathophysiology. The present study leverages recent advances in single-cell transcriptomics to localize the specific human brain cell types in which putative migraine susceptibility genes are expressed. Methods The cell-type specific expression of both familial and common migraine-associated genes was determined bioinformatically using data from 2,039 individual human brain cells across two published single-cell RNA sequencing datasets. Enrichment of migraine-associated genes was determined for each brain cell type. Results Analysis of single-brain cell RNA sequencing data from five major subtypes of cells in the human cortex (neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells) indicates that over 40% of known migraine-associated genes are enriched in the expression profiles of a specific brain cell type. Further analysis of neuronal migraine-associated genes demonstrated that approximately 70% were significantly enriched in inhibitory neurons and 30% in excitatory neurons. Conclusions This study takes the next step in understanding the human brain cell types in which putative migraine susceptibility genes are expressed. Both familial and common migraine may arise from dysfunction of discrete cell types within the neurovascular unit, and localization of the affected cell type(s) in an individual patient may provide insight into to their susceptibility to migraine.

The Brain.

ERIC Educational Resources Information Center

Hubel, David H.

1979-01-01

This article on the brain is part of an entire issue about neurobiology and the question of how the human brain works. The brain as an intricate tissue composed of cells is discussed based on the current knowledge and understanding of its composition and structure. (SA)

Neurophysiology of the esophagus.

PubMed

Brock, Christina; Brokjaer, Anne; Drewes, Asbjørn Mohr; Farmer, Adam D; Frøkjaer, Jens Brøndum; Gregersen, Hans; Lottrup, Christian

2014-09-01

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the methods and characteristics of esophageal afferents in humans; the pitfalls in characterization of mechanosensitive afferents; the sensitization of esophageal afferents in human studies; the brain source modeling in the understanding of the esophagus-brain axis; the use of evoked brain potentials in the esophagus; and measuring descending inhibition in animal and human studies. © 2014 New York Academy of Sciences.

Brain-mapping projects using the common marmoset.

PubMed

Okano, Hideyuki; Mitra, Partha

2015-04-01

Globally, there is an increasing interest in brain-mapping projects, including the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative project in the USA, the Human Brain Project (HBP) in Europe, and the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) project in Japan. These projects aim to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain. Brain/MINDS is focused on structural and functional mapping of the common marmoset (Callithrix jacchus) brain. This non-human primate has numerous advantages for brain mapping, including a well-developed frontal cortex and a compact brain size, as well as the availability of transgenic technologies. In the present review article, we discuss strategies for structural and functional mapping of the marmoset brain and the relation of the common marmoset to other animals models. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Building machines that adapt and compute like brains.

PubMed

Kriegeskorte, Nikolaus; Mok, Robert M

2017-01-01

Building machines that learn and think like humans is essential not only for cognitive science, but also for computational neuroscience, whose ultimate goal is to understand how cognition is implemented in biological brains. A new cognitive computational neuroscience should build cognitive-level and neural-level models, understand their relationships, and test both types of models with both brain and behavioral data.

The human parental brain: In vivo neuroimaging

PubMed Central

Swain, James E.

2015-01-01

Interacting parenting thoughts and behaviors, supported by key brain circuits, critically shape human infants’ current and future behavior. Indeed, the parent–infant relationship provides infants with their first social environment, forming templates for what they can expect from others, how to interact with them and ultimately how they go on to themselves to be parents. This review concentrates on magnetic resonance imaging experiments of the human parent brain, which link brain physiology with parental thoughts and behaviors. After reviewing brain imaging techniques, certain social cognitive and affective concepts are reviewed, including empathy and trust—likely critical to parenting. Following that is a thorough study-by-study review of the state-of-the-art with respect to human neuroimaging studies of the parental brain—from parent brain responses to salient infant stimuli, including emotionally charged baby cries and brief visual stimuli to the latest structural brain studies. Taken together, this research suggests that networks of highly conserved hypothalamic–midbrain–limbic–paralimbic–cortical circuits act in concert to support parental brain responses to infants, including circuits for limbic emotion response and regulation. Thus, a model is presented in which infant stimuli activate sensory analysis brain regions, affect corticolimbic limbic circuits that regulate emotional response, motivation and reward related to their infant, ultimately organizing parenting impulses, thoughts and emotions into coordinated behaviors as a map for future studies. Finally, future directions towards integrated understanding of the brain basis of human parenting are outlined with profound implications for understanding and contributing to long term parent and infant mental health. PMID:21036196

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

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.

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…

A mechanical model predicts morphological abnormalities in the developing human brain

NASA Astrophysics Data System (ADS)

Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

2014-07-01

The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism.

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

Cognitive neuroscience 2.0: building a cumulative science of human brain function

PubMed Central

Yarkoni, Tal; Poldrack, Russell A.; Van Essen, David C.; Wager, Tor D.

2010-01-01

Cognitive neuroscientists increasingly recognize that continued progress in understanding human brain function will require not only the acquisition of new data, but also the synthesis and integration of data across studies and laboratories. Here we review ongoing efforts to develop a more cumulative science of human brain function. We discuss the rationale for an increased focus on formal synthesis of the cognitive neuroscience literature, provide an overview of recently developed tools and platforms designed to facilitate the sharing and integration of neuroimaging data, and conclude with a discussion of several emerging developments that hold even greater promise in advancing the study of human brain function. PMID:20884276

A Culture-Behavior-Brain Loop Model of Human Development.

PubMed

Han, Shihui; Ma, Yina

2015-11-01

Increasing evidence suggests that cultural influences on brain activity are associated with multiple cognitive and affective processes. These findings prompt an integrative framework to account for dynamic interactions between culture, behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model of human development that proposes that culture shapes the brain by contextualizing behavior, and the brain fits and modifies culture via behavioral influences. Genes provide a fundamental basis for, and interact with, the CBB loop at both individual and population levels. The CBB loop model advances our understanding of the dynamic relationships between culture, behavior, and the brain, which are crucial for human phylogeny and ontogeny. Future brain changes due to cultural influences are discussed based on the CBB loop model. Copyright © 2015 Elsevier Ltd. All rights reserved.

Friends with social benefits: host-microbe interactions as a driver of brain evolution and development?

PubMed Central

Stilling, Roman M.; Bordenstein, Seth R.; Dinan, Timothy G.; Cryan, John F.

2014-01-01

The tight association of the human body with trillions of colonizing microbes that we observe today is the result of a long evolutionary history. Only very recently have we started to understand how this symbiosis also affects brain function and behavior. In this hypothesis and theory article, we propose how host-microbe associations potentially influenced mammalian brain evolution and development. In particular, we explore the integration of human brain development with evolution, symbiosis, and RNA biology, which together represent a “social triangle” that drives human social behavior and cognition. We argue that, in order to understand how inter-kingdom communication can affect brain adaptation and plasticity, it is inevitable to consider epigenetic mechanisms as important mediators of genome-microbiome interactions on an individual as well as a transgenerational time scale. Finally, we unite these interpretations with the hologenome theory of evolution. Taken together, we propose a tighter integration of neuroscience fields with host-associated microbiology by taking an evolutionary perspective. PMID:25401092

Brain evolution by brain pathway duplication

PubMed Central

Chakraborty, Mukta; Jarvis, Erich D.

2015-01-01

Understanding the mechanisms of evolution of brain pathways for complex behaviours is still in its infancy. Making further advances requires a deeper understanding of brain homologies, novelties and analogies. It also requires an understanding of how adaptive genetic modifications lead to restructuring of the brain. Recent advances in genomic and molecular biology techniques applied to brain research have provided exciting insights into how complex behaviours are shaped by selection of novel brain pathways and functions of the nervous system. Here, we review and further develop some insights to a new hypothesis on one mechanism that may contribute to nervous system evolution, in particular by brain pathway duplication. Like gene duplication, we propose that whole brain pathways can duplicate and the duplicated pathway diverge to take on new functions. We suggest that one mechanism of brain pathway duplication could be through gene duplication, although other mechanisms are possible. We focus on brain pathways for vocal learning and spoken language in song-learning birds and humans as example systems. This view presents a new framework for future research in our understanding of brain evolution and novel behavioural traits. PMID:26554045

The Molecular Basis of Human Brain Evolution.

PubMed

Enard, Wolfgang

2016-10-24

Humans are a remarkable species, especially because of the remarkable properties of their brain. Since the split from the chimpanzee lineage, the human brain has increased three-fold in size and has acquired abilities for vocal learning, language and intense cooperation. To better understand the molecular basis of these changes is of great biological and biomedical interest. However, all the about 16 million fixed genetic changes that occurred during human evolution are fully correlated with all molecular, cellular, anatomical and behavioral changes that occurred during this time. Hence, as humans and chimpanzees cannot be crossed or genetically manipulated, no direct evidence for linking particular genetic and molecular changes to human brain evolution can be obtained. Here, I sketch a framework how indirect evidence can be obtained and review findings related to the molecular basis of human cognition, vocal learning and brain size. In particular, I discuss how a comprehensive comparative approach, leveraging cellular systems and genomic technologies, could inform the evolution of our brain in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

Allometric Analysis Detects Brain Size-Independent Effects of Sex and Sex Chromosome Complement on Human Cerebellar Organization

PubMed Central

Mankiw, Catherine; Park, Min Tae M.; Reardon, P.K.; Fish, Ari M.; Clasen, Liv S.; Greenstein, Deanna; Blumenthal, Jonathan D.; Lerch, Jason P.; Chakravarty, M. Mallar

2017-01-01

The cerebellum is a large hindbrain structure that is increasingly recognized for its contribution to diverse domains of cognitive and affective processing in human health and disease. Although several of these domains are sex biased, our fundamental understanding of cerebellar sex differences—including their spatial distribution, potential biological determinants, and independence from brain volume variation—lags far behind that for the cerebrum. Here, we harness automated neuroimaging methods for cerebellar morphometrics in 417 individuals to (1) localize normative male–female differences in raw cerebellar volume, (2) compare these to sex chromosome effects estimated across five rare sex (X/Y) chromosome aneuploidy (SCA) syndromes, and (3) clarify brain size-independent effects of sex and SCA on cerebellar anatomy using a generalizable allometric approach that considers scaling relationships between regional cerebellar volume and brain volume in health. The integration of these approaches shows that (1) sex and SCA effects on raw cerebellar volume are large and distributed, but regionally heterogeneous, (2) human cerebellar volume scales with brain volume in a highly nonlinear and regionally heterogeneous fashion that departs from documented patterns of cerebellar scaling in phylogeny, and (3) cerebellar organization is modified in a brain size-independent manner by sex (relative expansion of total cerebellum, flocculus, and Crus II-lobule VIIIB volumes in males) and SCA (contraction of total cerebellar, lobule IV, and Crus I volumes with additional X- or Y-chromosomes; X-specific contraction of Crus II-lobule VIIIB). Our methods and results clarify the shifts in human cerebellar organization that accompany interwoven variations in sex, sex chromosome complement, and brain size. SIGNIFICANCE STATEMENT Cerebellar systems are implicated in diverse domains of sex-biased behavior and pathology, but we lack a basic understanding of how sex differences in the human cerebellum are distributed and determined. We leverage a rare neuroimaging dataset to deconvolve the interwoven effects of sex, sex chromosome complement, and brain size on human cerebellar organization. We reveal topographically variegated scaling relationships between regional cerebellar volume and brain size in humans, which (1) are distinct from those observed in phylogeny, (2) invalidate a traditional neuroimaging method for brain volume correction, and (3) allow more valid and accurate resolution of which cerebellar subcomponents are sensitive to sex and sex chromosome complement. These findings advance understanding of cerebellar organization in health and sex chromosome aneuploidy. PMID:28314818

What the Biology of the Brain Tells Us about Learning.

ERIC Educational Resources Information Center

Sylwester, Robert

1994-01-01

Dramatic developments in brain research and imaging technology are rapidly advancing our understanding of the human brain. The new biologically based brain theories suggest that "nature" dominates "nurture" and that many current beliefs about instruction, learning, and memory are wrong. This article explains neural Darwinism…

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.…

Research advances made in the avian brain and their relevance to poultry scientists.

PubMed

Kuenzel, Wayne J

2014-12-01

The year 2014 marked the tenth anniversary since the sequence of the chicken genome was published. Two other publications occurred during that time frame in different disciplines, and all 3 have affected poultry scientists. The purpose of this paper is to briefly review 2 publications that are better known to those in animal agriculture. The third paper will be addressed in more detail because it is one that many in poultry science probably have not read. The subject matter involves the avian brain and its future impact and is related to an announcement made by the president of the United States in April 2013. Due to the recent, rapid advances in the understanding of the vertebrate brain and behavior, a national goal was announced by President Obama to map the human brain in more detail than ever before to accelerate the understanding of brain function in health and disease. The main objective is to review the third paper published a decade ago to show that it laid the foundation for the chicken and other avian species to serve as relevant animal models to advance the understanding of the human brain. Emphasis will be placed on the forebrain. The overall goal is to show that the brain of birds is not that different from the mammalian brain and therefore can serve as an excellent comparative biomodel to understand fundamental principles of brain structure and function. ©2014 Poultry Science Association Inc.

Molecular networks and the evolution of human cognitive specializations.

PubMed

Fontenot, Miles; Konopka, Genevieve

2014-12-01

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

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.

A new wrinkle on the brain

NASA Astrophysics Data System (ADS)

Taber, Larry A.

2018-05-01

The folded structure of the human brain is a hallmark of our intelligence — an optimized packing of neurons into a confined space. Similar wrinkling in brain-on-a-chip experiments provides a way of understanding the physics of how this occurs.

A combination of experimental measurement, constitutive damage model, and diffusion tensor imaging to characterize the mechanical properties of the human brain.

PubMed

Karimi, Alireza; Rahmati, Seyed Mohammadali; Razaghi, Reza

2017-09-01

Understanding the mechanical properties of the human brain is deemed important as it may subject to various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the frontal lobe of the human brain. The constrained nonlinear minimization method was employed to identify the brain coefficients according to the axial and transversal compressive data. The pseudo-elastic damage model data was also well compared with that of the experimental data and it not only up to the primary loading but also the discontinuous softening could well address the mechanical behavior of the brain tissue.

Aging and Gene Expression in the Primate Brain

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

Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.

2005-02-18

It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes inmore » the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.« less

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.

Genetic control of postnatal human brain growth

PubMed Central

van Dyck, Laura I.; Morrow, Eric M.

2017-01-01

Purpose of review Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. Recent findings Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, postmortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. Summary In order to understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders. PMID:27898583

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.

Toward a Holistic Neurophysiological Understanding of Intrapersonal Communication.

ERIC Educational Resources Information Center

Stacks, Don W.; Andersen, Peter A.

To further the understanding of how the brain operates at the most basic level of interest to human communication theorists, intrapersonal communication, this paper reviews the arguments against the hemispheric dominance theory and for a neurological processing style model of brain functions and then focuses on the impact of the corpus callosum (a…

The Human Brainnetome Atlas: A New Brain Atlas Based on Connectional Architecture.

PubMed

Fan, Lingzhong; Li, Hai; Zhuo, Junjie; Zhang, Yu; Wang, Jiaojian; Chen, Liangfu; Yang, Zhengyi; Chu, Congying; Xie, Sangma; Laird, Angela R; Fox, Peter T; Eickhoff, Simon B; Yu, Chunshui; Jiang, Tianzi

2016-08-01

The human brain atlases that allow correlating brain anatomy with psychological and cognitive functions are in transition from ex vivo histology-based printed atlases to digital brain maps providing multimodal in vivo information. Many current human brain atlases cover only specific structures, lack fine-grained parcellations, and fail to provide functionally important connectivity information. Using noninvasive multimodal neuroimaging techniques, we designed a connectivity-based parcellation framework that identifies the subdivisions of the entire human brain, revealing the in vivo connectivity architecture. The resulting human Brainnetome Atlas, with 210 cortical and 36 subcortical subregions, provides a fine-grained, cross-validated atlas and contains information on both anatomical and functional connections. Additionally, we further mapped the delineated structures to mental processes by reference to the BrainMap database. It thus provides an objective and stable starting point from which to explore the complex relationships between structure, connectivity, and function, and eventually improves understanding of how the human brain works. The human Brainnetome Atlas will be made freely available for download at http://atlas.brainnetome.org, so that whole brain parcellations, connections, and functional data will be readily available for researchers to use in their investigations into healthy and pathological states. © The Author 2016. Published by Oxford University Press.

Neuroscience and education.

PubMed

Goswami, Usha

2004-03-01

Neuroscience is a relatively new discipline encompassing neurology, psychology and biology. It has made great strides in the last 100 years, during which many aspects of the physiology, biochemistry, pharmacology and structure of the vertebrate brain have been understood. Understanding of some of the basic perceptual, cognitive, attentional, emotional and mnemonic functions is also making progress, particularly since the advent of the cognitive neurosciences, which focus specifically on understanding higher level processes of cognition via imaging technology. Neuroimaging has enabled scientists to study the human brain at work in vivo, deepening our understanding of the very complex processes underpinning speech and language, thinking and reasoning, reading and mathematics. It seems timely, therefore, to consider how we might implement our increased understanding of brain development and brain function to explore educational questions.

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

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?

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.

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.

How cortical neurons help us see: visual recognition in the human brain

PubMed Central

Blumberg, Julie; Kreiman, Gabriel

2010-01-01

Through a series of complex transformations, the pixel-like input to the retina is converted into rich visual perceptions that constitute an integral part of visual recognition. Multiple visual problems arise due to damage or developmental abnormalities in the cortex of the brain. Here, we provide an overview of how visual information is processed along the ventral visual cortex in the human brain. We discuss how neurophysiological recordings in macaque monkeys and in humans can help us understand the computations performed by visual cortex. PMID:20811161

The Epigenetic Link between Prenatal Adverse Environments and Neurodevelopmental Disorders

PubMed Central

Kundakovic, Marija; Jaric, Ivana

2017-01-01

Prenatal adverse environments, such as maternal stress, toxicological exposures, and viral infections, can disrupt normal brain development and contribute to neurodevelopmental disorders, including schizophrenia, depression, and autism. Increasing evidence shows that these short- and long-term effects of prenatal exposures on brain structure and function are mediated by epigenetic mechanisms. Animal studies demonstrate that prenatal exposure to stress, toxins, viral mimetics, and drugs induces lasting epigenetic changes in the brain, including genes encoding glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf). These epigenetic changes have been linked to changes in brain gene expression, stress reactivity, and behavior, and often times, these effects are shown to be dependent on the gestational window of exposure, sex, and exposure level. Although evidence from human studies is more limited, gestational exposure to environmental risks in humans is associated with epigenetic changes in peripheral tissues, and future studies are required to understand whether we can use peripheral biomarkers to predict neurobehavioral outcomes. An extensive research effort combining well-designed human and animal studies, with comprehensive epigenomic analyses of peripheral and brain tissues over time, will be necessary to improve our understanding of the epigenetic basis of neurodevelopmental disorders. PMID:28335457

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.

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.

What the cognitive neurosciences mean to me.

PubMed

Pereira, Alfredo

2007-01-01

Cognitive Neuroscience is an interdisciplinary area of research that combines measurement of brain activity (mostly by means of neuroimaging) with a simultaneous performance of cognitive tasks by human subjects. These investigations have been successful in the task of connecting the sciences of the brain (Neurosciences) and the sciences of the mind (Cognitive Sciences). Advances on this kind of research provide a map of localization of cognitive functions in the human brain. Do these results help us to understand how mind relates to the brain? In my view, the results obtained by the Cognitive Neurosciences lead to new investigations in the domain of Molecular Neurobiology, aimed at discovering biophysical mechanisms that generate the activity measured by neuroimaging instruments. In this context, I argue that the understanding of how ionic/molecular processes support cognition and consciousness cannot be made by means of the standard reductionist explanations. Knowledge of ionic/molecular mechanisms can contribute to our understanding of the human mind as long as we assume an alternative form of explanation, based on psycho-physical similarities, together with an ontological view of mentality and spirituality as embedded in physical nature (and not outside nature, as frequently assumed in western culture).

What The Cognitive Neurosciences Mean To Me

PubMed Central

Pereira, Alfredo

2007-01-01

Cognitive Neuroscience is an interdisciplinary area of research that combines measurement of brain activity (mostly by means of neuroimaging) with a simultaneous performance of cognitive tasks by human subjects. These investigations have been successful in the task of connecting the sciences of the brain (Neurosciences) and the sciences of the mind (Cognitive Sciences). Advances on this kind of research provide a map of localization of cognitive functions in the human brain. Do these results help us to understand how mind relates to the brain? In my view, the results obtained by the Cognitive Neurosciences lead to new investigations in the domain of Molecular Neurobiology, aimed at discovering biophysical mechanisms that generate the activity measured by neuroimaging instruments. In this context, I argue that the understanding of how ionic/molecular processes support cognition and consciousness cannot be made by means of the standard reductionist explanations. Knowledge of ionic/molecular mechanisms can contribute to our understanding of the human mind as long as we assume an alternative form of explanation, based on psycho-physical similarities, together with an ontological view of mentality and spirituality as embedded in physical nature (and not outside nature, as frequently assumed in western culture). PMID:22058629

Allometric Analysis Detects Brain Size-Independent Effects of Sex and Sex Chromosome Complement on Human Cerebellar Organization.

PubMed

Mankiw, Catherine; Park, Min Tae M; Reardon, P K; Fish, Ari M; Clasen, Liv S; Greenstein, Deanna; Giedd, Jay N; Blumenthal, Jonathan D; Lerch, Jason P; Chakravarty, M Mallar; Raznahan, Armin

2017-05-24

The cerebellum is a large hindbrain structure that is increasingly recognized for its contribution to diverse domains of cognitive and affective processing in human health and disease. Although several of these domains are sex biased, our fundamental understanding of cerebellar sex differences-including their spatial distribution, potential biological determinants, and independence from brain volume variation-lags far behind that for the cerebrum. Here, we harness automated neuroimaging methods for cerebellar morphometrics in 417 individuals to (1) localize normative male-female differences in raw cerebellar volume, (2) compare these to sex chromosome effects estimated across five rare sex (X/Y) chromosome aneuploidy (SCA) syndromes, and (3) clarify brain size-independent effects of sex and SCA on cerebellar anatomy using a generalizable allometric approach that considers scaling relationships between regional cerebellar volume and brain volume in health. The integration of these approaches shows that (1) sex and SCA effects on raw cerebellar volume are large and distributed, but regionally heterogeneous, (2) human cerebellar volume scales with brain volume in a highly nonlinear and regionally heterogeneous fashion that departs from documented patterns of cerebellar scaling in phylogeny, and (3) cerebellar organization is modified in a brain size-independent manner by sex (relative expansion of total cerebellum, flocculus, and Crus II-lobule VIIIB volumes in males) and SCA (contraction of total cerebellar, lobule IV, and Crus I volumes with additional X- or Y-chromosomes; X-specific contraction of Crus II-lobule VIIIB). Our methods and results clarify the shifts in human cerebellar organization that accompany interwoven variations in sex, sex chromosome complement, and brain size. SIGNIFICANCE STATEMENT Cerebellar systems are implicated in diverse domains of sex-biased behavior and pathology, but we lack a basic understanding of how sex differences in the human cerebellum are distributed and determined. We leverage a rare neuroimaging dataset to deconvolve the interwoven effects of sex, sex chromosome complement, and brain size on human cerebellar organization. We reveal topographically variegated scaling relationships between regional cerebellar volume and brain size in humans, which (1) are distinct from those observed in phylogeny, (2) invalidate a traditional neuroimaging method for brain volume correction, and (3) allow more valid and accurate resolution of which cerebellar subcomponents are sensitive to sex and sex chromosome complement. These findings advance understanding of cerebellar organization in health and sex chromosome aneuploidy. Copyright © 2017 the authors 0270-6474/17/375222-11$15.00/0.

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

PubMed

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

2018-06-13

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

Expanding the Range, Dividing the Task: Educating the Human Brain in an Electronic Society.

ERIC Educational Resources Information Center

Sylwester, Robert

1990-01-01

Reviews five properties of the brain that are central to dividing educational tasks between minds and machines and creating curricula to help students understand the complementary relationships between the brain and supportive machinery. The curriculum should focus on knowledge, skills, and values that most characterize and enhance our brain's…

The Challenge of Connecting the Dots in the B.R.A.I.N

PubMed Central

Devor, Anna; Bandettini, Peter A.; Boas, David A.; Bower, James M.; Buxton, Richard B.; Cohen, Lawrence B.; Dale, Anders M.; Einevoll, Gaute T.; Fox, Peter T.; Franceschini, Maria Angela; Friston, Karl J.; Fujimoto, James G.; Geyer, Marc A.; Greenberg, Joel H.; Halgren, Eric; Hämäläinen, Matti S.; Helmchen, Fritjof; Hyman, Bradley T.; Jasanoff, Alan; Jernigan, Terry L.; Judd, Lewis L.; Kim, Seong-Gi; Kleinfeld, David; Kopell, Nancy J.; Kutas, Marta; Kwong, Kenneth K.; Larkum, Matthew E.; Lo, Eng H.; Magistretti, Pierre J.; Mandeville, Joseph B.; Masliah, Eliezer; Mitra, Partha P.; Mobley, William C.; Moskowitz, Michael A.; Nimmerjahn, Axel; Reynolds, John H.; Rosen, Bruce R.; Salzberg, Brian M.; Schaffer, Chris B.; Silva, Gabriel A.; So, Peter T. C.; Spitzer, Nicholas C.; Tootell, Roger B.; Van Essen, David C.; Vanduffel, Wim; Vinogradov, Sergei A.; Wald, Larry L.; Wang, Lihong V.; Weber, Bruno; Yodh, Arjun G.

2013-01-01

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative has focused scientific attention on the necessary tools to understand the human brain and mind. Here, we outline our collective vision for what we can achieve within a decade with properly targeted efforts, and discuss likely technological deliverables and neuroscience progress. PMID:24139032

Understand the cogs to understand cognition.

PubMed

Marblestone, Adam H; Wayne, Greg; Kording, Konrad P

2017-01-01

Lake et al. suggest that current AI systems lack the inductive biases that enable human learning. However, Lake et al.'s proposed biases may not directly map onto mechanisms in the developing brain. A convergence of fields may soon create a correspondence between biological neural circuits and optimization in structured architectures, allowing us to systematically dissect how brains learn.

Structural and functional correlates of visual field asymmetry in the human brain by diffusion kurtosis MRI and functional MRI.

PubMed

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

2016-11-09

Human visual performance has been observed to show 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 whether 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, respectively, in 15 healthy individuals at 3 T. 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 diffusion kurtosis MRI, the brain regions mapping to the lower visual field showed higher mean kurtosis, but not fractional anisotropy or mean diffusivity compared with 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.

Regional Variations in Brain Gyrification Are Associated with General Cognitive Ability in Humans

PubMed Central

Gregory, Michael D.; Kippenhan, J. Shane; Dickinson, Dwight; Carrasco, Jessica; Mattay, Venkata S.; Weinberger, Daniel R.; Berman, Karen F.

2016-01-01

Summary Searching for a neurobiological understanding of human intellectual capabilities has long occupied those very capabilities. Brain gyrification, or folding of the cortex, is as highly-evolved and variable a characteristic in humans as is intelligence. Indeed, gyrification scales with brain size, and relationships between brain size and intelligence have been demonstrated in humans [1-3]. However, gyrification shows a large degree of variability that is independent from brain size [4-6], suggesting that the former may independently contribute to cognitive abilities, and thus supporting a direct investigation of this parameter in the context of intelligence. Moreover, uncovering the regional pattern of such an association could offer insights into evolutionary and neural mechanisms. We tested for this brain-behavior relationship in two separate, independently-collected, large cohorts: 440 healthy adults and 662 healthy children, using high-resolution structural neuroimaging and comprehensive neuropsychometric batteries. In both samples, general cognitive ability was significantly associated (pfdr<0.01) with increasing gyrification in a network of neocortical regions, including large portions of the prefrontal cortex, inferior parietal lobule, and temporoparietal junction, as well as the insula, cingulate cortex, and fusiform gyrus, a regional distribution that was nearly identical in both samples (Dice similarity coefficient=0.80). This neuroanatomical pattern is consistent with an existing, well-known proposal, the Parieto-Frontal Integration Theory of Intelligence [7], and is also consistent with research in comparative evolutionary biology showing rapid neocortical expansion of these regions in humans relative to other species. These data provide a framework for understanding the neurobiology of human cognitive abilities, and suggest a potential neurocellular association. PMID:27133866

A meta-analysis of sex differences in human brain structure☆

PubMed Central

Ruigrok, Amber N.V.; Salimi-Khorshidi, Gholamreza; Lai, Meng-Chuan; Baron-Cohen, Simon; Lombardo, Michael V.; Tait, Roger J.; Suckling, John

2014-01-01

The prevalence, age of onset, and symptomatology of many neuropsychiatric conditions differ between males and females. To understand the causes and consequences of sex differences it is important to establish where they occur in the human brain. We report the first meta-analysis of typical sex differences on global brain volume, a descriptive account of the breakdown of studies of each compartmental volume by six age categories, and whole-brain voxel-wise meta-analyses on brain volume and density. Gaussian-process regression coordinate-based meta-analysis was used to examine sex differences in voxel-based regional volume and density. On average, males have larger total brain volumes than females. Examination of the breakdown of studies providing total volumes by age categories indicated a bias towards the 18–59 year-old category. Regional sex differences in volume and tissue density include the amygdala, hippocampus and insula, areas known to be implicated in sex-biased neuropsychiatric conditions. Together, these results suggest candidate regions for investigating the asymmetric effect that sex has on the developing brain, and for understanding sex-biased neurological and psychiatric conditions. PMID:24374381

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.

Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution

PubMed Central

Mendizabal, Isabel; Shi, Lei; Keller, Thomas E.; Konopka, Genevieve; Preuss, Todd M.; Hsieh, Tzung-Fu; Hu, Enzhi; Zhang, Zhe; Su, Bing; Yi, Soojin V.

2016-01-01

How do epigenetic modifications change across species and how do these modifications affect evolution? These are fundamental questions at the forefront of our evolutionary epigenomic understanding. Our previous work investigated human and chimpanzee brain methylomes, but it was limited by the lack of outgroup data which is critical for comparative (epi)genomic studies. Here, we compared whole genome DNA methylation maps from brains of humans, chimpanzees and also rhesus macaques (outgroup) to elucidate DNA methylation changes during human brain evolution. Moreover, we validated that our approach is highly robust by further examining 38 human-specific DMRs using targeted deep genomic and bisulfite sequencing in an independent panel of 37 individuals from five primate species. Our unbiased genome-scan identified human brain differentially methylated regions (DMRs), irrespective of their associations with annotated genes. Remarkably, over half of the newly identified DMRs locate in intergenic regions or gene bodies. Nevertheless, their regulatory potential is on par with those of promoter DMRs. An intriguing observation is that DMRs are enriched in active chromatin loops, suggesting human-specific evolutionary remodeling at a higher-order chromatin structure. These findings indicate that there is substantial reprogramming of epigenomic landscapes during human brain evolution involving noncoding regions. PMID:27563052

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.

Ecological Human Brain and Young Children's "Naturalist Intelligence" from the Perspective of Developmentally and Culturally Appropriate Practice (DCAP).

ERIC Educational Resources Information Center

Hyun, Eunsook

Based on the view that young children have a different intellectual culture from adults' in the way they know and understand nature, this paper explores ecological human brain development, children's intellectual culture of naturalist intelligence, and developmentally and culturally congruent curricula for young children. The paper discusses the…

Neural correlates of establishing, maintaining, and switching brain states

PubMed Central

Tang, Yi-Yuan; Rothbart, Mary K.; Posner, Michael I.

2012-01-01

Although the study of brain states is an old one in neuroscience, there has been growing interest in brain state specification owing to MRI studies tracing brain connectivity at rest. In this review, we summarize recent research on three relatively well-described brain states: the resting, alert, and meditation states. We explore the neural correlates of maintaining a state or switching between states, and argue that the anterior cingulate cortex and striatum play a critical role in state maintenance, whereas the insula has a major role in switching between states. Brain state may serve as a predictor of performance in a variety of perceptual, memory, and problem solving tasks. Thus, understanding brain states is critical for understanding human performance. PMID:22613871

Comparative Study of Human and Mouse Postsynaptic Proteomes Finds High Compositional Conservation and Abundance Differences for Key Synaptic Proteins

PubMed Central

Bayés, Àlex; Collins, Mark O.; Croning, Mike D. R.; van de Lagemaat, Louie N.; Choudhary, Jyoti S.; Grant, Seth G. N.

2012-01-01

Direct comparison of protein components from human and mouse excitatory synapses is important for determining the suitability of mice as models of human brain disease and to understand the evolution of the mammalian brain. The postsynaptic density is a highly complex set of proteins organized into molecular networks that play a central role in behavior and disease. We report the first direct comparison of the proteome of triplicate isolates of mouse and human cortical postsynaptic densities. The mouse postsynaptic density comprised 1556 proteins and the human one 1461. A large compositional overlap was observed; more than 70% of human postsynaptic density proteins were also observed in the mouse postsynaptic density. Quantitative analysis of postsynaptic density components in both species indicates a broadly similar profile of abundance but also shows that there is higher abundance variation between species than within species. Well known components of this synaptic structure are generally more abundant in the mouse postsynaptic density. Significant inter-species abundance differences exist in some families of key postsynaptic density proteins including glutamatergic neurotransmitter receptors and adaptor proteins. Furthermore, we have identified a closely interacting set of molecules enriched in the human postsynaptic density that could be involved in dendrite and spine structural plasticity. Understanding synapse proteome diversity within and between species will be important to further our understanding of brain complexity and disease. PMID:23071613

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…

Studying brain organization via spontaneous fMRI signal

PubMed Central

Power, Jonathan D; Schlaggar, Bradley L; Petersen, Steven E

2014-01-01

In recent years, some substantial advances in understanding human (and non-human) brain organization have emerged from a relatively unusual approach: the observation of spontaneous activity, and correlated patterns in spontaneous activity, in the “resting” brain. Most commonly, spontaneous neural activity is measured indirectly via fMRI signal in subjects who are lying quietly in the scanner, the so-called “resting state”. This Primer introduces the fMRI-based study of spontaneous brain activity, some of the methodological issues active in the field, and some ways in which resting state fMRI has been used to delineate aspects of area-level and supra-areal brain organization. PMID:25459408

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.

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.

Bovine brain ribonuclease is the functional homolog of human ribonuclease 1.

PubMed

Eller, Chelcie H; Lomax, Jo E; Raines, Ronald T

2014-09-19

Mounting evidence suggests that human pancreatic ribonuclease (RNase 1) plays important roles in vivo, ranging from regulating blood clotting and inflammation to directly counteracting tumorigenic cells. Understanding these putative roles has been pursued with continual comparisons of human RNase 1 to bovine RNase A, an enzyme that appears to function primarily in the ruminant gut. Our results imply a different physiology for human RNase 1. We demonstrate distinct functional differences between human RNase 1 and bovine RNase A. Moreover, we characterize another RNase 1 homolog, bovine brain ribonuclease, and find pronounced similarities between that enzyme and human RNase 1. We report that human RNase 1 and bovine brain ribonuclease share high catalytic activity against double-stranded RNA substrates, a rare quality among ribonucleases. Both human RNase 1 and bovine brain RNase are readily endocytosed by mammalian cells, aided by tight interactions with cell surface glycans. Finally, we show that both human RNase 1 and bovine brain RNase are secreted from endothelial cells in a regulated manner, implying a potential role in vascular homeostasis. Our results suggest that brain ribonuclease, not RNase A, is the true bovine homolog of human RNase 1, and provide fundamental insight into the ancestral roles and functional adaptations of RNase 1 in mammals. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Integrative Understanding of Emergent Brain Properties, Quantum Brain Hypotheses, and Connectome Alterations in Dementia are Key Challenges to Conquer Alzheimer's Disease.

PubMed

Kuljiš, Rodrigo O

2010-01-01

The biological substrate for cognition remains a challenge as much as defining this function of living beings. Here, we examine some of the difficulties to understand normal and disordered cognition in humans. We use aspects of Alzheimer's disease and related disorders to illustrate how the wealth of information at many conceptually separate, even intellectually decoupled, physical scales - in particular at the Molecular Neuroscience versus Systems Neuroscience/Neuropsychology levels - presents a challenge in terms of true interdisciplinary integration towards a coherent understanding. These unresolved dilemmas include critically the as yet untested quantum brain hypothesis, and the embryonic attempts to develop and define the so-called connectome in humans and in non-human models of disease. To mitigate these challenges, we propose a scheme incorporating the vast array of scales of the space and time (space-time) manifold from at least the subatomic through cognitive-behavioral dimensions of inquiry, to achieve a new understanding of both normal and disordered cognition, that is essential for a new era of progress in the Generative Sciences and its application to translational efforts for disease prevention and treatment.

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

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.

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.

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

Visual artistic creativity and the brain.

PubMed

Heilman, Kenneth M; Acosta, Lealani Mae

2013-01-01

Creativity is the development of a new or novel understanding--insight that leads to the expression of orderly relationships (e.g., finding and revealing the thread that unites). Visual artistic creativity plays an important role in the quality of human lives, and the goal of this chapter is to describe some of the brain mechanisms that may be important in visual artistic creativity. The initial major means of learning how the brain mediates any activity is to understand the anatomy and physiology that may support these processes. A further understanding of specific cognitive activities and behaviors may be gained by studying patients who have diseases of the brain and how these diseases influence these functions. Physiological recording such as electroencephalography and brain imaging techniques such as PET and fMRI have also allowed us to gain a better understanding of the brain mechanisms important in visual creativity. In this chapter, we discuss anatomic and physiological studies, as well as neuropsychological studies of healthy artists and patients with neurological disease that have helped us gain some insight into the brain mechanisms that mediate artistic creativity. © 2013 Elsevier B.V. All rights reserved.

In vivo Magnetic Resonance Spectroscopy of cerebral glycogen metabolism in animals and humans.

PubMed

Khowaja, Ameer; Choi, In-Young; Seaquist, Elizabeth R; Öz, Gülin

2015-02-01

Glycogen serves as an important energy reservoir in the human body. Despite the abundance of glycogen in the liver and skeletal muscles, its concentration in the brain is relatively low, hence its significance has been questioned. A major challenge in studying brain glycogen metabolism has been the lack of availability of non-invasive techniques for quantification of brain glycogen in vivo. Invasive methods for brain glycogen quantification such as post mortem extraction following high energy microwave irradiation are not applicable in the human brain. With the advent of (13)C Magnetic Resonance Spectroscopy (MRS), it has been possible to measure brain glycogen concentrations and turnover in physiological conditions, as well as under the influence of stressors such as hypoglycemia and visual stimulation. This review presents an overview of the principles of the (13)C MRS methodology and its applications in both animals and humans to further our understanding of glycogen metabolism under normal physiological and pathophysiological conditions such as hypoglycemia unawareness.

In vivo Magnetic Resonance Spectroscopy of cerebral glycogen metabolism in animals and humans

PubMed Central

Khowaja, Ameer; Choi, In-Young; Seaquist, Elizabeth R.; Öz, Gülin

2015-01-01

Glycogen serves as an important energy reservoir in the human body. Despite the abundance of glycogen in the liver and skeletal muscles, its concentration in the brain is relatively low, hence its significance has been questioned. A major challenge in studying brain glycogen metabolism has been the lack of availability of non-invasive techniques for quantification of brain glycogen in vivo. Invasive methods for brain glycogen quantification such as post mortem extraction following high energy microwave irradiation are not applicable in the human brain. With the advent of 13C Magnetic Resonance Spectroscopy (MRS), it has been possible to measure brain glycogen concentrations and turnover in physiological conditions, as well as under the influence of stressors such as hypoglycemia and visual stimulation. This review presents an overview of the principles of the 13C MRS methodology and its applications in both animals and humans to further our understanding of glycogen metabolism under normal physiological and pathophysiological conditions such as hypoglycemia unawareness. PMID:24676563

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…

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

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

Voxels in the Brain: Neuroscience, Informatics and Changing Notions of Objectivity.

ERIC Educational Resources Information Center

Beaulieu, Anne

2001-01-01

Examines a subset of tools (atlases of the brain) developed in the Human Brain Project (HBP) in order to understand how the use of these tools changes the practice of science. Discusses the redefinition of what constitutes 'objective' neuroscientific knowledge according to both technological possibilities built into these tools and the constraints…

Developmental patterns of chimpanzee cerebral tissues provide important clues for understanding the remarkable enlargement of the human brain.

PubMed

Sakai, Tomoko; Matsui, Mie; Mikami, Akichika; Malkova, Ludise; Hamada, Yuzuru; Tomonaga, Masaki; Suzuki, Juri; Tanaka, Masayuki; Miyabe-Nishiwaki, Takako; Makishima, Haruyuki; Nakatsukasa, Masato; Matsuzawa, Tetsuro

2013-02-22

Developmental prolongation is thought to contribute to the remarkable brain enlargement observed in modern humans (Homo sapiens). However, the developmental trajectories of cerebral tissues have not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, the development of cerebral tissues was tracked in growing chimpanzees during infancy and the juvenile stage, using three-dimensional magnetic resonance imaging and compared with that of humans and rhesus macaques (Macaca mulatta). Overall, cerebral development in chimpanzees demonstrated less maturity and a more protracted course during prepuberty, as observed in humans but not in macaques. However, the rapid increase in cerebral total volume and proportional dynamic change in the cerebral tissue in humans during early infancy, when white matter volume increases dramatically, did not occur in chimpanzees. A dynamic reorganization of cerebral tissues of the brain during early infancy, driven mainly by enhancement of neuronal connectivity, is likely to have emerged in the human lineage after the split between humans and chimpanzees and to have promoted the increase in brain volume in humans. Our findings may lead to powerful insights into the ontogenetic mechanism underlying human brain enlargement.

Developmental patterns of chimpanzee cerebral tissues provide important clues for understanding the remarkable enlargement of the human brain

PubMed Central

Sakai, Tomoko; Matsui, Mie; Mikami, Akichika; Malkova, Ludise; Hamada, Yuzuru; Tomonaga, Masaki; Suzuki, Juri; Tanaka, Masayuki; Miyabe-Nishiwaki, Takako; Makishima, Haruyuki; Nakatsukasa, Masato; Matsuzawa, Tetsuro

2013-01-01

Developmental prolongation is thought to contribute to the remarkable brain enlargement observed in modern humans (Homo sapiens). However, the developmental trajectories of cerebral tissues have not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, the development of cerebral tissues was tracked in growing chimpanzees during infancy and the juvenile stage, using three-dimensional magnetic resonance imaging and compared with that of humans and rhesus macaques (Macaca mulatta). Overall, cerebral development in chimpanzees demonstrated less maturity and a more protracted course during prepuberty, as observed in humans but not in macaques. However, the rapid increase in cerebral total volume and proportional dynamic change in the cerebral tissue in humans during early infancy, when white matter volume increases dramatically, did not occur in chimpanzees. A dynamic reorganization of cerebral tissues of the brain during early infancy, driven mainly by enhancement of neuronal connectivity, is likely to have emerged in the human lineage after the split between humans and chimpanzees and to have promoted the increase in brain volume in humans. Our findings may lead to powerful insights into the ontogenetic mechanism underlying human brain enlargement. PMID:23256194

Stem Cell Technology for (Epi)genetic Brain Disorders.

PubMed

Riemens, Renzo J M; Soares, Edilene S; Esteller, Manel; Delgado-Morales, Raul

2017-01-01

Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems. This, together with our incomplete knowledge of the multifactorial causes in the majority of these disorders, as well as a thorough understanding of associated (epi)genetic alterations, has been impeding progress in gaining more mechanistic insights from translational studies. Over the last years, however, stem cell technology has been offering an alternative approach to study and treat human brain disorders. Owing to this technology, we are now able to obtain a theoretically inexhaustible source of human neural cells and precursors in vitro that offer a platform for disease modeling and the establishment of therapeutic interventions. In addition to the potential to increase our general understanding of how (epi)genetic alterations contribute to the pathology of brain disorders, stem cells and derivatives allow for high-throughput drugs and toxicity testing, and provide a cell source for transplant therapies in regenerative medicine. In the current chapter, we will demonstrate the validity of human stem cell-based models and address the utility of other stem cell-based applications for several human brain disorders with multifactorial and (epi)genetic bases, including Parkinson's disease (PD), Alzheimer's disease (AD), fragile X syndrome (FXS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Rett syndrome (RTT).

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.

Targeting the ecology within: The role of the gut-brain axis and human microbiota in drug addiction.

PubMed

Skosnik, Patrick D; Cortes-Briones, Jose A

2016-08-01

Despite major advances in our understanding of the brain using traditional neuroscience, reliable and efficacious treatments for drug addiction have remained elusive. Hence, the time has come to utilize novel approaches, particularly those drawing upon contemporary advances in fields outside of established neuroscience and psychiatry. Put another way, the time has come for a paradigm shift in the addiction sciences. Apropos, a revolution in the area of human health is underway, which is occurring at the nexus between enteric microbiology and neuroscience. It has become increasingly clear that the human microbiota (the vast ecology of bacteria residing within the human organism), plays an important role in health and disease. This is not surprising, as it has been estimated that bacteria living in the human body (approximately 1kg of mass, roughly equivalent to that of the human brain) outnumber human cells 10 to 1. While advances in the understanding of the role of microbiota in other areas of human health have yielded intriguing results (e.g., Clostridium difficile, irritable bowel syndrome, autism, etc.), to date, no systematic programs of research have examined the role of microbiota in drug addiction. The current hypothesis, therefore, is that gut dysbiosis plays a key role in addictive disorders. In the context of this hypothesis, this paper provides a rationale for future research to target the "gut-brain axis" in addiction. A brief background of the gut-brain axis is provided, along with a series of hypothesis-driven ideas outlining potential treatments for addiction via manipulations of the "ecology within." Copyright © 2016 Elsevier Ltd. All rights reserved.

Bridging animal and human models of exercise-induced brain plasticity

PubMed Central

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

2015-01-01

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

Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution.

PubMed

Mendizabal, Isabel; Shi, Lei; Keller, Thomas E; Konopka, Genevieve; Preuss, Todd M; Hsieh, Tzung-Fu; Hu, Enzhi; Zhang, Zhe; Su, Bing; Yi, Soojin V

2016-11-01

How do epigenetic modifications change across species and how do these modifications affect evolution? These are fundamental questions at the forefront of our evolutionary epigenomic understanding. Our previous work investigated human and chimpanzee brain methylomes, but it was limited by the lack of outgroup data which is critical for comparative (epi)genomic studies. Here, we compared whole genome DNA methylation maps from brains of humans, chimpanzees and also rhesus macaques (outgroup) to elucidate DNA methylation changes during human brain evolution. Moreover, we validated that our approach is highly robust by further examining 38 human-specific DMRs using targeted deep genomic and bisulfite sequencing in an independent panel of 37 individuals from five primate species. Our unbiased genome-scan identified human brain differentially methylated regions (DMRs), irrespective of their associations with annotated genes. Remarkably, over half of the newly identified DMRs locate in intergenic regions or gene bodies. Nevertheless, their regulatory potential is on par with those of promoter DMRs. An intriguing observation is that DMRs are enriched in active chromatin loops, suggesting human-specific evolutionary remodeling at a higher-order chromatin structure. These findings indicate that there is substantial reprogramming of epigenomic landscapes during human brain evolution involving noncoding regions. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The emergence of mind and emotion in the evolution of neocortex.

PubMed

Freeman, Walter J

2011-01-01

The most deeply transformative concept for the growth of 21st Century psychiatry is the constellation of the chaotic dynamics of the brain. Brains are no longer seen as rational systems that are plagued with emotional disorders reflecting primitives inherited from our animal ancestors. Brains are dynamical systems that continually create patterns by acting intentionally into the environment and shaping themselves in accord with the sensory consequences of their intended actions. Emotions are now seen not as reversions to animal behaviors but as the sources of force and energy that brains require for the actions they take to understand the world and themselves. Humans are unique in experiencing consciousness of their own actions, which they experience as conscience: guilt, shame, pride and joy. Chaotic brain dynamics strives always for unity and harmony, but as a necessary condition for adaptation to a changing world, it repeatedly lapses into disorder. The successes are seen in the normal unity of consciousness; the failures are seen in the disorders that we rightly label the schizophrenias and the less severe character disorders. The foundation for healthy unity is revealed by studies in the evolution of brains, in particular the way in which neocortex of mammals emerged from the primitive allocortex of reptiles. The amazing facts of brain dynamics are now falling into several places. The power-law connectivity of cortex supports the scale-free dynamics of the global workspace in brains ranging from mouse to whale. That dynamics in humans holds the secrets of speech and symbol utilization. By recursive interactions in vast areas of human neocortex the scale-free connectivity supports our unified consciousness. Here in this dynamics are to be sought the keys to understanding and treating the disorders that uniquely plague the human mind.

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.

A meta-analysis of sex differences in human brain structure.

PubMed

Ruigrok, Amber N V; Salimi-Khorshidi, Gholamreza; Lai, Meng-Chuan; Baron-Cohen, Simon; Lombardo, Michael V; Tait, Roger J; Suckling, John

2014-02-01

The prevalence, age of onset, and symptomatology of many neuropsychiatric conditions differ between males and females. To understand the causes and consequences of sex differences it is important to establish where they occur in the human brain. We report the first meta-analysis of typical sex differences on global brain volume, a descriptive account of the breakdown of studies of each compartmental volume by six age categories, and whole-brain voxel-wise meta-analyses on brain volume and density. Gaussian-process regression coordinate-based meta-analysis was used to examine sex differences in voxel-based regional volume and density. On average, males have larger total brain volumes than females. Examination of the breakdown of studies providing total volumes by age categories indicated a bias towards the 18-59 year-old category. Regional sex differences in volume and tissue density include the amygdala, hippocampus and insula, areas known to be implicated in sex-biased neuropsychiatric conditions. Together, these results suggest candidate regions for investigating the asymmetric effect that sex has on the developing brain, and for understanding sex-biased neurological and psychiatric conditions. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neuroprotection of Sex Steroids

PubMed Central

Liu, Mingyue; Kelley, Melissa H.; Herson, Paco S.; Hurn, Patricia D.

2011-01-01

Sex steroids are essential for reproduction and development in animals and humans, and sex steroids also play an important role in neuroprotection following brain injury. New data indicate that sex-specific responses to brain injury occur at the cellular and molecular levels. This review summarizes the current understanding of neuroprotection by sex steroids, particularly estrogen, androgen, and progesterone, based on both in vitro and in vivo studies. Better understanding of the role of sex steroids under physiological and pathological conditions will help us to develop novel effective therapeutic strategies for brain injury. PMID:20595940

Unbalanced neuronal circuits in addiction.

PubMed

Volkow, Nora D; Wang, Gen-Jack; Tomasi, Dardo; Baler, Ruben D

2013-08-01

Through sequential waves of drug-induced neurochemical stimulation, addiction co-opts the brain's neuronal circuits that mediate reward, motivation to behavioral inflexibility and a severe disruption of self-control and compulsive drug intake. Brain imaging technologies have allowed neuroscientists to map out the neural landscape of addiction in the human brain and to understand how drugs modify it. Published by Elsevier Ltd.

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…

Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.

PubMed

Lojewski, Xenia; Srimasorn, Sumitra; Rauh, Juliane; Francke, Silvan; Wobus, Manja; Taylor, Verdon; Araúzo-Bravo, Marcos J; Hallmeyer-Elgner, Susanne; Kirsch, Matthias; Schwarz, Sigrid; Schwarz, Johannes; Storch, Alexander; Hermann, Andreas

2015-10-01

Brain perivascular cells have recently been identified as a novel mesodermal cell type in the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and, to a lesser extent, tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely proposed for use in cell therapy in many neurological disorders; therefore, it is of importance to better understand the "intrinsic" MSC population of the human brain. We systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells with fetal and adult human brain-derived neural stem cells (NSCs) and adult human bone marrow-derived MSCs. We found that adult human brain pericytes, which can be isolated from the hippocampus and from subcortical white matter, are-in contrast to adult human NSCs-easily expandable in monolayer cultures and show many similarities to human bone marrow-derived MSCs both regarding both surface marker expression and after whole transcriptome profile. Human brain pericytes showed a negligible propensity for neuroectodermal differentiation under various differentiation conditions but efficiently generated mesodermal progeny. Consequently, human brain pericytes resemble bone marrow-derived MSCs and might be very interesting for possible autologous and endogenous stem cell-based treatment strategies and cell therapeutic approaches for treating neurological diseases. Perivascular mesenchymal stem cells (MSCs) recently gained significant interest because of their appearance in many tissues including the human brain. MSCs were often reported as being beneficial after transplantation in the central nervous system in different neurological diseases; therefore, adult brain perivascular cells derived from human neural tissue were systematically characterized concerning neural stem cell and MSC marker expression, transcriptomics, and mesodermal and inherent neuroectodermal differentiation potential in vitro and in vivo after in utero transplantation. This study showed the lack of an innate neuronal but high mesodermal differentiation potential. Because of their relationship to mesenchymal stem cells, these adult brain perivascular mesodermal cells are of great interest for possible autologous therapeutic use. ©AlphaMed Press.

Infant fMRI: A Model System for Cognitive Neuroscience.

PubMed

Ellis, Cameron T; Turk-Browne, Nicholas B

2018-05-01

Our understanding of the typical human brain has benefitted greatly from studying different kinds of brains and their associated behavioral repertoires, including animal models and neuropsychological patients. This same comparative perspective can be applied to early development - the environment, behavior, and brains of infants provide a model system for understanding how the mature brain works. This approach requires noninvasive methods for measuring brain function in awake, behaving infants. fMRI is becoming increasingly viable for this purpose, with the unique ability to precisely measure the entire brain, including both cortical and subcortical structures. Here we discuss potential lessons from infant fMRI for several domains of adult cognition and consider the challenges of conducting such research and how they might be mitigated. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nonhuman Primate Optogenetics: Recent Advances and Future Directions

PubMed Central

Acker, Leah

2017-01-01

Optogenetics is the use of genetically coded, light-gated ion channels or pumps (opsins) for millisecond resolution control of neural activity. By targeting opsin expression to specific cell types and neuronal pathways, optogenetics can expand our understanding of the neural basis of normal and pathological behavior. To maximize the potential of optogenetics to study human cognition and behavior, optogenetics should be applied to the study of nonhuman primates (NHPs). The homology between NHPs and humans makes these animals the best experimental model for understanding human brain function and dysfunction. Moreover, for genetic tools to have translational promise, their use must be demonstrated effectively in large, wild-type animals such as Rhesus macaques. Here, we review recent advances in primate optogenetics. We highlight the technical hurdles that have been cleared, challenges that remain, and summarize how optogenetic experiments are expanding our understanding of primate brain function. PMID:29118219

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

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.

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.

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.

Exploring how musical rhythm entrains brain activity with electroencephalogram frequency-tagging

PubMed Central

Nozaradan, Sylvie

2014-01-01

The ability to perceive a regular beat in music and synchronize to this beat is a widespread human skill. Fundamental to musical behaviour, beat and meter refer to the perception of periodicities while listening to musical rhythms and often involve spontaneous entrainment to move on these periodicities. Here, we present a novel experimental approach inspired by the frequency-tagging approach to understand the perception and production of rhythmic inputs. This approach is illustrated here by recording the human electroencephalogram responses at beat and meter frequencies elicited in various contexts: mental imagery of meter, spontaneous induction of a beat from rhythmic patterns, multisensory integration and sensorimotor synchronization. Collectively, our observations support the view that entrainment and resonance phenomena subtend the processing of musical rhythms in the human brain. More generally, they highlight the potential of this approach to help us understand the link between the phenomenology of musical beat and meter and the bias towards periodicities arising under certain circumstances in the nervous system. Entrainment to music provides a highly valuable framework to explore general entrainment mechanisms as embodied in the human brain. PMID:25385771

Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD.

PubMed

Atasoy, Selen; Roseman, Leor; Kaelen, Mendel; Kringelbach, Morten L; Deco, Gustavo; Carhart-Harris, Robin L

2017-12-15

Recent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used 'connectome-harmonic decomposition', a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.

Immoral behaviour following brain damage: A review.

PubMed

Roberts, Stefanie; Henry, Julie D; Molenberghs, Pascal

2018-04-16

Despite the apparent sociability of human kind, immoral behaviour is ever present in society. The term 'immoral behaviour' represents a complex array of conduct, ranging from insensitivity to topics of conversation through to violent assault and murder. To better understand the neuroscience of immoral behaviour, this review investigates two clinical populations that commonly present with changes in moral behaviour - behavioural-variant frontotemporal dementia and acquired brain injuries. Based on evidence from these groups, it is argued that rather than a single underlying cause, immoral behaviour can result from three distinct types of cognitive failure: (1) problems understanding others; (2) difficulties controlling behaviour; or (3) deficits in the capacity to make appropriate emotional contributions. Each of these failures is associated with damage to different brain regions. A more nuanced approach to the neuroscience of immoral behaviour has important implications for our understanding of immoral behaviour in a wide range of clinical groups, as well as human society more broadly. © 2018 The British Psychological Society.

The impact of poverty on the development of brain networks

PubMed Central

Lipina, Sebastián J.; Posner, Michael I.

2012-01-01

Although the study of brain development in non-human animals is an old one, recent imaging methods have allowed non-invasive studies of the gray and white matter of the human brain over the lifespan. Classic animal studies show clearly that impoverished environments reduce cortical gray matter in relation to complex environments and cognitive and imaging studies in humans suggest which networks may be most influenced by poverty. Studies have been clear in showing the plasticity of many brain systems, but whether sensitivity to learning differs over the lifespan and for which networks is still unclear. A major task for current research is a successful integration of these methods to understand how development and learning shape the neural networks underlying achievements in literacy, numeracy, and attention. This paper seeks to foster further integration by reviewing the current state of knowledge relating brain changes to behavior and indicating possible future directions. PMID:22912613

The Encephalopathy of Prematurity: One Pediatric Neuropathologist’s Perspective

PubMed Central

Kinney, Hannah C.

2010-01-01

A major challenge in understanding brain injury in the premature brain is the establishment of the precise human neuropathology at the cellular and molecular levels, as such knowledge is the foundation upon which the elucidation of the cause(s), scientific experimentation, and therapies in the field is by necessity based. In this essay, I provide my perspective as a pediatric neuropathologist upon pathologic studies in the developing human brain itself, including a review of past, present, and future aspects. My focus is upon the path that has brought us to the current recognition that preterm brain injury is a complex of white and gray matter damage that results in the modification of key developmental pathways during a critical period, which in turn defines the adverse clinical outcomes as important as the primary insult itself. The evolution of this recognition, as well as the introduction of the term “encephalopathy of prematurity” for the complex of gray and white matter damage because of acquired and developmental mechanisms, is discussed. Our enhanced understanding of the fundamental neuropathology of the human preterm brain should bring us closer to more effective therapy as the need to prevent and treat injury to developing oligodendrocytes and neurons in combination is appreciated. PMID:19945652

Do Chimeras Have Minds?

PubMed

Capps, Benjamin

2017-10-01

Suppose that a colleague proposed a fantastic experiment: to introduce human stem cells into a neonatal mouse so that its entire brain developed into "human-like" neuronal structures. The colleague claimed it would still be a mouse, and that its chimeric brain would be nothing like a "human" one. It would not, as a result, have a moral status beyond its nonhuman animal origins. Thus, the "human neuron mouse" would allow scientists to tinker with human-like neurology in ways that would be precluded if it were a human being, and that would promise to lead to substantial understanding of the destructive and incurable brain diseases that befall humanity. The colleague does admit, however, that for reasons of comparative fidelity, experiments in human patients would be scientifically preferable, although in this case, neither ethically justified nor legally permitted. For that reason, it might be desirable to create a human brain in a nonhuman primate, where it would be more likely that significant human-like neuronal development would occur, but still could not become a person. This article explores the significance of a "human neuron chimpanzee," and suggests that contradictions in the design of the experiment make it unethical to proceed in either murine or primate models.

Mind and body: concepts of human cognition, physiology and false belief in children with autism or typical development.

PubMed

Peterson, Candida C

2005-08-01

This study examined theory of mind (ToM) and concepts of human biology (eyes, heart, brain, lungs and mind) in a sample of 67 children, including 25 high functioning children with autism (age 6-13), plus age-matched and preschool comparison groups. Contrary to Baron-Cohen [1989, Journal of Autism and Developmental Disorders, 19(4), 579-600], most children with autism correctly understood the functions of the brain (84%) and the mind (64%). Their explanations were predominantly mentalistic. They outperformed typically developing preschoolers in understanding inner physiological (heart, lungs) and cognitive (brain, mind) systems, and scored as high as age-matched typical children. Yet, in line with much previous ToM research, most children with autism (60%) failed false belief, and their ToM performance was unrelated to their understanding of. human biology. Results were discussed in relation to neurobiological and social-experiential accounts of the ToM deficit in autism.

Analysis of Brain Recurrence

NASA Astrophysics Data System (ADS)

Frilot, Clifton; Kim, Paul Y.; Carrubba, Simona; McCarty, David E.; Chesson, Andrew L.; Marino, Andrew A.

Analysis of Brain Recurrence (ABR) is a method for extracting physiologically significant information from the electroencephalogram (EEG), a non-stationary electrical output of the brain, the ultimate complex dynamical system. ABR permits quantification of temporal patterns in the EEG produced by the non-autonomous differential laws that govern brain metabolism. In the context of appropriate experimental and statistical designs, ABR is ideally suited to the task of interpreting the EEG. Present applications of ABR include discovery of a human magnetic sense, increased mechanistic understanding of neuronal membrane processes, diagnosis of degenerative neurological disease, detection of changes in brain metabolism caused by weak environmental electromagnetic fields, objective characterization of the quality of human sleep, and evaluation of sleep disorders. ABR has important beneficial implications for the development of clinical and experimental neuroscience.

How Learning Techniques Initiate Simulation of Human Mind

ERIC Educational Resources Information Center

Girija, C.

2014-01-01

The simulation of human mind often helps in the understanding of abstract concept by representing it in a realistic model and simplistic way so that a learner develops an understanding of the key concepts. Bian (1873) and James (1890) in their work suggested that thoughts and body activity result from interactions among neurons within the brain.…

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

Brain-Mind Dyad, Human Experience, the Consciousness Tetrad and Lattice of Mental Operations: And Further, The Need to Integrate Knowledge from Diverse Disciplines

PubMed Central

Singh, Ajai R.; Singh, Shakuntala A.

2011-01-01

Brain, Mind and Consciousness are the research concerns of psychiatrists, psychologists, neurologists, cognitive neuroscientists and philosophers. All of them are working in different and important ways to understand the workings of the brain, the mysteries of the mind and to grasp that elusive concept called consciousness. Although they are all justified in forwarding their respective researches, it is also necessary to integrate these diverse appearing understandings and try and get a comprehensive perspective that is, hopefully, more than the sum of their parts. There is also the need to understand what each one is doing, and by the other, to understand each other’s basic and fundamental ideological and foundational underpinnings. This must be followed by a comprehensive and critical dialogue between the respective disciplines. Moreover, the concept of mind and consciousness in Indian thought needs careful delineation and critical/evidential enquiry to make it internationally relevant. The brain-mind dyad must be understood, with brain as the structural correlate of the mind, and mind as the functional correlate of the brain. To understand human experience, we need a triad of external environment, internal environment and a consciousness that makes sense of both. We need to evolve a consensus on the definition of consciousness, for which a working definition in the form of a Consciousness Tetrad of Default, Aware, Operational and Evolved Consciousness is presented. It is equally necessary to understand the connection between physical changes in the brain and mental operations, and thereby untangle and comprehend the lattice of mental operations. Interdisciplinary work and knowledge sharing, in an atmosphere of healthy give and take of ideas, and with a view to understand the significance of each other’s work, and also to critically evaluate the present corpus of knowledge from these diverse appearing fields, and then carry forward from there in a spirit of cooperative but evidential and critical enquiry – this is the goal for this monograph, and the work to follow. PMID:21694960

Brain-mind dyad, human experience, the consciousness tetrad and lattice of mental operations: and further, the need to integrate knowledge from diverse disciplines.

PubMed

Singh, Ajai R; Singh, Shakuntala A

2011-01-01

Brain, Mind and Consciousness are the research concerns of psychiatrists, psychologists, neurologists, cognitive neuroscientists and philosophers. All of them are working in different and important ways to understand the workings of the brain, the mysteries of the mind and to grasp that elusive concept called consciousness. Although they are all justified in forwarding their respective researches, it is also necessary to integrate these diverse appearing understandings and try and get a comprehensive perspective that is, hopefully, more than the sum of their parts. There is also the need to understand what each one is doing, and by the other, to understand each other's basic and fundamental ideological and foundational underpinnings. This must be followed by a comprehensive and critical dialogue between the respective disciplines. Moreover, the concept of mind and consciousness in Indian thought needs careful delineation and critical/evidential enquiry to make it internationally relevant. The brain-mind dyad must be understood, with brain as the structural correlate of the mind, and mind as the functional correlate of the brain. To understand human experience, we need a triad of external environment, internal environment and a consciousness that makes sense of both. We need to evolve a consensus on the definition of consciousness, for which a working definition in the form of a Consciousness Tetrad of Default, Aware, Operational and Evolved Consciousness is presented. It is equally necessary to understand the connection between physical changes in the brain and mental operations, and thereby untangle and comprehend the lattice of mental operations. Interdisciplinary work and knowledge sharing, in an atmosphere of healthy give and take of ideas, and with a view to understand the significance of each other's work, and also to critically evaluate the present corpus of knowledge from these diverse appearing fields, and then carry forward from there in a spirit of cooperative but evidential and critical enquiry - this is the goal for this monograph, and the work to follow.

Neuroscience Meets Music Education: Exploring the Implications of Neural Processing Models on Music Education Practice

ERIC Educational Resources Information Center

Collins, Anita

2013-01-01

Over the past two decades, neuroscientists have been fascinated by the way the brain processes music. Using new technologies, neuroscientists offer us a better understanding of the human brain's structures and functions. They have further proposed explanatory models for how the brain processes music. While these models shed light on how the…

Maternal Support and Brain Development: Neuroscience Validation for the Importance of Early Caregiving Relationships

ERIC Educational Resources Information Center

Luby, Joan; Rogers, Cynthia

2013-01-01

Advances in brain imaging methods and technology over the last 2 decades have opened an unprecedented window into the understanding of the structure and function of the human brain. In this article, the authors describe their investigation of the relationship between maternal support, observed during the preschool period, and the size of key brain…

Conceptual learning by miniature brains

PubMed Central

Avarguès-Weber, Aurore; Giurfa, Martin

2013-01-01

Concepts act as a cornerstone of human cognition. Humans and non-human primates learn conceptual relationships such as ‘same’, ‘different’, ‘larger than’, ‘better than’, among others. In all cases, the relationships have to be encoded by the brain independently of the physical nature of objects linked by the relation. Consequently, concepts are associated with high levels of cognitive sophistication and are not expected in an insect brain. Yet, various works have shown that the miniature brain of honeybees rapidly learns conceptual relationships involving visual stimuli. Concepts such as ‘same’, ‘different’, ‘above/below of’ or ‘left/right are well mastered by bees. We review here evidence about concept learning in honeybees and discuss both its potential adaptive advantage and its possible neural substrates. The results reviewed here challenge the traditional view attributing supremacy to larger brains when it comes to the elaboration of concepts and have wide implications for understanding how brains can form conceptual relations. PMID:24107530

Three-Dimensional Models for Teaching Neuroanatomy to Blind Students.

ERIC Educational Resources Information Center

Pietsch, Paul

1980-01-01

An audio/tactile course enables blind college students to understand the anatomy of the human brain. Models were designed which allow tactile exploration of the visual fields, retina, optic nerves, and the subdivisions of the tracts and radiations in the brain. (Author/PHR)

A digital interactive human brain atlas based on Chinese visible human datasets for anatomy teaching.

PubMed

Li, Qiyu; Ran, Xu; Zhang, Shaoxiang; Tan, Liwen; Qiu, Mingguo

2014-01-01

As we know, the human brain is one of the most complicated organs in the human body, which is the key and difficult point in neuroanatomy and sectional anatomy teaching. With the rapid development and extensive application of imaging technology in clinical diagnosis, doctors are facing higher and higher requirement on their anatomy knowledge. Thus, to cultivate medical students to meet the needs of medical development today and to improve their ability to read and understand radiographic images have become urgent challenges for the medical teachers. In this context, we developed a digital interactive human brain atlas based on the Chinese visible human datasets for anatomy teaching (available for free download from http://www.chinesevisiblehuman.com/down/DHBA.rar). The atlas simultaneously provides views in all 3 primary planes of section. The main structures of the human brain have been anatomically labeled in all 3 views. It is potentially useful for anatomy browsing, user self-testing, and automatic student assessment. In a word, it is interactive, 3D, user friendly, and free of charge, which can provide a new, intuitive means for anatomy teaching.

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.

Elucidating the Role of Compression Waves and Impact Duration for Generating mild Traumatic Brain Injury in Rats

PubMed Central

Lucke-Wold, Brandon P.; Phillips, Michael; Turner, Ryan C.; Logsdon, Aric F.; Smith, Kelly E.; Huber, Jason D.; Rosen, Charles L.; Regele, Jonathan D.

2016-01-01

3 million concussions occur each year in the United States. The mechanisms linking acute injury to chronic deficits are poorly understood. Mild traumatic brain injury has been described clinically in terms of acute functional deficits, but the underlying histopathologic changes that occur are relatively unknown due to limited high-function imaging modalities. In order to improve our understanding of acute injury mechanisms, appropriately designed preclinical models must be utilized. The clinical relevance of compression wave injury models revolves around the ability to produce consistent histopathologic deficits. Repetitive mild traumatic brain injuries activate similar neuroinflammatory cascades, cell death markers, and increases in amyloid precursor protein in both humans and rodents. Humans however infrequently succumb to mild traumatic brain injuries and therefore the intensity and magnitude of impacts must be inferred. Understanding compression wave properties and mechanical loading could help link the histopathologic deficits seen in rodents to what might be happening in human brains following repetitive concussions. Advances in mathematical and computer modeling can help characterize the wave properties generated by the compression wave model. While this concept of linking duration and intensity of impact to subsequent histopathologic deficits makes sense, numerical modeling of compression waves has not been performed in this context. In this collaborative interdisciplinary work, numerical simulations were performed to study the creation of compression waves in our experimental model. This work was conducted in conjunction with a repetitive compression wave injury paradigm in rats in order to better understand how the wave generation correlates with validated histopathologic deficits. PMID:27880054

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

Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke.

PubMed

Tatebayashi, Kotaro; Tanaka, Yasue; Nakano-Doi, Akiko; Sakuma, Rika; Kamachi, Saeko; Shirakawa, Manabu; Uchida, Kazutaka; Kageyama, Hiroto; Takagi, Toshinori; Yoshimura, Shinichi; Matsuyama, Tomohiro; Nakagomi, Takayuki

2017-06-01

Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.

Escherichia coli K1 invasion of human brain microvascular endothelial cells.

PubMed

Loh, Lip Nam; Ward, Theresa H

2012-01-01

The pathogenic Escherichia coli strain E. coli K1 is a primary causative agent of neonatal meningitis. Understanding how these bacteria cross the blood-brain barrier is vital to develop therapeutics. Here, we describe the use of live-cell imaging techniques to study E. coli K1 interactions with cellular markers following infection of human brain microvascular endothelial cells, a model system of the blood-brain barrier. We also discuss optimization of endothelial cell transfection conditions using nonviral transfection technique, bacterial labeling techniques, and in vitro assays to screen for fluorescent bacteria that retain their ability to invade host cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Sense of agency in the human brain.

PubMed

Haggard, Patrick

2017-04-01

In adult life, people normally know what they are doing. This experience of controlling one's own actions and, through them, the course of events in the outside world is called 'sense of agency'. It forms a central feature of human experience; however, the brain mechanisms that produce the sense of agency have only recently begun to be investigated systematically. This recent progress has been driven by the development of better measures of the experience of agency, improved design of cognitive and behavioural experiments, and a growing understanding of the brain circuits that generate this distinctive but elusive experience. The sense of agency is a mental and neural state of cardinal importance in human civilization, because it is frequently altered in psychopathology and because it underpins the concept of responsibility in human societies.

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

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.

Multimodal Imaging of Human Brain Activity: Rational, Biophysical Aspects and Modes of Integration

PubMed Central

Blinowska, Katarzyna; Müller-Putz, Gernot; Kaiser, Vera; Astolfi, Laura; Vanderperren, Katrien; Van Huffel, Sabine; Lemieux, Louis

2009-01-01

Until relatively recently the vast majority of imaging and electrophysiological studies of human brain activity have relied on single-modality measurements usually correlated with readily observable or experimentally modified behavioural or brain state patterns. Multi-modal imaging is the concept of bringing together observations or measurements from different instruments. We discuss the aims of multi-modal imaging and the ways in which it can be accomplished using representative applications. Given the importance of haemodynamic and electrophysiological signals in current multi-modal imaging applications, we also review some of the basic physiology relevant to understanding their relationship. PMID:19547657

Event-Related Oscillations in Alcoholism Research: A Review

PubMed Central

Pandey, Ashwini K; Kamarajan, Chella; Rangaswamy, Madhavi; Porjesz, Bernice

2013-01-01

Alcohol dependence is characterized as a multi-factorial disorder caused by a complex interaction between genetic and environmental liabilities across development. A variety of neurocognitive deficits/dysfunctions involving impairments in different brain regions and/or neural circuitries have been associated with chronic alcoholism, as well as with a predisposition to develop alcoholism. Several neurobiological and neurobehavioral approaches and methods of analyses have been used to understand the nature of these neurocognitive impairments/deficits in alcoholism. In the present review, we have examined relatively novel methods of analyses of the brain signals that are collectively referred to as event-related oscillations (EROs) and show promise to further our understanding of human brain dynamics while performing various tasks. These new measures of dynamic brain processes have exquisite temporal resolution and allow the study of neural networks underlying responses to sensory and cognitive events, thus providing a closer link to the physiology underlying them. Here, we have reviewed EROs in the study of alcoholism, their usefulness in understanding dynamical brain functions/dysfunctions associated with alcoholism as well as their utility as effective endophenotypes to identify and understand genes associated with both brain oscillations and alcoholism. PMID:24273686

Mechanism of Chronic Pain in Rodent Brain Imaging

NASA Astrophysics Data System (ADS)

Chang, Pei-Ching

Chronic pain is a significant health problem that greatly impacts the quality of life of individuals and imparts high costs to society. Despite intense research effort in understanding of the mechanism of pain, chronic pain remains a clinical problem that has few effective therapies. The advent of human brain imaging research in recent years has changed the way that chronic pain is viewed. To further extend the use of human brain imaging techniques for better therapies, the adoption of imaging technique onto the animal pain models is essential, in which underlying brain mechanisms can be systematically studied using various combination of imaging and invasive techniques. The general goal of this thesis is to addresses how brain develops and maintains chronic pain in an animal model using fMRI. We demonstrate that nucleus accumbens, the central component of mesolimbic circuitry, is essential in development of chronic pain. To advance our imaging technique, we develop an innovative methodology to carry out fMRI in awake, conscious rat. Using this cutting-edge technique, we show that allodynia is assoicated with shift brain response toward neural circuits associated nucleus accumbens and prefrontal cortex that regulate affective and cognitive component of pain. Taken together, this thesis provides a deeper understanding of how brain mediates pain. It builds on the existing body of knowledge through maximizing the depth of insight into brain imaging of chronic pain.

Interactionist Neuroscience.

PubMed

Badre, David; Frank, Michael J; Moore, Christopher I

2015-12-02

We argue that bidirectional interaction between animal and human studies is essential for understanding the human brain. The revolution in meso-scale study of circuits in non-human species provides a historical opportunity. However, to fully realize its potential requires integration with human neuroscience. We describe three strategies for successful interactionist neuroscience. Copyright © 2015 Elsevier Inc. All rights reserved.

Dramatic Developments in the Neurosciences Challenge Educators.

ERIC Educational Resources Information Center

Sylwester, Robert

1986-01-01

Recent dramatic developments in brain research and technology suggest that a comprehensive understanding of how the human brain works may soon be within reach. Just as the ability of the medical profession to treat patients improved dramatically with the advent of effective research skills and technology concerning the structure, biochemistry, and…

Oxytocin and Maternal Brain Plasticity

ERIC Educational Resources Information Center

Kim, Sohye; Strathearn, Lane

2016-01-01

Although dramatic postnatal changes in maternal behavior have long been noted, we are only now beginning to understand the neurobiological mechanisms that support this transition. The present paper synthesizes growing insights from both animal and human research to provide an overview of the plasticity of the mother's brain, with a particular…

Structure Shapes Dynamics and Directionality in Diverse Brain Networks: Mathematical Principles and Empirical Confirmation in Three Species

NASA Astrophysics Data System (ADS)

Moon, Joon-Young; Kim, Junhyeok; Ko, Tae-Wook; Kim, Minkyung; Iturria-Medina, Yasser; Choi, Jee-Hyun; Lee, Joseph; Mashour, George A.; Lee, Uncheol

2017-04-01

Identifying how spatially distributed information becomes integrated in the brain is essential to understanding higher cognitive functions. Previous computational and empirical studies suggest a significant influence of brain network structure on brain network function. However, there have been few analytical approaches to explain the role of network structure in shaping regional activities and directionality patterns. In this study, analytical methods are applied to a coupled oscillator model implemented in inhomogeneous networks. We first derive a mathematical principle that explains the emergence of directionality from the underlying brain network structure. We then apply the analytical methods to the anatomical brain networks of human, macaque, and mouse, successfully predicting simulation and empirical electroencephalographic data. The results demonstrate that the global directionality patterns in resting state brain networks can be predicted solely by their unique network structures. This study forms a foundation for a more comprehensive understanding of how neural information is directed and integrated in complex brain networks.

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.

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.

Systems biology of human epilepsy applied to patients with brain tumors.

PubMed

Mittal, Sandeep; Shah, Aashit K; Barkmeier, Daniel T; Loeb, Jeffrey A

2013-12-01

Epilepsy is a disease of recurrent seizures that can be associated with a wide variety of acquired and developmental brain lesions. Current medications for patients with epilepsy can suppress seizures; they do not cure or modify the underlying disease process. On the other hand, surgical removal of focal brain regions that produce seizures can be curative. This surgical procedure can be more precise with the placement of intracranial recording electrodes to identify brain regions that generate seizure activity as well as those that are critical for normal brain function. The detail that goes into these surgeries includes extensive neuroimaging, electrophysiology, and clinical data. Combined with precisely localized tissues removed, these data provide an unparalleled opportunity to learn about the interrelationships of many "systems" in the human brain not possible in just about any other human brain disorder. Herein, we describe a systems biology approach developed to study patients who undergo brain surgery for epilepsy and how we have begun to apply these methods to patients whose seizures are associated with brain tumors. A central goal of this clinical and translational research program is to improve our understanding of epilepsy and brain tumors and to improve diagnosis and treatment outcomes of both. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

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).

Seeing responsibility: can neuroimaging teach us anything about moral and legal responsibility?

PubMed

Wasserman, David; Johnston, Josephine

2014-01-01

As imaging technologies help us understand the structure and function of the brain, providing insight into human capabilities as basic as vision and as complex as memory, and human conditions as impairing as depression and as fraught as psychopathy, some have asked whether they can also help us understand human agency. Specifically, could neuroimaging lead us to reassess the socially significant practice of assigning and taking responsibility? While responsibility itself is not a psychological process open to investigation through neuroimaging, decision-making is. Over the past decade, different researchers and scholars have sought to use neuroimaging (or the results of neuroimaging studies) to investigate what is going on in the brain when we make decisions. The results of this research raise the question whether neuroscience-especially now that it includes neuroimaging-can and should alter our understandings of responsibility and our related practice of holding people responsible. It is this question that we investigate here. © 2014 by The Hastings Center.

Exploring how musical rhythm entrains brain activity with electroencephalogram frequency-tagging.

PubMed

Nozaradan, Sylvie

2014-12-19

The ability to perceive a regular beat in music and synchronize to this beat is a widespread human skill. Fundamental to musical behaviour, beat and meter refer to the perception of periodicities while listening to musical rhythms and often involve spontaneous entrainment to move on these periodicities. Here, we present a novel experimental approach inspired by the frequency-tagging approach to understand the perception and production of rhythmic inputs. This approach is illustrated here by recording the human electroencephalogram responses at beat and meter frequencies elicited in various contexts: mental imagery of meter, spontaneous induction of a beat from rhythmic patterns, multisensory integration and sensorimotor synchronization. Collectively, our observations support the view that entrainment and resonance phenomena subtend the processing of musical rhythms in the human brain. More generally, they highlight the potential of this approach to help us understand the link between the phenomenology of musical beat and meter and the bias towards periodicities arising under certain circumstances in the nervous system. Entrainment to music provides a highly valuable framework to explore general entrainment mechanisms as embodied in the human brain. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Age, gender, and hemispheric differences in iron deposition in the human brain: an in vivo MRI study.

PubMed

Xu, Xiaojun; Wang, Qidong; Zhang, Minming

2008-03-01

It is well known that iron accumulates in the brains of patients with various neurodegenerative diseases. To better understand disease-related iron changes, it is necessary to know the physiological distribution and accumulation of iron in the human brain. Studies have shown that brain iron levels increase with aging. However, the effects of gender and hemispheric laterality on iron accumulation and distribution are not well established. In this study, we estimated the brain iron levels in vivo in 78 healthy adults ranging in age 22 to 78 years using magnetic susceptibility-weighted phase imaging. The effects of age, gender, and hemispheric location on brain iron levels were evaluated within the framework of a general linear model. We found that the left hemisphere had higher iron levels than the right in the putamen, globus pallidus, substantia nigra, thalamus, and frontal white matter. We argue that the hemispheric asymmetry of iron content may underlie that of the dopaminergic system and may be related to motor lateralization in humans. In addition, significant age-related iron accumulation occurred in the putamen, red nucleus, and frontal white matter, but no gender-related differences in iron levels were detected. The results of this study extend our knowledge of the physiological distribution and accumulation of iron in the human brain.

The maternal brain and its plasticity in humans

PubMed Central

Kim, Pilyoung; Strathearn, Lane; Swain, James E.

2015-01-01

Early mother-infant relationships play important roles in infants’ optimal development. New mothers undergo neurobiological changes that support developing mother-infant relationships regardless of great individual differences in those relationships. In this article, we review the neural plasticity in human mothers’ brains based on functional magnetic resonance imaging (fMRI) studies. First, we review the neural circuits that are involved in establishing and maintaining mother-infant relationships. Second, we discuss early postpartum factors (e.g., birth and feeding methods, hormones, and parental sensitivity) that are associated with individual differences in maternal brain neuroplasticity. Third, we discuss abnormal changes in the maternal brain related to psychopathology (i.e., postpartum depression, posttraumatic stress disorder, substance abuse) and potential brain remodeling associated with interventions. Last, we highlight potentially important future research directions to better understand normative changes in the maternal brain and risks for abnormal changes that may disrupt early mother-infant relationships. PMID:26268151

Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.

PubMed

Soreq, Lilach; Rose, Jamie; Soreq, Eyal; Hardy, John; Trabzuni, Daniah; Cookson, Mark R; Smith, Colin; Ryten, Mina; Patani, Rickie; Ule, Jernej

2017-01-10

Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Putting the brain to work: neuroergonomics past, present, and future.

PubMed

Parasuraman, Raja; Wilson, Glenn F

2008-06-01

The authors describe research and applications in prominent areas of neuroergonomics. Because human factors/ergonomics examines behavior and mind at work, it should include the study of brain mechanisms underlying human performance. Neuroergonomic studies are reviewed in four areas: workload and vigilance, adaptive automation, neuroengineering, and molecular genetics and individual differences. Neuroimaging studies have helped identify the components of mental workload, workload assessment in complex tasks, and resource depletion in vigilance. Furthermore, real-time neurocognitive assessment of workload can trigger adaptive automation. Neural measures can also drive brain-computer interfaces to provide disabled users new communication channels. Finally, variants of particular genes can be associated with individual differences in specific cognitive functions. Neuroergonomics shows that considering what makes work possible - the human brain - can enrich understanding of the use of technology by humans and can inform technological design. Applications of neuroergonomics include the assessment of operator workload and vigilance, implementation of real-time adaptive automation, neuroengineering for people with disabilities, and design of selection and training methods.

Natural and Artificial Intelligence, Language, Consciousness, Emotion, and Anticipation

NASA Astrophysics Data System (ADS)

Dubois, Daniel M.

2010-11-01

The classical paradigm of the neural brain as the seat of human natural intelligence is too restrictive. This paper defends the idea that the neural ectoderm is the actual brain, based on the development of the human embryo. Indeed, the neural ectoderm includes the neural crest, given by pigment cells in the skin and ganglia of the autonomic nervous system, and the neural tube, given by the brain, the spinal cord, and motor neurons. So the brain is completely integrated in the ectoderm, and cannot work alone. The paper presents fundamental properties of the brain as follows. Firstly, Paul D. MacLean proposed the triune human brain, which consists to three brains in one, following the species evolution, given by the reptilian complex, the limbic system, and the neo-cortex. Secondly, the consciousness and conscious awareness are analysed. Thirdly, the anticipatory unconscious free will and conscious free veto are described in agreement with the experiments of Benjamin Libet. Fourthly, the main section explains the development of the human embryo and shows that the neural ectoderm is the whole neural brain. Fifthly, a conjecture is proposed that the neural brain is completely programmed with scripts written in biological low-level and high-level languages, in a manner similar to the programmed cells by the genetic code. Finally, it is concluded that the proposition of the neural ectoderm as the whole neural brain is a breakthrough in the understanding of the natural intelligence, and also in the future design of robots with artificial intelligence.

Introductory overview of research instruments for recording the electrical activity of neurons in the human brain

NASA Astrophysics Data System (ADS)

Garell, P. C.; Granner, M. A.; Noh, M. D.; Howard, M. A.; Volkov, I. O.; Gillies, G. T.

1998-12-01

Scientific advancement is often spurred by the development of new instruments for investigation. Over the last several decades, many new instruments have been produced to further our understanding of the physiology of the human brain. We present a partial overview of some of these instruments, paying particular attention to those which record the electrical activity of the human brain. We preface the review with a brief primer on neuroanatomy and physiology, followed by a discussion of the latest types of apparatus used to investigate various properties of the central nervous system. A special focus is on microelectrode investigations that employ both intracellular and extracellular methods of recording the electrical activity of single neurons; another is on the modern electroencephalographic, electrocorticographic, and magnetoencephalographic methods used to study the spontaneous and evoked field potentials of the brain. Some examples of clinical applications are included, where appropriate.

The BRAIN Initiative: developing technology to catalyse neuroscience discovery.

PubMed

Jorgenson, Lyric A; Newsome, William T; Anderson, David J; Bargmann, Cornelia I; Brown, Emery N; Deisseroth, Karl; Donoghue, John P; Hudson, Kathy L; Ling, Geoffrey S F; MacLeish, Peter R; Marder, Eve; Normann, Richard A; Sanes, Joshua R; Schnitzer, Mark J; Sejnowski, Terrence J; Tank, David W; Tsien, Roger Y; Ugurbil, Kamil; Wingfield, John C

2015-05-19

The evolution of the field of neuroscience has been propelled by the advent of novel technological capabilities, and the pace at which these capabilities are being developed has accelerated dramatically in the past decade. Capitalizing on this momentum, the United States launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative to develop and apply new tools and technologies for revolutionizing our understanding of the brain. In this article, we review the scientific vision for this initiative set forth by the National Institutes of Health and discuss its implications for the future of neuroscience research. Particular emphasis is given to its potential impact on the mapping and study of neural circuits, and how this knowledge will transform our understanding of the complexity of the human brain and its diverse array of behaviours, perceptions, thoughts and emotions.

The BRAIN Initiative: developing technology to catalyse neuroscience discovery

PubMed Central

Jorgenson, Lyric A.; Newsome, William T.; Anderson, David J.; Bargmann, Cornelia I.; Brown, Emery N.; Deisseroth, Karl; Donoghue, John P.; Hudson, Kathy L.; Ling, Geoffrey S. F.; MacLeish, Peter R.; Marder, Eve; Normann, Richard A.; Sanes, Joshua R.; Schnitzer, Mark J.; Sejnowski, Terrence J.; Tank, David W.; Tsien, Roger Y.; Ugurbil, Kamil; Wingfield, John C.

2015-01-01

The evolution of the field of neuroscience has been propelled by the advent of novel technological capabilities, and the pace at which these capabilities are being developed has accelerated dramatically in the past decade. Capitalizing on this momentum, the United States launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative to develop and apply new tools and technologies for revolutionizing our understanding of the brain. In this article, we review the scientific vision for this initiative set forth by the National Institutes of Health and discuss its implications for the future of neuroscience research. Particular emphasis is given to its potential impact on the mapping and study of neural circuits, and how this knowledge will transform our understanding of the complexity of the human brain and its diverse array of behaviours, perceptions, thoughts and emotions. PMID:25823863

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

Decoding the time-course of object recognition in the human brain: From visual features to categorical decisions.

PubMed

Contini, Erika W; Wardle, Susan G; Carlson, Thomas A

2017-10-01

Visual object recognition is a complex, dynamic process. Multivariate pattern analysis methods, such as decoding, have begun to reveal how the brain processes complex visual information. Recently, temporal decoding methods for EEG and MEG have offered the potential to evaluate the temporal dynamics of object recognition. Here we review the contribution of M/EEG time-series decoding methods to understanding visual object recognition in the human brain. Consistent with the current understanding of the visual processing hierarchy, low-level visual features dominate decodable object representations early in the time-course, with more abstract representations related to object category emerging later. A key finding is that the time-course of object processing is highly dynamic and rapidly evolving, with limited temporal generalisation of decodable information. Several studies have examined the emergence of object category structure, and we consider to what degree category decoding can be explained by sensitivity to low-level visual features. Finally, we evaluate recent work attempting to link human behaviour to the neural time-course of object processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human-like brain hemispheric dominance in birdsong learning.

PubMed

Moorman, Sanne; Gobes, Sharon M H; Kuijpers, Maaike; Kerkhofs, Amber; Zandbergen, Matthijs A; Bolhuis, Johan J

2012-07-31

Unlike nonhuman primates, songbirds learn to vocalize very much like human infants acquire spoken language. In humans, Broca's area in the frontal lobe and Wernicke's area in the temporal lobe are crucially involved in speech production and perception, respectively. Songbirds have analogous brain regions that show a similar neural dissociation between vocal production and auditory perception and memory. In both humans and songbirds, there is evidence for lateralization of neural responsiveness in these brain regions. Human infants already show left-sided dominance in their brain activation when exposed to speech. Moreover, a memory-specific left-sided dominance in Wernicke's area for speech perception has been demonstrated in 2.5-mo-old babies. It is possible that auditory-vocal learning is associated with hemispheric dominance and that this association arose in songbirds and humans through convergent evolution. Therefore, we investigated whether there is similar song memory-related lateralization in the songbird brain. We exposed male zebra finches to tutor or unfamiliar song. We found left-sided dominance of neuronal activation in a Broca-like brain region (HVC, a letter-based name) of juvenile and adult zebra finch males, independent of the song stimulus presented. In addition, juvenile males showed left-sided dominance for tutor song but not for unfamiliar song in a Wernicke-like brain region (the caudomedial nidopallium). Thus, left-sided dominance in the caudomedial nidopallium was specific for the song-learning phase and was memory-related. These findings demonstrate a remarkable neural parallel between birdsong and human spoken language, and they have important consequences for our understanding of the evolution of auditory-vocal learning and its neural mechanisms.

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.

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.

The Human Brain Project and neuromorphic computing

PubMed Central

Calimera, Andrea; Macii, Enrico; Poncino, Massimo

Summary Understanding how the brain manages billions of processing units connected via kilometers of fibers and trillions of synapses, while consuming a few tens of Watts could provide the key to a completely new category of hardware (neuromorphic computing systems). In order to achieve this, a paradigm shift for computing as a whole is needed, which will see it moving away from current “bit precise” computing models and towards new techniques that exploit the stochastic behavior of simple, reliable, very fast, low-power computing devices embedded in intensely recursive architectures. In this paper we summarize how these objectives will be pursued in the Human Brain Project. PMID:24139655

Declarative and nondeclarative memory: multiple brain systems supporting learning and memory.

PubMed

Squire, L R

1992-01-01

Abstract The topic of multiple forms of memory is considered from a biological point of view. Fact-and-event (declarative, explicit) memory is contrasted with a collection of non conscious (non-declarative, implicit) memory abilities including skills and habits, priming, and simple conditioning. Recent evidence is reviewed indicating that declarative and non declarative forms of memory have different operating characteristics and depend on separate brain systems. A brain-systems framework for understanding memory phenomena is developed in light of lesion studies involving rats, monkeys, and humans, as well as recent studies with normal humans using the divided visual field technique, event-related potentials, and positron emission tomography (PET).

Superior pattern processing is the essence of the evolved human brain

PubMed Central

Mattson, Mark P.

2014-01-01

Humans have long pondered the nature of their mind/brain and, particularly why its capacities for reasoning, communication and abstract thought are far superior to other species, including closely related anthropoids. This article considers superior pattern processing (SPP) as the fundamental basis of most, if not all, unique features of the human brain including intelligence, language, imagination, invention, and the belief in imaginary entities such as ghosts and gods. SPP involves the electrochemical, neuronal network-based, encoding, integration, and transfer to other individuals of perceived or mentally-fabricated patterns. During human evolution, pattern processing capabilities became increasingly sophisticated as the result of expansion of the cerebral cortex, particularly the prefrontal cortex and regions involved in processing of images. Specific patterns, real or imagined, are reinforced by emotional experiences, indoctrination and even psychedelic drugs. Impaired or dysregulated SPP is fundamental to cognitive and psychiatric disorders. A broader understanding of SPP mechanisms, and their roles in normal and abnormal function of the human brain, may enable the development of interventions that reduce irrational decisions and destructive behaviors. PMID:25202234

A Model for Bridging the Gap between Neuroscience and Education

ERIC Educational Resources Information Center

Tommerdahl, Jodi

2010-01-01

As the brain sciences make advances in our understanding of how the human brain functions, many educators are looking to findings from the neurosciences to inform classroom teaching methodologies. This paper takes the view that the neurosciences are an excellent source of knowledge regarding learning processes, but also provides a warning…

Human white matter and knowledge representation

PubMed Central

2018-01-01

Understanding how knowledge is represented in the human brain is a fundamental challenge in neuroscience. To date, most of the work on this topic has focused on knowledge representation in cortical areas and debated whether knowledge is represented in a distributed or localized fashion. Fang and colleagues provide evidence that brain connections and the white matter supporting such connections might play a significant role. The work opens new avenues of investigation, breaking through disciplinary boundaries across network neuroscience, computational neuroscience, cognitive science, and classical lesion studies. PMID:29698391

Human white matter and knowledge representation.

PubMed

Pestilli, Franco

2018-04-01

Understanding how knowledge is represented in the human brain is a fundamental challenge in neuroscience. To date, most of the work on this topic has focused on knowledge representation in cortical areas and debated whether knowledge is represented in a distributed or localized fashion. Fang and colleagues provide evidence that brain connections and the white matter supporting such connections might play a significant role. The work opens new avenues of investigation, breaking through disciplinary boundaries across network neuroscience, computational neuroscience, cognitive science, and classical lesion studies.

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

Dog experts' brains distinguish socially relevant body postures similarly in dogs and humans.

PubMed

Kujala, Miiamaaria V; Kujala, Jan; Carlson, Synnöve; Hari, Riitta

2012-01-01

We read conspecifics' social cues effortlessly, but little is known about our abilities to understand social gestures of other species. To investigate the neural underpinnings of such skills, we used functional magnetic resonance imaging to study the brain activity of experts and non-experts of dog behavior while they observed humans or dogs either interacting with, or facing away from a conspecific. The posterior superior temporal sulcus (pSTS) of both subject groups dissociated humans facing toward each other from humans facing away, and in dog experts, a distinction also occurred for dogs facing toward vs. away in a bilateral area extending from the pSTS to the inferior temporo-occipital cortex: the dissociation of dog behavior was significantly stronger in expert than control group. Furthermore, the control group had stronger pSTS responses to humans than dogs facing toward a conspecific, whereas in dog experts, the responses were of similar magnitude. These findings suggest that dog experts' brains distinguish socially relevant body postures similarly in dogs and humans.

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

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.

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.

The Science of Human Interaction and Teaching

ERIC Educational Resources Information Center

Yano, Kazuo

2013-01-01

There is a missing link between our understanding of teaching as high-level social phenomenon and teaching as a physiological phenomenon of brain activity. We suggest that the science of human interaction is the missing link. Using over one-million days of human-behavior data, we have discovered that "collective activenes" (CA), which indicates…

Understanding the pathophysiology of schizophrenia: Contributions from the Melbourne Psychiatric Brain Bank.

PubMed

Dean, Brian; Copolov, David; Scarr, Elizabeth

2016-11-01

The Melbourne Psychiatric Brain Bank came into existence 25years ago. This review focusses on lines of research that have used tissue from the Brain Bank over periods of time. Hence there is a discussion on the significance of changes in levels of serotonin 2A receptors in the cortex of patients with schizophrenia and the relevance of such changes with regards to the pathophysiology of the disorder. The extensive contribution made by studies using tissue from the Melbourne Psychiatric Brain Bank to understanding the role of muscarinic receptors in the pathophysiology and treatment of schizophrenia is summarised. Finally, findings using brain bank tissue and "omics" technologies are reviewed. In each case, findings using tissue from the Melbourne Psychiatric Brain Bank is placed in context with research carried out on human postmortem CNS in schizophrenia and with findings in other lines of research that can help explain the causes or consequences of changes in CNS molecular cytoarchitecture. This timely review of data from the Melbourne Psychiatric Brain Bank reinforces the challenges faced in trying to increase our understanding of the molecular pathophysiology of schizophrenia. Continuing to increase our understanding of the disorder is important as a precursor to identifying new drug targets that can be exploited to improve the treatment of a disorder where treatment resistance remains a significant problem (Millan et al., 2016). Copyright © 2016 Elsevier B.V. All rights reserved.

Why do many psychiatric disorders emerge during adolescence?

PubMed Central

Giedd, Jay N.; Keshavan, Matcheri; Paus, Tomáš

2008-01-01

What do we know about the maturation of the human brain during adolescence? Do structural changes in cerebral cortex reflect synaptic pruning? Are increases in white-matter volume driven by myelination? Is the adolescent brain more or less sensitive to reward? These are but a few questions we ask in this review while attempting to indicate how findings obtained in the healthy brain help in furthering our understanding of mental health during adolescence. PMID:19002191

Spatial organization of neurons in the frontal pole sets humans apart from great apes.

PubMed

Semendeferi, Katerina; Teffer, Kate; Buxhoeveden, Dan P; Park, Min S; Bludau, Sebastian; Amunts, Katrin; Travis, Katie; Buckwalter, Joseph

2011-07-01

Few morphological differences have been identified so far that distinguish the human brain from the brains of our closest relatives, the apes. Comparative analyses of the spatial organization of cortical neurons, including minicolumns, can aid our understanding of the functionally relevant aspects of microcircuitry. We measured horizontal spacing distance and gray-level ratio in layer III of 4 regions of human and ape cortex in all 6 living hominoid species: frontal pole (Brodmann area [BA] 10), and primary motor (BA 4), primary somatosensory (BA 3), and primary visual cortex (BA 17). Our results identified significant differences between humans and apes in the frontal pole (BA 10). Within the human brain, there were also significant differences between the frontal pole and 2 of the 3 regions studied (BA 3 and BA 17). Differences between BA 10 and BA 4 were present but did not reach significance. These findings in combination with earlier findings on BA 44 and BA 45 suggest that human brain evolution was likely characterized by an increase in the number and width of minicolumns and the space available for interconnectivity between neurons in the frontal lobe, especially the prefrontal cortex.

Traumatic brain injury and delayed sequelae: a review--traumatic brain injury and mild traumatic brain injury (concussion) are precursors to later-onset brain disorders, including early-onset dementia.

PubMed

Kiraly, Michael; Kiraly, Stephen J

2007-11-12

Brain injuries are too common. Most people are unaware of the incidence of and horrendous consequences of traumatic brain injury (TBI) and mild traumatic brain injury (MTBI). Research and the advent of sophisticated imaging have led to progression in the understanding of brain pathophysiology following TBI. Seminal evidence from animal and human experiments demonstrate links between TBI and the subsequent onset of premature, psychiatric syndromes and neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Objectives of this summary are, therefore, to instill appreciation regarding the importance of brain injury prevention, diagnosis, and treatment, and to increase awareness regarding the long-term delayed consequences following TBI.

A theory of marks and mind: the effect of notational systems on hominid brain evolution and child development with an emphasis on exchanges between mothers and children.

PubMed

Sheridan, Susan Rich

2005-01-01

A model of human language requires a theory of meaningful marks. Humans are the only species who use marks to think. A theory of marks identifies children's scribbles as significant behavior, while hypothesizing the importance of rotational systems to hominid brain evolution. By recognizing the importance of children's scribbles and drawings in developmental terms as well as in evolutionary terms, a marks-based rather than a predominantly speech-based theory of the human brain, language, and consciousness emerges. Combined research in anthropology, primatology, art history, neurology, child development (including research with deaf and blind children), gender studies and literacy suggests the importance of notational systems to human language, revealing the importance of mother/child interactions around marks and sounds to the development of an expressive, communicative, symbolic human brain. An understanding of human language is enriched by identifying marks carved on bone 1.9 million years ago as observational lunar calendar-keeping, pushing proto-literacy back dramatically. Neurologically, children recapitulate the meaningful marks of early hominins when they scribble and draw, reminding us that literacy belongs to humankind's earliest history. Even more than speech, such meaningful marks played - and continue to play - decisive roles in human brain evolution. The hominid brain required a model for integrative, transformative neural transfer. The research strongly suggests that humankind's multiple literacies (art, literature, scientific writing, mathematics and music) depended upon dyadic exchanges between hominid mothers and children, and that this exchange and sharing of visuo-spatial information drove the elaboration of human speech in terms of syntax, grammar and vocabulary. The human brain was spatial before it was linguistic. The child scribbles and draws before it speaks or writes. Children babble and scribble within the first two years of life. Hands and mouths are proximal on the sensory-motor cortex. Gestures accompany speech. Illiterate brains mis-pronounce nonsense sounds. Literate brains do not. Written language (work of the hands) enhances spoken language (work of the mouth). Until brain scans map the neurological links between human gesture, speech and marks in the context of mother/caregiver/child interactions, and research with literate and illiterate brains document even more precisely the long-term differences between these brains, the evolutionary pressure of marks on especially flexible maternal and infant brain tissue that occurred 1.9 million years, radically changing primate brain capabilities, requires an integrated theory of marks and mind.

Neuroscience, moral reasoning, and the law.

PubMed

Knabb, Joshua J; Welsh, Robert K; Ziebell, Joseph G; Reimer, Kevin S

2009-01-01

Modern advancements in functional magnetic resonance imaging (fMRI) technology have given neuroscientists the opportunity to more fully appreciate the brain's contribution to human behavior and decision making. Morality and moral reasoning are relative newcomers to the growing literature on decision neuroscience. With recent attention given to the salience of moral factors (e.g. moral emotions, moral reasoning) in the process of decision making, neuroscientists have begun to offer helpful frameworks for understanding the interplay between the brain, morality, and human decision making. These frameworks are relatively unfamiliar to the community of forensic psychologists, despite the fact that they offer an improved understanding of judicial decision making from a biological perspective. This article presents a framework reviewing how event-feature-emotion complexes (EFEC) are relevant to jurors and understanding complex criminal behavior. Future directions regarding converging fields of neuroscience and legal decision making are considered. Copyright 2009 John Wiley & Sons, Ltd.

Seeking Synthesis: The Integrative Problem in Understanding Language and Its Evolution.

PubMed

Dale, Rick; Kello, Christopher T; Schoenemann, P Thomas

2016-04-01

We discuss two problems for a general scientific understanding of language, sequences and synergies: how language is an intricately sequenced behavior and how language is manifested as a multidimensionally structured behavior. Though both are central in our understanding, we observe that the former tends to be studied more than the latter. We consider very general conditions that hold in human brain evolution and its computational implications, and identify multimodal and multiscale organization as two key characteristics of emerging cognitive function in our species. This suggests that human brains, and cognitive function specifically, became more adept at integrating diverse information sources and operating at multiple levels for linguistic performance. We argue that framing language evolution, learning, and use in terms of synergies suggests new research questions, and it may be a fruitful direction for new developments in theory and modeling of language as an integrated system. Copyright © 2016 Cognitive Science Society, Inc.

Mars can wait: facing the challenges of our civilization.

PubMed

Goodman, Geoffrey; Gershwin, M Eric; Bercovich, Dani

2014-12-01

We are overwhelmed by warnings about inevitable geophysical and human problems. Earth is beset by escalating, manmade, environmental crises and our exploding population will eventually lack water, food and vital materials. This suggests, together with increasing poverty, deepening social unrest and advanced techniques for mass killing, that civilization will break down long before atmospheric CO2 or resistant microbes become catastrophic. Despite intensive searching, life has not been found in space, even though thousands of planets have been found and life there may be as problematic and unpredictable as on Earth. The human brain is already a 'universe', with 85 billion neurons and a hundred trillion synapses, more than the stars in our galaxy. Understanding consciousness, the brain, its aging and pathologies, and eliminating the propensity for human aggression are urgent challenges. During 1958-2012, NASA spent $800 billion. In contrast, the annual cost of brain disease in the U.S. is $600 billion, more than cardiovascular disease and cancer combined. We suggest that a massive switching of financial and human resources is required to explore the full potential of the human brain. Visiting Mars can wait. We further propose a novel Two-Brain Hypothesis: the animal 'brain' evolved as two fundamentally different though interdependent, complementary organs: one electroionic (tangible, known and accessible), and the other, electromagnetic (intangible and difficult to access)--a relatively independent, stable, structured and functional 3D compendium of variously induced interacting EM fields.

Human connectome module pattern detection using a new multi-graph MinMax cut model.

PubMed

De, Wang; Wang, Yang; Nie, Feiping; Yan, Jingwen; Cai, Weidong; Saykin, Andrew J; Shen, Li; Huang, Heng

2014-01-01

Many recent scientific efforts have been devoted to constructing the human connectome using Diffusion Tensor Imaging (DTI) data for understanding the large-scale brain networks that underlie higher-level cognition in human. However, suitable computational network analysis tools are still lacking in human connectome research. To address this problem, we propose a novel multi-graph min-max cut model to detect the consistent network modules from the brain connectivity networks of all studied subjects. A new multi-graph MinMax cut model is introduced to solve this challenging computational neuroscience problem and the efficient optimization algorithm is derived. In the identified connectome module patterns, each network module shows similar connectivity patterns in all subjects, which potentially associate to specific brain functions shared by all subjects. We validate our method by analyzing the weighted fiber connectivity networks. The promising empirical results demonstrate the effectiveness of our method.

Nora Volkow: motivated neuroscientist.

PubMed

Volkow, Nora

2004-10-01

Nora Volkow claims to have always been curious about the workings of the human brain. Even as a medical student in her native Mexico, she investigated animal behavior with the ultimate goal of understanding human motivation. Upon completing her medical studies, in the early 80s, she moved to the U.S. to take advantage of emerging neuroimaging technologies, first during her psychiatry residency at New York University and Brookhaven National Laboratory, and then as a faculty member at the University of Texas in Houston. In Houston, Volkow embarked on seminal studies into human drug use and the functioning brain, which she continued to pursue, again at Brookhaven, during the subsequent two decades. Volkow established herself as an eminent researcher and proponent of neuroscience, and her insights into the brain have greatly advanced our appreciation of human behavior and motivation. In 2003, she took up her present position as Director of the National Institute on Drug Abuse.

An environment-dependent transcriptional network specifies human microglia identity.

PubMed

Gosselin, David; Skola, Dylan; Coufal, Nicole G; Holtman, Inge R; Schlachetzki, Johannes C M; Sajti, Eniko; Jaeger, Baptiste N; O'Connor, Carolyn; Fitzpatrick, Conor; Pasillas, Martina P; Pena, Monique; Adair, Amy; Gonda, David D; Levy, Michael L; Ransohoff, Richard M; Gage, Fred H; Glass, Christopher K

2017-06-23

Microglia play essential roles in central nervous system (CNS) homeostasis and influence diverse aspects of neuronal function. However, the transcriptional mechanisms that specify human microglia phenotypes are largely unknown. We examined the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue ex vivo and after transition to an in vitro environment. Transfer to a tissue culture environment resulted in rapid and extensive down-regulation of microglia-specific genes that were induced in primitive mouse macrophages after migration into the fetal brain. Substantial subsets of these genes exhibited altered expression in neurodegenerative and behavioral diseases and were associated with noncoding risk variants. These findings reveal an environment-dependent transcriptional network specifying microglia-specific programs of gene expression and facilitate efforts to understand the roles of microglia in human brain diseases. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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.

RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis

PubMed Central

Hosonaga, Mari; Koya, Ikuko

2017-01-01

Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non–small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients. PMID:28210624

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

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.

Segmentation of human brain using structural MRI.

PubMed

Helms, Gunther

2016-04-01

Segmentation of human brain using structural MRI is a key step of processing in imaging neuroscience. The methods have undergone a rapid development in the past two decades and are now widely available. This non-technical review aims at providing an overview and basic understanding of the most common software. Starting with the basis of structural MRI contrast in brain and imaging protocols, the concepts of voxel-based and surface-based segmentation are discussed. Special emphasis is given to the typical contrast features and morphological constraints of cortical and sub-cortical grey matter. In addition to the use for voxel-based morphometry, basic applications in quantitative MRI, cortical thickness estimations, and atrophy measurements as well as assignment of cortical regions and deep brain nuclei are briefly discussed. Finally, some fields for clinical applications are given.

Imaging of convection enhanced delivery of toxins in humans.

PubMed

Mehta, Ankit I; Choi, Bryan D; Raghavan, Raghu; Brady, Martin; Friedman, Allan H; Bigner, Darell D; Pastan, Ira; Sampson, John H

2011-03-01

Drug delivery of immunotoxins to brain tumors circumventing the blood brain barrier is a significant challenge. Convection-enhanced delivery (CED) circumvents the blood brain barrier through direct intracerebral application using a hydrostatic pressure gradient to percolate therapeutic compounds throughout the interstitial spaces of infiltrated brain and tumors. The efficacy of CED is determined through the distribution of the therapeutic agent to the targeted region. The vast majority of patients fail to receive a significant amount of coverage of the area at risk for tumor recurrence. Understanding this challenge, it is surprising that so little work has been done to monitor the delivery of therapeutic agents using this novel approach. Here we present a review of imaging in convection enhanced delivery monitoring of toxins in humans, and discuss future challenges in the field.

Imaging of Convection Enhanced Delivery of Toxins in Humans

PubMed Central

Mehta, Ankit I.; Choi, Bryan D.; Raghavan, Raghu; Brady, Martin; Friedman, Allan H.; Bigner, Darell D.; Pastan, Ira; Sampson, John H.

2011-01-01

Drug delivery of immunotoxins to brain tumors circumventing the blood brain barrier is a significant challenge. Convection-enhanced delivery (CED) circumvents the blood brain barrier through direct intracerebral application using a hydrostatic pressure gradient to percolate therapeutic compounds throughout the interstitial spaces of infiltrated brain and tumors. The efficacy of CED is determined through the distribution of the therapeutic agent to the targeted region. The vast majority of patients fail to receive a significant amount of coverage of the area at risk for tumor recurrence. Understanding this challenge, it is surprising that so little work has been done to monitor the delivery of therapeutic agents using this novel approach. Here we present a review of imaging in convection enhanced delivery monitoring of toxins in humans, and discuss future challenges in the field. PMID:22069706

Spatial cluster analysis of nanoscopically mapped serotonin receptors for classification of fixed brain tissue

NASA Astrophysics Data System (ADS)

Sams, Michael; Silye, Rene; Göhring, Janett; Muresan, Leila; Schilcher, Kurt; Jacak, Jaroslaw

2014-01-01

We present a cluster spatial analysis method using nanoscopic dSTORM images to determine changes in protein cluster distributions within brain tissue. Such methods are suitable to investigate human brain tissue and will help to achieve a deeper understanding of brain disease along with aiding drug development. Human brain tissue samples are usually treated postmortem via standard fixation protocols, which are established in clinical laboratories. Therefore, our localization microscopy-based method was adapted to characterize protein density and protein cluster localization in samples fixed using different protocols followed by common fluorescent immunohistochemistry techniques. The localization microscopy allows nanoscopic mapping of serotonin 5-HT1A receptor groups within a two-dimensional image of a brain tissue slice. These nanoscopically mapped proteins can be confined to clusters by applying the proposed statistical spatial analysis. Selected features of such clusters were subsequently used to characterize and classify the tissue. Samples were obtained from different types of patients, fixed with different preparation methods, and finally stored in a human tissue bank. To verify the proposed method, samples of a cryopreserved healthy brain have been compared with epitope-retrieved and paraffin-fixed tissues. Furthermore, samples of healthy brain tissues were compared with data obtained from patients suffering from mental illnesses (e.g., major depressive disorder). Our work demonstrates the applicability of localization microscopy and image analysis methods for comparison and classification of human brain tissues at a nanoscopic level. Furthermore, the presented workflow marks a unique technological advance in the characterization of protein distributions in brain tissue sections.

Individual T1-weighted/T2-weighted ratio brain networks: Small-worldness, hubs and modular organization

NASA Astrophysics Data System (ADS)

Wu, Huijun; Wang, Hao; Lü, Linyuan

Applying network science to investigate the complex systems has become a hot topic. In neuroscience, understanding the architectures of complex brain networks was a vital issue. An enormous amount of evidence had supported the brain was cost/efficiency trade-off with small-worldness, hubness and modular organization through the functional MRI and structural MRI investigations. However, the T1-weighted/T2-weighted (T1w/T2w) ratio brain networks were mostly unexplored. Here, we utilized a KL divergence-based method to construct large-scale individual T1w/T2w ratio brain networks and investigated the underlying topological attributes of these networks. Our results supported that the T1w/T2w ratio brain networks were comprised of small-worldness, an exponentially truncated power-law degree distribution, frontal-parietal hubs and modular organization. Besides, there were significant positive correlations between the network metrics and fluid intelligence. Thus, the T1w/T2w ratio brain networks open a new avenue to understand the human brain and are a necessary supplement for future MRI studies.

Neuronal correlates of the five factor model (FFM) of human personality: Multimodal imaging in a large healthy sample.

PubMed

Bjørnebekk, Astrid; Fjell, Anders M; Walhovd, Kristine B; Grydeland, Håkon; Torgersen, Svenn; Westlye, Lars T

2013-01-15

Advances in neuroimaging techniques have recently provided glimpse into the neurobiology of complex traits of human personality. Whereas some intriguing findings have connected aspects of personality to variations in brain morphology, the relations are complex and our current understanding is incomplete. Therefore, we aimed to provide a comprehensive investigation of brain-personality relations using a multimodal neuroimaging approach in a large sample comprising 265 healthy individuals. The NEO Personality Inventory was used to provide measures of core aspects of human personality, and imaging phenotypes included measures of total and regional brain volumes, regional cortical thickness and arealization, and diffusion tensor imaging indices of white matter (WM) microstructure. Neuroticism was the trait most clearly linked to brain structure. Higher neuroticism including facets reflecting anxiety, depression and vulnerability to stress was associated with smaller total brain volume, widespread decrease in WM microstructure, and smaller frontotemporal surface area. Higher scores on extraversion were associated with thinner inferior frontal gyrus, and conscientiousness was negatively associated with arealization of the temporoparietal junction. No reliable associations between brain structure and agreeableness and openness, respectively, were found. The results provide novel evidence of the associations between brain structure and variations in human personality, and corroborate previous findings of a consistent neuroanatomical basis of negative emotionality. Copyright © 2012 Elsevier Inc. All rights reserved.

Human-like brain hemispheric dominance in birdsong learning

PubMed Central

Moorman, Sanne; Gobes, Sharon M. H.; Kuijpers, Maaike; Kerkhofs, Amber; Zandbergen, Matthijs A.; Bolhuis, Johan J.

2012-01-01

Unlike nonhuman primates, songbirds learn to vocalize very much like human infants acquire spoken language. In humans, Broca’s area in the frontal lobe and Wernicke’s area in the temporal lobe are crucially involved in speech production and perception, respectively. Songbirds have analogous brain regions that show a similar neural dissociation between vocal production and auditory perception and memory. In both humans and songbirds, there is evidence for lateralization of neural responsiveness in these brain regions. Human infants already show left-sided dominance in their brain activation when exposed to speech. Moreover, a memory-specific left-sided dominance in Wernicke’s area for speech perception has been demonstrated in 2.5-mo-old babies. It is possible that auditory-vocal learning is associated with hemispheric dominance and that this association arose in songbirds and humans through convergent evolution. Therefore, we investigated whether there is similar song memory-related lateralization in the songbird brain. We exposed male zebra finches to tutor or unfamiliar song. We found left-sided dominance of neuronal activation in a Broca-like brain region (HVC, a letter-based name) of juvenile and adult zebra finch males, independent of the song stimulus presented. In addition, juvenile males showed left-sided dominance for tutor song but not for unfamiliar song in a Wernicke-like brain region (the caudomedial nidopallium). Thus, left-sided dominance in the caudomedial nidopallium was specific for the song-learning phase and was memory-related. These findings demonstrate a remarkable neural parallel between birdsong and human spoken language, and they have important consequences for our understanding of the evolution of auditory-vocal learning and its neural mechanisms. PMID:22802637

Putting the Mind in the Brain: Promoting an Appreciation of the Biological Basis to Understanding Human Behavior

ERIC Educational Resources Information Center

Neumann, David L.

2010-01-01

A surprising number of students in psychology, behavioral science, and related social science classes fail to appreciate the importance of biological mechanisms to understanding behavior. To help teachers promote this understanding, this paper outlines six sources of evidence. These are (a) phylogenetic, (b) genetic/developmental, (c) clinical,…

Cerebral Dominance: Its Use in Understanding Learning Styles and Behavioral Patterns.

ERIC Educational Resources Information Center

Matthews, Doris B.

Studies of the human brain suggest that cerebral dominance, the preference for either the right or the left hemisphere to direct the body's behavior, plays a causal role in distinctive learning styles and behavior patterns. The two halves of the brain are physically almost identical at birth, but childhood experiences which utilize one hemisphere…

Big data and the industrialization of neuroscience: A safe roadmap for understanding the brain?

PubMed

Frégnac, Yves

2017-10-27

New technologies in neuroscience generate reams of data at an exponentially increasing rate, spurring the design of very-large-scale data-mining initiatives. Several supranational ventures are contemplating the possibility of achieving, within the next decade(s), full simulation of the human brain. Copyright © 2017, American Association for the Advancement of Science.

Understanding in an Instant: Neurophysiological Evidence for Mechanistic Language Circuits in the Brain

ERIC Educational Resources Information Center

Pulvermuller, Friedemann; Shtyrov, Yury; Hauk, Olaf

2009-01-01

How long does it take the human mind to grasp the idea when hearing or reading a sentence? Neurophysiological methods looking directly at the time course of brain activity indexes of comprehension are critical for finding the answer to this question. As the dominant cognitive approaches, models of serial/cascaded and parallel processing, make…

Understanding the mechanisms of familiar voice-identity recognition in the human brain.

PubMed

Maguinness, Corrina; Roswandowitz, Claudia; von Kriegstein, Katharina

2018-03-31

Humans have a remarkable skill for voice-identity recognition: most of us can remember many voices that surround us as 'unique'. In this review, we explore the computational and neural mechanisms which may support our ability to represent and recognise a unique voice-identity. We examine the functional architecture of voice-sensitive regions in the superior temporal gyrus/sulcus, and bring together findings on how these regions may interact with each other, and additional face-sensitive regions, to support voice-identity processing. We also contrast findings from studies on neurotypicals and clinical populations which have examined the processing of familiar and unfamiliar voices. Taken together, the findings suggest that representations of familiar and unfamiliar voices might dissociate in the human brain. Such an observation does not fit well with current models for voice-identity processing, which by-and-large assume a common sequential analysis of the incoming voice signal, regardless of voice familiarity. We provide a revised audio-visual integrative model of voice-identity processing which brings together traditional and prototype models of identity processing. This revised model includes a mechanism of how voice-identity representations are established and provides a novel framework for understanding and examining the potential differences in familiar and unfamiliar voice processing in the human brain. Copyright © 2018 Elsevier Ltd. All rights reserved.

Epigenetic and gene expression changes in the adolescent brain: What have we learned from animal models?

PubMed

Mychasiuk, Richelle; Metz, Gerlinde A S

2016-11-01

Adolescence is defined as the gradual period of transition between childhood and adulthood that is characterized by significant brain maturation, growth spurts, sexual maturation, and heightened social interaction. Although originally believed to be a uniquely human aspect of development, rodent and non-human primates demonstrate maturational patterns that distinctly support an adolescent stage. As epigenetic processes are essential for development and differentiation, but also transpire in mature cells in response to environmental influences, they are an important aspect of adolescent brain maturation. The purpose of this review article was to examine epigenetic programming in animal models of brain maturation during adolescence. The discussion focuses on animal models to examine three main concepts; epigenetic processes involved in normal adolescent brain maturation, the influence of fetal programming on adolescent brain development and the epigenome, and finally, postnatal experiences such as exercise and drugs that modify epigenetic processes important for adolescent brain maturation. This corollary emphasizes the utility of animal models to further our understanding of complex processes such as epigenetic regulation and brain development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Investigating large-scale brain dynamics using field potential recordings: analysis and interpretation.

PubMed

Pesaran, Bijan; Vinck, Martin; Einevoll, Gaute T; Sirota, Anton; Fries, Pascal; Siegel, Markus; Truccolo, Wilson; Schroeder, Charles E; Srinivasan, Ramesh

2018-06-25

New technologies to record electrical activity from the brain on a massive scale offer tremendous opportunities for discovery. Electrical measurements of large-scale brain dynamics, termed field potentials, are especially important to understanding and treating the human brain. Here, our goal is to provide best practices on how field potential recordings (electroencephalograms, magnetoencephalograms, electrocorticograms and local field potentials) can be analyzed to identify large-scale brain dynamics, and to highlight critical issues and limitations of interpretation in current work. We focus our discussion of analyses around the broad themes of activation, correlation, communication and coding. We provide recommendations for interpreting the data using forward and inverse models. The forward model describes how field potentials are generated by the activity of populations of neurons. The inverse model describes how to infer the activity of populations of neurons from field potential recordings. A recurring theme is the challenge of understanding how field potentials reflect neuronal population activity given the complexity of the underlying brain systems.

Multimodal imaging of temporal processing in typical and atypical language development.

PubMed

Kovelman, Ioulia; Wagley, Neelima; Hay, Jessica S F; Ugolini, Margaret; Bowyer, Susan M; Lajiness-O'Neill, Renee; Brennan, Jonathan

2015-03-01

New approaches to understanding language and reading acquisition propose that the human brain's ability to synchronize its neural firing rate to syllable-length linguistic units may be important to children's ability to acquire human language. Yet, little evidence from brain imaging studies has been available to support this proposal. Here, we summarize three recent brain imaging (functional near-infrared spectroscopy (fNIRS), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG)) studies from our laboratories with young English-speaking children (aged 6-12 years). In the first study (fNIRS), we used an auditory beat perception task to show that, in children, the left superior temporal gyrus (STG) responds preferentially to rhythmic beats at 1.5 Hz. In the second study (fMRI), we found correlations between children's amplitude rise-time sensitivity, phonological awareness, and brain activation in the left STG. In the third study (MEG), typically developing children outperformed children with autism spectrum disorder in extracting words from rhythmically rich foreign speech and displayed different brain activation during the learning phase. The overall findings suggest that the efficiency with which left temporal regions process slow temporal (rhythmic) information may be important for gains in language and reading proficiency. These findings carry implications for better understanding of the brain's mechanisms that support language and reading acquisition during both typical and atypical development. © 2014 New York Academy of Sciences.

Walking through Architectural Spaces: The Impact of Interior Forms on Human Brain Dynamics

PubMed Central

Banaei, Maryam; Hatami, Javad; Yazdanfar, Abbas; Gramann, Klaus

2017-01-01

Neuroarchitecture uses neuroscientific tools to better understand architectural design and its impact on human perception and subjective experience. The form or shape of the built environment is fundamental to architectural design, but not many studies have shown the impact of different forms on the inhabitants’ emotions. This study investigated the neurophysiological correlates of different interior forms on the perceivers’ affective state and the accompanying brain activity. To understand the impact of naturalistic three-dimensional (3D) architectural forms, it is essential to perceive forms from different perspectives. We computed clusters of form features extracted from pictures of residential interiors and constructed exemplary 3D room models based on and representing different formal clusters. To investigate human brain activity during 3D perception of architectural spaces, we used a mobile brain/body imaging (MoBI) approach recording the electroencephalogram (EEG) of participants while they naturally walk through different interior forms in virtual reality (VR). The results revealed a strong impact of curvature geometries on activity in the anterior cingulate cortex (ACC). Theta band activity in ACC correlated with specific feature types (rs (14) = 0.525, p = 0.037) and geometry (rs (14) = −0.579, p = 0.019), providing evidence for a role of this structure in processing architectural features beyond their emotional impact. The posterior cingulate cortex and the occipital lobe were involved in the perception of different room perspectives during the stroll through the rooms. This study sheds new light on the use of mobile EEG and VR in architectural studies and provides the opportunity to study human brain dynamics in participants that actively explore and realistically experience architectural spaces. PMID:29033807

Walking through Architectural Spaces: The Impact of Interior Forms on Human Brain Dynamics.

PubMed

Banaei, Maryam; Hatami, Javad; Yazdanfar, Abbas; Gramann, Klaus

2017-01-01

Neuroarchitecture uses neuroscientific tools to better understand architectural design and its impact on human perception and subjective experience. The form or shape of the built environment is fundamental to architectural design, but not many studies have shown the impact of different forms on the inhabitants' emotions. This study investigated the neurophysiological correlates of different interior forms on the perceivers' affective state and the accompanying brain activity. To understand the impact of naturalistic three-dimensional (3D) architectural forms, it is essential to perceive forms from different perspectives. We computed clusters of form features extracted from pictures of residential interiors and constructed exemplary 3D room models based on and representing different formal clusters. To investigate human brain activity during 3D perception of architectural spaces, we used a mobile brain/body imaging (MoBI) approach recording the electroencephalogram (EEG) of participants while they naturally walk through different interior forms in virtual reality (VR). The results revealed a strong impact of curvature geometries on activity in the anterior cingulate cortex (ACC). Theta band activity in ACC correlated with specific feature types ( r s (14) = 0.525, p = 0.037) and geometry ( r s (14) = -0.579, p = 0.019), providing evidence for a role of this structure in processing architectural features beyond their emotional impact. The posterior cingulate cortex and the occipital lobe were involved in the perception of different room perspectives during the stroll through the rooms. This study sheds new light on the use of mobile EEG and VR in architectural studies and provides the opportunity to study human brain dynamics in participants that actively explore and realistically experience architectural spaces.

Central Processing of the Chemical Senses: An Overview

PubMed Central

2010-01-01

Our knowledge regarding the neural processing of the three chemical senses has been considerably lagging behind that of our other senses. It is only during the last 25 years that significant advances have been made in our understanding of where in the human brain odors, tastants, and trigeminal stimuli are processed. Here, we provide an overview of the current knowledge of how the human brain processes chemical stimuli based on findings in neuroimaging studies using positron emission tomography and functional magnetic resonance imaging. Additionally, we provide new insights from recent meta-analyses, on the basis of all published neuroimaging studies of the chemical senses, of where the chemical senses converge in the brain. PMID:21503268

Creating a human brain proteome atlas--14th HUPO BPP workshop September 20-21, 2010, Sydney, Australia.

PubMed

Gröttrup, Bernd; Marcus, Katrin; Grinberg, Lea T; Lee, Sang K; Meyer, Helmut E; Park, Young M

2011-08-01

The HUPO Brain Proteome Project (HUPO BPP) held its 14th workshop during the HUPO 9th Annual World Congress in Sydney, Australia. The principal aim of this project is to discover prognostic and diagnostic biomarkers associated with neurodegenerative diseases and brain aging, with the ultimate objective of obtaining a better understanding of these conditions and creating roads for the development of novel diagnostic techniques and effective treatments. The attendees came together to discuss progress in the human clinical neuroproteomics and to define the needs and guidelines required for more advanced proteomics approaches. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The (Bio)Politicization of Neuroscience in Australian Early Years Policies: Fostering Brain-Resources "as" Human Capital

ERIC Educational Resources Information Center

Millei, Zsuzsa; Joronen, Mikko

2016-01-01

At the present, human capital theory (HCT) and neuroscience reasoning are dominant frameworks in early childhood education and care (ECEC) worldwide. Popular since the 1960s, HCT has provided an economic understanding of human beings and offered strategies to manage the population with the promise of bringing improvements to nations. Neuroscience…

From data processing to mental organs: an interdisciplinary path to cognitive neuroscience.

PubMed

Patharkar, Manoj

2011-01-01

Human brain is a highly evolved coordinating mechanism in the species Homo sapiens. It is only in the last 100 years that extensive knowledge of the intricate structure and complex functioning of the human brain has been acquired, though a lot is yet to be known. However, from the beginning of civilisation, people have been conscious of a 'mind' which has been considered the origin of all scientific and cultural development. Philosophers have discussed at length the various attributes of consciousness. At the same time, most of the philosophical or scientific frameworks have directly or indirectly implied mind-body duality. It is now imperative that we develop an integrated approach to understand the interconnection between mind and consciousness on one hand and brain on the other. This paper begins with the proposition that the structure of the brain is analogous, at least to certain extent, to that of the computer system. Of course, it is much more sophisticated and complex. The second proposition is that the Chomskyean concept of 'mental organs' is a good working hypothesis that tries to characterise this complexity in terms of an innate cognitive framework. By following this dual approach, brain as a data processing system and brain as a superstructure of intricately linked mental organs, we can move toward a better understanding of 'mind' within the framework of empirical science. The one 'mental organ' studied extensively in Chomskyean terms is 'language faculty' which is unique in its relation to brain, mind and consciousness.

Translational aspects of blood-brain barrier transport and central nervous system effects of drugs: from discovery to patients.

PubMed

de Lange, E C M; Hammarlund-Udenaes, M

2015-04-01

The development of CNS drugs is associated with high failure rates. It is postulated that too much focus has been put on BBB permeability and too little on understanding BBB transport, which is the main limiting factor in drug delivery to the brain. An integrated approach to collecting, understanding, and handling pharmacokinetic-pharmacodynamic information from early discovery stages to the clinic is therefore recommended in order to improve translation to human drug treatment. © 2015 American Society for Clinical Pharmacology and Therapeutics.

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

PubMed Central

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

2013-01-01

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

Brain temperature and its fundamental properties: a review for clinical neuroscientists

PubMed Central

Wang, Huan; Wang, Bonnie; Normoyle, Kieran P.; Jackson, Kevin; Spitler, Kevin; Sharrock, Matthew F.; Miller, Claire M.; Best, Catherine; Llano, Daniel; Du, Rose

2014-01-01

Brain temperature, as an independent therapeutic target variable, has received increasingly intense clinical attention. To date, brain hypothermia represents the most potent neuroprotectant in laboratory studies. Although the impact of brain temperature is prevalent in a number of common human diseases including: head trauma, stroke, multiple sclerosis, epilepsy, mood disorders, headaches, and neurodegenerative disorders, it is evident and well recognized that the therapeutic application of induced hypothermia is limited to a few highly selected clinical conditions such as cardiac arrest and hypoxic ischemic neonatal encephalopathy. Efforts to understand the fundamental aspects of brain temperature regulation are therefore critical for the development of safe, effective, and pragmatic clinical treatments for patients with brain injuries. Although centrally-mediated mechanisms to maintain a stable body temperature are relatively well established, very little is clinically known about brain temperature's spatial and temporal distribution, its physiological and pathological fluctuations, and the mechanism underlying brain thermal homeostasis. The human brain, a metabolically “expensive” organ with intense heat production, is sensitive to fluctuations in temperature with regards to its functional activity and energy efficiency. In this review, we discuss several critical aspects concerning the fundamental properties of brain temperature from a clinical perspective. PMID:25339859

Is the ferret a suitable species for studying perinatal brain injury?

PubMed Central

Empie, Kristen; Rangarajan, Vijayeta; Juul, Sandra E.

2016-01-01

Complications of prematurity often disrupt normal brain development and/or cause direct damage to the developing brain, resulting in poor neurodevelopmental outcomes. Physiologically relevant animal models of perinatal brain injury can advance our understanding of these influences and thereby provide opportunities to develop therapies and improve long-term outcomes. While there are advantages to currently available small animal models, there are also significant drawbacks that have limited translation of research findings to humans. Large animal models such as newborn pig, sheep and nonhuman primates have complex brain development more similar to humans, but these animals are expensive, and developmental testing of sheep and piglets is limited. Ferrets (Mustela putorius furo) are born lissencephalic and undergo postnatal cortical folding to form complex gyrencephalic brains. This review examines whether ferrets might provide a novel intermediate animal model of neonatal brain disease that has the benefit of a gyrified, altricial brain in a small animal. It summarizes attributes of ferret brain growth and development that make it an appealing animal in which to model perinatal brain injury. We postulate that because of their innate characteristics, ferrets have great potential in neonatal neurodevelopmental studies. PMID:26102988

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

SEGMA: An Automatic SEGMentation Approach for Human Brain MRI Using Sliding Window and Random Forests

PubMed Central

Serag, Ahmed; Wilkinson, Alastair G.; Telford, Emma J.; Pataky, Rozalia; Sparrow, Sarah A.; Anblagan, Devasuda; Macnaught, Gillian; Semple, Scott I.; Boardman, James P.

2017-01-01

Quantitative volumes from brain magnetic resonance imaging (MRI) acquired across the life course may be useful for investigating long term effects of risk and resilience factors for brain development and healthy aging, and for understanding early life determinants of adult brain structure. Therefore, there is an increasing need for automated segmentation tools that can be applied to images acquired at different life stages. We developed an automatic segmentation method for human brain MRI, where a sliding window approach and a multi-class random forest classifier were applied to high-dimensional feature vectors for accurate segmentation. The method performed well on brain MRI data acquired from 179 individuals, analyzed in three age groups: newborns (38–42 weeks gestational age), children and adolescents (4–17 years) and adults (35–71 years). As the method can learn from partially labeled datasets, it can be used to segment large-scale datasets efficiently. It could also be applied to different populations and imaging modalities across the life course. PMID:28163680

Human Brain Proteome Project - 12th HUPO BPP Workshop. 26 September 2009, Toronto, Canada.

PubMed

Gröttrup, Bernd; Eisenacher, Martin; Stephan, Christian; Marcus, Katrin; Lee, Bonghee; Meyer, Helmut E; Park, Young Mok

2010-06-01

The HUPO Brain Proteome Project (HUPO BPP) held its 12th workshop in Toronto on 26 September 2009 prior to the HUPO VIII World Congress. The principal aim of this project is to obtain a better understanding of neurodiseases and ageing, with the ultimate objective of discovering prognostic and diagnostic biomarkers, in addition to the development of novel diagnostic techniques and new medications. The attendees came together to discuss progress in the human clinical neuroproteomics and to define the needs and guidelines required for more advanced proteomic approaches.

Cortical representations of communication sounds.

PubMed

Heiser, Marc A; Cheung, Steven W

2008-10-01

This review summarizes recent research into cortical processing of vocalizations in animals and humans. There has been a resurgent interest in this topic accompanied by an increased number of studies using animal models with complex vocalizations and new methods in human brain imaging. Recent results from such studies are discussed. Experiments have begun to reveal the bilateral cortical fields involved in communication sound processing and the transformations of neural representations that occur among those fields. Advances have also been made in understanding the neuronal basis of interaction between developmental exposures and behavioral experiences with vocalization perception. Exposure to sounds during the developmental period produces large effects on brain responses, as do a variety of specific trained tasks in adults. Studies have also uncovered a neural link between the motor production of vocalizations and the representation of vocalizations in cortex. Parallel experiments in humans and animals are answering important questions about vocalization processing in the central nervous system. This dual approach promises to reveal microscopic, mesoscopic, and macroscopic principles of large-scale dynamic interactions between brain regions that underlie the complex phenomenon of vocalization perception. Such advances will yield a greater understanding of the causes, consequences, and treatment of disorders related to speech processing.

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

TNF-α enhancement of CD62E mediates adhesion of non-small cell lung cancer cells to brain endothelium via CD15 in lung-brain metastasis.

PubMed

Jassam, Samah A; Maherally, Zaynah; Smith, James R; Ashkan, Keyoumars; Roncaroli, Federico; Fillmore, Helen L; Pilkington, Geoffrey J

2016-05-01

CD15, which is overexpressed on various cancers, has been reported as a cell adhesion molecule that plays a key role in non-CNS metastasis. However, the role of CD15 in brain metastasis is largely unexplored. This study provides a better understanding of CD15/CD62E interaction, enhanced by tumor necrosis factor-α (TNF-α), and its correlation with brain metastasis in non-small cell lung cancer (NSCLC). CD15 and E-selectin (CD62E) expression was demonstrated in both human primary and metastatic NSCLC cells using flow cytometry, immunofluorescence, and Western blotting. The role of CD15 was investigated using an adhesion assay under static and physiological flow live-cell conditions. Human tissue sections were examined using immunohistochemistry. CD15, which was weakly expressed on hCMEC/D3 human brain endothelial cells, was expressed at high levels on metastatic NSCLC cells (NCI-H1299, SEBTA-001, and SEBTA-005) and at lower levels on primary NSCLC (COR-L105 and A549) cells (P < .001). The highest expression of CD62E was observed on hCMEC/D3 cells activated with TNF-α, with lower levels on metastatic NSCLC cells followed by primary NSCLC cells. Metastatic NSCLC cells adhered most strongly to hCMEC/D3 compared with primary NSCLC cells. CD15 immunoblocking decreased cancer cell adhesion to brain endothelium under static and shear stress conditions (P < .0001), confirming a correlation between CD15 and cerebral metastasis. Both CD15 and CD62E expression were detected in lung metastatic brain biopsies. This study enhances the understanding of cancer cell-brain endothelial adhesion and confirms that CD15 plays a crucial role in adhesion in concert with TNF-α activation of its binding partner, CD62E. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

TNF-α enhancement of CD62E mediates adhesion of non–small cell lung cancer cells to brain endothelium via CD15 in lung-brain metastasis

PubMed Central

Jassam, Samah A.; Maherally, Zaynah; Smith, James R.; Ashkan, Keyoumars; Roncaroli, Federico; Fillmore, Helen L.; Pilkington, Geoffrey J.

2016-01-01

Background CD15, which is overexpressed on various cancers, has been reported as a cell adhesion molecule that plays a key role in non-CNS metastasis. However, the role of CD15 in brain metastasis is largely unexplored. This study provides a better understanding of CD15/CD62E interaction, enhanced by tumor necrosis factor-α (TNF-α), and its correlation with brain metastasis in non–small cell lung cancer (NSCLC). Methods CD15 and E-selectin (CD62E) expression was demonstrated in both human primary and metastatic NSCLC cells using flow cytometry, immunofluorescence, and Western blotting. The role of CD15 was investigated using an adhesion assay under static and physiological flow live-cell conditions. Human tissue sections were examined using immunohistochemistry. Results CD15, which was weakly expressed on hCMEC/D3 human brain endothelial cells, was expressed at high levels on metastatic NSCLC cells (NCI-H1299, SEBTA-001, and SEBTA-005) and at lower levels on primary NSCLC (COR-L105 and A549) cells (P < .001). The highest expression of CD62E was observed on hCMEC/D3 cells activated with TNF-α, with lower levels on metastatic NSCLC cells followed by primary NSCLC cells. Metastatic NSCLC cells adhered most strongly to hCMEC/D3 compared with primary NSCLC cells. CD15 immunoblocking decreased cancer cell adhesion to brain endothelium under static and shear stress conditions (P < .0001), confirming a correlation between CD15 and cerebral metastasis. Both CD15 and CD62E expression were detected in lung metastatic brain biopsies. Conclusion This study enhances the understanding of cancer cell-brain endothelial adhesion and confirms that CD15 plays a crucial role in adhesion in concert with TNF-α activation of its binding partner, CD62E. PMID:26472821

Human brain metastatic stroma attracts breast cancer cells via chemokines CXCL16 and CXCL12.

PubMed

Chung, Brile; Esmaeili, Ali A; Gopalakrishna-Pillai, Sailesh; Murad, John P; Andersen, Emily S; Kumar Reddy, Naveen; Srinivasan, Gayathri; Armstrong, Brian; Chu, Caleb; Kim, Young; Tong, Tommy; Waisman, James; Yim, John H; Badie, Behnam; Lee, Peter P

2017-01-01

The tumor microenvironment is composed of heterogeneous populations of cells, including cancer, immune, and stromal cells. Progression of tumor growth and initiation of metastasis is critically dependent on the reciprocal interactions between cancer cells and stroma. Through RNA-Seq and protein analyses, we found that cancer-associated fibroblasts derived from human breast cancer brain metastasis express significantly higher levels of chemokines CXCL12 and CXCL16 than fibroblasts from primary breast tumors or normal breast. To further understand the interplay between cancer cells and cancer-associated fibroblasts from each site, we developed three-dimensional organoids composed of patient-derived primary or brain metastasis cancer cells with matching cancer-associated fibroblasts. Three-dimensional CAF aggregates generated from brain metastasis promote migration of cancer cells more effectively than cancer-associated fibroblast aggregates derived from primary tumor or normal breast stromal cells. Treatment with a CXCR4 antagonist and/or CXCL16 neutralizing antibody, alone or in combination, significantly inhibited migration of cancer cells to brain metastatic cancer-associated fibroblast aggregates. These results demonstrate that human brain metastasis cancer-associated fibroblasts potently attract breast cancer cells via chemokines CXCL12 and CXCL16, and blocking CXCR6-CXCL16/CXCR4-CXCL12 receptor-ligand interactions may be an effective therapy for preventing breast cancer brain metastasis.

Comprehensive cellular‐resolution atlas of the adult human brain

PubMed Central

Royall, Joshua J.; Sunkin, Susan M.; Ng, Lydia; Facer, Benjamin A.C.; Lesnar, Phil; Guillozet‐Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A.; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A.; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L.; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A.; Koch, Christof; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Zielke, H. Ronald; Hohmann, John G.; Jones, Allan R.; Bernard, Amy; Hawrylycz, Michael J.; Hof, Patrick R.; Fischl, Bruce

2016-01-01

ABSTRACT Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

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.

What can we learn from a two-brain approach to verbal interaction?

PubMed

Schoot, Lotte; Hagoort, Peter; Segaert, Katrien

2016-09-01

Verbal interaction is one of the most frequent social interactions humans encounter on a daily basis. In the current paper, we zoom in on what the multi-brain approach has contributed, and can contribute in the future, to our understanding of the neural mechanisms supporting verbal interaction. Indeed, since verbal interaction can only exist between individuals, it seems intuitive to focus analyses on inter-individual neural markers, i.e. between-brain neural coupling. To date, however, there is a severe lack of theoretically-driven, testable hypotheses about what between-brain neural coupling actually reflects. In this paper, we develop a testable hypothesis in which between-pair variation in between-brain neural coupling is of key importance. Based on theoretical frameworks and empirical data, we argue that the level of between-brain neural coupling reflects speaker-listener alignment at different levels of linguistic and extra-linguistic representation. We discuss the possibility that between-brain neural coupling could inform us about the highest level of inter-speaker alignment: mutual understanding. Copyright © 2016 Elsevier Ltd. All rights reserved.

White Matter Maturation Supports the Development of Reasoning Ability through Its Influence on Processing Speed

ERIC Educational Resources Information Center

Ferrer, Emilio; Whitaker, Kirstie J.; Steele, Joel S.; Green, Chloe T.; Wendelken, Carter; Bunge, Silvia A.

2013-01-01

The structure of the human brain changes in several ways throughout childhood and adolescence. Perhaps the most salient of these changes is the strengthening of white matter tracts that enable distal brain regions to communicate with one another more quickly and efficiently. Here, we sought to understand whether and how white matter changes…

Neurotechnology and Society: Strengthening Responsible Innovation in Brain Science.

PubMed

Garden, Hermann; Bowman, Diana M; Haesler, Sebastian; Winickoff, David E

2016-11-02

Technological advances have the potential to dramatically increase our understanding of the human brain, treat and cure injury and disease, and enhance our general well-being. While advances in neuroscience hold great promise, they also raise profound ethical, legal, and social questions. In this vein, the Organization for Economic Co-operation and Development (OECD) convened an international workshop in September 2016 to explore responsible research and innovation in brain science. Copyright © 2016 OECD. Published by Elsevier Inc. All rights reserved.

Temporal Loss of Tsc1: Neural Development and Brain Disease in Tuberous Sclerosis

DTIC Science & Technology

2014-06-01

funding. He was also was aware of my being named as a Simmons Foundation Autism Research Initiative (SFARI) investigator. !Regardless, the outcome is...2001). The thalamus has also been linked to the autism component in human TS (Asano et al., 2001) and is poised to play an important role in brain...nearly all TS patients and cognitive deficits and autism in a substantial cohort of TS patients. However, a deep understanding of how the TS brain

Perceptual elements in brain mechanisms of acoustic communication in humans and nonhuman primates.

PubMed

Reser, David H; Rosa, Marcello

2014-12-01

Ackermann et al. outline a model for elaboration of subcortical motor outputs as a driving force for the development of the apparently unique behaviour of language in humans. They emphasize circuits in the striatum and midbrain, and acknowledge, but do not explore, the importance of the auditory perceptual pathway for evolution of verbal communication. We suggest that understanding the evolution of language will also require understanding of vocalization perception, especially in the auditory cortex.

An isogenic blood-brain barrier model comprising brain endothelial cells, astrocytes, and neurons derived from human induced pluripotent stem cells.

PubMed

Canfield, Scott G; Stebbins, Matthew J; Morales, Bethsymarie Soto; Asai, Shusaku W; Vatine, Gad D; Svendsen, Clive N; Palecek, Sean P; Shusta, Eric V

2017-03-01

The blood-brain barrier (BBB) is critical in maintaining a physical and metabolic barrier between the blood and the brain. The BBB consists of brain microvascular endothelial cells (BMECs) that line the brain vasculature and combine with astrocytes, neurons and pericytes to form the neurovascular unit. We hypothesized that astrocytes and neurons generated from human-induced pluripotent stem cells (iPSCs) could induce BBB phenotypes in iPSC-derived BMECs, creating a robust multicellular human BBB model. To this end, iPSCs were used to form neural progenitor-like EZ-spheres, which were in turn differentiated to neurons and astrocytes, enabling facile neural cell generation. The iPSC-derived astrocytes and neurons induced barrier tightening in primary rat BMECs indicating their BBB inductive capacity. When co-cultured with human iPSC-derived BMECs, the iPSC-derived neurons and astrocytes significantly elevated trans-endothelial electrical resistance, reduced passive permeability, and improved tight junction continuity in the BMEC cell population, while p-glycoprotein efflux transporter activity was unchanged. A physiologically relevant neural cell mixture of one neuron: three astrocytes yielded optimal BMEC induction properties. Finally, an isogenic multicellular BBB model was successfully demonstrated employing BMECs, astrocytes, and neurons from the same donor iPSC source. It is anticipated that such an isogenic facsimile of the human BBB could have applications in furthering understanding the cellular interplay of the neurovascular unit in both healthy and diseased humans. Read the Editorial Highlight for this article on page 843. © 2016 International Society for Neurochemistry.

Dog Experts' Brains Distinguish Socially Relevant Body Postures Similarly in Dogs and Humans

PubMed Central

Kujala, Miiamaaria V.; Kujala, Jan; Carlson, Synnöve; Hari, Riitta

2012-01-01

We read conspecifics' social cues effortlessly, but little is known about our abilities to understand social gestures of other species. To investigate the neural underpinnings of such skills, we used functional magnetic resonance imaging to study the brain activity of experts and non-experts of dog behavior while they observed humans or dogs either interacting with, or facing away from a conspecific. The posterior superior temporal sulcus (pSTS) of both subject groups dissociated humans facing toward each other from humans facing away, and in dog experts, a distinction also occurred for dogs facing toward vs. away in a bilateral area extending from the pSTS to the inferior temporo-occipital cortex: the dissociation of dog behavior was significantly stronger in expert than control group. Furthermore, the control group had stronger pSTS responses to humans than dogs facing toward a conspecific, whereas in dog experts, the responses were of similar magnitude. These findings suggest that dog experts' brains distinguish socially relevant body postures similarly in dogs and humans. PMID:22720054

The Early Development of Human Mirror Mechanisms: Evidence from Electromyographic Recordings at 3 and 6 Months

ERIC Educational Resources Information Center

Turati, Chiara; Natale, Elena; Bolognini, Nadia; Senna, Irene; Picozzi, Marta; Longhi, Elena; Cassia, Viola Macchi

2013-01-01

In primates and adult humans direct understanding of others' action is provided by mirror mechanisms matching action observation and action execution (e.g. Casile, Caggiano & Ferrari, 2011). Despite the growing body of evidence detailing the existence of these mechanisms in the adult human brain, their origins and early development are…

Neuro-impressions: interpreting the nature of human creativity

PubMed Central

Siler, Todd Lael

2012-01-01

Understanding the creative process is essential for realizing human potential. Over the past four decades, the author has explored this subject through his brain-inspired drawings, paintings, symbolic sculptures, and experimental art installations that present myriad impressions of human creativity. These impressionistic artworks interpret rather than illustrate the complexities of the creative process. They draw insights from empirical studies that correlate how human beings create, learn, remember, innovate, and communicate. In addition to offering fresh aesthetic experiences, this metaphorical art raises fundamental questions concerning the deep connections between the brain and its creations. The author describes his artworks as embodiments of everyday observations about the neuropsychology of creativity, and its all-purpose applications for stimulating and accelerating innovation. PMID:23091455

Insight from animal models of environmentally-driven epigenetic changes in the developing and adult brain

PubMed Central

Doherty, Tiffany S.; Roth, Tania L.

2017-01-01

The efforts of many neuroscientists are directed toward understanding the appreciable plasticity of the brain and behavior. In recent years, epigenetics has become a core of this focus as a prime mechanistic candidate for behavioral modifications. Animal models have been instrumental in advancing our understanding of environmentally-driven changes to the epigenome in the developing and adult brain. This review focuses mainly on such discoveries driven by adverse environments along with their associated behavioral outcomes. While much of the evidence discussed focuses on epigenetics within the central nervous system, several peripheral studies in humans who have experienced significant adversity are also highlighted. As we continue to unravel the link between epigenetics and phenotype, discerning the complexity and specificity of epigenetic changes induced by environments is an important step toward understanding optimal development and how to prevent or ameliorate behavioral deficits bred by disruptive environments. PMID:27687803

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).

Toward the Language-Ready Brain: Biological Evolution and Primate Comparisons.

PubMed

Arbib, Michael A

2017-02-01

The approach to language evolution suggested here focuses on three questions: How did the human brain evolve so that humans can develop, use, and acquire languages? How can the evolutionary quest be informed by studying brain, behavior, and social interaction in monkeys, apes, and humans? How can computational modeling advance these studies? I hypothesize that the brain is language ready in that the earliest humans had protolanguages but not languages (i.e., communication systems endowed with rich and open-ended lexicons and grammars supporting a compositional semantics), and that it took cultural evolution to yield societies (a cultural constructed niche) in which language-ready brains could become language-using brains. The mirror system hypothesis is a well-developed example of this approach, but I offer it here not as a closed theory but as an evolving framework for the development and analysis of conflicting subhypotheses in the hope of their eventual integration. I also stress that computational modeling helps us understand the evolving role of mirror neurons, not in and of themselves, but only in their interaction with systems "beyond the mirror." Because a theory of evolution needs a clear characterization of what it is that evolved, I also outline ideas for research in neurolinguistics to complement studies of the evolution of the language-ready brain. A clear challenge is to go beyond models of speech comprehension to include sign language and models of production, and to link language to visuomotor interaction with the physical and social world.

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

PubMed

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

2018-01-01

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

Neural Plasticity following Abacus Training in Humans: A Review and Future Directions

PubMed Central

Li, Yongxin; Chen, Feiyan; Huang, Wenhua

2016-01-01

The human brain has an enormous capacity to adapt to a broad variety of environmental demands. Previous studies in the field of abacus training have shown that this training can induce specific changes in the brain. However, the neural mechanism underlying these changes remains elusive. Here, we reviewed the behavioral and imaging findings of comparisons between abacus experts and average control subjects and focused on changes in activation patterns and changes in brain structure. Finally, we noted the limitations and the future directions of this field. We concluded that although current studies have provided us with information about the mechanisms of abacus training, more research on abacus training is needed to understand its neural impact. PMID:26881089

Declarative Consciousness for Reconstruction

NASA Astrophysics Data System (ADS)

Seymour, Leslie G.

2013-12-01

Existing information technology tools are harnessed and integrated to provide digital specification of human consciousness of individual persons. An incremental compilation technology is proposed as a transformation of LifeLog derived persona specifications into a Canonical representation of the neocortex architecture of the human brain. The primary purpose is to gain an understanding of the semantical allocation of the neocortex capacity. Novel neocortex content allocation simulators with browsers are proposed to experiment with various approaches of relieving the brain from overload conditions. An IT model of the neocortex is maintained, which is then updated each time new stimuli are received from the LifeLog data stream; new information is gained from brain signal measurements; and new functional dependencies are discovered between live persona consumed/produced signals

Using repetitive transcranial magnetic stimulation to study the underlying neural mechanisms of human motor learning and memory.

PubMed

Censor, Nitzan; Cohen, Leonardo G

2011-01-01

In the last two decades, there has been a rapid development in the research of the physiological brain mechanisms underlying human motor learning and memory. While conventional memory research performed on animal models uses intracellular recordings, microfusion of protein inhibitors to specific brain areas and direct induction of focal brain lesions, human research has so far utilized predominantly behavioural approaches and indirect measurements of neural activity. Repetitive transcranial magnetic stimulation (rTMS), a safe non-invasive brain stimulation technique, enables the study of the functional role of specific cortical areas by evaluating the behavioural consequences of selective modulation of activity (excitation or inhibition) on memory generation and consolidation, contributing to the understanding of the neural substrates of motor learning. Depending on the parameters of stimulation, rTMS can also facilitate learning processes, presumably through purposeful modulation of excitability in specific brain regions. rTMS has also been used to gain valuable knowledge regarding the timeline of motor memory formation, from initial encoding to stabilization and long-term retention. In this review, we summarize insights gained using rTMS on the physiological and neural mechanisms of human motor learning and memory. We conclude by suggesting possible future research directions, some with direct clinical implications.

Region-specific protein misfolding cyclic amplification reproduces brain tropism of prion strains.

PubMed

Privat, Nicolas; Levavasseur, Etienne; Yildirim, Serfildan; Hannaoui, Samia; Brandel, Jean-Philippe; Laplanche, Jean-Louis; Béringue, Vincent; Seilhean, Danielle; Haïk, Stéphane

2017-10-06

Human prion diseases such as Creutzfeldt-Jakob disease are transmissible brain proteinopathies, characterized by the accumulation of a misfolded isoform of the host cellular prion protein (PrP) in the brain. According to the prion model, prions are defined as proteinaceous infectious particles composed solely of this abnormal isoform of PrP (PrP Sc ). Even in the absence of genetic material, various prion strains can be propagated in experimental models. They can be distinguished by the pattern of disease they produce and especially by the localization of PrP Sc deposits within the brain and the spongiform lesions they induce. The mechanisms involved in this strain-specific targeting of distinct brain regions still are a fundamental, unresolved question in prion research. To address this question, we exploited a prion conversion in vitro assay, protein misfolding cyclic amplification (PMCA), by using experimental scrapie and human prion strains as seeds and specific brain regions from mice and humans as substrates. We show here that region-specific PMCA in part reproduces the specific brain targeting observed in experimental, acquired, and sporadic Creutzfeldt-Jakob diseases. Furthermore, we provide evidence that, in addition to cellular prion protein, other region- and species-specific molecular factors influence the strain-dependent prion conversion process. This important step toward understanding prion strain propagation in the human brain may impact research on the molecular factors involved in protein misfolding and the development of ultrasensitive methods for diagnosing prion disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Pediatric Brain Tumors: Genomics and Epigenomics Pave the Way.

PubMed

Fontebasso, Adam M; Jabado, Nada

2015-01-01

Primary malignant brain tumors remain a disproportionate cause of morbidity and mortality in humans. A number of studies exploring the cancer genome of brain tumors across ages using integrated genetics and epigenetics and next-generation sequencing technologies have recently emerged. This has led to considerable advances in the understanding of the basic biology and pathogenesis of brain tumors, including the most malignant and common variants in children: gliomas and medulloblastoma. Notably, studies of pediatric brain tumors have identified unexpected oncogenic pathways implicated in tumorigenesis. These range from a single pathway/molecule defect such as abnormalities of the mitogen-activated protein kinase pathway, considered to be a hallmark of pilocytic astrocytomas, to alterations in the epigenome as a critical component altered in many subgroups of high-grade brain tumors. Importantly, the type, timing, and spatial clustering of these molecular alterations provide a better understanding of the pathogenesis of the respective brain tumor they target and critical markers for therapy that will help refine pathological grading. We summarize these novel findings in pediatric brain tumors, which also are put in the context of the evolving notion of molecular pathology, now a mandated tool for proper classification and therapy assignment in the clinical setting.

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.

State-dependencies of learning across brain scales

PubMed Central

Ritter, Petra; Born, Jan; Brecht, Michael; Dinse, Hubert R.; Heinemann, Uwe; Pleger, Burkhard; Schmitz, Dietmar; Schreiber, Susanne; Villringer, Arno; Kempter, Richard

2015-01-01

Learning is a complex brain function operating on different time scales, from milliseconds to years, which induces enduring changes in brain dynamics. The brain also undergoes continuous “spontaneous” shifts in states, which, amongst others, are characterized by rhythmic activity of various frequencies. Besides the most obvious distinct modes of waking and sleep, wake-associated brain states comprise modulations of vigilance and attention. Recent findings show that certain brain states, particularly during sleep, are essential for learning and memory consolidation. Oscillatory activity plays a crucial role on several spatial scales, for example in plasticity at a synaptic level or in communication across brain areas. However, the underlying mechanisms and computational rules linking brain states and rhythms to learning, though relevant for our understanding of brain function and therapeutic approaches in brain disease, have not yet been elucidated. Here we review known mechanisms of how brain states mediate and modulate learning by their characteristic rhythmic signatures. To understand the critical interplay between brain states, brain rhythms, and learning processes, a wide range of experimental and theoretical work in animal models and human subjects from the single synapse to the large-scale cortical level needs to be integrated. By discussing results from experiments and theoretical approaches, we illuminate new avenues for utilizing neuronal learning mechanisms in developing tools and therapies, e.g., for stroke patients and to devise memory enhancement strategies for the elderly. PMID:25767445

Brain entropy and human intelligence: A resting-state fMRI study

PubMed Central

Calderone, Daniel; Morales, Leah J.

2018-01-01

Human intelligence comprises comprehension of and reasoning about an infinitely variable external environment. A brain capable of large variability in neural configurations, or states, will more easily understand and predict variable external events. Entropy measures the variety of configurations possible within a system, and recently the concept of brain entropy has been defined as the number of neural states a given brain can access. This study investigates the relationship between human intelligence and brain entropy, to determine whether neural variability as reflected in neuroimaging signals carries information about intellectual ability. We hypothesize that intelligence will be positively associated with entropy in a sample of 892 healthy adults, using resting-state fMRI. Intelligence is measured with the Shipley Vocabulary and WASI Matrix Reasoning tests. Brain entropy was positively associated with intelligence. This relation was most strongly observed in the prefrontal cortex, inferior temporal lobes, and cerebellum. This relationship between high brain entropy and high intelligence indicates an essential role for entropy in brain functioning. It demonstrates that access to variable neural states predicts complex behavioral performance, and specifically shows that entropy derived from neuroimaging signals at rest carries information about intellectual capacity. Future work in this area may elucidate the links between brain entropy in both resting and active states and various forms of intelligence. This insight has the potential to provide predictive information about adaptive behavior and to delineate the subdivisions and nature of intelligence based on entropic patterns. PMID:29432427

Brain entropy and human intelligence: A resting-state fMRI study.

PubMed

Saxe, Glenn N; Calderone, Daniel; Morales, Leah J

2018-01-01

Human intelligence comprises comprehension of and reasoning about an infinitely variable external environment. A brain capable of large variability in neural configurations, or states, will more easily understand and predict variable external events. Entropy measures the variety of configurations possible within a system, and recently the concept of brain entropy has been defined as the number of neural states a given brain can access. This study investigates the relationship between human intelligence and brain entropy, to determine whether neural variability as reflected in neuroimaging signals carries information about intellectual ability. We hypothesize that intelligence will be positively associated with entropy in a sample of 892 healthy adults, using resting-state fMRI. Intelligence is measured with the Shipley Vocabulary and WASI Matrix Reasoning tests. Brain entropy was positively associated with intelligence. This relation was most strongly observed in the prefrontal cortex, inferior temporal lobes, and cerebellum. This relationship between high brain entropy and high intelligence indicates an essential role for entropy in brain functioning. It demonstrates that access to variable neural states predicts complex behavioral performance, and specifically shows that entropy derived from neuroimaging signals at rest carries information about intellectual capacity. Future work in this area may elucidate the links between brain entropy in both resting and active states and various forms of intelligence. This insight has the potential to provide predictive information about adaptive behavior and to delineate the subdivisions and nature of intelligence based on entropic patterns.

Prediction complements explanation in understanding the developing brain.

PubMed

Rosenberg, Monica D; Casey, B J; Holmes, Avram J

2018-02-21

A central aim of human neuroscience is understanding the neurobiology of cognition and behavior. Although we have made significant progress towards this goal, reliance on group-level studies of the developed adult brain has limited our ability to explain population variability and developmental changes in neural circuitry and behavior. In this review, we suggest that predictive modeling, a method for predicting individual differences in behavior from brain features, can complement descriptive approaches and provide new ways to account for this variability. Highlighting the outsized scientific and clinical benefits of prediction in developmental populations including adolescence, we show that predictive brain-based models are already providing new insights on adolescent-specific risk-related behaviors. Together with large-scale developmental neuroimaging datasets and complementary analytic approaches, predictive modeling affords us the opportunity and obligation to identify novel treatment targets and individually tailor the course of interventions for developmental psychopathologies that impact so many young people today.

From Data Processing to Mental Organs: An Interdisciplinary Path to Cognitive Neuroscience**

PubMed Central

Patharkar, Manoj

2011-01-01

Human brain is a highly evolved coordinating mechanism in the species Homo sapiens. It is only in the last 100 years that extensive knowledge of the intricate structure and complex functioning of the human brain has been acquired, though a lot is yet to be known. However, from the beginning of civilisation, people have been conscious of a ‘mind’ which has been considered the origin of all scientific and cultural development. Philosophers have discussed at length the various attributes of consciousness. At the same time, most of the philosophical or scientific frameworks have directly or indirectly implied mind-body duality. It is now imperative that we develop an integrated approach to understand the interconnection between mind and consciousness on one hand and brain on the other. This paper begins with the proposition that the structure of the brain is analogous, at least to certain extent, to that of the computer system. Of course, it is much more sophisticated and complex. The second proposition is that the Chomskyean concept of ‘mental organs’ is a good working hypothesis that tries to characterise this complexity in terms of an innate cognitive framework. By following this dual approach, brain as a data processing system and brain as a superstructure of intricately linked mental organs, we can move toward a better understanding of ‘mind’ within the framework of empirical science. The one ‘mental organ’ studied extensively in Chomskyean terms is ‘language faculty’ which is unique in its relation to brain, mind and consciousness. PMID:21694973

The Teaching Brain

ERIC Educational Resources Information Center

Battro, Antonio M.

2010-01-01

Animals cannot teach as humans do. Therefore, we lack the experimental support of animal studies that are so important to understand the evolution of our basic learning skills but are useless to explore the development of the teaching skills, unique to humans. And most important: children teach! We have at least two new challenges in our Mind,…

Tools for studying drug transport and metabolism in the brain.

PubMed

Pitcher, Meagan R; Quevedo, João

2016-01-01

Development of xenobiotics that cross the blood-brain barrier in therapeutically-relevant quantities is an expensive and time-consuming undertaking. However, central nervous system diseases are an under-addressed cause of high mortality and morbidity, and drug development in this field is a worthwhile venture. We aim to familiarize the reader with available methodologies for studying drug transport into the brain. Current understanding of the blood-brain barrier structure has been well-described in other manuscripts, and first we briefly review the path that xenobiotics take through the brain - from bloodstream, to endothelial cells of the blood-brain barrier, to interstitial space, to brain parenchymal cells, and then to an exit point from the central nervous system. The second half of the review discusses research tools available to determine if xenobiotics are making the journey through the brain successfully and offers commentary on the translational utility of each methodology. Theoretically, non-human mammalian and human blood-brain barriers are similar in composition; however, some findings demonstrate important differences across species. Translational methodologies may provide more reliable information about how a drug may act across species. The recent finding of lymphatic vessels within the central nervous system may provide new tools and strategies for drug delivery to the brain.

Understanding mental retardation in Down's syndrome using trisomy 16 mouse models.

PubMed

Galdzicki, Z; Siarey, R J

2003-06-01

Mental retardation in Down's syndrome, human trisomy 21, is characterized by developmental delays, language and memory deficits and other cognitive abnormalities. Neurophysiological and functional information is needed to understand the mechanisms of mental retardation in Down's syndrome. The trisomy mouse models provide windows into the molecular and developmental effects associated with abnormal chromosome numbers. The distal segment of mouse chromosome 16 is homologous to nearly the entire long arm of human chromosome 21. Therefore, mice with full or segmental trisomy 16 (Ts65Dn) are considered reliable animal models of Down's syndrome. Ts65Dn mice demonstrate impaired learning in spatial tests and abnormalities in hippocampal synaptic plasticity. We hypothesize that the physiological impairments in the Ts65Dn mouse hippocampus can model the suboptimal brain function occuring at various levels of Down's syndrome brain hierarchy, starting at a single neuron, and then affecting simple and complex neuronal networks. Once these elements create the gross brain structure, their dysfunctional activity cannot be overcome by extensive plasticity and redundancy, and therefore, at the end of the maturation period the mind inside this brain remains deficient and delayed in its capabilities. The complicated interactions that govern this aberrant developmental process cannot be rescued through existing compensatory mechanisms. In summary, overexpression of genes from chromosome 21 shifts biological homeostasis in the Down's syndrome brain to a new less functional state.

Gender Differences of Brain Glucose Metabolic Networks Revealed by FDG-PET: Evidence from a Large Cohort of 400 Young Adults

PubMed Central

Li, Kai; Zhu, Hong; Qi, Rongfeng; Zhang, Zhiqiang; Lu, Guangming

2013-01-01

Background Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. Materials and Methods FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25∼45 years, mean age±SD: 40.9±3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. Results Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. Conclusion This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients. PMID:24358312

Gender differences of brain glucose metabolic networks revealed by FDG-PET: evidence from a large cohort of 400 young adults.

PubMed

Hu, Yuxiao; Xu, Qiang; Li, Kai; Zhu, Hong; Qi, Rongfeng; Zhang, Zhiqiang; Lu, Guangming

2013-01-01

Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25:45 years, mean age ± SD: 40.9 ± 3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients.

Mechanistic Insights into Human Brain Impact Dynamics through Modal Analysis

NASA Astrophysics Data System (ADS)

Laksari, Kaveh; Kurt, Mehmet; Babaee, Hessam; Kleiven, Svein; Camarillo, David

2018-03-01

Although concussion is one of the greatest health challenges today, our physical understanding of the cause of injury is limited. In this Letter, we simulated football head impacts in a finite element model and extracted the most dominant modal behavior of the brain's deformation. We showed that the brain's deformation is most sensitive in low frequency regimes close to 30 Hz, and discovered that for most subconcussive head impacts, the dynamics of brain deformation is dominated by a single global mode. In this Letter, we show the existence of localized modes and multimodal behavior in the brain as a hyperviscoelastic medium. This dynamical phenomenon leads to strain concentration patterns, particularly in deep brain regions, which is consistent with reported concussion pathology.

Interfacing with the Brain using Organic Electronics

NASA Astrophysics Data System (ADS)

Malliaras, George

One of the most important scientific and technological frontiers of our time lies in the interface between electronics and the human brain. Interfacing the most advanced human engineering endeavor with nature's most refined creation promises to help elucidate aspects of the brain's working mechanism and deliver new tools for diagnosis and treatment of a host of pathologies including epilepsy and Parkinson's disease. Current solutions, however, are limited by the materials that are brought in contact with the tissue and transduce signals across the biotic/abiotic interface. The field of organic electronics has made available materials with a unique combination of attractive properties, including mechanical flexibility, mixed ionic/electronic conduction, enhanced biocompatibility, and capability for drug delivery. I will present examples of organic-based devices for recording and stimulation of brain activity, highlighting the connection between materials properties and device performance. I will show that organic electronic materials provide unparalleled opportunities to design devices that improve our understanding of brain physiology and pathology, and can be used to deliver new therapies.

Evolution of brain-computer interfaces: going beyond classic motor physiology

PubMed Central

Leuthardt, Eric C.; Schalk, Gerwin; Roland, Jarod; Rouse, Adam; Moran, Daniel W.

2010-01-01

The notion that a computer can decode brain signals to infer the intentions of a human and then enact those intentions directly through a machine is becoming a realistic technical possibility. These types of devices are known as brain-computer interfaces (BCIs). The evolution of these neuroprosthetic technologies could have significant implications for patients with motor disabilities by enhancing their ability to interact and communicate with their environment. The cortical physiology most investigated and used for device control has been brain signals from the primary motor cortex. To date, this classic motor physiology has been an effective substrate for demonstrating the potential efficacy of BCI-based control. However, emerging research now stands to further enhance our understanding of the cortical physiology underpinning human intent and provide further signals for more complex brain-derived control. In this review, the authors report the current status of BCIs and detail the emerging research trends that stand to augment clinical applications in the future. PMID:19569892

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

A Combination of Ontogeny and CNS Environment Establishes Microglial Identity.

PubMed

Bennett, F Chris; Bennett, Mariko L; Yaqoob, Fazeela; Mulinyawe, Sara B; Grant, Gerald A; Hayden Gephart, Melanie; Plowey, Edward D; Barres, Ben A

2018-05-22

Microglia, the brain's resident macrophages, are dynamic CNS custodians with surprising origins in the extra-embryonic yolk sac. The consequences of their distinct ontogeny are unknown but critical to understanding and treating brain diseases. We created a brain macrophage transplantation system to disentangle how environment and ontogeny specify microglial identity. We find that donor cells extensively engraft in the CNS of microglia-deficient mice, and even after exposure to a cell culture environment, microglia fully regain their identity when returned to the CNS. Though transplanted macrophages from multiple tissues can express microglial genes in the brain, only those of yolk-sac origin fully attain microglial identity. Transplanted macrophages of inappropriate origin, including primary human cells in a humanized host, express disease-associated genes and specific ontogeny markers. Through brain macrophage transplantation, we discover new principles of microglial identity that have broad applications to the study of disease and development of myeloid cell therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

Ageing and brain white matter structure in 3,513 UK Biobank participants

PubMed Central

Cox, Simon R.; Ritchie, Stuart J.; Tucker-Drob, Elliot M.; Liewald, David C.; Hagenaars, Saskia P.; Davies, Gail; Wardlaw, Joanna M.; Gale, Catharine R.; Bastin, Mark E.; Deary, Ian J.

2016-01-01

Quantifying the microstructural properties of the human brain's connections is necessary for understanding normal ageing and disease. Here we examine brain white matter magnetic resonance imaging (MRI) data in 3,513 generally healthy people aged 44.64–77.12 years from the UK Biobank. Using conventional water diffusion measures and newer, rarely studied indices from neurite orientation dispersion and density imaging, we document large age associations with white matter microstructure. Mean diffusivity is the most age-sensitive measure, with negative age associations strongest in the thalamic radiation and association fibres. White matter microstructure across brain tracts becomes increasingly correlated in older age. This may reflect an age-related aggregation of systemic detrimental effects. We report several other novel results, including age associations with hemisphere and sex, and comparative volumetric MRI analyses. Results from this unusually large, single-scanner sample provide one of the most extensive characterizations of age associations with major white matter tracts in the human brain. PMID:27976682

Plastic brains and the dialectics of dialectics

NASA Astrophysics Data System (ADS)

Loxley, Andrew; Murphy, Colette; Seery, Aidan

2014-09-01

This article advances the thinking of Lima, Ostermann and Rezende's "Marxism in Vygotskian approaches to cultural studies of science education" and Mark Zuss' response to their paper. Firstly, it introduces Catherine Malabou's concept of plasticity, from which Hegel's dialectic can be re-read as historical materialist self-determination in a way that embraces science but non-reductively, and which leads to the possibility of challenging theoretical rigidity as a form of transformative action. Secondly, this response article provides political analysis of scientific concepts as they reproduce and reinforce particular interests and are expropriated by policy makers and unaware teacher educators whose understanding lies within a technical-instrumentalism and diluted humanism framework. Both arguments feature the human brain as an object of research in science education. From Malabou, the emancipatory conceptualisation of the brain as material, historical and sociocultural; whilst `Brain Gym' exemplifies a non-science and nonsensical misappropriation of scientific concepts for commercial gain via a para-educational intervention.

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.

Complexity of EEG-signal in Time Domain - Possible Biomedical Application

NASA Astrophysics Data System (ADS)

Klonowski, Wlodzimierz; Olejarczyk, Elzbieta; Stepien, Robert

2002-07-01

Human brain is a highly complex nonlinear system. So it is not surprising that in analysis of EEG-signal, which represents overall activity of the brain, the methods of Nonlinear Dynamics (or Chaos Theory as it is commonly called) can be used. Even if the signal is not chaotic these methods are a motivating tool to explore changes in brain activity due to different functional activation states, e.g. different sleep stages, or to applied therapy, e.g. exposure to chemical agents (drugs) and physical factors (light, magnetic field). The methods supplied by Nonlinear Dynamics reveal signal characteristics that are not revealed by linear methods like FFT. Better understanding of principles that govern dynamics and complexity of EEG-signal can help to find `the signatures' of different physiological and pathological states of human brain, quantitative characteristics that may find applications in medical diagnostics.

Network Analysis: Applications for the Developing Brain

PubMed Central

Chu-Shore, Catherine J.; Kramer, Mark A.; Bianchi, Matt T.; Caviness, Verne S.; Cash, Sydney S.

2011-01-01

Development of the human brain follows a complex trajectory of age-specific anatomical and physiological changes. The application of network analysis provides an illuminating perspective on the dynamic interregional and global properties of this intricate and complex system. Here, we provide a critical synopsis of methods of network analysis with a focus on developing brain networks. After discussing basic concepts and approaches to network analysis, we explore the primary events of anatomical cortical development from gestation through adolescence. Upon this framework, we describe early work revealing the evolution of age-specific functional brain networks in normal neurodevelopment. Finally, we review how these relationships can be altered in disease and perhaps even rectified with treatment. While this method of description and inquiry remains in early form, there is already substantial evidence that the application of network models and analysis to understanding normal and abnormal human neural development holds tremendous promise for future discovery. PMID:21303762

Effect of Transcranial Magnetic Stimulation on Neuronal Networks

NASA Astrophysics Data System (ADS)

Unsal, Ahmet; Hadimani, Ravi; Jiles, David

2013-03-01

The human brain contains around 100 billion nerve cells controlling our day to day activities. Consequently, brain disorders often result in impairments such as paralysis, loss of coordination and seizure. It has been said that 1 in 5 Americans suffer some diagnosable mental disorder. There is an urgent need to understand the disorders, prevent them and if possible, develop permanent cure for them. As a result, a significant amount of research activities is being directed towards brain research. Transcranial Magnetic Stimulation (TMS) is a promising tool for diagnosing and treating brain disorders. It is a non-invasive treatment method that produces a current flow in the brain which excites the neurons. Even though TMS has been verified to have advantageous effects on various brain related disorders, there have not been enough studies on the impact of TMS on cells. In this study, we are investigating the electrophysiological effects of TMS on one dimensional neuronal culture grown in a circular pathway. Electrical currents are produced on the neuronal networks depending on the directionality of the applied field. This aids in understanding how neuronal networks react under TMS treatment.

Proposal Guidelines for Standardized Operating Procedures of Brain Autopsy: Brain Bank in South Korea.

PubMed

Lee, Kyung Hwa; Seo, Sang Won; Lim, Tae Sung; Kim, Eun Joo; Kim, Byeong Chae; Kim, Yeshin; Lee, Ho Won; Jeon, Jae Pil; Shim, Sung Mi; Na, Duk L; Huh, Gi Yeong; Lee, Min Cheol; Suh, Yeon Lim

2017-09-01

To obtain an in-depth understanding of brain diseases, including neurodegenerative diseases, psychiatric illnesses, and neoplasms, scientific approach and verification using postmortem human brain tissue with or without disease are essential. Compared to other countries that have run brain banks for decades, South Korea has limited experience with brain banking; nationwide brain banks started only recently. The goal of this study is to provide provisional guidelines for brain autopsy for hospitals and institutes that have not accumulated sufficient expertise. We hope that these provisional guidelines will serve as a useful reference for pathologists and clinicians who are involved and interested in the brain bank system. Also, we anticipate updating the provisional guidelines in the future based on collected data and further experience with the practice of brain autopsy in South Korea. © Copyright: Yonsei University College of Medicine 2017.

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

Nord, Alex S.; Pattabiraman, Kartik; Visel, Axel

The forebrain is the seat of higher-order brain functions, and many human neuropsychiatric disorders are due to genetic defects affecting forebrain development, making it imperative to understand the underlying genetic circuitry. We report that recent progress now makes it possible to begin fully elucidating the genomic regulatory mechanisms that control forebrain gene expression. Here, we discuss the current knowledge of how transcription factors drive gene expression programs through their interactions with cis-acting genomic elements, such as enhancers; how analyses of chromatin and DNA modifications provide insights into gene expression states; and how these approaches yield insights into the evolution ofmore » the human brain.« less

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

In vivo correlation between axon diameter and conduction velocity in the human brain.

PubMed

Horowitz, Assaf; Barazany, Daniel; Tavor, Ido; Bernstein, Moran; Yovel, Galit; Assaf, Yaniv

2015-01-01

The understanding of the relationship between structure and function has always characterized biology in general and neurobiology in particular. One such fundamental relationship is that between axon diameter and the axon's conduction velocity (ACV). Measurement of these neuronal properties, however, requires invasive procedures that preclude direct elucidation of this relationship in vivo. Here we demonstrate that diffusion-based MRI is sensitive to the fine microstructural elements of brain wiring and can be used to quantify axon diameter in vivo. Moreover, we demonstrate the in vivo correlation between the diameter of an axon and its conduction velocity in the human brain. Using AxCaliber, a novel magnetic resonance imaging technique that enables us to estimate in vivo axon diameter distribution (ADD) and by measuring the interhemispheric transfer time (IHTT) by electroencephalography, we found significant linear correlation, across a cohort of subjects, between brain microstructure morphology (ADD) and its physiology (ACV) in the tactile and visual sensory domains. The ability to make a quantitative assessment of a fundamental physiological property in the human brain from in vivo measurements of ADD may shed new light on neurological processes occurring in neuroplasticity as well as in neurological disorders and neurodegenerative diseases.

Effects of chromosomal sex and hormonal influences on shaping sex differences in brain and behavior: Lessons from cases of disorders of sex development.

PubMed

Bramble, Matthew S; Lipson, Allen; Vashist, Neerja; Vilain, Eric

2017-01-02

Sex differences in brain development and postnatal behavior are determined largely by genetic sex and in utero gonadal hormone secretions. In humans however, determining the weight that each of these factors contributes remains a challenge because social influences should also be considered. Cases of disorders of sex development (DSD) provide unique insight into how mutations in genes responsible for gonadal formation can perturb the subsequent developmental hormonal milieu and elicit changes in normal human brain maturation. Specific forms of DSDs such as complete androgen insensitivity syndrome (CAIS), congenital adrenal hyperplasia (CAH), and 5α-reductase deficiency syndrome have variable effects between males and females, and the developmental outcomes of such conditions are largely dependent on sex chromosome composition. Medical and psychological works focused on CAH, CAIS, and 5α-reductase deficiency have helped form the foundation for understanding the roles of genetic and hormonal factors necessary for guiding human brain development. Here we highlight how the three aforementioned DSDs contribute to brain and behavioral phenotypes that can uniquely affect 46,XY and 46,XX individuals in dramatically different fashions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The BRAIN Initiative Cell Census Consortium: Lessons Learned toward Generating a Comprehensive Brain Cell Atlas.

PubMed

Ecker, Joseph R; Geschwind, Daniel H; Kriegstein, Arnold R; Ngai, John; Osten, Pavel; Polioudakis, Damon; Regev, Aviv; Sestan, Nenad; Wickersham, Ian R; Zeng, Hongkui

2017-11-01

A comprehensive characterization of neuronal cell types, their distributions, and patterns of connectivity is critical for understanding the properties of neural circuits and how they generate behaviors. Here we review the experiences of the BRAIN Initiative Cell Census Consortium, ten pilot projects funded by the U.S. BRAIN Initiative, in developing, validating, and scaling up emerging genomic and anatomical mapping technologies for creating a complete inventory of neuronal cell types and their connections in multiple species and during development. These projects lay the foundation for a larger and longer-term effort to generate whole-brain cell atlases in species including mice and humans. Copyright © 2017 Elsevier Inc. All rights reserved.

Studying brain organization via spontaneous fMRI signal.

PubMed

Power, Jonathan D; Schlaggar, Bradley L; Petersen, Steven E

2014-11-19

In recent years, some substantial advances in understanding human (and nonhuman) brain organization have emerged from a relatively unusual approach: the observation of spontaneous activity, and correlated patterns in spontaneous activity, in the "resting" brain. Most commonly, spontaneous neural activity is measured indirectly via fMRI signal in subjects who are lying quietly in the scanner, the so-called "resting state." This Primer introduces the fMRI-based study of spontaneous brain activity, some of the methodological issues active in the field, and some ways in which resting-state fMRI has been used to delineate aspects of area-level and supra-areal brain organization. Copyright © 2014 Elsevier Inc. All rights reserved.

Cranial thickness changes in early childhood

NASA Astrophysics Data System (ADS)

Gajawelli, Niharika; Deoni, Sean; Shi, Jie; Dirks, Holly; Linguraru, Marius George; Nelson, Marvin D.; Wang, Yalin; Lepore, Natasha

2017-11-01

The neurocranium changes rapidly in early childhood to accommodate the developing brain. However, developmental disorders may cause abnormal growth of the neurocranium, the most common one being craniosynostosis, affecting about 1 in 2000 children. It is important to understand how the brain and neurocranium develop together to understand the role of the neurocranium in neurodevelopmental outcomes. However, the neurocranium is not as well studied as the human brain in early childhood, due to a lack of imaging data. CT is typically employed to investigate the cranium, but, due to ionizing radiation, may only be used for clinical cases. However, the neurocranium is also visible on magnetic resonance imaging (MRI). Here, we used a large dataset of MRI images from healthy children in the age range of 1 to 2 years old and extracted the neurocranium. A conformal geometry based analysis pipeline is implemented to determine a set of statistical atlases of the neurocranium. A growth model of the neurocranium will help us understand cranial bone and suture development with respect to the brain, which will in turn inform better treatment strategies for neurocranial disorders.

[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.

Joint genetic analysis of hippocampal size in mouse and human identifies a novel gene linked to neurodegenerative disease.

PubMed

Ashbrook, David G; Williams, Robert W; Lu, Lu; Stein, Jason L; Hibar, Derrek P; Nichols, Thomas E; Medland, Sarah E; Thompson, Paul M; Hager, Reinmar

2014-10-03

Variation in hippocampal volume has been linked to significant differences in memory, behavior, and cognition among individuals. To identify genetic variants underlying such differences and associated disease phenotypes, multinational consortia such as ENIGMA have used large magnetic resonance imaging (MRI) data sets in human GWAS studies. In addition, mapping studies in mouse model systems have identified genetic variants for brain structure variation with great power. A key challenge is to understand how genetically based differences in brain structure lead to the propensity to develop specific neurological disorders. We combine the largest human GWAS of brain structure with the largest mammalian model system, the BXD recombinant inbred mouse population, to identify novel genetic targets influencing brain structure variation that are linked to increased risk for neurological disorders. We first use a novel cross-species, comparative analysis using mouse and human genetic data to identify a candidate gene, MGST3, associated with adult hippocampus size in both systems. We then establish the coregulation and function of this gene in a comprehensive systems-analysis. We find that MGST3 is associated with hippocampus size and is linked to a group of neurodegenerative disorders, such as Alzheimer's.

Influence of sex steroid hormones on the adolescent brain and behavior: An update

PubMed Central

Vigil, Pilar; del Río, Juan Pablo; Carrera, BÁrbara; ArÁnguiz, Florencia C.

2016-01-01

This review explains the main effects exerted by sex steroids and other hormones on the adolescent brain. During the transition from puberty to adolescence, these hormones participate in the organizational phenomena that structurally shape some brain circuits. In adulthood, this will propitiate some specific behavior as responses to the hormones now activating those neural circuits. Adolescence is, then, a critical “organizational window” for the brain to develop adequately, since steroid hormones perform important functions at this stage. For this reason, the adolescent years are very important for future behaviors in human beings. Changes that occur or fail to occur during adolescence will determine behaviors for the rest of one's lifetime. Consequently, understanding the link between adolescent behavior and brain development as influenced by sex steroids and other hormones and compounds is very important in order to interpret various psycho-affective pathologies. Lay Summary: The effect of steroid hormones on the development of the adolescent brain, and therefore, on adolescent behavior, is noticeable. This review presents their main activational and organizational effects. During the transition from puberty to adolescence, organizational phenomena triggered by steroids structurally affect the remodeling of brain circuits. Later in adulthood, these changes will be reflected in behavioral responses to such hormones. Adolescence can then be seen as a fundamental “organizational window” during which sex steroids and other hormones and compounds play relevant roles. The understanding of the relationship between adolescent behavior and the way hormones influence brain development help understand some psychological disorders. PMID:27833209

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.

Postmortem changes in the neuroanatomical characteristics of the primate brain: the hippocampal formation

PubMed Central

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L.; Amaral, David G.

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused, or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger, as compared to perfusion-fixed tissue. Non-phosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well-stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences. PMID:18972553

Postmortem changes in the neuroanatomical characteristics of the primate brain: hippocampal formation.

PubMed

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L; Amaral, David G

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger as compared to perfusion-fixed tissue. Nonphosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells, and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences.

The shape of the human language-ready brain

PubMed Central

Boeckx, Cedric; Benítez-Burraco, Antonio

2014-01-01

Our core hypothesis is that the emergence of our species-specific language-ready brain ought to be understood in light of the developmental changes expressed at the levels of brain morphology and neural connectivity that occurred in our species after the split from Neanderthals–Denisovans and that gave us a more globular braincase configuration. In addition to changes at the cortical level, we hypothesize that the anatomical shift that led to globularity also entailed significant changes at the subcortical level. We claim that the functional consequences of such changes must also be taken into account to gain a fuller understanding of our linguistic capacity. Here we focus on the thalamus, which we argue is central to language and human cognition, as it modulates fronto-parietal activity. With this new neurobiological perspective in place, we examine its possible molecular basis. We construct a candidate gene set whose members are involved in the development and connectivity of the thalamus, in the evolution of the human head, and are known to give rise to language-associated cognitive disorders. We submit that the new gene candidate set opens up new windows into our understanding of the genetic basis of our linguistic capacity. Thus, our hypothesis aims at generating new testing grounds concerning core aspects of language ontogeny and phylogeny. PMID:24772099

Olfaction

PubMed Central

Pinto1, Jayant M.

2011-01-01

Olfaction represents an ancient, evolutionarily critical physiologic system. In humans, chemosensation mediates safety, nutrition, sensation of pleasure, and general well-being. Factors that affect human olfaction included structural aspects of the nasal cavity that can modulate airflow and therefore odorant access to the olfactory cleft, and inflammatory disease, which can affect both airflow as well as olfactory nerve function. After signals are generated, olfactory information is processed and coded in the olfactory bulb and disseminated to several areas in the brain. The discovery of olfactory receptors by Axel and Buck sparked greater understanding of the molecular basis of olfaction. However, the precise mechanisms used by this system are still under great scrutiny due to the complexity of understanding how an enormous number of chemically diverse odorant molecules are coded into signals understood by the brain. Additionally, it has been challenging to dissect olfactory sensation due to the multiple areas of areas of the brain that receive and modulate this information. Consequently, our knowledge of olfactory dysfunction in humans remains primitive. Aging represents the major cause of loss of smell, although a number of clinical and environmental factors are thought to affect chemosensory function. Treatment options focus on reducing sinonasal inflammation when present, ruling out other treatable causes, and counseling patients on safety measures. PMID:21364221

Neurocognition: the food–brain connection.

PubMed

Hill, James O; Berridge, Kent; Avena, Nicole M; Ziauddeen, Hisham; Alonso-Alonso, Miguel; Allison, David B; Khan, Naiman A; Kelley, Michael

2014-09-01

This article summarizes presentations from “Neurocognition: The Food–Brain Connection” symposium held at the ASN Scientific Sessions and Annual Meeting at Experimental Biology 2014 in San Diego, CA on 28 April 2014. Presenters reviewed research from several disciplines, including neurobiology, neuropsychology, cognitive neuroscience, and nutrition, concerning the role of the brain in food-intake regulation, reward, and addiction. A transdisciplinary approach was taken to evaluate the state of the science regarding addiction models, as well as research gaps and future research necessary to understand neurocircuitry and pathways involved in food-intake control and behavior in humans.

Driving working memory with frequency-tuned noninvasive brain stimulation.

PubMed

Albouy, Philippe; Baillet, Sylvain; Zatorre, Robert J

2018-04-29

Frequency-tuned noninvasive brain stimulation is a recent approach in cognitive neuroscience that involves matching the frequency of transcranially applied electromagnetic fields to that of specific oscillatory components of the underlying neurophysiology. The objective of this method is to modulate ongoing/intrinsic brain oscillations, which correspond to rhythmic fluctuations of neural excitability, to causally change behavior. We review the impact of frequency-tuned noninvasive brain stimulation on the research field of human working memory. We argue that this is a powerful method to probe and understand the mechanisms of memory functions, targeting specifically task-related oscillatory dynamics, neuronal representations, and brain networks. We report the main behavioral and neurophysiological outcomes published to date, in particular, how functionally relevant oscillatory signatures in signal power and interregional connectivity yield causal changes of working memory abilities. We also present recent developments of the technique that aim to modulate cross-frequency coupling in polyrhythmic neural activity. Overall, the method has led to significant advances in our understanding of the mechanisms of systems neuroscience, and the role of brain oscillations in cognition and behavior. We also emphasize the translational impact of noninvasive brain stimulation techniques in the development of therapeutic approaches. © 2018 New York Academy of Sciences.

Exploring Deep Space - Uncovering the Anatomy of Periventricular Structures to Reveal the Lateral Ventricles of the Human Brain.

PubMed

Colibaba, Alexandru S; Calma, Aicee Dawn B; Webb, Alexandra L; Valter, Krisztina

2017-10-22

Anatomy students are typically provided with two-dimensional (2D) sections and images when studying cerebral ventricular anatomy and students find this challenging. Because the ventricles are negative spaces located deep within the brain, the only way to understand their anatomy is by appreciating their boundaries formed by related structures. Looking at a 2D representation of these spaces, in any of the cardinal planes, will not enable visualisation of all of the structures that form the boundaries of the ventricles. Thus, using 2D sections alone requires students to compute their own mental image of the 3D ventricular spaces. The aim of this study was to develop a reproducible method for dissecting the human brain to create an educational resource to enhance student understanding of the intricate relationships between the ventricles and periventricular structures. To achieve this, we created a video resource that features a step-by-step guide using a fiber dissection method to reveal the lateral and third ventricles together with the closely related limbic system and basal ganglia structures. One of the advantages of this method is that it enables delineation of the white matter tracts that are difficult to distinguish using other dissection techniques. This video is accompanied by a written protocol that provides a systematic description of the process to aid in the reproduction of the brain dissection. This package offers a valuable anatomy teaching resource for educators and students alike. By following these instructions educators can create teaching resources and students can be guided to produce their own brain dissection as a hands-on practical activity. We recommend that this video guide be incorporated into neuroanatomy teaching to enhance student understanding of the morphology and clinical relevance of the ventricles.

Consumer nueroscience: a new area of study for biomedical engineers.

PubMed

Babiloni, Fabio

2012-01-01

In scientific literature, the most accepted definition of consumer neuroscience or neuromarketing is that it is a field of study concerning the application of neuroscience methods to analyze and understand human behavior related to markets and marketing exchanges. First, it might seem strange that marketers would be interested in using neuroscience to understand consumer's preferences. Yet in practice, the basic goal of marketers is to guide the design and presentation of products in such a way that they are highly compatible with consumer preferences. To understand consumers preferences, several standard research tools are commonly used by marketers, such as personal interviews with the consumers, scoring questionnaries gathered from consumers, and focus groups. The reason marketing researchers are interested in using brain imaging tools instead of simply asking people for their preferences in front of marketing stimuli, arises from the assumption that people cannot (or do not want to) fully explain their preference when explicitly asked. Researchers in the field hypothesize that neuroimaging tools can access information within the consumer's brain during the generation of a preference or the observation of a commercial advertisement. The question of will this information be useful in further promoting the product is still up for debate in marketing literature. From the marketing researchers point of view, there is a hope that this body of brain imaging techniques will provide an efficient tradeoff between costs and benefits of the research. Currently, neuroscience methodology includes powerful brain imaging tools based on the gathering of hemodynamic or electromagnetic signals related to the human brain activity during the performance of a relevant task for marketing objectives. These tools are briefly reviewed in this article.

A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases.

PubMed

Stehle, Jörg H; Saade, Anastasia; Rawashdeh, Oliver; Ackermann, Katrin; Jilg, Antje; Sebestény, Tamás; Maronde, Erik

2011-08-01

The human pineal gland is a neuroendocrine transducer that forms an integral part of the brain. Through the nocturnally elevated synthesis and release of the neurohormone melatonin, the pineal gland encodes and disseminates information on circadian time, thus coupling the outside world to the biochemical and physiological internal demands of the body. Approaches to better understand molecular details behind the rhythmic signalling in the human pineal gland are limited but implicitly warranted, as human chronobiological dysfunctions are often associated with alterations in melatonin synthesis. Current knowledge on melatonin synthesis in the human pineal gland is based on minimally invasive analyses, and by the comparison of signalling events between different vertebrate species, with emphasis put on data acquired in sheep and other primates. Together with investigations using autoptic pineal tissue, a remnant silhouette of premortem dynamics within the hormone's biosynthesis pathway can be constructed. The detected biochemical scenario behind the generation of dynamics in melatonin synthesis positions the human pineal gland surprisingly isolated. In this neuroendocrine brain structure, protein-protein interactions and nucleo-cytoplasmic protein shuttling indicate furthermore a novel twist in the molecular dynamics in the cells of this neuroendocrine brain structure. These findings have to be seen in the light that an impaired melatonin synthesis is observed in elderly and/or demented patients, in individuals affected by Alzheimer's disease, Smith-Magenis syndrome, autism spectrum disorder and sleep phase disorders. Already, recent advances in understanding signalling dynamics in the human pineal gland have significantly helped to counteract chronobiological dysfunctions through a proper restoration of the nocturnal melatonin surge. © 2011 John Wiley & Sons A/S.

The orthotopic xenotransplant of human glioblastoma successfully recapitulates glioblastoma-microenvironment interactions in a non-immunosuppressed mouse model.

PubMed

Garcia, Celina; Dubois, Luiz Gustavo; Xavier, Anna Lenice; Geraldo, Luiz Henrique; da Fonseca, Anna Carolina Carvalho; Correia, Ana Helena; Meirelles, Fernanda; Ventura, Grasiella; Romão, Luciana; Canedo, Nathalie Henriques Silva; de Souza, Jorge Marcondes; de Menezes, João Ricardo Lacerda; Moura-Neto, Vivaldo; Tovar-Moll, Fernanda; Lima, Flavia Regina Souza

2014-12-08

Glioblastoma (GBM) is the most common primary brain tumor and the most aggressive glial tumor. This tumor is highly heterogeneous, angiogenic, and insensitive to radio- and chemotherapy. Here we have investigated the progression of GBM produced by the injection of human GBM cells into the brain parenchyma of immunocompetent mice. Xenotransplanted animals were submitted to magnetic resonance imaging (MRI) and histopathological analyses. Our data show that two weeks after injection, the produced tumor presents histopathological characteristics recommended by World Health Organization for the diagnosis of GBM in humans. The tumor was able to produce reactive gliosis in the adjacent parenchyma, angiogenesis, an intense recruitment of macrophage and microglial cells, and presence of necrosis regions. Besides, MRI showed that tumor mass had enhanced contrast, suggesting a blood-brain barrier disruption. This study demonstrated that the xenografted tumor in mouse brain parenchyma develops in a very similar manner to those found in patients affected by GBM and can be used to better understand the biology of GBM as well as testing potential therapies.

Becoming a Truly Helpful Teacher: Considerably More Challenging, and Potentially More Fun, than Merely Doing Business as Usual

ERIC Educational Resources Information Center

Jason, Hilliard

2007-01-01

Few medical faculty members are adequately prepared for their instructional responsibilities. Our educational traditions were established before we had research-based understandings of the teaching-learning process and before brain research began informing our understandings of how humans achieve lasting learning. Yet, there are several advantages…

Gaining Insight of Fetal Brain Development with Diffusion MRI and Histology

PubMed Central

Huang, Hao; Vasung, Lana

2013-01-01

Human brain is extraordinarily complex and yet its origin is a simple tubular structure. Its development during the fetal period is characterized by a series of accurately organized events which underlie the mechanisms of dramatic structural changes during fetal development. Revealing detailed anatomy at different stages of human fetal brain development provides insight on understanding not only this highly ordered process, but also the neurobiological foundations of cognitive brain disorders such as mental retardation, autism, schizophrenia, bipolar and language impairment. Diffusion tensor imaging (DTI) and histology are complementary tools which are capable of delineating the fetal brain structures at both macroscopic and microscopic level. In this review, the structural development of the fetal brains has been characterized with DTI and histology. Major components of the fetal brain, including cortical plate, fetal white matter and cerebral wall layer between the ventricle and subplate, have been delineated with DTI and histology. Anisotropic metrics derived from DTI were used to quantify the microstructural changes during the dynamic process of human fetal cortical development and prenatal development of other animal models. Fetal white matter pathways have been traced with DTI-based tractography to reveal growth patterns of individual white matter tracts and corticocortical connectivity. These detailed anatomical accounts of the structural changes during fetal period may provide the clues of detecting developmental and cognitive brain disorders at their early stages. The anatomical information from DTI and histology may also provide reference standards for diagnostic radiology of premature newborns. PMID:23796901

Time resolved dosimetry of human brain exposed to low frequency pulsed magnetic fields.

PubMed

Paffi, Alessandra; Camera, Francesca; Lucano, Elena; Apollonio, Francesca; Liberti, Micaela

2016-06-21

An accurate dosimetry is a key issue to understanding brain stimulation and related interaction mechanisms with neuronal tissues at the basis of the increasing amount of literature revealing the effects on human brain induced by low-level, low frequency pulsed magnetic fields (PMFs). Most literature on brain dosimetry estimates the maximum E field value reached inside the tissue without considering its time pattern or tissue dispersivity. Nevertheless a time-resolved dosimetry, accounting for dispersive tissues behavior, becomes necessary considering that the threshold for an effect onset may vary depending on the pulse waveform and that tissues may filter the applied stimulatory fields altering the predicted stimulatory waveform's size and shape. In this paper a time-resolved dosimetry has been applied on a realistic brain model exposed to the signal presented in Capone et al (2009 J. Neural Transm. 116 257-65), accounting for the broadband dispersivity of brain tissues up to several kHz, to accurately reconstruct electric field and current density waveforms inside different brain tissues. The results obtained by exposing the Duke's brain model to this PMF signal show that the E peak in the brain is considerably underestimated if a simple monochromatic dosimetry is carried out at the pulse repetition frequency of 75 Hz.

Time resolved dosimetry of human brain exposed to low frequency pulsed magnetic fields

NASA Astrophysics Data System (ADS)

Paffi, Alessandra; Camera, Francesca; Lucano, Elena; Apollonio, Francesca; Liberti, Micaela

2016-06-01

An accurate dosimetry is a key issue to understanding brain stimulation and related interaction mechanisms with neuronal tissues at the basis of the increasing amount of literature revealing the effects on human brain induced by low-level, low frequency pulsed magnetic fields (PMFs). Most literature on brain dosimetry estimates the maximum E field value reached inside the tissue without considering its time pattern or tissue dispersivity. Nevertheless a time-resolved dosimetry, accounting for dispersive tissues behavior, becomes necessary considering that the threshold for an effect onset may vary depending on the pulse waveform and that tissues may filter the applied stimulatory fields altering the predicted stimulatory waveform’s size and shape. In this paper a time-resolved dosimetry has been applied on a realistic brain model exposed to the signal presented in Capone et al (2009 J. Neural Transm. 116 257-65), accounting for the broadband dispersivity of brain tissues up to several kHz, to accurately reconstruct electric field and current density waveforms inside different brain tissues. The results obtained by exposing the Duke’s brain model to this PMF signal show that the E peak in the brain is considerably underestimated if a simple monochromatic dosimetry is carried out at the pulse repetition frequency of 75 Hz.

Human development XIII: the connection between the structure of the overtone system and the tone language of music. Some implications for our understanding of the human brain.

PubMed

Ventegodt, Søren; Hermansen, Tyge Dahl; Kandel, Isack; Merrick, Joav

2008-07-13

The functioning brain behaves like one highly-structured, coherent, informational field. It can be popularly described as a "coherent ball of energy", making the idea of a local highly-structured quantum field that carries the consciousness very appealing. If that is so, the structure of the experience of music might be a quite unique window into a hidden quantum reality of the brain, and even of life itself. The structure of music is then a mirror of a much more complex, but similar, structure of the energetic field of the working brain. This paper discusses how the perception of music is organized in the human brain with respect to the known tone scales of major and minor. The patterns used by the brain seem to be similar to the overtones of vibrating matter, giving a positive experience of harmonies in major. However, we also like the minor scale, which can explain brain patterns as fractal-like, giving a symmetric "downward reflection" of the major scale into the minor scale. We analyze the implication of beautiful and ugly tones and harmonies for the model. We conclude that when it comes to simple perception of harmonies, the most simple is the most beautiful and the most complex is the most ugly, but in music, even the most disharmonic harmony can be beautiful, if experienced as a part of a dynamic release of musical tension. This can be taken as a general metaphor of painful, yet meaningful, and developing experiences in human life.

A simpler primate brain: the visual system of the marmoset monkey

PubMed Central

Solomon, Samuel G.; Rosa, Marcello G. P.

2014-01-01

Humans are diurnal primates with high visual acuity at the center of gaze. Although primates share many similarities in the organization of their visual centers with other mammals, and even other species of vertebrates, their visual pathways also show unique features, particularly with respect to the organization of the cerebral cortex. Therefore, in order to understand some aspects of human visual function, we need to study non-human primate brains. Which species is the most appropriate model? Macaque monkeys, the most widely used non-human primates, are not an optimal choice in many practical respects. For example, much of the macaque cerebral cortex is buried within sulci, and is therefore inaccessible to many imaging techniques, and the postnatal development and lifespan of macaques are prohibitively long for many studies of brain maturation, plasticity, and aging. In these and several other respects the marmoset, a small New World monkey, represents a more appropriate choice. Here we review the visual pathways of the marmoset, highlighting recent work that brings these advantages into focus, and identify where additional work needs to be done to link marmoset brain organization to that of macaques and humans. We will argue that the marmoset monkey provides a good subject for studies of a complex visual system, which will likely allow an important bridge linking experiments in animal models to humans. PMID:25152716

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

Parallel Computing for Brain Simulation.

PubMed

Pastur-Romay, L A; Porto-Pazos, A B; Cedron, F; Pazos, A

2017-01-01

The human brain is the most complex system in the known universe, it is therefore one of the greatest mysteries. It provides human beings with extraordinary abilities. However, until now it has not been understood yet how and why most of these abilities are produced. For decades, researchers have been trying to make computers reproduce these abilities, focusing on both understanding the nervous system and, on processing data in a more efficient way than before. Their aim is to make computers process information similarly to the brain. Important technological developments and vast multidisciplinary projects have allowed creating the first simulation with a number of neurons similar to that of a human brain. This paper presents an up-to-date review about the main research projects that are trying to simulate and/or emulate the human brain. They employ different types of computational models using parallel computing: digital models, analog models and hybrid models. This review includes the current applications of these works, as well as future trends. It is focused on various works that look for advanced progress in Neuroscience and still others which seek new discoveries in Computer Science (neuromorphic hardware, machine learning techniques). Their most outstanding characteristics are summarized and the latest advances and future plans are presented. In addition, this review points out the importance of considering not only neurons: Computational models of the brain should also include glial cells, given the proven importance of astrocytes in information processing. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The impact of stress on the structure of the adolescent brain: Implications for adolescent mental health.

PubMed

Romeo, Russell D

2017-01-01

Adolescent development is associated with major changes in emotional and cognitive functions, as well as a rise in stress-related psychological disorders such as anxiety and depression. It is also a time of significant maturation of the brain, marked by structural alterations in many limbic and cortical regions. Though many elegant human neuroimaging studies have described the adolescent-related changes in these regions, relatively little is known about these changes in non-human animals. Moreover, both human and non-human data are lacking on how exposure to chronic stress may disrupt this structural maturation. Given the fundamental structure-function relationship in the nervous system, it will be important to understand how these normative and stress-induced structural alterations during adolescence influence psychological function, which in turn can modify future neural development. The purpose of this brief review is to describe the impact of stress on the structure of brain regions that continue to show structural maturation during adolescence and are highly sensitive to the effects of chronic stress exposure. Specifically, this review will focus on the amygdala, hippocampal formation, and prefrontal cortex, particularly from a morphological perspective. As many unanswered questions remain in this area of investigation, potential future lines of research are also discussed. A deeper appreciation of how stress affects adolescent brain development will be needed if we are to gain a better understanding of the mechanisms that mediate the increase in stress-related psychological dysfunctions often observed during this stage of development. This article is part of a Special Issue entitled SI: Adolescent plasticity. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuroanatomical Markers of Social Hierarchy Recognition in Humans: A Combined ERP/MRI Study.

PubMed

Santamaría-García, Hernando; Burgaleta, Miguel; Sebastián-Gallés, Nuria

2015-07-29

Social hierarchy is an ubiquitous principle of social organization across animal species. Although some progress has been made in our understanding of how humans infer hierarchical identity, the neuroanatomical basis for perceiving key social dimensions of others remains unexplored. Here, we combined event-related potentials and structural MRI to reveal the neuroanatomical substrates of early status recognition. We designed a covertly simulated hierarchical setting in which participants performed a task either with a superior or with an inferior player. Participants showed higher amplitude in the N170 component when presented with a picture of a superior player compared with an inferior player. Crucially, the magnitude of this effect correlated with brain morphology of the posterior cingulate cortex, superior temporal gyrus, insula, fusiform gyrus, and caudate nucleus. We conclude that early recognition of social hierarchies relies on the structural properties of a network involved in the automatic recognition of social identity. Humans can perceive social hierarchies very rapidly, an ability that is key for social interactions. However, some individuals are more sensitive to hierarchical information than others. Currently, it is unknown how brain structure supports such fast-paced processes of social hierarchy perception and their individual differences. Here, we addressed this issue for the first time by combining the high temporal resolution of event-related potentials (ERPs) and the high spatial resolution of structural MRI. This methodological approach allowed us to unveil a novel association between ERP neuromarkers of social hierarchy perception and the morphology of several cortical and subcortical brain regions typically assumed to play a role in automatic processes of social cognition. Our results are a step forward in our understanding of the human social brain. Copyright © 2015 the authors 0270-6474/15/3510843-08$15.00/0.

Functional connectivity-based parcellation and connectome of cortical midline structures in the mouse: a perfusion autoradiography study

PubMed Central

Holschneider, Daniel P.; Wang, Zhuo; Pang, Raina D.

2014-01-01

Rodent cortical midline structures (CMS) are involved in emotional, cognitive and attentional processes. Tract tracing has revealed complex patterns of structural connectivity demonstrating connectivity-based integration and segregation for the prelimbic, cingulate area 1, retrosplenial dysgranular cortices dorsally, and infralimbic, cingulate area 2, and retrosplenial granular cortices ventrally. Understanding of CMS functional connectivity (FC) remains more limited. Here we present the first subregion-level FC analysis of the mouse CMS, and assess whether fear results in state-dependent FC changes analogous to what has been reported in humans. Brain mapping using [14C]-iodoantipyrine was performed in mice during auditory-cued fear conditioned recall and in controls. Regional cerebral blood flow (CBF) was analyzed in 3-D images reconstructed from brain autoradiographs. Regions-of-interest were selected along the CMS anterior-posterior and dorsal-ventral axes. In controls, pairwise correlation and graph theoretical analyses showed strong FC within each CMS structure, strong FC along the dorsal-ventral axis, with segregation of anterior from posterior structures. Seed correlation showed FC of anterior regions to limbic/paralimbic areas, and FC of posterior regions to sensory areas–findings consistent with functional segregation noted in humans. Fear recall increased FC between the cingulate and retrosplenial cortices, but decreased FC between dorsal and ventral structures. In agreement with reports in humans, fear recall broadened FC of anterior structures to the amygdala and to somatosensory areas, suggesting integration and processing of both limbic and sensory information. Organizational principles learned from animal models at the mesoscopic level (brain regions and pathways) will not only critically inform future work at the microscopic (single neurons and synapses) level, but also have translational value to advance our understanding of human brain architecture. PMID:24966831

Functional connectivity-based parcellation and connectome of cortical midline structures in the mouse: a perfusion autoradiography study.

PubMed

Holschneider, Daniel P; Wang, Zhuo; Pang, Raina D

2014-01-01

Rodent cortical midline structures (CMS) are involved in emotional, cognitive and attentional processes. Tract tracing has revealed complex patterns of structural connectivity demonstrating connectivity-based integration and segregation for the prelimbic, cingulate area 1, retrosplenial dysgranular cortices dorsally, and infralimbic, cingulate area 2, and retrosplenial granular cortices ventrally. Understanding of CMS functional connectivity (FC) remains more limited. Here we present the first subregion-level FC analysis of the mouse CMS, and assess whether fear results in state-dependent FC changes analogous to what has been reported in humans. Brain mapping using [(14)C]-iodoantipyrine was performed in mice during auditory-cued fear conditioned recall and in controls. Regional cerebral blood flow (CBF) was analyzed in 3-D images reconstructed from brain autoradiographs. Regions-of-interest were selected along the CMS anterior-posterior and dorsal-ventral axes. In controls, pairwise correlation and graph theoretical analyses showed strong FC within each CMS structure, strong FC along the dorsal-ventral axis, with segregation of anterior from posterior structures. Seed correlation showed FC of anterior regions to limbic/paralimbic areas, and FC of posterior regions to sensory areas-findings consistent with functional segregation noted in humans. Fear recall increased FC between the cingulate and retrosplenial cortices, but decreased FC between dorsal and ventral structures. In agreement with reports in humans, fear recall broadened FC of anterior structures to the amygdala and to somatosensory areas, suggesting integration and processing of both limbic and sensory information. Organizational principles learned from animal models at the mesoscopic level (brain regions and pathways) will not only critically inform future work at the microscopic (single neurons and synapses) level, but also have translational value to advance our understanding of human brain architecture.

On the Edge of Language Acquisition: Inherent Constraints on Encoding Multisyllabic Sequences in the Neonate Brain

ERIC Educational Resources Information Center

Ferry, Alissa L.; Fló, Ana; Brusini, Perrine; Cattarossi, Luigi; Macagno, Francesco; Nespor, Marina; Mehler, Jacques

2016-01-01

To understand language, humans must encode information from rapid, sequential streams of syllables--tracking their order and organizing them into words, phrases, and sentences. We used Near-Infrared Spectroscopy (NIRS) to determine whether human neonates are born with the capacity to track the positions of syllables in multisyllabic sequences.…

Cortical Evolution: Judge the Brain by Its Cover

PubMed Central

Geschwind, Daniel H.; Rakic, Pasko

2014-01-01

To understand the emergence of human higher cognition, we must understand its biological substrate—the cerebral cortex, which considers itself the crowning achievement of evolution. Here, we describe how advances in developmental neurobiology, coupled with those in genetics, including adaptive protein evolution via gene duplications and the emergence of novel regulatory elements, can provide insights into the evolutionary mechanisms culminating in the human cerebrum. Given that the massive expansion of the cortical surface and elaboration of its connections in humans originates from developmental events, understanding the genetic regulation of cell number, neuronal migration to proper layers, columns, and regions, and ultimately their differentiation into specific phenotypes, is critical. The pre- and postnatal environment also interacts with the cellular substrate to yield a basic network that is refined via selection and elimination of synaptic connections, a process that is prolonged in humans. This knowledge provides essential insight into the pathogenesis of human-specific neuropsychiatric disorders. PMID:24183016

Automating cell detection and classification in human brain fluorescent microscopy images using dictionary learning and sparse coding.

PubMed

Alegro, Maryana; Theofilas, Panagiotis; Nguy, Austin; Castruita, Patricia A; Seeley, William; Heinsen, Helmut; Ushizima, Daniela M; Grinberg, Lea T

2017-04-15

Immunofluorescence (IF) plays a major role in quantifying protein expression in situ and understanding cell function. It is widely applied in assessing disease mechanisms and in drug discovery research. Automation of IF analysis can transform studies using experimental cell models. However, IF analysis of postmortem human tissue relies mostly on manual interaction, often subjected to low-throughput and prone to error, leading to low inter and intra-observer reproducibility. Human postmortem brain samples challenges neuroscientists because of the high level of autofluorescence caused by accumulation of lipofuscin pigment during aging, hindering systematic analyses. We propose a method for automating cell counting and classification in IF microscopy of human postmortem brains. Our algorithm speeds up the quantification task while improving reproducibility. Dictionary learning and sparse coding allow for constructing improved cell representations using IF images. These models are input for detection and segmentation methods. Classification occurs by means of color distances between cells and a learned set. Our method successfully detected and classified cells in 49 human brain images. We evaluated our results regarding true positive, false positive, false negative, precision, recall, false positive rate and F1 score metrics. We also measured user-experience and time saved compared to manual countings. We compared our results to four open-access IF-based cell-counting tools available in the literature. Our method showed improved accuracy for all data samples. The proposed method satisfactorily detects and classifies cells from human postmortem brain IF images, with potential to be generalized for applications in other counting tasks. Copyright © 2017 Elsevier B.V. All rights reserved.

Dissociable brain biomarkers of fluid intelligence.

PubMed

Paul, Erick J; Larsen, Ryan J; Nikolaidis, Aki; Ward, Nathan; Hillman, Charles H; Cohen, Neal J; Kramer, Arthur F; Barbey, Aron K

2016-08-15

Cognitive neuroscience has long sought to understand the biological foundations of human intelligence. Decades of research have revealed that general intelligence is correlated with two brain-based biomarkers: the concentration of the brain biochemical N-acetyl aspartate (NAA) measured by proton magnetic resonance spectroscopy (MRS) and total brain volume measured using structural MR imaging (MRI). However, the relative contribution of these biomarkers in predicting performance on core facets of human intelligence remains to be well characterized. In the present study, we sought to elucidate the role of NAA and brain volume in predicting fluid intelligence (Gf). Three canonical tests of Gf (BOMAT, Number Series, and Letter Sets) and three working memory tasks (Reading, Rotation, and Symmetry span tasks) were administered to a large sample of healthy adults (n=211). We conducted exploratory factor analysis to investigate the factor structure underlying Gf independent from working memory and observed two Gf components (verbal/spatial and quantitative reasoning) and one working memory component. Our findings revealed a dissociation between two brain biomarkers of Gf (controlling for age and sex): NAA concentration correlated with verbal/spatial reasoning, whereas brain volume correlated with quantitative reasoning and working memory. A follow-up analysis revealed that this pattern of findings is observed for males and females when analyzed separately. Our results provide novel evidence that distinct brain biomarkers are associated with specific facets of human intelligence, demonstrating that NAA and brain volume are independent predictors of verbal/spatial and quantitative facets of Gf. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Foundations for a New Science of Learning

PubMed Central

Meltzoff, Andrew N.; Kuhl, Patricia K.; Movellan, Javier; Sejnowski, Terrence J.

2009-01-01

Human learning is distinguished by the range and complexity of skills that can be learned and the degree of abstraction that can be achieved compared to other species. Humans are also the only species that has developed formal ways to enhance learning: teachers, schools, and curricula. Human infants have an intense interest in people and their behavior, and possess powerful implicit learning mechanisms that are affected by social interaction. Neuroscientists are beginning to understand the brain mechanisms underlying learning and how shared brain systems for perception and action support social learning. Machine learning algorithms are being developed that allow robots and computers to learn autonomously. New insights from many different fields are converging to create a new science of learning that may transform educational practices. PMID:19608908

A network engineering perspective on probing and perturbing cognition with neurofeedback

PubMed Central

Khambhati, Ankit N.

2017-01-01

Network science and engineering provide a flexible and generalizable tool set to describe and manipulate complex systems characterized by heterogeneous interaction patterns among component parts. While classically applied to social systems, these tools have recently proven to be particularly useful in the study of the brain. In this review, we describe the nascent use of these tools to understand human cognition, and we discuss their utility in informing the meaningful and predictable perturbation of cognition in combination with the emerging capabilities of neurofeedback. To blend these disparate strands of research, we build on emerging conceptualizations of how the brain functions (as a complex network) and how we can develop and target interventions or modulations (as a form of network control). We close with an outline of current frontiers that bridge neurofeedback, connectomics, and network control theory to better understand human cognition. PMID:28445589

A Multiscale Parallel Computing Architecture for Automated Segmentation of the Brain Connectome

PubMed Central

Knobe, Kathleen; Newton, Ryan R.; Schlimbach, Frank; Blower, Melanie; Reid, R. Clay

2015-01-01

Several groups in neurobiology have embarked into deciphering the brain circuitry using large-scale imaging of a mouse brain and manual tracing of the connections between neurons. Creating a graph of the brain circuitry, also called a connectome, could have a huge impact on the understanding of neurodegenerative diseases such as Alzheimer’s disease. Although considerably smaller than a human brain, a mouse brain already exhibits one billion connections and manually tracing the connectome of a mouse brain can only be achieved partially. This paper proposes to scale up the tracing by using automated image segmentation and a parallel computing approach designed for domain experts. We explain the design decisions behind our parallel approach and we present our results for the segmentation of the vasculature and the cell nuclei, which have been obtained without any manual intervention. PMID:21926011

A guide to using functional magnetic resonance imaging to study Alzheimer's disease in animal models.

PubMed

Asaad, Mazen; Lee, Jin Hyung

2018-05-18

Alzheimer's disease is a leading healthcare challenge facing our society today. Functional magnetic resonance imaging (fMRI) of the brain has played an important role in our efforts to understand how Alzheimer's disease alters brain function. Using fMRI in animal models of Alzheimer's disease has the potential to provide us with a more comprehensive understanding of the observations made in human clinical fMRI studies. However, using fMRI in animal models of Alzheimer's disease presents some unique challenges. Here, we highlight some of these challenges and discuss potential solutions for researchers interested in performing fMRI in animal models. First, we briefly summarize our current understanding of Alzheimer's disease from a mechanistic standpoint. We then overview the wide array of animal models available for studying this disease and how to choose the most appropriate model to study, depending on which aspects of the condition researchers seek to investigate. Finally, we discuss the contributions of fMRI to our understanding of Alzheimer's disease and the issues to consider when designing fMRI studies for animal models, such as differences in brain activity based on anesthetic choice and ways to interrogate more specific questions in rodents beyond those that can be addressed in humans. The goal of this article is to provide information on the utility of fMRI, and approaches to consider when using fMRI, for studies of Alzheimer's disease in animal models. © 2018. Published by The Company of Biologists Ltd.

A guide to using functional magnetic resonance imaging to study Alzheimer's disease in animal models

PubMed Central

Asaad, Mazen

2018-01-01

ABSTRACT Alzheimer's disease is a leading healthcare challenge facing our society today. Functional magnetic resonance imaging (fMRI) of the brain has played an important role in our efforts to understand how Alzheimer's disease alters brain function. Using fMRI in animal models of Alzheimer's disease has the potential to provide us with a more comprehensive understanding of the observations made in human clinical fMRI studies. However, using fMRI in animal models of Alzheimer's disease presents some unique challenges. Here, we highlight some of these challenges and discuss potential solutions for researchers interested in performing fMRI in animal models. First, we briefly summarize our current understanding of Alzheimer's disease from a mechanistic standpoint. We then overview the wide array of animal models available for studying this disease and how to choose the most appropriate model to study, depending on which aspects of the condition researchers seek to investigate. Finally, we discuss the contributions of fMRI to our understanding of Alzheimer's disease and the issues to consider when designing fMRI studies for animal models, such as differences in brain activity based on anesthetic choice and ways to interrogate more specific questions in rodents beyond those that can be addressed in humans. The goal of this article is to provide information on the utility of fMRI, and approaches to consider when using fMRI, for studies of Alzheimer's disease in animal models. PMID:29784664

Genetics of human hydrocephalus

PubMed Central

Williams, Michael A.; Rigamonti, Daniele

2006-01-01

Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders. A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus. Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human hydrocephalus. This review summarizes the recent findings on this issue among human and animal models, especially with reference to the molecular genetics, pathological, physiological and cellular studies, and identifies future research directions. PMID:16773266

Annual Research Review: Growth connectomics – the organization and reorganization of brain networks during normal and abnormal development

PubMed Central

Vértes, Petra E; Bullmore, Edward T

2015-01-01

Background We first give a brief introduction to graph theoretical analysis and its application to the study of brain network topology or connectomics. Within this framework, we review the existing empirical data on developmental changes in brain network organization across a range of experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans). Synthesis We discuss preliminary evidence and current hypotheses for how the emergence of network properties correlates with concomitant cognitive and behavioural changes associated with development. We highlight some of the technical and conceptual challenges to be addressed by future developments in this rapidly moving field. Given the parallels previously discovered between neural systems across species and over a range of spatial scales, we also review some recent advances in developmental network studies at the cellular scale. We highlight the opportunities presented by such studies and how they may complement neuroimaging in advancing our understanding of brain development. Finally, we note that many brain and mind disorders are thought to be neurodevelopmental in origin and that charting the trajectory of brain network changes associated with healthy development also sets the stage for understanding abnormal network development. Conclusions We therefore briefly review the clinical relevance of network metrics as potential diagnostic markers and some recent efforts in computational modelling of brain networks which might contribute to a more mechanistic understanding of neurodevelopmental disorders in future. PMID:25441756

The role of the microbiome for human health: from basic science to clinical applications.

PubMed

Mohajeri, M Hasan; Brummer, Robert J M; Rastall, Robert A; Weersma, Rinse K; Harmsen, Hermie J M; Faas, Marijke; Eggersdorfer, Manfred

2018-05-10

The 2017 annual symposium organized by the University Medical Center Groningen in The Netherlands focused on the role of the gut microbiome in human health and disease. Experts from academia and industry examined interactions of prebiotics, probiotics, or vitamins with the gut microbiome in health and disease, the development of the microbiome in early-life and the role of the microbiome on the gut-brain axis. The gut microbiota changes dramatically during pregnancy and intrinsic factors (such as stress), in addition to extrinsic factors (such as diet, and drugs) influence the composition and activity of the gut microbiome throughout life. Microbial metabolites, e.g. short-chain fatty acids affect gut-brain signaling and the immune response. The gut microbiota has a regulatory role on anxiety, mood, cognition and pain which is exerted via the gut-brain axis. Ingestion of prebiotics or probiotics has been used to treat a range of conditions including constipation, allergic reactions and infections in infancy, and IBS. Fecal microbiota transplantation (FMT) highly effective for treating recurrent Clostridium difficile infections. The gut microbiome affects virtually all aspects of human health, but the degree of scientific evidence, the models and technologies and the understanding of mechanisms of action vary considerably from one benefit area to the other. For a clinical practice to be broadly accepted, the mode of action, the therapeutic window, and potential side effects need to thoroughly be investigated. This calls for further coordinated state-of-the art research to better understand and document the human gut microbiome's effects on human health.

The art of seeing and painting.

PubMed

Grossberg, Stephen

2008-01-01

The human urge to represent the three-dimensional world using two-dimensional pictorial representations dates back at least to Paleolithic times. Artists from ancient to modern times have struggled to understand how a few contours or color patches on a flat surface can induce mental representations of a three-dimensional scene. This article summarizes some of the recent breakthroughs in scientifically understanding how the brain sees that shed light on these struggles. These breakthroughs illustrate how various artists have intuitively understood paradoxical properties about how the brain sees, and have used that understanding to create great art. These paradoxical properties arise from how the brain forms the units of conscious visual perception; namely, representations of three-dimensional boundaries and surfaces. Boundaries and surfaces are computed in parallel cortical processing streams that obey computationally complementary properties. These streams interact at multiple levels to overcome their complementary weaknesses and to transform their complementary properties into consistent percepts. The article describes how properties of complementary consistency have guided the creation of many great works of art.

Neurolaw: A brief introduction

PubMed Central

Petoft, Arian

2015-01-01

Neurolaw, as an interdisciplinary field which links the brain to law, facilitates the pathway to better understanding of human behavior in order to regulate it accurately through incorporating neuroscience achievements in legal studies. Since 1990’s, this emerging field, by study on human nervous system as a new dimension of legal phenomena, leads to a more precise explanation for human behavior to revise legal rules and decision-makings. This paper strives to bring about significantly a brief introduction to neurolaw so as to take effective steps toward exploring and expanding the scope of law and more thorough understanding of legal issues in the field at hand. PMID:25874060

Content of endoplasmic reticulum and Golgi complex membranes positively correlates with the proliferative status of brain cells.

PubMed

Silvestre, David C; Maccioni, Hugo J F; Caputto, Beatriz L

2009-03-01

Although the molecular and cellular basis of particular events that lead to the biogenesis of membranes in eukaryotic cells has been described in detail, understanding of the intrinsic complexity of the pleiotropic response by which a cell adjusts the overall activity of its endomembrane system to accomplish these requirements is limited. Here we carried out an immunocytochemical and biochemical examination of the content and quality of the endoplasmic reticulum (ER) and Golgi apparatus membranes in two in vivo situations characterized by a phase of active cell proliferation followed by a phase of declination in proliferation (rat brain tissue at early and late developmental stages) or by permanent active proliferation (gliomas and their most malignant manifestation, glioblastomas multiforme). It was found that, in highly proliferative phases of brain development (early embryo brain cells), the content of ER and Golgi apparatus membranes, measured as total lipid phosphorous content, is higher than in adult brain cells. In addition, the concentration of protein markers of ER and Golgi is also higher in early embryo brain cells and in human glioblastoma multiforme cells than in adult rat brain or in nonpathological human brain cells. Results suggest that the amount of endomembranes and the concentration of constituent functional proteins diminish as cells decline in their proliferative activity.

Physical biology of human brain development.

PubMed

Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

2015-01-01

Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view toward surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level toward form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.

Genomic Perspectives of Transcriptional Regulation in Forebrain Development

DOE PAGES

Nord, Alex S.; Pattabiraman, Kartik; Visel, Axel; ...

2015-01-07

The forebrain is the seat of higher-order brain functions, and many human neuropsychiatric disorders are due to genetic defects affecting forebrain development, making it imperative to understand the underlying genetic circuitry. We report that recent progress now makes it possible to begin fully elucidating the genomic regulatory mechanisms that control forebrain gene expression. Here, we discuss the current knowledge of how transcription factors drive gene expression programs through their interactions with cis-acting genomic elements, such as enhancers; how analyses of chromatin and DNA modifications provide insights into gene expression states; and how these approaches yield insights into the evolution ofmore » the human brain.« less

Brain correlates of music-evoked emotions.

PubMed

Koelsch, Stefan

2014-03-01

Music is a universal feature of human societies, partly owing to its power to evoke strong emotions and influence moods. During the past decade, the investigation of the neural correlates of music-evoked emotions has been invaluable for the understanding of human emotion. Functional neuroimaging studies on music and emotion show that music can modulate activity in brain structures that are known to be crucially involved in emotion, such as the amygdala, nucleus accumbens, hypothalamus, hippocampus, insula, cingulate cortex and orbitofrontal cortex. The potential of music to modulate activity in these structures has important implications for the use of music in the treatment of psychiatric and neurological disorders.

Establishment and characterization of a new conditionally immortalized human astrocyte cell line.

PubMed

Furihata, Tomomi; Ito, Ryo; Kamiichi, Atsuko; Saito, Kosuke; Chiba, Kan

2016-01-01

Astrocytes are the most abundant cell types in mammalian brains, within which they participate in various neuronal activities, partly by utilizing the numerous transporters expressed at their plasma membranes. Accordingly, detailed characterization of astrocytic functions, including transporters, are essential for understanding of mechanistic basis of normal brain functions, as well as the pathogenesis and treatment of various brain diseases. As a part of overall efforts to facilitate such studies, this study reports on the establishment of a new human astrocyte cell line, which is hereafter referred to as human astrocyte/conditionally immortalized, clone 35 (HASTR/ci35). This line, which was developed utilizing a cell immortalization method, showed excellent proliferative ability and expressed various astrocyte markers, including glial fibrillary acidic protein. When co-cultured with neuronal cells, HASTR/ci35 cells could facilitate their dendritic network formation. Furthermore, HASTR/ci35 cells not only possessed significant glutamate and adenosine transporter activities but also exhibited organic ion transporter activities. To summarize, HASTR/ci35 cells possess several key astrocytic characteristics, including various transporter functions, while simultaneously showing infinite proliferation and scalability. Based on these findings, HASTR/ci35 cells can be expected to contribute significantly to various human astrocyte study fields. In vitro astrocyte models are valuable experimental tools in various astrocyte studies. Here, we report the establishment of a new human astrocyte cell line, HASTR/ci35, which show various key astrocyte properties, including astrocytic transporter activities, glycogen storage and facilitation of neuronal cell differentiation. Thus, HASTR/ci35 is expected to significantly contribute to advances toward detailed understanding of human astrocyte functions. © 2015 International Society for Neurochemistry.

The neural bases for valuing social equality.

PubMed

Aoki, Ryuta; Yomogida, Yukihito; Matsumoto, Kenji

2015-01-01

The neural basis of how humans value and pursue social equality has become a major topic in social neuroscience research. Although recent studies have identified a set of brain regions and possible mechanisms that are involved in the neural processing of equality of outcome between individuals, how the human brain processes equality of opportunity remains unknown. In this review article, first we describe the importance of the distinction between equality of outcome and equality of opportunity, which has been emphasized in philosophy and economics. Next, we discuss possible approaches for empirical characterization of human valuation of equality of opportunity vs. equality of outcome. Understanding how these two concepts are distinct and interact with each other may provide a better explanation of complex human behaviors concerning fairness and social equality. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Understanding Fluid Shifts in the Brain: Choroidal Regulation Involved in the Cerebral Fluid Response to Altered Gravity

NASA Technical Reports Server (NTRS)

Gabrion, Jaqueline; Vasques, Marilyn; Aquilina, Rudy (Technical Monitor)

2002-01-01

Fluid balance and regulation of body fluid production are critical aspects of life and survival on Earth. In space, without gravity exerting its usual downward pulling effect, the fluids of the human body shift in an unnatural, headward direction. After awhile, humans and other mammalian species adapt to the microgravity environment which leads to changes in the regulation and distribution of these body fluids. Previous spaceflight experiments have indicated that production of fluid in the brain and spinal cord, cerebrospinal fluid (CSF), might be reduced in rats exposed to microgravity. In this experiment conducted by Dr. Jacqueline Gabrion (University of Pierre and Marie Curie, France), proteins important for CSF production, and several molecules that regulate water and mineral transport, will be investigated in rats flown on the Shuttle. Dr. Gabrion and her team will determine the amounts of these proteins and molecules present in the brain in order to evaluate whether any changes have taken place during the rats' adaptation to microgravity. The levels of different aquaporins (proteins that act as a channel for water transport in and out of cells) will also be investigated in other areas of the brain and body to better understand the regulatory responses affecting these important water channel proteins. In addition to producing essential and basic information about fluid production in the brain and body, this experiment will reveal fundamental information about the mechanisms involved in cerebral adaptation and fluid balance during spaceflight.

Prairie Voles as a Model for Understanding the Genetic and Epigenetic Regulation of Attachment Behaviors.

PubMed

Sadino, Julie M; Donaldson, Zoe R

2018-04-06

Over a lifetime, humans build relationships with family, friends, and partners that are critically important for our mental and physical health. Unlike commonly used laboratory mice and rats, Microtine rodents provide a unique model to study the neurobiology underlying pair bonding and the selective attachments that form between adults. Comparisons between monogamous prairie voles and the closely related but nonmonogamous meadow and montane voles have revealed that brain-region-specific neuropeptide receptor patterning modulates social behavior between and within species. In particular, diversity in vasopressin 1a receptor (V1aR) distribution has been linked to individual and species differences in monogamy-related behaviors such as partner preference, mate guarding, and space use. Given the importance of differential receptor expression for regulating social behavior, a critical question has emerged: What are the genetic and epigenetic mechanisms that underlie brain-region-specific receptor patterns? This review will summarize what is known about how the vasopressin (AVP)-V1aR axis regulates social behaviors via signaling in discrete brain regions. From this work, we propose that brain-region-specific regulatory mechanisms facilitate robust evolvability of V1aR expression to generate diverse sociobehavioral traits. Translationally, we provide a perspective on how these studies have contributed to our understanding of human social behaviors and how brain-region-specific regulatory mechanisms might be harnessed for targeted therapies to treat social deficits in psychiatric disorders such as depression, complicated grief, and autism spectrum disorder.

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.

Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis.

PubMed

Stillman, Chelsea M; Cohen, Jamie; Lehman, Morgan E; Erickson, Kirk I

2016-01-01

Physical activity (PA) is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts.

Naturalistic Field Studies of Sleep and Performance

DTIC Science & Technology

2011-05-01

delight: The affective pleasures and pains of  brain   system  for eating and energy regulation  In, L. Dube, A. Bechara, A. Drewnowski, J.  LeBel, P. James...understanding the  brain  organization of sleep in humans and animals and on using  this understanding to link sleep, by way of the underlying...homeostatic (use dependent) drive for sleep. Thompson et al.  (2010) found biological markers at the molecular level of sleep deprivation in the  mouse  brain

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.

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

NASA Astrophysics Data System (ADS)

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

2017-04-01

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

Machine Understanding of Human Implicit Intention

DTIC Science & Technology

2013-05-18

Cognitive Neurodynamics , Hokkaido, Japan, June 2011, Hokkaido, Japan (Plenary Talk) - Soo-Young Lee, Implicit Intention Recognition and Hierarchical...subject’s response with the accuracy of about 80% by SVM. 15. SUBJECT TERMS Brain Science and Engineering; Cognitive Neuroscience; Human-Computer...oscillations have been related to a variety of functions such as perception, cognition , sleep, etc. For a long time, researchers have found the sensory and

Mapping Neurodegenerative Disease Onset and Progression.

PubMed

Seeley, William W

2017-08-01

Brain networks have been of long-standing interest to neurodegeneration researchers, including but not limited to investigators focusing on conventional prion diseases, which are known to propagate along neural pathways. Tools for human network mapping, however, remained inadequate, limiting our understanding of human brain network architecture and preventing clinical research applications. Until recently, neuropathological studies were the only viable approach to mapping disease onset and progression in humans but required large autopsy cohorts and laborious methods for whole-brain sectioning and staining. Despite important advantages, postmortem studies cannot address in vivo, physiological, or longitudinal questions and have limited potential to explore early-stage disease except for the most common disorders. Emerging in vivo network-based neuroimaging strategies have begun to address these issues, providing data that complement the neuropathological tradition. Overall, findings to date highlight several fundamental principles of neurodegenerative disease anatomy and pathogenesis, as well as some enduring mysteries. These principles and mysteries provide a road map for future research. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Hypothesis-driven methods to augment human cognition by optimizing cortical oscillations

PubMed Central

Horschig, Jörn M.; Zumer, Johanna M.; Bahramisharif, Ali

2014-01-01

Cortical oscillations have been shown to represent fundamental functions of a working brain, e.g., communication, stimulus binding, error monitoring, and inhibition, and are directly linked to behavior. Recent studies intervening with these oscillations have demonstrated effective modulation of both the oscillations and behavior. In this review, we collect evidence in favor of how hypothesis-driven methods can be used to augment cognition by optimizing cortical oscillations. We elaborate their potential usefulness for three target groups: healthy elderly, patients with attention deficit/hyperactivity disorder, and healthy young adults. We discuss the relevance of neuronal oscillations in each group and show how each of them can benefit from the manipulation of functionally-related oscillations. Further, we describe methods for manipulation of neuronal oscillations including direct brain stimulation as well as indirect task alterations. We also discuss practical considerations about the proposed techniques. In conclusion, we propose that insights from neuroscience should guide techniques to augment human cognition, which in turn can provide a better understanding of how the human brain works. PMID:25018706

Soluble Amyloid-beta Aggregates from Human Alzheimer’s Disease Brains

PubMed Central

Esparza, Thomas J.; Wildburger, Norelle C.; Jiang, Hao; Gangolli, Mihika; Cairns, Nigel J.; Bateman, Randall J.; Brody, David L.

2016-01-01

Soluble amyloid-beta (Aβ) aggregates likely contribute substantially to the dementia that characterizes Alzheimer’s disease. However, despite intensive study of in vitro preparations and animal models, little is known about the characteristics of soluble Aβ aggregates in the human Alzheimer’s disease brain. Here we present a new method for extracting soluble Aβ aggregates from human brains, separating them from insoluble aggregates and Aβ monomers using differential ultracentrifugation, and purifying them >6000 fold by dual antibody immunoprecipitation. The method resulted in <40% loss of starting material, no detectible ex vivo aggregation of monomeric Aβ, and no apparent ex vivo alterations in soluble aggregate sizes. By immunoelectron microscopy, soluble Aβ aggregates typically appear as clusters of 10–20 nanometer diameter ovoid structures with 2-3 amino-terminal Aβ antibody binding sites, distinct from previously characterized structures. This approach may facilitate investigation into the characteristics of native soluble Aβ aggregates, and deepen our understanding of Alzheimer’s dementia. PMID:27917876

Mechanisms and functions of brain and behavioural asymmetries

PubMed Central

Tommasi, Luca

2008-01-01

For almost a century the field of brain and behavioural asymmetries has been dominated by studies on humans, resting on the evidence that the anatomical structures underlying language functions are asymmetrical, and that human handedness is lateralized at the population level. Today, there is not only evidence of population-level lateralization of brain and behaviour across a variety of vertebrate and invertebrate species, but also a growing consensus that the comparative analysis of the environmental and developmental factors that give origin to neural and behavioural laterality in animal models, together with theoretical analyses of their costs and benefits, will be crucial for understanding the evolutionary pathways that led to such a multifaceted phenomenon. The present theme issue provides a survey of theoretical, review and research work cutting across the biological and the cognitive sciences, focusing on various species of fishes, birds and primates (including humans) and emphasizing an integrative approach to the study of lateralization encompassing neural, behavioural, cognitive, developmental and environmental aspects. PMID:19064348

Evidence for a distributed hierarchy of action representation in the brain

PubMed Central

Grafton, Scott T.; de C. Hamilton, Antonia F.

2007-01-01

Complex human behavior is organized around temporally distal outcomes. Behavioral studies based on tasks such as normal prehension, multi-step object use and imitation establish the existence of relative hierarchies of motor control. The retrieval errors in apraxia also support the notion of a hierarchical model for representing action in the brain. In this review, three functional brain imaging studies of action observation using the method of repetition suppression are used to identify a putative neural architecture that supports action understanding at the level of kinematics, object centered goals and ultimately, motor outcomes. These results, based on observation, may match a similar functional anatomic hierarchy for action planning and execution. If this is true, then the findings support a functional anatomic model that is distributed across a set of interconnected brain areas that are differentially recruited for different aspects of goal oriented behavior, rather than a homogeneous mirror neuron system for organizing and understanding all behavior. PMID:17706312

Future Directions for Examination of Brain Networks in Neurodevelopmental Disorders.

PubMed

Uddin, Lucina Q; Karlsgodt, Katherine H

2018-01-01

Neurodevelopmental disorders are associated with atypical development and maturation of brain networks. A recent focus on human connectomics research and the growing popularity of open science initiatives has created the ideal climate in which to make real progress toward understanding the neurobiology of disorders affecting youth. Here we outline future directions for neuroscience researchers examining brain networks in neurodevelopmental disorders, highlighting gaps in the current literature. We emphasize the importance of leveraging large neuroimaging and phenotypic data sets recently made available to the research community, and we suggest specific novel methodological approaches, including analysis of brain dynamics and structural connectivity, that have the potential to produce the greatest clinical insight. Transdiagnostic approaches will also become increasingly necessary as the Research Domain Criteria framework put forth by the National Institute of Mental Health permeates scientific discourse. During this exciting era of big data and increased computational sophistication of analytic tools, the possibilities for significant advancement in understanding neurodevelopmental disorders are limitless.

Neuroscience, neurohistory, and the history of science: a tale of two brain images.

PubMed

Fuller, Steve

2014-03-01

This essay introduces a Focus section on "Neurohistory and History of Science" by distinguishing images of the brain as governor and as transducer: the former treat the brain as the executive control center of the body, the latter as an interface between the organism and reality at large. Most of the consternation expressed in the symposium about the advent of neurohistory derives from the brain-as-governor conception, which is rooted in a "biologistic" understanding of humanity that in recent years has become bound up in various nefarious "neoliberal" political and economic agendas. However, given the sophisticated attitude that neurohistory's leading champion, Daniel Smail, displays toward evolutionary theory's potential impact on historical practice, he is perhaps better understood as part of the brain-as-transducer tradition. This tradition, largely suppressed in current representations of neuroscience, has a strong theological provenance, ultimately concerned with our becoming attuned to the divine frequency, not least by extending the powers of the human nervous system through technology. This essay sympathetically explores the implications of this perspective for historical practice.

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

Human Development XIII: The Connection Between the Structure of the Overtone System and the Tone Language of Music. Some Implications for Our Understanding of the Human Brain

PubMed Central

Ventegodt, Søren; Hermansen, Tyge Dahl; Kandel, Isack; Merrick, Joav

2008-01-01

The functioning brain behaves like one highly-structured, coherent, informational field. It can be popularly described as a “coherent ball of energy”, making the idea of a local highly-structured quantum field that carries the consciousness very appealing. If that is so, the structure of the experience of music might be a quite unique window into a hidden quantum reality of the brain, and even of life itself. The structure of music is then a mirror of a much more complex, but similar, structure of the energetic field of the working brain. This paper discusses how the perception of music is organized in the human brain with respect to the known tone scales of major and minor. The patterns used by the brain seem to be similar to the overtones of vibrating matter, giving a positive experience of harmonies in major. However, we also like the minor scale, which can explain brain patterns as fractal-like, giving a symmetric “downward reflection” of the major scale into the minor scale. We analyze the implication of beautiful and ugly tones and harmonies for the model. We conclude that when it comes to simple perception of harmonies, the most simple is the most beautiful and the most complex is the most ugly, but in music, even the most disharmonic harmony can be beautiful, if experienced as a part of a dynamic release of musical tension. This can be taken as a general metaphor of painful, yet meaningful, and developing experiences in human life. PMID:18661052

Selective Limbic Blood–Brain Barrier Breakdown in a Feline Model of Limbic Encephalitis with LGI1 Antibodies

PubMed Central

Tröscher, Anna R.; Klang, Andrea; French, Maria; Quemada-Garrido, Lucía; Kneissl, Sibylle Maria; Bien, Christian G.; Pákozdy, Ákos; Bauer, Jan

2017-01-01

Human leucine-rich glioma-inactivated protein 1 encephalitis (LGI1) is an autoimmune limbic encephalitis in which serum and cerebrospinal fluid contain antibodies targeting LGI1, a protein of the voltage gated potassium channel (VGKC) complex. Recently, we showed that a feline model of limbic encephalitis with LGI1 antibodies, called feline complex partial seizures with orofacial involvement (FEPSO), is highly comparable to human LGI1 encephalitis. In human LGI1 encephalitis, neuropathological investigations are difficult because very little material is available. Taking advantage of this natural animal model to study pathological mechanisms will, therefore, contribute to a better understanding of its human counterpart. Here, we present a brain-wide histopathological analysis of FEPSO. We discovered that blood–brain barrier (BBB) leakage was present not only in all regions of the hippocampus but also in other limbic structures such as the subiculum, amygdale, and piriform lobe. However, in other regions, such as the cerebellum, no leakage was observed. In addition, this brain-region-specific immunoglobulin leakage was associated with the breakdown of endothelial tight junctions. Brain areas affected by BBB dysfunction also revealed immunoglobulin and complement deposition as well as neuronal cell death. These neuropathological findings were supported by magnetic resonance imaging showing signal and volume increase in the amygdala and the piriform lobe. Importantly, we could show that BBB disturbance in LGI1 encephalitis does not depend on T cell infiltrates, which were present brain-wide. This finding points toward another, so far unknown, mechanism of opening the BBB. The limbic predilection sites of immunoglobulin antibody leakage into the brain may explain why most patients with LGI1 antibodies have a limbic phenotype even though LGI1, the target protein, is ubiquitously distributed across the central nervous system. PMID:29093718

Selective Limbic Blood-Brain Barrier Breakdown in a Feline Model of Limbic Encephalitis with LGI1 Antibodies.

PubMed

Tröscher, Anna R; Klang, Andrea; French, Maria; Quemada-Garrido, Lucía; Kneissl, Sibylle Maria; Bien, Christian G; Pákozdy, Ákos; Bauer, Jan

2017-01-01

Human leucine-rich glioma-inactivated protein 1 encephalitis (LGI1) is an autoimmune limbic encephalitis in which serum and cerebrospinal fluid contain antibodies targeting LGI1, a protein of the voltage gated potassium channel (VGKC) complex. Recently, we showed that a feline model of limbic encephalitis with LGI1 antibodies, called feline complex partial seizures with orofacial involvement (FEPSO), is highly comparable to human LGI1 encephalitis. In human LGI1 encephalitis, neuropathological investigations are difficult because very little material is available. Taking advantage of this natural animal model to study pathological mechanisms will, therefore, contribute to a better understanding of its human counterpart. Here, we present a brain-wide histopathological analysis of FEPSO. We discovered that blood-brain barrier (BBB) leakage was present not only in all regions of the hippocampus but also in other limbic structures such as the subiculum, amygdale, and piriform lobe. However, in other regions, such as the cerebellum, no leakage was observed. In addition, this brain-region-specific immunoglobulin leakage was associated with the breakdown of endothelial tight junctions. Brain areas affected by BBB dysfunction also revealed immunoglobulin and complement deposition as well as neuronal cell death. These neuropathological findings were supported by magnetic resonance imaging showing signal and volume increase in the amygdala and the piriform lobe. Importantly, we could show that BBB disturbance in LGI1 encephalitis does not depend on T cell infiltrates, which were present brain-wide. This finding points toward another, so far unknown, mechanism of opening the BBB. The limbic predilection sites of immunoglobulin antibody leakage into the brain may explain why most patients with LGI1 antibodies have a limbic phenotype even though LGI1, the target protein, is ubiquitously distributed across the central nervous system.

Beyond human intentions and emotions

PubMed Central

Juan, Elsa; Frum, Chris; Bianchi-Demicheli, Francesco; Wang, Yi-Wen; Lewis, James W.; Cacioppo, Stephanie

2013-01-01

Although significant advances have been made in our understanding of the neural basis of action observation and intention understanding in the last few decades by studies demonstrating the involvement of a specific brain network (action observation network; AON), these have been largely based on experimental studies in which people have been considered as strictly isolated entities. However, we, as social species, spend much more of our time performing actions interacting with others. Research shows that a person's position along the continuum of perceived social isolation/bonding to others is associated with a variety of physical and mental health effects. Thus, there is a crucial need to better understand the neural basis of intention understanding performed in interpersonal and emotional contexts. To address this issue, we performed a meta-analysis using of functional magnetic resonance imaging (fMRI) studies over the past decade that examined brain and cortical network processing associated with understanding the intention of others actions vs. those associated with passionate love for others. Both overlapping and distinct cortical and subcortical regions were identified for intention and love, respectively. These findings provide scientists and clinicians with a set of brain regions that can be targeted for future neuroscientific studies on intention understanding, and help develop neurocognitive models of pair-bonding. PMID:23543838

Review: Leon N. Cooper's Science and Human Experience: Values, Culture, and the Mind.

PubMed

Lynch, Gary S

2015-01-01

Why are we reviewing a book written by someone who shared in the 1972 Nobel Prize in Physics for work on superconductivity? Because shortly after winning the prize, Leon N. Cooper transitioned into brain research-specifically, the biological basis of memory. He became director of the Brown University Institute for Brain and Neural Systems, whose interdisciplinary program allowed him to integrate research on the brain, physics, and even philosophy. His new book tackles a diverse spectrum of topics and questions, including these: Does science have limits? Where does order come from? Can we understand consciousness?

Review: Leon N. Cooper’s Science and Human Experience: Values, Culture, and the Mind

PubMed Central

Lynch, Gary S.

2015-01-01

Why are we reviewing a book written by someone who shared in the 1972 Nobel Prize in Physics for work on superconductivity? Because shortly after winning the prize, Leon N. Cooper transitioned into brain research—specifically, the biological basis of memory. He became director of the Brown University Institute for Brain and Neural Systems, whose interdisciplinary program allowed him to integrate research on the brain, physics, and even philosophy. His new book tackles a diverse spectrum of topics and questions, including these: Does science have limits? Where does order come from? Can we understand consciousness? PMID:27358665

A technical guide to tDCS, and related non-invasive brain stimulation tools

PubMed Central

Woods, AJ; Antal, A; Bikson, M; Boggio, PS; Brunoni, AR; Celnik, P; Cohen, LG; Fregni, F; Herrmann, CS; Kappenman, ES; Knotkova, H; Liebetanz, D; Miniussi, C; Miranda, PC; Paulus, W; Priori, A; Reato, D; Stagg, C; Wenderoth, N; Nitsche, MA

2015-01-01

Transcranial electrical stimulation (tES), including transcranial direct and alternating current stimulation (tDCS, tACS) are non-invasive brain stimulation techniques increasingly used for modulation of central nervous system excitability in humans. Here we address methodological issues required for tES application. This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches. It aims to help the reader to appropriately design and conduct studies involving these brain stimulation techniques, understand limitations and avoid shortcomings, which might hamper the scientific rigor and potential applications in the clinical domain. PMID:26652115

Interactive natural language acquisition in a multi-modal recurrent neural architecture

NASA Astrophysics Data System (ADS)

Heinrich, Stefan; Wermter, Stefan

2018-01-01

For the complex human brain that enables us to communicate in natural language, we gathered good understandings of principles underlying language acquisition and processing, knowledge about sociocultural conditions, and insights into activity patterns in the brain. However, we were not yet able to understand the behavioural and mechanistic characteristics for natural language and how mechanisms in the brain allow to acquire and process language. In bridging the insights from behavioural psychology and neuroscience, the goal of this paper is to contribute a computational understanding of appropriate characteristics that favour language acquisition. Accordingly, we provide concepts and refinements in cognitive modelling regarding principles and mechanisms in the brain and propose a neurocognitively plausible model for embodied language acquisition from real-world interaction of a humanoid robot with its environment. In particular, the architecture consists of a continuous time recurrent neural network, where parts have different leakage characteristics and thus operate on multiple timescales for every modality and the association of the higher level nodes of all modalities into cell assemblies. The model is capable of learning language production grounded in both, temporal dynamic somatosensation and vision, and features hierarchical concept abstraction, concept decomposition, multi-modal integration, and self-organisation of latent representations.

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.

Gaining insight of fetal brain development with diffusion MRI and histology.

PubMed

Huang, Hao; Vasung, Lana

2014-02-01

Human brain is extraordinarily complex and yet its origin is a simple tubular structure. Its development during the fetal period is characterized by a series of accurately organized events which underlie the mechanisms of dramatic structural changes during fetal development. Revealing detailed anatomy at different stages of human fetal brain development provides insight on understanding not only this highly ordered process, but also the neurobiological foundations of cognitive brain disorders such as mental retardation, autism, schizophrenia, bipolar and language impairment. Diffusion tensor imaging (DTI) and histology are complementary tools which are capable of delineating the fetal brain structures at both macroscopic and microscopic levels. In this review, the structural development of the fetal brains has been characterized with DTI and histology. Major components of the fetal brain, including cortical plate, fetal white matter and cerebral wall layer between the ventricle and subplate, have been delineated with DTI and histology. Anisotropic metrics derived from DTI were used to quantify the microstructural changes during the dynamic process of human fetal cortical development and prenatal development of other animal models. Fetal white matter pathways have been traced with DTI-based tractography to reveal growth patterns of individual white matter tracts and corticocortical connectivity. These detailed anatomical accounts of the structural changes during fetal period may provide the clues of detecting developmental and cognitive brain disorders at their early stages. The anatomical information from DTI and histology may also provide reference standards for diagnostic radiology of premature newborns. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

A Novel Method for Quantifying Human In Situ Whole Brain Deformation under Rotational Loading Using Sonomicrometry.

PubMed

Alshareef, Ahmed; Giudice, J Sebastian; Forman, Jason; Salzar, Robert S; Panzer, Matthew B

2018-03-01

Traumatic brain injuries (TBI) are one of the least understood injuries to the body. Finite element (FE) models of the brain have been crucial for understanding concussion and for developing injury mitigation systems; however, the experimental brain deformation data currently used to validate these models are limited. The objective of this study was to develop a methodology for the investigation of in situ three-dimensional brain deformation during pure rotational loading of the head, using sonomicrometry. Sonomicrometry uses ultrasonic pulses to measure the dynamic distances between piezoelectric crystals implanted in any sound-transmitting media. A human cadaveric head-neck specimen was acquired 14 h postmortem and was instrumented with an array of 32 small sonomicrometry crystals embedded in the head: 24 crystals were implanted in the brain, and 8 were fixed to the inner skull. A dynamic rotation was then applied to the head using a closed-loop controlled test device. Four pulses with different severity levels were applied around three orthogonal anatomical axes of rotation. A repeated test of the highest severity rotation was conducted in each axis to assess repeatability. All tests were completed within 56 h postmortem. Overall, the combined experimental and sonomicrometry methods were demonstrated to reliably and repeatedly capture three-dimensional dynamic deformation of an intact human brain. These methods provide a framework for using sonomicrometry to acquire multidimensional experimental data required for FE model development and validation, and will lend insight into the deformations sustained by the brain during impact.

Development of a computational model on the neural activity patterns of a visual working memory in a hierarchical feedforward Network

NASA Astrophysics Data System (ADS)

An, Soyoung; Choi, Woochul; Paik, Se-Bum

2015-11-01

Understanding the mechanism of information processing in the human brain remains a unique challenge because the nonlinear interactions between the neurons in the network are extremely complex and because controlling every relevant parameter during an experiment is difficult. Therefore, a simulation using simplified computational models may be an effective approach. In the present study, we developed a general model of neural networks that can simulate nonlinear activity patterns in the hierarchical structure of a neural network system. To test our model, we first examined whether our simulation could match the previously-observed nonlinear features of neural activity patterns. Next, we performed a psychophysics experiment for a simple visual working memory task to evaluate whether the model could predict the performance of human subjects. Our studies show that the model is capable of reproducing the relationship between memory load and performance and may contribute, in part, to our understanding of how the structure of neural circuits can determine the nonlinear neural activity patterns in the human brain.

The mirror neuron system: grasping others' actions from birth?

PubMed

Lepage, Jean-François; Théoret, Hugo

2007-09-01

In the adult human brain, the presence of a system matching the observation and the execution of actions is well established. This mechanism is thought to rely primarily on the contribution of so-called 'mirror neurons', cells that are active when a specific gesture is executed as well as when it is seen or heard. Despite the wealth of evidence detailing the existence of a mirror neuron system (MNS) in the adult brain, little is known about its normal development. Yet, a better understanding of the MNS in infants would be of considerable theoretical and clinical interest, as dysfunctions within the MNS have been demonstrated in neurodevelopmental disorders such as autism spectrum disorder. Arguments in favor of an innate, or very early, mechanism underlying action understanding mainly come from studies of neonatal imitation, the existence of which has been questioned by some. Here, we review evidence suggesting the presence of an MNS in the human child, as well as work that suggests, although indirectly, the existence of a mechanism matching the perception and the execution of actions in the human newborn.

Identification of the Upward Movement of Human CSF In Vivo and its Relation to the Brain Venous System.

PubMed

Dreha-Kulaczewski, Steffi; Joseph, Arun A; Merboldt, Klaus-Dietmar; Ludwig, Hans-Christoph; Gärtner, Jutta; Frahm, Jens

2017-03-01

CSF flux is involved in the pathophysiology of neurodegenerative diseases and cognitive impairment after traumatic brain injury, all hallmarked by the accumulation of cellular metabolic waste. Its effective disposal via various CSF routes has been demonstrated in animal models. In contrast, the CSF dynamics in humans are still poorly understood. Using novel real-time MRI, forced inspiration has been identified recently as a main driving force of CSF flow in the human brain. Exploiting technical advances toward real-time phase-contrast MRI, the current work analyzed directions, velocities, and volumes of human CSF flow within the brain aqueduct as part of the internal ventricular system and in the spinal canal during respiratory cycles. A consistent upward CSF movement toward the brain in response to forced inspiration was seen in all subjects at the aqueduct, in 11/12 subjects at thoracic level 2, and in 4/12 subjects at thoracic level 5. Concomitant analyses of CSF dynamics and cerebral venous blood flow, that is, in epidural veins at cervical level 3, uniquely demonstrated CSF and venous flow to be closely communicating cerebral fluid systems in which inspiration-induced downward flow of venous blood due to reduced intrathoracic pressure is counterbalanced by an upward movement of CSF. The results extend our understanding of human CSF flux and open important clinical implications, including concepts for drug delivery and new classifications and therapeutic options for various forms of hydrocephalus and idiopathic intracranial hypertension. SIGNIFICANCE STATEMENT Effective disposal of brain cellular waste products via CSF has been demonstrated repeatedly in animal models. However, CSF dynamics in humans are still poorly understood. A novel quantitative real-time MRI technique yielded in vivo CSF flow directions, velocities, and volumes in the human brain and upper spinal canal. CSF moved upward toward the head in response to forced inspiration. Concomitant analysis of brain venous blood flow indicated that CSF and venous flux act as closely communicating systems. The finding of a human CSF-venous network with upward CSF net movement opens new clinical concepts for drug delivery and new classifications and therapeutic options for various forms of hydrocephalus and ideopathic intracranial hypertension. Copyright © 2017 the authors 0270-6474/17/372395-08$15.00/0.

Enhanced functional connectivity properties of human brains during in-situ nature experience

PubMed Central

2016-01-01

In this study, we investigated the impacts of in-situ nature and urban exposure on human brain activities and their dynamics. We randomly assigned 32 healthy right-handed college students (mean age = 20.6 years, SD = 1.6; 16 males) to a 20 min in-situ sitting exposure in either a nature (n = 16) or urban environment (n = 16) and measured their Electroencephalography (EEG) signals. Analyses revealed that a brief in-situ restorative nature experience may induce more efficient and stronger brain connectivity with enhanced small-world properties compared with a stressful urban experience. The enhanced small-world properties were found to be correlated with “coherent” experience measured by Perceived Restorativeness Scale (PRS). Exposure to nature also induces stronger long-term correlated activity across different brain regions with a right lateralization. These findings may advance our understanding of the functional activities during in-situ environmental exposures and imply that a nature or nature-like environment may potentially benefit cognitive processes and mental well-being. PMID:27547533

Mapping population-based structural connectomes.

PubMed

Zhang, Zhengwu; Descoteaux, Maxime; Zhang, Jingwen; Girard, Gabriel; Chamberland, Maxime; Dunson, David; Srivastava, Anuj; Zhu, Hongtu

2018-05-15

Advances in understanding the structural connectomes of human brain require improved approaches for the construction, comparison and integration of high-dimensional whole-brain tractography data from a large number of individuals. This article develops a population-based structural connectome (PSC) mapping framework to address these challenges. PSC simultaneously characterizes a large number of white matter bundles within and across different subjects by registering different subjects' brains based on coarse cortical parcellations, compressing the bundles of each connection, and extracting novel connection weights. A robust tractography algorithm and streamline post-processing techniques, including dilation of gray matter regions, streamline cutting, and outlier streamline removal are applied to improve the robustness of the extracted structural connectomes. The developed PSC framework can be used to reproducibly extract binary networks, weighted networks and streamline-based brain connectomes. We apply the PSC to Human Connectome Project data to illustrate its application in characterizing normal variations and heritability of structural connectomes in healthy subjects. Copyright © 2018 Elsevier Inc. All rights reserved.

"Sexy stimulants": the interaction between psychomotor stimulants and sexual behavior in the female brain.

PubMed

Guarraci, Fay A; Bolton, Jessica L

2014-06-01

Research indicates gender differences in sensitivity to psychomotor stimulants. Preclinical work investigating the interaction between drugs of abuse and sex-specific behaviors, such as sexual behavior, is critical to our understanding of such gender differences in humans. A number of behavioral paradigms can be used to model aspects of human sexual behavior in animal subjects. Although traditional assessment of the reflexive, lordosis posture of the female rat has been used to map the neuroanatomical and neurochemical systems that contribute to uniquely female copulatory behavior, the additional behavioral paradigms discussed in the current review have helped us expand our description of the appetitive and consummatory patterns of sexual behavior in the female rat. Measuring appetitive behavior is particularly important for assessing sexual motivation, the equivalent of "desire" in humans. By investigating the effects of commonly abused drugs on female sexual motivation, we are beginning to elucidate the role of dopaminergic neurotransmission, a neural system also known to be critical to the neurobiology of drug addiction, in female sexual motivation. A better understanding of the nexus of sex and drugs in the female brain will help advance our understanding of motivation in general and explain how psychomotor stimulants affect males and females differently. Copyright © 2013 Elsevier Inc. All rights reserved.

Brain structures in the sciences and humanities.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Sassa, Yuko; Kawashima, Ryuta

2015-11-01

The areas of academic interest (sciences or humanities) and area of study have been known to be associated with a number of factors associated with autistic traits. However, despite the vast amount of literature on the psychological and physiological characteristics associated with faculty membership, brain structural characteristics associated with faculty membership have never been investigated directly. In this study, we used voxel-based morphometry to investigate differences in regional gray matter volume (rGMV)/regional white matter volume (rWMV) between science and humanities students to test our hypotheses that brain structures previously robustly shown to be altered in autistic subjects are related to differences in faculty membership. We examined 312 science students (225 males and 87 females) and 179 humanities students (105 males and 74 females). Whole-brain analyses of covariance revealed that after controlling for age, sex, and total intracranial volume, the science students had significantly larger rGMV in an anatomical cluster around the medial prefrontal cortex and the frontopolar area, whereas the humanities students had significantly larger rWMV in an anatomical cluster mainly concentrated around the right hippocampus. These anatomical structures have been linked to autism in previous studies and may mediate cognitive functions that characterize differences in faculty membership. The present results may support the ideas that autistic traits and characteristics of the science students compared with the humanities students share certain characteristics from neuroimaging perspectives. This study improves our understanding of differences in faculty membership which is the link among cognition, biological factors, disorders, and education (academia).

Brain Connectivity Networks and the Aesthetic Experience of Music.

PubMed

Reybrouck, Mark; Vuust, Peter; Brattico, Elvira

2018-06-12

Listening to music is above all a human experience, which becomes an aesthetic experience when an individual immerses himself/herself in the music, dedicating attention to perceptual-cognitive-affective interpretation and evaluation. The study of these processes where the individual perceives, understands, enjoys and evaluates a set of auditory stimuli has mainly been focused on the effect of music on specific brain structures, as measured with neurophysiology and neuroimaging techniques. The very recent application of network science algorithms to brain research allows an insight into the functional connectivity between brain regions. These studies in network neuroscience have identified distinct circuits that function during goal-directed tasks and resting states. We review recent neuroimaging findings which indicate that music listening is traceable in terms of network connectivity and activations of target regions in the brain, in particular between the auditory cortex, the reward brain system and brain regions active during mind wandering.

Deregulated proliferation and differentiation in brain tumors

PubMed Central

Swartling, Fredrik J; Čančer, Matko; Frantz, Aaron; Weishaupt, Holger; Persson, Anders I

2014-01-01

Neurogenesis, the generation of new neurons, is deregulated in neural stem cell (NSC)- and progenitor-derived murine models of malignant medulloblastoma and glioma, the most common brain tumors of children and adults, respectively. Molecular characterization of human malignant brain tumors, and in particular brain tumor stem cells (BTSCs), has identified neurodevelopmental transcription factors, microRNAs, and epigenetic factors known to inhibit neuronal and glial differentiation. We are starting to understand how these factors are regulated by the major oncogenic drivers in malignant brain tumors. In this review, we will focus on the molecular switches that block normal neuronal differentiation and induce brain tumor formation. Genetic or pharmacological manipulation of these switches in BTSCs has been shown to restore the ability of tumor cells to differentiate. We will discuss potential brain tumor therapies that will promote differentiation in order to reduce treatment-resistance, suppress tumor growth, and prevent recurrence in patients. PMID:25416506

Neuroscience thinks big (and collaboratively).

PubMed

Kandel, Eric R; Markram, Henry; Matthews, Paul M; Yuste, Rafael; Koch, Christof

2013-09-01

Despite cash-strapped times for research, several ambitious collaborative neuroscience projects have attracted large amounts of funding and media attention. In Europe, the Human Brain Project aims to develop a large-scale computer simulation of the brain, whereas in the United States, the Brain Activity Map is working towards establishing a functional connectome of the entire brain, and the Allen Institute for Brain Science has embarked upon a 10-year project to understand the mouse visual cortex (the MindScope project). US President Barack Obama's announcement of the BRAIN Initiative (Brain Research through Advancing Innovative Neurotechnologies Initiative) in April 2013 highlights the political commitment to neuroscience and is expected to further foster interdisciplinary collaborations, accelerate the development of new technologies and thus fuel much needed medical advances. In this Viewpoint article, five prominent neuroscientists explain the aims of the projects and how they are addressing some of the questions (and criticisms) that have arisen.

Population based MRI and DTI templates of the adult ferret brain and tools for voxelwise analysis.

PubMed

Hutchinson, E B; Schwerin, S C; Radomski, K L; Sadeghi, N; Jenkins, J; Komlosh, M E; Irfanoglu, M O; Juliano, S L; Pierpaoli, C

2017-05-15

Non-invasive imaging has the potential to play a crucial role in the characterization and translation of experimental animal models to investigate human brain development and disorders, especially when employed to study animal models that more accurately represent features of human neuroanatomy. The purpose of this study was to build and make available MRI and DTI templates and analysis tools for the ferret brain as the ferret is a well-suited species for pre-clinical MRI studies with folded cortical surface, relatively high white matter volume and body dimensions that allow imaging with pre-clinical MRI scanners. Four ferret brain templates were built in this study - in-vivo MRI and DTI and ex-vivo MRI and DTI - using brain images across many ferrets and region of interest (ROI) masks corresponding to established ferret neuroanatomy were generated by semi-automatic and manual segmentation. The templates and ROI masks were used to create a web-based ferret brain viewing software for browsing the MRI and DTI volumes with annotations based on the ROI masks. A second objective of this study was to provide a careful description of the imaging methods used for acquisition, processing, registration and template building and to demonstrate several voxelwise analysis methods including Jacobian analysis of morphometry differences between the female and male brain and bias-free identification of DTI abnormalities in an injured ferret brain. The templates, tools and methodological optimization presented in this study are intended to advance non-invasive imaging approaches for human-similar animal species that will enable the use of pre-clinical MRI studies for understanding and treating brain disorders. Published by Elsevier Inc.

Genetic-gonadal-genitals sex (3G-sex) and the misconception of brain and gender, or, why 3G-males and 3G-females have intersex brain and intersex gender

PubMed Central

2012-01-01

The categorization of individuals as “male” or “female” is based on chromosome complement and gonadal and genital phenotype. This combined genetic-gonadal-genitals sex, here referred to as 3G-sex, is internally consistent in ~99% of humans (i.e., one has either the “female” form at all levels, or the “male” form at all levels). About 1% of the human population is identified as “intersex” because of either having an intermediate form at one or more levels, or having the “male” form at some levels and the “female” form at other levels. These two types of “intersex” reflect the facts, respectively, that the different levels of 3G-sex are not completely dimorphic nor perfectly consistent. Using 3G-sex as a model to understand sex differences in other domains (e.g., brain, behavior) leads to the erroneous assumption that sex differences in these other domains are also highly dimorphic and highly consistent. But parallel lines of research have led to the conclusion that sex differences in the brain and in behavior, cognition, personality, and other gender characteristics are for the most part not dimorphic and not internally consistent (i.e., having one brain/gender characteristic with the “male” form is not a reliable predictor for the form of other brain/gender characteristics). Therefore although only ~1% percent of humans are 3G-“intersex”, when it comes to brain and gender, we all have an intersex gender (i.e., an array of masculine and feminine traits) and an intersex brain (a mosaic of “male” and “female” brain characteristics). PMID:23244600

Genetic-gonadal-genitals sex (3G-sex) and the misconception of brain and gender, or, why 3G-males and 3G-females have intersex brain and intersex gender.

PubMed

Joel, Daphna

2012-12-17

The categorization of individuals as "male" or "female" is based on chromosome complement and gonadal and genital phenotype. This combined genetic-gonadal-genitals sex, here referred to as 3G-sex, is internally consistent in ~99% of humans (i.e., one has either the "female" form at all levels, or the "male" form at all levels). About 1% of the human population is identified as "intersex" because of either having an intermediate form at one or more levels, or having the "male" form at some levels and the "female" form at other levels. These two types of "intersex" reflect the facts, respectively, that the different levels of 3G-sex are not completely dimorphic nor perfectly consistent. Using 3G-sex as a model to understand sex differences in other domains (e.g., brain, behavior) leads to the erroneous assumption that sex differences in these other domains are also highly dimorphic and highly consistent. But parallel lines of research have led to the conclusion that sex differences in the brain and in behavior, cognition, personality, and other gender characteristics are for the most part not dimorphic and not internally consistent (i.e., having one brain/gender characteristic with the "male" form is not a reliable predictor for the form of other brain/gender characteristics). Therefore although only ~1% percent of humans are 3G-"intersex", when it comes to brain and gender, we all have an intersex gender (i.e., an array of masculine and feminine traits) and an intersex brain (a mosaic of "male" and "female" brain characteristics).

Automating Cell Detection and Classification in Human Brain Fluorescent Microscopy Images Using Dictionary Learning and Sparse Coding

PubMed Central

Alegro, Maryana; Theofilas, Panagiotis; Nguy, Austin; Castruita, Patricia A.; Seeley, William; Heinsen, Helmut; Ushizima, Daniela M.

2017-01-01

Background Immunofluorescence (IF) plays a major role in quantifying protein expression in situ and understanding cell function. It is widely applied in assessing disease mechanisms and in drug discovery research. Automation of IF analysis can transform studies using experimental cell models. However, IF analysis of postmortem human tissue relies mostly on manual interaction, often subjected to low-throughput and prone to error, leading to low inter and intra-observer reproducibility. Human postmortem brain samples challenges neuroscientists because of the high level of autofluorescence caused by accumulation of lipofuscin pigment during aging, hindering systematic analyses. We propose a method for automating cell counting and classification in IF microscopy of human postmortem brains. Our algorithm speeds up the quantification task while improving reproducibility. New method Dictionary learning and sparse coding allow for constructing improved cell representations using IF images. These models are input for detection and segmentation methods. Classification occurs by means of color distances between cells and a learned set. Results Our method successfully detected and classified cells in 49 human brain images. We evaluated our results regarding true positive, false positive, false negative, precision, recall, false positive rate and F1 score metrics. We also measured user-experience and time saved compared to manual countings. Comparison with existing methods We compared our results to four open-access IF-based cell-counting tools available in the literature. Our method showed improved accuracy for all data samples. Conclusion The proposed method satisfactorily detects and classifies cells from human postmortem brain IF images, with potential to be generalized for applications in other counting tasks. PMID:28267565

427th Brookhaven Lecture

ScienceCinema

Gene-Jack Wang

2017-12-09

The increasing number of obese individuals in the U.S. and other countries world-wide adds urgency to the need to understand the mechanisms underlying pathological overeating. Research by the speaker and others at Brookhaven National Laboratory and elsewhere is compiling evidence that the brain circuits disrupted in obesity are similar to those involved in drug addiction. Using positron emission tomography (PET), the speaker and his colleagues have implicated brain dopamine in the normal and the pathological intake of food by humans.

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

Specialization in the Human Brain: The Case of Numbers

PubMed Central

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

2011-01-01

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

On the edge of language acquisition: inherent constraints on encoding multisyllabic sequences in the neonate brain.

PubMed

Ferry, Alissa L; Fló, Ana; Brusini, Perrine; Cattarossi, Luigi; Macagno, Francesco; Nespor, Marina; Mehler, Jacques

2016-05-01

To understand language, humans must encode information from rapid, sequential streams of syllables - tracking their order and organizing them into words, phrases, and sentences. We used Near-Infrared Spectroscopy (NIRS) to determine whether human neonates are born with the capacity to track the positions of syllables in multisyllabic sequences. After familiarization with a six-syllable sequence, the neonate brain responded to the change (as shown by an increase in oxy-hemoglobin) when the two edge syllables switched positions but not when two middle syllables switched positions (Experiment 1), indicating that they encoded the syllables at the edges of sequences better than those in the middle. Moreover, when a 25 ms pause was inserted between the middle syllables as a segmentation cue, neonates' brains were sensitive to the change (Experiment 2), indicating that subtle cues in speech can signal a boundary, with enhanced encoding of the syllables located at the edges of that boundary. These findings suggest that neonates' brains can encode information from multisyllabic sequences and that this encoding is constrained. Moreover, subtle segmentation cues in a sequence of syllables provide a mechanism with which to accurately encode positional information from longer sequences. Tracking the order of syllables is necessary to understand language and our results suggest that the foundations for this encoding are present at birth. © 2015 John Wiley & Sons Ltd.

Toward effective immunotherapy for the treatment of malignant brain tumors.

PubMed

Mitchell, Duane A; Sampson, John H

2009-07-01

The immunologic treatment of cancer has long been heralded as a targeted molecular therapeutic with the promise of eradicating tumor cells with minimal damage to surrounding normal tissues. However, a demonstrative example of the efficacy of immunotherapy in modulating cancer progression is still lacking for most human cancers. Recent breakthroughs in our understanding of the mechanisms leading to full T-cell activation, and recognition of the importance of overcoming tumor-induced immunosuppressive mechanisms, have shed new light on how to generate effective anti-tumor immune responses in humans, and sparked a renewed and enthusiastic effort to realize the full potential of cancer immunotherapy. The immunologic treatment of invasive malignant brain tumors has not escaped this re-invigorated endeavor, and promising therapies are currently under active investigation in dozens of clinical trials at several institutions worldwide. This review will focus on some of the most important breakthroughs in our understanding of how to generate potent anti-tumor immune responses, and some of the clear challenges that lie ahead in achieving effective immunotherapy for the majority of patients with malignant brain tumors. A review of immunotherapeutic strategies currently under clinical evaluation, as well as an outline of promising novel approaches on the horizon, is included to provide perspective on the active and stalwart progress toward effective immunotherapy for the treatment of malignant brain tumors.

[Stem Cells in the Brain of Mammals and Human: Fundamental and Applied Aspects].

PubMed

Aleksandrova, M A; Marey, M V

2015-01-01

Brain stem cells represent an extremely intriguing phenomenon. The aim of our review is to present an integrity vision of their role in the brain of mammals and humans, and their clinical perspectives. Over last two decades, investigations of biology of the neural stem cells produced significant changes in general knowledge about the processes of development and functioning of the brain. Researches on the cellular and molecular mechanisms of NSC differentiation and behavior led to new understanding of their involvement in learning and memory. In the regenerative medicine, original therapeutic approaches to neurodegenerative brain diseases have been elaborated due to fundamental achievements in this field. They are based on specific regenerative potential of neural stem cells and progenitor cells, which possess the ability to replace dead cells and express crucially significant biologically active factors that are missing in the pathological brain. For the needs of cell substitution therapy in the neural diseases, adequate methods of maintaining stem cells in culture and their differentiation into different types of neurons and glial cells, have been developed currently. The success of modern cellular technologies has significantly expanded the range of cells used for cell therapy. The near future may bring new perspective and distinct progress in brain cell therapy due to optimizing the cells types most promising for medical needs.

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.

Alkmaion's discovery that brain creates mind: a revolution in human knowledge comparable to that of Copernicus and of Darwin.

PubMed

Doty, Robert W

2007-07-13

Without special examination the brain offers no clue that it is the organ of the mind. From the dawn of time man thus either ignored the problem as to the source of thought, or attributed it to a variety of anatomical structures, usually the heart. The brain held no place in such intuitions, and in most languages it is analogized to bone marrow. Furthermore, nothing in early medical systems claimed any intellectual capacity for the brain; and the Egyptians, so fastidious in care for their afterlife, heedlessly discarded the brain in funerary practice. It was thus a unique event in world history when Alkmaion of Kroton (Alcmaeon, ca. 500 bc), based on anatomical evidence, proposed that the brain was essential for perception. Although no writings of Alkmaion survived, it was probably via a fortuitous linkage that his idea of the mental primacy of the brain was transmitted to, and preserved within, the teachings of the Hippocratic school. Nothing, of course, was secure as to mechanism, two millennia unfolding until the search for mind passed from the ventricles to the cerebral cortex. Nonetheless, Alkmaion was the beginning, and the ensuing understanding that he initiated is still transforming humanity's perception of the natural world, and their place within it.

Internal benchmarking of a human blood-brain barrier cell model for screening of nanoparticle uptake and transcytosis.

PubMed

Ragnaill, Michelle Nic; Brown, Meredith; Ye, Dong; Bramini, Mattia; Callanan, Sean; Lynch, Iseult; Dawson, Kenneth A

2011-04-01

Transport of drugs across the blood-brain barrier, which protects the brain from harmful agents, is considered the holy grail of targeted delivery, due to the extreme effectiveness of this barrier at preventing passage of non-essential molecules through to the brain. This has caused severe limitations for therapeutics for many brain-associated diseases, such as HIV and neurodegenerative diseases. Nanomaterials, as a result of their small size (in the order of many protein-lipid clusters routinely transported by cells) and their large surface area (which acts as a scaffold for proteins thereby rendering nanoparticles as biological entities) offer great promise for neuro-therapeutics. However, in parallel with developing neuro-therapeutic applications based on nanotechnology, it is essential to ensure their safety and long-term consequences upon reaching the brain. One approach to determining safe application of nanomaterials in biology is to obtain a deep mechanistic understanding of the interactions between nanomaterials and living systems (bionanointeractions). To this end, we report here on the establishment and internal round robin validation of a human cell model of the blood-brain barrier for use as a tool for screening nanoparticles interactions, and assessing the critical nanoscale parameters that determine transcytosis. Copyright © 2011 Elsevier B.V. All rights reserved.

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

Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated networkmore » (p < 10{sup -53}) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease.« less

TALEN-based generation of a cynomolgus monkey disease model for human microcephaly

PubMed Central

Ke, Qiong; Li, Weiqiang; Lai, Xingqiang; Chen, Hong; Huang, Lihua; Kang, Zhuang; Li, Kai; Ren, Jie; Lin, Xiaofeng; Zheng, Haiqing; Huang, Weijun; Ma, Yunhan; Xu, Dongdong; Chen, Zheng; Song, Xinming; Lin, Xinyi; Zhuang, Min; Wang, Tao; Zhuang, Fengfeng; Xi, Jianzhong; Mao, Frank Fuxiang; Xia, Huimin; Lahn, Bruce T; Zhou, Qi; Yang, Shihua; Xiang, Andy Peng

2016-01-01

Gene editing in non-human primates may lead to valuable models for exploring the etiologies and therapeutic strategies of genetically based neurological disorders in humans. However, a monkey model of neurological disorders that closely mimics pathological and behavioral deficits in humans has not yet been successfully generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation. Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic MCPH1 mutations using transcription activator-like effector nucleases. The monkey recapitulated most of the important clinical features observed in patients, including marked reductions in head circumference, premature chromosome condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity. Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC syndrome. This monkey model may help us elucidate the role of MCPH1 in the pathogenesis of human microcephaly and better understand the function of this protein in the evolution of primate brain size. PMID:27502025

Determining Changes in Neural Circuits in Tuberous Sclerosis

DTIC Science & Technology

2013-05-01

features of human Tuberous Sclerosis including mosaicism, autism and epilepsy. This research progress deepened our understanding of Tuberous Sclerosis by... autism and epilepsy. This research progress deepened our understanding of Tuberous Sclerosis by linking temporal gene function, mTOR function, physiology...of function of Tsc1 in the brain causes intellectual disability, seizures, sleep disorders, and autism . We took advantage of our CreER/loxP based

Graph-based network analysis of resting-state functional MRI.

PubMed

Wang, Jinhui; Zuo, Xinian; He, Yong

2010-01-01

In the past decade, resting-state functional MRI (R-fMRI) measures of brain activity have attracted considerable attention. Based on changes in the blood oxygen level-dependent signal, R-fMRI offers a novel way to assess the brain's spontaneous or intrinsic (i.e., task-free) activity with both high spatial and temporal resolutions. The properties of both the intra- and inter-regional connectivity of resting-state brain activity have been well documented, promoting our understanding of the brain as a complex network. Specifically, the topological organization of brain networks has been recently studied with graph theory. In this review, we will summarize the recent advances in graph-based brain network analyses of R-fMRI signals, both in typical and atypical populations. Application of these approaches to R-fMRI data has demonstrated non-trivial topological properties of functional networks in the human brain. Among these is the knowledge that the brain's intrinsic activity is organized as a small-world, highly efficient network, with significant modularity and highly connected hub regions. These network properties have also been found to change throughout normal development, aging, and in various pathological conditions. The literature reviewed here suggests that graph-based network analyses are capable of uncovering system-level changes associated with different processes in the resting brain, which could provide novel insights into the understanding of the underlying physiological mechanisms of brain function. We also highlight several potential research topics in the future.

Brain activity during driving with distraction: an immersive fMRI study

PubMed Central

Schweizer, Tom A.; Kan, Karen; Hung, Yuwen; Tam, Fred; Naglie, Gary; Graham, Simon J.

2013-01-01

Introduction: Non-invasive measurements of brain activity have an important role to play in understanding driving ability. The current study aimed to identify the neural underpinnings of human driving behavior by visualizing the areas of the brain involved in driving under different levels of demand, such as driving while distracted or making left turns at busy intersections. Materials and Methods: To capture brain activity during driving, we placed a driving simulator with a fully functional steering wheel and pedals in a 3.0 Tesla functional magnetic resonance imaging (fMRI) system. To identify the brain areas involved while performing different real-world driving maneuvers, participants completed tasks ranging from simple (right turns) to more complex (left turns at busy intersections). To assess the effects of driving while distracted, participants were asked to perform an auditory task while driving analogous to speaking on a hands-free device and driving. Results: A widely distributed brain network was identified, especially when making left turns at busy intersections compared to more simple driving tasks. During distracted driving, brain activation shifted dramatically from the posterior, visual and spatial areas to the prefrontal cortex. Conclusions: Our findings suggest that the distracted brain sacrificed areas in the posterior brain important for visual attention and alertness to recruit enough brain resources to perform a secondary, cognitive task. The present findings offer important new insights into the scientific understanding of the neuro-cognitive mechanisms of driving behavior and lay down an important foundation for future clinical research. PMID:23450757

Translating birdsong: songbirds as a model for basic and applied medical research.

PubMed

Brainard, Michael S; Doupe, Allison J

2013-07-08

Songbirds, long of interest to basic neuroscience, have great potential as a model system for translational neuroscience. Songbirds learn their complex vocal behavior in a manner that exemplifies general processes of perceptual and motor skill learning and, more specifically, resembles human speech learning. Song is subserved by circuitry that is specialized for vocal learning and production but that has strong similarities to mammalian brain pathways. The combination of highly quantifiable behavior and discrete neural substrates facilitates understanding links between brain and behavior, both in normal states and in disease. Here we highlight (a) behavioral and mechanistic parallels between birdsong and aspects of speech and social communication, including insights into mirror neurons, the function of auditory feedback, and genes underlying social communication disorders, and (b) contributions of songbirds to understanding cortical-basal ganglia circuit function and dysfunction, including the possibility of harnessing adult neurogenesis for brain repair.

Translating Birdsong: Songbirds as a model for basic and applied medical research

PubMed Central

2014-01-01

Songbirds, long of interest to basic neuroscientists, have great potential as a model system for translational neuroscience. Songbirds learn their complex vocal behavior in a manner that exemplifies general processes of perceptual and motor skill learning, and more specifically resembles human speech learning. Song is subserved by circuitry that is specialized for vocal learning and production, but that has strong similarities to mammalian brain pathways. The combination of a highly quantifiable behavior and discrete neural substrates facilitates understanding links between brain and behavior, both normally and in disease. Here we highlight 1) behavioral and mechanistic parallels between birdsong and aspects of speech and social communication, including insights into mirror neurons, the function of auditory feedback, and genes underlying social communication disorders, and 2) contributions of songbirds to understanding cortical-basal ganglia circuit function and dysfunction, including the possibility of harnessing adult neurogenesis for brain repair. PMID:23750515

Quantum and Multidimensional Explanations in a Neurobiological Context of Mind.

PubMed

Korf, Jakob

2015-08-01

This article examines the possible relevance of physical-mathematical multidimensional or quantum concepts aiming at understanding the (human) mind in a neurobiological context. Some typical features of the quantum and multidimensional concepts are briefly introduced, including entanglement, superposition, holonomic, and quantum field theories. Next, we consider neurobiological principles, such as the brain and its emerging (physical) mind, evolutionary and ontological origins, entropy, syntropy/neg-entropy, causation, and brain energy metabolism. In many biological processes, including biochemical conversions, protein folding, and sensory perception, the ubiquitous involvement of quantum mechanisms is well recognized. Quantum and multidimensional approaches might be expected to help describe and model both brain and mental processes, but an understanding of their direct involvement in mental activity, that is, without mediation by molecular processes, remains elusive. More work has to be done to bridge the gap between current neurobiological and physical-mathematical concepts with their associated quantum-mind theories. © The Author(s) 2014.

Developmental trajectories during adolescence in males and females: a cross-species understanding of underlying brain changes

PubMed Central

Brenhouse, Heather C.; Andersen, Susan L.

2011-01-01

Adolescence is a transitional period between childhood and adulthood that encompasses vast changes within brain systems that parallel some, but not all, behavioral changes. Elevations in emotional reactivity and reward processing follow an inverted U shape in terms of onset and remission, with the peak occurring during adolescence. However, cognitive processing follows a more linear course of development. This review will focus on changes within key structures and will highlight the relationships between brain changes and behavior, with evidence spanning from functional magnetic resonance imaging (fMRI) in humans to molecular studies of receptor and signaling factors in animals. Adolescent changes in neuronal substrates will be used to understand how typical and atypical behaviors arise during adolescence. We draw upon clinical and preclinical studies to provide a neural framework for defining adolescence and its role in the transition to adulthood. PMID:21600919

Why Study Music?

ERIC Educational Resources Information Center

Hodges, Donald A.

2005-01-01

Cognitive neuroscience is identifying neural networks in the brain that support multiple ways of knowing. This notion is also supported by evidence from psychology, anthropology, sociology, and other related disciplines. These human knowledge systems provide a means for sharing, expressing, understanding, knowing, and gaining insights into one's…

On the other hand: including left-handers in cognitive neuroscience and neurogenetics.

PubMed

Willems, Roel M; Van der Haegen, Lise; Fisher, Simon E; Francks, Clyde

2014-03-01

Left-handers are often excluded from study cohorts in neuroscience and neurogenetics in order to reduce variance in the data. However, recent investigations have shown that the inclusion or targeted recruitment of left-handers can be informative in studies on a range of topics, such as cerebral lateralization and the genetic underpinning of asymmetrical brain development. Left-handed individuals represent a substantial portion of the human population and therefore left-handedness falls within the normal range of human diversity; thus, it is important to account for this variation in our understanding of brain functioning. We call for neuroscientists and neurogeneticists to recognize the potential of studying this often-discarded group of research subjects.

Maintaining the Brain: Insight into Human Neurodegeneration From Drosophila Mutants

PubMed Central

Lessing, Derek; Bonini, Nancy M.

2009-01-01

The fruit fly Drosophila melanogaster has brought significant advances to research in neurodegenerative disease, notably in the identification of genes that are required to maintain the structural integrity of the brain, defined by recessive mutations that cause adult-onset neurodegeneration. Here, we survey these genes in the fly and classify them according to five key cell biological processes. Over half of these genes have counterparts in mouse or human that are also associated with neurodegeneration. Fly genetics continues to be instrumental in the analysis of degenerative disease, with notable recent advances in our understanding of several inherited disorders, as well as Parkinson’s Disease and the central role of mitochondria in neuronal maintenance. PMID:19434080

Creating a human brain proteome atlas--13th HUPO BPP Workshop March 30-31, 2010, Ochang, Korea.

PubMed

Gröttrup, Bernd; Stephan, Christian; Marcus, Katrin; Grinberg, Lea T; Wiltfang, Jens; Lee, Sang K; Kim, Young H; Meyer, Helmut E; Park, Young M

2011-07-01

The HUPO Brain Proteome Project (HUPO BPP) held its 13th workshop in Ochang from March 30th to 31st, 2010 prior to the Korean HUPO 10th Annual International Proteomics Conference. The principal aim of this project is to obtain a better understanding of neurodiseases and aging with the ultimate objective of discovering prognostic and diagnostic biomarkers, in addition to the development of novel diagnostic techniques and new medications. The attendees came together to discuss progress in the clinical neuroproteomics of human and to define the needs and guidelines required for more advanced proteomics approaches. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular Mechanisms of Cannabis Signaling in the Brain.

PubMed

Ronan, Patrick J; Wongngamnit, Narin; Beresford, Thomas P

2016-01-01

Cannabis has been cultivated and used by humans for thousands of years. Research for decades was focused on understanding the mechanisms of an illegal/addictive drug. This led to the discovery of the vast endocannabinoid system. Research has now shifted to understanding fundamental biological questions related to one of the most widespread signaling systems in both the brain and the body. Our understanding of cannabinoid signaling has advanced significantly in the last two decades. In this review, we discuss the state of knowledge on mechanisms of Cannabis signaling in the brain and the modulation of key brain neurotransmitter systems involved in both brain reward/addiction and psychiatric disorders. It is highly probable that various cannabinoids will be found to be efficacious in the treatment of a number of psychiatric disorders. However, while there is clearly much potential, marijuana has not been properly vetted by the medical-scientific evaluation process and there are clearly a range of potentially adverse side-effects-including addiction. We are at crossroads for research on endocannabinoid function and therapeutics (including the use of exogenous treatments such as Cannabis). With over 100 cannabinoid constituents, the majority of which have not been studied, there is much Cannabis research yet to be done. With more states legalizing both the medicinal and recreational use of marijuana the rigorous scientific investigation into cannabinoid signaling is imperative. Copyright © 2016. Published by Elsevier Inc.

Cryopreservation, Culture, and Transplantation of Human Fetal Mesencephalic Tissue into Monkeys

NASA Astrophysics Data System (ADS)

Redmond, D. E.; Naftolin, F.; Collier, T. J.; Leranth, C.; Robbins, R. J.; Sladek, C. D.; Roth, R. H.; Sladek, J. R.

1988-11-01

Studies in animals suggest that fetal neural grafts might restore lost neurological function in Parkinson's disease. In monkeys, such grafts survive for many months and reverse signs of parkinsonism, without attendant graft rejection. The successful and reliable application of a similar transplantation procedure to human patients, however, will require neural tissue obtained from human fetal cadavers, with demonstrated cellular identity, viability, and biological safety. In this report, human fetal neural tissue was successfully grafted into the brains of monkeys. Neural tissue was collected from human fetal cadavers after 9 to 12 weeks of gestation and cryopreserved in liquid nitrogen. Viability after up to 2 months of storage was demonstrated by cell culture and by transplantation into monkeys. Cryopreservation and storage of human fetal neural tissue would allow formation of a tissue bank. The stored cells could then be specifically tested to assure their cellular identity, viability, and bacteriological and virological safety before clinical use. The capacity to collect and maintain viable human fetal neural tissue would also facilitate research efforts to understand the development and function of the human brain and provide opportunities to study neurological diseases.

Enhanced cortical connectivity in absolute pitch musicians: a model for local hyperconnectivity.

PubMed

Loui, Psyche; Li, H Charles; Hohmann, Anja; Schlaug, Gottfried

2011-04-01

Connectivity in the human brain has received increased scientific interest in recent years. Although connection disorders can affect perception, production, learning, and memory, few studies have associated brain connectivity with graded variations in human behavior, especially among normal individuals. One group of normal individuals who possess unique characteristics in both behavior and brain structure is absolute pitch (AP) musicians, who can name the appropriate pitch class of any given tone without a reference. Using diffusion tensor imaging and tractography, we observed hyperconnectivity in bilateral superior temporal lobe structures linked to AP possession. Furthermore, volume of tracts connecting left superior temporal gyrus to left middle temporal gyrus predicted AP performance. These findings extend previous reports of exaggerated temporal lobe asymmetry, may explain the higher incidence of AP in special populations, and may provide a model for understanding the heightened connectivity that is thought to underlie savant skills and cases of exceptional creativity.

Enhanced Cortical Connectivity in Absolute Pitch Musicians: A Model for Local Hyperconnectivity

PubMed Central

Loui, Psyche; Charles Li, Hui C.; Hohmann, Anja; Schlaug, Gottfried

2010-01-01

Connectivity in the human brain has received increased scientific interest in recent years. Although connection disorders can affect perception, production, learning, and memory, few studies have associated brain connectivity with graded variations in human behavior, especially among normal individuals. One group of normal individuals who possess unique characteristics in both behavior and brain structure is absolute pitch (AP) musicians, who can name the appropriate pitch class of any given tone without a reference. Using diffusion tensor imaging and tractography, we observed hyperconnectivity in bilateral superior temporal lobe structures linked to AP possession. Furthermore, volume of tracts connecting left superior temporal gyrus to left middle temporal gyrus predicted AP performance. These findings extend previous reports of exaggerated temporal lobe asymmetry, may explain the higher incidence of AP in developmental disorders, and may provide a model for understanding the heightened connectivity that is thought to underlie savant skills and cases of exceptional creativity. PMID:20515408

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.

Using human brain imaging studies as a guide towards animal models of schizophrenia

PubMed Central

BOLKAN, Scott S.; DE CARVALHO, Fernanda D.; KELLENDONK, Christoph

2015-01-01

Schizophrenia is a heterogeneous and poorly understood mental disorder that is presently defined solely by its behavioral symptoms. Advances in genetic, epidemiological and brain imaging techniques in the past half century, however, have significantly advanced our understanding of the underlying biology of the disorder. In spite of these advances clinical research remains limited in its power to establish the causal relationships that link etiology with pathophysiology and symptoms. In this context, animal models provide an important tool for causally testing hypotheses about biological processes postulated to be disrupted in the disorder. While animal models can exploit a variety of entry points towards the study of schizophrenia, here we describe an approach that seeks to closely approximate functional alterations observed with brain imaging techniques in patients. By modeling these intermediate pathophysiological alterations in animals, this approach offers an opportunity to (1) tightly link a single functional brain abnormality with its behavioral consequences, and (2) to determine whether a single pathophysiology can causally produce alterations in other brain areas that have been described in patients. In this review we first summarize a selection of well-replicated biological abnormalities described in the schizophrenia literature. We then provide examples of animal models that were studied in the context of patient imaging findings describing enhanced striatal dopamine D2 receptor function, alterations in thalamo-prefrontal circuit function, and metabolic hyperfunction of the hippocampus. Lastly, we discuss the implications of findings from these animal models for our present understanding of schizophrenia, and consider key unanswered questions for future research in animal models and human patients. PMID:26037801

Connectomic Insights into Topologically Centralized Network Edges and Relevant Motifs in the Human Brain

PubMed Central

Xia, Mingrui; Lin, Qixiang; Bi, Yanchao; He, Yong

2016-01-01

White matter (WM) tracts serve as important material substrates for information transfer across brain regions. However, the topological roles of WM tracts in global brain communications and their underlying microstructural basis remain poorly understood. Here, we employed diffusion magnetic resonance imaging and graph-theoretical approaches to identify the pivotal WM connections in human whole-brain networks and further investigated their wiring substrates (including WM microstructural organization and physical consumption) and topological contributions to the brain's network backbone. We found that the pivotal WM connections with highly topological-edge centrality were primarily distributed in several long-range cortico-cortical connections (including the corpus callosum, cingulum and inferior fronto-occipital fasciculus) and some projection tracts linking subcortical regions. These pivotal WM connections exhibited high levels of microstructural organization indicated by diffusion measures (the fractional anisotropy, the mean diffusivity and the axial diffusivity) and greater physical consumption indicated by streamline lengths, and contributed significantly to the brain's hubs and the rich-club structure. Network motif analysis further revealed their heavy participations in the organization of communication blocks, especially in routes involving inter-hemispheric heterotopic and extremely remote intra-hemispheric systems. Computational simulation models indicated the sharp decrease of global network integrity when attacking these highly centralized edges. Together, our results demonstrated high building-cost consumption and substantial communication capacity contributions for pivotal WM connections, which deepens our understanding of the topological mechanisms that govern the organization of human connectomes. PMID:27148015

Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity.

PubMed

Lopes, Kryslaine O; Sparks, D Larry; Streit, Wolfgang J

2008-08-01

Degeneration of microglial cells may be important for understanding the pathogenesis of aging-related neurodegeneration and neurodegenerative diseases. In this study, we analyzed the morphological characteristics of microglial cells in the nondemented and Alzheimer's disease (AD) human brain using ferritin immunohistochemistry. The central hypothesis was that expression of the iron storage protein ferritin increases the susceptibility of microglia to degeneration, particularly in the aged brain since senescent microglia might become less efficient in maintaining iron homeostasis and free iron can promote oxidative damage. In a primary set of 24 subjects (age range 34-97 years) examined, microglial cells immunoreactive for ferritin were found to constitute a subpopulation of the larger microglial pool labeled with an antibody for HLA-DR antigens. The majority of these ferritin-positive microglia exhibited aberrant morphological (dystrophic) changes in the aged and particularly in the AD brain. No spatial correlation was found between ferritin-positive dystrophic microglia and senile plaques in AD tissues. Analysis of a secondary set of human postmortem brain tissues with a wide range of postmortem intervals (PMI, average 10.94 +/- 5.69 h) showed that the occurrence of microglial dystrophy was independent of PMI and consequently not a product of tissue autolysis. Collectively, these results suggest that microglial involvement in iron storage and metabolism contributes to their degeneration, possibly through increased exposure of the cells to oxidative stress. We conclude that ferritin immunohistochemistry may be a useful method for detecting degenerating microglia in the human brain. (c) 2008 Wiley-Liss, Inc.

Connectomic Insights into Topologically Centralized Network Edges and Relevant Motifs in the Human Brain.

PubMed

Xia, Mingrui; Lin, Qixiang; Bi, Yanchao; He, Yong

2016-01-01

White matter (WM) tracts serve as important material substrates for information transfer across brain regions. However, the topological roles of WM tracts in global brain communications and their underlying microstructural basis remain poorly understood. Here, we employed diffusion magnetic resonance imaging and graph-theoretical approaches to identify the pivotal WM connections in human whole-brain networks and further investigated their wiring substrates (including WM microstructural organization and physical consumption) and topological contributions to the brain's network backbone. We found that the pivotal WM connections with highly topological-edge centrality were primarily distributed in several long-range cortico-cortical connections (including the corpus callosum, cingulum and inferior fronto-occipital fasciculus) and some projection tracts linking subcortical regions. These pivotal WM connections exhibited high levels of microstructural organization indicated by diffusion measures (the fractional anisotropy, the mean diffusivity and the axial diffusivity) and greater physical consumption indicated by streamline lengths, and contributed significantly to the brain's hubs and the rich-club structure. Network motif analysis further revealed their heavy participations in the organization of communication blocks, especially in routes involving inter-hemispheric heterotopic and extremely remote intra-hemispheric systems. Computational simulation models indicated the sharp decrease of global network integrity when attacking these highly centralized edges. Together, our results demonstrated high building-cost consumption and substantial communication capacity contributions for pivotal WM connections, which deepens our understanding of the topological mechanisms that govern the organization of human connectomes.

Old World Monkeys Compare to Apes in the Primate Cognition Test Battery

PubMed Central

Schmitt, Vanessa; Pankau, Birte; Fischer, Julia

2012-01-01

Understanding the evolution of intelligence rests on comparative analyses of brain sizes as well as the assessment of cognitive skills of different species in relation to potential selective pressures such as environmental conditions and social organization. Because of the strong interest in human cognition, much previous work has focused on the comparison of the cognitive skills of human toddlers to those of our closest living relatives, i.e. apes. Such analyses revealed that apes and children have relatively similar competencies in the physical domain, while human children excel in the socio-cognitive domain; in particular in terms of attention sharing, cooperation, and mental state attribution. To develop a full understanding of the evolutionary dynamics of primate intelligence, however, comparative data for monkeys are needed. We tested 18 Old World monkeys (long-tailed macaques and olive baboons) in the so-called Primate Cognition Test Battery (PCTB) (Herrmann et al. 2007, Science). Surprisingly, our tests revealed largely comparable results between Old World monkeys and the Great apes. Single comparisons showed that chimpanzees performed only better than the macaques in experiments on spatial understanding and tool use, but in none of the socio-cognitive tasks. These results question the clear-cut relationship between cognitive performance and brain size and – prima facie – support the view of an accelerated evolution of social intelligence in humans. One limitation, however, is that the initial experiments were devised to tap into human specific skills in the first place, thus potentially underestimating both true nonhuman primate competencies as well as species differences. PMID:22485130

Pathophysiology of Migraine: A Disorder of Sensory Processing

PubMed Central

Holland, Philip R.; Martins-Oliveira, Margarida; Hoffmann, Jan; Schankin, Christoph; Akerman, Simon

2017-01-01

Plaguing humans for more than two millennia, manifest on every continent studied, and with more than one billion patients having an attack in any year, migraine stands as the sixth most common cause of disability on the planet. The pathophysiology of migraine has emerged from a historical consideration of the “humors” through mid-20th century distraction of the now defunct Vascular Theory to a clear place as a neurological disorder. It could be said there are three questions: why, how, and when? Why: migraine is largely accepted to be an inherited tendency for the brain to lose control of its inputs. How: the now classical trigeminal durovascular afferent pathway has been explored in laboratory and clinic; interrogated with immunohistochemistry to functional brain imaging to offer a roadmap of the attack. When: migraine attacks emerge due to a disorder of brain sensory processing that itself likely cycles, influenced by genetics and the environment. In the first, premonitory, phase that precedes headache, brain stem and diencephalic systems modulating afferent signals, light-photophobia or sound-phonophobia, begin to dysfunction and eventually to evolve to the pain phase and with time the resolution or postdromal phase. Understanding the biology of migraine through careful bench-based research has led to major classes of therapeutics being identified: triptans, serotonin 5-HT1B/1D receptor agonists; gepants, calcitonin gene-related peptide (CGRP) receptor antagonists; ditans, 5-HT1F receptor agonists, CGRP mechanisms monoclonal antibodies; and glurants, mGlu5 modulators; with the promise of more to come. Investment in understanding migraine has been very successful and leaves us at a new dawn, able to transform its impact on a global scale, as well as understand fundamental aspects of human biology. PMID:28179394

Toward an operational model of decision making, emotional regulation, and mental health impact.

PubMed

Collura, Thomas Francis; Zalaquett, Ronald P; Bonnstetter, Carlos Joyce; Chatters, Seria J

2014-01-01

Current brain research increasingly reveals the underlying mechanisms and processes of human behavior, cognition, and emotion. In addition to being of interest to a wide range of scientists, educators, and professionals, as well as laypeople, brain-based models are of particular value in a clinical setting. Psychiatrists, psychologists, counselors, and other mental health professionals are in need of operational models that integrate recent findings in the physical, cognitive, and emotional domains, and offer a common language for interdisciplinary understanding and communication. Based on individual traits, predispositions, and responses to stimuli, we can begin to identify emotional and behavioral pathways and mental processing patterns. The purpose of this article is to present a brain-path activation model to understand individual differences in decision making and psychopathology. The first section discusses the role of frontal lobe electroencephalography (EEG) asymmetry, summarizes state- and trait-based models of decision making, and provides a more complex analysis that supplements the traditional simple left-right brain model. Key components of the new model are the introduction of right hemisphere parallel and left hemisphere serial scanning in rendering decisions, and the proposition of pathways that incorporate both past experiences as well as future implications into the decision process. Main attributes of each decision-making mechanism are provided. The second section applies the model within the realm of clinical mental health as a tool to understand specific human behavior and pathology. Applications include general and chronic anxiety, depression, paranoia, risk taking, and the pathways employed when well-functioning operational integration is observed. Finally, specific applications such as meditation and mindfulness are offered to facilitate positive functioning.

Brain Neuromodulation Techniques: A Review.

PubMed

Lewis, Philip M; Thomson, Richard H; Rosenfeld, Jeffrey V; Fitzgerald, Paul B

2016-08-01

The modulation of brain function via the application of weak direct current was first observed directly in the early 19th century. In the past 3 decades, transcranial magnetic stimulation and deep brain stimulation have undergone clinical translation, offering alternatives to pharmacological treatment of neurological and neuropsychiatric disorders. Further development of novel neuromodulation techniques employing ultrasound, micro-scale magnetic fields and optogenetics is being propelled by a rapidly improving understanding of the clinical and experimental applications of artificially stimulating or depressing brain activity in human health and disease. With the current rapid growth in neuromodulation technologies and applications, it is timely to review the genesis of the field and the current state of the art in this area. © The Author(s) 2016.

A technical guide to tDCS, and related non-invasive brain stimulation tools.

PubMed

Woods, A J; Antal, A; Bikson, M; Boggio, P S; Brunoni, A R; Celnik, P; Cohen, L G; Fregni, F; Herrmann, C S; Kappenman, E S; Knotkova, H; Liebetanz, D; Miniussi, C; Miranda, P C; Paulus, W; Priori, A; Reato, D; Stagg, C; Wenderoth, N; Nitsche, M A

2016-02-01

Transcranial electrical stimulation (tES), including transcranial direct and alternating current stimulation (tDCS, tACS) are non-invasive brain stimulation techniques increasingly used for modulation of central nervous system excitability in humans. Here we address methodological issues required for tES application. This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches. It aims to help the reader to appropriately design and conduct studies involving these brain stimulation techniques, understand limitations and avoid shortcomings, which might hamper the scientific rigor and potential applications in the clinical domain. Copyright © 2015 International Federation of Clinical Neurophysiology. All rights reserved.

Dreaming and the brain: from phenomenology to neurophysiology.

PubMed

Nir, Yuval; Tononi, Giulio

2010-02-01

Dreams are a remarkable experiment in psychology and neuroscience, conducted every night in every sleeping person. They show that the human brain, disconnected from the environment, can generate an entire world of conscious experiences by itself. Content analysis and developmental studies have promoted understanding of dream phenomenology. In parallel, brain lesion studies, functional imaging and neurophysiology have advanced current knowledge of the neural basis of dreaming. It is now possible to start integrating these two strands of research to address fundamental questions that dreams pose for cognitive neuroscience: how conscious experiences in sleep relate to underlying brain activity; why the dreamer is largely disconnected from the environment; and whether dreaming is more closely related to mental imagery or to perception. Published by Elsevier Ltd.

Aiding the Eye, Watching the Brain: James Weiland, IEEE Fellow, explores the unique challenges of retinal prostheses.

PubMed

Grifantini, Kristina

2017-01-01

The retina is a sophisticated neural network that provides humans with high-resolution vision. And for those who suffer from retinal disease or deterioration, particularly age-related macular degeneration (the leading cause of blindness among people over the age of 50 in the United States), a better understanding of how to stimulate the retina or completely override its path to the area of the brain that processes vision may offer hope to restore sight.

Logical Interactions in AN Expanded Space

NASA Astrophysics Data System (ADS)

Tadić, Bosiljka

Understanding the emergent behavior in many complex systems in the physical world and society requires a detailed study of dynamical phenomena occurring and mutually coupled at different scales. The brain processes underlying the social conduct of each, and the emergent social behavior of interacting individuals on a larger scale, represent striking examples of the multiscale complexity. Studies of the human brain, a paradigm of a complex functional system, are enabled by a wealth of brain imaging data that provide clues of how we comprehend space, time, languages, numbers, and differentiate normal from diseased individuals, for example. The social brain, a neural basis for social cognition, represents a dynamically organized part of the brain which is involved in the inference of thoughts, feelings, and intentions going on in the brains of others. Research in this currently unexplored area opens a new perspective on the genesis of the societal organization at different levels and the associated social values...

SELECTIVE CHANGES IN BRAIN PROTEIN KINASE C ISOFORMS FOLLOWING DEVELOPMENTAL EXPOSURE TO A PCB MIXTURE.

EPA Science Inventory

Introduction
Polychlorinated biphenyls (PCBs) offer a unique model to understand the major issues related to complex environmental mixtures. These environmental pollutants are ubiquitous, persistent, bioaccumulate in human body through the food chain, and exist as mixtures of ...

The Muscle Sensor for on-site neuroscience lectures to pave the way for a better understanding of brain-machine-interface research.

PubMed

Koizumi, Amane; Nagata, Osamu; Togawa, Morio; Sazi, Toshiyuki

2014-01-01

Neuroscience is an expanding field of science to investigate enigmas of brain and human body function. However, the majority of the public have never had the chance to learn the basics of neuroscience and new knowledge from advanced neuroscience research through hands-on experience. Here, we report that we produced the Muscle Sensor, a simplified electromyography, to promote educational understanding in neuroscience. The Muscle Sensor can detect myoelectric potentials which are filtered and processed as 3-V pulse signals to shine a light bulb and emit beep sounds. With this educational tool, we delivered "On-Site Neuroscience Lectures" in Japanese junior-high schools to facilitate hands-on experience of neuroscientific electrophysiology and to connect their text-book knowledge to advanced neuroscience researches. On-site neuroscience lectures with the Muscle Sensor pave the way for a better understanding of the basics of neuroscience and the latest topics such as how brain-machine-interface technology could help patients with disabilities such as spinal cord injuries. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

A network engineering perspective on probing and perturbing cognition with neurofeedback.

PubMed

Bassett, Danielle S; Khambhati, Ankit N

2017-05-01

Network science and engineering provide a flexible and generalizable tool set to describe and manipulate complex systems characterized by heterogeneous interaction patterns among component parts. While classically applied to social systems, these tools have recently proven to be particularly useful in the study of the brain. In this review, we describe the nascent use of these tools to understand human cognition, and we discuss their utility in informing the meaningful and predictable perturbation of cognition in combination with the emerging capabilities of neurofeedback. To blend these disparate strands of research, we build on emerging conceptualizations of how the brain functions (as a complex network) and how we can develop and target interventions or modulations (as a form of network control). We close with an outline of current frontiers that bridge neurofeedback, connectomics, and network control theory to better understand human cognition. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

What is a representative brain? Neuroscience meets population science.

PubMed

Falk, Emily B; Hyde, Luke W; Mitchell, Colter; Faul, Jessica; Gonzalez, Richard; Heitzeg, Mary M; Keating, Daniel P; Langa, Kenneth M; Martz, Meghan E; Maslowsky, Julie; Morrison, Frederick J; Noll, Douglas C; Patrick, Megan E; Pfeffer, Fabian T; Reuter-Lorenz, Patricia A; Thomason, Moriah E; Davis-Kean, Pamela; Monk, Christopher S; Schulenberg, John

2013-10-29

The last decades of neuroscience research have produced immense progress in the methods available to understand brain structure and function. Social, cognitive, clinical, affective, economic, communication, and developmental neurosciences have begun to map the relationships between neuro-psychological processes and behavioral outcomes, yielding a new understanding of human behavior and promising interventions. However, a limitation of this fast moving research is that most findings are based on small samples of convenience. Furthermore, our understanding of individual differences may be distorted by unrepresentative samples, undermining findings regarding brain-behavior mechanisms. These limitations are issues that social demographers, epidemiologists, and other population scientists have tackled, with solutions that can be applied to neuroscience. By contrast, nearly all social science disciplines, including social demography, sociology, political science, economics, communication science, and psychology, make assumptions about processes that involve the brain, but have incorporated neural measures to differing, and often limited, degrees; many still treat the brain as a black box. In this article, we describe and promote a perspective--population neuroscience--that leverages interdisciplinary expertise to (i) emphasize the importance of sampling to more clearly define the relevant populations and sampling strategies needed when using neuroscience methods to address such questions; and (ii) deepen understanding of mechanisms within population science by providing insight regarding underlying neural mechanisms. Doing so will increase our confidence in the generalizability of the findings. We provide examples to illustrate the population neuroscience approach for specific types of research questions and discuss the potential for theoretical and applied advances from this approach across areas.

Optimized magnetic resonance diffusion protocol for ex-vivo whole human brain imaging with a clinical scanner

NASA Astrophysics Data System (ADS)

Scherrer, Benoit; Afacan, Onur; Stamm, Aymeric; Singh, Jolene; Warfield, Simon K.

2015-03-01

Diffusion-weighted magnetic resonance imaging (DW-MRI) provides a novel insight into the brain to facilitate our understanding of the brain connectivity and microstructure. While in-vivo DW-MRI enables imaging of living patients and longitudinal studies of brain changes, post-mortem ex-vivo DW-MRI has numerous advantages. Ex-vivo imaging benefits from greater resolution and sensitivity due to the lack of imaging time constraints; the use of tighter fitting coils; and the lack of movement artifacts. This allows characterization of normal and abnormal tissues with unprecedented resolution and sensitivity, facilitating our ability to investigate anatomical structures that are inaccessible in-vivo. This also offers the opportunity to develop today novel imaging biomarkers that will, with tomorrow's MR technology, enable improved in-vivo assessment of the risk of disease in an individual. Post-mortem studies, however, generally rely on the fixation of specimen to inhibit tissue decay which starts as soon as tissue is deprived from its blood supply. Unfortunately, fixation of tissues substantially alters tissue diffusivity profiles. In addition, ex-vivo DW-MRI requires particular care when packaging the specimen because the presence of microscopic air bubbles gives rise to geometric and intensity image distortion. In this work, we considered the specific requirements of post-mortem imaging and designed an optimized protocol for ex-vivo whole brain DW-MRI using a human clinical 3T scanner. Human clinical 3T scanners are available to a large number of researchers and, unlike most animal scanners, have a bore diameter large enough to image a whole human brain. Our optimized protocol will facilitate widespread ex-vivo investigations of large specimen.

Neuroimaging is a novel tool to understand the impact of environmental chemicals on neurodevelopment.

PubMed

Horton, Megan K; Margolis, Amy E; Tang, Cheuk; Wright, Robert

2014-04-01

The prevalence of childhood neurodevelopmental disorders has been increasing over the last several decades. Prenatal and early childhood exposure to environmental toxicants is increasingly recognized as contributing to the growing rate of neurodevelopmental disorders. Very little information is known about the mechanistic processes by which environmental chemicals alter brain development. We review the recent advances in brain imaging modalities and discuss their application in epidemiologic studies of prenatal and early childhood exposure to environmental toxicants. Neuroimaging techniques (volumetric and functional MRI, diffusor tensor imaging, and magnetic resonance spectroscopy) have opened unprecedented access to study the developing human brain. These techniques are noninvasive and free of ionization radiation making them suitable for research applications in children. Using these techniques, we now understand much about structural and functional patterns in the typically developing brain. This knowledge allows us to investigate how prenatal exposure to environmental toxicants may alter the typical developmental trajectory. MRI is a powerful tool that allows in-vivo visualization of brain structure and function. Used in epidemiologic studies of environmental exposure, it offers the promise to causally link exposure with behavioral and cognitive manifestations and ultimately to inform programs to reduce exposure and mitigate adverse effects of exposure.

The structure of brain glycogen phosphorylase-from allosteric regulation mechanisms to clinical perspectives.

PubMed

Mathieu, Cécile; Dupret, Jean-Marie; Rodrigues Lima, Fernando

2017-02-01

Glycogen phosphorylase (GP) is the key enzyme that regulates glycogen mobilization in cells. GP is a complex allosteric enzyme that comprises a family of three isozymes: muscle GP (mGP), liver GP (lGP), and brain GP (bGP). Although the three isozymes display high similarity and catalyze the same reaction, they differ in their sensitivity to the allosteric activator adenosine monophosphate (AMP). Moreover, inactivating mutations in mGP and lGP have been known to be associated with glycogen storage diseases (McArdle and Hers disease, respectively). The determination, decades ago, of the structure of mGP and lGP have allowed to better understand the allosteric regulation of these two isoforms and the development of specific inhibitors. Despite its important role in brain glycogen metabolism, the structure of the brain GP had remained elusive. Here, we provide an overview of the human brain GP structure and its relationship with the two other members of this key family of the metabolic enzymes. We also summarize how this structure provides valuable information to understand the regulation of bGP and to design specific ligands of potential pharmacological interest. © 2016 Federation of European Biochemical Societies.

Brain connectivity dynamics during social interaction reflect social network structure

PubMed Central

Schmälzle, Ralf; Brook O’Donnell, Matthew; Garcia, Javier O.; Cascio, Christopher N.; Bayer, Joseph; Vettel, Jean M.

2017-01-01

Social ties are crucial for humans. Disruption of ties through social exclusion has a marked effect on our thoughts and feelings; however, such effects can be tempered by broader social network resources. Here, we use fMRI data acquired from 80 male adolescents to investigate how social exclusion modulates functional connectivity within and across brain networks involved in social pain and understanding the mental states of others (i.e., mentalizing). Furthermore, using objectively logged friendship network data, we examine how individual variability in brain reactivity to social exclusion relates to the density of participants’ friendship networks, an important aspect of social network structure. We find increased connectivity within a set of regions previously identified as a mentalizing system during exclusion relative to inclusion. These results are consistent across the regions of interest as well as a whole-brain analysis. Next, examining how social network characteristics are associated with task-based connectivity dynamics, we find that participants who showed greater changes in connectivity within the mentalizing system when socially excluded by peers had less dense friendship networks. This work provides insight to understand how distributed brain systems respond to social and emotional challenges and how such brain dynamics might vary based on broader social network characteristics. PMID:28465434

Advanced lesion symptom mapping analyses and implementation as BCBtoolkit.

PubMed

Foulon, Chris; Cerliani, Leonardo; Kinkingnéhun, Serge; Levy, Richard; Rosso, Charlotte; Urbanski, Marika; Volle, Emmanuelle; Thiebaut de Schotten, Michel

2018-03-01

Patients with brain lesions provide a unique opportunity to understand the functioning of the human mind. However, even when focal, brain lesions have local and remote effects that impact functionally and structurally connected circuits. Similarly, function emerges from the interaction between brain areas rather than their sole activity. For instance, category fluency requires the associations between executive, semantic, and language production functions. Here, we provide, for the first time, a set of complementary solutions for measuring the impact of a given lesion on the neuronal circuits. Our methods, which were applied to 37 patients with a focal frontal brain lesions, revealed a large set of directly and indirectly disconnected brain regions that had significantly impacted category fluency performance. The directly disconnected regions corresponded to areas that are classically considered as functionally engaged in verbal fluency and categorization tasks. These regions were also organized into larger directly and indirectly disconnected functional networks, including the left ventral fronto-parietal network, whose cortical thickness correlated with performance on category fluency. The combination of structural and functional connectivity together with cortical thickness estimates reveal the remote effects of brain lesions, provide for the identification of the affected networks, and strengthen our understanding of their relationship with cognitive and behavioral measures. The methods presented are available and freely accessible in the BCBtoolkit as supplementary software [1].

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.

Fear extinction in the human brain: A meta-analysis of fMRI studies in healthy participants.

PubMed

Fullana, Miquel A; Albajes-Eizagirre, Anton; Soriano-Mas, Carles; Vervliet, Bram; Cardoner, Narcís; Benet, Olívia; Radua, Joaquim; Harrison, Ben J

2018-05-01

The study of fear extinction represents an important example of translational neuroscience in psychiatry and promises to improve the understanding and treatment of anxiety and fear-related disorders. We present the results of a set of meta-analyses of human fear extinction studies in healthy participants, conducted with functional magnetic resonance imaging (fMRI) and reporting whole-brain results. Meta-analyses of fear extinction learning primarily implicate consistent activation of brain regions linked to threat appraisal and experience, including the dorsal anterior cingulate and anterior insular cortices. An overlapping anatomical result was obtained from the meta-analysis of extinction recall studies, except when studies directly compared an extinguished threat stimulus to an unextinguished threat stimulus (instead of a safety stimulus). In this latter instance, more consistent activation was observed in dorsolateral and ventromedial prefrontal cortex regions, together with other areas including the hippocampus. While our results partially support the notion of a shared neuroanatomy between human and rodent models of extinction processes, they also encourage an expanded account of the neural basis of human fear extinction. Copyright © 2018 Elsevier Ltd. All rights reserved.

Insights into Brain Glycogen Metabolism

PubMed Central

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

2016-01-01

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. PMID:27402852

Multiple brain atlas database and atlas-based neuroimaging system.

PubMed

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

1997-01-01

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

Understanding face perception by means of human electrophysiology.

PubMed

Rossion, Bruno

2014-06-01

Electrophysiological recordings on the human scalp provide a wealth of information about the temporal dynamics and nature of face perception at a global level of brain organization. The time window between 100 and 200 ms witnesses the transition between low-level and high-level vision, an N170 component correlating with conscious interpretation of a visual stimulus as a face. This face representation is rapidly refined as information accumulates during this time window, allowing the individualization of faces. To improve the sensitivity and objectivity of face perception measures, it is increasingly important to go beyond transient visual stimulation by recording electrophysiological responses at periodic frequency rates. This approach has recently provided face perception thresholds and the first objective signature of integration of facial parts in the human brain. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Development of Open Brain Simulator for Human Biomechatronics

NASA Astrophysics Data System (ADS)

Otake, Mihoko; Takagi, Toshihisa; Asama, Hajime

Modeling and simulation based on mechanisms is important in order to design and control mechatronic systems. In particular, in-depth understanding and realistic modeling of biological systems is indispensable for biomechatronics. This paper presents open brain simulator, which estimates the neural state of human through external measurement for the purpose of improving motor and social skills. Macroscopic anatomical nervous systems model was built which can be connected to the musculoskeletal model. Microscopic anatomical and physiological neural models were interfaced to the macroscopic model. Neural activities of somatosensory area and Purkinje cell were calculated from motion capture data. The simulator provides technical infrastructure for human biomechatronics, which is promising for the novel diagnosis of neurological disorders and their treatments through medication and movement therapy, and for motor learning support system supporting acquisition of motor skill considering neural mechanism.

Quantitative imaging of brain energy metabolisms and neuroenergetics using in vivo X-nuclear 2H, 17O and 31P MRS at ultra-high field.

PubMed

Zhu, Xiao-Hong; Lu, Ming; Chen, Wei

2018-07-01

Brain energy metabolism relies predominantly on glucose and oxygen utilization to generate biochemical energy in the form of adenosine triphosphate (ATP). ATP is essential for maintaining basal electrophysiological activities in a resting brain and supporting evoked neuronal activity under an activated state. Studying complex neuroenergetic processes in the brain requires sophisticated neuroimaging techniques enabling noninvasive and quantitative assessment of cerebral energy metabolisms and quantification of metabolic rates. Recent state-of-the-art in vivo X-nuclear MRS techniques, including 2 H, 17 O and 31 P MRS have shown promise, especially at ultra-high fields, in the quest for understanding neuroenergetics and brain function using preclinical models and in human subjects under healthy and diseased conditions. Copyright © 2018 Elsevier Inc. All rights reserved.

Establishment of a new conditionally immortalized cell line from human brain microvascular endothelial cells: a promising tool for human blood-brain barrier studies.

PubMed

Kamiichi, Atsuko; Furihata, Tomomi; Kishida, Satoshi; Ohta, Yuki; Saito, Kosuke; Kawamatsu, Shinya; Chiba, Kan

2012-12-07

The blood-brain barrier (BBB) is formed by brain microvascular endothelial cells (BMEC) working together with astrocytes and pericytes, in which tight junctions and various transporters strictly regulate the penetration of diverse compounds into the brain. Clarification of the molecular machinery that provides such regulation using in vitro BBB models has provided important insights into the roles of the BBB in central nervous system (CNS) disorders and CNS drug development. In this study, we succeeded in establishing a new cell line, hereinafter referred to as human BMEC/conditionally immortalized, clone β (HBMEC/ciβ), as part of our ongoing efforts to develop an in vitro human BBB model. Our results showed that HBMEC/ciβ proliferated well. Furthermore, we found that HBMEC/ciβ exhibited the barrier property of restricting small molecule intercellular penetration and possessed effective efflux transporter functions, both of which are essential to a functioning BBB. Because higher temperatures are known to terminate immortalization signals, we specifically examined the effects of higher temperatures on the HBMEC/ciβ differentiation status. The results showed that higher temperatures stimulated HBMEC/ciβ differentiation, marked by morphological alteration and increases in several mRNA levels. To summarize, our data indicates that the newly established HBMEC/ciβ offers a promising tool for use in the development of a practical in vitro human BBB model that could make significant contributions toward understanding the molecular biology of CNS disorders, as well as to CNS drug development. It is also believed that the development of a specific culture method for HBMEC/ciβ will add significant value to the HBMEC/ciβ-based BBB model. Copyright © 2012 Elsevier B.V. All rights reserved.

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

Integrative Analysis of Genetic, Genomic, and Phenotypic Data for Ethanol Behaviors: A Network-Based Pipeline for Identifying Mechanisms and Potential Drug Targets.

PubMed

Bogenpohl, James W; Mignogna, Kristin M; Smith, Maren L; Miles, Michael F

2017-01-01

Complex behavioral traits, such as alcohol abuse, are caused by an interplay of genetic and environmental factors, producing deleterious functional adaptations in the central nervous system. The long-term behavioral consequences of such changes are of substantial cost to both the individual and society. Substantial progress has been made in the last two decades in understanding elements of brain mechanisms underlying responses to ethanol in animal models and risk factors for alcohol use disorder (AUD) in humans. However, treatments for AUD remain largely ineffective and few medications for this disease state have been licensed. Genome-wide genetic polymorphism analysis (GWAS) in humans, behavioral genetic studies in animal models and brain gene expression studies produced by microarrays or RNA-seq have the potential to produce nonbiased and novel insight into the underlying neurobiology of AUD. However, the complexity of such information, both statistical and informational, has slowed progress toward identifying new targets for intervention in AUD. This chapter describes one approach for integrating behavioral, genetic, and genomic information across animal model and human studies. The goal of this approach is to identify networks of genes functioning in the brain that are most relevant to the underlying mechanisms of a complex disease such as AUD. We illustrate an example of how genomic studies in animal models can be used to produce robust gene networks that have functional implications, and to integrate such animal model genomic data with human genetic studies such as GWAS for AUD. We describe several useful analysis tools for such studies: ComBAT, WGCNA, and EW_dmGWAS. The end result of this analysis is a ranking of gene networks and identification of their cognate hub genes, which might provide eventual targets for future therapeutic development. Furthermore, this combined approach may also improve our understanding of basic mechanisms underlying gene x environmental interactions affecting brain functioning in health and disease.

INTEGRATIVE ANALYSIS OF GENETIC, GENOMIC AND PHENOTYPIC DATA FOR ETHANOL BEHAVIORS: A NETWORK-BASED PIPELINE FOR IDENTIFYING MECHANISMS AND POTENTIAL DRUG TARGETS

PubMed Central

Bogenpohl, James W.; Mignogna, Kristin M.; Smith, Maren L.; Miles, Michael F.

2016-01-01

Complex behavioral traits, such as alcohol abuse, are caused by an interplay of genetic and environmental factors, producing deleterious functional adaptations in the central nervous system. The long-term behavioral consequences of such changes are of substantial cost to both the individual and society. Substantial progress has been made in the last two decades in understanding elements of brain mechanisms underlying responses to ethanol in animal models and risk factors for alcohol use disorder (AUD) in humans. However, treatments for AUD remain largely ineffective and few medications for this disease state have been licensed. Genome-wide genetic polymorphism analysis (GWAS) in humans, behavioral genetic studies in animal models and brain gene expression studies produced by microarrays or RNA-seq have the potential to produce non-biased and novel insight into the underlying neurobiology of AUD. However, the complexity of such information, both statistical and informational, has slowed progress toward identifying new targets for intervention in AUD. This chapter describes one approach for integrating behavioral, genetic, and genomic information across animal model and human studies. The goal of this approach is to identify networks of genes functioning in the brain that are most relevant to the underlying mechanisms of a complex disease such as AUD. We illustrate an example of how genomic studies in animal models can be used to produce robust gene networks that have functional implications, and to integrate such animal model genomic data with human genetic studies such as GWAS for AUD. We describe several useful analysis tools for such studies: ComBAT, WGCNA and EW_dmGWAS. The end result of this analysis is a ranking of gene networks and identification of their cognate hub genes, which might provide eventual targets for future therapeutic development. Furthermore, this combined approach may also improve our understanding of basic mechanisms underlying gene x environmental interactions affecting brain functioning in health and disease. PMID:27933543

A model for brain life history evolution.

PubMed

González-Forero, Mauricio; Faulwasser, Timm; Lehmann, Laurent

2017-03-01

Complex cognition and relatively large brains are distributed across various taxa, and many primarily verbal hypotheses exist to explain such diversity. Yet, mathematical approaches formalizing verbal hypotheses would help deepen the understanding of brain and cognition evolution. With this aim, we combine elements of life history and metabolic theories to formulate a metabolically explicit mathematical model for brain life history evolution. We assume that some of the brain's energetic expense is due to production (learning) and maintenance (memory) of energy-extraction skills (or cognitive abilities, knowledge, information, etc.). We also assume that individuals use such skills to extract energy from the environment, and can allocate this energy to grow and maintain the body, including brain and reproductive tissues. The model can be used to ask what fraction of growth energy should be allocated at each age, given natural selection, to growing brain and other tissues under various biological settings. We apply the model to find uninvadable allocation strategies under a baseline setting ("me vs nature"), namely when energy-extraction challenges are environmentally determined and are overcome individually but possibly with maternal help, and use modern-human data to estimate model's parameter values. The resulting uninvadable strategies yield predictions for brain and body mass throughout ontogeny and for the ages at maturity, adulthood, and brain growth arrest. We find that: (1) a me-vs-nature setting is enough to generate adult brain and body mass of ancient human scale and a sequence of childhood, adolescence, and adulthood stages; (2) large brains are favored by intermediately challenging environments, moderately effective skills, and metabolically expensive memory; and (3) adult skill is proportional to brain mass when metabolic costs of memory saturate the brain metabolic rate allocated to skills.

Neuroimaging and Drug Taking in Primates Abbreviated title: Neuroimaging and Drug taking

PubMed Central

Murnane, Kevin S.; Howell, Leonard L.

2011-01-01

Rationale Neuroimaging techniques have led to significant advances in our understanding of the neurobiology of drug-taking and the treatment of drug addiction in humans. Neuroimaging approaches provide a powerful translational approach that can link findings from humans and laboratory animals. Objective This review describes the utility of neuroimaging toward understanding the neurobiological basis of drug taking, and documents the close concordance that can be achieved among neuroimaging, neurochemical and behavioral endpoints. Results The study of drug interactions with dopamine and serotonin transporters in vivo has identified pharmacological mechanisms of action associated with the abuse liability of stimulants. Neuroimaging has identified the extended limbic system, including the prefrontal cortex and anterior cingulate, as important neuronal circuitry that underlies drug taking. The ability to conduct within-subject, longitudinal assessments of brain chemistry and neuronal function has enhanced our efforts to document long-term changes in dopamine D2 receptors, monoamine transporters, and prefrontal metabolism due to chronic drug exposure. Dysregulation of dopamine function and brain metabolic changes in areas involved in reward circuitry have been linked to drug-taking behavior, cognitive impairment and treatment response. Conclusions Experimental designs employing neuroimaging should consider well-documented determinants of drug taking, including pharmacokinetic considerations, subject history and environmental variables. Methodological issues to consider include limited molecular probes, lack of neurochemical specificity in brain activation studies, and the potential influence of anesthetics in animal studies. Nevertheless, these integrative approaches should have important implications for understanding drug-taking behavior and the treatment of drug addiction. PMID:21360099

Human brain MRI at 500 MHz, scientific perspectives and technological challenges

NASA Astrophysics Data System (ADS)

Le Bihan, Denis; Schild, Thierry

2017-03-01

The understanding of the human brain is one of the main scientific challenges of the 21st century. In the early 2000s the French Alternative Energies and Atomic Energy Commission launched a program to conceive and build a ‘human brain explorer’, the first human MRI scanner operating at 11.7 T. This scanner was envisioned to be part of the ambitious French-German project Iseult, bridging together industrial and academic partners to push the limits of molecular neuroimaging, from mouse to man, using ultra-high field MRI. In this article we provide a summary of the main neuroscience and medical targets of the Iseult project, mainly to acquire within timescales compatible with human tolerances images at a scale of 100 μm at which everything remains to discover, and to create new approaches to develop new imaging biomarkers for specific neurological and psychiatric disorders. The system specifications, the technological challenges, in terms of magnet design, winding technology, cryogenics, quench protection, stability control, and the solutions which have been chosen to overcome them and build this outstanding instrument are provided. Lines of the research and development which will be necessary to fully exploit the potential of this and other UHF MRI scanners are also outlined.

Where the thoughts dwell: the physiology of neuronal-glial "diffuse neural net".

PubMed

Verkhratsky, Alexei; Parpura, Vladimir; Rodríguez, José J

2011-01-07

The mechanisms underlying the production of thoughts by exceedingly complex cellular networks that construct the human brain constitute the most challenging problem of natural sciences. Our understanding of the brain function is very much shaped by the neuronal doctrine that assumes that neuronal networks represent the only substrate for cognition. These neuronal networks however are embedded into much larger and probably more complex network formed by neuroglia. The latter, although being electrically silent, employ many different mechanisms for intercellular signalling. It appears that astrocytes can control synaptic networks and in such a capacity they may represent an integral component of the computational power of the brain rather than being just brain "connective tissue". The fundamental question of whether neuroglia is involved in cognition and information processing remains, however, open. Indeed, a remarkable increase in the number of glial cells that distinguishes the human brain can be simply a result of exceedingly high specialisation of the neuronal networks, which delegated all matters of survival and maintenance to the neuroglia. At the same time potential power of analogue processing offered by internally connected glial networks may represent the alternative mechanism involved in cognition. Copyright © 2010 Elsevier B.V. All rights reserved.

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".

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.

Human development II: we need an integrated theory for matter, life and consciousness to understand life and healing.

PubMed

Ventegodt, Søren; Hermansen, Tyge Dahl; Nielsen, Maj Lyck; Clausen, Birgitte; Merrick, Joav

2006-07-06

For almost a decade, we have experimented with supporting the philosophical development of severely ill patients to induce recovery and spontaneous healing. Recently, we have observed a new pattern of extremely rapid, spontaneous healing that apparently can facilitate even the spontaneous remission of cancer and the spontaneous recovery of mental diseases like schizophrenia and borderline schizophrenia. Our working hypothesis is that the accelerated healing is a function of the patient's brain-mind and body-mind coming closer together due to the development of what we call "deep" cosmology. To understand and describe what happens at a biological level, we have suggested naming the process adult human metamorphosis, a possibility that is opened by the human genome showing full generic equipment for metamorphosis. To understand the mechanistic details in the complicated interaction between consciousness and biology, we need an adequate theory for biological information. In a series of papers, we propose what we call "holistic biology for holistic medicine". We suggest that a relatively simple model based on interacting wholenesses instead of isolated parts can shed a new light on a number of difficult issues that we need to explain and understand in biology and medicine in order to understand and use metamorphosis in the holistic medical clinic. We aim to give a holistic theoretical interpretation of biological phenomena at large, morphogenesis, evolution, immune system regulation (self-nonself discrimination), brain function, consciousness, and health in particular. We start at the most fundamental problem: what is biological information at the subcellular, cellular, and supracellular levels if we presume that it is the same phenomenon on all levels (using Occam's razor), and how can this be described scientifically? The problems we address are all connected to the information flow in the functioning, living organism: function of the brain and consciousness, the regulations of the immune system and cell growth, the dynamics of health and disease. We suggest that life utilizes an unseen fine structure of the physical energy of the universe at a subparticular or quantum level to give information-directed self-organization; we give a first sketch of a possible fractal structure of the energy able to both contain and communicate biological information and carry individual and collective consciousness. Finally, thorough our analysis, we put up a model for adult human metamorphosis.

Convergent models of handedness and brain lateralization

PubMed Central

Sainburg, Robert L.

2014-01-01

The pervasive nature of handedness across human history and cultures is a salient consequence of brain lateralization. This paper presents evidence that provides a structure for understanding the motor control processes that give rise to handedness. According to the Dynamic Dominance Model, the left hemisphere (in right handers) is proficient for processes that predict the effects of body and environmental dynamics, while the right hemisphere is proficient at impedance control processes that can minimize potential errors when faced with unexpected mechanical conditions, and can achieve accurate steady-state positions. This model can be viewed as a motor component for the paradigm of brain lateralization that has been proposed by Rogers et al. (MacNeilage et al., 2009) that is based upon evidence from a wide range of behaviors across many vertebrate species. Rogers proposed a left-hemisphere specialization for well-established patterns of behavior performed in familiar environmental conditions, and a right hemisphere specialization for responding to unforeseen environmental events. The dynamic dominance hypothesis provides a framework for understanding the biology of motor lateralization that is consistent with Roger's paradigm of brain lateralization. PMID:25339923

Current state of the use of neuroimaging techniques to understand and alter appetite control in humans.

PubMed

Spetter, Maartje S

2018-06-20

It is in the brain where the decision is made what and how much to eat. In the last decades neuroimaging research has contributed extensively to new knowledge about appetite control by revealing the underlying brain processes. Interestingly, there is the fast growing idea of using these methods to develop new treatments for obesity and eating disorders. In this review, we summarize the findings of the importance of the use of neuropharmacology and neuroimaging techniques in understanding and modifying appetite control. Appetite control is a complex interplay between homeostatic, hedonic, and cognitive processes. Administration of the neuropeptides insulin and oxytocin curb food intake and alter brain responses in reward and cognitive control areas. Additionally, these areas can be targeted for neuromodulation or neurofeedback to reduce food cravings and increase self-control to alter food intake. The recent findings reveal the potential of intranasal administration of hormones or modifying appetite control brain networks to reduce food consumption in volunteers with overweight and obesity or individuals with an eating disorder. Although long-term clinical studies are still needed.

How beliefs about self-creation inflate value in the human brain.

PubMed

Koster, Raphael; Sharot, Tali; Yuan, Rachel; De Martino, Benedetto; Norton, Michael I; Dolan, Raymond J

2015-01-01

Humans have a tendency to overvalue their own ideas and creations. Understanding how these errors in judgement emerge is important for explaining suboptimal decisions, as when individuals and groups choose self-created alternatives over superior or equal ones. We show that such overvaluation is a reconstructive process that emerges when participants believe they have created an item, regardless of whether this belief is true or false. This overvaluation is observed both when false beliefs of self-creation are elicited (Experiment 1) or implanted (Experiment 2). Using brain imaging data we highlight the brain processes mediating an interaction between value and belief of self-creation. Specifically, following the creation manipulation there is an increased functional connectivity during valuation between the right caudate nucleus, where we show BOLD activity correlated with subjective value, and the left amygdala, where we show BOLD activity is linked to subjective belief. Our study highlights psychological and neurobiological processes through which false beliefs alter human valuation and in doing so throw light on a common source of error in judgements of value.

Hypnosis and imaging of the living human brain.

PubMed

Landry, Mathieu; Raz, Amir

2015-01-01

Over more than two decades, studies using imaging techniques of the living human brain have begun to explore the neural correlates of hypnosis. The collective findings provide a gripping, albeit preliminary, account of the underlying neurobiological mechanisms involved in hypnotic phenomena. While substantial advances lend support to different hypotheses pertaining to hypnotic modulation of attention, control, and monitoring processes, the complex interactions among the many mediating variables largely hinder our ability to isolate robust commonalities across studies. The present account presents a critical integrative synthesis of neuroimaging studies targeting hypnosis as a function of suggestion. Specifically, hypnotic induction without task-specific suggestion is examined, as well as suggestions concerning sensation and perception, memory, and ideomotor response. The importance of carefully designed experiments is highlighted to better tease apart the neural correlates that subserve hypnotic phenomena. Moreover, converging findings intimate that hypnotic suggestions seem to induce specific neural patterns. These observations propose that suggestions may have the ability to target focal brain networks. Drawing on evidence spanning several technological modalities, neuroimaging studies of hypnosis pave the road to a more scientific understanding of a dramatic, yet largely evasive, domain of human behavior.

Influence of White and Gray Matter Connections on Endogenous Human Cortical Oscillations

PubMed Central

Hawasli, Ammar H.; Kim, DoHyun; Ledbetter, Noah M.; Dahiya, Sonika; Barbour, Dennis L.; Leuthardt, Eric C.

2016-01-01

Brain oscillations reflect changes in electrical potentials summated across neuronal populations. Low- and high-frequency rhythms have different modulation patterns. Slower rhythms are spatially broad, while faster rhythms are more local. From this observation, we hypothesized that low- and high-frequency oscillations reflect white- and gray-matter communications, respectively, and synchronization between low-frequency phase with high-frequency amplitude represents a mechanism enabling distributed brain-networks to coordinate local processing. Testing this common understanding, we selectively disrupted white or gray matter connections to human cortex while recording surface field potentials. Counter to our original hypotheses, we found that cortex consists of independent oscillatory-units (IOUs) that maintain their own complex endogenous rhythm structure. IOUs are differentially modulated by white and gray matter connections. White-matter connections maintain topographical anatomic heterogeneity (i.e., separable processing in cortical space) and gray-matter connections segregate cortical synchronization patterns (i.e., separable temporal processing through phase-power coupling). Modulation of distinct oscillatory modules enables the functional diversity necessary for complex processing in the human brain. PMID:27445767

How beliefs about self-creation inflate value in the human brain

PubMed Central

Koster, Raphael; Sharot, Tali; Yuan, Rachel; De Martino, Benedetto; Norton, Michael I.; Dolan, Raymond J.

2015-01-01

Humans have a tendency to overvalue their own ideas and creations. Understanding how these errors in judgement emerge is important for explaining suboptimal decisions, as when individuals and groups choose self-created alternatives over superior or equal ones. We show that such overvaluation is a reconstructive process that emerges when participants believe they have created an item, regardless of whether this belief is true or false. This overvaluation is observed both when false beliefs of self-creation are elicited (Experiment 1) or implanted (Experiment 2). Using brain imaging data we highlight the brain processes mediating an interaction between value and belief of self-creation. Specifically, following the creation manipulation there is an increased functional connectivity during valuation between the right caudate nucleus, where we show BOLD activity correlated with subjective value, and the left amygdala, where we show BOLD activity is linked to subjective belief. Our study highlights psychological and neurobiological processes through which false beliefs alter human valuation and in doing so throw light on a common source of error in judgements of value. PMID:26388755

'Faceness' and affectivity: evidence for genetic contributions to distinct components of electrocortical response to human faces.

PubMed

Shannon, Robert W; Patrick, Christopher J; Venables, Noah C; He, Sheng

2013-12-01

The ability to recognize a variety of different human faces is undoubtedly one of the most important and impressive functions of the human perceptual system. Neuroimaging studies have revealed multiple brain regions (including the FFA, STS, OFA) and electrophysiological studies have identified differing brain event-related potential (ERP) components (e.g., N170, P200) possibly related to distinct types of face information processing. To evaluate the heritability of ERP components associated with face processing, including N170, P200, and LPP, we examined ERP responses to fearful and neutral face stimuli in monozygotic (MZ) and dizygotic (DZ) twins. Concordance levels for early brain response indices of face processing (N170, P200) were found to be stronger for MZ than DZ twins, providing evidence of a heritable basis to each. These findings support the idea that certain key neural mechanisms for face processing are genetically coded. Implications for understanding individual differences in recognition of facial identity and the emotional content of faces are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

A cross-validated cytoarchitectonic atlas of the human ventral visual stream.

PubMed

Rosenke, Mona; Weiner, Kevin S; Barnett, Michael A; Zilles, Karl; Amunts, Katrin; Goebel, Rainer; Grill-Spector, Kalanit

2018-04-15

The human ventral visual stream consists of several areas that are considered processing stages essential for perception and recognition. A fundamental microanatomical feature differentiating areas is cytoarchitecture, which refers to the distribution, size, and density of cells across cortical layers. Because cytoarchitectonic structure is measured in 20-micron-thick histological slices of postmortem tissue, it is difficult to assess (a) how anatomically consistent these areas are across brains and (b) how they relate to brain parcellations obtained with prevalent neuroimaging methods, acquired at the millimeter and centimeter scale. Therefore, the goal of this study was to (a) generate a cross-validated cytoarchitectonic atlas of the human ventral visual stream on a whole brain template that is commonly used in neuroimaging studies and (b) to compare this atlas to a recently published retinotopic parcellation of visual cortex (Wang et al., 2014). To achieve this goal, we generated an atlas of eight cytoarchitectonic areas: four areas in the occipital lobe (hOc1-hOc4v) and four in the fusiform gyrus (FG1-FG4), then we tested how the different alignment techniques affect the accuracy of the resulting atlas. Results show that both cortex-based alignment (CBA) and nonlinear volumetric alignment (NVA) generate an atlas with better cross-validation performance than affine volumetric alignment (AVA). Additionally, CBA outperformed NVA in 6/8 of the cytoarchitectonic areas. Finally, the comparison of the cytoarchitectonic atlas to a retinotopic atlas shows a clear correspondence between cytoarchitectonic and retinotopic areas in the ventral visual stream. The successful performance of CBA suggests a coupling between cytoarchitectonic areas and macroanatomical landmarks in the human ventral visual stream, and furthermore, that this coupling can be utilized for generating an accurate group atlas. In addition, the coupling between cytoarchitecture and retinotopy highlights the potential use of this atlas in understanding how anatomical features contribute to brain function. We make this cytoarchitectonic atlas freely available in both BrainVoyager and FreeSurfer formats (http://vpnl.stanford.edu/vcAtlas). The availability of this atlas will enable future studies to link cytoarchitectonic organization to other parcellations of the human ventral visual stream with potential to advance the understanding of this pathway in typical and atypical populations. Copyright © 2017 Elsevier Inc. All rights reserved.

The 'selfish brain' is regulated by aquaporins and autophagy under nutrient deprivation.

PubMed

Ye, Qiao; Wu, Yonghong; Gao, Yan; Li, Zhihui; Li, Weiguang; Zhang, Chenggang

2016-05-01

The brain maintains its mass and physiological functional capacity compared with other organs under harsh conditions such as starvation, a mechanism termed the 'selfish brain' theory. To further investigate this phenomenon, mice were examined following water and/or food deprivation. Although the body weights of the mice, the weight of the organs except the brain and blood glucose levels were significantly reduced in the absence of water and/or food, the brain weight maintained its original state. Furthermore, no significant differences in the water content of the brain or its energy balance were observed when the mice were subjected to water and/or food deprivation. To further investigate the mechanism underlying the brain maintenance of water and substance homeostasis, the expression levels of aquaporins (AQPs) and autophagy‑specific protein long‑chain protein 3 (LC3) were examined. During the process of water and food deprivation, no significant differences in the transcriptional levels of AQPs were observed. However, autophagy activity levels were initially stimulated, then suppressed in a time‑dependent manner. LC3 and AQPs have important roles for the survival of the brain under conditions of food and water deprivation, which provided further understanding of the mechanism underlying the 'selfish brain' phenomenon. Although not involved in the energy regulation of the 'selfish brain', AQPs were observed to have important roles in water and food deprivation, specifically with regards to the control of water content. Additionally, the brain exhibits an 'unselfish strategy' using autophagy during water and/or food deprivation. The present study furthered current understanding of the 'selfish brain' theory, and identified additional regulating target genes of AQPs and autophagy, with the aim of providing a basis for the prevention of nutrient shortage in humans and animals.

The 'selfish brain' is regulated by aquaporins and autophagy under nutrient deprivation

PubMed Central

YE, QIAO; WU, YONGHONG; GAO, YAN; LI, ZHIHUI; LI, WEIGUANG; ZHANG, CHENGGANG

2016-01-01

The brain maintains its mass and physiological functional capacity compared with other organs under harsh conditions such as starvation, a mechanism termed the 'selfish brain' theory. To further investigate this phenomenon, mice were examined following water and/or food deprivation. Although the body weights of the mice, the weight of the organs except the brain and blood glucose levels were significantly reduced in the absence of water and/or food, the brain weight maintained its original state. Furthermore, no significant differences in the water content of the brain or its energy balance were observed when the mice were subjected to water and/or food deprivation. To further investigate the mechanism underlying the brain maintenance of water and substance homeostasis, the expression levels of aquaporins (AQPs) and autophagy-specific protein long-chain protein 3 (LC3) were examined. During the process of water and food deprivation, no significant differences in the transcriptional levels of AQPs were observed. However, autophagy activity levels were initially stimulated, then suppressed in a time-dependent manner. LC3 and AQPs have important roles for the survival of the brain under conditions of food and water deprivation, which provided further understanding of the mechanism underlying the 'selfish brain' phenomenon. Although not involved in the energy regulation of the 'selfish brain', AQPs were observed to have important roles in water and food deprivation, specifically with regards to the control of water content. Additionally, the brain exhibits an 'unselfish strategy' using autophagy during water and/or food deprivation. The present study furthered current understanding of the 'selfish brain' theory, and identified additional regulating target genes of AQPs and autophagy, with the aim of providing a basis for the prevention of nutrient shortage in humans and animals. PMID:26986971

Advances in memory research: single-neuron recordings from the human medial temporal lobe aid our understanding of declarative memory.

PubMed

Viskontas, Indre V

2008-12-01

To gain a complete understanding of how the brain functions, both in illness and good health, data from multiple levels of analysis must be integrated. Technical advances have made direct recordings of neuronal activity deep inside the human brain tractable, providing a rare glimpse into cellular processes during long-term memory formation. Recent findings using intracranial recordings in the medial temporal lobe inform current neural network models of memory, and may lead to a more comprehensive understanding of the neural basis of memory-related processes. These recordings have shown that cells in the hippocampus appear to support declarative learning by distinguishing novel and familiar stimuli via changes in firing patterns. Some cells with highly selective and invariant responses have also been described, and these responses seem to represent abstract concepts such as identity, rather than superficial perceptual features of items. Importantly, however, both selective and globally responsive cells are capable of changing their preferred stimulus depending on the conscious demands of the task. Firing patterns of human medial temporal lobe neurons indicate that cells can be both plastic and stable in terms of the information that they code; although some cells show highly selective and reproducible excitatory responses when presented with a familiar object, other cells change their receptive fields in line with changes in experience and the cognitive environment.

CARBARYL EFFECTS ON OXIDATIVE STRESS IN BRAIN REGIONS OF ADOLESCENT AND SENESCENT BROWN NORWAY RATS

EPA Science Inventory

Oxidative stress (OS) plays an important role in susceptibility and disease in old age. Understanding age-related susceptibility is crucial in assessing the human health risks of chemicals. Growing evidence implicates as in carbamate toxicity in addition to cholinesterase-inhibit...

Effect of alcohol use disorder on oxytocin peptide and receptor mRNA expression in human brain: A post-mortem case-control study.

PubMed

Lee, Mary R; Schwandt, Melanie L; Sankar, Vignesh; Suchankova, Petra; Sun, Hui; Leggio, Lorenzo

2017-11-01

Animal and human evidence supports a role for oxytocin in alcohol-seeking behaviors. There is interest, therefore, in targeting the oxytocin pathway as a new pharmacologic approach to treat alcohol use disorder. To this end, it is important to understand the effect of alcohol use disorder on endogenous oxytocin in brain regions that are relevant for the initiation and maintenance of alcohol use disorder. We examined human post-mortem brain tissue from males with alcohol use disorder (n=11) compared to nonalcohol dependent male controls (n=16). We a priori targeted five brain regions that in rodent studies, are projection areas for oxytocin neurons: nucleus accumbens, amygdala, hippocampus, ventral tegmental area and prefrontal cortex. Fold change in mRNA levels of oxytocin peptide and receptor were measured in each of the brain regions studied. Fold change for oxytocin peptide mRNA was significantly elevated in the prefrontal cortex of subjects with alcohol use disorder compared to controls (uncorrected p=0.0001; FDR-corrected p=0.001). For the entire sample of 27 subjects, there was a significant positive correlation between the fold change in oxytocin peptide mRNA in the prefrontal cortex and both daily alcohol intake (r 2 =0.38; p=0.002) and drinks per week (r 2 =0.24; p=0.02). Results are discussed in light of the previous animal and human literature on changes in the endogenous oxytocin system as an effect of chronic alcohol exposure. Copyright © 2017. Published by Elsevier Ltd.

Neurocognitive Aging and the Hippocampus Across Species

PubMed Central

Leal, Stephanie L; Yassa, Michael A.

2016-01-01

There is extensive evidence that aging is associated with impairments in episodic memory. Many of these changes have been ascribed to neurobiological alterations to the hippocampal network and its input pathways. A cross-species consensus is beginning to emerge suggesting that subtle synaptic and functional changes within this network may underlie the majority of age-related memory impairments. In this review, we survey convergent data from animal and human studies that have contributed significantly to our understanding of the brain-behavior relationships in this network, particularly in the aging brain. We utilize a cognitive as well as a neurobiological perspective, and synthesize data across approaches and species to reach a more detailed understanding of age-related alterations in hippocampal memory function. PMID:26607684

Multistability and metastability: understanding dynamic coordination in the brain

PubMed Central

Kelso, J. A. Scott

2012-01-01

Multistable coordination dynamics exists at many levels, from multifunctional neural circuits in vertebrates and invertebrates to large-scale neural circuitry in humans. Moreover, multistability spans (at least) the domains of action and perception, and has been found to place constraints upon, even dictating the nature of, intentional change and the skill-learning process. This paper reviews some of the key evidence for multistability in the aforementioned areas, and illustrates how it has been measured, modelled and theoretically understood. It then suggests how multistability—when combined with essential aspects of coordination dynamics such as instability, transitions and (especially) metastability—provides a platform for understanding coupling and the creative dynamics of complex goal-directed systems, including the brain and the brain–behaviour relation. PMID:22371613

Asymmetry of the Brain: Development and Implications.

PubMed

Duboc, Véronique; Dufourcq, Pascale; Blader, Patrick; Roussigné, Myriam

2015-01-01

Although the left and right hemispheres of our brains develop with a high degree of symmetry at both the anatomical and functional levels, it has become clear that subtle structural differences exist between the two sides and that each is dominant in processing specific cognitive tasks. As the result of evolutionary conservation or convergence, lateralization of the brain is found in both vertebrates and invertebrates, suggesting that it provides significant fitness for animal life. This widespread feature of hemispheric specialization has allowed the emergence of model systems to study its development and, in some cases, to link anatomical asymmetries to brain function and behavior. Here, we present some of what is known about brain asymmetry in humans and model organisms as well as what is known about the impact of environmental and genetic factors on brain asymmetry development. We specifically highlight the progress made in understanding the development of epithalamic asymmetries in zebrafish and how this model provides an exciting opportunity to address brain asymmetry at different levels of complexity.

Neuroinflamm-aging and neurodegenerative diseases: an overview.

PubMed

Pizza, Vincenzo; Agresta, Anella; D'Acunto, Cosimo W; Festa, Michela; Capasso, Anna

2011-08-01

Neuroinflammation is considered a chronic activation of the immune response in the central nervous system (CNS) in response to different injuries. This brain immune activation results in various events: circulating immune cells infiltrate the CNS; resident cells are activated; and pro-inflammatory mediators produced and released induce neuroinflammatory brain disease. The effect of immune diffusible mediators on synaptic plasticity might result in CNS dysfunction during neuroinflammatory brain diseases. The CNS dysfunction may induce several human pathological conditions associated with both cognitive impairment and a variable degree of neuroinflammation. Furthermore, age has a powerful effect on enhanced susceptibility to neurodegenerative diseases and age-dependent enhanced neuroinflammatory processes may play an important role in toxin generation that causes death or dysfunction of neurons in neurodegenerative diseases This review will address current understanding of the relationship between ageing, neuroinflammation and neurodegenerative disease by focusing on the principal mechanisms by which the immune system influences the brain plastic phenomena. Also, the present review considers the principal human neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis and psychiatric disorders caused by aging and neuroinflammation.

Recent advances in basic neurosciences and brain disease: from synapses to behavior

PubMed Central

Bi, Guo-Qiang; Bolshakov, Vadim; Bu, Guojun; Cahill, Catherine M; Chen, Zhou-Feng; Collingridge, Graham L; Cooper, Robin L; Coorssen, Jens R; El-Husseini, Alaa; Galhardo, Vasco; Gan, Wen-Biao; Gu, Jianguo; Inoue, Kazuhide; Isaac, John; Iwata, Koichi; Jia, Zhengping; Kaang, Bong-Kiun; Kawamata, Mikito; Kida, Satoshi; Klann, Eric; Kohno, Tatsuro; Li, Min; Li, Xiao-Jiang; MacDonald, John F; Nader, Karim; Nguyen, Peter V; Oh, Uhtaek; Ren, Ke; Roder, John C; Salter, Michael W; Song, Weihong; Sugita, Shuzo; Tang, Shao-Jun; Tao, Yuanxiang; Wang, Yu Tian; Woo, Newton; Woodin, Melanie A; Yan, Zhen; Yoshimura, Megumu; Xu, Ming; Xu, Zao C; Zhang, Xia; Zhen, Mei; Zhuo, Min

2006-01-01

Understanding basic neuronal mechanisms hold the hope for future treatment of brain disease. The 1st international conference on synapse, memory, drug addiction and pain was held in beautiful downtown Toronto, Canada on August 21–23, 2006. Unlike other traditional conferences, this new meeting focused on three major aims: (1) to promote new and cutting edge research in neuroscience; (2) to encourage international information exchange and scientific collaborations; and (3) to provide a platform for active scientists to discuss new findings. Up to 64 investigators presented their recent discoveries, from basic synaptic mechanisms to genes related to human brain disease. This meeting was in part sponsored by Molecular Pain, together with University of Toronto (Faculty of Medicine, Department of Physiology as well as Center for the Study of Pain). Our goal for this meeting is to promote future active scientific collaborations and improve human health through fundamental basic neuroscience researches. The second international meeting on Neurons and Brain Disease will be held in Toronto (August 29–31, 2007). PMID:17196111

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

Non-invasive measurement of brain glycogen by NMR spectroscopy and its application to the study of brain metabolism

PubMed Central

Tesfaye, Nolawit; Seaquist, Elizabeth R.; Öz, Gülin

2011-01-01

Glycogen is the reservoir for glucose in the brain. Beyond the general agreement that glycogen serves as an energy source in the central nervous system, its exact role in brain energy metabolism has yet to be elucidated. Experiments performed in cell and tissue culture and animals have shown that glycogen content is affected by several factors including glucose, insulin, neurotransmitters, and neuronal activation. The study of in vivo glycogen metabolism has been hindered by the inability to measure glycogen non-invasively, but in the past several years, the development of a non-invasive localized 13C nuclear magnetic resonance (NMR) spectroscopy method has enabled the study of glycogen metabolism in the conscious human. With this technique, 13C-glucose is administered intravenously and its incorporation into and wash-out from brain glycogen is tracked. One application of this method has been to the study of brain glycogen metabolism in humans during hypoglycemia: data have shown that mobilization of brain glycogen is augmented during hypoglycemia and, after a single episode of hypoglycemia, glycogen synthesis rate is increased, suggesting that glycogen stores rebound to levels greater than baseline. Such studies suggest glycogen may serve as a potential energy reservoir in hypoglycemia and may participate in the brain's adaptation to recurrent hypoglycemia and eventual development of hypoglycemia unawareness. Beyond this focused area of study, 13C NMR spectroscopy has a broad potential for application in the study of brain glycogen metabolism and carries the promise of a better understanding of the role of brain glycogen in diabetes and other conditions. PMID:21732401

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

The social brain hypothesis of schizophrenia.

PubMed

Burns, Jonathan

2006-06-01

The social brain hypothesis is a useful heuristic for understanding schizophrenia. It focuses attention on the core Bleulerian concept of autistic alienation and is consistent with well-replicated findings of social brain dysfunction in schizophrenia as well as contemporary theories of human cognitive and brain evolution. The contributions of Heidegger, Merleau-Ponty and Wittgenstein allow us to arrive at a new "philosophy of interpersonal relatedness", which better reflects the "embodied mind" and signifies the end of Cartesian dualistic thinking. In this paper I review the evolution, development and neurobiology of the social brain - the anatomical and functional substrate for adaptive social behaviour and cognition. Functional imaging identifies fronto-temporal and fronto-parietal cortical networks as comprising the social brain, while the discovery of "mirror neurons" provides an understanding of social cognition at a cellular level. Patients with schizophrenia display abnormalities in a wide range of social cognition tasks such as emotion recognition, theory of mind and affective responsiveness. Furthermore, recent research indicates that schizophrenia is a disorder of functional and structural connectivity of social brain networks. These findings lend support to the claim that schizophrenia represents a costly by-product of social brain evolution in Homo sapiens. Individuals with this disorder find themselves seriously disadvantaged in the social arena and vulnerable to the stresses of their complex social environments. This state of "disembodiment" and interpersonal alienation is the core phenomenon of schizophrenia and the root cause of intolerable suffering in the lives of those affected.

The social brain hypothesis of schizophrenia

PubMed Central

BURNS, JONATHAN

2006-01-01

The social brain hypothesis is a useful heuristic for understanding schizophrenia. It focuses attention on the core Bleulerian concept of autistic alienation and is consistent with well-replicated findings of social brain dysfunction in schizophrenia as well as contemporary theories of human cognitive and brain evolution. The contributions of Heidegger, Merleau-Ponty and Wittgenstein allow us to arrive at a new "philosophy of interpersonal relatedness", which better reflects the "embodied mind" and signifies the end of Cartesian dualistic thinking. In this paper I review the evolution, development and neurobiology of the social brain - the anatomical and functional substrate for adaptive social behaviour and cognition. Functional imaging identifies fronto-temporal and fronto-parietal cortical networks as comprising the social brain, while the discovery of "mirror neurons" provides an understanding of social cognition at a cellular level. Patients with schizophrenia display abnormalities in a wide range of social cognition tasks such as emotion recognition, theory of mind and affective responsiveness. Furthermore, recent research indicates that schizophrenia is a disorder of functional and structural connectivity of social brain networks. These findings lend support to the claim that schizophrenia represents a costly by-product of social brain evolution in Homo sapiens. Individuals with this disorder find themselves seriously disadvantaged in the social arena and vulnerable to the stresses of their complex social environments. This state of "disembodiment" and interpersonal alienation is the core phenomenon of schizophrenia and the root cause of intolerable suffering in the lives of those affected. PMID:16946939

The retention time of inorganic mercury in the brain — A systematic review of the evidence

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

Rooney, James P.K., E-mail: jrooney@rcsi.ie

2014-02-01

Reports from human case studies indicate a half-life for inorganic mercury in the brain in the order of years—contradicting older radioisotope studies that estimated half-lives in the order of weeks to months in duration. This study systematically reviews available evidence on the retention time of inorganic mercury in humans and primates to better understand this conflicting evidence. A broad search strategy was used to capture 16,539 abstracts on the Pubmed database. Abstracts were screened to include only study types containing relevant information. 131 studies of interest were identified. Only 1 primate study made a numeric estimate for the half-life ofmore » inorganic mercury (227–540 days). Eighteen human mercury poisoning cases were followed up long term including autopsy. Brain inorganic mercury concentrations at death were consistent with a half-life of several years or longer. 5 radionucleotide studies were found, one of which estimated head half-life (21 days). This estimate has sometimes been misinterpreted to be equivalent to brain half-life—which ignores several confounding factors including limited radioactive half-life and radioactive decay from surrounding tissues including circulating blood. No autopsy cohort study estimated a half-life for inorganic mercury, although some noted bioaccumulation of brain mercury with age. Modelling studies provided some extreme estimates (69 days vs 22 years). Estimates from modelling studies appear sensitive to model assumptions, however predications based on a long half-life (27.4 years) are consistent with autopsy findings. In summary, shorter estimates of half-life are not supported by evidence from animal studies, human case studies, or modelling studies based on appropriate assumptions. Evidence from such studies point to a half-life of inorganic mercury in human brains of several years to several decades. This finding carries important implications for pharmcokinetic modelling of mercury and potentially for the regulatory toxicology of mercury.« less

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

Frozen tissue preparation for high-resolution multiplex histological analyses of human brain specimens.

PubMed

Shao, Fangjie; Jiang, Wenhong; Gao, Qingqing; Li, Baizhou; Sun, Chongran; Wang, Qiyuan; Chen, Qin; Sun, Bing; Shen, Hong; Zhu, Keqing; Zhang, Jianmin; Liu, Chong

2017-10-01

The availability of a comprehensive tissue library is essential for elucidating the function and pathology of human brains. Considering the irreplaceable status of the formalin-fixation-paraffin-embedding (FFPE) preparation in routine pathology and the advantage of ultra-low temperature to preserve nucleic acids and proteins for multi-omics studies, these methods have become major modalities for the construction of brain tissue libraries. Nevertheless, the use of FFPE and snap-frozen samples is limited in high-resolution histological analyses because the preparation destroys tissue integrity and/or many important cellular markers. To overcome these limitations, we detailed a protocol to prepare and analyze frozen human brain samples that is particularly suitable for high-resolution multiplex immunohistological studies. As an alternative, we offered an optimized procedure to rescue snap-frozen tissues for the same purpose. Importantly, we provided a guideline to construct libraries of frozen tissue with minimal effort, cost and space. Taking advantage of this new tissue preparation modality to nicely preserve the cellular information that was otherwise damaged using conventional methods and to effectively remove tissue autofluorescence, we described the high-resolution landscape of the cellular composition in both lower-grade gliomas and glioblastoma multiforme samples. Our work showcases the great value of fixed frozen tissue in understanding the cellular mechanisms of CNS functions and abnormalities.

Connectivity in the human brain dissociates entropy and complexity of auditory inputs☆

PubMed Central

Nastase, Samuel A.; Iacovella, Vittorio; Davis, Ben; Hasson, Uri

2015-01-01

Complex systems are described according to two central dimensions: (a) the randomness of their output, quantified via entropy; and (b) their complexity, which reflects the organization of a system's generators. Whereas some approaches hold that complexity can be reduced to uncertainty or entropy, an axiom of complexity science is that signals with very high or very low entropy are generated by relatively non-complex systems, while complex systems typically generate outputs with entropy peaking between these two extremes. In understanding their environment, individuals would benefit from coding for both input entropy and complexity; entropy indexes uncertainty and can inform probabilistic coding strategies, whereas complexity reflects a concise and abstract representation of the underlying environmental configuration, which can serve independent purposes, e.g., as a template for generalization and rapid comparisons between environments. Using functional neuroimaging, we demonstrate that, in response to passively processed auditory inputs, functional integration patterns in the human brain track both the entropy and complexity of the auditory signal. Connectivity between several brain regions scaled monotonically with input entropy, suggesting sensitivity to uncertainty, whereas connectivity between other regions tracked entropy in a convex manner consistent with sensitivity to input complexity. These findings suggest that the human brain simultaneously tracks the uncertainty of sensory data and effectively models their environmental generators. PMID:25536493

A model for brain life history evolution

PubMed Central

Lehmann, Laurent

2017-01-01

Complex cognition and relatively large brains are distributed across various taxa, and many primarily verbal hypotheses exist to explain such diversity. Yet, mathematical approaches formalizing verbal hypotheses would help deepen the understanding of brain and cognition evolution. With this aim, we combine elements of life history and metabolic theories to formulate a metabolically explicit mathematical model for brain life history evolution. We assume that some of the brain’s energetic expense is due to production (learning) and maintenance (memory) of energy-extraction skills (or cognitive abilities, knowledge, information, etc.). We also assume that individuals use such skills to extract energy from the environment, and can allocate this energy to grow and maintain the body, including brain and reproductive tissues. The model can be used to ask what fraction of growth energy should be allocated at each age, given natural selection, to growing brain and other tissues under various biological settings. We apply the model to find uninvadable allocation strategies under a baseline setting (“me vs nature”), namely when energy-extraction challenges are environmentally determined and are overcome individually but possibly with maternal help, and use modern-human data to estimate model’s parameter values. The resulting uninvadable strategies yield predictions for brain and body mass throughout ontogeny and for the ages at maturity, adulthood, and brain growth arrest. We find that: (1) a me-vs-nature setting is enough to generate adult brain and body mass of ancient human scale and a sequence of childhood, adolescence, and adulthood stages; (2) large brains are favored by intermediately challenging environments, moderately effective skills, and metabolically expensive memory; and (3) adult skill is proportional to brain mass when metabolic costs of memory saturate the brain metabolic rate allocated to skills. PMID:28278153

Foundations for a new science of learning.

PubMed

Meltzoff, Andrew N; Kuhl, Patricia K; Movellan, Javier; Sejnowski, Terrence J

2009-07-17

Human learning is distinguished by the range and complexity of skills that can be learned and the degree of abstraction that can be achieved compared with those of other species. Homo sapiens is also the only species that has developed formal ways to enhance learning: teachers, schools, and curricula. Human infants have an intense interest in people and their behavior and possess powerful implicit learning mechanisms that are affected by social interaction. Neuroscientists are beginning to understand the brain mechanisms underlying learning and how shared brain systems for perception and action support social learning. Machine learning algorithms are being developed that allow robots and computers to learn autonomously. New insights from many different fields are converging to create a new science of learning that may transform educational practices.

The neural representation of social networks.

PubMed

Weaverdyck, Miriam E; Parkinson, Carolyn

2018-05-24

The computational demands associated with navigating large, complexly bonded social groups are thought to have significantly shaped human brain evolution. Yet, research on social network representation and cognitive neuroscience have progressed largely independently. Thus, little is known about how the human brain encodes the structure of the social networks in which it is embedded. This review highlights recent work seeking to bridge this gap in understanding. While the majority of research linking social network analysis and neuroimaging has focused on relating neuroanatomy to social network size, researchers have begun to define the neural architecture that encodes social network structure, cognitive and behavioral consequences of encoding this information, and individual differences in how people represent the structure of their social world. Copyright © 2018 Elsevier Ltd. All rights reserved.

Brain, calvarium, cladistics: A new approach to an old question, who are modern humans and Neandertals?

PubMed

Mounier, Aurélien; Balzeau, Antoine; Caparros, Miguel; Grimaud-Hervé, Dominique

2016-03-01

The evolutionary history of the genus Homo is the focus of major research efforts in palaeoanthropology. However, the use of palaeoneurology to infer phylogenies of our genus is rare. Here we use cladistics to test the importance of the brain in differentiating and defining Neandertals and modern humans. The analysis is based on morphological data from the calvarium and endocast of Pleistocene fossils and results in a single most parsimonious cladogram. We demonstrate that the joint use of endocranial and calvarial features with cladistics provides a unique means to understand the evolution of the genus Homo. The main results of this study indicate that: (i) the endocranial features are more phylogenetically informative than the characters from the calvarium; (ii) the specific differentiation of Neandertals and modern humans is mostly supported by well-known calvarial autapomorphies; (iii) the endocranial anatomy of modern humans and Neandertals show strong similarities, which appeared in the fossil record with the last common ancestor of both species; and (iv) apart from encephalisation, human endocranial anatomy changed tremendously during the end of the Middle Pleistocene. This may be linked to major cultural and technological novelties that had happened by the end of the Middle Pleistocene (e.g., expansion of the Middle Stone Age (MSA) in Africa and Mousterian in Europe). The combined study of endocranial and exocranial anatomy offers opportunities to further understand human evolution and the implication for the phylogeny of our genus. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Promise of Neurotechnology in Clinical Translational Science.

PubMed

White, Susan W; Richey, John A; Gracanin, Denis; Bell, Martha Ann; LaConte, Stephen; Coffman, Marika; Trubanova, Andrea; Kim, Inyoung

2015-09-01

Neurotechnology is broadly defined as a set of devices used to understand neural processes and applications that can potentially facilitate the brain's ability to repair itself. In the past decade, an increasingly explicit understanding of basic biological mechanisms of brain-related illnesses has produced applications that allow a direct yet noninvasive method to index and manipulate the functioning of the human nervous system. Clinical scientists are poised to apply this technology to assess, treat, and better understand complex socioemotional processes that underlie many forms of psychopathology. In this review, we describe the potential benefits and hurdles, both technical and methodological, of neurotechnology in the context of clinical dysfunction. We also offer a framework for developing and evaluating neurotechnologies that is intended to expedite progress at the nexus of clinical science and neural interface designs by providing a comprehensive vocabulary to describe the necessary features of neurotechnology in the clinic.

Quantitative and Qualitative Analysis of Transient Fetal Compartments during Prenatal Human Brain Development

PubMed Central

Vasung, Lana; Lepage, Claude; Radoš, Milan; Pletikos, Mihovil; Goldman, Jennifer S.; Richiardi, Jonas; Raguž, Marina; Fischi-Gómez, Elda; Karama, Sherif; Huppi, Petra S.; Evans, Alan C.; Kostovic, Ivica

2016-01-01

The cerebral wall of the human fetal brain is composed of transient cellular compartments, which show characteristic spatiotemporal relationships with intensity of major neurogenic events (cell proliferation, migration, axonal growth, dendritic differentiation, synaptogenesis, cell death, and myelination). The aim of the present study was to obtain new quantitative data describing volume, surface area, and thickness of transient compartments in the human fetal cerebrum. Forty-four postmortem fetal brains aged 13–40 postconceptional weeks (PCW) were included in this study. High-resolution T1 weighted MR images were acquired on 19 fetal brain hemispheres. MR images were processed using in-house software (MNI-ACE toolbox). Delineation of fetal compartments was performed semi-automatically by co-registration of MRI with histological sections of the same brains, or with the age-matched brains from Zagreb Neuroembryological Collection. Growth trajectories of transient fetal compartments were reconstructed. The composition of telencephalic wall was quantitatively assessed. Between 13 and 25 PCW, when the intensity of neuronal proliferation decreases drastically, the relative volume of proliferative (ventricular and subventricular) compartments showed pronounced decline. In contrast, synapse- and extracellular matrix-rich subplate compartment continued to grow during the first two trimesters, occupying up to 45% of telencephalon and reaching its maximum volume and thickness around 30 PCW. This developmental maximum coincides with a period of intensive growth of long cortico-cortical fibers, which enter and wait in subplate before approaching the cortical plate. Although we did not find significant age related changes in mean thickness of the cortical plate, the volume, gyrification index, and surface area of the cortical plate continued to exponentially grow during the last phases of prenatal development. This cortical expansion coincides developmentally with the transformation of embryonic cortical columns, dendritic differentiation, and ingrowth of axons. These results provide a quantitative description of transient human fetal brain compartments observable with MRI. Moreover, they will improve understanding of structural-functional relationships during brain development, will enable correlation between in vitro/in vivo imaging and fine structural histological studies, and will serve as a reference for study of perinatal brain injuries. PMID:26941612

Human FGF1 promoter is active in ependymal cells and dopaminergic neurons in the brains of F1B-GFP transgenic mice.

PubMed

Chen, Mei-Shu; Lin, Hua-Kuo; Chiu, Hsun; Lee, Don-Ching; Chung, Yu-Fen; Chiu, Ing-Ming

2015-03-01

FGF1 is involved in multiple biological functions and exhibits the importance in neuroprotective effects. Our previous studies indicated that, in human brain and retina, the FGF1B promoter controlled the expression of FGF1. However, the exact function and regulation of FGF1 in brain is still unclear. Here, we generated F1B-GFP transgenic mice that expressed the GFP reporter gene under the control of human FGF1B promoter (-540 to +31). Using the fresh brain sections of F1B-GFP transgenic mice, we found that the F1B-GFP cells expressed strong fluorescent signals in the ventricular system throughout the brain. The results of immunohistochemistry further showed that two distinct populations of F1B-GFP(+) cells existed in the brains of F1B-GFP transgenic mice. We demonstrated that one population of F1B-GFP(+) cells was ependymal cells, which distributed along the entire ventricles, and the second population of F1B-GFP(+) cells was neuronal cells that projected their long processes into multiple directions in specific areas of the brain. The double labeling of F1B-GFP(+) cells and tyrosine hydroxylase indicated that a subpopulation of F1B-GFP(+) -neuronal cells was dopaminergic neurons. Importantly, these F1B-GFP(+) /TH(+) cells were distributed in the main dopaminergic neuronal groups including hypothalamus, ventral tegmental area, and raphe nuclei. These results suggested that human FGF1B promoter was active in ependymal cells, neurons, and a portion of dopaminergic neurons. Thus, the F1B-GFP transgenic mice provide an animal model not only for studying FGF1 gene expression in vivo but also for understanding the role of FGF1 contribution in neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. © 2014 The Authors Developmental Neurobiology Published by Wiley Periodicals, Inc.

Brain aromatase: roles in reproduction and neuroprotection.

PubMed

Roselli, Charles F

2007-01-01

It is well established that aromatization constitutes an essential part of testosterone's signaling pathway in brain and that estrogen metabolites, often together with testosterone, organize and activate masculine neural circuits. This paper summarizes the current understanding regarding the distribution, regulation and function of brain aromatase in mammals. Data from our laboratory are presented that highlight the important function of aromatase in the regulation of androgen feedback sensitivity in non-human primates and the possible role that aromatase plays in determining the brain structure and sexual partner preferences of rams. In addition, new data is presented indicating that the capacity for aromatization in cortical astrocytes is associated with cell survival and may be important for neuroprotection. It is anticipated that a better appreciation of the physiological and pathophysiological functions of aromatase will lead to important clinical insights.

Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer's disease.

PubMed

Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J

2009-01-01

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy and environmental nuclear contamination as well as for Earth-orbit and space missions. Analyses of transcriptome profiles of mouse brain tissue after whole-body irradiation showed that low-dose exposures (10 cGy) induced genes not affected by high-dose radiation (2 Gy) and that low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues and pathways that were specific for brain tissue. Low-dose genes clustered into a saturated network (P < 10(-53)) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose irradiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down-regulated in normal human aging and Alzheimer's disease.

Being fat and smart: A comparative analysis of the fat-brain trade-off in mammals.

PubMed

Heldstab, Sandra A; van Schaik, Carel P; Isler, Karin

2016-11-01

Humans stand out among non-aquatic mammals by having both an extremely large brain and a relatively large amount of body fat. To understand the evolution of this human peculiarity we report a phylogenetic comparative study of 120 mammalian species, including 30 primates, using seasonal variation in adult body mass as a proxy of the tendency to store fat. Species that rely on storing fat to survive lean periods are expected to be less active because of higher costs of locomotion and have increased predation risk due to reduced agility. Because a fat-storage strategy reduces the net cognitive benefit of a large brain without reducing its cost, such species should be less likely to evolve a larger brain than non-fat-storing species. We therefore predict that the two strategies to buffer food shortages (storing body fat and cognitive flexibility) are compensatory, and therefore predict negative co-evolution between relative brain size and seasonal variation in body mass. This trade-off is expected to be stronger in predominantly arboreal species than in more terrestrial ones, as the cost of transporting additional adipose depots is higher for climbing than for horizontal locomotion. We did, indeed, find a significant negative correlation between brain size and coefficient of variation (CV) in body mass in both sexes for the subsample of arboreal species, both in all mammals and within primates. In predominantly terrestrial species, in contrast, this correlation was not significant. We therefore suggest that the adoption of habitually terrestrial locomotor habits, accompanied by a reduced reliance on climbing, has allowed for a primate of our body size the unique human combination of unusually large brains and unusually large adipose depots. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuroscience and morality.

PubMed

Allison, T

2001-10-01

Humans are social animals who use specialized brain mechanisms to assess the actions of others. This system for social cognition can be studied by imaging techniques, and its damage can lead to inappropriate social and moral behavior. Neuroscience can thus enrich our understanding of behaviors traditionally thought to be outside the province of science.

Brain Matters: Practicing Religion, Forming the Faithful

ERIC Educational Resources Information Center

Hogue, David A.

2012-01-01

Religious practices have long drawn on the social sciences to broaden our understanding of how human beings develop, learn, relate, and are formed. While the religion and science conversations have not always been friendly, a growing number of theologians and scientists are engaged in promising dialogues where the interests of both parties…

Neurodevelopment and Thyroid Hormone Synthesis Inhibition in the Rat: Quantitative Understanding Within the Adverse Outcome Pathway Framework

EPA Science Inventory

Adequate levels of thyroid hormones (TH) are needed for proper brain development, deficiencies may lead to adverse neurological outcomes in humans and animal models. Environmental chemicals have been linked to TH disruption, yet the relationship between developmental exposures an...

Principles of Learning, Implications for Teaching: A Cognitive Neuroscience Perspective

ERIC Educational Resources Information Center

Goswami, Usha

2008-01-01

Cognitive neuroscience aims to improve our understanding of aspects of human learning and performance by combining data acquired with the new brain imaging technologies with data acquired in cognitive psychology paradigms. Both neuroscience and psychology use the philosophical assumptions underpinning the natural sciences, namely the scientific…

New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections

USDA-ARS?s Scientific Manuscript database

Toxoplasma gondii, the most common parasitic infection of the human brain and eye, persists across lifetimes, can progressively damage sight, and is currently incurable. New, curative medicines are needed urgently. Herein, we developed novel models to facilitate drug development: EGS strain T. gondi...

Neuroscience, Education and Mental Health

ERIC Educational Resources Information Center

Arboccó de los Heros, Manuel

2016-01-01

The following article presents a series of investigations, reflections, and quotes about neuroscience, education, and psychology. Each area is specialized in some matters but at some point they share territory and mutually benefit one another, and help us to increasingly understand the complex world of learning, the brain, and human behavior. We…

Modeling Spatial and Temporal Aspects of Visual Backward Masking

ERIC Educational Resources Information Center

Hermens, Frouke; Luksys, Gediminas; Gerstner, Wulfram; Herzog, Michael H.; Ernst, Udo

2008-01-01

Visual backward masking is a versatile tool for understanding principles and limitations of visual information processing in the human brain. However, the mechanisms underlying masking are still poorly understood. In the current contribution, the authors show that a structurally simple mathematical model can explain many spatial and temporal…

Ozone-induced changes in oxidative stress parameters in brains of adult, middle-age, and senescent Brown Norway rats

EPA Science Inventory

Understanding life-stage susceptibility is a critical part of community based human health risk assessment following chemical exposure. Recently there is growing concern over a common air pollutant, ozone (03), and adverse health effects including dysfunction of the pulmonary, ca...

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

Serotonergic Psychedelics Temporarily Modify Information Transfer in Humans

PubMed Central

Alonso, Joan Francesc; Romero, Sergio; Mañanas, Miquel Àngel

2015-01-01

Background: Psychedelics induce intense modifications in the sensorium, the sense of “self,” and the experience of reality. Despite advances in our understanding of the molecular and cellular level mechanisms of these drugs, knowledge of their actions on global brain dynamics is still incomplete. Recent imaging studies have found changes in functional coupling between frontal and parietal brain structures, suggesting a modification in information flow between brain regions during acute effects. Methods: Here we assessed the psychedelic-induced changes in directionality of information flow during the acute effects of a psychedelic in humans. We measured modifications in connectivity of brain oscillations using transfer entropy, a nonlinear measure of directed functional connectivity based on information theory. Ten healthy male volunteers with prior experience with psychedelics participated in 2 experimental sessions. They received a placebo or a dose of ayahuasca, a psychedelic preparation containing the serotonergic 5-HT2A agonist N,N-dimethyltryptamine. Results: The analysis showed significant changes in the coupling of brain oscillations between anterior and posterior recording sites. Transfer entropy analysis showed that frontal sources decreased their influence over central, parietal, and occipital sites. Conversely, sources in posterior locations increased their influence over signals measured at anterior locations. Exploratory correlations found that anterior-to-posterior transfer entropy decreases were correlated with the intensity of subjective effects, while the imbalance between anterior-to-posterior and posterior-to-anterior transfer entropy correlated with the degree of incapacitation experienced. Conclusions: These results suggest that psychedelics induce a temporary disruption of neural hierarchies by reducing top-down control and increasing bottom-up information transfer in the human brain. PMID:25820842

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.

Decoding the neural signatures of emotions expressed through sound.

PubMed

Sachs, Matthew E; Habibi, Assal; Damasio, Antonio; Kaplan, Jonas T

2018-07-01

Effective social functioning relies in part on the ability to identify emotions from auditory stimuli and respond appropriately. Previous studies have uncovered brain regions engaged by the affective information conveyed by sound. But some of the acoustical properties of sounds that express certain emotions vary remarkably with the instrument used to produce them, for example the human voice or a violin. Do these brain regions respond in the same way to different emotions regardless of the sound source? To address this question, we had participants (N = 38, 20 females) listen to brief audio excerpts produced by the violin, clarinet, and human voice, each conveying one of three target emotions-happiness, sadness, and fear-while brain activity was measured with fMRI. We used multivoxel pattern analysis to test whether emotion-specific neural responses to the voice could predict emotion-specific neural responses to musical instruments and vice-versa. A whole-brain searchlight analysis revealed that patterns of activity within the primary and secondary auditory cortex, posterior insula, and parietal operculum were predictive of the affective content of sound both within and across instruments. Furthermore, classification accuracy within the anterior insula was correlated with behavioral measures of empathy. The findings suggest that these brain regions carry emotion-specific patterns that generalize across sounds with different acoustical properties. Also, individuals with greater empathic ability have more distinct neural patterns related to perceiving emotions. These results extend previous knowledge regarding how the human brain extracts emotional meaning from auditory stimuli and enables us to understand and connect with others effectively. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Disaster-Proofing Senior Leadership: Preventing Technological Failure in Future Nano-War

DTIC Science & Technology

2009-02-01

phenomenon beyond Globalization 3.0, where the empowered individual becomes the empowered machine-enhanced human or cyborg in 50 to 100 years. This merging...gain control of their bodies, could turn into superhuman cyborg - like upgrades. Further, the ability to understand and replicate brain functions in...The implications of nano-enhanced humans and cyborgs on the battlefield are legion. With ubiquitous sensing via the quantum dot-sized sensor nets

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

PubMed Central

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

2017-01-01

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

Evolving knowledge of sex differences in brain structure, function, and chemistry.

PubMed

Cosgrove, Kelly P; Mazure, Carolyn M; Staley, Julie K

2007-10-15

Clinical and epidemiologic evidence demonstrates sex differences in the prevalence and course of various psychiatric disorders. Understanding sex-specific brain differences in healthy individuals is a critical first step toward understanding sex-specific expression of psychiatric disorders. Here, we evaluate evidence on sex differences in brain structure, chemistry, and function using imaging methodologies, including functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), and structural magnetic resonance imaging (MRI) in mentally healthy individuals. MEDLINE searches of English-language literature (1980-November 2006) using the terms sex, gender, PET, SPECT, MRI, fMRI, morphometry, neurochemistry, and neurotransmission were performed to extract relevant sources. The literature suggests that while there are many similarities in brain structure, function, and neurotransmission in healthy men and women, there are important differences that distinguish the male from the female brain. Overall, brain volume is greater in men than women; yet, when controlling for total volume, women have a higher percentage of gray matter and men a higher percentage of white matter. Regional volume differences are less consistent. Global cerebral blood flow is higher in women than in men. Sex-specific differences in dopaminergic, serotonergic, and gamma-aminobutyric acid (GABA)ergic markers indicate that male and female brains are neurochemically distinct. Insight into the etiology of sex differences in the normal living human brain provides an important foundation to delineate the pathophysiological mechanisms underlying sex differences in neuropsychiatric disorders and to guide the development of sex-specific treatments for these devastating brain disorders.

Graph theoretical modeling of baby brain networks.

PubMed

Zhao, Tengda; Xu, Yuehua; He, Yong

2018-06-12

The human brain undergoes explosive growth during the prenatal period and the first few postnatal years, establishing an early infrastructure for the later development of behaviors and cognitions. Revealing the developmental rules during the early phrase is essential in understanding the emergence of brain function and the origin of developmental disorders. The graph-theoretical network modeling in combination with multiple neuroimaging probes provides an important research framework to explore early development of the topological wiring and organizational paradigms of the brain. Here, we reviewed studies which employed neuroimaging and graph-theoretical modeling to investigate brain network development from approximately 20 gestational weeks to 2 years of age. Specifically, the structural and functional brain networks have evolved to highly efficient topological architectures in the early stage; where the structural network remains ahead and paves the way for the development of functional network. The brain network develops in a heterogeneous order, from primary to higher-order systems and from a tendency of network segregation to network integration in the prenatal and postnatal periods. The early brain network topologies show abilities in predicting certain cognitive and behavior performance in later life, and their impairments are likely to continue into childhood and even adulthood. These macroscopic topological changes are found to be associated with possible microstructural maturations, such as axonal growth and myelinations. Collectively, this review provides a detailed delineation of the early changes of the baby brains in the graph-theoretical modeling framework, which opens up a new avenue to understand the developmental principles of the connectome. Copyright © 2018. Published by Elsevier Inc.

Blood-brain barrier-on-a-chip: Microphysiological systems that capture the complexity of the blood-central nervous system interface.

PubMed

Phan, Duc Tt; Bender, R Hugh F; Andrejecsk, Jillian W; Sobrino, Agua; Hachey, Stephanie J; George, Steven C; Hughes, Christopher Cw

2017-11-01

The blood-brain barrier is a dynamic and highly organized structure that strictly regulates the molecules allowed to cross the brain vasculature into the central nervous system. The blood-brain barrier pathology has been associated with a number of central nervous system diseases, including vascular malformations, stroke/vascular dementia, Alzheimer's disease, multiple sclerosis, and various neurological tumors including glioblastoma multiforme. There is a compelling need for representative models of this critical interface. Current research relies heavily on animal models (mostly mice) or on two-dimensional (2D) in vitro models, neither of which fully capture the complexities of the human blood-brain barrier. Physiological differences between humans and mice make translation to the clinic problematic, while monolayer cultures cannot capture the inherently three-dimensional (3D) nature of the blood-brain barrier, which includes close association of the abluminal side of the endothelium with astrocyte foot-processes and pericytes. Here we discuss the central nervous system diseases associated with blood-brain barrier pathology, recent advances in the development of novel 3D blood-brain barrier -on-a-chip systems that better mimic the physiological complexity and structure of human blood-brain barrier, and provide an outlook on how these blood-brain barrier-on-a-chip systems can be used for central nervous system disease modeling. Impact statement The field of microphysiological systems is rapidly evolving as new technologies are introduced and our understanding of organ physiology develops. In this review, we focus on Blood-Brain Barrier (BBB) models, with a particular emphasis on how they relate to neurological disorders such as Alzheimer's disease, multiple sclerosis, stroke, cancer, and vascular malformations. We emphasize the importance of capturing the three-dimensional nature of the brain and the unique architecture of the BBB - something that until recently had not been well modeled by in vitro systems. Our hope is that this review will provide a launch pad for new ideas and methodologies that can provide us with truly physiological BBB models capable of yielding new insights into the function of this critical interface.

Neuromagnetic brain activity associated with anticipatory postural adjustments for bimanual load lifting.

PubMed

Ng, Tommy H B; Sowman, Paul F; Brock, Jon; Johnson, Blake W

2013-02-01

During bimanual load lifting, the brain must anticipate the effects of unloading upon the load-bearing arm. Little is currently known about the neural networks that coordinate these anticipatory postural adjustments. We measured neuromagnetic brain activity with whole-head magnetoencephalography while participants performed a bimanual load-lifting task. Anticipatory adjustments were associated with reduction in biceps brachii muscle activity of the load-bearing arm and pre-movement desynchronization of the cortical beta rhythm. Beamforming analyses localized anticipatory brain activity to the precentral gyrus, basal ganglia, supplementary motor area, and thalamus, contralateral to the load-bearing arm. To our knowledge this is the first human neuroimaging study to directly investigate anticipatory postural adjustments and to explicitly partition the anticipatory and volitional aspects of brain activity in bimanual load lifting. These data contribute to our understanding of the neural systems supporting anticipatory postural adjustments in healthy adults. Copyright © 2012 Elsevier Inc. All rights reserved.

Quantitative analysis of nanoparticle transport through in vitro blood-brain barrier models

PubMed Central

Åberg, Christoffer

2016-01-01

ABSTRACT Nanoparticle transport through the blood-brain barrier has received much attention of late, both from the point of view of nano-enabled drug delivery, as well as due to concerns about unintended exposure of nanomaterials to humans and other organisms. In vitro models play a lead role in efforts to understand the extent of transport through the blood-brain barrier, but unique features of the nanoscale challenge their direct adaptation. Here we highlight some of the differences compared to molecular species when utilizing in vitro blood-brain barrier models for nanoparticle studies. Issues that may arise with transwell systems are discussed, together with some potential alternative methodologies. We also briefly review the biomolecular corona concept and its importance for how nanoparticles interact with the blood-brain barrier. We end with considering future directions, including indirect effects and application of shear and fluidics-technologies. PMID:27141425