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.

Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation

PubMed Central

Paulk, Angelique C.; Zhou, Yanqiong; Stratton, Peter; Liu, Li

2013-01-01

Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel “whole brain” readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior. PMID:23864378

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-11-11

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

Brain vascular heterogeneity: implications for disease pathogenesis and design of in vitro blood-brain barrier models.

PubMed

Noumbissi, Midrelle E; Galasso, Bianca; Stins, Monique F

2018-04-23

The vertebrate blood-brain barrier (BBB) is composed of cerebral microvascular endothelial cells (CEC). The BBB acts as a semi-permeable cellular interface that tightly regulates bidirectional molecular transport between blood and the brain parenchyma in order to maintain cerebral homeostasis. The CEC phenotype is regulated by a variety of factors, including cells in its immediate environment and within functional neurovascular units. The cellular composition of the brain parenchyma surrounding the CEC varies between different brain regions; this difference is clearly visible in grey versus white matter. In this review, we discuss evidence for the existence of brain vascular heterogeneity, focusing on differences between the vessels of the grey and white matter. The region-specific differences in the vasculature of the brain are reflective of specific functions of those particular brain areas. This BBB-endothelial heterogeneity may have implications for the course of pathogenesis of cerebrovascular diseases and neurological disorders involving vascular activation and dysfunction. This heterogeneity should be taken into account when developing BBB-neuro-disease models representative of specific brain areas.

Intelligence is associated with the modular structure of intrinsic brain networks.

PubMed

Hilger, Kirsten; Ekman, Matthias; Fiebach, Christian J; Basten, Ulrike

2017-11-22

General intelligence is a psychological construct that captures in a single metric the overall level of behavioural and cognitive performance in an individual. While previous research has attempted to localise intelligence in circumscribed brain regions, more recent work focuses on functional interactions between regions. However, even though brain networks are characterised by substantial modularity, it is unclear whether and how the brain's modular organisation is associated with general intelligence. Modelling subject-specific brain network graphs from functional MRI resting-state data (N = 309), we found that intelligence was not associated with global modularity features (e.g., number or size of modules) or the whole-brain proportions of different node types (e.g., connector hubs or provincial hubs). In contrast, we observed characteristic associations between intelligence and node-specific measures of within- and between-module connectivity, particularly in frontal and parietal brain regions that have previously been linked to intelligence. We propose that the connectivity profile of these regions may shape intelligence-relevant aspects of information processing. Our data demonstrate that not only region-specific differences in brain structure and function, but also the network-topological embedding of fronto-parietal as well as other cortical and subcortical brain regions is related to individual differences in higher cognitive abilities, i.e., intelligence.

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

PubMed Central

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

2011-01-01

Functional neuroimaging methods hold promise for the identification of cognitive function and communication capacity in some severely brain-injured patients who may not retain sufficient motor function to demonstrate their abilities. We studied seven severely brain-injured patients and a control group of 14 subjects using a novel hierarchical functional magnetic resonance imaging assessment utilizing mental imagery responses. Whereas the control group showed consistent and accurate (for communication) blood-oxygen-level-dependent responses without exception, the brain-injured subjects showed a wide variation in the correlation of blood-oxygen-level-dependent responses and overt behavioural responses. Specifically, the brain-injured subjects dissociated bedside and functional magnetic resonance imaging-based command following and communication capabilities. These observations reveal significant challenges in developing validated functional magnetic resonance imaging-based methods for clinical use and raise interesting questions about underlying brain function assayed using these methods in brain-injured subjects. PMID:21354974

Brain Structure-function Couplings (FY11)

DTIC Science & Technology

2012-01-01

influence time-evolving models of global brain function and dynamic changes in cognitive performance. Both structural and functional connections change on...Artifact Resistant Measure to Detect Cognitive EEG Activity During Locomotion. Journal of NeuroEngineering and Rehabilitation, submitted. 10...Specifically, identifying the communication between brain regions that occurs during tasks may provide information regarding the cognitive processes involved in

The Effects of Spaceflight on Neurocognitive Performance: Extent, Longevity, and Neural Bases

NASA Technical Reports Server (NTRS)

Seidler, Rachael D.; Bloomberg, Jacob; Wood, Scott; Mason, Sara; Mulavara, Ajit; Kofman, Igor; De Dios, Yiri; Gadd, Nicole; Stepanyan, Vahagn; Szecsy, Darcy

2017-01-01

Spaceflight effects on gait, balance, & manual motor control have been well studied; some evidence for cognitive deficits. Rodent cortical motor & sensory systems show neural structural alterations with spaceflight. We found extensive changes in behavior, brain structure & brain function following 70 days of HDBR. Specific Aim: Aim 1-Identify changes in brain structure, function, and network integrity as a function of spaceflight and characterize their time course. Aim 2-Specify relationships between structural and functional brain changes and performance and characterize their time course.

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

ERIC Educational Resources Information Center

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

2012-01-01

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

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

NASA Astrophysics Data System (ADS)

Bressler, Steven L.

2014-09-01

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

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

ERIC Educational Resources Information Center

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

2008-01-01

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

Build-a-Brain Project: Students Design and Model the Brain of an Imaginary Animal

ERIC Educational Resources Information Center

Demetrikopoulos, Melissa K.; Pecore, John; Rose, Jordan D.; Fobbs, Archibald J., Jr.; Johnson, John I.; Carruth, Laura L.

2006-01-01

The brain is a truly fascinating structure! It controls the body and allows everyone to think, learn, speak, move, feel, remember, and experience emotions. Although the brain is a single organ, it is very complex and has several regions, each having a specific function. These functionally diverse regions work together to allow for coordination of…

A Window into the Brain: Advances in Psychiatric fMRI

PubMed Central

Zhan, Xiaoyan

2015-01-01

Functional magnetic resonance imaging (fMRI) plays a key role in modern psychiatric research. It provides a means to assay differences in brain systems that underlie psychiatric illness, treatment response, and properties of brain structure and function that convey risk factor for mental diseases. Here we review recent advances in fMRI methods in general use and progress made in understanding the neural basis of mental illness. Drawing on concepts and findings from psychiatric fMRI, we propose that mental illness may not be associated with abnormalities in specific local regions but rather corresponds to variation in the overall organization of functional communication throughout the brain network. Future research may need to integrate neuroimaging information drawn from different analysis methods and delineate spatial and temporal patterns of brain responses that are specific to certain types of psychiatric disorders. PMID:26413531

Generality and specificity in cognitive aging: a volumetric brain analysis.

PubMed

Staff, Roger T; Murray, Alison D; Deary, Ian J; Whalley, Lawrence J

2006-05-01

To investigate whether, in old age, brain volume differences are associated with age-related change in general mental ability and/or specific cognitive abilities. The authors investigate the association between brain volumes and current cognitive function in a well-characterized sample of healthy old people (aged 79-80) whose intelligence was recorded at age 11. This allowed estimation of intellectual change over the life span. After accounting for childhood intelligence, associations were found between specific cognitive measures and brain volumes. An association was also found between volumes and the general intelligence factor g. After removing the influence of g from each of the specific cognitive measures, no remaining significant associations were found between brain volumes and the specific part of each test. Generalized cognitive aging is associated with brain volume differences, but there is no evidence in this sample that specific components of cognitive aging are associated with differences in brain volume.

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

PubMed

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

2011-10-01

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

Functional neuroimaging insights into the physiology of human sleep.

PubMed

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

2010-12-01

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

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

NASA Astrophysics Data System (ADS)

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

1999-05-01

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

Connectivity-based neurofeedback: Dynamic causal modeling for real-time fMRI☆

PubMed Central

Koush, Yury; Rosa, Maria Joao; Robineau, Fabien; Heinen, Klaartje; W. Rieger, Sebastian; Weiskopf, Nikolaus; Vuilleumier, Patrik; Van De Ville, Dimitri; Scharnowski, Frank

2013-01-01

Neurofeedback based on real-time fMRI is an emerging technique that can be used to train voluntary control of brain activity. Such brain training has been shown to lead to behavioral effects that are specific to the functional role of the targeted brain area. However, real-time fMRI-based neurofeedback so far was limited to mainly training localized brain activity within a region of interest. Here, we overcome this limitation by presenting near real-time dynamic causal modeling in order to provide feedback information based on connectivity between brain areas rather than activity within a single brain area. Using a visual–spatial attention paradigm, we show that participants can voluntarily control a feedback signal that is based on the Bayesian model comparison between two predefined model alternatives, i.e. the connectivity between left visual cortex and left parietal cortex vs. the connectivity between right visual cortex and right parietal cortex. Our new approach thus allows for training voluntary control over specific functional brain networks. Because most mental functions and most neurological disorders are associated with network activity rather than with activity in a single brain region, this novel approach is an important methodological innovation in order to more directly target functionally relevant brain networks. PMID:23668967

Involvement of specific macrophage-lineage cells surrounding arterioles in barrier and scavenger function in brain cortex.

PubMed Central

Mato, M; Ookawara, S; Sakamoto, A; Aikawa, E; Ogawa, T; Mitsuhashi, U; Masuzawa, T; Suzuki, H; Honda, M; Yazaki, Y; Watanabe, E; Luoma, J; Yla-Herttuala, S; Fraser, I; Gordon, S; Kodama, T

1996-01-01

The transport of solutes between blood and brain is regulated by a specific barrier. Capillary endothelial cells of brain are known to mediate barrier function and facilitate transport. Here we report that specific cells surrounding arterioles, known as Mato's fluorescent granular perithelial (FGP) cells or perivascular microglial cells, contribute to the barrier function. Immunohistochemical and in situ hybridization studies indicate that, in normal brain cortex, type I and type II macrophage scavenger receptors are expressed only in FGP/perivascular microglial cells, and surface markers of macrophage lineage are also detected on them. These cells mediate the uptake of macromolecules, including modified low density lipoprotein, horseradish peroxidase, and ferritin injected either into the blood or into the cerebral ventricles. Accumulation of scavenged materials with aging or after the administration of a high-fat diet results in the formation of honeycomb-like foam cells and the narrowing of the lumen of arterioles in the brain cortex. These results indicate involvement of FGP/perivascular microglial cells in the barrier and scavenger functions in the central nervous system. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:8622926

The "silent" imprint of musical training.

PubMed

Klein, Carina; Liem, Franziskus; Hänggi, Jürgen; Elmer, Stefan; Jäncke, Lutz

2016-02-01

Playing a musical instrument at a professional level is a complex multimodal task requiring information integration between different brain regions supporting auditory, somatosensory, motor, and cognitive functions. These kinds of task-specific activations are known to have a profound influence on both the functional and structural architecture of the human brain. However, until now, it is widely unknown whether this specific imprint of musical practice can still be detected during rest when no musical instrument is used. Therefore, we applied high-density electroencephalography and evaluated whole-brain functional connectivity as well as small-world topologies (i.e., node degree) during resting state in a sample of 15 professional musicians and 15 nonmusicians. As expected, musicians demonstrate increased intra- and interhemispheric functional connectivity between those brain regions that are typically involved in music perception and production, such as the auditory, the sensorimotor, and prefrontal cortex as well as Broca's area. In addition, mean connectivity within this specific network was positively related to musical skill and the total number of training hours. Thus, we conclude that musical training distinctively shapes intrinsic functional network characteristics in such a manner that its signature can still be detected during a task-free condition. Hum Brain Mapp 37:536-546, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Selective impairment of hippocampus and posterior hub areas in Alzheimer's disease: an MEG-based multiplex network study.

PubMed

Yu, Meichen; Engels, Marjolein M A; Hillebrand, Arjan; van Straaten, Elisabeth C W; Gouw, Alida A; Teunissen, Charlotte; van der Flier, Wiesje M; Scheltens, Philip; Stam, Cornelis J

2017-05-01

Although frequency-specific network analyses have shown that functional brain networks are altered in patients with Alzheimer's disease, the relationships between these frequency-specific network alterations remain largely unknown. Multiplex network analysis is a novel network approach to study complex systems consisting of subsystems with different types of connectivity patterns. In this study, we used magnetoencephalography to integrate five frequency-band specific brain networks in a multiplex framework. Previous structural and functional brain network studies have consistently shown that hub brain areas are selectively disrupted in Alzheimer's disease. Accordingly, we hypothesized that hub regions in the multiplex brain networks are selectively targeted in patients with Alzheimer's disease in comparison to healthy control subjects. Eyes-closed resting-state magnetoencephalography recordings from 27 patients with Alzheimer's disease (60.6 ± 5.4 years, 12 females) and 26 controls (61.8 ± 5.5 years, 14 females) were projected onto atlas-based regions of interest using beamforming. Subsequently, source-space time series for both 78 cortical and 12 subcortical regions were reconstructed in five frequency bands (delta, theta, alpha 1, alpha 2 and beta band). Multiplex brain networks were constructed by integrating frequency-specific magnetoencephalography networks. Functional connections between all pairs of regions of interests were quantified using a phase-based coupling metric, the phase lag index. Several multiplex hub and heterogeneity metrics were computed to capture both overall importance of each brain area and heterogeneity of the connectivity patterns across frequency-specific layers. Different nodal centrality metrics showed consistently that several hub regions, particularly left hippocampus, posterior parts of the default mode network and occipital regions, were vulnerable in patients with Alzheimer's disease compared to control subjects. Of note, these detected vulnerable hubs in Alzheimer's disease were absent in each individual frequency-specific network, thus showing the value of integrating the networks. The connectivity patterns of these vulnerable hub regions in the patients were heterogeneously distributed across layers. Perturbed cognitive function and abnormal cerebrospinal fluid amyloid-β42 levels correlated positively with the vulnerability of the hub regions in patients with Alzheimer's disease. Our analysis therefore demonstrates that the magnetoencephalography-based multiplex brain networks contain important information that cannot be revealed by frequency-specific brain networks. Furthermore, this indicates that functional networks obtained in different frequency bands do not act as independent entities. Overall, our multiplex network study provides an effective framework to integrate the frequency-specific networks with different frequency patterns and reveal neuropathological mechanism of hub disruption in Alzheimer's disease. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Functional Neuroimaging Insights into the Physiology of Human Sleep

PubMed Central

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

2010-01-01

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

Effects of resting state condition on reliability, trait specificity, and network connectivity of brain function measured with arterial spin labeled perfusion MRI.

PubMed

Li, Zhengjun; Vidorreta, Marta; Katchmar, Natalie; Alsop, David C; Wolf, Daniel H; Detre, John A

2018-06-01

Resting state fMRI (rs-fMRI) provides imaging biomarkers of task-independent brain function that can be associated with clinical variables or modulated by interventions such as behavioral training or pharmacological manipulations. These biomarkers include time-averaged regional brain function as manifested by regional cerebral blood flow (CBF) measured using arterial spin labeled (ASL) perfusion MRI and correlated temporal fluctuations of function across brain networks with either ASL or blood oxygenation level dependent (BOLD) fMRI. Resting-state studies are typically carried out using just one of several prescribed state conditions such as eyes closed (EC), eyes open (EO), or visual fixation on a cross-hair (FIX), which may affect the reliability and specificity of rs-fMRI. In this study, we collected test-retest ASL MRI data during 4 resting-state task conditions: EC, EO, FIX and PVT (low-frequency psychomotor vigilance task), and examined the effects of these task conditions on reliability and reproducibility as well as trait specificity of regional brain function. We also acquired resting-state BOLD fMRI under FIX and compared the network connectivity reliabilities between the four ASL conditions and the BOLD FIX condition. For resting-state ASL data, EC provided the highest CBF reliability, reproducibility, trait specificity, and network connectivity reliability, followed by EO, while FIX was lowest on all of these measures. PVT demonstrated lower CBF reliability, reproducibility and trait specificity than EO and EC. Overall network connectivity reliability was comparable between ASL and BOLD. Our findings confirm ASL CBF as a reliable, stable, and consistent measure of resting-state regional brain function and support the use of EC or EO over FIX and PVT as the resting-state condition. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Concerted and mosaic evolution of functional modules in songbird brains

PubMed Central

DeVoogd, Timothy J.

2017-01-01

Vertebrate brains differ in overall size, composition and functional capacities, but the evolutionary processes linking these traits are unclear. Two leading models offer opposing views: the concerted model ascribes major dimensions of covariation in brain structures to developmental events, whereas the mosaic model relates divergent structures to functional capabilities. The models are often cast as incompatible, but they must be unified to explain how adaptive changes in brain structure arise from pre-existing architectures and developmental mechanisms. Here we show that variation in the sizes of discrete neural systems in songbirds, a species-rich group exhibiting diverse behavioural and ecological specializations, supports major elements of both models. In accordance with the concerted model, most variation in nucleus volumes is shared across functional domains and allometry is related to developmental sequence. Per the mosaic model, residual variation in nucleus volumes is correlated within functional systems and predicts specific behavioural capabilities. These comparisons indicate that oscine brains evolved primarily as a coordinated whole but also experienced significant, independent modifications to dedicated systems from specific selection pressures. Finally, patterns of covariation between species and brain areas hint at underlying developmental mechanisms. PMID:28490627

The power of using functional fMRI on small rodents to study brain pharmacology and disease

PubMed Central

Jonckers, Elisabeth; Shah, Disha; Hamaide, Julie; Verhoye, Marleen; Van der Linden, Annemie

2015-01-01

Functional magnetic resonance imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD) fMRI techniques, including resting state (rsfMRI), stimulus-evoked (st-fMRI), and pharmacological MRI (phMRI). Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimulation and/or a pharmacological challenge. The first part of this review describes the physiological basis of BOLD fMRI and the hemodynamic response on which the MRI contrast is based. Specific emphasis goes to possible effects of anesthesia and the animal’s physiological conditions on neural activity and the hemodynamic response. The second part of this review describes applications of the aforementioned techniques in pharmacologically induced, as well as in traumatic and transgenic disease models and illustrates how multiple fMRI methods can be applied successfully to evaluate different aspects of a specific disorder. For example, fMRI techniques can be used to pinpoint the neural substrate of a disease beyond previously defined hypothesis-driven regions-of-interest. In addition, fMRI techniques allow one to dissect how specific modifications (e.g., treatment, lesion etc.) modulate the functioning of specific brain areas (st-fMRI, phMRI) and how functional connectivity (rsfMRI) between several brain regions is affected, both in acute and extended time frames. Furthermore, fMRI techniques can be used to assess/explore the efficacy of novel treatments in depth, both in fundamental research as well as in preclinical settings. In conclusion, by describing several exemplary studies, we aim to highlight the advantages of functional MRI in exploring the acute and long-term effects of pharmacological substances and/or pathology on brain functioning along with several methodological considerations. PMID:26539115

Electro-acupuncture at different acupoints modulating the relative specific brain functional network

NASA Astrophysics Data System (ADS)

Fang, Jiliang; Wang, Xiaoling; Wang, Yin; Liu, Hesheng; Hong, Yang; Liu, Jun; Zhou, Kehua; Wang, Lei; Xue, Chao; Song, Ming; Liu, Baoyan; Zhu, Bing

2010-11-01

Objective: The specific brain effects of acupoint are important scientific concern in acupuncture. However, previous acupuncture fMRI studies focused on acupoints in muscle layer on the limb. Therefore, researches on acupoints within connective tissue at trunk are warranted. Material and Methods: Brain effects of acupuncture on abdomen at acupoints Guanyuan (CV4) and Zhongwan (CV12) were tested using fMRI on 21 healthy volunteers. The data acquisition was performed at resting state, during needle retention, electroacupuncture (EA) and post-EA resting state. Needling sensations were rated after every electroacupuncture (EA) procedure. The needling sensations and the brain functional activity and connectivity were compared between CV4 and CV12 using SPSS, SPM2 and the local and remote connectivity maps. Results and conclusion: EA at CV4 and CV12 induced apparent deactivation effects in the limbic-paralimbic-neocortical network. The default mode of the brain was modified by needle retention and EA, respectively. The functional brain network was significantly changed post EA. However, the minor differences existed between these two acupoints. The results demonstrated similarity between functional brain network mode of acupuncture modulation and functional circuits of emotional and cognitive regulation. Acupuncture may produce analgesia, anti-anxiety and anti-depression via the limbic-paralimbic-neocortical network (LPNN).

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

PubMed

Shehzad, Zarrar; McCarthy, Gregory

2018-06-01

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

Is functional integration of resting state brain networks an unspecific biomarker for working memory performance?

PubMed

Alavash, Mohsen; Doebler, Philipp; Holling, Heinz; Thiel, Christiane M; Gießing, Carsten

2015-03-01

Is there one optimal topology of functional brain networks at rest from which our cognitive performance would profit? Previous studies suggest that functional integration of resting state brain networks is an important biomarker for cognitive performance. However, it is still unknown whether higher network integration is an unspecific predictor for good cognitive performance or, alternatively, whether specific network organization during rest predicts only specific cognitive abilities. Here, we investigated the relationship between network integration at rest and cognitive performance using two tasks that measured different aspects of working memory; one task assessed visual-spatial and the other numerical working memory. Network clustering, modularity and efficiency were computed to capture network integration on different levels of network organization, and to statistically compare their correlations with the performance in each working memory test. The results revealed that each working memory aspect profits from a different resting state topology, and the tests showed significantly different correlations with each of the measures of network integration. While higher global network integration and modularity predicted significantly better performance in visual-spatial working memory, both measures showed no significant correlation with numerical working memory performance. In contrast, numerical working memory was superior in subjects with highly clustered brain networks, predominantly in the intraparietal sulcus, a core brain region of the working memory network. Our findings suggest that a specific balance between local and global functional integration of resting state brain networks facilitates special aspects of cognitive performance. In the context of working memory, while visual-spatial performance is facilitated by globally integrated functional resting state brain networks, numerical working memory profits from increased capacities for local processing, especially in brain regions involved in working memory performance. Copyright © 2014 Elsevier Inc. All rights reserved.

Functional expression of SGLTs in rat brain.

PubMed

Yu, Amy S; Hirayama, Bruce A; Timbol, Gerald; Liu, Jie; Basarah, Ernest; Kepe, Vladimir; Satyamurthy, Nagichettiar; Huang, Sung-Cheng; Wright, Ernest M; Barrio, Jorge R

2010-12-01

This work provides evidence of previously unrecognized uptake of glucose via sodium-coupled glucose transporters (SGLTs) in specific regions of the brain. The current understanding of functional glucose utilization in brain is largely based on studies using positron emission tomography (PET) with the glucose tracer 2-deoxy-2-[F-18]fluoro-D-glucose (2-FDG). However, 2-FDG is only a good substrate for facilitated-glucose transporters (GLUTs), not for SGLTs. Thus, glucose accumulation measured by 2-FDG omits the role of SGLTs. We designed and synthesized two high-affinity tracers: one, α-methyl-4-[F-18]fluoro-4-deoxy-D-glucopyranoside (Me-4FDG), is a highly specific SGLT substrate and not transported by GLUTs; the other one, 4-[F-18]fluoro-4-deoxy-D-glucose (4-FDG), is transported by both SGLTs and GLUTs and will pass through the blood brain barrier (BBB). In vitro Me-4FDG autoradiography was used to map the distribution of uptake by functional SGLTs in brain slices with a comparable result from in vitro 4-FDG autoradiography. Immunohistochemical assays showed that uptake was consistent with the distribution of SGLT protein. Ex vivo 4-FDG autoradiography showed that SGLTs in these areas are functionally active in the normal in vivo brain. The results establish that SGLTs are a normal part of the physiology of specific areas of the brain, including hippocampus, amygdala, hypothalamus, and cerebral cortices. 4-FDG PET imaging also established that this BBB-permeable SGLT tracer now offers a functional imaging approach in humans to assess regulation of SGLT activity in health and disease.

Extraversion and neuroticism relate to topological properties of resting-state brain networks.

PubMed

Gao, Qing; Xu, Qiang; Duan, Xujun; Liao, Wei; Ding, Jurong; Zhang, Zhiqiang; Li, Yuan; Lu, Guangming; Chen, Huafu

2013-01-01

With the advent and development of modern neuroimaging techniques, there is an increasing interest in linking extraversion and neuroticism to anatomical and functional brain markers. Here, we aimed to test the theoretically derived biological personality model as proposed by Eysenck using graph theoretical analyses. Specifically, the association between the topological organization of whole-brain functional networks and extraversion/neuroticism was explored. To construct functional brain networks, functional connectivity among 90 brain regions was measured by temporal correlation using resting-state functional magnetic resonance imaging (fMRI) data of 71 healthy subjects. Graph theoretical analysis revealed a positive association of extraversion scores and normalized clustering coefficient values. These results suggested a more clustered configuration in brain networks of individuals high in extraversion, which could imply a higher arousal threshold and higher levels of arousal tolerance in the cortex of extraverts. On a local network level, we observed that a specific nodal measure, i.e., betweenness centrality (BC), was positively associated with neuroticism scores in the right precentral gyrus (PreCG), right caudate nucleus, right olfactory cortex, and bilateral amygdala. For individuals high in neuroticism, these results suggested a more frequent participation of these specific regions in information transition within the brain network and, in turn, may partly explain greater regional activation levels and lower arousal thresholds in these regions. In contrast, extraversion scores were positively correlated with BC in the right insula, while negatively correlated with BC in the bilateral middle temporal gyrus (MTG), indicating that the relationship between extraversion and regional arousal is not as simple as proposed by Eysenck.

Laminar fMRI and computational theories of brain function.

PubMed

Stephan, K E; Petzschner, F H; Kasper, L; Bayer, J; Wellstein, K V; Stefanics, G; Pruessmann, K P; Heinzle, J

2017-11-02

Recently developed methods for functional MRI at the resolution of cortical layers (laminar fMRI) offer a novel window into neurophysiological mechanisms of cortical activity. Beyond physiology, laminar fMRI also offers an unprecedented opportunity to test influential theories of brain function. Specifically, hierarchical Bayesian theories of brain function, such as predictive coding, assign specific computational roles to different cortical layers. Combined with computational models, laminar fMRI offers a unique opportunity to test these proposals noninvasively in humans. This review provides a brief overview of predictive coding and related hierarchical Bayesian theories, summarises their predictions with regard to layered cortical computations, examines how these predictions could be tested by laminar fMRI, and considers methodological challenges. We conclude by discussing the potential of laminar fMRI for clinically useful computational assays of layer-specific information processing. Copyright © 2017 Elsevier Inc. All rights reserved.

Genes that mediate breast cancer metastasis to the brain.

PubMed

Bos, Paula D; Zhang, Xiang H-F; Nadal, Cristina; Shu, Weiping; Gomis, Roger R; Nguyen, Don X; Minn, Andy J; van de Vijver, Marc J; Gerald, William L; Foekens, John A; Massagué, Joan

2009-06-18

The molecular basis for breast cancer metastasis to the brain is largely unknown. Brain relapse typically occurs years after the removal of a breast tumour, suggesting that disseminated cancer cells must acquire specialized functions to take over this organ. Here we show that breast cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of blood-brain barrier crossing and brain colonization. We isolated cells that preferentially infiltrate the brain from patients with advanced disease. Gene expression analysis of these cells and of clinical samples, coupled with functional analysis, identified the cyclooxygenase COX2 (also known as PTGS2), the epidermal growth factor receptor (EGFR) ligand HBEGF, and the alpha2,6-sialyltransferase ST6GALNAC5 as mediators of cancer cell passage through the blood-brain barrier. EGFR ligands and COX2 were previously linked to breast cancer infiltration of the lungs, but not the bones or liver, suggesting a sharing of these mediators in cerebral and pulmonary metastases. In contrast, ST6GALNAC5 specifically mediates brain metastasis. Normally restricted to the brain, the expression of ST6GALNAC5 in breast cancer cells enhances their adhesion to brain endothelial cells and their passage through the blood-brain barrier. This co-option of a brain sialyltransferase highlights the role of cell-surface glycosylation in organ-specific metastatic interactions.

Sleep loss and structural plasticity.

PubMed

Areal, Cassandra C; Warby, Simon C; Mongrain, Valérie

2017-06-01

Wakefulness and sleep are dynamic states during which brain functioning is modified and shaped. Sleep loss is detrimental to many brain functions and results in structural changes localized at synapses in the nervous system. In this review, we present and discuss some of the latest observations of structural changes following sleep loss in some vertebrates and insects. We also emphasize that these changes are region-specific and cell type-specific and that, most importantly, these structural modifications have functional roles in sleep regulation and brain functions. Selected mechanisms driving structural modifications occurring with sleep loss are also discussed. Overall, recent research highlights that extending wakefulness impacts synapse number and shape, which in turn regulate sleep need and sleep-dependent learning/memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

The DoD Civilian Equal Employment Opportunity (EEO) Program

DTIC Science & Technology

1987-05-21

as mental retardation, organic brain syndrome , emotional or mental illness, and specific learning disabilities. b. Major Life Activities. Functions...mental or psychological disorder, such as mental retardation, organic brain syndrome , emotional or mental illness, and specific learning disabilities

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

ERIC Educational Resources Information Center

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

2011-01-01

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

Rehabilitation of executive functioning in patients with frontal lobe brain damage with goal management training.

PubMed

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

2011-01-01

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

Transcripts with in silico predicted RNA structure are enriched everywhere in the mouse brain

PubMed Central

2012-01-01

Background Post-transcriptional control of gene expression is mostly conducted by specific elements in untranslated regions (UTRs) of mRNAs, in collaboration with specific binding proteins and RNAs. In several well characterized cases, these RNA elements are known to form stable secondary structures. RNA secondary structures also may have major functional implications for long noncoding RNAs (lncRNAs). Recent transcriptional data has indicated the importance of lncRNAs in brain development and function. However, no methodical efforts to investigate this have been undertaken. Here, we aim to systematically analyze the potential for RNA structure in brain-expressed transcripts. Results By comprehensive spatial expression analysis of the adult mouse in situ hybridization data of the Allen Mouse Brain Atlas, we show that transcripts (coding as well as non-coding) associated with in silico predicted structured probes are highly and significantly enriched in almost all analyzed brain regions. Functional implications of these RNA structures and their role in the brain are discussed in detail along with specific examples. We observe that mRNAs with a structure prediction in their UTRs are enriched for binding, transport and localization gene ontology categories. In addition, after manual examination we observe agreement between RNA binding protein interaction sites near the 3’ UTR structures and correlated expression patterns. Conclusions Our results show a potential use for RNA structures in expressed coding as well as noncoding transcripts in the adult mouse brain, and describe the role of structured RNAs in the context of intracellular signaling pathways and regulatory networks. Based on this data we hypothesize that RNA structure is widely involved in transcriptional and translational regulatory mechanisms in the brain and ultimately plays a role in brain function. PMID:22651826

Long-range functional interactions of anterior insula and medial frontal cortex are differently modulated by visuospatial and inductive reasoning tasks.

PubMed

Ebisch, Sjoerd J H; Mantini, Dante; Romanelli, Roberta; Tommasi, Marco; Perrucci, Mauro G; Romani, Gian Luca; Colom, Roberto; Saggino, Aristide

2013-09-01

The brain is organized into functionally specific networks as characterized by intrinsic functional relationships within discrete sets of brain regions. However, it is poorly understood whether such functional networks are dynamically organized according to specific task-states. The anterior insular cortex (aIC)-dorsal anterior cingulate cortex (dACC)/medial frontal cortex (mFC) network has been proposed to play a central role in human cognitive abilities. The present functional magnetic resonance imaging (fMRI) study aimed at testing whether functional interactions of the aIC-dACC/mFC network in terms of temporally correlated patterns of neural activity across brain regions are dynamically modulated by transitory, ongoing task demands. For this purpose, functional interactions of the aIC-dACC/mFC network are compared during two distinguishable fluid reasoning tasks, Visualization and Induction. The results show an increased functional coupling of bilateral aIC with visual cortices in the occipital lobe during the Visualization task, whereas coupling of mFC with right anterior frontal cortex was enhanced during the Induction task. These task-specific modulations of functional interactions likely reflect ability related neural processing. Furthermore, functional connectivity strength between right aIC and right dACC/mFC reliably predicts general task performance. The findings suggest that the analysis of long-range functional interactions may provide complementary information about brain-behavior relationships. On the basis of our results, it is proposed that the aIC-dACC/mFC network contributes to the integration of task-common and task-specific information based on its within-network as well as its between-network dynamic functional interactions. Copyright © 2013 Elsevier Inc. All rights reserved.

A Factor Analysis of Functional Independence and Functional Assessment Measure Scores Among Focal and Diffuse Brain Injury Patients: The Importance of Bifactor Models.

PubMed

Gunn, Sarah; Burgess, Gerald H; Maltby, John

2018-04-30

To explore the factor structure of the UK Functional Independence Measure and Functional Assessment Measure (FIM+FAM) among focal and diffuse acquired brain injury patients. Criterion standard. A National Health Service acute acquired brain injury inpatient rehabilitation hospital. Referred sample of N=447 adults admitted for inpatient treatment following an acquired brain injury significant enough to justify intensive inpatient neurorehabilitation INTERVENTION: Not applicable. Functional Independence Measure and Functional Assessment Measure. Exploratory factor analysis suggested a 2-factor structure to FIM+FAM scores, among both focal-proximate and diffuse-proximate acquired brain injury aetiologies. Confirmatory factor analysis suggested a 3-factor bifactor structure presented the best fit of the FIM+FAM score data across both aetiologies. However, across both analyses, a convergence was found towards a general factor, demonstrated by high correlations between factors in the exploratory factor analysis, and by a general factor explaining the majority of the variance in scores on confirmatory factor analysis. Our findings suggested that although factors describing specific functional domains can be derived from FIM+FAM item scores, there is a convergence towards a single factor describing overall functioning. This single factor informs the specific group factors (eg, motor, psychosocial, and communication function) after brain injury. Further research into the comparative value of the general and group factors as evaluative/prognostic measures is indicated. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

[Dextrals and sinistrals (right-handers and left-handers): specificity of interhemispheric brain asymmetry and EEG coherence parameters].

PubMed

Zhavoronkova, L A

2007-01-01

Data of literature about morphological, functional and biochemical specificity of the brain interhemispheric asymmetry of healthy right-handers and left-handers and about peculiarity of dynamics of cerebral pathology in patients with different individual asymmetry profiles are presented at the present article. Results of our investigation by using coherence parameters of electroencephalogram (EEG) in healthy right-handers and left-handers in state of rest, during functional tests and sleeping and in patients with different forms of the brain organic damage were analyzed too. EEG coherence analysis revealed the reciprocal changing of alpha-beta and theta-delta spectral bands in right-handers whilein left-handers synchronous changing of all EEG spectral bands were observed. Data about regional-frequent specificity of EEG coherence, peculiarity of EEG asymmetry in right-handers and left-handers, aslo about specificity of EEG spectral band genesis and point of view about a role of the brain regulator systems in forming of interhemispheric asymmetry in different functional states allowed to propose the conception about principle of interhermispheric brain asymmetry formation in left-handers and left-handers. Following this conception in dextrals elements of concurrent (summary-reciprocal) cooperation are predominant at the character of interhemispheric and cortical-subcortical interaction while in sinistrals a principle of concordance (supplementary) is preferable. These peculiarities the brain organization determine, from the first side, the quicker revovery of functions damaged after cranio-cerebral trauma in left-handers in comparison right-handers and from the other side - they determine the forming of the more expressed pathology in the remote terms after exposure the low dose of radiation.

The effects of vitamin D on brain development and adult brain function.

PubMed

Kesby, James P; Eyles, Darryl W; Burne, Thomas H J; McGrath, John J

2011-12-05

A role for vitamin D in brain development and function has been gaining support over the last decade. Multiple lines of evidence suggest that this vitamin is actually a neuroactive steroid that acts on brain development, leading to alterations in brain neurochemistry and adult brain function. Early deficiencies have been linked with neuropsychiatric disorders, such as schizophrenia, and adult deficiencies have been associated with a host of adverse brain outcomes, including Parkinson's disease, Alzheimer's disease, depression and cognitive decline. This review summarises the current state of research on the actions of vitamin D in the brain and the consequences of deficiencies in this vitamin. Furthermore, we discuss specific implications of vitamin D status on the neurotransmitter, dopamine. Copyright © 2011 Elsevier Ltd. All rights reserved.

A review on functional and structural brain connectivity in numerical cognition

PubMed Central

Moeller, Korbinian; Willmes, Klaus; Klein, Elise

2015-01-01

Only recently has the complex anatomo-functional system underlying numerical cognition become accessible to evaluation in the living brain. We identified 27 studies investigating brain connectivity in numerical cognition. Despite considerable heterogeneity regarding methodological approaches, populations investigated, and assessment procedures implemented, the results provided largely converging evidence regarding the underlying brain connectivity involved in numerical cognition. Analyses of both functional/effective as well as structural connectivity have consistently corroborated the assumption that numerical cognition is subserved by a fronto-parietal network including (intra)parietal as well as (pre)frontal cortex sites. Evaluation of structural connectivity has indicated the involvement of fronto-parietal association fibers encompassing the superior longitudinal fasciculus dorsally and the external capsule/extreme capsule system ventrally. Additionally, commissural fibers seem to connect the bilateral intraparietal sulci when number magnitude information is processed. Finally, the identification of projection fibers such as the superior corona radiata indicates connections between cortex and basal ganglia as well as the thalamus in numerical cognition. Studies on functional/effective connectivity further indicated a specific role of the hippocampus. These specifications of brain connectivity augment the triple-code model of number processing and calculation with respect to how gray matter areas associated with specific number-related representations may work together. PMID:26029075

Brain foods: the effects of nutrients on brain function

PubMed Central

Gómez-Pinilla, Fernando

2009-01-01

It has long been suspected that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that are responsible for the action of diet on brain health and mental function. Several gut hormones that can enter the brain, or that are produced in the brain itself, influence cognitive ability. In addition, well-established regulators of synaptic plasticity, such as brain-derived neurotrophic factor, can function as metabolic modulators, responding to peripheral signals such as food intake. Understanding the molecular basis of the effects of food on cognition will help us to determine how best to manipulate diet in order to increase the resistance of neurons to insults and promote mental fitness. PMID:18568016

Region-specific RNA m6A methylation represents a new layer of control in the gene regulatory network in the mouse brain.

PubMed

Chang, Mengqi; Lv, Hongyi; Zhang, Weilong; Ma, Chunhui; He, Xue; Zhao, Shunli; Zhang, Zhi-Wei; Zeng, Yi-Xin; Song, Shuhui; Niu, Yamei; Tong, Wei-Min

2017-09-01

N 6 -methyladenosine (m 6 A) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite the relatively high m 6 A levels in the brain, its potential functions in the brain remain largely unexplored. We performed a transcriptome-wide methylation analysis using the mouse brain to depict its region-specific methylation profile. RNA methylation levels in mouse cerebellum are generally higher than those in the cerebral cortex. Heterogeneity of RNA methylation exists across different brain regions and different types of neural cells including the mRNAs to be methylated, their methylation levels and methylation site selection. Common and region-specific methylation have different preferences for methylation site selection and thereby different impacts on their biological functions. In addition, high methylation levels of fragile X mental retardation protein (FMRP) target mRNAs suggest that m 6 A methylation is likely to be used for selective recognition of target mRNAs by FMRP in the synapse. Overall, we provide a region-specific map of RNA m 6 A methylation and characterize the distinct features of specific and common methylation in mouse cerebellum and cerebral cortex. Our results imply that RNA m 6 A methylation is a newly identified element in the region-specific gene regulatory network in the mouse brain. © 2017 The Authors.

Videogame training strategy-induced change in brain function during a complex visuomotor task.

PubMed

Lee, Hyunkyu; Voss, Michelle W; Prakash, Ruchika Shaurya; Boot, Walter R; Vo, Loan T K; Basak, Chandramallika; Vanpatter, Matt; Gratton, Gabriele; Fabiani, Monica; Kramer, Arthur F

2012-07-01

Although changes in brain function induced by cognitive training have been examined, functional plasticity associated with specific training strategies is still relatively unexplored. In this study, we examined changes in brain function during a complex visuomotor task following training using the Space Fortress video game. To assess brain function, participants completed functional magnetic resonance imaging (fMRI) before and after 30 h of training with one of two training regimens: Hybrid Variable-Priority Training (HVT), with a focus on improving specific skills and managing task priority, or Full Emphasis Training (FET), in which participants simply practiced the game to obtain the highest overall score. Control participants received only 6 h of FET. Compared to FET, HVT learners reached higher performance on the game and showed less brain activation in areas related to visuo-spatial attention and goal-directed movement after training. Compared to the control group, HVT exhibited less brain activation in right dorsolateral prefrontal cortex (DLPFC), coupled with greater performance improvement. Region-of-interest analysis revealed that the reduction in brain activation was correlated with improved performance on the task. This study sheds light on the neurobiological mechanisms of improved learning from directed training (HVT) over non-directed training (FET), which is related to visuo-spatial attention and goal-directed motor planning, while separating the practice-based benefit, which is related to executive control and rule management. Copyright © 2012 Elsevier B.V. All rights reserved.

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

PubMed

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

2015-01-01

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

Novel Nanotechnologies for Brain Cancer Therapeutics and Imaging.

PubMed

Ferroni, Letizia; Gardin, Chiara; Della Puppa, Alessandro; Sivolella, Stefano; Brunello, Giulia; Scienza, Renato; Bressan, Eriberto; D'Avella, Domenico; Zavan, Barbara

2015-11-01

Despite progress in surgery, radiotherapy, and in chemotherapy, an effective curative treatment of brain cancer, specifically malignant gliomas, does not yet exist. The efficacy of current anti-cancer strategies in brain tumors is limited by the lack of specific therapies against malignant cells. Besides, the delivery of the drugs to brain tumors is limited by the presence of the blood-brain barrier. Nanotechnology today offers a unique opportunity to develop more effective brain cancer imaging and therapeutics. In particular, the development of nanocarriers that can be conjugated with several functional molecules including tumor-specific ligands, anticancer drugs, and imaging probes, can provide new devices which are able to overcome the difficulties of the classical strategies. Nanotechnology-based approaches hold great promise for revolutionizing brain cancer medical treatments, imaging, and diagnosis.

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.…

Learning Control Over Emotion Networks Through Connectivity-Based Neurofeedback.

PubMed

Koush, Yury; Meskaldji, Djalel-E; Pichon, Swann; Rey, Gwladys; Rieger, Sebastian W; Linden, David E J; Van De Ville, Dimitri; Vuilleumier, Patrik; Scharnowski, Frank

2017-02-01

Most mental functions are associated with dynamic interactions within functional brain networks. Thus, training individuals to alter functional brain networks might provide novel and powerful means to improve cognitive performance and emotions. Using a novel connectivity-neurofeedback approach based on functional magnetic resonance imaging (fMRI), we show for the first time that participants can learn to change functional brain networks. Specifically, we taught participants control over a key component of the emotion regulation network, in that they learned to increase top-down connectivity from the dorsomedial prefrontal cortex, which is involved in cognitive control, onto the amygdala, which is involved in emotion processing. After training, participants successfully self-regulated the top-down connectivity between these brain areas even without neurofeedback, and this was associated with concomitant increases in subjective valence ratings of emotional stimuli of the participants. Connectivity-based neurofeedback goes beyond previous neurofeedback approaches, which were limited to training localized activity within a brain region. It allows to noninvasively and nonpharmacologically change interconnected functional brain networks directly, thereby resulting in specific behavioral changes. Our results demonstrate that connectivity-based neurofeedback training of emotion regulation networks enhances emotion regulation capabilities. This approach can potentially lead to powerful therapeutic emotion regulation protocols for neuropsychiatric disorders. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Optogenetic Functional MRI

PubMed Central

Lin, Peter; Fang, Zhongnan; Liu, Jia; Lee, Jin Hyung

2016-01-01

The investigation of the functional connectivity of precise neural circuits across the entire intact brain can be achieved through optogenetic functional magnetic resonance imaging (ofMRI), which is a novel technique that combines the relatively high spatial resolution of high-field fMRI with the precision of optogenetic stimulation. Fiber optics that enable delivery of specific wavelengths of light deep into the brain in vivo are implanted into regions of interest in order to specifically stimulate targeted cell types that have been genetically induced to express light-sensitive trans-membrane conductance channels, called opsins. fMRI is used to provide a non-invasive method of determining the brain's global dynamic response to optogenetic stimulation of specific neural circuits through measurement of the blood-oxygen-level-dependent (BOLD) signal, which provides an indirect measurement of neuronal activity. This protocol describes the construction of fiber optic implants, the implantation surgeries, the imaging with photostimulation and the data analysis required to successfully perform ofMRI. In summary, the precise stimulation and whole-brain monitoring ability of ofMRI are crucial factors in making ofMRI a powerful tool for the study of the connectomics of the brain in both healthy and diseased states. PMID:27167840

Variability in functional brain networks predicts expertise during action observation.

PubMed

Amoruso, Lucía; Ibáñez, Agustín; Fonseca, Bruno; Gadea, Sebastián; Sedeño, Lucas; Sigman, Mariano; García, Adolfo M; Fraiman, Ricardo; Fraiman, Daniel

2017-02-01

Observing an action performed by another individual activates, in the observer, similar circuits as those involved in the actual execution of that action. This activation is modulated by prior experience; indeed, sustained training in a particular motor domain leads to structural and functional changes in critical brain areas. Here, we capitalized on a novel graph-theory approach to electroencephalographic data (Fraiman et al., 2016) to test whether variability in functional brain networks implicated in Tango observation can discriminate between groups differing in their level of expertise. We found that experts and beginners significantly differed in the functional organization of task-relevant networks. Specifically, networks in expert Tango dancers exhibited less variability and a more robust functional architecture. Notably, these expertise-dependent effects were captured within networks derived from electrophysiological brain activity recorded in a very short time window (2s). In brief, variability in the organization of task-related networks seems to be a highly sensitive indicator of long-lasting training effects. This finding opens new methodological and theoretical windows to explore the impact of domain-specific expertise on brain plasticity, while highlighting variability as a fruitful measure in neuroimaging research. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional organization of the transcriptome in human brain

PubMed Central

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

2009-01-01

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

Sugar for the brain: the role of glucose in physiological and pathological brain function

PubMed Central

Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A.; Meisel, Andreas

2013-01-01

The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We aim at synthesizing these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation which lead to disease. PMID:23968694

ABERRANT SPLICING OF A BRAIN-ENRICHED ALTERNATIVE EXON ELIMINATES TUMOR SUPPRESSOR FUNCTION AND PROMOTES ONCOGENE FUNCTION DURING BRAIN TUMORIGENESIS

PubMed Central

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

2014-01-01

BACKGROUND: Tissue-specific alternative splicing is known to be critical to emergence of tissue identity during development, yet its role in malignant transformation is undefined. Tissue-specific splicing involves evolutionary-conserved, alternative exons, which represent only a minority of total alternative exons. Many, however, have functional features that influence activity in signaling pathways to profound biological effect. Given that tissue-specific splicing has a determinative role in brain development and the enrichment of genes containing tissue-specific exons for proteins with roles in signaling and development, it is thus plausible that changes in such exons could rewire normal neurogenesis towards malignant transformation. METHODS: We used integrated molecular genetic and cell biology analyses, computational biology, animal modeling, and clinical patient profiles to characterize the effect of aberrant splicing of a brain-enriched alternative exon in the membrane-binding tumor suppressor Annexin A7 (ANXA7) on oncogene regulation and brain tumorigenesis. RESULTS: We show that aberrant splicing of a tissue-specific cassette exon in ANXA7 diminishes endosomal targeting and consequent termination of the signal of the EGFR oncoprotein during brain tumorigenesis. Splicing of this exon is mediated by the ribonucleoprotein Polypyrimidine Tract-Binding Protein 1 (PTBP1), which is normally repressed during brain development but, we find, is excessively expressed in glioblastomas through either gene amplification or loss of a neuron-specific microRNA, miR-124. Silencing of PTBP1 attenuates both malignancy and angiogenesis in a stem cell-derived glioblastoma animal model characterized by a high native propensity to generate tumor endothelium or vascular pericytes to support tumor growth. We show that EGFR amplification and PTBP1 overexpression portend a similarly poor clinical outcome, further highlighting the importance of PTBP1-mediated activation of EGFR. CONCLUSIONS: Our data illustrate how anomalous splicing of a tissue-regulated exon in a constituent of an oncogenic signaling pathway eliminates its tumor suppressor function and promotes tumorigenesis. This paradigm of malignant glial transformation as a consequence of tissue-specific alternative exon splicing in a tumor suppressor, may have widespread applicability in explaining how changes in critical tissue-specific regulatory mechanisms reprogram normal development to oncogenesis. SECONDARY CATEGORY: n/a.

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

ERIC Educational Resources Information Center

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

2009-01-01

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

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

PubMed

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

2015-06-01

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

Identification of alterations associated with age in the clustering structure of functional brain networks.

PubMed

Guzman, Grover E C; Sato, Joao R; Vidal, Maciel C; Fujita, Andre

2018-01-01

Initial studies using resting-state functional magnetic resonance imaging on the trajectories of the brain network from childhood to adulthood found evidence of functional integration and segregation over time. The comprehension of how healthy individuals' functional integration and segregation occur is crucial to enhance our understanding of possible deviations that may lead to brain disorders. Recent approaches have focused on the framework wherein the functional brain network is organized into spatially distributed modules that have been associated with specific cognitive functions. Here, we tested the hypothesis that the clustering structure of brain networks evolves during development. To address this hypothesis, we defined a measure of how well a brain region is clustered (network fitness index), and developed a method to evaluate its association with age. Then, we applied this method to a functional magnetic resonance imaging data set composed of 397 males under 31 years of age collected as part of the Autism Brain Imaging Data Exchange Consortium. As results, we identified two brain regions for which the clustering change over time, namely, the left middle temporal gyrus and the left putamen. Since the network fitness index is associated with both integration and segregation, our finding suggests that the identified brain region plays a role in the development of brain systems.

Traffic pollution exposure is associated with altered brain connectivity in school children.

PubMed

Pujol, Jesus; Martínez-Vilavella, Gerard; Macià, Dídac; Fenoll, Raquel; Alvarez-Pedrerol, Mar; Rivas, Ioar; Forns, Joan; Blanco-Hinojo, Laura; Capellades, Jaume; Querol, Xavier; Deus, Joan; Sunyer, Jordi

2016-04-01

Children are more vulnerable to the effects of environmental elements due to their active developmental processes. Exposure to urban air pollution has been associated with poorer cognitive performance, which is thought to be a result of direct interference with brain maturation. We aimed to assess the extent of such potential effects of urban pollution on child brain maturation using general indicators of vehicle exhaust measured in the school environment and a comprehensive imaging evaluation. A group of 263 children, aged 8 to 12 years, underwent MRI to quantify regional brain volumes, tissue composition, myelination, cortical thickness, neural tract architecture, membrane metabolites, functional connectivity in major neural networks and activation/deactivation dynamics during a sensory task. A combined measurement of elemental carbon and NO2 was used as a putative marker of vehicle exhaust. Air pollution exposure was associated with brain changes of a functional nature, with no evident effect on brain anatomy, structure or membrane metabolites. Specifically, a higher content of pollutants was associated with lower functional integration and segregation in key brain networks relevant to both inner mental processes (the default mode network) and stimulus-driven mental operations. Age and performance (motor response speed) both showed the opposite effect to that of pollution, thus indicating that higher exposure is associated with slower brain maturation. In conclusion, urban air pollution appears to adversely affect brain maturation in a critical age with changes specifically concerning the functional domain. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain Entropy Mapping Using fMRI

PubMed Central

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

2014-01-01

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

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

PubMed Central

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

2011-01-01

Executive functioning deficits due to brain disease affecting frontal lobe functions cause significant real-life disability, yet solid evidence in support of executive functioning interventions is lacking. Goal Management Training (GMT), an executive functioning intervention that draws upon theories concerning goal processing and sustained attention, has received empirical support in studies of patients with traumatic brain injury, normal aging, and case studies. GMT promotes a mindful approach to complex real-life tasks that pose problems for patients with executive functioning deficits, with a main goal of periodically stopping ongoing behavior to monitor and adjust goals. In this controlled trial, an expanded version of GMT was compared to an alternative intervention, Brain Health Workshop that was matched to GMT on non-specific characteristics that can affect intervention outcome. Participants included 19 individuals in the chronic phase of recovery from brain disease (predominantly stroke) affecting frontal lobe function. Outcome data indicated specific effects of GMT on the Sustained Attention to Response Task as well as the Tower Test, a visuospatial problem-solving measure that reflected far transfer of training effects. There were no significant effects on self-report questionnaires, likely owing to the complexity of these measures in this heterogeneous patient sample. Overall, these data support the efficacy of GMT in the rehabilitation of executive functioning deficits. PMID:21369362

Microglia promote learning-dependent synapse formation through BDNF

PubMed Central

Parkhurst, Christopher N.; Yang, Guang; Ninan, Ipe; Savas, Jeffrey N.; Yates, John R.; Lafaille, Juan J.; Hempstead, Barbara L.; Littman, Dan R.; Gan, Wen-Biao

2014-01-01

SUMMARY Microglia are the resident macrophages of the central nervous system and their functions have been extensively studied in various brain pathologies. The physiological roles of microglia in brain plasticity and function, however, remain unclear. To address this question, we generated CX3CR1CreER mice expressing tamoxifen-inducible Cre recombinase that allow for specific manipulation of gene function in microglia. Using CX3CR1CreER to drive diphtheria toxin receptor expression in microglia, we found that microglia could be specifically depleted from the brain upon diphtheria toxin administration. Mice depleted of microglia show deficits in multiple learning tasks and a significant reduction in motor learning-dependent synapse formation. Furthermore, Cre-dependent removal of brain-derived neurotrophic factor (BDNF) from microglia largely recapitulated the effects of microglia depletion. Microglial BDNF increases neuronal TrkB phosphorylation, a key mediator of synaptic plasticity. Together, our findings reveal important physiological functions of microglia in learning and memory by promoting learning-related synapse formation through BDNF signaling. PMID:24360280

Peroxisomes in brain development and function☆

PubMed Central

Berger, Johannes; Dorninger, Fabian; Forss-Petter, Sonja; Kunze, Markus

2016-01-01

Peroxisomes contain numerous enzymatic activities that are important for mammalian physiology. Patients lacking either all peroxisomal functions or a single enzyme or transporter function typically develop severe neurological deficits, which originate from aberrant development of the brain, demyelination and loss of axonal integrity, neuroinflammation or other neurodegenerative processes. Whilst correlating peroxisomal properties with a compilation of pathologies observed in human patients and mouse models lacking all or individual peroxisomal functions, we discuss the importance of peroxisomal metabolites and tissue- and cell type-specific contributions to the observed brain pathologies. This enables us to deconstruct the local and systemic contribution of individual metabolic pathways to specific brain functions. We also review the recently discovered variability of pathological symptoms in cases with unexpectedly mild presentation of peroxisome biogenesis disorders. Finally, we explore the emerging evidence linking peroxisomes to more common neurological disorders such as Alzheimer’s disease, autism and amyotrophic lateral sclerosis. This article is part of a Special Issue entitled: Peroxisomes edited by Ralf Erdmann. PMID:26686055

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

PubMed

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

2006-05-01

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

Sculpting the Intrinsic Modular Organization of Spontaneous Brain Activity by Art.

PubMed

Lin, Chia-Shu; Liu, Yong; Huang, Wei-Yuan; Lu, Chia-Feng; Teng, Shin; Ju, Tzong-Ching; He, Yong; Wu, Yu-Te; Jiang, Tianzi; Hsieh, Jen-Chuen

2013-01-01

Artistic training is a complex learning that requires the meticulous orchestration of sophisticated polysensory, motor, cognitive, and emotional elements of mental capacity to harvest an aesthetic creation. In this study, we investigated the architecture of the resting-state functional connectivity networks from professional painters, dancers and pianists. Using a graph-based network analysis, we focused on the art-related changes of modular organization and functional hubs in the resting-state functional connectivity network. We report that the brain architecture of artists consists of a hierarchical modular organization where art-unique and artistic form-specific brain states collectively mirror the mind states of virtuosos. We show that even in the resting state, this type of extraordinary and long-lasting training can macroscopically imprint a neural network system of spontaneous activity in which the related brain regions become functionally and topologically modularized in both domain-general and domain-specific manners. The attuned modularity reflects a resilient plasticity nurtured by long-term experience.

Sculpting the Intrinsic Modular Organization of Spontaneous Brain Activity by Art

PubMed Central

Lin, Chia-Shu; Liu, Yong; Huang, Wei-Yuan; Lu, Chia-Feng; Teng, Shin; Ju, Tzong-Ching; He, Yong; Wu, Yu-Te; Jiang, Tianzi; Hsieh, Jen-Chuen

2013-01-01

Artistic training is a complex learning that requires the meticulous orchestration of sophisticated polysensory, motor, cognitive, and emotional elements of mental capacity to harvest an aesthetic creation. In this study, we investigated the architecture of the resting-state functional connectivity networks from professional painters, dancers and pianists. Using a graph-based network analysis, we focused on the art-related changes of modular organization and functional hubs in the resting-state functional connectivity network. We report that the brain architecture of artists consists of a hierarchical modular organization where art-unique and artistic form-specific brain states collectively mirror the mind states of virtuosos. We show that even in the resting state, this type of extraordinary and long-lasting training can macroscopically imprint a neural network system of spontaneous activity in which the related brain regions become functionally and topologically modularized in both domain-general and domain-specific manners. The attuned modularity reflects a resilient plasticity nurtured by long-term experience. PMID:23840527

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.

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2012-08-01

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

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

PubMed Central

Kanwisher, Nancy

2010-01-01

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

Temporal Dynamics Assessment of Spatial Overlap Pattern of Functional Brain Networks Reveals Novel Functional Architecture of Cerebral Cortex.

PubMed

Jiang, Xi; Li, Xiang; Lv, Jinglei; Zhao, Shijie; Zhang, Shu; Zhang, Wei; Zhang, Tuo; Han, Junwei; Guo, Lei; Liu, Tianming

2018-06-01

Various studies in the brain mapping field have demonstrated that there exist multiple concurrent functional networks that are spatially overlapped and interacting with each other during specific task performance to jointly realize the total brain function. Assessing such spatial overlap patterns of functional networks (SOPFNs) based on functional magnetic resonance imaging (fMRI) has thus received increasing interest for brain function studies. However, there are still two crucial issues to be addressed. First, the SOPFNs are assessed over the entire fMRI scan assuming the temporal stationarity, while possibly time-dependent dynamics of the SOPFNs is not sufficiently explored. Second, the SOPFNs are assessed within individual subjects, while group-wise consistency of the SOPFNs is largely unknown. To address the two issues, we propose a novel computational framework of group-wise sparse representation of whole-brain fMRI temporal segments to assess the temporal dynamic spatial patterns of SOPFNs that are consistent across different subjects. Experimental results based on the recently publicly released Human Connectome Project grayordinate task fMRI data demonstrate that meaningful SOPFNs exhibiting dynamic spatial patterns across different time periods are effectively and robustly identified based on the reconstructed concurrent functional networks via the proposed framework. Specifically, those SOPFNs locate significantly more on gyral regions than on sulcal regions across different time periods. These results reveal novel functional architecture of cortical gyri and sulci. Moreover, these results help better understand functional dynamics mechanisms of cerebral cortex in the future.

Episodic memory in aspects of large-scale brain networks

PubMed Central

Jeong, Woorim; Chung, Chun Kee; Kim, June Sic

2015-01-01

Understanding human episodic memory in aspects of large-scale brain networks has become one of the central themes in neuroscience over the last decade. Traditionally, episodic memory was regarded as mostly relying on medial temporal lobe (MTL) structures. However, recent studies have suggested involvement of more widely distributed cortical network and the importance of its interactive roles in the memory process. Both direct and indirect neuro-modulations of the memory network have been tried in experimental treatments of memory disorders. In this review, we focus on the functional organization of the MTL and other neocortical areas in episodic memory. Task-related neuroimaging studies together with lesion studies suggested that specific sub-regions of the MTL are responsible for specific components of memory. However, recent studies have emphasized that connectivity within MTL structures and even their network dynamics with other cortical areas are essential in the memory process. Resting-state functional network studies also have revealed that memory function is subserved by not only the MTL system but also a distributed network, particularly the default-mode network (DMN). Furthermore, researchers have begun to investigate memory networks throughout the entire brain not restricted to the specific resting-state network (RSN). Altered patterns of functional connectivity (FC) among distributed brain regions were observed in patients with memory impairments. Recently, studies have shown that brain stimulation may impact memory through modulating functional networks, carrying future implications of a novel interventional therapy for memory impairment. PMID:26321939

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

PubMed

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

2017-03-01

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

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

PubMed Central

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

2017-01-01

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

miRNAs in brain development

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

Petri, Rebecca; Malmevik, Josephine; Fasching, Liana

2014-02-01

MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In the brain, a large number of miRNAs are expressed and there is a growing body of evidence demonstrating that miRNAs are essential for brain development and neuronal function. Conditional knockout studies of the core components in the miRNA biogenesis pathway, such as Dicer and DGCR8, have demonstrated a crucial role for miRNAs during the development of the central nervous system. Furthermore, mice deleted for specific miRNAs and miRNA-clusters demonstrate diverse functional roles for different miRNAs during the development of different brain structures. miRNAs havemore » been proposed to regulate cellular functions such as differentiation, proliferation and fate-determination of neural progenitors. In this review we summarise the findings from recent studies that highlight the importance of miRNAs in brain development with a focus on the mouse model. We also discuss the technical limitations of current miRNA studies that still limit our understanding of this family of non-coding RNAs and propose the use of novel and refined technologies that are needed in order to fully determine the impact of specific miRNAs in brain development. - Highlights: • miRNAs are essential for brain development and neuronal function. • KO of Dicer is embryonically lethal. • Conditional Dicer KO results in defective proliferation or increased apoptosis. • KO of individual miRNAs or miRNA families is necessary to determine function.« less

Mapping cell-specific functional connections in the mouse brain using ChR2-evoked hemodynamics (Conference Presentation)

NASA Astrophysics Data System (ADS)

Bauer, Adam Q.; Kraft, Andrew; Baxter, Grant A.; Bruchas, Michael; Lee, Jin-Moo; Culver, Joseph P.

2017-02-01

Functional magnetic resonance imaging (fMRI) has transformed our understanding of the brain's functional organization. However, mapping subunits of a functional network using hemoglobin alone presents several disadvantages. Evoked and spontaneous hemodynamic fluctuations reflect ensemble activity from several populations of neurons making it difficult to discern excitatory vs inhibitory network activity. Still, blood-based methods of brain mapping remain powerful because hemoglobin provides endogenous contrast in all mammalian brains. To add greater specificity to hemoglobin assays, we integrated optical intrinsic signal(OIS) imaging with optogenetic stimulation to create an Opto-OIS mapping tool that combines the cell-specificity of optogenetics with label-free, hemoglobin imaging. Before mapping, titrated photostimuli determined which stimulus parameters elicited linear hemodynamic responses in the cortex. Optimized stimuli were then scanned over the left hemisphere to create a set of optogenetically-defined effective connectivity (Opto-EC) maps. For many sites investigated, Opto-EC maps exhibited higher spatial specificity than those determined using spontaneous hemodynamic fluctuations. For example, resting-state functional connectivity (RS-FC) patterns exhibited widespread ipsilateral connectivity while Opto-EC maps contained distinct short- and long-range constellations of ipsilateral connectivity. Further, RS-FC maps were usually symmetric about midline while Opto-EC maps displayed more heterogeneous contralateral homotopic connectivity. Both Opto-EC and RS-FC patterns were compared to mouse connectivity data from the Allen Institute. Unlike RS-FC maps, Thy1-based maps collected in awake, behaving mice closely recapitulated the connectivity structure derived using ex vivo anatomical tracer methods. Opto-OIS mapping could be a powerful tool for understanding cellular and molecular contributions to network dynamics and processing in the mouse brain.

Neurocognitive mechanisms of mathematical giftedness: A literature review.

PubMed

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

2017-01-01

Mathematically gifted children/adolescents have demonstrated exceptional abilities and traits in logical reasoning, mental imagery, and creative thinking. In the field of cognitive neuroscience, the past studies on mathematically gifted brains have concentrated on investigating event-related brain activation regions, cerebral laterality of cognitive functions, functional specialization that is uniquely dedicated for specific cognitive purposes, and functional interactions among discrete brain regions. From structural and functional perspectives, these studies have witnessed both "general" and "unique" neural characteristics of mathematically gifted brains. In this article, the theoretical background, empirical studies, and neurocognitive mechanisms of mathematically gifted children/adolescents are reviewed. Based on the integration of the findings, some potential directions for the future research are identified and discussed.

Functional MRI registration with tissue-specific patch-based functional correlation tensors.

PubMed

Zhou, Yujia; Zhang, Han; Zhang, Lichi; Cao, Xiaohuan; Yang, Ru; Feng, Qianjin; Yap, Pew-Thian; Shen, Dinggang

2018-06-01

Population studies of brain function with resting-state functional magnetic resonance imaging (rs-fMRI) rely on accurate intersubject registration of functional areas. This is typically achieved through registration using high-resolution structural images with more spatial details and better tissue contrast. However, accumulating evidence has suggested that such strategy cannot align functional regions well because functional areas are not necessarily consistent with anatomical structures. To alleviate this problem, a number of registration algorithms based directly on rs-fMRI data have been developed, most of which utilize functional connectivity (FC) features for registration. However, most of these methods usually extract functional features only from the thin and highly curved cortical grey matter (GM), posing great challenges to accurate estimation of whole-brain deformation fields. In this article, we demonstrate that additional useful functional features can also be extracted from the whole brain, not restricted to the GM, particularly the white-matter (WM), for improving the overall functional registration. Specifically, we quantify local anisotropic correlation patterns of the blood oxygenation level-dependent (BOLD) signals using tissue-specific patch-based functional correlation tensors (ts-PFCTs) in both GM and WM. Functional registration is then performed by integrating the features from different tissues using the multi-channel large deformation diffeomorphic metric mapping (mLDDMM) algorithm. Experimental results show that our method achieves superior functional registration performance, compared with conventional registration methods. © 2018 Wiley Periodicals, Inc.

Executive Functions and Social Skills in Survivors of Pediatric Brain Tumor

PubMed Central

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

2012-01-01

Medical advances have resulted in increased survival rates for children with brain tumors. Consequently, issues related to survivorship have become more critical. The use of multimodal treatment, in particular cranial radiation therapy, has been associated with subsequent cognitive decline. Specifically, deficits in executive functions have been reported in survivors of various types of pediatric brain tumor. Survivors are left with difficulties, particularly in self-monitoring, initiation, inhibition, and planning, to name a few. Another domain in which survivors of pediatric brain tumor have been reported to show difficulty is that of social skills. Parents, teachers, and survivors themselves have reported decreased social functioning following treatment. Deficits in executive functions and social skills are likely interrelated in this population, as executive skills are needed to navigate various aspects of social interaction; however, this has yet to be studied empirically. Twenty-four survivors of pediatric brain tumor were assessed using a computerized task of executive functions, as well as paper and pencil measures of social skills and real world executive skills. Social functioning was related to a specific aspect of executive functions, i.e., the survivors’ variability in response time, such that inconsistent responding was associated with better parent-report and survivor-report social skills, independent of intellectual abilities. Additionally, parent-reported real-world global executive abilities predicted parent-reported social skills. The implications of these findings for social skills interventions and future research are discussed. PMID:22420326

Brain Connectivity and Visual Attention

PubMed Central

Parks, Emily L.

2013-01-01

Abstract Emerging hypotheses suggest that efficient cognitive functioning requires the integration of separate, but interconnected cortical networks in the brain. Although task-related measures of brain activity suggest that a frontoparietal network is associated with the control of attention, little is known regarding how components within this distributed network act together or with other networks to achieve various attentional functions. This review considers both functional and structural studies of brain connectivity, as complemented by behavioral and task-related neuroimaging data. These studies show converging results: The frontal and parietal cortical regions are active together, over time, and identifiable frontoparietal networks are active in relation to specific task demands. However, the spontaneous, low-frequency fluctuations of brain activity that occur in the resting state, without specific task demands, also exhibit patterns of connectivity that closely resemble the task-related, frontoparietal attention networks. Both task-related and resting-state networks exhibit consistent relations to behavioral measures of attention. Further, anatomical structure, particularly white matter pathways as defined by diffusion tensor imaging, places constraints on intrinsic functional connectivity. Lastly, connectivity analyses applied to investigate cognitive differences across individuals in both healthy and diseased states suggest that disconnection of attentional networks is linked to deficits in cognitive functioning, and in extreme cases, to disorders of attention. Thus, comprehensive theories of visual attention and their clinical translation depend on the continued integration of behavioral, task-related neuroimaging, and brain connectivity measures. PMID:23597177

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

PubMed

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

2015-01-01

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

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

PubMed Central

2015-01-01

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

Correspondence Between Aberrant Intrinsic Network Connectivity and Gray-Matter Volume in the Ventral Brain of Preterm Born Adults.

PubMed

Bäuml, Josef G; Daamen, Marcel; Meng, Chun; Neitzel, Julia; Scheef, Lukas; Jaekel, Julia; Busch, Barbara; Baumann, Nicole; Bartmann, Peter; Wolke, Dieter; Boecker, Henning; Wohlschläger, Afra M; Sorg, Christian

2015-11-01

Widespread brain changes are present in preterm born infants, adolescents, and even adults. While neurobiological models of prematurity facilitate powerful explanations for the adverse effects of preterm birth on the developing brain at microscale, convincing linking principles at large-scale level to explain the widespread nature of brain changes are still missing. We investigated effects of preterm birth on the brain's large-scale intrinsic networks and their relation to brain structure in preterm born adults. In 95 preterm and 83 full-term born adults, structural and functional magnetic resonance imaging at-rest was used to analyze both voxel-based morphometry and spatial patterns of functional connectivity in ongoing blood oxygenation level-dependent activity. Differences in intrinsic functional connectivity (iFC) were found in cortical and subcortical networks. Structural differences were located in subcortical, temporal, and cingulate areas. Critically, for preterm born adults, iFC-network differences were overlapping and correlating with aberrant regional gray-matter (GM) volume specifically in subcortical and temporal areas. Overlapping changes were predicted by prematurity and in particular by neonatal medical complications. These results provide evidence that preterm birth has long-lasting effects on functional connectivity of intrinsic networks, and these changes are specifically related to structural alterations in ventral brain GM. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

PubMed Central

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

2015-01-01

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

Sex-specific differences in transcriptome profiles of brain and muscle tissue of the tropical gar.

PubMed

Cribbin, Kayla M; Quackenbush, Corey R; Taylor, Kyle; Arias-Rodriguez, Lenin; Kelley, Joanna L

2017-04-07

The tropical gar (Atractosteus tropicus) is the southernmost species of the seven extant species of gar fishes in the world. In Mexico and Central America, the species is an important food source due to its nutritional quality and low price. Despite its regional importance and increasing concerns about overexploitation and habitat degradation, basic genetic information on the tropical gar is lacking. Determining genetic information on the tropical gar is important for the sustainable management of wild populations, implementation of best practices in aquaculture settings, evolutionary studies of ancient lineages, and an understanding of sex-specific gene expression. In this study, the transcriptome of the tropical gar was sequenced and assembled de novo using tissues from three males and three females using Illumina sequencing technology. Sex-specific and highly differentially expressed transcripts in brain and muscle tissues between adult males and females were subsequently identified. The transcriptome was assembled de novo resulting in 80,611 transcripts with a contig N50 of 3,355 base pairs and over 168 kilobases in total length. Male muscle, brain, and gonad as well as female muscle and brain were included in the assembly. The assembled transcriptome was annotated to identify the putative function of expressed transcripts using Trinotate and SwissProt, a database of well-annotated proteins. The brain and muscle datasets were then aligned to the assembled transcriptome to identify transcripts that were differentially expressed between males and females. The contrast between male and female brain identified 109 transcripts from 106 genes that were significantly differentially expressed. In the muscle comparison, 82 transcripts from 80 genes were identified with evidence for significant differential expression. Almost all genes identified as differentially expressed were sex-specific. The differentially expressed transcripts were enriched for genes involved in cellular functioning, signaling, immune response, and tissue-specific functions. This study identified differentially expressed transcripts between male and female gar in muscle and brain tissue. The majority of differentially expressed transcripts had sex-specific expression. Expanding on these findings to other developmental stages, populations, and species may lead to the identification of genetic factors contributing to the skewed sex ratio seen in the tropical gar and of sex-specific differences in expression in other species. Finally, the transcriptome assembly will open future research avenues on tropical gar development, cell function, environmental resistance, and evolution in the context of other early vertebrates.

Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues.

PubMed

Anafi, Ron C; Pellegrino, Renata; Shockley, Keith R; Romer, Micah; Tufik, Sergio; Pack, Allan I

2013-05-30

Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times. In each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the influence of an artificial deprivation protocol, we identified a subset of these transcripts as specifically sleep-enhanced or sleep-repressed by requiring that their expression also change over the course of unperturbed sleep. 3% and 6% of the assayed transcripts showed "sleep specific" changes in the lung and heart respectively. Sleep specific transcripts in these tissues demonstrated highly significant overlap and shared temporal dynamics. Markers of cellular stress and the unfolded protein response were reduced during sleep in both tissues. These results mirror previous findings in brain. Sleep-enhanced pathways reflected the unique metabolic functions of each tissue. Transcripts related to carbohydrate and sulfur metabolic processes were enhanced by sleep in the lung, and collectively favor buffering from oxidative stress. DNA repair and protein metabolism annotations were significantly enriched among the sleep-enhanced transcripts in the heart. Our results also suggest that sleep may provide a Zeitgeber, or synchronizing cue, in the lung as a large cluster of transcripts demonstrated systematic changes in inter-animal variability as a function of both sleep duration and circadian time. Our data support the notion that the molecular consequences of sleep/wake behavioral state extend beyond the brain to include peripheral tissues. Sleep state induces a highly overlapping response in both heart and lung. We conclude that sleep enhances organ specific molecular functions and that it has a ubiquitous role in reducing cellular metabolic stress in both brain and peripheral tissues. Finally, our data suggest a novel role for sleep in synchronizing transcription in peripheral tissues.

Sugar for the brain: the role of glucose in physiological and pathological brain function.

PubMed

Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A; Meisel, Andreas

2013-10-01

The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We synthesize these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation that lead to disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Developing Brain Vital Signs: Initial Framework for Monitoring Brain Function Changes Over Time

PubMed Central

Ghosh Hajra, Sujoy; Liu, Careesa C.; Song, Xiaowei; Fickling, Shaun; Liu, Luke E.; Pawlowski, Gabriela; Jorgensen, Janelle K.; Smith, Aynsley M.; Schnaider-Beeri, Michal; Van Den Broek, Rudi; Rizzotti, Rowena; Fisher, Kirk; D'Arcy, Ryan C. N.

2016-01-01

Clinical assessment of brain function relies heavily on indirect behavior-based tests. Unfortunately, behavior-based assessments are subjective and therefore susceptible to several confounding factors. Event-related brain potentials (ERPs), derived from electroencephalography (EEG), are often used to provide objective, physiological measures of brain function. Historically, ERPs have been characterized extensively within research settings, with limited but growing clinical applications. Over the past 20 years, we have developed clinical ERP applications for the evaluation of functional status following serious injury and/or disease. This work has identified an important gap: the need for a clinically accessible framework to evaluate ERP measures. Crucially, this enables baseline measures before brain dysfunction occurs, and might enable the routine collection of brain function metrics in the future much like blood pressure measures today. Here, we propose such a framework for extracting specific ERPs as potential “brain vital signs.” This framework enabled the translation/transformation of complex ERP data into accessible metrics of brain function for wider clinical utilization. To formalize the framework, three essential ERPs were selected as initial indicators: (1) the auditory N100 (Auditory sensation); (2) the auditory oddball P300 (Basic attention); and (3) the auditory speech processing N400 (Cognitive processing). First step validation was conducted on healthy younger and older adults (age range: 22–82 years). Results confirmed specific ERPs at the individual level (86.81–98.96%), verified predictable age-related differences (P300 latency delays in older adults, p < 0.05), and demonstrated successful linear transformation into the proposed brain vital sign (BVS) framework (basic attention latency sub-component of BVS framework reflects delays in older adults, p < 0.05). The findings represent an initial critical step in developing, extracting, and characterizing ERPs as vital signs, critical for subsequent evaluation of dysfunction in conditions like concussion and/or dementia. PMID:27242415

Assisting Students with a Traumatic Brain Injury in School Interventions

ERIC Educational Resources Information Center

Aldrich, Erin M.; Obrzut, John E.

2012-01-01

Traumatic brain injury (TBI) in children and adolescents can significantly affect their lives and educational needs. Deficits are often exhibited in areas such as attention, concentration, memory, executive function, emotional regulation, and behavioral functioning, but specific outcomes are not particular to any one child or adolescent with a…

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

PubMed Central

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

2012-01-01

The development of large-scale functional brain networks is a complex, lifelong process that can be investigated using resting-state functional connectivity MRI (rs-fcMRI). In this study, we aimed to decode the developmental dynamics of the whole-brain functional network in seven decades (8–79 years) of the human lifespan. We first used parametric curve fitting to examine linear and nonlinear age effect on the resting human brain, and then combined manifold learning and support vector machine methods to predict individuals' “brain ages” from rs-fcMRI data. We found that age-related changes in interregional functional connectivity exhibited spatially and temporally specific patterns. During brain development from childhood to senescence, functional connections tended to linearly increase in the emotion system and decrease in the sensorimotor system; while quadratic trajectories were observed in functional connections related to higher-order cognitive functions. The complex patterns of age effect on the whole-brain functional network could be effectively represented by a low-dimensional, nonlinear manifold embedded in the functional connectivity space, which uncovered the inherent structure of brain maturation and aging. Regression of manifold coordinates with age further showed that the manifold representation extracted sufficient information from rs-fcMRI data to make prediction about individual brains' functional development levels. Our study not only gives insights into the neural substrates that underlie behavioral and cognitive changes over age, but also provides a possible way to quantitatively describe the typical and atypical developmental progression of human brain function using rs-fcMRI. PMID:22952990

Decoding lifespan changes of the human brain using resting-state functional connectivity MRI.

PubMed

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

2012-01-01

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

Brain networks and their origins. Comment on “Understanding brain networks and brain organization” by Luiz Pessoa

NASA Astrophysics Data System (ADS)

Cisek, Paul

2014-09-01

Nearly every textbook on psychology or neuroscience contains theories of function described with box and arrow diagrams. Sometimes, the boxes stand for purely theoretical constructs, such as attention or working memory, and sometimes they also correspond to specific brain regions or systems, such as parietal or prefrontal cortex, and the arrows between them to known anatomical pathways. It is common for scientists (present company included) to summarize their theories in this way and to think of the brain as a set of interacting modules with clearly distinguishable functions.

Human brain networks function in connectome-specific harmonic waves.

PubMed

Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

2016-01-21

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

Functional brain networks reconstruction using group sparsity-regularized learning.

PubMed

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

2018-06-01

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

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

PubMed

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

2011-09-27

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

Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z

PubMed Central

Badgaiyan, Rajendra D.; Thanos, Panayotis K.; Kulkarni, Praveen; Giordano, John; Baron, David; Gold, Mark S.

2017-01-01

Dopaminergic reward dysfunction in addictive behaviors is well supported in the literature. There is evidence that alterations in synchronous neural activity between brain regions subserving reward and various cognitive functions may significantly contribute to substance-related disorders. This study presents the first evidence showing that a pro-dopaminergic nutraceutical (KB220Z) significantly enhances, above placebo, functional connectivity between reward and cognitive brain areas in the rat. These include the nucleus accumbens, anterior cingulate gyrus, anterior thalamic nuclei, hippocampus, prelimbic and infralimbic loci. Significant functional connectivity, increased brain connectivity volume recruitment (potentially neuroplasticity), and dopaminergic functionality were found across the brain reward circuitry. Increases in functional connectivity were specific to these regions and were not broadly distributed across the brain. While these initial findings have been observed in drug naïve rodents, this robust, yet selective response implies clinical relevance for addicted individuals at risk for relapse, who show reductions in functional connectivity after protracted withdrawal. Future studies will evaluate KB220Z in animal models of addiction. PMID:28445527

Musical training influences linguistic abilities in 8-year-old children: more evidence for brain plasticity.

PubMed

Moreno, Sylvain; Marques, Carlos; Santos, Andreia; Santos, Manuela; Castro, São Luís; Besson, Mireille

2009-03-01

We conducted a longitudinal study with 32 nonmusician children over 9 months to determine 1) whether functional differences between musician and nonmusician children reflect specific predispositions for music or result from musical training and 2) whether musical training improves nonmusical brain functions such as reading and linguistic pitch processing. Event-related brain potentials were recorded while 8-year-old children performed tasks designed to test the hypothesis that musical training improves pitch processing not only in music but also in speech. Following the first testing sessions nonmusician children were pseudorandomly assigned to music or to painting training for 6 months and were tested again after training using the same tests. After musical (but not painting) training, children showed enhanced reading and pitch discrimination abilities in speech. Remarkably, 6 months of musical training thus suffices to significantly improve behavior and to influence the development of neural processes as reflected in specific pattern of brain waves. These results reveal positive transfer from music to speech and highlight the influence of musical training. Finally, they demonstrate brain plasticity in showing that relatively short periods of training have strong consequences on the functional organization of the children's brain.

Cortical thickness and surface area correlates with cognitive dysfunction among first-episode psychosis patients.

PubMed

Haring, L; Müürsepp, A; Mõttus, R; Ilves, P; Koch, K; Uppin, K; Tarnovskaja, J; Maron, E; Zharkovsky, A; Vasar, E; Vasar, V

2016-07-01

In studies using magnetic resonance imaging (MRI), some have reported specific brain structure-function relationships among first-episode psychosis (FEP) patients, but findings are inconsistent. We aimed to localize the brain regions where cortical thickness (CTh) and surface area (cortical area; CA) relate to neurocognition, by performing an MRI on participants and measuring their neurocognitive performance using the Cambridge Neuropsychological Test Automated Battery (CANTAB), in order to investigate any significant differences between FEP patients and control subjects (CS). Exploration of potential correlations between specific cognitive functions and brain structure was performed using CANTAB computer-based neurocognitive testing and a vertex-by-vertex whole-brain MRI analysis of 63 FEP patients and 30 CS. Significant correlations were found between cortical parameters in the frontal, temporal, cingular and occipital brain regions and performance in set-shifting, working memory manipulation, strategy usage and sustained attention tests. These correlations were significantly dissimilar between FEP patients and CS. Significant correlations between CTh and CA with neurocognitive performance were localized in brain areas known to be involved in cognition. The results also suggested a disrupted structure-function relationship in FEP patients compared with CS.

Advantages in functional imaging of the brain.

PubMed

Mier, Walter; Mier, Daniela

2015-01-01

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

Analysis of structure-function network decoupling in the brain systems of spastic diplegic cerebral palsy.

PubMed

Lee, Dongha; Pae, Chongwon; Lee, Jong Doo; Park, Eun Sook; Cho, Sung-Rae; Um, Min-Hee; Lee, Seung-Koo; Oh, Maeng-Keun; Park, Hae-Jeong

2017-10-01

Manifestation of the functionalities from the structural brain network is becoming increasingly important to understand a brain disease. With the aim of investigating the differential structure-function couplings according to network systems, we investigated the structural and functional brain networks of patients with spastic diplegic cerebral palsy with periventricular leukomalacia compared to healthy controls. The structural and functional networks of the whole brain and motor system, constructed using deterministic and probabilistic tractography of diffusion tensor magnetic resonance images and Pearson and partial correlation analyses of resting-state functional magnetic resonance images, showed differential embedding of functional networks in the structural networks in patients. In the whole-brain network of patients, significantly reduced global network efficiency compared to healthy controls were found in the structural networks but not in the functional networks, resulting in reduced structural-functional coupling. On the contrary, the motor network of patients had a significantly lower functional network efficiency over the intact structural network and a lower structure-function coupling than the control group. This reduced coupling but reverse directionality in the whole-brain and motor networks of patients was prominent particularly between the probabilistic structural and partial correlation-based functional networks. Intact (or less deficient) functional network over impaired structural networks of the whole brain and highly impaired functional network topology over the intact structural motor network might subserve relatively preserved cognitions and impaired motor functions in cerebral palsy. This study suggests that the structure-function relationship, evaluated specifically using sparse functional connectivity, may reveal important clues to functional reorganization in cerebral palsy. Hum Brain Mapp 38:5292-5306, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

2016-11-03

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

Meta-analysis of functional brain imaging in specific phobia.

PubMed

Ipser, Jonathan C; Singh, Leesha; Stein, Dan J

2013-07-01

Although specific phobia is a prevalent anxiety disorder, evidence regarding its underlying functional neuroanatomy is inconsistent. A meta-analysis was undertaken to identify brain regions that were consistently responsive to phobic stimuli, and to characterize changes in brain activation following cognitive behavioral therapy (CBT). We searched the PubMed, SCOPUS and PsycINFO databases to identify positron emission tomography and functional magnetic resonance imaging studies comparing brain activation in specific phobia patients and healthy controls. Two raters independently extracted study data from all the eligible studies, and pooled coordinates from these studies using activation likelihood estimation, a quantitative meta-analytic technique. Resulting statistical parametric maps were compared between patients and healthy controls, in response to phobic versus fear-evoking stimuli, and before and after therapy. Thirteen studies were included, comprising 327 participants. Regions that were consistently activated in response to phobic stimuli included the left insula, amygdala, and globus pallidus. Compared to healthy controls, phobic subjects had increased activation in response to phobic stimuli in the left amygdala/globus pallidus, left insula, right thalamus (pulvinar), and cerebellum. Following exposure-based therapy widespread deactivation was observed in the right frontal cortex, limbic cortex, basal ganglia and cerebellum, with increased activation detected in the thalamus. Exposure to phobia-specific stimuli elicits brain activation that is consistent with current understandings of the neuroanatomy of fear conditioning and extinction. There is evidence that the effects of CBT in specific phobia may be mediated through the same underlying neurocircuitry. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Circular RNA: a new star in neurological diseases.

PubMed

Li, Tao-Ran; Jia, Yan-Jie; Wang, Qun; Shao, Xiao-Qiu; Lv, Rui-Juan

2017-08-01

Circular RNAs (circRNAs) are novel endogenous non-coding RNAs characterized by the presence of a covalent bond linking the 3' and 5' ends generated by backsplicing. In this review, we summarize a number of the latest theories regarding the biogenesis, properties and functions of circRNAs. Specifically, we focus on the advancing characteristics and functions of circRNAs in the brain and neurological diseases. CircRNAs exhibit the characteristics of species conservation, abundance and tissue/developmental-stage-specific expression in the brain. We also describe the relationship between circRNAs and several neurological diseases and highlight their functions in neurological diseases.

Neuroendocrine tests of monoamine function in man: a review of basic theory and its application to the study of depressive illness.

PubMed

Checkley, S A

1980-02-01

Neuroendocrine tests are now available for studying monoamine function in the brains of patients with mental illness. Great care is required in the selection of drugs which act upon specific monoamine receptors to produce specific hormonal responses. Equal care is required in the control of biological variables which may influence hormonal release. Recently reported neuroendocrine studies of depressive illness are assessed in these terms. The results of these studies support the hypothesis that there is defective noradrenergic function in the brains of some patients with depressive illness.

Modafinil Reverses Phencyclidine-Induced Deficits in Cognitive Flexibility, Cerebral Metabolism, and Functional Brain Connectivity

PubMed Central

Dawson, Neil; Thompson, Rhiannon J.; McVie, Allan; Thomson, David M.; Morris, Brian J.; Pratt, Judith A.

2012-01-01

Objective: In the present study, we employ mathematical modeling (partial least squares regression, PLSR) to elucidate the functional connectivity signatures of discrete brain regions in order to identify the functional networks subserving PCP-induced disruption of distinct cognitive functions and their restoration by the procognitive drug modafinil. Methods: We examine the functional connectivity signatures of discrete brain regions that show overt alterations in metabolism, as measured by semiquantitative 2-deoxyglucose autoradiography, in an animal model (subchronic phencyclidine [PCP] treatment), which shows cognitive inflexibility with relevance to the cognitive deficits seen in schizophrenia. Results: We identify the specific components of functional connectivity that contribute to the rescue of this cognitive inflexibility and to the restoration of overt cerebral metabolism by modafinil. We demonstrate that modafinil reversed both the PCP-induced deficit in the ability to switch attentional set and the PCP-induced hypometabolism in the prefrontal (anterior prelimbic) and retrosplenial cortices. Furthermore, modafinil selectively enhanced metabolism in the medial prelimbic cortex. The functional connectivity signatures of these regions identified a unifying functional subsystem underlying the influence of modafinil on cerebral metabolism and cognitive flexibility that included the nucleus accumbens core and locus coeruleus. In addition, these functional connectivity signatures identified coupling events specific to each brain region, which relate to known anatomical connectivity. Conclusions: These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction. PMID:20810469

[Neuropsychological evaluation of a case of organic personality disorder due to penetrating brain injury].

PubMed

Sanz de la Torre, J C; Pérez-Ríos, M

1996-06-01

In this paper, an organic personality disorder case by penetrating brain injury, predominantly localized in the right frontal lobe, is presented. Neuropsychological and neuroimaging (CT scan studies) were performed. We assessed the main cognitive aspect: orientation, attention, memory, intelligence, language, visual-spatial functioning, motor functioning, executive functioning and personality. The results obtained, point out disorders in the patient's behavior and in the executive functions. Likewise, other cognitive functions as: attention, memory, language and visual-spatial functioning, show specific deficits.

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

ERIC Educational Resources Information Center

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

2008-01-01

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

Joint Analysis of Band-Specific Functional Connectivity and Signal Complexity in Autism

ERIC Educational Resources Information Center

Ghanbari, Yasser; Bloy, Luke; Edgar, J. Christopher; Blaskey, Lisa; Verma, Ragini; Roberts, Timothy P. L.

2015-01-01

Examination of resting state brain activity using electrophysiological measures like complexity as well as functional connectivity is of growing interest in the study of autism spectrum disorders (ASD). The present paper jointly examined complexity and connectivity to obtain a more detailed characterization of resting state brain activity in ASD.…

Left and Right Hemisphere Brain Functions and Symbolic vs. Spontaneous Communication Processes.

ERIC Educational Resources Information Center

Buck, Ross

Recent findings on the communicative functions of the left versus the right hemisphere of the brain may suggest that there is a distinction between the intentional use of symbols for the sending of specific messages or propositions (language, signing, pantomime) and spontaneous expressive behaviors that signal their meaning through a natural…

Face Patch Resting State Networks Link Face Processing to Social Cognition

PubMed Central

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

2015-01-01

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

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

PubMed Central

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

2009-01-01

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

On the integrity of functional brain networks in schizophrenia, Parkinson's disease, and advanced age: Evidence from connectivity-based single-subject classification.

PubMed

Pläschke, Rachel N; Cieslik, Edna C; Müller, Veronika I; Hoffstaedter, Felix; Plachti, Anna; Varikuti, Deepthi P; Goosses, Mareike; Latz, Anne; Caspers, Svenja; Jockwitz, Christiane; Moebus, Susanne; Gruber, Oliver; Eickhoff, Claudia R; Reetz, Kathrin; Heller, Julia; Südmeyer, Martin; Mathys, Christian; Caspers, Julian; Grefkes, Christian; Kalenscher, Tobias; Langner, Robert; Eickhoff, Simon B

2017-12-01

Previous whole-brain functional connectivity studies achieved successful classifications of patients and healthy controls but only offered limited specificity as to affected brain systems. Here, we examined whether the connectivity patterns of functional systems affected in schizophrenia (SCZ), Parkinson's disease (PD), or normal aging equally translate into high classification accuracies for these conditions. We compared classification performance between pre-defined networks for each group and, for any given network, between groups. Separate support vector machine classifications of 86 SCZ patients, 80 PD patients, and 95 older adults relative to their matched healthy/young controls, respectively, were performed on functional connectivity in 12 task-based, meta-analytically defined networks using 25 replications of a nested 10-fold cross-validation scheme. Classification performance of the various networks clearly differed between conditions, as those networks that best classified one disease were usually non-informative for the other. For SCZ, but not PD, emotion-processing, empathy, and cognitive action control networks distinguished patients most accurately from controls. For PD, but not SCZ, networks subserving autobiographical or semantic memory, motor execution, and theory-of-mind cognition yielded the best classifications. In contrast, young-old classification was excellent based on all networks and outperformed both clinical classifications. Our pattern-classification approach captured associations between clinical and developmental conditions and functional network integrity with a higher level of specificity than did previous whole-brain analyses. Taken together, our results support resting-state connectivity as a marker of functional dysregulation in specific networks known to be affected by SCZ and PD, while suggesting that aging affects network integrity in a more global way. Hum Brain Mapp 38:5845-5858, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Brain dynamics in ASD during movie-watching show idiosyncratic functional integration and segregation.

PubMed

Bolton, Thomas A W; Jochaut, Delphine; Giraud, Anne-Lise; Van De Ville, Dimitri

2018-06-01

To refine our understanding of autism spectrum disorders (ASD), studies of the brain in dynamic, multimodal and ecological experimental settings are required. One way to achieve this is to compare the neural responses of ASD and typically developing (TD) individuals when viewing a naturalistic movie, but the temporal complexity of the stimulus hampers this task, and the presence of intrinsic functional connectivity (FC) may overshadow movie-driven fluctuations. Here, we detected inter-subject functional correlation (ISFC) transients to disentangle movie-induced functional changes from underlying resting-state activity while probing FC dynamically. When considering the number of significant ISFC excursions triggered by the movie across the brain, connections between remote functional modules were more heterogeneously engaged in the ASD population. Dynamically tracking the temporal profiles of those ISFC changes and tying them to specific movie subparts, this idiosyncrasy in ASD responses was then shown to involve functional integration and segregation mechanisms such as response inhibition, background suppression, or multisensory integration, while low-level visual processing was spared. Through the application of a new framework for the study of dynamic experimental paradigms, our results reveal a temporally localized idiosyncrasy in ASD responses, specific to short-lived episodes of long-range functional interplays. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Low frequency steady-state brain responses modulate large scale functional networks in a frequency-specific means.

PubMed

Wang, Yi-Feng; Long, Zhiliang; Cui, Qian; Liu, Feng; Jing, Xiu-Juan; Chen, Heng; Guo, Xiao-Nan; Yan, Jin H; Chen, Hua-Fu

2016-01-01

Neural oscillations are essential for brain functions. Research has suggested that the frequency of neural oscillations is lower for more integrative and remote communications. In this vein, some resting-state studies have suggested that large scale networks function in the very low frequency range (<1 Hz). However, it is difficult to determine the frequency characteristics of brain networks because both resting-state studies and conventional frequency tagging approaches cannot simultaneously capture multiple large scale networks in controllable cognitive activities. In this preliminary study, we aimed to examine whether large scale networks can be modulated by task-induced low frequency steady-state brain responses (lfSSBRs) in a frequency-specific pattern. In a revised attention network test, the lfSSBRs were evoked in the triple network system and sensory-motor system, indicating that large scale networks can be modulated in a frequency tagging way. Furthermore, the inter- and intranetwork synchronizations as well as coherence were increased at the fundamental frequency and the first harmonic rather than at other frequency bands, indicating a frequency-specific modulation of information communication. However, there was no difference among attention conditions, indicating that lfSSBRs modulate the general attention state much stronger than distinguishing attention conditions. This study provides insights into the advantage and mechanism of lfSSBRs. More importantly, it paves a new way to investigate frequency-specific large scale brain activities. © 2015 Wiley Periodicals, Inc.

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

NASA Astrophysics Data System (ADS)

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

2014-02-01

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

Nuclear receptor coactivators: regulators of steroid action in brain and behaviour.

PubMed

Tetel, M J; Acharya, K D

2013-11-01

Steroid hormones act in specific regions of the brain to alter behaviour and physiology. Although it has been well established that the bioavailability of the steroid and the expression of its receptor is critical for understanding steroid action in the brain, the importance of nuclear receptor coactivators in the brain is becoming more apparent. The present review focuses on the function of the p160 family of coactivators, which includes steroid receptor coactivator-1 (SRC-1), SRC-2 and SRC-3, in steroid receptor action in the brain. The expression, regulation and function of these coactivators in steroid-dependent gene expression in both brain and behaviour are discussed. © 2013 British Society for Neuroendocrinology.

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

Toward Developmental Connectomics of the Human Brain

PubMed Central

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

2016-01-01

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

Mitochondrial Chaperones in the Brain: Safeguarding Brain Health and Metabolism?

PubMed

Castro, José Pedro; Wardelmann, Kristina; Grune, Tilman; Kleinridders, André

2018-01-01

The brain orchestrates organ function and regulates whole body metabolism by the concerted action of neurons and glia cells in the central nervous system. To do so, the brain has tremendously high energy consumption and relies mainly on glucose utilization and mitochondrial function in order to exert its function. As a consequence of high rate metabolism, mitochondria in the brain accumulate errors over time, such as mitochondrial DNA (mtDNA) mutations, reactive oxygen species, and misfolded and aggregated proteins. Thus, mitochondria need to employ specific mechanisms to avoid or ameliorate the rise of damaged proteins that contribute to aberrant mitochondrial function and oxidative stress. To maintain mitochondria homeostasis (mitostasis), cells evolved molecular chaperones that shuttle, refold, or in coordination with proteolytic systems, help to maintain a low steady-state level of misfolded/aggregated proteins. Their importance is exemplified by the occurrence of various brain diseases which exhibit reduced action of chaperones. Chaperone loss (expression and/or function) has been observed during aging, metabolic diseases such as type 2 diabetes and in neurodegenerative diseases such as Alzheimer's (AD), Parkinson's (PD) or even Huntington's (HD) diseases, where the accumulation of damage proteins is evidenced. Within this perspective, we propose that proper brain function is maintained by the joint action of mitochondrial chaperones to ensure and maintain mitostasis contributing to brain health, and that upon failure, alter brain function which can cause metabolic diseases.

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

PubMed Central

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

2010-01-01

Investigators have linked rare copy number variation (CNVs) to neuropsychiatric diseases, such as schizophrenia. One hypothesis is that CNV events cause disease by affecting genes with specific brain functions. Under these circumstances, we expect that CNV events in cases should impact brain-function genes more frequently than those events in controls. Previous publications have applied “pathway” analyses to genes within neuropsychiatric case CNVs to show enrichment for brain-functions. While such analyses have been suggestive, they often have not rigorously compared the rates of CNVs impacting genes with brain function in cases to controls, and therefore do not address important confounders such as the large size of brain genes and overall differences in rates and sizes of CNVs. To demonstrate the potential impact of confounders, we genotyped rare CNV events in 2,415 unaffected controls with Affymetrix 6.0; we then applied standard pathway analyses using four sets of brain-function genes and observed an apparently highly significant enrichment for each set. The enrichment is simply driven by the large size of brain-function genes. Instead, we propose a case-control statistical test, cnv-enrichment-test, to compare the rate of CNVs impacting specific gene sets in cases versus controls. With simulations, we demonstrate that cnv-enrichment-test is robust to case-control differences in CNV size, CNV rate, and systematic differences in gene size. Finally, we apply cnv-enrichment-test to rare CNV events published by the International Schizophrenia Consortium (ISC). This approach reveals nominal evidence of case-association in neuronal-activity and the learning gene sets, but not the other two examined gene sets. The neuronal-activity genes have been associated in a separate set of schizophrenia cases and controls; however, testing in independent samples is necessary to definitively confirm this association. Our method is implemented in the PLINK software package. PMID:20838587

Sex-Specific Patterns of Aberrant Brain Function in First-Episode Treatment-Naive Patients with Schizophrenia.

PubMed

Lei, Wei; Li, Mingli; Deng, Wei; Zhou, Yi; Ma, Xiaohong; Wang, Qiang; Guo, Wanjun; Li, Yinfei; Jiang, Lijun; Han, Yuanyuan; Huang, Chaohua; Hu, Xun; Li, Tao

2015-07-16

Male and female patients with schizophrenia show significant differences in a number of important clinical features, yet the neural substrates of these differences are still poorly understood. Here we explored the sex differences in the brain functional aberrations in 124 treatment-naïve patients with first-episode schizophrenia (61 males), compared with 102 age-matched healthy controls (50 males). Maps of degree centrality (DC) and amplitude of low-frequency fluctuations (ALFF) were constructed using resting-state functional magnetic resonance imaging data and compared between groups. We found that: (1) Selective DC reduction was observed in the right putamen (Put_R) in male patients and the left middle frontal gyrus (MFG) in female patients; (2) Functional connectivity analysis (using Put_R and MFG as seeds) found that male and female patients have disturbed functional integration in two separate networks, i.e., the sensorimotor network and the default mode network; (3) Significant ALFF alterations were also observed in these two networks in both genders; (4) Sex specific brain functional alterations were associated with various symptoms in patients. These results suggested that sex-specific patterns of functional aberration existed in schizophrenia, and these patterns were associated with the clinical features both in male and female patients.

TALE transcription factors during early development of the vertebrate brain and eye.

PubMed

Schulte, Dorothea; Frank, Dale

2014-01-01

Our brain's cognitive performance arises from the coordinated activities of billions of nerve cells. Despite a high degree of morphological and functional differences, all neurons of the vertebrate central nervous system (CNS) arise from a common field of multipotent progenitors. Cell fate specification and differentiation are directed by multistep processes that include inductive/external cues, such as the extracellular matrix or growth factors, and cell-intrinsic determinants, such as transcription factors and epigenetic modulators of proteins and DNA. Here we review recent findings implicating TALE-homeodomain proteins in these processes. Although originally identified as HOX-cofactors, TALE proteins also contribute to many physiological processes that do not require HOX-activity. Particular focus is, therefore, given to HOX-dependent and -independent functions of TALE proteins during early vertebrate brain development. Additionally, we provide an overview about known upstream and downstream factors of TALE proteins in the developing vertebrate brain and discuss general concepts of how TALE proteins function to modulate neuronal cell fate specification. Copyright © 2013 Wiley Periodicals, Inc.

Nutritional Supplements and the Brain.

PubMed

Meeusen, Romain; Decroix, Lieselot

2018-03-01

Cognitive function plays an important role in athletic performance, and it seems that brain functioning can be influenced by nutrition and dietary components. Thus, the central nervous system might be manipulated through changes in diet or supplementation with specific nutrients including branched-chain amino acids, tyrosine, carbohydrates, and caffeine. Despite some evidence that branched-chained amino acids can influence ratings of perceived exertion and mental performance, several well-controlled studies have failed to demonstrate a positive effect on exercise performance. Evidence of an ergogenic benefit of tyrosine supplementation during prolonged exercise is limited. There is evidence that mild dehydration can impair cognitive performance and mood. The beneficial effect of carbohydrate supplementation during prolonged exercise could relate to increased substrate delivery for the brain, with numerous studies indicating that hypoglycemia affects brain function and cognitive performance. Caffeine can enhance performance and reduce perception of effort during prolonged exercise and will influence specific reward centers of the brain. Plant products and herbal extracts such as polyphenols, ginseng, ginkgo biloba, etc. are marketed as supplements to enhance performance. In several animal studies, positive effects of these products were shown, however the literature on their effects on sports performance is scarce. Polyphenols have the potential to protect neurons against injury induced by neurotoxins, suppress neuroinflammation, and to promote memory, learning, and cognitive function. In general, there remains a need for controlled randomized studies with a strong design, sufficient statistical power, and well-defined outcome measures before "claims" on its beneficial effects on brain functioning can be established.

Gender similarities and differences in brain activation strategies: Voxel-based meta-analysis on fMRI studies.

PubMed

AlRyalat, Saif Aldeen

2017-01-01

Gender similarities and differences have long been a matter of debate in almost all human research, especially upon reaching the discussion about brain functions. This large scale meta-analysis was performed on functional MRI studies. It included more than 700 active brain foci from more than 70 different experiments to study gender related similarities and differences in brain activation strategies for three of the main brain functions: Visual-spatial cognition, memory, and emotion. Areas that are significantly activated by both genders (i.e. core areas) for the tested brain function are mentioned, whereas those areas significantly activated exclusively in one gender are the gender specific areas. During visual-spatial cognition task, and in addition to the core areas, males significantly activated their left superior frontal gyrus, compared with left superior parietal lobule in females. For memory tasks, several different brain areas activated by each gender, but females significantly activated two areas from the limbic system during memory retrieval tasks. For emotional task, males tend to recruit their bilateral prefrontal regions, whereas females tend to recruit their bilateral amygdalae. This meta-analysis provides an overview based on functional MRI studies on how males and females use their brain.

Exploring time- and frequency- dependent functional connectivity and brain networks during deception with single-trial event-related potentials

NASA Astrophysics Data System (ADS)

Gao, Jun-Feng; Yang, Yong; Huang, Wen-Tao; Lin, Pan; Ge, Sheng; Zheng, Hong-Mei; Gu, Ling-Yun; Zhou, Hui; Li, Chen-Hong; Rao, Ni-Ni

2016-11-01

To better characterize the cognitive processes and mechanisms that are associated with deception, wavelet coherence was employed to evaluate functional connectivity between different brain regions. Two groups of subjects were evaluated for this purpose: 32 participants were required to either tell the truth or to lie when facing certain stimuli, and their electroencephalogram signals on 12 electrodes were recorded. The experimental results revealed that deceptive responses elicited greater connectivity strength than truthful responses, particularly in the θ band on specific electrode pairs primarily involving connections between the prefrontal/frontal and central regions and between the prefrontal/frontal and left parietal regions. These results indicate that these brain regions play an important role in executing lying responses. Additionally, three time- and frequency-dependent functional connectivity networks were proposed to thoroughly reflect the functional coupling of brain regions that occurs during lying. Furthermore, the wavelet coherence values for the connections shown in the networks were extracted as features for support vector machine training. High classification accuracy suggested that the proposed network effectively characterized differences in functional connectivity between the two groups of subjects over a specific time-frequency area and hence could be a sensitive measurement for identifying deception.

Genes and Social Behavior

PubMed Central

Robinson, Gene E.; Fernald, Russell D.; Clayton, David F.

2011-01-01

What specific genes and regulatory sequences contribute to the organization and functioning of brain circuits that support social behavior? How does social experience interact with information in the genome to modulate these brain circuits? Here we address these questions by highlighting progress that has been made in identifying and understanding two key “vectors of influence” that link genes, brain, and social behavior: 1) social information alters gene readout in the brain to influence behavior; and 2) genetic variation influences brain function and social behavior. We also briefly discuss how evolutionary changes in genomic elements influence social behavior and outline prospects for a systems biology of social behavior. PMID:18988841

Effects of different correlation metrics and preprocessing factors on small-world brain functional networks: a resting-state functional MRI study.

PubMed

Liang, Xia; Wang, Jinhui; Yan, Chaogan; Shu, Ni; Xu, Ke; Gong, Gaolang; He, Yong

2012-01-01

Graph theoretical analysis of brain networks based on resting-state functional MRI (R-fMRI) has attracted a great deal of attention in recent years. These analyses often involve the selection of correlation metrics and specific preprocessing steps. However, the influence of these factors on the topological properties of functional brain networks has not been systematically examined. Here, we investigated the influences of correlation metric choice (Pearson's correlation versus partial correlation), global signal presence (regressed or not) and frequency band selection [slow-5 (0.01-0.027 Hz) versus slow-4 (0.027-0.073 Hz)] on the topological properties of both binary and weighted brain networks derived from them, and we employed test-retest (TRT) analyses for further guidance on how to choose the "best" network modeling strategy from the reliability perspective. Our results show significant differences in global network metrics associated with both correlation metrics and global signals. Analysis of nodal degree revealed differing hub distributions for brain networks derived from Pearson's correlation versus partial correlation. TRT analysis revealed that the reliability of both global and local topological properties are modulated by correlation metrics and the global signal, with the highest reliability observed for Pearson's-correlation-based brain networks without global signal removal (WOGR-PEAR). The nodal reliability exhibited a spatially heterogeneous distribution wherein regions in association and limbic/paralimbic cortices showed moderate TRT reliability in Pearson's-correlation-based brain networks. Moreover, we found that there were significant frequency-related differences in topological properties of WOGR-PEAR networks, and brain networks derived in the 0.027-0.073 Hz band exhibited greater reliability than those in the 0.01-0.027 Hz band. Taken together, our results provide direct evidence regarding the influences of correlation metrics and specific preprocessing choices on both the global and nodal topological properties of functional brain networks. This study also has important implications for how to choose reliable analytical schemes in brain network studies.

Brain serotonergic circuitries

PubMed Central

Charnay, Yves; Leger, Lucienne

2010-01-01

Brain serotonergic circuitries interact with other neurotransmitter systems on a multitude of different molecular levels. In humans, as in other mammalian species, serotonin (5-HT) plays a modulatory role in almost every physiological function. Furthermore, serotonergic dysfunction is thought to be implicated in several psychiatric and neurodegenerative disorders. We describe the neuroanatomy and neurochemistry of brain serotonergic circuitries. The contribution of emergent in vivo imaging methods to the regional localization of binding site receptors and certain aspects of their functional connectivity in correlation to behavior is also discussed. 5-HT cell bodies, mainly localized in the raphe nuclei, send axons to almost every brain region. It is argued that the specificity of the local chemocommunication between 5-HT and other neuronal elements mainly depends on mechanisms regulating the extracellular concentration of 5-HT, the diversity of high-affinity membrane receptors, and their specific transduction modalities. PMID:21319493

Genetic and epigenetic factors underlying sex differences in the regulation of gene expression in the brain

PubMed Central

Ratnu, Vikram S.; Emami, Michael R.; Bredy, Timothy W.

2016-01-01

There are inherent biological differences between males and females that contribute to sex differences in brain function and to many sex-specific illnesses and disorders. Traditionally, it has been thought that such differences are largely due to hormonal regulation; however, there are also genetic and epigenetic effects caused by the inheritance and unequal dosage of genes located on the X- and Y-chromosomes. Here we discuss the evidence in favor of a genetic and epigenetic basis for sexually dimorphic behavior, as a consequence of underlying differences in the regulation of genes that drive brain function. A better understanding of sex-specific molecular processes in the brain will provide further insight for the development of novel therapeutic approaches for the treatment of neuropsychiatric disorders characterized by gender/sex differences. PMID:27870402

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

ERIC Educational Resources Information Center

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

2004-01-01

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

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.

Network dysfunction predicts speech production after left hemisphere stroke.

PubMed

Geranmayeh, Fatemeh; Leech, Robert; Wise, Richard J S

2016-03-09

To investigate the role of multiple distributed brain networks, including the default mode, fronto-temporo-parietal, and cingulo-opercular networks, which mediate domain-general and task-specific processes during speech production after aphasic stroke. We conducted an observational functional MRI study to investigate the effects of a previous left hemisphere stroke on functional connectivity within and between distributed networks as patients described pictures. Study design included various baseline tasks, and we compared results to those of age-matched healthy participants performing the same tasks. We used independent component and psychophysiological interaction analyses. Although activity within individual networks was not predictive of speech production, relative activity between networks was a predictor of both within-scanner and out-of-scanner language performance, over and above that predicted from lesion volume, age, sex, and years of education. Specifically, robust functional imaging predictors were the differential activity between the default mode network and both the left and right fronto-temporo-parietal networks, respectively activated and deactivated during speech. We also observed altered between-network functional connectivity of these networks in patients during speech production. Speech production is dependent on complex interactions among widely distributed brain networks, indicating that residual speech production after stroke depends on more than the restoration of local domain-specific functions. Our understanding of the recovery of function following focal lesions is not adequately captured by consideration of ipsilesional or contralesional brain regions taking over lost domain-specific functions, but is perhaps best considered as the interaction between what remains of domain-specific networks and domain-general systems that regulate behavior. © 2016 American Academy of Neurology.

Network dysfunction predicts speech production after left hemisphere stroke

PubMed Central

Leech, Robert; Wise, Richard J.S.

2016-01-01

Objective: To investigate the role of multiple distributed brain networks, including the default mode, fronto-temporo-parietal, and cingulo-opercular networks, which mediate domain-general and task-specific processes during speech production after aphasic stroke. Methods: We conducted an observational functional MRI study to investigate the effects of a previous left hemisphere stroke on functional connectivity within and between distributed networks as patients described pictures. Study design included various baseline tasks, and we compared results to those of age-matched healthy participants performing the same tasks. We used independent component and psychophysiological interaction analyses. Results: Although activity within individual networks was not predictive of speech production, relative activity between networks was a predictor of both within-scanner and out-of-scanner language performance, over and above that predicted from lesion volume, age, sex, and years of education. Specifically, robust functional imaging predictors were the differential activity between the default mode network and both the left and right fronto-temporo-parietal networks, respectively activated and deactivated during speech. We also observed altered between-network functional connectivity of these networks in patients during speech production. Conclusions: Speech production is dependent on complex interactions among widely distributed brain networks, indicating that residual speech production after stroke depends on more than the restoration of local domain-specific functions. Our understanding of the recovery of function following focal lesions is not adequately captured by consideration of ipsilesional or contralesional brain regions taking over lost domain-specific functions, but is perhaps best considered as the interaction between what remains of domain-specific networks and domain-general systems that regulate behavior. PMID:26962070

Sex steroid hormones and brain function: PET imaging as a tool for research.

PubMed

Moraga-Amaro, R; van Waarde, A; Doorduin, J; de Vries, E F J

2018-02-01

Sex steroid hormones are major regulators of sexual characteristic among species. These hormones, however, are also produced in the brain. Steroidal hormone-mediated signalling via the corresponding hormone receptors can influence brain function at the cellular level and thus affect behaviour and higher brain functions. Altered steroid hormone signalling has been associated with psychiatric disorders, such as anxiety and depression. Neurosteroids are also considered to have a neuroprotective effect in neurodegenerative diseases. So far, the role of steroid hormone receptors in physiological and pathological conditions has mainly been investigated post mortem on animal or human brain tissues. To study the dynamic interplay between sex steroids, their receptors, brain function and behaviour in psychiatric and neurological disorders in a longitudinal manner, however, non-invasive techniques are needed. Positron emission tomography (PET) is a non-invasive imaging tool that is used to quantitatively investigate a variety of physiological and biochemical parameters in vivo. PET uses radiotracers aimed at a specific target (eg, receptor, enzyme, transporter) to visualise the processes of interest. In this review, we discuss the current status of the use of PET imaging for studying sex steroid hormones in the brain. So far, PET has mainly been investigated as a tool to measure (changes in) sex hormone receptor expression in the brain, to measure a key enzyme in the steroid synthesis pathway (aromatase) and to evaluate the effects of hormonal treatment by imaging specific downstream processes in the brain. Although validated radiotracers for a number of targets are still warranted, PET can already be a useful technique for steroid hormone research and facilitate the translation of interesting findings in animal studies to clinical trials in patients. © 2017 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.

Oxytocin And Vasopressin Modulation Of The Neural Correlates Of Motivation And Emotion: Results From Functional MRI Studies In Awake Rats

PubMed Central

Febo, Marcelo; Ferris, Craig F.

2014-01-01

Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings. Oxytocin is released within the lactating rat brain during suckling stimulation and activates specific subcortical networks in the maternal brain. Both vasopressin and oxytocin modulate brain regions involved unconditioned fear, processing of social stimuli and the expression of agonistic behaviors. Across studies there are relatively consistent brain networks associated with internal motivational drives and emotional states that are modulated by oxytocin and vasopressin. PMID:24486356

Resting state fMRI: A review on methods in resting state connectivity analysis and resting state networks.

PubMed

Smitha, K A; Akhil Raja, K; Arun, K M; Rajesh, P G; Thomas, Bejoy; Kapilamoorthy, T R; Kesavadas, Chandrasekharan

2017-08-01

The inquisitiveness about what happens in the brain has been there since the beginning of humankind. Functional magnetic resonance imaging is a prominent tool which helps in the non-invasive examination, localisation as well as lateralisation of brain functions such as language, memory, etc. In recent years, there is an apparent shift in the focus of neuroscience research to studies dealing with a brain at 'resting state'. Here the spotlight is on the intrinsic activity within the brain, in the absence of any sensory or cognitive stimulus. The analyses of functional brain connectivity in the state of rest have revealed different resting state networks, which depict specific functions and varied spatial topology. However, different statistical methods have been introduced to study resting state functional magnetic resonance imaging connectivity, yet producing consistent results. In this article, we introduce the concept of resting state functional magnetic resonance imaging in detail, then discuss three most widely used methods for analysis, describe a few of the resting state networks featuring the brain regions, associated cognitive functions and clinical applications of resting state functional magnetic resonance imaging. This review aims to highlight the utility and importance of studying resting state functional magnetic resonance imaging connectivity, underlining its complementary nature to the task-based functional magnetic resonance imaging.

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.

Local cerebral glucose metabolism in patients with long-term behavioral and cognitive deficits following mild traumatic brain injury.

PubMed

Gross, H; Kling, A; Henry, G; Herndon, C; Lavretsky, H

1996-01-01

A retrospective study of 20 patients with mild traumatic brain injury (MTBI) examined brain regions of interest by comparing [18F]-2-deoxyglucose PET, neuropsychological test results, and continuing behavioral dysfunction. Abnormal local cerebral metabolic rates (rLCMs) were most prominent in midtemporal, anterior cingulate, precuneus, anterior temporal, frontal white, and corpus callosum brain regions. Abnormal rLCMs were significantly correlated statistically with 1) overall clinical complaints, most specifically with inconsistent attention/concentration and 2) overall neuropsychological test results. The authors conclude that 1) even mild TBI may result in continuing brain behavioral deficits; 2) PET can help elucidate dysfunctional brain circuitry in neurobehavioral disorders; and 3) specific brain areas may correlate with deficits in daily neurobehavioral functioning and neuropsychological test findings.

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

PubMed

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

2013-10-01

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

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

PubMed

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

2018-06-18

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

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

PubMed Central

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

2013-01-01

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

Cerebral energy metabolism and the brain's functional network architecture: an integrative review.

PubMed

Lord, Louis-David; Expert, Paul; Huckins, Jeremy F; Turkheimer, Federico E

2013-09-01

Recent functional magnetic resonance imaging (fMRI) studies have emphasized the contributions of synchronized activity in distributed brain networks to cognitive processes in both health and disease. The brain's 'functional connectivity' is typically estimated from correlations in the activity time series of anatomically remote areas, and postulated to reflect information flow between neuronal populations. Although the topological properties of functional brain networks have been studied extensively, considerably less is known regarding the neurophysiological and biochemical factors underlying the temporal coordination of large neuronal ensembles. In this review, we highlight the critical contributions of high-frequency electrical oscillations in the γ-band (30 to 100 Hz) to the emergence of functional brain networks. After describing the neurobiological substrates of γ-band dynamics, we specifically discuss the elevated energy requirements of high-frequency neural oscillations, which represent a mechanistic link between the functional connectivity of brain regions and their respective metabolic demands. Experimental evidence is presented for the high oxygen and glucose consumption, and strong mitochondrial performance required to support rhythmic cortical activity in the γ-band. Finally, the implications of mitochondrial impairments and deficits in glucose metabolism for cognition and behavior are discussed in the context of neuropsychiatric and neurodegenerative syndromes characterized by large-scale changes in the organization of functional brain networks.

Age-related functional brain changes in young children.

PubMed

Long, Xiangyu; Benischek, Alina; Dewey, Deborah; Lebel, Catherine

2017-07-15

Brain function and structure change significantly during the toddler and preschool years. However, most studies focus on older or younger children, so the specific nature of these changes is unclear. In the present study, we analyzed 77 functional magnetic resonance imaging datasets from 44 children aged 2-6 years. We extracted measures of both local (amplitude of low frequency fluctuation and regional homogeneity) and global (eigenvector centrality mapping) activity and connectivity, and examined their relationships with age using robust linear correlation analysis and strict control for head motion. Brain areas within the default mode network and the frontoparietal network, such as the middle frontal gyrus, the inferior parietal lobule and the posterior cingulate cortex, showed increases in local and global functional features with age. Several brain areas such as the superior parietal lobule and superior temporal gyrus presented opposite development trajectories of local and global functional features, suggesting a shifting connectivity framework in early childhood. This development of functional connectivity in early childhood likely underlies major advances in cognitive abilities, including language and development of theory of mind. These findings provide important insight into the development patterns of brain function during the preschool years, and lay the foundation for future studies of altered brain development in young children with brain disorders or injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Targeted Knockdown of Bone Morphogenetic Protein Signaling within Neural Progenitors Protects the Brain and Improves Motor Function following Postnatal Hypoxia-Ischemia

PubMed Central

Dettman, Robert W.; Birch, Derin; Fernando, Augusta; Kessler, John A.; Dizon, Maria L.V.

2018-01-01

Hypoxic-ischemic injury (HI) to the neonatal human brain results in myelin loss that, in some children, can manifest as cerebral palsy. Previously, we had found that neuronal overexpression of the bone morphogenic protein (BMP) inhibitor noggin during development increased oligodendroglia and improved motor function in an experimental model of HI utilizing unilateral common carotid artery ligation followed by hypoxia. As BMPs are known to negatively regulate oligodendroglial fate specification of neural stem cells and alter differentiation of committed oligodendroglia, BMP signaling is likely an important mechanism leading to myelin loss. Here, we showed that BMP signaling is upregulated within oligodendroglia of the neonatal brain. We tested the hypothesis that inhibition of BMP signaling specifically within neural progenitor cells (NPCs) is sufficient to protect oligodendroglia. We conditionally deleted the BMP receptor 2 subtype (BMPR2) in NG2-expressing cells after HI. We found that BMPR2 deletion globally protects the brain as assessed by MRI and protects motor function as assessed by digital gait analysis, and that conditional deletion of BMPR2 maintains oligodendrocyte marker expression by immunofluorescence and Western blot and prevents loss of oligodendroglia. Finally, BMPR2 deletion after HI results in an increase in noncompacted myelin. Thus, our data indicate that inhibition of BMP signaling specifically in NPCs may be a tractable strategy to protect the newborn brain from HI. PMID:29324456

Educational games for brain health: revealing their unexplored potential through a neurocognitive approach.

PubMed

Fissler, Patrick; Kolassa, Iris-Tatjana; Schrader, Claudia

2015-01-01

Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control), and second, educational learning experiences (e.g., studying foreign languages) improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research.

Educational games for brain health: revealing their unexplored potential through a neurocognitive approach

PubMed Central

Fissler, Patrick; Kolassa, Iris-Tatjana; Schrader, Claudia

2015-01-01

Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control), and second, educational learning experiences (e.g., studying foreign languages) improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research. PMID:26257697

Search for Patterns of Functional Specificity in the Brain: A Nonparametric Hierarchical Bayesian Model for Group fMRI Data

PubMed Central

Sridharan, Ramesh; Vul, Edward; Hsieh, Po-Jang; Kanwisher, Nancy; Golland, Polina

2012-01-01

Functional MRI studies have uncovered a number of brain areas that demonstrate highly specific functional patterns. In the case of visual object recognition, small, focal regions have been characterized with selectivity for visual categories such as human faces. In this paper, we develop an algorithm that automatically learns patterns of functional specificity from fMRI data in a group of subjects. The method does not require spatial alignment of functional images from different subjects. The algorithm is based on a generative model that comprises two main layers. At the lower level, we express the functional brain response to each stimulus as a binary activation variable. At the next level, we define a prior over sets of activation variables in all subjects. We use a Hierarchical Dirichlet Process as the prior in order to learn the patterns of functional specificity shared across the group, which we call functional systems, and estimate the number of these systems. Inference based on our model enables automatic discovery and characterization of dominant and consistent functional systems. We apply the method to data from a visual fMRI study comprised of 69 distinct stimulus images. The discovered system activation profiles correspond to selectivity for a number of image categories such as faces, bodies, and scenes. Among systems found by our method, we identify new areas that are deactivated by face stimuli. In empirical comparisons with perviously proposed exploratory methods, our results appear superior in capturing the structure in the space of visual categories of stimuli. PMID:21884803

Modalities of Thinking: State and Trait Effects on Cross-Frequency Functional Independent Brain Networks.

PubMed

Milz, Patricia; Pascual-Marqui, Roberto D; Lehmann, Dietrich; Faber, Pascal L

2016-05-01

Functional states of the brain are constituted by the temporally attuned activity of spatially distributed neural networks. Such networks can be identified by independent component analysis (ICA) applied to frequency-dependent source-localized EEG data. This methodology allows the identification of networks at high temporal resolution in frequency bands of established location-specific physiological functions. EEG measurements are sensitive to neural activity changes in cortical areas of modality-specific processing. We tested effects of modality-specific processing on functional brain networks. Phasic modality-specific processing was induced via tasks (state effects) and tonic processing was assessed via modality-specific person parameters (trait effects). Modality-specific person parameters and 64-channel EEG were obtained from 70 male, right-handed students. Person parameters were obtained using cognitive style questionnaires, cognitive tests, and thinking modality self-reports. EEG was recorded during four conditions: spatial visualization, object visualization, verbalization, and resting. Twelve cross-frequency networks were extracted from source-localized EEG across six frequency bands using ICA. RMANOVAs, Pearson correlations, and path modelling examined effects of tasks and person parameters on networks. Results identified distinct state- and trait-dependent functional networks. State-dependent networks were characterized by decreased, trait-dependent networks by increased alpha activity in sub-regions of modality-specific pathways. Pathways of competing modalities showed opposing alpha changes. State- and trait-dependent alpha were associated with inhibitory and automated processing, respectively. Antagonistic alpha modulations in areas of competing modalities likely prevent intruding effects of modality-irrelevant processing. Considerable research suggested alpha modulations related to modality-specific states and traits. This study identified the distinct electrophysiological cortical frequency-dependent networks within which they operate.

Electrophysiological Source Imaging: A Noninvasive Window to Brain Dynamics.

PubMed

He, Bin; Sohrabpour, Abbas; Brown, Emery; Liu, Zhongming

2018-06-04

Brain activity and connectivity are distributed in the three-dimensional space and evolve in time. It is important to image brain dynamics with high spatial and temporal resolution. Electroencephalography (EEG) and magnetoencephalography (MEG) are noninvasive measurements associated with complex neural activations and interactions that encode brain functions. Electrophysiological source imaging estimates the underlying brain electrical sources from EEG and MEG measurements. It offers increasingly improved spatial resolution and intrinsically high temporal resolution for imaging large-scale brain activity and connectivity on a wide range of timescales. Integration of electrophysiological source imaging and functional magnetic resonance imaging could further enhance spatiotemporal resolution and specificity to an extent that is not attainable with either technique alone. We review methodological developments in electrophysiological source imaging over the past three decades and envision its future advancement into a powerful functional neuroimaging technology for basic and clinical neuroscience applications.

FMRI connectivity analysis of acupuncture effects on an amygdala-associated brain network

PubMed Central

Qin, Wei; Tian, Jie; Bai, Lijun; Pan, Xiaohong; Yang, Lin; Chen, Peng; Dai, Jianping; Ai, Lin; Zhao, Baixiao; Gong, Qiyong; Wang, Wei; von Deneen, Karen M; Liu, Yijun

2008-01-01

Background Recently, increasing evidence has indicated that the primary acupuncture effects are mediated by the central nervous system. However, specific brain networks underpinning these effects remain unclear. Results In the present study using fMRI, we employed a within-condition interregional covariance analysis method to investigate functional connectivity of brain networks involved in acupuncture. The fMRI experiment was performed before, during and after acupuncture manipulations on healthy volunteers at an acupuncture point, which was previously implicated in a neural pathway for pain modulation. We first identified significant fMRI signal changes during acupuncture stimulation in the left amygdala, which was subsequently selected as a functional reference for connectivity analyses. Our results have demonstrated that there is a brain network associated with the amygdala during a resting condition. This network encompasses the brain structures that are implicated in both pain sensation and pain modulation. We also found that such a pain-related network could be modulated by both verum acupuncture and sham acupuncture. Furthermore, compared with a sham acupuncture, the verum acupuncture induced a higher level of correlations among the amygdala-associated network. Conclusion Our findings indicate that acupuncture may change this amygdala-specific brain network into a functional state that underlies pain perception and pain modulation. PMID:19014532

Artistic creativity, style and brain disorders.

PubMed

Bogousslavsky, Julien

2005-01-01

The production of novel, motivated or useful material defines creativity, which appears to be one of the higher, specific, human brain functions. While creativity can express itself in virtually any domain, art might particularly well illustrate how creativity may be modulated by the normal or pathological brain. Evidence emphasizes global brain functioning in artistic creativity and output, but critical steps which link perception processing to execution of a work, such as extraction-abstraction, as well as major developments of non-esthetic values attached to art also underline complex activation and inhibition processes mainly localized in the frontal lobe. Neurological diseases in artists provide a unique opportunity to study brain-creativity relationships, in particular through the stylistic changes which may develop after brain lesion. (c) 2005 S. Karger AG, Basel

Small-worldness characteristics and its gender relation in specific hemispheric networks.

PubMed

Miraglia, F; Vecchio, F; Bramanti, P; Rossini, P M

2015-12-03

Aim of this study was to verify whether the topological organization of human brain functional networks is different for males and females in resting state EEGs. Undirected and weighted brain networks were computed by eLORETA lagged linear connectivity in 130 subjects (59 males and 71 females) within each hemisphere and in four resting state networks (Attentional Network (AN), Frontal Network (FN), Sensorimotor Network (SN), Default Mode Network (DMN)). We found that small-world (SW) architecture in the left hemisphere Frontal network presented differences in both delta and alpha band, in particular lower values in delta and higher in alpha 2 in males respect to females while in the right hemisphere differences were found in lower values of SW in males respect to females in gamma Attentional, delta Sensorimotor and delta and gamma DMNs. Gender small-worldness differences in some of resting state networks indicated that there are specific brain differences in the EEG rhythms when the brain is in the resting-state condition. These specific regions could be considered related to the functions of behavior and cognition and should be taken into account both for research on healthy and brain diseased subjects. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Her versus his migraine: multiple sex differences in brain function and structure

PubMed Central

Linnman, Clas; Brawn, Jennifer; Burstein, Rami; Becerra, Lino; Borsook, David

2012-01-01

Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a ‘sex phenotype’ in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs. PMID:22843414

Her versus his migraine: multiple sex differences in brain function and structure.

PubMed

Maleki, Nasim; Linnman, Clas; Brawn, Jennifer; Burstein, Rami; Becerra, Lino; Borsook, David

2012-08-01

Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a 'sex phenotype' in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs.

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

PubMed

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

2017-07-13

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

Passive language mapping combining real-time oscillation analysis with cortico-cortical evoked potentials for awake craniotomy.

PubMed

Tamura, Yukie; Ogawa, Hiroshi; Kapeller, Christoph; Prueckl, Robert; Takeuchi, Fumiya; Anei, Ryogo; Ritaccio, Anthony; Guger, Christoph; Kamada, Kyousuke

2016-12-01

OBJECTIVE Electrocortical stimulation (ECS) is the gold standard for functional brain mapping; however, precise functional mapping is still difficult in patients with language deficits. High gamma activity (HGA) between 80 and 140 Hz on electrocorticography is assumed to reflect localized cortical processing, whereas the cortico-cortical evoked potential (CCEP) can reflect bidirectional responses evoked by monophasic pulse stimuli to the language cortices when there is no patient cooperation. The authors propose the use of "passive" mapping by combining HGA mapping and CCEP recording without active tasks during conscious resections of brain tumors. METHODS Five patients, each with an intraaxial tumor in their dominant hemisphere, underwent conscious resection of their lesion with passive mapping. The authors performed functional localization for the receptive language area, using real-time HGA mapping, by listening passively to linguistic sounds. Furthermore, single electrical pulses were delivered to the identified receptive temporal language area to detect CCEPs in the frontal lobe. All mapping results were validated by ECS, and the sensitivity and specificity were evaluated. RESULTS Linguistic HGA mapping quickly identified the language area in the temporal lobe. Electrical stimulation by linguistic HGA mapping to the identified temporal receptive language area evoked CCEPs on the frontal lobe. The combination of linguistic HGA and frontal CCEPs needed no patient cooperation or effort. In this small case series, the sensitivity and specificity were 93.8% and 89%, respectively. CONCLUSIONS The described technique allows for simple and quick functional brain mapping with higher sensitivity and specificity than ECS mapping. The authors believe that this could improve the reliability of functional brain mapping and facilitate rational and objective operations. Passive mapping also sheds light on the underlying physiological mechanisms of language in the human brain.

Development of the Adolescent Brain: Implications for Executive Function and Social Cognition

ERIC Educational Resources Information Center

Blakemore, Sarah-Jayne; Choudhury, Suparna

2006-01-01

Adolescence is a time of considerable development at the level of behaviour, cognition and the brain. This article reviews histological and brain imaging studies that have demonstrated specific changes in neural architecture during puberty and adolescence, outlining trajectories of grey and white matter development. The implications of brain…

Sex Differences in the Effects of Unilateral Brain Damage on Intelligence

NASA Astrophysics Data System (ADS)

Inglis, James; Lawson, J. S.

1981-05-01

A sexual dimorphism in the functional asymmetry of the damaged human brain is reflected in a test-specific laterality effect in male but not in female patients. This sex difference explains some contradictions concerning the effects of unilateral brain damage on intelligence in studies in which the influence of sex was overlooked.

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

PubMed Central

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

2013-01-01

Recent studies have shown that multivariate pattern analysis (MVPA) can be useful for distinguishing brain disorders into categories. Such analyses can substantially enrich and facilitate clinical diagnoses. Using MPVA methods, whole brain functional networks, especially those derived using different frequency windows, can be applied to detect brain states. We constructed whole brain functional networks for groups of vascular dementia (VaD) patients and controls using resting state BOLD-fMRI (rsfMRI) data from three frequency bands - slow-5 (0.01∼0.027 Hz), slow-4 (0.027∼0.073 Hz), and whole-band (0.01∼0.073 Hz). Then we used the support vector machine (SVM), a type of MVPA classifier, to determine the patterns of functional connectivity. Our results showed that the brain functional networks derived from rsfMRI data (19 VaD patients and 20 controls) in these three frequency bands appear to reflect neurobiological changes in VaD patients. Such differences could be used to differentiate the brain states of VaD patients from those of healthy individuals. We also found that the functional connectivity patterns of the human brain in the three frequency bands differed, as did their ability to differentiate brain states. Specifically, the ability of the functional connectivity pattern to differentiate VaD brains from healthy ones was more efficient in the slow-5 (0.01∼0.027 Hz) band than in the other two frequency bands. Our findings suggest that the MVPA approach could be used to detect abnormalities in the functional connectivity of VaD patients in distinct frequency bands. Identifying such abnormalities may contribute to our understanding of the pathogenesis of VaD. PMID:23359801

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

PubMed

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

2018-03-01

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

Causal Interactions between Frontalθ – Parieto-Occipitalα2 Predict Performance on a Mental Arithmetic Task

PubMed Central

Dimitriadis, Stavros I.; Sun, Yu; Thakor, Nitish V.; Bezerianos, Anastasios

2016-01-01

Many neuroimaging studies have demonstrated the different functional contributions of spatially distinct brain areas to working memory (WM) subsystems in cognitive tasks that demand both local information processing and interregional coordination. In WM cognitive task paradigms employing electroencephalography (EEG), brain rhythms such as θ and α have been linked to specific functional roles over given brain areas, but their functional coupling has not been extensively studied. Here we analyzed an arithmetic task with five cognitive workload levels (CWLs) and demonstrated functional/effective coupling between the two WM subsystems: the central executive located over frontal (F) brain areas that oscillates on the dominant θ rhythm (Frontalθ/Fθ) and the storage buffer located over parieto-occipital (PO) brain areas that operates on the α2 dominant brain rhythm (Parieto-Occipitalα2/POα2). We focused on important differences between and within WM subsystems in relation to behavioral performance. A repertoire of brain connectivity estimators was employed to elucidate the distinct roles of amplitude, phase within and between frequencies, and the hierarchical role of functionally specialized brain areas related to the task. Specifically, for each CWL, we conducted a) a conventional signal power analysis within both frequency bands at Fθ and POα2, b) the intra- and inter-frequency phase interactions between Fθ and POα2, and c) their causal phase and amplitude relationship. We found no significant statistical difference of signal power or phase interactions between correct and wrong answers. Interestingly, the study of causal interactions between Fθ and POα2 revealed frontal brain region(s) as the leader, while the strength differentiated between correct and wrong responses in every CWL with absolute accuracy. Additionally, zero time-lag between bilateral Fθ and right POa2 could serve as an indicator of mental calculation failure. Overall, our study highlights the significant role of coordinated activity between Fθ and POα2 via their causal interactions and the timing for arithmetic performance. PMID:27683547

Current technical approaches to brain energy metabolism.

PubMed

Barros, L Felipe; Bolaños, Juan P; Bonvento, Gilles; Bouzier-Sore, Anne-Karine; Brown, Angus; Hirrlinger, Johannes; Kasparov, Sergey; Kirchhoff, Frank; Murphy, Anne N; Pellerin, Luc; Robinson, Michael B; Weber, Bruno

2018-06-01

Neuroscience is a technology-driven discipline and brain energy metabolism is no exception. Once satisfied with mapping metabolic pathways at organ level, we are now looking to learn what it is exactly that metabolic enzymes and transporters do and when, where do they reside, how are they regulated, and how do they relate to the specific functions of neurons, glial cells, and their subcellular domains and organelles, in different areas of the brain. Moreover, we aim to quantify the fluxes of metabolites within and between cells. Energy metabolism is not just a necessity for proper cell function and viability but plays specific roles in higher brain functions such as memory processing and behavior, whose mechanisms need to be understood at all hierarchical levels, from isolated proteins to whole subjects, in both health and disease. To this aim, the field takes advantage of diverse disciplines including anatomy, histology, physiology, biochemistry, bioenergetics, cellular biology, molecular biology, developmental biology, neurology, and mathematical modeling. This article presents a well-referenced synopsis of the technical side of brain energy metabolism research. Detail and jargon are avoided whenever possible and emphasis is given to comparative strengths, limitations, and weaknesses, information that is often not available in regular articles. © 2017 Wiley Periodicals, Inc.

Conserved and divergent functions of Pax6 underlie species-specific neurogenic patterns in the developing amniote brain.

PubMed

Yamashita, Wataru; Takahashi, Masanori; Kikkawa, Takako; Gotoh, Hitoshi; Osumi, Noriko; Ono, Katsuhiko; Nomura, Tadashi

2018-04-16

The evolution of unique organ structures is associated with changes in conserved developmental programs. However, characterizing the functional conservation and variation of homologous transcription factors (TFs) that dictate species-specific cellular dynamics has remained elusive. Here, we dissect shared and divergent functions of Pax6 during amniote brain development. Comparative functional analyses revealed that the neurogenic function of Pax6 is highly conserved in the developing mouse and chick pallium, whereas stage-specific binary functions of Pax6 in neurogenesis are unique to mouse neuronal progenitors, consistent with Pax6-dependent temporal regulation of Notch signaling. Furthermore, we identified that Pax6-dependent enhancer activity of Dbx1 is extensively conserved between mammals and chick, although Dbx1 expression in the developing pallium is highly divergent in these species. Our results suggest that spatiotemporal changes in Pax6-dependent regulatory programs contributed to species-specific neurogenic patterns in mammalian and avian lineages, which underlie the morphological divergence of the amniote pallial architectures. © 2018. Published by The Company of Biologists Ltd.

Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan.

PubMed

Nomi, Jason S; Bolt, Taylor S; Ezie, C E Chiemeka; Uddin, Lucina Q; Heller, Aaron S

2017-05-31

Variability of neuronal responses is thought to underlie flexible and optimal brain function. Because previous work investigating BOLD signal variability has been conducted within task-based fMRI contexts on adults and older individuals, very little is currently known regarding regional changes in spontaneous BOLD signal variability in the human brain across the lifespan. The current study used resting-state fMRI data from a large sample of male and female human participants covering a wide age range (6-85 years) across two different fMRI acquisition parameters (TR = 0.645 and 1.4 s). Variability in brain regions including a key node of the salience network (anterior insula) increased linearly across the lifespan across datasets. In contrast, variability in most other large-scale networks decreased linearly over the lifespan. These results demonstrate unique lifespan trajectories of BOLD variability related to specific regions of the brain and add to a growing literature demonstrating the importance of identifying normative trajectories of functional brain maturation. SIGNIFICANCE STATEMENT Although brain signal variability has traditionally been considered a source of unwanted noise, recent work demonstrates that variability in brain signals during task performance is related to brain maturation in old age as well as individual differences in behavioral performance. The current results demonstrate that intrinsic fluctuations in resting-state variability exhibit unique maturation trajectories in specific brain regions and systems, particularly those supporting salience detection. These results have implications for investigations of brain development and aging, as well as interpretations of brain function underlying behavioral changes across the lifespan. Copyright © 2017 the authors 0270-6474/17/375539-10$15.00/0.

Brain tumor specifies intermediate progenitor cell identity by attenuating β-catenin/Armadillo activity

PubMed Central

Komori, Hideyuki; Xiao, Qi; McCartney, Brooke M.; Lee, Cheng-Yu

2014-01-01

During asymmetric stem cell division, both the daughter stem cell and the presumptive intermediate progenitor cell inherit cytoplasm from their parental stem cell. Thus, proper specification of intermediate progenitor cell identity requires an efficient mechanism to rapidly extinguish the activity of self-renewal factors, but the mechanisms remain unknown in most stem cell lineages. During asymmetric division of a type II neural stem cell (neuroblast) in the Drosophila larval brain, the Brain tumor (Brat) protein segregates unequally into the immature intermediate neural progenitor (INP), where it specifies INP identity by attenuating the function of the self-renewal factor Klumpfuss (Klu), but the mechanisms are not understood. Here, we report that Brat specifies INP identity through its N-terminal B-boxes via a novel mechanism that is independent of asymmetric protein segregation. Brat-mediated specification of INP identity is critically dependent on the function of the Wnt destruction complex, which attenuates the activity of β-catenin/Armadillo (Arm) in immature INPs. Aberrantly increasing Arm activity in immature INPs further exacerbates the defects in the specification of INP identity and enhances the supernumerary neuroblast mutant phenotype in brat mutant brains. By contrast, reducing Arm activity in immature INPs suppresses supernumerary neuroblast formation in brat mutant brains. Finally, reducing Arm activity also strongly suppresses supernumerary neuroblasts induced by overexpression of klu. Thus, the Brat-dependent mechanism extinguishes the function of the self-renewal factor Klu in the presumptive intermediate progenitor cell by attenuating Arm activity, balancing stem cell maintenance and progenitor cell specification. PMID:24257623

Behavioral and brain asymmetries in primates: a preliminary evaluation of two evolutionary hypotheses

PubMed Central

Hopkins, William D.; Misiura, Maria; Pope, Sarah M.; Latash, Elitaveta M.

2015-01-01

Contrary to many historical views, recent evidence suggest that species-level behavioral and brain asymmetries are evident in nonhuman species. Here, we briefly present evidence of behavioral, perceptual, cognitive, functional, and neuroanatomical asymmetries in nonhuman primates. In addition, we describe two historical accounts of the evolutionary origins of hemispheric specialization and present data from nonhuman primates that address these specific theories. Specifically, we first discuss the evidence of that genes play specific roles in determining left–right differences in anatomical and functional asymmetries in primates. We next consider and present data on the hypothesis that hemispheric specialization evolved as a by-product of increasing brain size relative to the size of the corpus callosum in different primate species. Lastly, we discuss some of the challenges in the study of hemispheric specialization in primates and offer some suggestions on how to advance the field. PMID:26426409

Behavioral and brain asymmetries in primates: a preliminary evaluation of two evolutionary hypotheses.

PubMed

Hopkins, William D; Misiura, Maria; Pope, Sarah M; Latash, Elitaveta M

2015-11-01

Contrary to many historical views, recent evidence suggests that species-level behavioral and brain asymmetries are evident in nonhuman species. Here, we briefly present evidence of behavioral, perceptual, cognitive, functional, and neuroanatomical asymmetries in nonhuman primates. In addition, we describe two historical accounts of the evolutionary origins of hemispheric specialization and present data from nonhuman primates that address these specific theories. Specifically, we first discuss the evidence that genes play specific roles in determining left-right differences in anatomical and functional asymmetries in primates. We next consider and present data on the hypothesis that hemispheric specialization evolved as a by-product of increasing brain size relative to the surface area of the corpus callosum in different primate species. Last, we discuss some of the challenges in the study of hemispheric specialization in primates and offer some suggestions on how to advance the field. © 2015 New York Academy of Sciences.

Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI

PubMed Central

Xu, Tingting; Cullen, Kathryn R.; Mueller, Bryon; Schreiner, Mindy W.; Lim, Kelvin O.; Schulz, S. Charles; Parhi, Keshab K.

2016-01-01

Borderline personality disorder (BPD) is associated with symptoms such as affect dysregulation, impaired sense of self, and self-harm behaviors. Neuroimaging research on BPD has revealed structural and functional abnormalities in specific brain regions and connections. However, little is known about the topological organizations of brain networks in BPD. We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 patients with BPD and 10 healthy controls, and constructed frequency-specific functional brain networks by correlating wavelet-filtered fMRI signals from 82 cortical and subcortical regions. We employed graph-theory based complex network analysis to investigate the topological properties of the brain networks, and employed network-based statistic to identify functional dysconnections in patients. In the 0.03–0.06 Hz frequency band, compared to controls, patients with BPD showed significantly larger measures of global network topology, including the size of largest connected graph component, clustering coefficient, small-worldness, and local efficiency, indicating increased local cliquishness of the functional brain network. Compared to controls, patients showed lower nodal centrality at several hub nodes but greater centrality at several non-hub nodes in the network. Furthermore, an interconnected subnetwork in 0.03–0.06 Hz frequency band was identified that showed significantly lower connectivity in patients. The links in the subnetwork were mainly long-distance connections between regions located at different lobes; and the mean connectivity of this subnetwork was negatively correlated with the increased global topology measures. Lastly, the key network measures showed high correlations with several clinical symptom scores, and classified BPD patients against healthy controls with high accuracy based on linear discriminant analysis. The abnormal topological properties and connectivity found in this study may add new knowledge to the current understanding of functional brain networks in BPD. However, due to limitation of small sample sizes, the results of the current study should be viewed as exploratory and need to be validated on large samples in future works. PMID:26977400

Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI.

PubMed

Xu, Tingting; Cullen, Kathryn R; Mueller, Bryon; Schreiner, Mindy W; Lim, Kelvin O; Schulz, S Charles; Parhi, Keshab K

2016-01-01

Borderline personality disorder (BPD) is associated with symptoms such as affect dysregulation, impaired sense of self, and self-harm behaviors. Neuroimaging research on BPD has revealed structural and functional abnormalities in specific brain regions and connections. However, little is known about the topological organizations of brain networks in BPD. We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 patients with BPD and 10 healthy controls, and constructed frequency-specific functional brain networks by correlating wavelet-filtered fMRI signals from 82 cortical and subcortical regions. We employed graph-theory based complex network analysis to investigate the topological properties of the brain networks, and employed network-based statistic to identify functional dysconnections in patients. In the 0.03-0.06 Hz frequency band, compared to controls, patients with BPD showed significantly larger measures of global network topology, including the size of largest connected graph component, clustering coefficient, small-worldness, and local efficiency, indicating increased local cliquishness of the functional brain network. Compared to controls, patients showed lower nodal centrality at several hub nodes but greater centrality at several non-hub nodes in the network. Furthermore, an interconnected subnetwork in 0.03-0.06 Hz frequency band was identified that showed significantly lower connectivity in patients. The links in the subnetwork were mainly long-distance connections between regions located at different lobes; and the mean connectivity of this subnetwork was negatively correlated with the increased global topology measures. Lastly, the key network measures showed high correlations with several clinical symptom scores, and classified BPD patients against healthy controls with high accuracy based on linear discriminant analysis. The abnormal topological properties and connectivity found in this study may add new knowledge to the current understanding of functional brain networks in BPD. However, due to limitation of small sample sizes, the results of the current study should be viewed as exploratory and need to be validated on large samples in future works.

A prenatal interruption of DISC1 function in the brain exhibits a lasting impact on adult behaviors, brain metabolism, and interneuron development.

PubMed

Deng, Dazhi; Jian, Chongdong; Lei, Ling; Zhou, Yijing; McSweeney, Colleen; Dong, Fengping; Shen, Yilun; Zou, Donghua; Wang, Yonggang; Wu, Yuan; Zhang, Limin; Mao, Yingwei

2017-10-17

Mental illnesses like schizophrenia (SCZ) and major depression disorder (MDD) are devastating brain disorders. The SCZ risk gene, disrupted in schizophrenia 1 ( DISC1 ), has been associated with neuropsychiatric conditions. However, little is known regarding the long-lasting impacts on brain metabolism and behavioral outcomes from genetic insults on fetal NPCs during early life. We have established a new mouse model that specifically interrupts DISC1 functions in NPCs in vivo by a dominant-negative DISC1 (DN-DISC1) with a precise temporal and spatial regulation. Interestingly, prenatal interruption of mouse Disc1 function in NPCs leads to abnormal depression-like deficit in adult mice. Here we took a novel unbiased metabonomics approach to identify brain-specific metabolites that are significantly changed in DN-DISC1 mice. Surprisingly, the inhibitory neurotransmitter, GABA, is augmented. Consistently, parvalbumin (PV) interneurons are increased in the cingulate cortex, retrosplenial granular cortex, and motor cortex. Interestingly, somatostatin (SST) positive and neuropeptide Y (NPY) interneurons are decreased in some brain regions, suggesting that DN-DISC1 expression affects the localization of interneuron subtypes. To further explore the cellular mechanisms that cause this change, DN-DISC1 suppresses proliferation and promotes the cell cycle exit of progenitors in the medial ganglionic eminence (MGE), whereas it stimulates ectopic proliferation of neighboring cells through cell non-autonomous effect. Mechanistically, it modulates GSK3 activity and interrupts Dlx2 activity in the Wnt activation. In sum, our results provide evidence that specific genetic insults on NSCs at a short period of time could lead to prolonged changes of brain metabolism and development, eventually behavioral defects.

INVESTIGATING DIFFERENCES IN BRAIN FUNCTIONAL NETWORKS USING HIERARCHICAL COVARIATE-ADJUSTED INDEPENDENT COMPONENT ANALYSIS.

PubMed

Shi, Ran; Guo, Ying

2016-12-01

Human brains perform tasks via complex functional networks consisting of separated brain regions. A popular approach to characterize brain functional networks in fMRI studies is independent component analysis (ICA), which is a powerful method to reconstruct latent source signals from their linear mixtures. In many fMRI studies, an important goal is to investigate how brain functional networks change according to specific clinical and demographic variabilities. Existing ICA methods, however, cannot directly incorporate covariate effects in ICA decomposition. Heuristic post-ICA analysis to address this need can be inaccurate and inefficient. In this paper, we propose a hierarchical covariate-adjusted ICA (hc-ICA) model that provides a formal statistical framework for estimating covariate effects and testing differences between brain functional networks. Our method provides a more reliable and powerful statistical tool for evaluating group differences in brain functional networks while appropriately controlling for potential confounding factors. We present an analytically tractable EM algorithm to obtain maximum likelihood estimates of our model. We also develop a subspace-based approximate EM that runs significantly faster while retaining high accuracy. To test the differences in functional networks, we introduce a voxel-wise approximate inference procedure which eliminates the need of computationally expensive covariance matrix estimation and inversion. We demonstrate the advantages of our methods over the existing method via simulation studies. We apply our method to an fMRI study to investigate differences in brain functional networks associated with post-traumatic stress disorder (PTSD).

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.

The embodied brain: towards a radical embodied cognitive neuroscience

PubMed Central

Kiverstein, Julian; Miller, Mark

2015-01-01

In this programmatic paper we explain why a radical embodied cognitive neuroscience is needed. We argue for such a claim based on problems that have arisen in cognitive neuroscience for the project of localizing function to specific brain structures. The problems come from research concerned with functional and structural connectivity that strongly suggests that the function a brain region serves is dynamic, and changes over time. We argue that in order to determine the function of a specific brain area, neuroscientists need to zoom out and look at the larger organism-environment system. We therefore argue that instead of looking to cognitive psychology for an analysis of psychological functions, cognitive neuroscience should look to an ecological dynamical psychology. A second aim of our paper is to develop an account of embodied cognition based on the inseparability of cognitive and emotional processing in the brain. We argue that emotions are best understood in terms of action readiness (Frijda, 1986, 2007) in the context of the organism’s ongoing skillful engagement with the environment (Rietveld, 2008; Bruineberg and Rietveld, 2014; Kiverstein and Rietveld, 2015, forthcoming). States of action readiness involve the whole living body of the organism, and are elicited by possibilities for action in the environment that matter to the organism. Since emotion and cognition are inseparable processes in the brain it follows that what is true of emotion is also true of cognition. Cognitive processes are likewise processes taking place in the whole living body of an organism as it engages with relevant possibilities for action. PMID:25999836

Structural variations in prefrontal cortex mediate the relationship between early childhood stress and spatial working memory

PubMed Central

Hanson, Jamie L.; Chung, Moo K.; Avants, Brian B.; Rudolph, Karen D.; Shirtcliff, Elizabeth A.; Gee, James C.; Davidson, Richard J.; Pollak, Seth D.

2012-01-01

A large corpus of research indicates exposure to stress impairs cognitive abilities, specifically executive functioning dependent on the prefrontal cortex (PFC). We collected structural MRI scans (n=61), well-validated assessments of executive functioning, and detailed interviews assessing stress exposure in humans, to examine whether cumulative life stress affected brain morphometry and one type of executive functioning, spatial working memory, during adolescence—a critical time of brain development and reorganization. Analysis of variations in brain structure revealed that cumulative life stress and spatial working memory were related to smaller volumes in the PFC, specifically prefrontal gray and white matter between the anterior cingulate and the frontal poles. Mediation analyses revealed that individual differences in prefrontal volumes accounted for the association between cumulative life stress and spatial working memory. These results suggest that structural changes in the PFC may serve as a mediating mechanism through which greater cumulative life stress engenders decrements in cognitive functioning. PMID:22674267

Functional Specialization in the Human Brain Estimated By Intrinsic Hemispheric Interaction

PubMed Central

Wang, Danhong; Buckner, Randy L.

2014-01-01

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

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

PubMed Central

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

2014-01-01

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

Inferring consistent functional interaction patterns from natural stimulus FMRI data

PubMed Central

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

2014-01-01

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

Training the Brain: Practical Applications of Neural Plasticity From the Intersection of Cognitive Neuroscience, Developmental Psychology, and Prevention Science

PubMed Central

Bryck, Richard L.; Fisher, Philip A.

2012-01-01

Prior researchers have shown that the brain has a remarkable ability for adapting to environmental changes. The positive effects of such neural plasticity include enhanced functioning in specific cognitive domains and shifts in cortical representation following naturally occurring cases of sensory deprivation; however, maladaptive changes in brain function and development owing to early developmental adversity and stress have also been well documented. Researchers examining enriched rearing environments in animals have revealed the potential for inducing positive brain plasticity effects and have helped to popularize methods for training the brain to reverse early brain deficits or to boost normal cognitive functioning. In this paper, two classes of empirically based methods of brain training in children are reviewed and critiqued: laboratory-based, mental process training paradigms and ecological interventions based upon neurocognitive conceptual models. Given the susceptibility of executive function disruption, special attention is paid to training programs that emphasize executive function enhancement. In addition, a third approach to brain training, aimed at tapping into compensatory processes, is postulated. Study results showing the effectiveness of this strategy in the field of neurorehabilitation and in terms of naturally occurring compensatory processing in human aging lend credence to the potential of this approach. PMID:21787037

Training the brain: practical applications of neural plasticity from the intersection of cognitive neuroscience, developmental psychology, and prevention science.

PubMed

Bryck, Richard L; Fisher, Philip A

2012-01-01

Prior researchers have shown that the brain has a remarkable ability for adapting to environmental changes. The positive effects of such neural plasticity include enhanced functioning in specific cognitive domains and shifts in cortical representation following naturally occurring cases of sensory deprivation; however, maladaptive changes in brain function and development owing to early developmental adversity and stress have also been well documented. Researchers examining enriched rearing environments in animals have revealed the potential for inducing positive brain plasticity effects and have helped to popularize methods for training the brain to reverse early brain deficits or to boost normal cognitive functioning. In this article, two classes of empirically based methods of brain training in children are reviewed and critiqued: laboratory-based, mental process training paradigms and ecological interventions based upon neurocognitive conceptual models. Given the susceptibility of executive function disruption, special attention is paid to training programs that emphasize executive function enhancement. In addition, a third approach to brain training, aimed at tapping into compensatory processes, is postulated. Study results showing the effectiveness of this strategy in the field of neurorehabilitation and in terms of naturally occurring compensatory processing in human aging lend credence to the potential of this approach. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Altered brain functional networks in people with Internet gaming disorder: Evidence from resting-state fMRI.

PubMed

Wang, Lingxiao; Wu, Lingdan; Lin, Xiao; Zhang, Yifen; Zhou, Hongli; Du, Xiaoxia; Dong, Guangheng

2016-08-30

Although numerous neuroimaging studies have detected structural and functional abnormality in specific brain regions and connections in subjects with Internet gaming disorder (IGD), the topological organization of the whole-brain network in IGD remain unclear. In this study, we applied graph theoretical analysis to explore the intrinsic topological properties of brain networks in Internet gaming disorder (IGD). 37 IGD subjects and 35 matched healthy control (HC) subjects underwent a resting-state functional magnetic resonance imaging scan. The functional networks were constructed by thresholding partial correlation matrices of 90 brain regions. Then we applied graph-based approaches to analysis their topological attributes, including small-worldness, nodal metrics, and efficiency. Both IGD and HC subjects show efficient and economic brain network, and small-world topology. Although there was no significant group difference in global topology metrics, the IGD subjects showed reduced regional centralities in the prefrontal cortex, left posterior cingulate cortex, right amygdala, and bilateral lingual gyrus, and increased functional connectivity in sensory-motor-related brain networks compared to the HC subjects. These results imply that people with IGD may be associated with functional network dysfunction, including impaired executive control and emotional management, but enhanced coordination among visual, sensorimotor, auditory and visuospatial systems. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Formation and remodeling of the brain extracellular matrix in neural plasticity: Roles of chondroitin sulfate and hyaluronan.

PubMed

Miyata, Shinji; Kitagawa, Hiroshi

2017-10-01

The extracellular matrix (ECM) of the brain is rich in glycosaminoglycans such as chondroitin sulfate (CS) and hyaluronan. These glycosaminoglycans are organized into either diffuse or condensed ECM. Diffuse ECM is distributed throughout the brain and fills perisynaptic spaces, whereas condensed ECM selectively surrounds parvalbumin-expressing inhibitory neurons (PV cells) in mesh-like structures called perineuronal nets (PNNs). The brain ECM acts as a non-specific physical barrier that modulates neural plasticity and axon regeneration. Here, we review recent progress in understanding of the molecular basis of organization and remodeling of the brain ECM, and the involvement of several types of experience-dependent neural plasticity, with a particular focus on the mechanism that regulates PV cell function through specific interactions between CS chains and their binding partners. We also discuss how the barrier function of the brain ECM restricts dendritic spine dynamics and limits axon regeneration after injury. The brain ECM not only forms physical barriers that modulate neural plasticity and axon regeneration, but also forms molecular brakes that actively controls maturation of PV cells and synapse plasticity in which sulfation patterns of CS chains play a key role. Structural remodeling of the brain ECM modulates neural function during development and pathogenesis. Genetic or enzymatic manipulation of the brain ECM may restore neural plasticity and enhance recovery from nerve injury. This article is part of a Special Issue entitled Neuro-glycoscience, edited by Kenji Kadomatsu and Hiroshi Kitagawa. Copyright © 2017 Elsevier B.V. All rights reserved.

How the brain attunes to sentence processing: Relating behavior, structure, and function

PubMed Central

Fengler, Anja; Meyer, Lars; Friederici, Angela D.

2016-01-01

Unlike other aspects of language comprehension, the ability to process complex sentences develops rather late in life. Brain maturation as well as verbal working memory (vWM) expansion have been discussed as possible reasons. To determine the factors contributing to this functional development, we assessed three aspects in different age-groups (5–6 years, 7–8 years, and adults): first, functional brain activity during the processing of increasingly complex sentences; second, brain structure in language-related ROIs; and third, the behavioral comprehension performance on complex sentences and the performance on an independent vWM test. At the whole-brain level, brain functional data revealed a qualitatively similar neural network in children and adults including the left pars opercularis (PO), the left inferior parietal lobe together with the posterior superior temporal gyrus (IPL/pSTG), the supplementary motor area, and the cerebellum. While functional activation of the language-related ROIs PO and IPL/pSTG predicted sentence comprehension performance for all age-groups, only adults showed a functional selectivity in these brain regions with increased activation for more complex sentences. The attunement of both the PO and IPL/pSTG toward a functional selectivity for complex sentences is predicted by region-specific gray matter reduction while that of the IPL/pSTG is additionally predicted by vWM span. Thus, both structural brain maturation and vWM expansion provide the basis for the emergence of functional selectivity in language-related brain regions leading to more efficient sentence processing during development. PMID:26777477

Fasting mediated increase in p-BAD(ser155) and p-AKT(ser473) in the prefrontal cortex of mice.

PubMed

Pitchaimani, Vigneshwaran; Arumugam, Somasundaram; Thandavarayan, Rajarajan Amirthalingam; Karuppagounder, Vengadeshprabhu; Sreedhar, Remya; Afrin, Rejina; Harima, Meilei; Suzuki, Hiroshi; Miyashita, Shizuka; Nomoto, Mayumi; Sone, Hirohito; Suzuki, Kenji; Watanabe, Kenichi

2014-09-05

BAD-deficient mice and fasting have several common functional roles in seizures, beta-hydroxybutyrate (BHB) uptake in brain and alteration in counterregulatory hormonal regulation during hypoglycemia. Neuronal specific insulin receptor knockout (NIRKO) mice display impaired counterregulatory hormonal responses during hypoglycemia. In this study we investigated the fasting mediated expression of p-BAD(ser155) and p-AKT(ser473) in different regions of brain (prefrontal cortex, hippocampus, midbrain and hypothalamus). Fasting specifically increases p-BAD(ser155) and p-AKT(ser473) in prefrontal cortex and decreases in other regions of brain. Our results suggest that fasting may increase the uptake BHB by decreasing p-BAD(ser155) in the brain during hypoglycemia except prefrontal cortex and it uncovers specific functional area of p-BAD(ser155) and p-AKT(ser473) that may regulates counter regulatory hormonal response. Overall in support with previous findings, fasting mediated hypoglycemia activates prefrontal cortex insulin signaling which influences the hypothalamic paraventricular nucleus mediated activation of sympathoadrenal hormonal responses. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Evaluating Alzheimer's disease biomarkers as mediators of age-related cognitive decline.

PubMed

Hohman, Timothy J; Tommet, Doug; Marks, Shawn; Contreras, Joey; Jones, Rich; Mungas, Dan

2017-10-01

Age-related changes in cognition are partially mediated by the presence of neuropathology and neurodegeneration. This manuscript evaluates the degree to which biomarkers of Alzheimer's disease, (AD) neuropathology and longitudinal changes in brain structure, account for age-related differences in cognition. Data from the AD Neuroimaging Initiative (n = 1012) were analyzed, including individuals with normal cognition and mild cognitive impairment. Parallel process mixed effects regression models characterized longitudinal trajectories of cognitive variables and time-varying changes in brain volumes. Baseline age was associated with both memory and executive function at baseline (p's < 0.001) and change in memory and executive function performances over time (p's < 0.05). After adjusting for clinical diagnosis, baseline, and longitudinal changes in brain volume, and baseline levels of cerebrospinal fluid biomarkers, age effects on change in episodic memory and executive function were fully attenuated, age effects on baseline memory were substantially attenuated, but an association remained between age and baseline executive function. Results support previous studies that show that age effects on cognitive decline are fully mediated by disease and neurodegeneration variables but also show domain-specific age effects on baseline cognition, specifically an age pathway to executive function that is independent of brain and disease pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Enhancing health leadership performance using neurotherapy.

PubMed

Swingle, Paul G; Hartney, Elizabeth

2018-05-01

The discovery of neuroplasticity means the brain can change, functionally, in response to the environment and to learning. While individuals can develop harmful patterns of brain activity in response to stressors, they can also learn to modify or control neurological conditions associated with specific behaviors. Neurotherapy is one way of changing brain functioning to modify troubling conditions which can impair leadership performance, through responding to feedback on their own brain activity, and enhancing optimal leadership functioning through learning to maximize such cognitive strengths as mental efficiency, focus, creativity, perseverance, and executive functioning. The present article outlines the application of the concept of optimal performance training to organizational leadership in a healthcare context, by describing approaches to neurotherapy and illustrating their application through a case study of a health leader learning to overcome the neurological and emotional sequelae of workplace stress and trauma.

Brain and Behavioral Assessment of Executive Functions for Self-Regulating Levels of Language in Reading Brain.

PubMed

Berninger, Virginia W; Richards, Todd L; Abbott, Robert D

2017-11-01

This brief research report examines brain-behavioral relationships specific to levels of language in the complex reading brain. The first specific aim was to examine prior findings for significant fMRI connectivity from four seeds (left precuneus, left occipital temporal, left supramarginal, left inferior frontal) for each of four levels of language-subword, word (word-specific spelling or affixed words), syntax (with and without homonym foils or affix foils), and multi-sentence text to identify significant fMRI connectivity (a) unique to the lower level of language when compared to the immediately higher adjacent level of language across subword-word, word-syntax, and syntax-text comparisons; and (b) involving a brain region associated with executive functions. The second specific aim was to correlate the magnitude of that connectivity with standard scores on tests of Focused Attention (D-K EFS Color Word Form Inhibition) and Switching Attention (Wolf & Denckla Rapid Automatic Switching). Seven correlations were significant. Focused Attention was significantly correlated with the word level (word-specific spellings of real words) fMRI task in left cingulum from left inferior frontal seed. Switching Attention was significantly correlated with the (a) subword level (grapheme-phoneme correspondence) fMRI task in left and right Cerebellum V from left supramarginal seed; (b) the word level (word-specific spelling) fMRI task in right Cerebellum V from left precuneus seed; (c) the syntax level (with and without homonym foils) fMRI task in right Cerebellum V from left precuneus seed and from left supramarginal seed; and (d) syntax level (with and without affix foils) fMRI task in right Cerebellum V from left precuneus seed. Results are discussed in reference to neuropsychological assessment of supervisory attention (focused and switching) for specific levels of language related to reading acquisition in students with and without language-related specific learning disabilities and self-regulation of the complex reading brain.

Brain and Behavioral Assessment of Executive Functions for Self-Regulating Levels of Language in Reading Brain

PubMed Central

Berninger, Virginia W.; Richards, Todd L.; Abbott, Robert D.

2017-01-01

This brief research report examines brain-behavioral relationships specific to levels of language in the complex reading brain. The first specific aim was to examine prior findings for significant fMRI connectivity from four seeds (left precuneus, left occipital temporal, left supramarginal, left inferior frontal) for each of four levels of language—subword, word (word-specific spelling or affixed words), syntax (with and without homonym foils or affix foils), and multi-sentence text to identify significant fMRI connectivity (a) unique to the lower level of language when compared to the immediately higher adjacent level of language across subword-word, word-syntax, and syntax-text comparisons; and (b) involving a brain region associated with executive functions. The second specific aim was to correlate the magnitude of that connectivity with standard scores on tests of Focused Attention (D-K EFS Color Word Form Inhibition) and Switching Attention (Wolf & Denckla Rapid Automatic Switching). Seven correlations were significant. Focused Attention was significantly correlated with the word level (word-specific spellings of real words) fMRI task in left cingulum from left inferior frontal seed. Switching Attention was significantly correlated with the (a) subword level (grapheme-phoneme correspondence) fMRI task in left and right Cerebellum V from left supramarginal seed; (b) the word level (word-specific spelling) fMRI task in right Cerebellum V from left precuneus seed; (c) the syntax level (with and without homonym foils) fMRI task in right Cerebellum V from left precuneus seed and from left supramarginal seed; and (d) syntax level (with and without affix foils) fMRI task in right Cerebellum V from left precuneus seed. Results are discussed in reference to neuropsychological assessment of supervisory attention (focused and switching) for specific levels of language related to reading acquisition in students with and without language-related specific learning disabilities and self-regulation of the complex reading brain. PMID:29104930

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

PubMed Central

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

2014-01-01

Tissue-specific alternative splicing is critical for the emergence of tissue identity during development, yet the role of this process in malignant transformation is undefined. Tissue-specific splicing involves evolutionarily conserved, alternative exons that represent only a minority of the total alternative exons identified. Many of these conserved exons have functional features that influence signaling pathways to profound biological effect. Here, we determined that lineage-specific splicing of a brain-enriched cassette exon in the membrane-binding tumor suppressor annexin A7 (ANXA7) diminishes endosomal targeting of the EGFR oncoprotein, consequently enhancing EGFR signaling during brain tumor progression. ANXA7 exon splicing was mediated by the ribonucleoprotein PTBP1, which is normally repressed during neuronal development. PTBP1 was highly expressed in glioblastomas due to loss of a brain-enriched microRNA (miR-124) and to PTBP1 amplification. The alternative ANXA7 splicing trait was present in precursor cells, suggesting that glioblastoma cells inherit the trait from a potential tumor-initiating ancestor and that these cells exploit this trait through accumulation of mutations that enhance EGFR signaling. Our data illustrate that lineage-specific splicing of a tissue-regulated alternative exon in a constituent of an oncogenic pathway eliminates tumor suppressor functions and promotes glioblastoma progression. This paradigm may offer a general model as to how tissue-specific regulatory mechanisms can reprogram normal developmental processes into oncogenic ones. PMID:24865424

A chemical proteomic atlas of brain serine hydrolases identifies cell type-specific pathways regulating neuroinflammation

PubMed Central

Viader, Andreu; Ogasawara, Daisuke; Joslyn, Christopher M; Sanchez-Alavez, Manuel; Mori, Simone; Nguyen, William; Conti, Bruno; Cravatt, Benjamin F

2016-01-01

Metabolic specialization among major brain cell types is central to nervous system function and determined in large part by the cellular distribution of enzymes. Serine hydrolases are a diverse enzyme class that plays fundamental roles in CNS metabolism and signaling. Here, we perform an activity-based proteomic analysis of primary mouse neurons, astrocytes, and microglia to furnish a global portrait of the cellular anatomy of serine hydrolases in the brain. We uncover compelling evidence for the cellular compartmentalization of key chemical transmission pathways, including the functional segregation of endocannabinoid (eCB) biosynthetic enzymes diacylglycerol lipase-alpha (DAGLα) and –beta (DAGLβ) to neurons and microglia, respectively. Disruption of DAGLβ perturbed eCB-eicosanoid crosstalk specifically in microglia and suppressed neuroinflammatory events in vivo independently of broader effects on eCB content. Mapping the cellular distribution of metabolic enzymes thus identifies pathways for regulating specialized inflammatory responses in the brain while avoiding global alterations in CNS function. DOI: http://dx.doi.org/10.7554/eLife.12345.001 PMID:26779719

Targeting Neuronal-like Metabolism of Metastatic Tumor Cells as a Novel Therapy for Breast Cancer Brain Metastasis

DTIC Science & Technology

2016-03-01

Currently, no effective drug treatments are available for brain metastasis. In this proposal, we hypothesize: interactions with reactive brain astrocytes...neurological drugs . In this project, we propose two specific aims to explore the functional importance of the early metastatic evolution and the...feasibility of targeting metastatic evolution by repurposing neurological drugs . Aim 1: Study the spatial and temporal interactions between brain

Large-Scale functional network overlap is a general property of brain functional organization: Reconciling inconsistent fMRI findings from general-linear-model-based analyses

PubMed Central

Xu, Jiansong; Potenza, Marc N.; Calhoun, Vince D.; Zhang, Rubin; Yip, Sarah W.; Wall, John T.; Pearlson, Godfrey D.; Worhunsky, Patrick D.; Garrison, Kathleen A.; Moran, Joseph M.

2016-01-01

Functional magnetic resonance imaging (fMRI) studies regularly use univariate general-linear-model-based analyses (GLM). Their findings are often inconsistent across different studies, perhaps because of several fundamental brain properties including functional heterogeneity, balanced excitation and inhibition (E/I), and sparseness of neuronal activities. These properties stipulate heterogeneous neuronal activities in the same voxels and likely limit the sensitivity and specificity of GLM. This paper selectively reviews findings of histological and electrophysiological studies and fMRI spatial independent component analysis (sICA) and reports new findings by applying sICA to two existing datasets. The extant and new findings consistently demonstrate several novel features of brain functional organization not revealed by GLM. They include overlap of large-scale functional networks (FNs) and their concurrent opposite modulations, and no significant modulations in activity of most FNs across the whole brain during any task conditions. These novel features of brain functional organization are highly consistent with the brain’s properties of functional heterogeneity, balanced E/I, and sparseness of neuronal activity, and may help reconcile inconsistent GLM findings. PMID:27592153

[The Influence of the Functioning of Brain Regulatory Systems onto the Voluntary Regulation of Cognitive Performance in Children. Report 2. Neuropsychological and Electrophysiological Assessment of Brain Regulatory Functions in Children Aged 10-12 with Learning Difficulties].

PubMed

Semenova, O A; Machinskaya, R I

2015-01-01

A total number of 172 children aged 10-12 were electrophysiologically and neuropsychologically assessed in order to analyze the influence of the functioning of brain regulatory systems onto the voluntary regulation of cognitive performance during the preteen years. EEG patterns associated with the nonoptimal functioning of brain regulatory systems, particularly fronto-thalamic, limbic and fronto-striatal structures were significantly more often observed in children with learning and behavioral difficulties, as compared to the control group. Neuropsychological assessment showed that the nonoptimal functioning of different brain regulatory systems specifically affect the voluntary regulation of cognitive performance. Children with EEG patterns of fronto-thalamic nonoptimal functioning demonstrated poor voluntary regulation such as impulsiveness and difficulties in continuing the same algorithms. Children with EEG patterns of limbic nonoptimal functioning showed a less pronounced executive dysfunction manifested only in poor switching between program units within a task. Children with EEG patterns of fronto-striatal nonoptimal functioning struggled with such executive dysfunctions as motor and tactile perseverations and emotional-motivational deviations such as poor motivation and communicative skills.

Cognitive impairment in neuromyelitis optica spectrum disorders: A comparison of the Wechsler Adult Intelligence Scale-III and the Wechsler Memory Scale Revised with the Rao Brief Repeatable Neuropsychological Battery.

PubMed

Fujimori, Juichi; Nakashima, Ichiro; Baba, Toru; Meguro, Yuko; Ogawa, Ryo; Fujihara, Kazuo

2017-12-01

Approximately 55% of patients with neuromyelitis optica spectrum disorder (NMOSD) show cognitive impairment as evaluated using the Rao Brief Repeatable Neuropsychological Battery (BRBN), but this frequency appears to be higher than the frequency of specific brain lesions in NMOSD. We studied whether cognitive impairment could be observed in NMOSD patients with no or minor non-specific brain lesions. We evaluated cognitive function in 12 NMOSD and 14 MS patients using the Wechsler Adult Intelligence Scale-III (WAIS-III), the Wechsler Memory Scale-Revised (WMS-R), and the BRBN. We judged as cognitively impaired patients whose scores were below the average by 2 standard deviations or greater in 2 or more cognitive domains. Cognitive impairment was observed in 5 MS patients (35.7%) and in the only NMOSD patient (8.3%) with symptomatic brain lesions, but not in the other NMOSD patients who had no or minor non-specific brain lesions. Meanwhile, 5 NMOSD (41.7%) and 4 MS (28.6%) patients who had normal cognition according to the WAIS-III and WMS-R were assessed as cognitively impaired by the BRBN (which is not standardized for age). Cognitive function in NMOSD patients with no or mild non-specific brain lesions was preserved according to the WAIS-III and WMS-R.

Synchronized delta oscillations correlate with the resting-state functional MRI signal

PubMed Central

Lu, Hanbing; Zuo, Yantao; Gu, Hong; Waltz, James A.; Zhan, Wang; Scholl, Clara A.; Rea, William; Yang, Yihong; Stein, Elliot A.

2007-01-01

Synchronized low-frequency spontaneous fluctuations of the functional MRI (fMRI) signal have recently been applied to investigate large-scale neuronal networks of the brain in the absence of specific task instructions. However, the underlying neural mechanisms of these fluctuations remain largely unknown. To this end, electrophysiological recordings and resting-state fMRI measurements were conducted in α-chloralose-anesthetized rats. Using a seed-voxel analysis strategy, region-specific, anesthetic dose-dependent fMRI resting-state functional connectivity was detected in bilateral primary somatosensory cortex (S1FL) of the resting brain. Cortical electroencephalographic signals were also recorded from bilateral S1FL; a visual cortex locus served as a control site. Results demonstrate that, unlike the evoked fMRI response that correlates with power changes in the γ bands, the resting-state fMRI signal correlates with the power coherence in low-frequency bands, particularly the δ band. These data indicate that hemodynamic fMRI signal differentially registers specific electrical oscillatory frequency band activity, suggesting that fMRI may be able to distinguish the ongoing from the evoked activity of the brain. PMID:17991778

Novel frontiers in ultra-structural and molecular MRI of the brain.

PubMed

Duyn, Jeff H; Koretsky, Alan P

2011-08-01

Recent developments in the MRI of the brain continue to expand its use in basic and clinical neuroscience. This review highlights some areas of recent progress. Higher magnetic field strengths and improved signal detectors have allowed improved visualization of the various properties of the brain, facilitating the anatomical definition of function-specific areas and their connections. For example, by sensitizing the MRI signal to the magnetic susceptibility of tissue, it is starting to become possible to reveal the laminar structure of the cortex and identify millimeter-scale fiber bundles. Using exogenous contrast agents, and innovative ways to manipulate contrast, it is becoming possible to highlight specific fiber tracts and cell populations. These techniques are bringing us closer to understanding the evolutionary blueprint of the brain, improving the detection and characterization of disease, and help to guide treatment. Recent MRI techniques are leading to more detailed and more specific contrast in the study of the brain.

Age-and Brain Region-Specific Differences in Mitochondrial ...

EPA Pesticide Factsheets

Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cerebellum (CER), striatum (STR), hippocampus (HIP)] of four diverse age groups [1 Month (young), 4 Month (adult), 12 Month (middle-aged), 24 Month (old age)] to understand age-related differences in selected brain regions and their contribution to age-related chemical sensitivity. Mitochondrial bioenergetics parameters and enzyme activity were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State 111 respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12 and 24 Month age groups. Activities of mitochondrial pyruvate dehydrogenase complex (PDHC) and electron transport chain (ETC) complexes I, II, and IV enzymes were also age- and brain-region specific. In general changes associated with age were more pronounced, with

Multiple Brain Markers are Linked to Age-Related Variation in Cognition

PubMed Central

Hedden, Trey; Schultz, Aaron P.; Rieckmann, Anna; Mormino, Elizabeth C.; Johnson, Keith A.; Sperling, Reisa A.; Buckner, Randy L.

2016-01-01

Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65–90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70–80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health. PMID:25316342

On the Application of Quantitative EEG for Characterizing Autistic Brain: A Systematic Review

PubMed Central

Billeci, Lucia; Sicca, Federico; Maharatna, Koushik; Apicella, Fabio; Narzisi, Antonio; Campatelli, Giulia; Calderoni, Sara; Pioggia, Giovanni; Muratori, Filippo

2013-01-01

Autism-Spectrum Disorders (ASD) are thought to be associated with abnormalities in neural connectivity at both the global and local levels. Quantitative electroencephalography (QEEG) is a non-invasive technique that allows a highly precise measurement of brain function and connectivity. This review encompasses the key findings of QEEG application in subjects with ASD, in order to assess the relevance of this approach in characterizing brain function and clustering phenotypes. QEEG studies evaluating both the spontaneous brain activity and brain signals under controlled experimental stimuli were examined. Despite conflicting results, literature analysis suggests that QEEG features are sensitive to modification in neuronal regulation dysfunction which characterize autistic brain. QEEG may therefore help in detecting regions of altered brain function and connectivity abnormalities, in linking behavior with brain activity, and subgrouping affected individuals within the wide heterogeneity of ASD. The use of advanced techniques for the increase of the specificity and of spatial localization could allow finding distinctive patterns of QEEG abnormalities in ASD subjects, paving the way for the development of tailored intervention strategies. PMID:23935579

Gradual emergence of spontaneous correlated brain activity during fading of general anesthesia in rats: Evidences from fMRI and local field potentials

PubMed Central

Bettinardi, Ruggero G.; Tort-Colet, Núria; Ruiz-Mejias, Marcel; Sanchez-Vives, Maria V.; Deco, Gustavo

2015-01-01

Intrinsic brain activity is characterized by the presence of highly structured networks of correlated fluctuations between different regions of the brain. Such networks encompass different functions, whose properties are known to be modulated by the ongoing global brain state and are altered in several neurobiological disorders. In the present study, we induced a deep state of anesthesia in rats by means of a ketamine/medetomidine peritoneal injection, and analyzed the time course of the correlation between the brain activity in different areas while anesthesia spontaneously decreased over time. We compared results separately obtained from fMRI and local field potentials (LFPs) under the same anesthesia protocol, finding that while most profound phases of anesthesia can be described by overall sparse connectivity, stereotypical activity and poor functional integration, during lighter states different frequency-specific functional networks emerge, endowing the gradual restoration of structured large-scale activity seen during rest. Noteworthy, our in vivo results show that those areas belonging to the same functional network (the default-mode) exhibited sustained correlated oscillations around 10 Hz throughout the protocol, suggesting the presence of a specific functional backbone that is preserved even during deeper phases of anesthesia. Finally, the overall pattern of results obtained from both imaging and in vivo-recordings suggests that the progressive emergence from deep anesthesia is reflected by a corresponding gradual increase of organized correlated oscillations across the cortex. PMID:25804643

Closed-loop brain training: the science of neurofeedback.

PubMed

Sitaram, Ranganatha; Ros, Tomas; Stoeckel, Luke; Haller, Sven; Scharnowski, Frank; Lewis-Peacock, Jarrod; Weiskopf, Nikolaus; Blefari, Maria Laura; Rana, Mohit; Oblak, Ethan; Birbaumer, Niels; Sulzer, James

2017-02-01

Neurofeedback is a psychophysiological procedure in which online feedback of neural activation is provided to the participant for the purpose of self-regulation. Learning control over specific neural substrates has been shown to change specific behaviours. As a progenitor of brain-machine interfaces, neurofeedback has provided a novel way to investigate brain function and neuroplasticity. In this Review, we examine the mechanisms underlying neurofeedback, which have started to be uncovered. We also discuss how neurofeedback is being used in novel experimental and clinical paradigms from a multidisciplinary perspective, encompassing neuroscientific, neuroengineering and learning-science viewpoints.

A primer on brain-machine interfaces, concepts, and technology: a key element in the future of functional neurorestoration.

PubMed

Lee, Brian; Liu, Charles Y; Apuzzo, Michael L J

2013-01-01

Conventionally, the practice of neurosurgery has been characterized by the removal of pathology, congenital or acquired. The emerging complement to the removal of pathology is surgery for the specific purpose of restoration of function. Advents in neuroscience, technology, and the understanding of neural circuitry are creating opportunities to intervene in disease processes in a reparative manner, thereby advancing toward the long-sought-after concept of neurorestoration. Approaching the issue of neurorestoration from a biomedical engineering perspective is the rapidly growing arena of implantable devices. Implantable devices are becoming more common in medicine and are making significant advancements to improve a patient's functional outcome. Devices such as deep brain stimulators, vagus nerve stimulators, and spinal cord stimulators are now becoming more commonplace in neurosurgery as we utilize our understanding of the nervous system to interpret neural activity and restore function. One of the most exciting prospects in neurosurgery is the technologically driven field of brain-machine interface, also known as brain-computer interface, or neuroprosthetics. The successful development of this technology will have far-reaching implications for patients suffering from a great number of diseases, including but not limited to spinal cord injury, paralysis, stroke, or loss of limb. This article provides an overview of the issues related to neurorestoration using implantable devices with a specific focus on brain-machine interface technology. Copyright © 2013 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2017-01-01

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

Effects of Different Correlation Metrics and Preprocessing Factors on Small-World Brain Functional Networks: A Resting-State Functional MRI Study

PubMed Central

Liang, Xia; Wang, Jinhui; Yan, Chaogan; Shu, Ni; Xu, Ke; Gong, Gaolang; He, Yong

2012-01-01

Graph theoretical analysis of brain networks based on resting-state functional MRI (R-fMRI) has attracted a great deal of attention in recent years. These analyses often involve the selection of correlation metrics and specific preprocessing steps. However, the influence of these factors on the topological properties of functional brain networks has not been systematically examined. Here, we investigated the influences of correlation metric choice (Pearson's correlation versus partial correlation), global signal presence (regressed or not) and frequency band selection [slow-5 (0.01–0.027 Hz) versus slow-4 (0.027–0.073 Hz)] on the topological properties of both binary and weighted brain networks derived from them, and we employed test-retest (TRT) analyses for further guidance on how to choose the “best” network modeling strategy from the reliability perspective. Our results show significant differences in global network metrics associated with both correlation metrics and global signals. Analysis of nodal degree revealed differing hub distributions for brain networks derived from Pearson's correlation versus partial correlation. TRT analysis revealed that the reliability of both global and local topological properties are modulated by correlation metrics and the global signal, with the highest reliability observed for Pearson's-correlation-based brain networks without global signal removal (WOGR-PEAR). The nodal reliability exhibited a spatially heterogeneous distribution wherein regions in association and limbic/paralimbic cortices showed moderate TRT reliability in Pearson's-correlation-based brain networks. Moreover, we found that there were significant frequency-related differences in topological properties of WOGR-PEAR networks, and brain networks derived in the 0.027–0.073 Hz band exhibited greater reliability than those in the 0.01–0.027 Hz band. Taken together, our results provide direct evidence regarding the influences of correlation metrics and specific preprocessing choices on both the global and nodal topological properties of functional brain networks. This study also has important implications for how to choose reliable analytical schemes in brain network studies. PMID:22412922

Neuropsychological functioning and brain structure in schizophrenia.

PubMed

Crespo-Facorro, Benedicto; Barbadillo, Laura; Pelayo-Terán, José Maria; Rodríguez-Sánchez, José Manuel

2007-08-01

Cognitive deficits are core features of schizophrenia that are already evident at early phases of the illness. The study of specific relationships between cognition and brain structure might provide valuable clues about neural basis of schizophrenia and its phenomenology. The aim of this article was to review the most consistent findings of the studies exploring the relationships between cognitive deficits and brain anomalies in schizophrenia. Besides several important methodological shortcomings to bear in mind before drawing any consistent conclusion from the revised literature, we have attempted to systematically summarize these findings. Thus, this review has revealed that whole brain volume tends to positively correlate with a range of cognitive domains in healthy volunteers and female patients. An association between prefrontal morphological characteristics and general inability to control behaviour seems to be present in schizophrenia patients. Parahippocampal volume is related to semantic cognitive functions. Thalamic anomalies have been associated with executive deficits specifically in patients. Available evidence on the relationship between cognitive functions and cerebellar structure is still contradictory. Nonetheless, a larger cerebellum appears to be associated with higher IQ in controls and in female patients. Enlarged ventricles, including lateral and third ventricles, are associated with deficits in attention, executive and premorbid cognitive functioning in patients. Several of these reported findings seem to be counterintuitive according to neural basis of cognitive functioning drawn from animal, lesion, and functional imaging investigations. Therefore, there is still a great need for more methodologically stringent investigations that would help in the advance of our understanding of the cognition/brain structure relationships in schizophrenia.

Implantable fiber-optic interface for parallel multisite long-term optical dynamic brain interrogation in freely moving mice

PubMed Central

Doronina-Amitonova, L. V.; Fedotov, I. V.; Ivashkina, O. I.; Zots, M. A.; Fedotov, A. B.; Anokhin, K. V.; Zheltikov, A. M.

2013-01-01

Seeing the big picture of functional responses within large neural networks in a freely functioning brain is crucial for understanding the cellular mechanisms behind the higher nervous activity, including the most complex brain functions, such as cognition and memory. As a breakthrough toward meeting this challenge, implantable fiber-optic interfaces integrating advanced optogenetic technologies and cutting-edge fiber-optic solutions have been demonstrated, enabling a long-term optogenetic manipulation of neural circuits in freely moving mice. Here, we show that a specifically designed implantable fiber-optic interface provides a powerful tool for parallel long-term optical interrogation of distinctly separate, functionally different sites in the brain of freely moving mice. This interface allows the same groups of neurons lying deeply in the brain of a freely behaving mouse to be reproducibly accessed and optically interrogated over many weeks, providing a long-term dynamic detection of genome activity in response to a broad variety of pharmacological and physiological stimuli. PMID:24253232

Mapping Multiplex Hubs in Human Functional Brain Networks

PubMed Central

De Domenico, Manlio; Sasai, Shuntaro; Arenas, Alex

2016-01-01

Typical brain networks consist of many peripheral regions and a few highly central ones, i.e., hubs, playing key functional roles in cerebral inter-regional interactions. Studies have shown that networks, obtained from the analysis of specific frequency components of brain activity, present peculiar architectures with unique profiles of region centrality. However, the identification of hubs in networks built from different frequency bands simultaneously is still a challenging problem, remaining largely unexplored. Here we identify each frequency component with one layer of a multiplex network and face this challenge by exploiting the recent advances in the analysis of multiplex topologies. First, we show that each frequency band carries unique topological information, fundamental to accurately model brain functional networks. We then demonstrate that hubs in the multiplex network, in general different from those ones obtained after discarding or aggregating the measured signals as usual, provide a more accurate map of brain's most important functional regions, allowing to distinguish between healthy and schizophrenic populations better than conventional network approaches. PMID:27471443

Oxytocin and vasopressin modulation of the neural correlates of motivation and emotion: results from functional MRI studies in awake rats.

PubMed

Febo, Marcelo; Ferris, Craig F

2014-09-11

Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings. Oxytocin is released within the lactating rat brain during suckling stimulation and activates specific subcortical networks in the maternal brain. Both vasopressin and oxytocin modulate brain regions involved unconditioned fear, processing of social stimuli and the expression of agonistic behaviors. Across studies there are relatively consistent brain networks associated with internal motivational drives and emotional states that are modulated by oxytocin and vasopressin. This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2014 Elsevier B.V. All rights reserved.

Functional Brain Networks Are Dominated by Stable Group and Individual Factors, Not Cognitive or Daily Variation.

PubMed

Gratton, Caterina; Laumann, Timothy O; Nielsen, Ashley N; Greene, Deanna J; Gordon, Evan M; Gilmore, Adrian W; Nelson, Steven M; Coalson, Rebecca S; Snyder, Abraham Z; Schlaggar, Bradley L; Dosenbach, Nico U F; Petersen, Steven E

2018-04-18

The organization of human brain networks can be measured by capturing correlated brain activity with fMRI. There is considerable interest in understanding how brain networks vary across individuals or neuropsychiatric populations or are altered during the performance of specific behaviors. However, the plausibility and validity of such measurements is dependent on the extent to which functional networks are stable over time or are state dependent. We analyzed data from nine high-quality, highly sampled individuals to parse the magnitude and anatomical distribution of network variability across subjects, sessions, and tasks. Critically, we find that functional networks are dominated by common organizational principles and stable individual features, with substantially more modest contributions from task-state and day-to-day variability. Sources of variation were differentially distributed across the brain and differentially linked to intrinsic and task-evoked sources. We conclude that functional networks are suited to measuring stable individual characteristics, suggesting utility in personalized medicine. Copyright © 2018 Elsevier Inc. All rights reserved.

Implantable fiber-optic interface for parallel multisite long-term optical dynamic brain interrogation in freely moving mice

NASA Astrophysics Data System (ADS)

Doronina-Amitonova, L. V.; Fedotov, I. V.; Ivashkina, O. I.; Zots, M. A.; Fedotov, A. B.; Anokhin, K. V.; Zheltikov, A. M.

2013-11-01

Seeing the big picture of functional responses within large neural networks in a freely functioning brain is crucial for understanding the cellular mechanisms behind the higher nervous activity, including the most complex brain functions, such as cognition and memory. As a breakthrough toward meeting this challenge, implantable fiber-optic interfaces integrating advanced optogenetic technologies and cutting-edge fiber-optic solutions have been demonstrated, enabling a long-term optogenetic manipulation of neural circuits in freely moving mice. Here, we show that a specifically designed implantable fiber-optic interface provides a powerful tool for parallel long-term optical interrogation of distinctly separate, functionally different sites in the brain of freely moving mice. This interface allows the same groups of neurons lying deeply in the brain of a freely behaving mouse to be reproducibly accessed and optically interrogated over many weeks, providing a long-term dynamic detection of genome activity in response to a broad variety of pharmacological and physiological stimuli.

Intrinsic and task-evoked network architectures of the human brain

PubMed Central

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

2014-01-01

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

Analyzing the association between functional connectivity of the brain and intellectual performance

PubMed Central

Pamplona, Gustavo S. P.; Santos Neto, Gérson S.; Rosset, Sara R. E.; Rogers, Baxter P.; Salmon, Carlos E. G.

2015-01-01

Measurements of functional connectivity support the hypothesis that the brain is composed of distinct networks with anatomically separated nodes but common functionality. A few studies have suggested that intellectual performance may be associated with greater functional connectivity in the fronto-parietal network and enhanced global efficiency. In this fMRI study, we performed an exploratory analysis of the relationship between the brain's functional connectivity and intelligence scores derived from the Portuguese language version of the Wechsler Adult Intelligence Scale (WAIS-III) in a sample of 29 people, born and raised in Brazil. We examined functional connectivity between 82 regions, including graph theoretic properties of the overall network. Some previous findings were extended to the Portuguese-speaking population, specifically the presence of small-world organization of the brain and relationships of intelligence with connectivity of frontal, pre-central, parietal, occipital, fusiform and supramarginal gyrus, and caudate nucleus. Verbal comprehension was associated with global network efficiency, a new finding. PMID:25713528

Structural Brain Atlases: Design, Rationale, and Applications in Normal and Pathological Cohorts

PubMed Central

Mandal, Pravat K.; Mahajan, Rashima; Dinov, Ivo D.

2015-01-01

Structural magnetic resonance imaging (MRI) provides anatomical information about the brain in healthy as well as in diseased conditions. On the other hand, functional MRI (fMRI) provides information on the brain activity during performance of a specific task. Analysis of fMRI data requires the registration of the data to a reference brain template in order to identify the activated brain regions. Brain templates also find application in other neuroimaging modalities, such as diffusion tensor imaging and multi-voxel spectroscopy. Further, there are certain differences (e.g., brain shape and size) in the brains of populations of different origin and during diseased conditions like in Alzheimer’s disease (AD), population and disease-specific brain templates may be considered crucial for accurate registration and subsequent analysis of fMRI as well as other neuroimaging data. This manuscript provides a comprehensive review of the history, construction and application of brain atlases. A chronological outline of the development of brain template design, starting from the Talairach and Tournoux atlas to the Chinese brain template (to date), along with their respective detailed construction protocols provides the backdrop to this manuscript. The manuscript also provides the automated workflow-based protocol for designing a population-specific brain atlas from structural MRI data using LONI Pipeline graphical workflow environment. We conclude by discussing the scope of brain templates as a research tool and their application in various neuroimaging modalities. PMID:22647262

Neuroethics vs neurophysiologically and neuropsychologically uninformed influences in child-rearing, education, emerging hunter-gatherers, and artificial intelligence models of the brain.

PubMed

Pontius, A A

1993-04-01

Potentially negative long-term consequences in four areas are emphasized, if specific neuromaturational, neurophysiological, and neuropsychological facts within a neurodevelopmental and ecological context are neglected in normal functional levels of child development and maturational lag of the frontal lobe system in "Attention Deficit Disorder," in education (reading/writing and arithmetic), in assessment of cognitive functioning in hunter-gatherer populations, specifically modified in the service of their survival, and in constructing computer models of the brain, neglecting consciousness and intentionality as criticized recently by Searle.

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

PubMed Central

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

2018-01-01

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

Brain STAT5 signaling modulates learning and memory formation.

PubMed

Furigo, Isadora C; Melo, Helen M; Lyra E Silva, Natalia M; Ramos-Lobo, Angela M; Teixeira, Pryscila D S; Buonfiglio, Daniella C; Wasinski, Frederick; Lima, Eliana R; Higuti, Eliza; Peroni, Cibele N; Bartolini, Paolo; Soares, Carlos R J; Metzger, Martin; de Felice, Fernanda G; Donato, Jose

2018-06-01

The signal transducer and activator of transcription 5 (STAT5) is a transcription factor recruited by numerous cytokines. STAT5 is important for several physiological functions, including body and tissue growth, mammary gland development, immune system and lipid metabolism. However, the role of STAT5 signaling for brain functions is still poorly investigated, especially regarding cognitive aspects. Therefore, the objective of the present study was to investigate whether brain STAT5 signaling modulates learning and memory formation. For this purpose, brain-specific STAT5 knockout (STAT5 KO) mice were studied in well-established memory tests. Initially, we confirmed a robust reduction in STAT5a and STAT5b mRNA levels in different brain structures of STAT5 KO mice. STAT5 KO mice showed no significant alterations in metabolism, growth, somatotropic axis and spontaneous locomotor activity. In contrast, brain-specific STAT5 ablation impaired learning and memory formation in the novel object recognition, Barnes maze and contextual fear conditioning tests. To unravel possible mechanisms that might underlie the memory deficits of STAT5 KO mice, we assessed neurogenesis in the hippocampus, but no significant differences were observed between groups. On the other hand, reduced insulin-like growth factor-1 (IGF-1) mRNA expression was found in the hippocampus and hypothalamus of STAT5 KO mice. These findings collectively indicate that brain STAT5 signaling is required to attain normal learning and memory. Therefore, STAT5 is an important downstream cellular mechanism shared by several cytokines to regulate cognitive functions.

Mapping the Alzheimer’s Brain with Connectomics

PubMed Central

Xie, Teng; He, Yong

2012-01-01

Alzheimer’s disease (AD) is the most common form of dementia. As an incurable, progressive, and neurodegenerative disease, it causes cognitive and memory deficits. However, the biological mechanisms underlying the disease are not thoroughly understood. In recent years, non-invasive neuroimaging and neurophysiological techniques [e.g., structural magnetic resonance imaging (MRI), diffusion MRI, functional MRI, and EEG/MEG] and graph theory based network analysis have provided a new perspective on structural and functional connectivity patterns of the human brain (i.e., the human connectome) in health and disease. Using these powerful approaches, several recent studies of patients with AD exhibited abnormal topological organization in both global and regional properties of neuronal networks, indicating that AD not only affects specific brain regions, but also alters the structural and functional associations between distinct brain regions. Specifically, disruptive organization in the whole-brain networks in AD is involved in the loss of small-world characters and the re-organization of hub distributions. These aberrant neuronal connectivity patterns were associated with cognitive deficits in patients with AD, even with genetic factors in healthy aging. These studies provide empirical evidence to support the existence of an aberrant connectome of AD. In this review we will summarize recent advances discovered in large-scale brain network studies of AD, mainly focusing on graph theoretical analysis of brain connectivity abnormalities. These studies provide novel insights into the pathophysiological mechanisms of AD and could be helpful in developing imaging biomarkers for disease diagnosis and monitoring. PMID:22291664

MRI Guided Brain Stimulation without the Use of a Neuronavigation System

PubMed Central

Vaghefi, Ehsan; Byblow, Winston D.; Stinear, Cathy M.; Thompson, Benjamin

2015-01-01

A key issue in the field of noninvasive brain stimulation (NIBS) is the accurate localization of scalp positions that correspond to targeted cortical areas. The current gold standard is to combine structural and functional brain imaging with a commercially available “neuronavigation” system. However, neuronavigation systems are not commonplace outside of specialized research environments. Here we describe a technique that allows for the use of participant-specific functional and structural MRI data to guide NIBS without a neuronavigation system. Surface mesh representations of the head were generated using Brain Voyager and vectors linking key anatomical landmarks were drawn on the mesh. Our technique was then used to calculate the precise distances on the scalp corresponding to these vectors. These calculations were verified using actual measurements of the head and the technique was used to identify a scalp position corresponding to a brain area localized using functional MRI. PMID:26413537

Symmetry and asymmetry in the human brain

NASA Astrophysics Data System (ADS)

Hugdahl, Kenneth

2005-10-01

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

Thyroid hormone and cerebellar development.

PubMed

Anderson, Grant W

2008-01-01

Thyroid hormone (TH) plays a key role in mammalian brain development. The developing brain is sensitive to both TH deficiency and excess. Brain development in the absence of TH results in motor skill deficiencies and reduced intellectual development. These functional abnormalities can be attributed to maldevelopment of specific cell types and regions of the brain including the cerebellum. TH functions at the molecular level by regulating gene transcription. Therefore, understanding how TH regulates cerebellar development requires identification of TH-regulated gene targets and the cells expressing these genes. Additionally, the process of TH-dependent regulation of gene expression is tightly controlled by mechanisms including regulation of TH transport, TH metabolism, toxicologic inhibition of TH signaling, and control of the nuclear TH response apparatus. This review will describe the functional, cellular, and molecular effects of TH deficit in the developing cerebellum and emphasize the most recent findings regarding TH action in this important brain region.

Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.

PubMed

Fears, Scott C; Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C; Aldana, Ileana; Teshiba, Terri M; Abaryan, Zvart; Al-Sharif, Noor B; Navarro, Linda; Tishler, Todd A; Altshuler, Lori; Bartzokis, George; Escobar, Javier I; Glahn, David C; Thompson, Paul M; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I; Sabatti, Chiara; Cantor, Rita M; Freimer, Nelson B; Bearden, Carrie E

2015-07-01

Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family members. Additionally, while age had a relatively strong impact on all neurocognitive traits, the effects of age on cognition did not differ between diagnostic groups. Most brain-behaviour associations were also similar across the age range, with the exception of cortical and ventricular volume and lingual gyrus thickness, which showed weak correlations with verbal fluency and inhibitory control at younger ages that increased in magnitude in older subjects, regardless of diagnosis. Findings indicate that neuroanatomical traits potentially impacted by bipolar disorder are significantly associated with multiple neurobehavioural domains. Structure-function relationships are generally preserved across diagnostic groups, with the notable exception of ventrolateral prefrontal and parietal association cortex, volumetric increases in which may be associated with cognitive resilience specifically in individuals with bipolar disorder. Although age impacted all neurobehavioural traits, we did not find any evidence of accelerated cognitive decline specific to bipolar disorder subjects. Regardless of diagnosis, greater global brain volume may represent a protective factor for the effects of ageing on executive functioning. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Big words, halved brains and small worlds: complex brain networks of figurative language comprehension.

PubMed

Arzouan, Yossi; Solomon, Sorin; Faust, Miriam; Goldstein, Abraham

2011-04-27

Language comprehension is a complex task that involves a wide network of brain regions. We used topological measures to qualify and quantify the functional connectivity of the networks used under various comprehension conditions. To that aim we developed a technique to represent functional networks based on EEG recordings, taking advantage of their excellent time resolution in order to capture the fast processes that occur during language comprehension. Networks were created by searching for a specific causal relation between areas, the negative feedback loop, which is ubiquitous in many systems. This method is a simple way to construct directed graphs using event-related activity, which can then be analyzed topologically. Brain activity was recorded while subjects read expressions of various types and indicated whether they found them meaningful. Slightly different functional networks were obtained for event-related activity evoked by each expression type. The differences reflect the special contribution of specific regions in each condition and the balance of hemispheric activity involved in comprehending different types of expressions and are consistent with the literature in the field. Our results indicate that representing event-related brain activity as a network using a simple temporal relation, such as the negative feedback loop, to indicate directional connectivity is a viable option for investigation which also derives new information about aspects not reflected in the classical methods for investigating brain activity.

The Hierarchy of Brain Networks Is Related to Insulin Growth Factor-1 in a Large, Middle-Aged, Healthy Cohort: An Exploratory Magnetoencephalography Study.

PubMed

Sorrentino, Pierpaolo; Nieboer, Dagmar; Twisk, Jos W R; Stam, Cornelis J; Douw, Linda; Hillebrand, Arjan

2017-06-01

Recently, a large study demonstrated that lower serum levels of insulin growth factor-1 (IGF-1) relate to brain atrophy and to a greater risk for developing Alzheimer's disease in a healthy elderly population. We set out to test if functional brain networks relate to IGF-1 levels in the middle aged. Hence, we studied the association between IGF-1 and magnetoencephalography-based functional network characteristics in a middle-aged population. The functional connections between brain areas were estimated for six frequency bands (delta, theta, alpha1, alpha2, beta, gamma) using the phase lag index. Subsequently, the topology of the frequency-specific functional networks was characterized using the minimum spanning tree. Our results showed that lower levels of serum IGF-1 relate to a globally less integrated functional network in the beta and theta band. The associations remained significant when correcting for gender and systemic effects of IGF-1 that might indirectly affect the brain. The value of this exploratory study is the demonstration that lower levels of IGF-1 are associated with brain network topology in the middle aged.

Brain-based treatment-A new approach or a well-forgotten old one?

PubMed

Matanova, Vanya; Kostova, Zlatomira; Kolev, Martin

2018-04-24

For a relatively long period of time, mental functioning was mainly associated with personal profile while brain functioning went by the wayside. After the 90s of the 20th century, or the so called "Decade of the Brain", today, contemporary specialists work on the boundary between fundamental science and medicine. This brings neuroscience, neuropsychology, psychiatry, and psychotherapy closer to each other. Today, we definitely know that brain structures are being built and altered thanks to experience. Psychotherapy can be more effective when based on a neuropsychological approach-this implies identification of the neural foundations of various disorders and will lead to specific psychotherapeutic conclusions. The knowledge about the brain is continually enriched, which leads to periodic rethinking and updating of the therapeutic approaches to various diseases of the nervous system and brain dysfunctions. The aim of translational studies is to match and combine scientific areas, resources, experience and techniques to improve prevention, diagnosis and therapies, and "transformation" of scientific discoveries into potential treatments of various diseases done in laboratory conditions. Neuropsychological studies prove that cognition is a key element that links together brain functioning and behaviour. According to Dr. Kandel, all experimental events, including psychotherapeutic interventions, affect the structure and function of neuronal synapses. The story of why psychotherapy works is a story of understanding the brain mechanisms of psychic processes, a story of how the brain has been evolving to ensure learning, forgetting, and the mechanisms of permanent psychological change. The new evidence on brain functioning necessitates the integration of neuropsychological achievements in the psychotherapeutic process. An integrative approach is needed to take into account the dynamic interaction between brain functioning, psyche, soul, spirit, and social interaction, ie, development of a model of psychotherapeutic work based on cerebral plasticity! Brain-based psychotherapy aims at changing brain functioning not directly, but through experiences. This is neuro-psychologically informed psychotherapy. © 2018 John Wiley & Sons, Ltd.

Increased gray-matter volume in medication-naive high-functioning children with autism spectrum disorder.

PubMed

Palmen, Saskia J M C; Hulshoff Pol, Hilleke E; Kemner, Chantal; Schnack, Hugo G; Durston, Sarah; Lahuis, Bertine E; Kahn, René S; Van Engeland, Herman

2005-04-01

To establish whether high-functioning children with autism spectrum disorder (ASD) have enlarged brains in later childhood, and if so, whether this enlargement is confined to the gray and/or to the white matter and whether it is global or more prominent in specific brain regions. Brain MRI scans were acquired from 21 medication-naive, high-functioning children with ASD between 7 and 15 years of age and 21 comparison subjects matched for gender, age, IQ, height, weight, handedness, and parental education, but not pubertal status. Patients showed a significant increase of 6% in intracranium, total brain, cerebral gray matter, cerebellum, and of more than 40% in lateral and third ventricles compared to controls. The cortical gray-matter volume was evenly affected in all lobes. After correction for brain volume, ventricular volumes remained significantly larger in patients. High-functioning children with ASD showed a global increase in gray-matter, but not white-matter and cerebellar volume, proportional to the increase in brain volume, and a disproportional increase in ventricular volumes, still present after correction for brain volume. Advanced pubertal development in the patients compared to the age-matched controls may have contributed to the findings reported in the present study.

A resting state functional magnetic resonance imaging study of concussion in collegiate athletes.

PubMed

Czerniak, Suzanne M; Sikoglu, Elif M; Liso Navarro, Ana A; McCafferty, Joseph; Eisenstock, Jordan; Stevenson, J Herbert; King, Jean A; Moore, Constance M

2015-06-01

Sports-related concussions are currently diagnosed through multi-domain assessment by a medical professional and may utilize neurocognitive testing as an aid. However, these tests have only been able to detect differences in the days to week post-concussion. Here, we investigate a measure of brain function, namely resting state functional connectivity, which may detect residual brain differences in the weeks to months after concussion. Twenty-one student athletes (9 concussed within 6 months of enrollment; 12 non-concussed; between ages 18 and 22 years) were recruited for this study. All participants completed the Wisconsin Card Sorting Task and the Color-Word Interference Test. Neuroimaging data, specifically resting state functional Magnetic Resonance Imaging data, were acquired to examine resting state functional connectivity. Two sample t-tests were used to compare the neurocognitive scores and resting state functional connectivity patterns among concussed and non-concussed participants. Correlations between neurocognitive scores and resting state functional connectivity measures were also determined across all subjects. There were no significant differences in neurocognitive performance between concussed and non-concussed groups. Concussed subjects had significantly increased connections between areas of the brain that underlie executive function. Across all subjects, better neurocognitive performance corresponded to stronger brain connectivity. Even at rest, brains of concussed athletes may have to 'work harder' than their healthy peers to achieve similar neurocognitive results. Resting state brain connectivity may be able to detect prolonged brain differences in concussed athletes in a more quantitative manner than neurocognitive test scores.

Longitudinal Dynamics of 3-Dimensional Components of Selfhood After Severe Traumatic Brain Injury: A qEEG Case Study.

PubMed

Fingelkurts, Andrew A; Fingelkurts, Alexander A

2017-09-01

In this report, we describe the case of a patient who sustained extremely severe traumatic brain damage with diffuse axonal injury in a traffic accident and whose recovery was monitored during 6 years. Specifically, we were interested in the recovery dynamics of 3-dimensional components of selfhood (a 3-dimensional construct model for the complex experiential selfhood has been recently proposed based on the empirical findings on the functional-topographical specialization of 3 operational modules of brain functional network responsible for the self-consciousness processing) derived from the electroencephalographic (EEG) signal. The analysis revealed progressive (though not monotonous) restoration of EEG functional connectivity of 3 modules of brain functional network responsible for the self-consciousness processing, which was also paralleled by the clinically significant functional recovery. We propose that restoration of normal integrity of the operational modules of the self-referential brain network may underlie the positive dynamics of 3 aspects of selfhood and provide a neurobiological mechanism for their recovery. The results are discussed in the context of recent experimental studies that support this inference. Studies of ongoing recovery after severe brain injury utilizing knowledge about each separate aspect of complex selfhood will likely help to develop more efficient and targeted rehabilitation programs for patients with brain trauma.

Finding the imposter: brain connectivity of lesions causing delusional misidentifications.

PubMed

Darby, R Ryan; Laganiere, Simon; Pascual-Leone, Alvaro; Prasad, Sashank; Fox, Michael D

2017-02-01

SEE MCKAY AND FURL DOI101093/AWW323 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Focal brain injury can sometimes lead to bizarre symptoms, such as the delusion that a family member has been replaced by an imposter (Capgras syndrome). How a single brain lesion could cause such a complex disorder is unclear, leading many to speculate that concurrent delirium, psychiatric disease, dementia, or a second lesion is required. Here we instead propose that Capgras and other delusional misidentification syndromes arise from single lesions at unique locations within the human brain connectome. This hypothesis is motivated by evidence that symptoms emerge from sites functionally connected to a lesion location, not just the lesion location itself. First, 17 cases of lesion-induced delusional misidentifications were identified and lesion locations were mapped to a common brain atlas. Second, lesion network mapping was used to identify brain regions functionally connected to the lesion locations. Third, regions involved in familiarity perception and belief evaluation, two processes thought to be abnormal in delusional misidentifications, were identified using meta-analyses of previous functional magnetic resonance imaging studies. We found that all 17 lesion locations were functionally connected to the left retrosplenial cortex, the region most activated in functional magnetic resonance imaging studies of familiarity. Similarly, 16 of 17 lesion locations were functionally connected to the right frontal cortex, the region most activated in functional magnetic resonance imaging studies of expectation violation, a component of belief evaluation. This connectivity pattern was highly specific for delusional misidentifications compared to four other lesion-induced neurological syndromes (P < 0.0001). Finally, 15 lesions causing other types of delusions were connected to expectation violation (P < 0.0001) but not familiarity regions, demonstrating specificity for delusion content. Our results provide potential neuroanatomical correlates for impaired familiarity perception and belief evaluation in patients with delusional misidentifications. More generally, we demonstrate a mechanism by which a single lesion can cause a complex neuropsychiatric syndrome based on that lesion's unique pattern of functional connectivity, without the need for pre-existing or hidden pathology. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

An in vitro and in vivo study of peptide-functionalized nanoparticles for brain targeting: The importance of selective blood-brain barrier uptake.

PubMed

Bode, Gerard H; Coué, Gregory; Freese, Christian; Pickl, Karin E; Sanchez-Purrà, Maria; Albaiges, Berta; Borrós, Salvador; van Winden, Ewoud C; Tziveleka, Leto-Aikaterini; Sideratou, Zili; Engbersen, Johan F J; Singh, Smriti; Albrecht, Krystyna; Groll, Jürgen; Möller, Martin; Pötgens, Andy J G; Schmitz, Christoph; Fröhlich, Eleonore; Grandfils, Christian; Sinner, Frank M; Kirkpatrick, C James; Steinbusch, Harry W M; Frank, Hans-Georg; Unger, Ronald E; Martinez-Martinez, Pilar

2017-04-01

Targeted delivery of drugs across endothelial barriers remains a formidable challenge, especially in the case of the brain, where the blood-brain barrier severely limits entry of drugs into the central nervous system. Nanoparticle-mediated transport of peptide/protein-based drugs across endothelial barriers shows great potential as a therapeutic strategy in a wide variety of diseases. Functionalizing nanoparticles with peptides allows for more efficient targeting to specific organs. We have evaluated the hemocompatibilty, cytotoxicity, endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with peptides targeting brain endothelial receptors, in vitro and in vivo. We used an ELISA-based method for the detection of nanoparticles in biological fluids, investigating the blood clearance rate and in vivo biodistribution of labeled nanoparticles in the brain after intravenous injection in Wistar rats. Herein, we provide a detailed report of in vitro and in vivo observations. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain Oscillatory Correlates of Altered Executive Functioning in Positive and Negative Symptomatic Schizophrenia Patients and Healthy Controls.

PubMed

Berger, Barbara; Minarik, Tamas; Griesmayr, Birgit; Stelzig-Schoeler, Renate; Aichhorn, Wolfgang; Sauseng, Paul

2016-01-01

Working Memory and executive functioning deficits are core characteristics of patients suffering from schizophrenia. Electrophysiological research indicates that altered patterns of neural oscillatory mechanisms underpinning executive functioning are associated with the psychiatric disorder. Such brain oscillatory changes have been found in local amplitude differences at gamma and theta frequencies in task-specific cortical areas. Moreover, interregional interactions are also disrupted as signified by decreased phase coherence of fronto-posterior theta activity in schizophrenia patients. However, schizophrenia is not a one-dimensional psychiatric disorder but has various forms and expressions. A common distinction is between positive and negative symptomatology but most patients have both negative and positive symptoms to some extent. Here, we examined three groups-healthy controls, predominantly negative, and predominantly positive symptomatic schizophrenia patients-when performing a working memory task with increasing cognitive demand and increasing need for executive control. We analyzed brain oscillatory activity in the three groups separately and investigated how predominant symptomatology might explain differences in brain oscillatory patterns. Our results indicate that differences in task specific fronto-posterior network activity (i.e., executive control network) expressed by interregional phase synchronization are able to account for working memory dysfunctions between groups. Local changes in the theta and gamma frequency range also show differences between patients and healthy controls, and more importantly, between the two patient groups. We conclude that differences in oscillatory brain activation patterns related to executive processing can be an indicator for positive and negative symptomatology in schizophrenia. Furthermore, changes in cognitive and especially executive functioning in patients are expressed by alterations in a task-specific fronto-posterior connectivity even in the absence of behavioral impairment.

Specialization in the default mode: Task-induced brain deactivations dissociate between visual working memory and attention.

PubMed

Mayer, Jutta S; Roebroeck, Alard; Maurer, Konrad; Linden, David E J

2010-01-01

The idea of an organized mode of brain function that is present as default state and suspended during goal-directed behaviors has recently gained much interest in the study of human brain function. The default mode hypothesis is based on the repeated observation that certain brain areas show task-induced deactivations across a wide range of cognitive tasks. In this event-related functional resonance imaging study we tested the default mode hypothesis by comparing common and selective patterns of BOLD deactivation in response to the demands on visual attention and working memory (WM) that were independently modulated within one task. The results revealed task-induced deactivations within regions of the default mode network (DMN) with a segregation of areas that were additively deactivated by an increase in the demands on both attention and WM, and areas that were selectively deactivated by either high attentional demand or WM load. Attention-selective deactivations appeared in the left ventrolateral and medial prefrontal cortex and the left lateral temporal cortex. Conversely, WM-selective deactivations were found predominantly in the right hemisphere including the medial-parietal, the lateral temporo-parietal, and the medial prefrontal cortex. Moreover, during WM encoding deactivated regions showed task-specific functional connectivity. These findings demonstrate that task-induced deactivations within parts of the DMN depend on the specific characteristics of the attention and WM components of the task. The DMN can thus be subdivided into a set of brain regions that deactivate indiscriminately in response to cognitive demand ("the core DMN") and a part whose deactivation depends on the specific task. 2009 Wiley-Liss, Inc.

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

PubMed Central

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

2013-01-01

The perception of emotional cues from voice and face is essential for social interaction. However, this process is altered in various psychiatric conditions along with impaired social functioning. Emotion communication trainings have been demonstrated to improve social interaction in healthy individuals and to reduce emotional communication deficits in psychiatric patients. Here, we investigated the impact of a non-verbal emotion communication training (NECT) on cerebral activation and brain structure in a controlled and combined functional magnetic resonance imaging (fMRI) and voxel-based morphometry study. NECT-specific reductions in brain activity occurred in a distributed set of brain regions including face and voice processing regions as well as emotion processing- and motor-related regions presumably reflecting training-induced familiarization with the evaluation of face/voice stimuli. Training-induced changes in non-verbal emotion sensitivity at the behavioral level and the respective cerebral activation patterns were correlated in the face-selective cortical areas in the posterior superior temporal sulcus and fusiform gyrus for valence ratings and in the temporal pole, lateral prefrontal cortex and midbrain/thalamus for the response times. A NECT-induced increase in gray matter (GM) volume was observed in the fusiform face area. Thus, NECT induces both functional and structural plasticity in the face processing system as well as functional plasticity in the emotion perception and evaluation system. We propose that functional alterations are presumably related to changes in sensory tuning in the decoding of emotional expressions. Taken together, these findings highlight that the present experimental design may serve as a valuable tool to investigate the altered behavioral and neuronal processing of emotional cues in psychiatric disorders as well as the impact of therapeutic interventions on brain function and structure. PMID:24146641

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

PubMed

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

2013-01-01

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

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

PubMed

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

2016-07-01

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

Theory of Mind Performance in Children Correlates with Functional Specialization of a Brain Region for Thinking about Thoughts

ERIC Educational Resources Information Center

Gweon, Hyowon; Dodell-Feder, David; Bedny, Marina; Saxe, Rebecca

2012-01-01

Thinking about other people's thoughts recruits a specific group of brain regions, including the temporo-parietal junctions (TPJ), precuneus (PC), and medial prefrontal cortex (MPFC). The same brain regions were recruited when children (N = 20, 5-11 years) and adults (N = 8) listened to descriptions of characters' mental states, compared to…

A wireless beta-microprobe based on pixelated silicon for in vivo brain studies in freely moving rats

NASA Astrophysics Data System (ADS)

Märk, J.; Benoit, D.; Balasse, L.; Benoit, M.; Clémens, J. C.; Fieux, S.; Fougeron, D.; Graber-Bolis, J.; Janvier, B.; Jevaud, M.; Genoux, A.; Gisquet-Verrier, P.; Menouni, M.; Pain, F.; Pinot, L.; Tourvielle, C.; Zimmer, L.; Morel, C.; Laniece, P.

2013-07-01

The investigation of neurophysiological mechanisms underlying the functional specificity of brain regions requires the development of technologies that are well adjusted to in vivo studies in small animals. An exciting challenge remains the combination of brain imaging and behavioural studies, which associates molecular processes of neuronal communications to their related actions. A pixelated intracerebral probe (PIXSIC) presents a novel strategy using a submillimetric probe for beta+ radiotracer detection based on a pixelated silicon diode that can be stereotaxically implanted in the brain region of interest. This fully autonomous detection system permits time-resolved high sensitivity measurements of radiotracers with additional imaging features in freely moving rats. An application-specific integrated circuit (ASIC) allows for parallel signal processing of each pixel and enables the wireless operation. All components of the detector were tested and characterized. The beta+ sensitivity of the system was determined with the probe dipped into radiotracer solutions. Monte Carlo simulations served to validate the experimental values and assess the contribution of gamma noise. Preliminary implantation tests on anaesthetized rats proved PIXSIC's functionality in brain tissue. High spatial resolution allows for the visualization of radiotracer concentration in different brain regions with high temporal resolution.

Adolescent Emotional Maturation through Divergent Models of Brain Organization

PubMed Central

Oron Semper, Jose V.; Murillo, Jose I.; Bernacer, Javier

2016-01-01

In this article we introduce the hypothesis that neuropsychological adolescent maturation, and in particular emotional management, may have opposing explanations depending on the interpretation of the assumed brain architecture, that is, whether a componential computational account (CCA) or a dynamic systems perspective (DSP) is used. According to CCA, cognitive functions are associated with the action of restricted brain regions, and this association is temporally stable; by contrast, DSP argues that cognitive functions are better explained by interactions between several brain areas, whose engagement in specific functions is temporal and context-dependent and based on neural reuse. We outline the main neurobiological facts about adolescent maturation, focusing on the neuroanatomical and neurofunctional processes associated with adolescence. We then explain the importance of emotional management in adolescent maturation. We explain the interplay between emotion and cognition under the scope of CCA and DSP, both at neural and behavioral levels. Finally, we justify why, according to CCA, emotional management is understood as regulation, specifically because the cognitive aspects of the brain are in charge of regulating emotion-related modules. However, the key word in DSP is integration, since neural information from different brain areas is integrated from the beginning of the process. Consequently, although the terms should not be conceptually confused, there is no cognition without emotion, and vice versa. Thus, emotional integration is not an independent process that just happens to the subject, but a crucial part of personal growth. Considering the importance of neuropsychological research in the development of educational and legal policies concerning adolescents, we intend to expose that the holistic view of adolescents is dependent on whether one holds the implicit or explicit interpretation of brain functioning. PMID:27602012

Altered resting brain function and structure in professional badminton players.

PubMed

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

2012-01-01

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

Quantitative and functional interrogation of parent-of-origin allelic expression biases in the brain

PubMed Central

Perez, Julio D; Rubinstein, Nimrod D; Fernandez, Daniel E; Santoro, Stephen W; Needleman, Leigh A; Ho-Shing, Olivia; Choi, John J; Zirlinger, Mariela; Chen, Shau-Kwaun; Liu, Jun S; Dulac, Catherine

2015-01-01

The maternal and paternal genomes play different roles in mammalian brains as a result of genomic imprinting, an epigenetic regulation leading to differential expression of the parental alleles of some genes. Here we investigate genomic imprinting in the cerebellum using a newly developed Bayesian statistical model that provides unprecedented transcript-level resolution. We uncover 160 imprinted transcripts, including 41 novel and independently validated imprinted genes. Strikingly, many genes exhibit parentally biased—rather than monoallelic—expression, with different magnitudes according to age, organ, and brain region. Developmental changes in parental bias and overall gene expression are strongly correlated, suggesting combined roles in regulating gene dosage. Finally, brain-specific deletion of the paternal, but not maternal, allele of the paternally-biased Bcl-x, (Bcl2l1) results in loss of specific neuron types, supporting the functional significance of parental biases. These findings reveal the remarkable complexity of genomic imprinting, with important implications for understanding the normal and diseased brain. DOI: http://dx.doi.org/10.7554/eLife.07860.001 PMID:26140685

Age-specific function of α5β1 integrin in microglial migration during early colonization of the developing mouse cortex.

PubMed

Smolders, Sophie Marie-Thérèse; Swinnen, Nina; Kessels, Sofie; Arnauts, Kaline; Smolders, Silke; Le Bras, Barbara; Rigo, Jean-Michel; Legendre, Pascal; Brône, Bert

2017-07-01

Microglia, the immune cells of the central nervous system, take part in brain development and homeostasis. They derive from primitive myeloid progenitors that originate in the yolk sac and colonize the brain mainly through intensive migration. During development, microglial migration speed declines which suggests that their interaction with the microenvironment changes. However, the matrix-cell interactions allowing dispersion within the parenchyma are unknown. Therefore, we aimed to better characterize the migration behavior and to assess the role of matrix-integrin interactions during microglial migration in the embryonic brain ex vivo. We focused on microglia-fibronectin interactions mediated through the fibronectin receptor α5β1 integrin because in vitro work indirectly suggested a role for this ligand-receptor pair. Using 2-photon time-lapse microscopy on acute ex vivo embryonic brain slices, we found that migration occurs in a saltatory pattern and is developmentally regulated. Most importantly, there is an age-specific function of the α5β1 integrin during microglial cortex colonization. At embryonic day (E) 13.5, α5β1 facilitates migration while from E15.5, it inhibits migration. These results indicate a developmentally regulated function of α5β1 integrin in microglial migration during colonization of the embryonic brain. © 2017 Wiley Periodicals, Inc.

Differences in Brain Function and Changes with Intervention in Children with Poor Spelling and Reading Abilities

PubMed Central

Gebauer, Daniela; Fink, Andreas; Kargl, Reinhard; Reishofer, Gernot; Koschutnig, Karl; Purgstaller, Christian; Fazekas, Franz; Enzinger, Christian

2012-01-01

Previous fMRI studies in English-speaking samples suggested that specific interventions may alter brain function in language-relevant networks in children with reading and spelling difficulties, but this research strongly focused on reading impaired individuals. Only few studies so far investigated characteristics of brain activation associated with poor spelling ability and whether a specific spelling intervention may also be associated with distinct changes in brain activity patterns. We here investigated such effects of a morpheme-based spelling intervention on brain function in 20 children with comparatively poor spelling and reading abilities using repeated fMRI. Relative to 10 matched controls, children with comparatively poor spelling and reading abilities showed increased activation in frontal medial and right hemispheric regions and decreased activation in left occipito-temporal regions prior to the intervention, during processing of a lexical decision task. After five weeks of intervention, spelling and reading comprehension significantly improved in the training group, along with increased activation in the left temporal, parahippocampal and hippocampal regions. Conversely, the waiting group showed increases in right posterior regions. Our findings could indicate an increased left temporal activation associated with the recollection of the new learnt morpheme-based strategy related to successful training. PMID:22693600

Neural signatures of third-party punishment: evidence from penetrating traumatic brain injury

PubMed Central

Glass, Leila; Moody, Lara; Grafman, Jordan

2016-01-01

The ability to survive within a cooperative society depends on impartial third-party punishment (TPP) of social norm violations. Two cognitive mechanisms have been postulated as necessary for the successful completion of TPP: evaluation of legal responsibility and selection of a suitable punishment given the magnitude of the crime. Converging neuroimaging research suggests two supporting domain-general networks; a mentalizing network for evaluation of legal responsibility and a central-executive network for determination of punishment. A whole-brain voxel-based lesion-symptom mapping approach was used in conjunction with a rank-order TPP task to identify brain regions necessary for TPP in a large sample of patients with penetrating traumatic brain injury. Patients who demonstrated atypical TPP had specific lesions in core regions of the mentalizing (dorsomedial prefrontal cortex [PFC], ventromedial PFC) and central-executive (bilateral dorsolateral PFC, right intraparietal sulcus) networks. Altruism and executive functioning (concept formation skills) were significant predictors of TPP: altruism was uniquely associated with TPP in patients with lesions in right dorsolateral PFC and executive functioning was uniquely associated with TPP in individuals with lesions in left PFC. Our findings contribute to the extant literature to support underlying neural networks associated with TPP, with specific brain-behavior causal relationships confirming recent functional neuroimaging research. PMID:26276809

Technical principles of direct bipolar electrostimulation for cortical and subcortical mapping in awake craniotomy.

PubMed

Pallud, J; Mandonnet, E; Corns, R; Dezamis, E; Parraga, E; Zanello, M; Spena, G

2017-06-01

Intraoperative application of electrical current to the brain is a standard technique during brain surgery for inferring the function of the underlying brain. The purpose of intraoperative functional mapping is to reliably identify cortical areas and subcortical pathways involved in eloquent functions, especially motor, sensory, language and cognitive functions. The aim of this article is to review the rationale and the electrophysiological principles of the use of direct bipolar electrostimulation for cortical and subcortical mapping under awake conditions. Direct electrical stimulation is a window into the whole functional network that sustains a particular function. It is an accurate (spatial resolution of about 5mm) and a reproducible technique particularly adapted to clinical practice for brain resection in eloquent areas. If the procedure is rigorously applied, the sensitivity of direct electrical stimulation for the detection of cortical and subcortical eloquent areas is nearly 100%. The main disadvantage of this technique is its suboptimal specificity. Another limitation is the identification of eloquent areas during surgery, which, however, could have been functionally compensated postoperatively if removed surgically. Direct electrical stimulation is an easy, accurate, reliable and safe invasive technique for the intraoperative detection of both cortical and subcortical functional brain connectivity for clinical purpose. In our opinion, it is the optimal technique for minimizing the risk of neurological sequelae when resecting in eloquent brain areas. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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.

Early alterations of social brain networks in young children with autism

PubMed Central

Kojovic, Nada; Rihs, Tonia Anahi; Jan, Reem Kais; Franchini, Martina; Plomp, Gijs; Vulliemoz, Serge; Eliez, Stephan; Michel, Christoph Martin; Schaer, Marie

2018-01-01

Social impairments are a hallmark of Autism Spectrum Disorders (ASD), but empirical evidence for early brain network alterations in response to social stimuli is scant in ASD. We recorded the gaze patterns and brain activity of toddlers with ASD and their typically developing peers while they explored dynamic social scenes. Directed functional connectivity analyses based on electrical source imaging revealed frequency specific network atypicalities in the theta and alpha frequency bands, manifesting as alterations in both the driving and the connections from key nodes of the social brain associated with autism. Analyses of brain-behavioural relationships within the ASD group suggested that compensatory mechanisms from dorsomedial frontal, inferior temporal and insular cortical regions were associated with less atypical gaze patterns and lower clinical impairment. Our results provide strong evidence that directed functional connectivity alterations of social brain networks is a core component of atypical brain development at early stages of ASD. PMID:29482718

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

PubMed

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

2017-12-01

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

Lipidomics of human brain aging and Alzheimer's disease pathology.

PubMed

Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

2015-01-01

Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

The Effects of Spaceflight and Head Down Tilt Bed Rest on Neurocognitive Performance: Extent, Longevity, and Neural Bases

NASA Technical Reports Server (NTRS)

Seidler, Rachael D.; Bloomberg, Jacob; Wood, Scott; Mulavara, Ajit; Kofman, Igor; De Dios, Yiri; Gadd, Nicole; Stepanyan, Vahagn

2017-01-01

Spaceflight effects on gait, balance, & manual motor control have been well studied; some evidence for cognitive deficits. Rodent cortical motor & sensory systems show neural structural alterations with spaceflight. specific Aims: Aim 1-Identify changes in brain structure, function, and network integrity as a function of head down tilt bed rest and spaceflight, and characterize their time course. Aim 2-Specify relationships between structural and functional brain changes and performance and characterize their time course.

Advancing multiscale structural mapping of the brain through fluorescence imaging and analysis across length scales

PubMed Central

Hogstrom, L. J.; Guo, S. M.; Murugadoss, K.; Bathe, M.

2016-01-01

Brain function emerges from hierarchical neuronal structure that spans orders of magnitude in length scale, from the nanometre-scale organization of synaptic proteins to the macroscopic wiring of neuronal circuits. Because the synaptic electrochemical signal transmission that drives brain function ultimately relies on the organization of neuronal circuits, understanding brain function requires an understanding of the principles that determine hierarchical neuronal structure in living or intact organisms. Recent advances in fluorescence imaging now enable quantitative characterization of neuronal structure across length scales, ranging from single-molecule localization using super-resolution imaging to whole-brain imaging using light-sheet microscopy on cleared samples. These tools, together with correlative electron microscopy and magnetic resonance imaging at the nanoscopic and macroscopic scales, respectively, now facilitate our ability to probe brain structure across its full range of length scales with cellular and molecular specificity. As these imaging datasets become increasingly accessible to researchers, novel statistical and computational frameworks will play an increasing role in efforts to relate hierarchical brain structure to its function. In this perspective, we discuss several prominent experimental advances that are ushering in a new era of quantitative fluorescence-based imaging in neuroscience along with novel computational and statistical strategies that are helping to distil our understanding of complex brain structure. PMID:26855758

Effects of age and sex on developmental neural networks of visual-spatial attention allocation.

PubMed

Rubia, Katya; Hyde, Zoe; Halari, Rozmin; Giampietro, Vincent; Smith, Anna

2010-06-01

Compared to our understanding of the functional maturation of brain networks underlying complex cognitive abilities, hardly anything is known of the neurofunctional development of simpler cognitive abilities such as visuo-spatial attention allocation. Furthermore, nothing is known on the effect of gender on the functional development of attention allocation. This study employed event related functional magnetic resonance imaging to investigate effects of age, sex, and sex by age interactions on the brain activation of 63 males and females, between 13 to 38years, during a visual-spatial oddball task. Behaviourally, with increasing age, speed was traded for accuracy, indicative of a less impulsive performance style in older subjects. Increasing age was associated with progressively increased activation in typical areas of selective attention of lateral fronto-striatal and temporo-parietal brain regions. Sex difference analysis showed enhanced activation in right-hemispheric inferior frontal and superior temporal regions in females, and in left-hemispheric inferior temporo-parietal regions in males. Importantly, the age by sex interaction findings showed that these sex-dimorphic patterns of brain activation may be the result of underlying sex differences in the functional maturation of these brain regions, as females had sex-specific progressive age-correlations in the same right inferior fronto-striato-temporal areas, while male-specific age-correlations were in left medial temporal and parietal areas. The findings demonstrate progressive functional maturation of fronto-striato-parieto-temporal networks of the relatively simple function of attention allocation between early adolescence and mid-adulthood. They furthermore show that sex-dimorphic patterns of enhanced reliance on right inferior frontal, striatal and superior temporal regions in females and of left temporo-parietal regions in males during attention allocation may be the result of underlying sex differences in the functional maturation of these brain regions. Copyright 2010 Elsevier Inc. All rights reserved.

Robust Transient Dynamics and Brain Functions

PubMed Central

Rabinovich, Mikhail I.; Varona, Pablo

2011-01-01

In the last few decades several concepts of dynamical systems theory (DST) have guided psychologists, cognitive scientists, and neuroscientists to rethink about sensory motor behavior and embodied cognition. A critical step in the progress of DST application to the brain (supported by modern methods of brain imaging and multi-electrode recording techniques) has been the transfer of its initial success in motor behavior to mental function, i.e., perception, emotion, and cognition. Open questions from research in genetics, ecology, brain sciences, etc., have changed DST itself and lead to the discovery of a new dynamical phenomenon, i.e., reproducible and robust transients that are at the same time sensitive to informational signals. The goal of this review is to describe a new mathematical framework – heteroclinic sequential dynamics – to understand self-organized activity in the brain that can explain certain aspects of robust itinerant behavior. Specifically, we discuss a hierarchy of coarse-grain models of mental dynamics in the form of kinetic equations of modes. These modes compete for resources at three levels: (i) within the same modality, (ii) among different modalities from the same family (like perception), and (iii) among modalities from different families (like emotion and cognition). The analysis of the conditions for robustness, i.e., the structural stability of transient (sequential) dynamics, give us the possibility to explain phenomena like the finite capacity of our sequential working memory – a vital cognitive function –, and to find specific dynamical signatures – different kinds of instabilities – of several brain functions and mental diseases. PMID:21716642

Hemispheric asymmetry of electroencephalography-based functional brain networks.

PubMed

Jalili, Mahdi

2014-11-12

Electroencephalography (EEG)-based functional brain networks have been investigated frequently in health and disease. It has been shown that a number of graph theory metrics are disrupted in brain disorders. EEG-based brain networks are often studied in the whole-brain framework, where all the nodes are grouped into a single network. In this study, we studied the brain networks in two hemispheres and assessed whether there are any hemispheric-specific patterns in the properties of the networks. To this end, resting state closed-eyes EEGs from 44 healthy individuals were processed and the network structures were extracted separately for each hemisphere. We examined neurophysiologically meaningful graph theory metrics: global and local efficiency measures. The global efficiency did not show any hemispheric asymmetry, whereas the local connectivity showed rightward asymmetry for a range of intermediate density values for the constructed networks. Furthermore, the age of the participants showed significant direct correlations with the global efficiency of the left hemisphere, but only in the right hemisphere, with local connectivity. These results suggest that only local connectivity of EEG-based functional networks is associated with brain hemispheres.

Non-neurogenic SVZ-like niche in dolphins, mammals devoid of olfaction.

PubMed

Parolisi, Roberta; Cozzi, Bruno; Bonfanti, Luca

2017-08-01

Adult neurogenesis has been implicated in brain plasticity and brain repair. In mammals, it is mostly restricted to specific brain regions and specific physiological functions. The function and evolutionary history of mammalian adult neurogenesis has been elusive so far. The largest neurogenic site in mammals (subventricular zone, SVZ) generates neurons destined to populate the olfactory bulb. The SVZ neurogenic activity appears to be related to the dependence of the species on olfaction since it occurs at high rates throughout life in animals strongly dependent on this function for their survival. Indeed, it dramatically decreases in humans, who do not depend so much on it. This study investigates whether the SVZ neurogenic site exists in mammals devoid of olfaction and olfactory brain structures, such as dolphins. Our results demonstate that a small SVZ-like region persists in these aquatic mammals. However, this region seems to have lost its neurogenic capabilities since neonatal stages. In addition, instead of the typical newly generated neuroblasts, some mature neurons were observed in the dolphin SVZ. Since cetaceans evolved from terrestrial ancestors, non-neurogenic SVZ may indicate extinction of adult neurogenesis in the absence of olfactory function, with the retention of an SVZ-like anatomical region either vestigial or of still unknown role.

Bioavailability and transport of peptides and peptide drugs into the brain.

PubMed

Egleton, R D; Davis, T P

1997-01-01

Rational drug design and the targeting of specific organs has become a reality in modern drug development, with the emergence of molecular biology and receptor chemistry as powerful tools for the pharmacologist. A greater understanding of peptide function as one of the major extracellular message systems has made neuropeptides an important target in neuropharmaceutical drug design. The major obstacle to targeting the brain with therapeutics is the presence of the blood-brain barrier (BBB), which controls the concentration and entry of solutes into the central nervous system. Peptides are generally polar in nature, do not easily cross the blood-brain barrier by diffusion, and except for a small number do not have specific transport systems. Peptides can also undergo metabolic deactivation by peptidases of the blood, brain and the endothelial cells that comprise the BBB. In this review, we discuss a number of the recent strategies which have been used to promote peptide stability and peptide entry into the brain. In addition, we approach the subject of targeting specific transport systems that can be found on the brain endothelial cells, and describe the limitations of the methodologies that are currently used to study brain entry of neuropharmaceuticals.

What’s New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment

PubMed Central

Reis, Cesar; Wang, Yuechun; Akyol, Onat; Ho, Wing Mann; Applegate II, Richard; Stier, Gary; Martin, Robert; Zhang, John H.

2015-01-01

Traumatic brain injury (TBI), defined as an alteration in brain functions caused by an external force, is responsible for high morbidity and mortality around the world. It is important to identify and treat TBI victims as early as possible. Tracking and monitoring TBI with neuroimaging technologies, including functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), positron emission tomography (PET), and high definition fiber tracking (HDFT) show increasing sensitivity and specificity. Classical electrophysiological monitoring, together with newly established brain-on-chip, cerebral microdialysis techniques, both benefit TBI. First generation molecular biomarkers, based on genomic and proteomic changes following TBI, have proven effective and economical. It is conceivable that TBI-specific biomarkers will be developed with the combination of systems biology and bioinformation strategies. Advances in treatment of TBI include stem cell-based and nanotechnology-based therapy, physical and pharmaceutical interventions and also new use in TBI for approved drugs which all present favorable promise in preventing and reversing TBI. PMID:26016501

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

PubMed

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

2014-01-01

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

The impacts of pesticide and nicotine exposures on functional brain networks in Latino immigrant workers.

PubMed

Bahrami, Mohsen; Laurienti, Paul J; Quandt, Sara A; Talton, Jennifer; Pope, Carey N; Summers, Phillip; Burdette, Jonathan H; Chen, Haiying; Liu, Jing; Howard, Timothy D; Arcury, Thomas A; Simpson, Sean L

2017-09-01

Latino immigrants that work on farms experience chronic exposures to potential neurotoxicants, such as pesticides, as part of their work. For tobacco farmworkers there is the additional risk of exposure to moderate to high doses of nicotine. Pesticide and nicotine exposures have been associated with neurological changes in the brain. Long-term exposure to cholinesterase-inhibiting pesticides, such as organophosphates and carbamates, and nicotine place this vulnerable population at risk for developing neurological dysfunction. In this study we examined whole-brain connectivity patterns and brain network properties of Latino immigrant workers. Comparisons were made between farmworkers and non-farmworkers using resting-state functional magnetic resonance imaging data and a mixed-effects modeling framework. We also evaluated how measures of pesticide and nicotine exposures contributed to the findings. Our results indicate that despite having the same functional connectivity density and strength, brain networks in farmworkers had more clustered and modular structures when compared to non-farmworkers. Our findings suggest increased functional specificity and decreased functional integration in farmworkers when compared to non-farmworkers. Cholinesterase activity was associated with population differences in community structure and the strength of brain network functional connections. Urinary cotinine, a marker of nicotine exposure, was associated with the differences in network community structure. Brain network differences between farmworkers and non-farmworkers, as well as pesticide and nicotine exposure effects on brain functional connections in this study, may illuminate underlying mechanisms that cause neurological implications in later life. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a multichannel optical system for differential cortical measurement

NASA Astrophysics Data System (ADS)

Maki, Atsushi; Yamashita, Yuichi; Watanabe, Eiju; Koizumi, Hideaki

1997-08-01

A prototype system based on intensity-modulation spectroscopy (IMS) was produced with the goal of developing 'optoencephalography' as a new instrument for clinical application and for investigating human brain functions. This system can use dual wavelengths (787 and 827 nm) to simultaneously measure reflectances at 8 measurement positions on the human head. Using the system, we measured the changes in blood circulation and oxygenation changes caused by epileptic seizures and specific brain functions. The former measurements were made simultaneously with tests to determine the epileptic focus by using single-photon-emission computed tomography (SPECT) and electrodes set in the brian. Four measurement positions were fixed in each temporal region. The areas where cerebral blood flow increased, as observed by SPECT, corresponded to the positions where the regional cerebral blood volume (rCBV) increased, as measured by the IMS system. Furthermore, the timing of the epileptic seizures, as measured by the depth-electrodes, corresponded to the timing of the increase in rCBV measured by the prototype system. Our measurements of changes in blood circulation as a result of brain functions were made for motor functions to compare the differences between the right and left hemisphere in how they respond to specific functions. Four measurement positions were set in bilateral motor areas. Significant differences in blood circulation in connection with brain activities were observed between the right and left hemispheres.

A decade of imaging surgeons' brain function (part II): A systematic review of applications for technical and nontechnical skills assessment.

PubMed

Modi, Hemel Narendra; Singh, Harsimrat; Yang, Guang-Zhong; Darzi, Ara; Leff, Daniel Richard

2017-11-01

Functional neuroimaging technologies enable assessment of operator brain function and can deepen our understanding of skills learning, ergonomic optima, and cognitive processes in surgeons. Although there has been a critical mass of data detailing surgeons' brain function, this literature has not been reviewed systematically. A systematic search of original neuroimaging studies assessing surgeons' brain function and published up until November 2016 was conducted using Medline, Embase, and PsycINFO databases. Twenty-seven studies fulfilled the inclusion criteria, including 3 feasibility studies, 14 studies exploring the neural correlates of technical skill acquisition, and the remainder investigating brain function in the context of intraoperative decision-making (n = 1), neurofeedback training (n = 1), robot-assisted technology (n = 5), and surgical teaching (n = 3). Early stages of learning open surgical tasks (knot-tying) are characterized by prefrontal cortical activation, which subsequently attenuates with deliberate practice. However, with complex laparoscopic skills (intracorporeal suturing), prefrontal cortical engagement requires substantial training, and attenuation occurs over a longer time course, after years of refinement. Neurofeedback and interventions that improve neural efficiency may enhance technical performance and skills learning. Imaging surgeons' brain function has identified neural signatures of expertise that might help inform objective assessment and selection processes. Interventions that improve neural efficiency may target skill-specific brain regions and augment surgical performance. Copyright © 2017 Elsevier Inc. All rights reserved.

In Vivo Characterization of Traumatic Brain Injury Neuropathology with Structural and Functional Neuroimaging

PubMed Central

LEVINE, BRIAN; FUJIWARA, ESTHER; O’CONNOR, CHARLENE; RICHARD, NADINE; KOVACEVIC, NATASA; MANDIC, MARINA; RESTAGNO, ADRIANA; EASDON, CRAIG; ROBERTSON, IAN H.; GRAHAM, SIMON J.; CHEUNG, GORDON; GAO, FUQIANG; SCHWARTZ, MICHAEL L.; BLACK, SANDRA E.

2007-01-01

Quantitative neuroimaging is increasingly used to study the effects of traumatic brain injury (TBI) on brain structure and function. This paper reviews quantitative structural and functional neuroimaging studies of patients with TBI, with an emphasis on the effects of diffuse axonal injury (DAI), the primary neuropathology in TBI. Quantitative structural neuroimaging has evolved from simple planometric measurements through targeted region-of-interest analyses to whole-brain analysis of quantified tissue compartments. Recent studies converge to indicate widespread volume loss of both gray and white matter in patients with moderate-to-severe TBI. These changes can be documented even when patients with focal lesions are excluded. Broadly speaking, performance on standard neuropsychological tests of speeded information processing are related to these changes, but demonstration of specific brain-behavior relationships requires more refined experimental behavioral measures. The functional consequences of these structural changes can be imaged with activation functional neuroimaging. Although this line of research is at an early stage, results indicate that TBI causes a more widely dispersed activation in frontal and posterior cortices. Further progress in analysis of the consequences of TBI on neural structure and function will require control of variability in neuropathology and behavior. PMID:17020478

Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice.

PubMed

Zhang, Hongsheng; Kang, Eunchai; Wang, Yaqing; Yang, Chaojuan; Yu, Hui; Wang, Qin; Chen, Zheyu; Zhang, Chen; Christian, Kimberly M; Song, Hongjun; Ming, Guo-Li; Xu, Zhiheng

2016-06-01

Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown of crmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.

Disruption to control network function correlates with altered dynamic connectivity in the wider autism spectrum.

PubMed

de Lacy, N; Doherty, D; King, B H; Rachakonda, S; Calhoun, V D

2017-01-01

Autism is a common developmental condition with a wide, variable range of co-occurring neuropsychiatric symptoms. Contrasting with most extant studies, we explored whole-brain functional organization at multiple levels simultaneously in a large subject group reflecting autism's clinical diversity, and present the first network-based analysis of transient brain states, or dynamic connectivity , in autism. Disruption to inter-network and inter-system connectivity, rather than within individual networks, predominated. We identified coupling disruption in the anterior-posterior default mode axis, and among specific control networks specialized for task start cues and the maintenance of domain-independent task positive status, specifically between the right fronto-parietal and cingulo-opercular networks and default mode network subsystems. These appear to propagate downstream in autism, with significantly dampened subject oscillations between brain states, and dynamic connectivity configuration differences. Our account proposes specific motifs that may provide candidates for neuroimaging biomarkers within heterogeneous clinical populations in this diverse condition.

Mapping behavioural evolution onto brain evolution: the strategic roles of conserved organization in individuals and species.

PubMed

Finlay, Barbara L; Hinz, Flora; Darlington, Richard B

2011-07-27

The pattern of individual variation in brain component structure in pigs, minks and laboratory mice is very similar to variation across species in the same components, at a reduced scale. This conserved pattern of allometric scaling resembles robotic architectures designed to be robust to changes in computing power and task demands, and may reflect the mechanism by which both growing and evolving brains defend basic sensory, motor and homeostatic functions at multiple scales. Conserved scaling rules also have implications for species-specific sensory and social communication systems, motor competencies and cognitive abilities. The role of relative changes in neuron number in the central nervous system in producing species-specific behaviour is thus highly constrained, while changes in the sensory and motor periphery, and in motivational and attentional systems increase in probability as the principal loci producing important changes in functional neuroanatomy between species. By their nature, these loci require renewed attention to development and life history in the initial organization and production of species-specific behavioural abilities.

The contribution of single case studies to the neuroscience of vision.

PubMed

Zihl, Josef; Heywood, Charles A

2016-03-01

Visual neuroscience is concerned with the neurobiological foundations of visual perception, that is, the morphological, physiological, and functional organization of the visual brain and its co-operative partners. One important approach for understanding the functional organization of the visual brain is the study of visual perception from the pathological perspective. The study of patients with focal injury to the visual brain allows conclusions about the representation of visual perceptual functions in the framework of association and dissociation of functions. Selective disorders have been reported for more "elementary" visual capabilities, for example, color and movement vision, but also for visuo-cognitive capacities, such as visual agnosia or the visual field of attention. Because these visual disorders occur rather seldom as selective and specific dysfunctions, single cases have always played, and still play, a significant role in gaining insights into the functional organization of the visual brain. © 2016 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Neuronal survival in the brain: neuron type-specific mechanisms.

PubMed

Pfisterer, Ulrich; Khodosevich, Konstantin

2017-03-02

Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation. Furthermore, pro-survival factors and intracellular responses depend on the type of neuron and region of the brain. Thus, in addition to some common neuronal pro-survival signaling, different types of neurons possess a variety of 'neuron type-specific' pro-survival constituents that might help them to adapt for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various types of immature neurons. Importantly, we mainly focus on in vivo data to describe neuronal survival specifically in the brain, without extrapolating data obtained in the PNS or spinal cord, and thus emphasize the influence of the complex brain environment on neuronal survival during development.

Distinct structure and activity of monoamine oxidase in the brain of zebrafish (Danio rerio).

PubMed

Anichtchik, Oleg; Sallinen, Ville; Peitsaro, Nina; Panula, Pertti

2006-10-10

Monoamine oxidase (MAO) is a mitochondrial flavoprotein involved in the metabolism of, e.g., aminergic neurotransmitters and the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). We have reported earlier MPTP-related alterations of brain catecholaminergic system in zebrafish (Danio rerio) brain. Here we describe the structural and functional properties of zebrafish MAO and the distribution of MAO mRNA and activity in zebrafish brain. The gene is located in chromosome 9 and consists of 15 exons. The amino acid composition of the active center resembles both human MAO-A and MAO-B. The enzyme displayed the highest substrate specificity for tyramine, followed by serotonin, phenylethylamine, MPTP, and dopamine; isoform-specific antagonists blocked the activity of the enzyme with equal potency. Zebrafish MAO mRNA, which was present in several tissues, and enzyme displayed differential distribution in the brain; dopaminergic cell clusters had low to moderate levels of MAO activity, whereas the highest levels of MAO activity were detected in noradrenergic and serotonergic cell groups and the habenulointerpeduncular pathway, including its caudal projection to the medial ventral rhombencephalon. The results of this study confirm the presence of functionally active MAO in zebrafish brain and other tissues and characterize the neural systems that express MAO and areas of intense activity in the brain. They also suggest that MPTP toxicity not related to MAO may affect the zebrafish brain.

Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach.

PubMed

Stampanoni Bassi, Mario; Gilio, Luana; Buttari, Fabio; Maffei, Pierpaolo; Marfia, Girolama A; Restivo, Domenico A; Centonze, Diego; Iezzi, Ennio

2017-01-01

Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the "clinico-radiological paradox." The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

Advances in Targeted Drug Delivery Approaches for the Central Nervous System Tumors: The Inspiration of Nanobiotechnology.

PubMed

Meng, Jianing; Agrahari, Vivek; Youm, Ibrahima

2017-03-01

At present, brain tumor is among the most challenging diseases to treat and the therapy is limited by the lack of effective methods to deliver anticancer agents across the blood-brain barrier (BBB). BBB is a selective barrier that separates the circulating blood from the brain extracellular fluid. In its neuroprotective function, BBB prevents the entry of toxins, as well as most of anticancer agents and is the main impediment for brain targeted drug delivery approaches. Nanotechnology-based delivery systems provide an attractive strategy to cross the BBB and reach the central nervous system (CNS). The incorporation of anticancer agents in various nanovehicles facilitates their delivery across the BBB. Moreover, a more powerful tool in brain tumor therapy has relied surface modifications of nanovehicles with specific ligands that can promote their passage through the BBB and favor the accumulation of the drug in CNS tumors. This review describes the physiological and anatomical features of the brain tumor and the BBB, and summarizes the recent advanced approaches to deliver anticancer drugs into brain tumor using nanobiotechnology-based drug carrier systems. The role of specific ligands in the design of functionalized nanovehicles for targeted delivery to brain tumor is reviewed. The current trends and future approaches in the CNS delivery of therapeutic molecules to tumors are also discussed.

Advances in fMRI Real-Time Neurofeedback.

PubMed

Watanabe, Takeo; Sasaki, Yuka; Shibata, Kazuhisa; Kawato, Mitsuo

2017-12-01

Functional magnetic resonance imaging (fMRI) neurofeedback is a type of biofeedback in which real-time online fMRI signals are used to self-regulate brain function. Since its advent in 2003 significant progress has been made in fMRI neurofeedback techniques. Specifically, the use of implicit protocols, external rewards, multivariate analysis, and connectivity analysis has allowed neuroscientists to explore a possible causal involvement of modified brain activity in modified behavior. These techniques have also been integrated into groundbreaking new neurofeedback technologies, specifically decoded neurofeedback (DecNef) and functional connectivity-based neurofeedback (FCNef). By modulating neural activity and behavior, DecNef and FCNef have substantially advanced both basic and clinical research. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Resting State Network Estimation in Individual Subjects

PubMed Central

Hacker, Carl D.; Laumann, Timothy O.; Szrama, Nicholas P.; Baldassarre, Antonello; Snyder, Abraham Z.

2014-01-01

Resting-state functional magnetic resonance imaging (fMRI) has been used to study brain networks associated with both normal and pathological cognitive function. The objective of this work is to reliably compute resting state network (RSN) topography in single participants. We trained a supervised classifier (multi-layer perceptron; MLP) to associate blood oxygen level dependent (BOLD) correlation maps corresponding to pre-defined seeds with specific RSN identities. Hard classification of maps obtained from a priori seeds was highly reliable across new participants. Interestingly, continuous estimates of RSN membership retained substantial residual error. This result is consistent with the view that RSNs are hierarchically organized, and therefore not fully separable into spatially independent components. After training on a priori seed-based maps, we propagated voxel-wise correlation maps through the MLP to produce estimates of RSN membership throughout the brain. The MLP generated RSN topography estimates in individuals consistent with previous studies, even in brain regions not represented in the training data. This method could be used in future studies to relate RSN topography to other measures of functional brain organization (e.g., task-evoked responses, stimulation mapping, and deficits associated with lesions) in individuals. The multi-layer perceptron was directly compared to two alternative voxel classification procedures, specifically, dual regression and linear discriminant analysis; the perceptron generated more spatially specific RSN maps than either alternative. PMID:23735260

Alpha oscillations and their impairment in affective and post-traumatic stress disorders.

PubMed

Eidelman-Rothman, Moranne; Levy, Jonathan; Feldman, Ruth

2016-09-01

Affective and anxiety disorders are debilitating conditions characterized by impairments in cognitive and social functioning. Elucidating their neural underpinnings may assist in improving diagnosis and developing targeted interventions. Neural oscillations are fundamental for brain functioning. Specifically, oscillations in the alpha frequency range (alpha rhythms) are prevalent in the awake, conscious brain and play an important role in supporting perceptual, cognitive, and social processes. We review studies utilizing various alpha power measurements to assess abnormalities in brain functioning in affective and anxiety disorders as well as obsessive compulsive and post-traumatic stress disorders. Despite some inconsistencies, studies demonstrate associations between aberrant alpha patterns and these disorders both in response to specific cognitive and emotional tasks and during a resting state. We conclude by discussing methodological considerations and future directions, and underscore the need for much further research on the role of alpha functionality in social contexts. As social dysfunction accompanies most psychiatric conditions, research on alpha's involvement in social processes may provide a unique window into the neural mechanisms underlying these disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues.

PubMed

George, M S; Anton, R F; Bloomer, C; Teneback, C; Drobes, D J; Lorberbaum, J P; Nahas, Z; Vincent, D J

2001-04-01

Functional imaging studies have recently demonstrated that specific brain regions become active in cocaine addicts when they are exposed to cocaine stimuli. To test whether there are regional brain activity differences during alcohol cue exposure between alcoholic subjects and social drinkers, we designed a functional magnetic resonance imaging (fMRI) protocol involving alcohol-specific cues. Ten non-treatment-seeking adult alcoholic subjects (2 women) (mean [SD] age, 29.9 [9.9] years) as well as 10 healthy social drinking controls of similar age (2 women) (mean [SD] age, 29.4 [8.9] years) were recruited, screened, and scanned. In the 1.5-T magnetic resonance imaging scanner, subjects were serially rated for alcohol craving before and after a sip of alcohol, and after a 9-minute randomized presentation of pictures of alcoholic beverages, control nonalcoholic beverages, and 2 different visual control tasks. During picture presentation, changes in regional brain activity were measured with the blood oxygen level-dependent technique. Alcoholic subjects, compared with the social drinking subjects, reported higher overall craving ratings for alcohol. After a sip of alcohol, while viewing alcohol cues compared with viewing other beverage cues, only the alcoholic subjects had increased activity in the left dorsolateral prefrontal cortex and the anterior thalamus. The social drinkers exhibited specific activation only while viewing the control beverage pictures. When exposed to alcohol cues, alcoholic subjects have increased brain activity in the prefrontal cortex and anterior thalamus-brain regions associated with emotion regulation, attention, and appetitive behavior.

Transcriptome analyses of adult mouse brain reveal enrichment of lncRNAs in specific brain regions and neuronal populations

PubMed Central

Kadakkuzha, Beena M.; Liu, Xin-An; McCrate, Jennifer; Shankar, Gautam; Rizzo, Valerio; Afinogenova, Alina; Young, Brandon; Fallahi, Mohammad; Carvalloza, Anthony C.; Raveendra, Bindu; Puthanveettil, Sathyanarayanan V.

2015-01-01

Despite the importance of the long non-coding RNAs (lncRNAs) in regulating biological functions, the expression profiles of lncRNAs in the sub-regions of the mammalian brain and neuronal populations remain largely uncharacterized. By analyzing RNASeq datasets, we demonstrate region specific enrichment of populations of lncRNAs and mRNAs in the mouse hippocampus and pre-frontal cortex (PFC), the two major regions of the brain involved in memory storage and neuropsychiatric disorders. We identified 2759 lncRNAs and 17,859 mRNAs in the hippocampus and 2561 lncRNAs and 17,464 mRNAs expressed in the PFC. The lncRNAs identified correspond to ~14% of the transcriptome of the hippocampus and PFC and ~70% of the lncRNAs annotated in the mouse genome (NCBIM37) and are localized along the chromosomes as varying numbers of clusters. Importantly, we also found that a few of the tested lncRNA-mRNA pairs that share a genomic locus display specific co-expression in a region-specific manner. Furthermore, we find that sub-regions of the brain and specific neuronal populations have characteristic lncRNA expression signatures. These results reveal an unexpected complexity of the lncRNA expression in the mouse brain. PMID:25798087

Functional magnetic resonance imaging can be used to explore tactile and nociceptive processing in the infant brain

PubMed Central

Williams, Gemma; Fabrizi, Lorenzo; Meek, Judith; Jackson, Deborah; Tracey, Irene; Robertson, Nicola; Slater, Rebeccah; Fitzgerald, Maria

2015-01-01

Aim Despite the importance of neonatal skin stimulation, little is known about activation of the newborn human infant brain by sensory stimulation of the skin. We carried out functional magnetic resonance imaging (fMRI) to assess the feasibility of measuring brain activation to a range of mechanical stimuli applied to the skin of neonatal infants. Methods We studied 19 term infants with a mean age of 13 days. Brain activation was measured in response to brushing, von Frey hair (vFh) punctate stimulation and, in one case, nontissue damaging pinprick stimulation of the plantar surface of the foot. Initial whole brain analysis was followed by region of interest analysis of specific brain areas. Results Distinct patterns of functional brain activation were evoked by brush and vFh punctate stimulation, which were reduced, but still present, under chloral hydrate sedation. Brain activation increased with increasing stimulus intensity. The feasibility of using pinprick stimulation in fMRI studies was established in one unsedated healthy full-term infant. Conclusion Distinct brain activity patterns can be measured in response to different modalities and intensities of skin sensory stimulation in term infants. This indicates the potential for fMRI studies in exploring tactile and nociceptive processing in the infant brain. PMID:25358870

A variational Bayes spatiotemporal model for electromagnetic brain mapping.

PubMed

Nathoo, F S; Babul, A; Moiseev, A; Virji-Babul, N; Beg, M F

2014-03-01

In this article, we present a new variational Bayes approach for solving the neuroelectromagnetic inverse problem arising in studies involving electroencephalography (EEG) and magnetoencephalography (MEG). This high-dimensional spatiotemporal estimation problem involves the recovery of time-varying neural activity at a large number of locations within the brain, from electromagnetic signals recorded at a relatively small number of external locations on or near the scalp. Framing this problem within the context of spatial variable selection for an underdetermined functional linear model, we propose a spatial mixture formulation where the profile of electrical activity within the brain is represented through location-specific spike-and-slab priors based on a spatial logistic specification. The prior specification accommodates spatial clustering in brain activation, while also allowing for the inclusion of auxiliary information derived from alternative imaging modalities, such as functional magnetic resonance imaging (fMRI). We develop a variational Bayes approach for computing estimates of neural source activity, and incorporate a nonparametric bootstrap for interval estimation. The proposed methodology is compared with several alternative approaches through simulation studies, and is applied to the analysis of a multimodal neuroimaging study examining the neural response to face perception using EEG, MEG, and fMRI. © 2013, The International Biometric Society.

Adaptive Plasticity in the Healthy Language Network: Implications for Language Recovery after Stroke

PubMed Central

2016-01-01

Across the last three decades, the application of noninvasive brain stimulation (NIBS) has substantially increased the current knowledge of the brain's potential to undergo rapid short-term reorganization on the systems level. A large number of studies applied transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) in the healthy brain to probe the functional relevance and interaction of specific areas for different cognitive processes. NIBS is also increasingly being used to induce adaptive plasticity in motor and cognitive networks and shape cognitive functions. Recently, NIBS has been combined with electrophysiological techniques to modulate neural oscillations of specific cortical networks. In this review, we will discuss recent advances in the use of NIBS to modulate neural activity and effective connectivity in the healthy language network, with a special focus on the combination of NIBS and neuroimaging or electrophysiological approaches. Moreover, we outline how these results can be transferred to the lesioned brain to unravel the dynamics of reorganization processes in poststroke aphasia. We conclude with a critical discussion on the potential of NIBS to facilitate language recovery after stroke and propose a phase-specific model for the application of NIBS in language rehabilitation. PMID:27830094

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

PubMed

Fiori, Simona; Guzzetta, Andrea

2015-03-01

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

Neural basis of exertional fatigue in the heat: A review of magnetic resonance imaging methods.

PubMed

Tan, X R; Low, I C C; Stephenson, M C; Soong, T W; Lee, J K W

2018-03-01

The central nervous system, specifically the brain, is implicated in the development of exertional fatigue under a hot environment. Diverse neuroimaging techniques have been used to visualize the brain activity during or after exercise. Notably, the use of magnetic resonance imaging (MRI) has become prevalent due to its excellent spatial resolution and versatility. This review evaluates the significance and limitations of various brain MRI techniques in exercise studies-brain volumetric analysis, functional MRI, functional connectivity MRI, and arterial spin labeling. The review aims to provide a summary on the neural basis of exertional fatigue and proposes future directions for brain MRI studies. A systematic literature search was performed where a total of thirty-seven brain MRI studies associated with exercise, fatigue, or related physiological factors were reviewed. The findings suggest that with moderate dehydration, there is a decrease in total brain volume accompanied with expansion of ventricular volume. With exercise fatigue, there is increased activation of sensorimotor and cognitive brain areas, increased thalamo-insular activation and decreased interhemispheric connectivity in motor cortex. Under passive hyperthermia, there are regional changes in cerebral perfusion, a reduction in local connectivity in functional brain networks and an impairment to executive function. Current literature suggests that the brain structure and function are influenced by exercise, fatigue, and related physiological perturbations. However, there is still a dearth of knowledge and it is hoped that through understanding of MRI advantages and limitations, future studies will shed light on the central origin of exertional fatigue in the heat. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Behavioral Analysis of Genetically Modified Mice Indicates Essential Roles of Neurosteroidal Estrogen

PubMed Central

Honda, Shin-Ichiro; Wakatsuki, Toru; Harada, Nobuhiro

2011-01-01

Aromatase in the mouse brain is expressed only in the nerve cells of specific brain regions with a transient peak during the neonatal period when sexual behaviors become organized. The aromatase-knockout (ArKO) mouse, generated to shed light on the physiological functions of estrogen in the brain, exhibited various abnormal behaviors, concomitant with undetectable estrogen and increased androgen in the blood. To further elucidate the effects of neurosteroidal estrogens on behavioral phenotypes, we first prepared an brain-specific aromatase transgenic (bsArTG) mouse by introduction of a human aromatase transgene controlled under a −6.5 kb upstream region of the brain-specific promoter of the mouse aromatase gene into fertilized mouse eggs, because the −6.5 kb promoter region was previously shown to contain the minimal essential element responsible for brain-specific spatiotemporal expression. Then, an ArKO mouse expressing the human aromatase only in the brain was generated by crossing the bsArTG mouse with the ArKO mouse. The resulting mice (ArKO/bsArTG mice) nearly recovered from abnormal sexual, aggressive, and locomotive (exploratory) behaviors, in spite of having almost the same serum levels of estrogen and androgen as the adult ArKO mouse. These results suggest that estrogens locally synthesized in the specific neurons of the perinatal mouse brain directly act on the neurons and play crucial roles in the organization of neuronal networks participating in the control of sexual, aggressive, and locomotive (exploratory) behaviors. PMID:22654807

Specificities of Awake Craniotomy and Brain Mapping in Children for Resection of Supratentorial Tumors in the Language Area.

PubMed

Delion, Matthieu; Terminassian, Aram; Lehousse, Thierry; Aubin, Ghislaine; Malka, Jean; N'Guyen, Sylvie; Mercier, Philippe; Menei, Philippe

2015-12-01

In the pediatric population, awake craniotomy began to be used for the resection of brain tumor located close to eloquent areas. Some specificities must be taken into account to adapt this method to children. The aim of this clinical study is to not only confirm the feasibility of awake craniotomy and language brain mapping in the pediatric population but also identify the specificities and necessary adaptations of the procedure. Six children aged 11 to 16 were operated on while awake under local anesthesia with language brain mapping for supratentorial brain lesions (tumor and cavernoma). The preoperative planning comprised functional magnetic resonance imaging (MRI) and neuropsychologic and psychologic assessment. The specific preoperative preparation is clearly explained including hypnosis conditioning and psychiatric evaluation. The success of the procedure was based on the ability to perform the language brain mapping and the tumor removal without putting the patient to sleep. We investigated the pediatric specificities, psychological experience, and neuropsychologic follow-up. The children experienced little anxiety, probably in large part due to the use of hypnosis. We succeeded in doing the cortical-subcortical mapping and removing the tumor without putting the patient to sleep in all cases. The psychological experience was good, and the neuropsychologic follow-up showed a favorable evolution. Preoperative preparation and hypnosis in children seemed important for performing awake craniotomy and contributing language brain mapping with the best possible psychological experience. The pediatrics specificities are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

The Role of Sleep in Emotional Brain Function

PubMed Central

Goldstein, Andrea N.; Walker, Matthew P.

2014-01-01

Rapidly emerging evidence continues to describe an intimate and causal relationship between sleep and emotional brain function. These findings are mirrored by longstanding clinical observations demonstrating that nearly all mood and anxiety disorders co-occur with one or more sleep abnormalities. This review aims to (1) provide a synthesis of recent findings describing the emotional brain and behavioral benefits triggered by sleep, and conversely, the detrimental impairments following a lack of sleep, (2) outline a proposed framework in which sleep, and specifically rapid-eye movement (REM) sleep, supports a process of affective brain homeostasis, optimally preparing the organism for next-day social and emotional functioning, and (3) describe how this hypothesized framework can explain the prevalent relationships between sleep and psychiatric disorders, with a particular focus on post-traumatic stress disorder and major depression. PMID:24499013

Recent developments of functional magnetic resonance imaging research for drug development in Alzheimer's disease.

PubMed

Hampel, Harald; Prvulovic, David; Teipel, Stefan J; Bokde, Arun L W

2011-12-01

The objective of this review is to evaluate recent advances in functional magnetic resonance imaging (fMRI) research in Alzheimer's disease for the development of therapeutic agents. The basic building block underpinning cognition is a brain network. The measured brain activity serves as an integrator of the various components, from genes to structural integrity, that impact the function of networks underpinning cognition. Specific networks can be interrogated using cognitive paradigms such as a learning task or a working memory task. In addition, recent advances in our understanding of neural networks allow one to investigate the function of a brain network by investigating the inherent coherency of the brain networks that can be measured during resting state. The coherent resting state networks allow testing in cognitively impaired patients that may not be possible with the use of cognitive paradigms. In particular the default mode network (DMN) includes the medial temporal lobe and posterior cingulate, two key regions that support episodic memory function and are impaired in the earliest stages of Alzheimer's disease (AD). By investigating the effects of a prospective drug compound on this network, it could illuminate the specificity of the compound with a network supporting memory function. This could provide valuable information on the methods of action at physiological and behaviourally relevant levels. Utilizing fMRI opens up new areas of research and a new approach for drug development, as it is an integrative tool to investigate entire networks within the brain. The network based approach provides a new independent method from previous ones to translate preclinical knowledge into the clinical domain. Copyright © 2011 Elsevier Ltd. All rights reserved.

Hallucination- and speech-specific hypercoupling in frontotemporal auditory and language networks in schizophrenia using combined task-based fMRI data: An fBIRN study.

PubMed

Lavigne, Katie M; Woodward, Todd S

2018-04-01

Hypercoupling of activity in speech-perception-specific brain networks has been proposed to play a role in the generation of auditory-verbal hallucinations (AVHs) in schizophrenia; however, it is unclear whether this hypercoupling extends to nonverbal auditory perception. We investigated this by comparing schizophrenia patients with and without AVHs, and healthy controls, on task-based functional magnetic resonance imaging (fMRI) data combining verbal speech perception (SP), inner verbal thought generation (VTG), and nonverbal auditory oddball detection (AO). Data from two previously published fMRI studies were simultaneously analyzed using group constrained principal component analysis for fMRI (group fMRI-CPCA), which allowed for comparison of task-related functional brain networks across groups and tasks while holding the brain networks under study constant, leading to determination of the degree to which networks are common to verbal and nonverbal perception conditions, and which show coordinated hyperactivity in hallucinations. Three functional brain networks emerged: (a) auditory-motor, (b) language processing, and (c) default-mode (DMN) networks. Combining the AO and sentence tasks allowed the auditory-motor and language networks to separately emerge, whereas they were aggregated when individual tasks were analyzed. AVH patients showed greater coordinated activity (deactivity for DMN regions) than non-AVH patients during SP in all networks, but this did not extend to VTG or AO. This suggests that the hypercoupling in AVH patients in speech-perception-related brain networks is specific to perceived speech, and does not extend to perceived nonspeech or inner verbal thought generation. © 2017 Wiley Periodicals, Inc.

Gender-Specific Gene Expression in Post-Mortem Human Brain: Localization to Sex Chromosomes

PubMed Central

Vawter, Marquis P; Evans, Simon; Choudary, Prabhakara; Tomita, Hiroaki; Meador-Woodruff, Jim; Molnar, Margherita; Li, Jun; Lopez, Juan F; Myers, Rick; Cox, David; Watson, Stanley J; Akil, Huda; Jones, Edward G; Bunney, William E

2011-01-01

Gender differences in brain development and in the prevalence of neuropsychiatric disorders such as depression have been reported. Gender differences in human brain might be related to patterns of gene expression. Microarray technology is one useful method for investigation of gene expression in brain. We investigated gene expression, cell types, and regional expression patterns of differentially expressed sex chromosome genes in brain. We profiled gene expression in male and female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum using the Affymetrix oligonucleotide microarray platform. Differentially expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY, RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR measurements. In situ hybridization confirmed the differential expression of gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in three brain regions examined. The XIST gene, which silences gene expression on regions of the X chromosome, is expressed in a subset of neurons. Since a subset of neurons express gender-specific genes, neural subpopulations may exhibit a subtle sexual dimorphism at the level of differences in gene regulation and function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY, and UTY and other sex chromosome genes in neuronal subpopulations may possibly contribute to gender differences in prevalence noted for some neuropsychiatric disorders. Studies of the protein expression of these sex- chromosome-linked genes in brain tissue are required to address the functional consequences of the observed gene expression differences. PMID:14583743

A genome-wide supported psychiatric risk variant in NCAN influences brain function and cognitive performance in healthy subjects.

PubMed

Raum, Heidelore; Dietsche, Bruno; Nagels, Arne; Witt, Stephanie H; Rietschel, Marcella; Kircher, Tilo; Krug, Axel

2015-01-01

The A allele of the single nucleotide polymorphism (SNP) rs1064395 in the NCAN gene has recently been identified as a susceptibility factor for bipolar disorder and schizophrenia. NCAN encodes neurocan, a brain-specific chondroitin sulfate proteoglycan that is thought to influence neuronal adhesion and migration. Several lines of research suggest an impact of NCAN on neurocognitive functioning. In the present study, we investigated the effects of rs1064395 genotype on neural processing and cognitive performance in healthy subjects. Brain activity was measured with functional magnetic resonance imaging (fMRI) during an overt semantic verbal fluency task in 110 healthy subjects who were genotyped for the NCAN SNP rs1064395. Participants additionally underwent comprehensive neuropsychological testing. Whole brain analyses revealed that NCAN risk status, defined as AA or AG genotype, was associated with a lack of task-related deactivation in a large left lateral temporal cluster extending from the middle temporal gyrus to the temporal pole. Regarding neuropsychological measures, risk allele carriers demonstrated poorer immediate and delayed verbal memory performance when compared to subjects with GG genotype. Better verbal memory performance was significantly associated with greater deactivation of the left temporal cluster during the fMRI task in subjects with GG genotype. The current data demonstrate that common genetic variation in NCAN influences both neural processing and cognitive performance in healthy subjects. Our study provides new evidence for a specific genetic influence on human brain function. © 2014 Wiley Periodicals, Inc.

Brain volume and cognitive function in patients with revascularized coronary artery disease.

PubMed

Ottens, Thomas H; Hendrikse, Jeroen; Nathoe, Hendrik M; Biessels, Geert Jan; van Dijk, Diederik

2017-03-01

The pathogenesis of cognitive dysfunction in patients with CAD remains unclear. CAD is associated with brain atrophy and specific lesions. Detailed knowledge about the association of brain volume measured with MRI, and cognitive function in patients with CAD is lacking. We therefore investigated brain volume and cognitive function in patients with revascularized coronary artery disease (CAD), and controls without CAD. Brain MRI scans and cognitive tests from patients with CAD were compared with data from control subjects without CAD. Cognitive performance was assessed with the Rey Auditory Verbal Learning (short term memory) and Trailmaking (divided attention) tests. Multivariable regression analysis was used to study associations between CAD, brain volume and cognitive function. A total of 102 patients with CAD and 48 control subjects were included. Level of education and age were comparable between the groups. Compared with controls, patients with CAD had smaller total brain volume (expressed as fraction of intracranial volume) [%ICV, mean (SD), 0.78 (0.03) vs 0.80 (0.02), P=0.001] and larger volume of non-ventricular cerebrospinal fluid [%ICV, median (IQR) 0.19 (0.18 to 0.21) vs 0.18 (0.17 to 0.20), P=0.001]. Patients in the CAD group had poorer cognitive function [mean (SD) Z-score -0.16 (0.72) vs 0.41 (0.69), P<0.01]. Multivariable regression showed that CAD, higher age, lower level of education and greater cerebrospinal fluid volume were independent predictors of poorer cognitive function. CAD patients had a smaller total brain volume and poorer cognitive function than controls. Greater volume of cerebrospinal fluid was an independent predictor of poorer cognitive function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues

PubMed Central

2013-01-01

Background Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times. Results In each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the influence of an artificial deprivation protocol, we identified a subset of these transcripts as specifically sleep-enhanced or sleep-repressed by requiring that their expression also change over the course of unperturbed sleep. 3% and 6% of the assayed transcripts showed “sleep specific” changes in the lung and heart respectively. Sleep specific transcripts in these tissues demonstrated highly significant overlap and shared temporal dynamics. Markers of cellular stress and the unfolded protein response were reduced during sleep in both tissues. These results mirror previous findings in brain. Sleep-enhanced pathways reflected the unique metabolic functions of each tissue. Transcripts related to carbohydrate and sulfur metabolic processes were enhanced by sleep in the lung, and collectively favor buffering from oxidative stress. DNA repair and protein metabolism annotations were significantly enriched among the sleep-enhanced transcripts in the heart. Our results also suggest that sleep may provide a Zeitgeber, or synchronizing cue, in the lung as a large cluster of transcripts demonstrated systematic changes in inter-animal variability as a function of both sleep duration and circadian time. Conclusion Our data support the notion that the molecular consequences of sleep/wake behavioral state extend beyond the brain to include peripheral tissues. Sleep state induces a highly overlapping response in both heart and lung. We conclude that sleep enhances organ specific molecular functions and that it has a ubiquitous role in reducing cellular metabolic stress in both brain and peripheral tissues. Finally, our data suggest a novel role for sleep in synchronizing transcription in peripheral tissues. PMID:23721503

Spectral fingerprints of large-scale neuronal interactions.

PubMed

Siegel, Markus; Donner, Tobias H; Engel, Andreas K

2012-01-11

Cognition results from interactions among functionally specialized but widely distributed brain regions; however, neuroscience has so far largely focused on characterizing the function of individual brain regions and neurons therein. Here we discuss recent studies that have instead investigated the interactions between brain regions during cognitive processes by assessing correlations between neuronal oscillations in different regions of the primate cerebral cortex. These studies have opened a new window onto the large-scale circuit mechanisms underlying sensorimotor decision-making and top-down attention. We propose that frequency-specific neuronal correlations in large-scale cortical networks may be 'fingerprints' of canonical neuronal computations underlying cognitive processes.

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

PubMed Central

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

2012-01-01

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

Real-time fMRI: a tool for local brain regulation.

PubMed

Caria, Andrea; Sitaram, Ranganatha; Birbaumer, Niels

2012-10-01

Real-time fMRI permits simultaneous measurement and observation of brain activity during an ongoing task. One of the most challenging applications of real-time fMRI in neuroscientific and clinical research is the possibility of acquiring volitional control of localized brain activity using real-time fMRI-based neurofeedback protocols. Real-time fMRI allows the experimenter to noninvasively manipulate brain activity as an independent variable to observe the effects on behavior. Real-time fMRI neurofeedback studies demonstrated that learned control of the local brain activity leads to specific changes in behavior. Here, the authors describe the implementation and application of real-time fMRI with particular emphasis on the self-regulation of local brain activity and the investigation of brain-function relationships. Real-time fMRI represents a promising new approach to cognitive neuroscience that could complement traditional neuroimaging techniques by providing more causal insights into the functional role of circumscribed brain regions in behavior.

Dynamic reconfiguration of human brain functional networks through neurofeedback.

PubMed

Haller, Sven; Kopel, Rotem; Jhooti, Permi; Haas, Tanja; Scharnowski, Frank; Lovblad, Karl-Olof; Scheffler, Klaus; Van De Ville, Dimitri

2013-11-01

Recent fMRI studies demonstrated that functional connectivity is altered following cognitive tasks (e.g., learning) or due to various neurological disorders. We tested whether real-time fMRI-based neurofeedback can be a tool to voluntarily reconfigure brain network interactions. To disentangle learning-related from regulation-related effects, we first trained participants to voluntarily regulate activity in the auditory cortex (training phase) and subsequently asked participants to exert learned voluntary self-regulation in the absence of feedback (transfer phase without learning). Using independent component analysis (ICA), we found network reconfigurations (increases in functional network connectivity) during the neurofeedback training phase between the auditory target region and (1) the auditory pathway; (2) visual regions related to visual feedback processing; (3) insula related to introspection and self-regulation and (4) working memory and high-level visual attention areas related to cognitive effort. Interestingly, the auditory target region was identified as the hub of the reconfigured functional networks without a-priori assumptions. During the transfer phase, we again found specific functional connectivity reconfiguration between auditory and attention network confirming the specific effect of self-regulation on functional connectivity. Functional connectivity to working memory related networks was no longer altered consistent with the absent demand on working memory. We demonstrate that neurofeedback learning is mediated by widespread changes in functional connectivity. In contrast, applying learned self-regulation involves more limited and specific network changes in an auditory setup intended as a model for tinnitus. Hence, neurofeedback training might be used to promote recovery from neurological disorders that are linked to abnormal patterns of brain connectivity. Copyright © 2013 Elsevier Inc. All rights reserved.

Dissecting gene expression at the blood-brain barrier

PubMed Central

Huntley, Melanie A.; Bien-Ly, Nga; Daneman, Richard; Watts, Ryan J.

2014-01-01

The availability of genome-wide expression data for the blood-brain barrier is an invaluable resource that has recently enabled the discovery of several genes and pathways involved in the development and maintenance of the blood-brain barrier, particularly in rodent models. The broad distribution of published data sets represents a viable starting point for the molecular dissection of the blood-brain barrier and will further direct the discovery of novel mechanisms of blood-brain barrier formation and function. Technical advances in purifying brain endothelial cells, the key cell that forms the critical barrier, have allowed for greater specificity in gene expression comparisons with other central nervous system cell types, and more systematic characterizations of the molecular composition of the blood-brain barrier. Nevertheless, our understanding of how the blood-brain barrier changes during aging and disease is underrepresented. Blood-brain barrier data sets from a wider range of experimental paradigms and species, including invertebrates and primates, would be invaluable for investigating the function and evolution of the blood-brain barrier. Newer technologies in gene expression profiling, such as RNA-sequencing, now allow for finer resolution of transcriptomic changes, including isoform specificity and RNA-editing. As our field continues to utilize more advanced expression profiling in its ongoing efforts to elucidate the blood-brain barrier, including in disease and drug delivery, we will continue to see rapid advances in our understanding of the molecular mediators of barrier biology. We predict that the recently published data sets, combined with forthcoming genomic and proteomic blood-brain barrier data sets, will continue to fuel the molecular genetic revolution of blood-brain barrier biology. PMID:25414634

Anomalous brain functional connectivity contributing to poor adaptive behavior in Down syndrome.

PubMed

Pujol, Jesus; del Hoyo, Laura; Blanco-Hinojo, Laura; de Sola, Susana; Macià, Dídac; Martínez-Vilavella, Gerard; Amor, Marta; Deus, Joan; Rodríguez, Joan; Farré, Magí; Dierssen, Mara; de la Torre, Rafael

2015-03-01

Research in Down syndrome has substantially progressed in the understanding of the effect of gene overexpression at the molecular level, but there is a paucity of information on the ultimate consequences on overall brain functional organization. We have assessed the brain functional status in Down syndrome using functional connectivity MRI. Resting-state whole-brain connectivity degree maps were generated in 20 Down syndrome individuals and 20 control subjects to identify sites showing anomalous synchrony with other areas. A subsequent region-of-interest mapping served to detail the anomalies and to assess their potential contribution to poor adaptive behavior. Down syndrome individuals showed higher regional connectivity in a ventral brain system involving the amygdala/anterior temporal region and the ventral aspect of both the anterior cingulate and frontal cortices. By contrast, lower functional connectivity was identified in dorsal executive networks involving dorsal prefrontal and anterior cingulate cortices and posterior insula. Both functional connectivity increases and decreases contributed to account for patient scoring on adaptive behavior related to communication skills. The data overall suggest a distinctive functional organization with system-specific anomalies associated with reduced adaptive efficiency. Opposite effects were identified on distinct frontal and anterior temporal structures and relative sparing of posterior brain areas, which is generally consistent with Down syndrome cognitive profile. Relevantly, measurable connectivity changes, as a marker of the brain functional anomaly, could have a role in the development of therapeutic strategies addressed to improve the quality of life in Down syndrome individuals. Copyright © 2014 Elsevier Ltd. All rights reserved.

PET evaluation of the dopamine system of the human brain

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

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

1996-07-01

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

A close look at brain dynamics: cells and vessels seen by in vivo two-photon microscopy.

PubMed

Fumagalli, Stefano; Ortolano, Fabrizio; De Simoni, Maria-Grazia

2014-10-01

The cerebral vasculature has a unique role in providing a constant supply of oxygen and nutrients to ensure normal brain functions. Blood vessels that feed the brain are far from being simply channels for passive transportation of fluids. They form complex structures made up of different cell types. These structures regulate blood supply, local concentrations of O2 and CO2, transport of small molecules, trafficking of plasma cells and fine cerebral functions in normal and diseased brains. Until few years ago, analysis of these functions has been typically based on post mortem techniques, whose interpretation is limited by the need for tissue processing at specific times. For a reliable and effective picture of the dynamic processes in the central nervous system, real-time information in vivo is required. There are now few in vivo systems, among which two-photon microscopy (2-PM) is a truly innovative tool for studying the brain. 2-PM has been used to dissect specific aspects of vascular and immune cell dynamics in the context of neurological diseases, providing exciting results that could not have been obtained with conventional methods. This review summarizes the latest findings on vascular and immune system action in the brain, with particular focus on the dynamic responses after ischemic brain injury. 2-PM has helped define the hierarchical architecture of the brain vasculature, the dynamic interaction between the vasculature and immune cells recruited to lesion sites, the effects of blood flow on neuronal and microglial activity and the ability of cells of the neurovascular unit to regulate blood flow. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brain biomarkers and pre-injury cognition are associated with long-term cognitive outcome in children with traumatic brain injury.

PubMed

Wilkinson, Amy A; Dennis, Maureen; Simic, Nevena; Taylor, Margot J; Morgan, Benjamin R; Frndova, Helena; Choong, Karen; Campbell, Craig; Fraser, Douglas; Anderson, Vicki; Guerguerian, Anne-Marie; Schachar, Russell; Hutchison, Jamie

2017-07-24

Children with traumatic brain injury (TBI) are frequently at risk of long-term impairments of attention and executive functioning but these problems are difficult to predict. Although deficits have been reported to vary with injury severity, age at injury and sex, prognostication of outcome remains imperfect at a patient-specific level. The objective of this proof of principle study was to evaluate a variety of patient variables, along with six brain-specific and inflammatory serum protein biomarkers, as predictors of long-term cognitive outcome following paediatric TBI. Outcome was assessed in 23 patients via parent-rated questionnaires related to attention deficit hyperactivity disorder (ADHD) and executive functioning, using the Conners 3rd Edition Rating Scales (Conners-3) and Behaviour Rating Inventory of Executive Function (BRIEF) at a mean time since injury of 3.1 years. Partial least squares (PLS) analyses were performed to identify factors measured at the time of injury that were most closely associated with outcome on (1) the Conners-3 and (2) the Behavioural Regulation Index (BRI) and (3) Metacognition Index (MI) of the BRIEF. Higher levels of neuron specific enolase (NSE) and lower levels of soluble neuron cell adhesion molecule (sNCAM) were associated with higher scores on the inattention, hyperactivity/impulsivity and executive functioning scales of the Conners-3, as well as working memory and initiate scales of the MI from the BRIEF. Higher levels of NSE only were associated with higher scores on the inhibit scale of the BRI. NSE and sNCAM show promise as reliable, early predictors of long-term attention-related and executive functioning problems following paediatric TBI.

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 changes detected by functional magnetic resonance imaging and spectroscopy in patients with Crohn's disease.

PubMed

Lv, Kun; Fan, Yi-Hong; Xu, Li; Xu, Mao-Sheng

2017-05-28

Crohn's disease (CD) is a chronic, non-specific granulomatous inflammatory disorder that commonly affects the small intestine and is a phenotype of inflammatory bowel disease (IBD). CD is prone to relapse, and its incidence displays a persistent increase in developing countries. However, the pathogenesis of CD is poorly understood, with some studies emphasizing the link between CD and the intestinal microbiota. Specifically, studies point to the brain-gut-enteric microbiota axis as a key player in the occurrence and development of CD. Furthermore, investigations have shown white-matter lesions and neurologic deficits in patients with IBD. Based on these findings, brain activity changes in CD patients have been detected by blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI). BOLD-fMRI functions by detecting a local increase in relative blood oxygenation that results from neurotransmitter activity and thus reflects local neuronal firing rates. Therefore, biochemical concentrations of neurotransmitters or metabolites may change in corresponding brain regions of CD patients. To further study this phenomenon, brain changes of CD patients can be detected non-invasively, effectively and accurately by BOLD-fMRI combined with magnetic resonance spectroscopy (MRS). This approach can further shed light on the mechanisms of the occurrence and development of neurological CD. Overall, this paper reviews the current status and prospects on fMRI and MRS for evaluation of patients with CD based on the brain-gut-enteric microbiota axis.

Altered blood-brain barrier transport in neuro-inflammatory disorders.

PubMed

Schenk, Geert J; de Vries, Helga E

2016-06-01

During neurodegenerative and neuroinflammatory disorders of the central nervous system (CNS), such as Alzheimer's disease (AD) and multiple sclerosis (MS), the protective function of the blood-brain barrier (BBB) may be severely impaired. The general neuro-inflammatory response, ranging from activation of glial cells to immune cell infiltration that is frequently associated with such brain diseases may underlie the loss of the integrity and function of the BBB. Consequentially, the delivery and disposition of drugs to the brain will be altered and may influence the treatment efficiency of such diseases. Altered BBB transport of drugs into the CNS during diseases may be the result of changes in both specific transport and non-specific transport pathways. Potential alterations in transport routes like adsorptive mediated endocytosis and receptor-mediated endocytosis may affect drug delivery to the brain. As such, drugs that normally are unable to traverse the BBB may reach their target in the diseased brain due to increased permeability. In contrast, the delivery of (targeted) drugs could be hampered during inflammatory conditions due to disturbed transport mechanisms. Therefore, the inventory of the neuro-inflammatory status of the neurovasculature (or recovery thereof) is of utmost importance in choosing and designing an adequate drug targeting strategy under disease conditions. Within this review we will briefly discuss how the function of the BBB can be affected during disease and how this may influence the delivery of drugs into the diseased CNS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nanotools for Neuroscience and Brain Activity Mapping

PubMed Central

Alivisatos, A. Paul; Andrews, Anne M.; Boyden, Edward S.; Chun, Miyoung; Church, George M.; Deisseroth, Karl; Donoghue, John P.; Fraser, Scott E.; Lippincott-Schwartz, Jennifer; Looger, Loren L.; Masmanidis, Sotiris; McEuen, Paul L.; Nurmikko, Arto V.; Park, Hongkun; Peterka, Darcy S.; Reid, Clay; Roukes, Michael L.; Scherer, Axel; Schnitzer, Mark; Sejnowski, Terrence J.; Shepard, Kenneth L.; Tsao, Doris; Turrigiano, Gina; Weiss, Paul S.; Xu, Chris; Yuste, Rafael; Zhuang, Xiaowei

2013-01-01

Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function. PMID:23514423

Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor

PubMed Central

Gibson, William S.; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P.; Welker, Kirk M.; Klassen, Bryan T.; Min, Hoon-Ki

2016-01-01

Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson’s disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal modelling revealed a correlation between therapeutic effectiveness and attenuated within-region inhibitory connectivity in cerebellum. Finally, specific subregions of sensorimotor cortex were identified in which deep brain stimulation-evoked activation correlated with the presence of unwanted paraesthesias. These results suggest that thalamic deep brain stimulation in tremor likely exerts its effects through modulation of both olivocerebellar and thalamocortical circuits. In addition, our findings indicate that deep brain stimulation-evoked functional activation maps obtained intraoperatively may contain predictive information pertaining to the therapeutic and adverse effects induced by deep brain stimulation. PMID:27329768

Molecular Mechanisms of Neuroplasticity: An Expanding Universe.

PubMed

Gulyaeva, N V

2017-03-01

Biochemical processes in synapses and other neuronal compartments underlie neuroplasticity (functional and structural alterations in the brain enabling adaptation to the environment, learning, memory, as well as rehabilitation after brain injury). This basic molecular level of brain plasticity covers numerous specific proteins (enzymes, receptors, structural proteins, etc.) participating in many coordinated and interacting signal and metabolic processes, their modulation forming a molecular basis for brain plasticity. The articles in this issue are focused on different "hot points" in the research area of biochemical mechanisms supporting neuroplasticity.

Brain structure and executive functions in children with cerebral palsy: a systematic review.

PubMed

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

2013-05-01

This systematic review aimed to establish the current knowledge about brain structure and executive function (EF) in children with cerebral palsy (CP). Five databases were searched (up till July 2012). Six articles met the inclusion criteria, all included structural brain imaging though no functional brain imaging. Study quality was assessed using the STROBE checklist. All articles scored between 58.7% and 70.5% for quality (100% is the maximum score). The included studies all reported poorer performance on EF tasks for children with CP compared to children without CP. For the selected EF measures non-significant effect sizes were found for the CP group compared to a semi-control group (children without cognitive deficits but not included in a control group). This could be due to the small sample sizes, group heterogeneity and lack of comparison of the CP group to typically developing children. The included studies did not consider specific brain areas associated with EF performance. To conclude, there is a paucity of brain imaging studies focused on EF in children with CP, especially of studies that include functional brain imaging. Outcomes of the present studies are difficult to compare as each study included different EF measures and cortical abnormality measures. Copyright © 2013 Elsevier Ltd. All rights reserved.

Improving Functional MRI Registration Using Whole-Brain Functional Correlation Tensors.

PubMed

Zhou, Yujia; Yap, Pew-Thian; Zhang, Han; Zhang, Lichi; Feng, Qianjin; Shen, Dinggang

2017-09-01

Population studies of brain function with resting-state functional magnetic resonance imaging (rs-fMRI) largely rely on the accurate inter-subject registration of functional areas. This is typically achieved through registration of the corresponding T1-weighted MR images with more structural details. However, accumulating evidence has suggested that such strategy cannot well-align functional regions which are not necessarily confined by the anatomical boundaries defined by the T1-weighted MR images. To mitigate this problem, various registration algorithms based directly on rs-fMRI data have been developed, most of which have utilized functional connectivity (FC) as features for registration. However, most of the FC-based registration methods usually extract the functional features only from the thin and highly curved cortical grey matter (GM), posing a great challenge in accurately estimating the whole-brain deformation field. In this paper, we demonstrate that the additional useful functional features can be extracted from brain regions beyond the GM, particularly, white-matter (WM) based on rs-fMRI, for improving the overall functional registration. Specifically, we quantify the local anisotropic correlation patterns of the blood oxygenation level-dependent (BOLD) signals, modeled by functional correlation tensors (FCTs), in both GM and WM. Functional registration is then performed based on multiple components of the whole-brain FCTs using a multichannel Large Deformation Diffeomorphic Metric Mapping (mLDDMM) algorithm. Experimental results show that our proposed method achieves superior functional registration performance, compared with other conventional registration methods.

[Clinical interest of fMRI and functional exploration methods of brain activity and interactivity: physical and neurophysiological considerations].

PubMed

de Marco, G; Menuel, C; Guillevin, R; Vallée, J-N; Lehmann, P; Fall, S; Quaglino, V; Bourdin, B; Devauchelle, B; Chiras, J

2008-07-01

After having provided a brief reminder of the principle of the blood oxygen level-dependent (BOLD) contrast effect, the physiological bases of brain activity and the concepts of functional integration and effective connectivity, we describe the most recent approaches, which permit to explore brain activity and putative networks of interconnected active areas in order to examine the normal brain physiology and its dysfunctions. We present various methods and studies of brain activity analysis clinically applicable, and we detail the concepts of functional and effective connectivity, which allow to study the cerebral plasticity which occurs at the child's during the maturation (e.g., dyslexia), at the adult during the ageing (e.g., Alzheimer disease), or still in schizophrenia or Parkinson disease. The study of specific circuits in networks has to allow defining in a more realistic way the dynamic of the central nervous system, which underlies various cerebral functions, both in physiological and pathological conditions. This connectivity approach should improve the diagnostic and facilitate the development of new therapeutic strategies.

Some Current Findings on Brain Characteristics of the Mathematically Gifted Adolescent

ERIC Educational Resources Information Center

O'Boyle, Michael W.

2005-01-01

A number of studies investigating the brain characteristics of mathematically gifted youth indicate that they possess a unique functional organisation as compared to those of average math ability (O'Boyle, et al., 1995). Specifically, data from a variety of behavioural and psychophysiological experiments tend to suggest enhanced processing…

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

PubMed Central

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

2014-01-01

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

Integrative Analysis of Brain Region-specific Shank3 Interactomes for Understanding the Heterogeneity of Neuronal Pathophysiology Related to SHANK3 Mutations

PubMed Central

Lee, Yeunkum; Kang, Hyojin; Lee, Bokyoung; Zhang, Yinhua; Kim, Yoonhee; Kim, Shinhyun; Kim, Won-Ki; Han, Kihoon

2017-01-01

Recent molecular genetic studies have identified 100s of risk genes for various neurodevelopmental and neuropsychiatric disorders. As the number of risk genes increases, it is becoming clear that different mutations of a single gene could cause different types of disorders. One of the best examples of such a gene is SHANK3, which encodes a core scaffold protein of the neuronal excitatory post-synapse. Deletions, duplications, and point mutations of SHANK3 are associated with autism spectrum disorders, intellectual disability, schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Nevertheless, how the different mutations of SHANK3 can lead to such phenotypic diversity remains largely unknown. In this study, we investigated whether Shank3 could form protein complexes in a brain region-specific manner, which might contribute to the heterogeneity of neuronal pathophysiology caused by SHANK3 mutations. To test this, we generated a medial prefrontal cortex (mPFC) Shank3 in vivo interactome consisting of 211 proteins, and compared this protein list with a Shank3 interactome previously generated from mixed hippocampal and striatal (HP+STR) tissues. Unexpectedly, we found that only 47 proteins (about 20%) were common between the two interactomes, while 164 and 208 proteins were specifically identified in the mPFC and HP+STR interactomes, respectively. Each of the mPFC- and HP+STR-specific Shank3 interactomes represents a highly interconnected network. Upon comparing the brain region-enriched proteomes, we found that the large difference between the mPFC and HP+STR Shank3 interactomes could not be explained by differential protein expression profiles among the brain regions. Importantly, bioinformatic pathway analysis revealed that the representative biological functions of the mPFC- and HP+STR-specific Shank3 interactomes were different, suggesting that these interactors could mediate the brain region-specific functions of Shank3. Meanwhile, the same analysis on the common Shank3 interactors, including Homer and GKAP/SAPAP proteins, suggested that they could mainly function as scaffolding proteins at the post-synaptic density. Lastly, we found that the mPFC- and HP+STR-specific Shank3 interactomes contained a significant number of proteins associated with neurodevelopmental and neuropsychiatric disorders. These results suggest that Shank3 can form protein complexes in a brain region-specific manner, which might contribute to the pathophysiological and phenotypic diversity of disorders related to SHANK3 mutations. PMID:28469556

The Major Histocompatibility Complex and Autism Spectrum Disorder

PubMed Central

Needleman, Leigh A.; McAllister, A. Kimberley

2015-01-01

Autism spectrum disorder (ASD) is a complex disorder that appears to be caused by interactions between genetic changes and environmental insults during early development. A wide range of factors have been linked to the onset of ASD, but recently both genetic associations and environmental factors point to a central role for immune- related genes and immune responses to environmental stimuli. Specifically, many of the proteins encoded by the major histocompatibility complex (MHC) play a vital role in the formation, refinement, maintenance, and plasticity of the brain. Manipulations of levels of MHC molecules have illustrated how disrupted MHC signaling can significantly alter brain connectivity and function. Thus, an emerging hypothesis in our field is that disruptions in MHC expression in the developing brain caused by mutations and/or immune dysregulation may contribute to the altered brain connectivity and function characteristic of ASD. This review provides an overview of the structure and function of the three classes of MHC molecules in the immune system, healthy brain, and their possible involvement in ASD. PMID:22760919

The maturing architecture of the brain's default network

PubMed Central

Fair, Damien A.; Cohen, Alexander L.; Dosenbach, Nico U. F.; Church, Jessica A.; Miezin, Francis M.; Barch, Deanna M.; Raichle, Marcus E.; Petersen, Steven E.; Schlaggar, Bradley L.

2008-01-01

In recent years, the brain's “default network,” a set of regions characterized by decreased neural activity during goal-oriented tasks, has generated a significant amount of interest, as well as controversy. Much of the discussion has focused on the relationship of these regions to a “default mode” of brain function. In early studies, investigators suggested that, the brain's default mode supports “self-referential” or “introspective” mental activity. Subsequently, regions of the default network have been more specifically related to the “internal narrative,” the “autobiographical self,” “stimulus independent thought,” “mentalizing,” and most recently “self-projection.” However, the extant literature on the function of the default network is limited to adults, i.e., after the system has reached maturity. We hypothesized that further insight into the network's functioning could be achieved by characterizing its development. In the current study, we used resting-state functional connectivity MRI (rs-fcMRI) to characterize the development of the brain's default network. We found that the default regions are only sparsely functionally connected at early school age (7–9 years old); over development, these regions integrate into a cohesive, interconnected network. PMID:18322013

Altered Resting Brain Function and Structure in Professional Badminton Players

PubMed Central

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

2012-01-01

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

Intranasal epidermal growth factor treatment rescues neonatal brain injury.

PubMed

Scafidi, Joseph; Hammond, Timothy R; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J; Hyder, Fahmeed; Horvath, Tamas L; Gallo, Vittorio

2014-02-13

There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

Intranasal epidermal growth factor treatment rescues neonatal brain injury

NASA Astrophysics Data System (ADS)

Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

2014-02-01

There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

Verbal Memory in Parkinson’s Disease: A Combined DTI and fMRI Study

PubMed Central

Lucas-Jiménez, Olaia; Díez-Cirarda, María; Ojeda, Natalia; Peña, Javier; Cabrera-Zubizarreta, Alberto; Ibarretxe-Bilbao, Naroa

2015-01-01

Background: While significant progress has been made to determine the functional role of specific gray matter areas underlying verbal memory in Parkinson’s disease (PD), very little is known about the relationship between these regions and their underlying white matter structures. Objective: The objectives of this study were (1) to investigate verbal memory, fractional anisotropy and brain activation differences between PD patients and healthy controls (HC), (2) to explore the neuroanatomical and neurofunctional correlates of verbal memory in PD, and (3) to investigate the relationship between these neuroanatomical and neurofunctional verbal memory correlates in PD. Methods: Functional magnetic resonance imaging (fMRI) while performing a verbal memory paradigm and diffusion tensor imaging data (DTI), were acquired in 37 PD patients and 15 age-, sex-, and education-matched HC. Results: PD patients showed verbal recognition memory impairment, lower fractional anisotropy in the anterior cingulate tract, and lower brain activation in the inferior orbitofrontal cortex compared to HC. Brain activation in the inferior orbitofrontal cortex correlated significantly with verbal recognition memory impairment in PD patients. In addition, a relationship between brain activation in the inferior orbitofrontal cortex and fractional anisotropy of the uncinate fasciculus was found in PD. Conclusions: These results reveal that deficits in verbal memory in PD are accompanied by functional brain activation changes, but also have specific structural correlates related to white matter microstructural integrity. PMID:27070003

Neural signatures of third-party punishment: evidence from penetrating traumatic brain injury.

PubMed

Glass, Leila; Moody, Lara; Grafman, Jordan; Krueger, Frank

2016-02-01

The ability to survive within a cooperative society depends on impartial third-party punishment (TPP) of social norm violations. Two cognitive mechanisms have been postulated as necessary for the successful completion of TPP: evaluation of legal responsibility and selection of a suitable punishment given the magnitude of the crime. Converging neuroimaging research suggests two supporting domain-general networks; a mentalizing network for evaluation of legal responsibility and a central-executive network for determination of punishment. A whole-brain voxel-based lesion-symptom mapping approach was used in conjunction with a rank-order TPP task to identify brain regions necessary for TPP in a large sample of patients with penetrating traumatic brain injury. Patients who demonstrated atypical TPP had specific lesions in core regions of the mentalizing (dorsomedial prefrontal cortex [PFC], ventromedial PFC) and central-executive (bilateral dorsolateral PFC, right intraparietal sulcus) networks. Altruism and executive functioning (concept formation skills) were significant predictors of TPP: altruism was uniquely associated with TPP in patients with lesions in right dorsolateral PFC and executive functioning was uniquely associated with TPP in individuals with lesions in left PFC. Our findings contribute to the extant literature to support underlying neural networks associated with TPP, with specific brain-behavior causal relationships confirming recent functional neuroimaging research. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Self-averaging in complex brain neuron signals

NASA Astrophysics Data System (ADS)

Bershadskii, A.; Dremencov, E.; Fukayama, D.; Yadid, G.

2002-12-01

Nonlinear statistical properties of Ventral Tegmental Area (VTA) of limbic brain are studied in vivo. VTA plays key role in generation of pleasure and in development of psychological drug addiction. It is shown that spiking time-series of the VTA dopaminergic neurons exhibit long-range correlations with self-averaging behavior. This specific VTA phenomenon has no relation to VTA rewarding function. Last result reveals complex role of VTA in limbic brain.

Optimizing real time fMRI neurofeedback for therapeutic discovery and development

PubMed Central

Stoeckel, L.E.; Garrison, K.A.; Ghosh, S.; Wighton, P.; Hanlon, C.A.; Gilman, J.M.; Greer, S.; Turk-Browne, N.B.; deBettencourt, M.T.; Scheinost, D.; Craddock, C.; Thompson, T.; Calderon, V.; Bauer, C.C.; George, M.; Breiter, H.C.; Whitfield-Gabrieli, S.; Gabrieli, J.D.; LaConte, S.M.; Hirshberg, L.; Brewer, J.A.; Hampson, M.; Van Der Kouwe, A.; Mackey, S.; Evins, A.E.

2014-01-01

While reducing the burden of brain disorders remains a top priority of organizations like the World Health Organization and National Institutes of Health, the development of novel, safe and effective treatments for brain disorders has been slow. In this paper, we describe the state of the science for an emerging technology, real time functional magnetic resonance imaging (rtfMRI) neurofeedback, in clinical neurotherapeutics. We review the scientific potential of rtfMRI and outline research strategies to optimize the development and application of rtfMRI neurofeedback as a next generation therapeutic tool. We propose that rtfMRI can be used to address a broad range of clinical problems by improving our understanding of brain–behavior relationships in order to develop more specific and effective interventions for individuals with brain disorders. We focus on the use of rtfMRI neurofeedback as a clinical neurotherapeutic tool to drive plasticity in brain function, cognition, and behavior. Our overall goal is for rtfMRI to advance personalized assessment and intervention approaches to enhance resilience and reduce morbidity by correcting maladaptive patterns of brain function in those with brain disorders. PMID:25161891

Interventional programmes to improve cognition during healthy and pathological ageing: Cortical modulations and evidence for brain plasticity.

PubMed

Cespón, Jesús; Miniussi, Carlo; Pellicciari, Maria Concetta

2018-05-01

A growing body of evidence suggests that healthy elderly individuals and patients with Alzheimer's disease retain an important potential for neuroplasticity. This review summarizes studies investigating the modulation of neural activity and structural brain integrity in response to interventions involving cognitive training, physical exercise and non-invasive brain stimulation in healthy elderly and cognitively impaired subjects (including patients with mild cognitive impairment (MCI) and Alzheimer's disease). Moreover, given the clinical relevance of neuroplasticity, we discuss how evidence for neuroplasticity can be inferred from the functional and structural brain changes observed after implementing these interventions. We emphasize that multimodal programmes, which combine several types of interventions, improve cognitive function to a greater extent than programmes that use a single interventional approach. We suggest specific methods for weighting the relative importance of cognitive training, physical exercise and non-invasive brain stimulation according to the functional and structural state of the brain of the targeted subject to maximize the cognitive improvements induced by multimodal programmes. Copyright © 2018 Elsevier B.V. All rights reserved.

Self-regulation of brain oscillations as a treatment for aberrant brain connections in children with autism.

PubMed

Pineda, J A; Juavinett, A; Datko, M

2012-12-01

Autism is a highly varied developmental disorder typically characterized by deficits in reciprocal social interaction, difficulties with verbal and nonverbal communication, and restricted interests and repetitive behaviors. Although a wide range of behavioral, pharmacological, and alternative medicine strategies have been reported to ameliorate specific symptoms for some individuals, there is at present no cure for the condition. Nonetheless, among the many incompatible observations about aspects of the development, anatomy, and functionality of the autistic brain, it is widely agreed that it is characterized by widespread aberrant connectivity. Such disordered connectivity, be it increased, decreased, or otherwise compromised, may complicate healthy synchronization and communication among and within different neural circuits, thereby producing abnormal processing of sensory inputs necessary for normal social life. It is widely accepted that the innate properties of brain electrical activity produce pacemaker elements and linked networks that oscillate synchronously or asynchronously, likely reflecting a type of functional connectivity. Using phase coherence in multiple frequency EEG bands as a measure of functional connectivity, studies have shown evidence for both global hypoconnectivity and local hyperconnectivity in individuals with ASD. However, the nature of the brain's experience-dependent structural plasticity suggests that these abnormal patterns may be reversed with the proper type of treatment. Indeed, neurofeedback (NF) training, an intervention based on operant conditioning that results in self-regulation of brain electrical oscillations, has shown promise in addressing marked abnormalities in functional and structural connectivity. It is hypothesized that neurofeedback produces positive behavioral changes in ASD children by normalizing the aberrant connections within and between neural circuits. NF exploits the brain's plasticity to normalize aberrant connectivity patterns apparent in the autistic brain. By grounding this training in known anatomical (e.g., mirror neuron system) and functional markers (e.g., mu rhythms) of autism, NF training holds promise to support current treatments for this complex disorder. The proposed hypothesis specifically states that neurofeedback-induced alpha mu (8-12Hz) rhythm suppression or desynchronization, a marker of cortical activation, should induce neuroplastic changes and lead to normalization in relevant mirroring networks that have been associated with higher-order social cognition. Copyright © 2012 Elsevier Ltd. All rights reserved.

The hubs of the human connectome are generally implicated in the anatomy of brain disorders.

PubMed

Crossley, Nicolas A; Mechelli, Andrea; Scott, Jessica; Carletti, Francesco; Fox, Peter T; McGuire, Philip; Bullmore, Edward T

2014-08-01

Brain networks or 'connectomes' include a minority of highly connected hub nodes that are functionally valuable, because their topological centrality supports integrative processing and adaptive behaviours. Recent studies also suggest that hubs have higher metabolic demands and longer-distance connections than other brain regions, and therefore could be considered biologically costly. Assuming that hubs thus normally combine both high topological value and high biological cost, we predicted that pathological brain lesions would be concentrated in hub regions. To test this general hypothesis, we first identified the hubs of brain anatomical networks estimated from diffusion tensor imaging data on healthy volunteers (n = 56), and showed that computational attacks targeted on hubs disproportionally degraded the efficiency of brain networks compared to random attacks. We then prepared grey matter lesion maps, based on meta-analyses of published magnetic resonance imaging data on more than 20 000 subjects and 26 different brain disorders. Magnetic resonance imaging lesions that were common across all brain disorders were more likely to be located in hubs of the normal brain connectome (P < 10(-4), permutation test). Specifically, nine brain disorders had lesions that were significantly more likely to be located in hubs (P < 0.05, permutation test), including schizophrenia and Alzheimer's disease. Both these disorders had significantly hub-concentrated lesion distributions, although (almost completely) distinct subsets of cortical hubs were lesioned in each disorder: temporal lobe hubs specifically were associated with higher lesion probability in Alzheimer's disease, whereas in schizophrenia lesions were concentrated in both frontal and temporal cortical hubs. These results linking pathological lesions to the topological centrality of nodes in the normal diffusion tensor imaging connectome were generally replicated when hubs were defined instead by the meta-analysis of more than 1500 task-related functional neuroimaging studies of healthy volunteers to create a normative functional co-activation network. We conclude that the high cost/high value hubs of human brain networks are more likely to be anatomically abnormal than non-hubs in many (if not all) brain disorders. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Finding the imposter: brain connectivity of lesions causing delusional misidentifications

PubMed Central

Darby, R Ryan; Laganiere, Simon; Pascual-Leone, Alvaro; Prasad, Sashank; Fox, Michael D

2017-01-01

Abstract See McKay and Furl (doi:10.1093/aww323) for a scientific commentary on this article. Focal brain injury can sometimes lead to bizarre symptoms, such as the delusion that a family member has been replaced by an imposter (Capgras syndrome). How a single brain lesion could cause such a complex disorder is unclear, leading many to speculate that concurrent delirium, psychiatric disease, dementia, or a second lesion is required. Here we instead propose that Capgras and other delusional misidentification syndromes arise from single lesions at unique locations within the human brain connectome. This hypothesis is motivated by evidence that symptoms emerge from sites functionally connected to a lesion location, not just the lesion location itself. First, 17 cases of lesion-induced delusional misidentifications were identified and lesion locations were mapped to a common brain atlas. Second, lesion network mapping was used to identify brain regions functionally connected to the lesion locations. Third, regions involved in familiarity perception and belief evaluation, two processes thought to be abnormal in delusional misidentifications, were identified using meta-analyses of previous functional magnetic resonance imaging studies. We found that all 17 lesion locations were functionally connected to the left retrosplenial cortex, the region most activated in functional magnetic resonance imaging studies of familiarity. Similarly, 16 of 17 lesion locations were functionally connected to the right frontal cortex, the region most activated in functional magnetic resonance imaging studies of expectation violation, a component of belief evaluation. This connectivity pattern was highly specific for delusional misidentifications compared to four other lesion-induced neurological syndromes (P < 0.0001). Finally, 15 lesions causing other types of delusions were connected to expectation violation (P < 0.0001) but not familiarity regions, demonstrating specificity for delusion content. Our results provide potential neuroanatomical correlates for impaired familiarity perception and belief evaluation in patients with delusional misidentifications. More generally, we demonstrate a mechanism by which a single lesion can cause a complex neuropsychiatric syndrome based on that lesion’s unique pattern of functional connectivity, without the need for pre-existing or hidden pathology. PMID:28082298

Brain Region–Specific Alterations in the Gene Expression of Cytokines, Immune Cell Markers and Cholinergic System Components during Peripheral Endotoxin–Induced Inflammation

PubMed Central

Silverman, Harold A; Dancho, Meghan; Regnier-Golanov, Angelique; Nasim, Mansoor; Ochani, Mahendar; Olofsson, Peder S; Ahmed, Mohamed; Miller, Edmund J; Chavan, Sangeeta S; Golanov, Eugene; Metz, Christine N; Tracey, Kevin J; Pavlov, Valentin A

2014-01-01

Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune–brain communication, including the impact of peripheral inflammation on brain region–specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels), remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum and thalamus in mice after an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of interleukin (IL)-1β, IL-6 and other cytokines and brain region–specific increases in Il1b (the highest increase, relative to basal level, was in cortex; the lowest increase was in cerebellum) and Il6 (highest increase in cerebellum; lowest increase in striatum) mRNA expression. Gene expression of brain Gfap (astrocyte marker) was also differentially increased. However, Iba1 (microglia marker) mRNA expression was decreased in the cortex, hippocampus and other brain regions in parallel with morphological changes, indicating microglia activation. Brain choline acetyltransferase (Chat ) mRNA expression was decreased in the striatum, acetylcholinesterase (Ache) mRNA expression was decreased in the cortex and increased in the hippocampus, and M1 muscarinic acetylcholine receptor (Chrm1) mRNA expression was decreased in the cortex and the brainstem. These results reveal a previously unrecognized regional specificity in brain immunoregulatory and cholinergic system gene expression in the context of peripheral inflammation and are of interest for designing future antiinflammatory approaches. PMID:25299421

Why the Brain Knows More than We Do: Non-Conscious Representations and Their Role in the Construction of Conscious Experience

PubMed Central

Dresp-Langley, Birgitta

2011-01-01

Scientific studies have shown that non-conscious stimuli and representations influence information processing during conscious experience. In the light of such evidence, questions about potential functional links between non-conscious brain representations and conscious experience arise. This article discusses neural model capable of explaining how statistical learning mechanisms in dedicated resonant circuits could generate specific temporal activity traces of non-conscious representations in the brain. How reentrant signaling, top-down matching, and statistical coincidence of such activity traces may lead to the progressive consolidation of temporal patterns that constitute the neural signatures of conscious experience in networks extending across large distances beyond functionally specialized brain regions is then explained. PMID:24962683

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.

Acupuncture inhibits cue-induced heroin craving and brain activation★

PubMed Central

Cai, Xinghui; Song, Xiaoge; Li, Chuanfu; Xu, Chunsheng; Li, Xiliang; Lu, Qi

2012-01-01

Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point (ST36) without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving. PMID:25368637

Acupuncture inhibits cue-induced heroin craving and brain activation.

PubMed

Cai, Xinghui; Song, Xiaoge; Li, Chuanfu; Xu, Chunsheng; Li, Xiliang; Lu, Qi

2012-11-25

Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point (ST36) without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving.

A Magnetic Resonance Compatible Soft Wearable Robotic Glove for Hand Rehabilitation and Brain Imaging.

PubMed

Hong Kai Yap; Kamaldin, Nazir; Jeong Hoon Lim; Nasrallah, Fatima A; Goh, James Cho Hong; Chen-Hua Yeow

2017-06-01

In this paper, we present the design, fabrication and evaluation of a soft wearable robotic glove, which can be used with functional Magnetic Resonance imaging (fMRI) during the hand rehabilitation and task specific training. The soft wearable robotic glove, called MR-Glove, consists of two major components: a) a set of soft pneumatic actuators and b) a glove. The soft pneumatic actuators, which are made of silicone elastomers, generate bending motion and actuate finger joints upon pressurization. The device is MR-compatible as it contains no ferromagnetic materials and operates pneumatically. Our results show that the device did not cause artifacts to fMRI images during hand rehabilitation and task-specific exercises. This study demonstrated the possibility of using fMRI and MR-compatible soft wearable robotic device to study brain activities and motor performances during hand rehabilitation, and to unravel the functional effects of rehabilitation robotics on brain stimulation.

Improved Mitochondrial Function in Brain Aging and Alzheimer Disease – the New Mechanism of Action of the Old Metabolic Enhancer Piracetam

PubMed Central

Leuner, Kristina; Kurz, Christopher; Guidetti, Giorgio; Orgogozo, Jean-Marc; Müller, Walter E.

2010-01-01

Piracetam, the prototype of the so-called nootropic drugs’ is used since many years in different countries to treat cognitive impairment in aging and dementia. Findings that piracetam enhances fluidity of brain mitochondrial membranes led to the hypothesis that piracetam might improve mitochondrial function, e.g., might enhance ATP synthesis. This assumption has recently been supported by a number of observations showing enhanced mitochondrial membrane potential, enhanced ATP production, and reduced sensitivity for apoptosis in a variety of cell and animal models for aging and Alzheimer disease. As a specific consequence, substantial evidence for elevated neuronal plasticity as a specific effect of piracetam has emerged. Taken together, this new findings can explain many of the therapeutic effects of piracetam on cognition in aging and dementia as well as different situations of brain dysfunctions. PMID:20877425

Modal demultiplexing properties of tapered and nanostructured optical fibers for in vivo optogenetic control of neural activity.

PubMed

Pisanello, Marco; Della Patria, Andrea; Sileo, Leonardo; Sabatini, Bernardo L; De Vittorio, Massimo; Pisanello, Ferruccio

2015-10-01

Optogenetic approaches to manipulate neural activity have revolutionized the ability of neuroscientists to uncover the functional connectivity underlying brain function. At the same time, the increasing complexity of in vivo optogenetic experiments has increased the demand for new techniques to precisely deliver light into the brain, in particular to illuminate selected portions of the neural tissue. Tapered and nanopatterned gold-coated optical fibers were recently proposed as minimally invasive multipoint light delivery devices, allowing for site-selective optogenetic stimulation in the mammalian brain [Pisanello , Neuron82, 1245 (2014)]. Here we demonstrate that the working principle behind these devices is based on the mode-selective photonic properties of the fiber taper. Using analytical and ray tracing models we model the finite conductance of the metal coating, and show that single or multiple optical windows located at specific taper sections can outcouple only specific subsets of guided modes injected into the fiber.

Visible rodent brain-wide networks at single-neuron resolution

PubMed Central

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

2015-01-01

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

The structural and functional brain networks that support human social networks.

PubMed

Noonan, M P; Mars, R B; Sallet, J; Dunbar, R I M; Fellows, L K

2018-02-20

Social skills rely on a specific set of cognitive processes, raising the possibility that individual differences in social networks are related to differences in specific brain structural and functional networks. Here, we tested this hypothesis with multimodality neuroimaging. With diffusion MRI (DMRI), we showed that differences in structural integrity of particular white matter (WM) tracts, including cingulum bundle, extreme capsule and arcuate fasciculus were associated with an individual's social network size (SNS). A voxel-based morphology analysis demonstrated correlations between gray matter (GM) volume and SNS in limbic and temporal lobe regions. These structural changes co-occured with functional network differences. As a function of SNS, dorsomedial and dorsolateral prefrontal cortex showed altered resting-state functional connectivity with the default mode network (DMN). Finally, we integrated these three complementary methods, interrogating the relationship between social GM clusters and specific WM and resting-state networks (RSNs). Probabilistic tractography seeded in these GM nodes utilized the SNS-related WM pathways. Further, the spatial and functional overlap between the social GM clusters and the DMN was significantly closer than other control RSNs. These integrative analyses provide convergent evidence of the role of specific circuits in SNS, likely supporting the adaptive behavior necessary for success in extensive social environments. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumors

NASA Astrophysics Data System (ADS)

Xu, Hui; Li, Zhongyu; Yu, Yue; Sizdahkhani, Saman; Ho, Winson S.; Yin, Fangchao; Wang, Li; Zhu, Guoli; Zhang, Min; Jiang, Lei; Zhuang, Zhengping; Qin, Jianhua

2016-11-01

The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes-permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors. The complex BBB microenvironment is reproduced in this system via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research.

Resting-State Network Topology Differentiates Task Signals across the Adult Life Span.

PubMed

Chan, Micaela Y; Alhazmi, Fahd H; Park, Denise C; Savalia, Neil K; Wig, Gagan S

2017-03-08

Brain network connectivity differs across individuals. For example, older adults exhibit less segregated resting-state subnetworks relative to younger adults (Chan et al., 2014). It has been hypothesized that individual differences in network connectivity impact the recruitment of brain areas during task execution. While recent studies have described the spatial overlap between resting-state functional correlation (RSFC) subnetworks and task-evoked activity, it is unclear whether individual variations in the connectivity pattern of a brain area (topology) relates to its activity during task execution. We report data from 238 cognitively normal participants (humans), sampled across the adult life span (20-89 years), to reveal that RSFC-based network organization systematically relates to the recruitment of brain areas across two functionally distinct tasks (visual and semantic). The functional activity of brain areas (network nodes) were characterized according to their patterns of RSFC: nodes with relatively greater connections to nodes in their own functional system ("non-connector" nodes) exhibited greater activity than nodes with relatively greater connections to nodes in other systems ("connector" nodes). This "activation selectivity" was specific to those brain systems that were central to each of the tasks. Increasing age was accompanied by less differentiated network topology and a corresponding reduction in activation selectivity (or differentiation) across relevant network nodes. The results provide evidence that connectional topology of brain areas quantified at rest relates to the functional activity of those areas during task. Based on these findings, we propose a novel network-based theory for previous reports of the "dedifferentiation" in brain activity observed in aging. SIGNIFICANCE STATEMENT Similar to other real-world networks, the organization of brain networks impacts their function. As brain network connectivity patterns differ across individuals, we hypothesized that individual differences in network connectivity would relate to differences in brain activity. Using functional MRI in a group of individuals sampled across the adult life span (20-89 years), we measured correlations at rest and related the functional connectivity patterns to measurements of functional activity during two independent tasks. Brain activity varied in relation to connectivity patterns revealed by large-scale network analysis. This relationship tracked the differences in connectivity patterns accompanied by older age, providing important evidence for a link between the topology of areal connectivity measured at rest and the functional recruitment of these areas during task performance. Copyright © 2017 Chan et al.

Whole-brain functional hypoconnectivity as an endophenotype of autism in adolescents

PubMed Central

Moseley, R.L.; Ypma, R.J.F.; Holt, R.J.; Floris, D.; Chura, L.R.; Spencer, M.D.; Baron-Cohen, S.; Suckling, J.; Bullmore, E.; Rubinov, M.

2015-01-01

Endophenotypes are heritable and quantifiable markers that may assist in the identification of the complex genetic underpinnings of psychiatric conditions. Here we examined global hypoconnectivity as an endophenotype of autism spectrum conditions (ASCs). We studied well-matched groups of adolescent males with autism, genetically-related siblings of individuals with autism, and typically-developing control participants. We parcellated the brain into 258 regions and used complex-network analysis to detect a robust hypoconnectivity endophenotype in our participant group. We observed that whole-brain functional connectivity was highest in controls, intermediate in siblings, and lowest in ASC, in task and rest conditions. We identified additional, local endophenotype effects in specific networks including the visual processing and default mode networks. Our analyses are the first to show that whole-brain functional hypoconnectivity is an endophenotype of autism in adolescence, and may thus underlie the heritable similarities seen in adolescents with ASC and their relatives. PMID:26413477

[Processes of logical thought in a case of cerebral vascular lesion].

PubMed

Blanco Men ndez, R; Aguado Balsas, A M

Reasoning and logical thought processes have traditionally been attributed to frontal lobe function or,on the other hand, have been considered as diffuse functions of the brain. However, there is today evidence enough about the possibility to find dissociations in thought processes, depending on logical structure of the experimental tasks and referring to different areas of the brain, frontal and post rolandic ones. To study possible dissociations between thought structures corresponding to categorical and relational logic, on one hand, and propositional logic on the other hand. The case of a brain injured patient with vascular etiology, localized in left frontal parietal cortex, is presented. A specific battery of reasoning tests has been administered. . A differential performance at some reasoning experimental tasks has been found depending on such logical conceptual structures. The possibility of establishing dissociations among certain logical thought and intelectual functions depending on localization of possible brain lesion (frontal versus temporal) is discussed.

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

PubMed Central

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

2017-01-01

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

Cognitive accuracy and intelligent executive function in the brain and in business.

PubMed

Bailey, Charles E

2007-11-01

This article reviews research on cognition, language, organizational culture, brain, behavior, and evolution to posit the value of operating with a stable reference point based on cognitive accuracy and a rational bias. Drawing on rational-emotive behavioral science, social neuroscience, and cognitive organizational science on the one hand and a general model of brain and frontal lobe executive function on the other, I suggest implications for organizational success. Cognitive thought processes depend on specific brain structures functioning as effectively as possible under conditions of cognitive accuracy. However, typical cognitive processes in hierarchical business structures promote the adoption and application of subjective organizational beliefs and, thus, cognitive inaccuracies. Applying informed frontal lobe executive functioning to cognition, emotion, and organizational behavior helps minimize the negative effects of indiscriminate application of personal and cultural belief systems to business. Doing so enhances cognitive accuracy and improves communication and cooperation. Organizations operating with cognitive accuracy will tend to respond more nimbly to market pressures and achieve an overall higher level of performance and employee satisfaction.

The effect of the COMT val(158)met polymorphism on neural correlates of semantic verbal fluency.

PubMed

Krug, Axel; Markov, Valentin; Sheldrick, Abigail; Krach, Sören; Jansen, Andreas; Zerres, Klaus; Eggermann, Thomas; Stöcker, Tony; Shah, N Jon; Kircher, Tilo

2009-12-01

Variation in the val(158)met polymorphism of the COMT gene has been found to be associated with cognitive performance. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal areas. Given the complex modulation and functional heterogeneity of frontal lobe systems, further specification of COMT gene-related phenotypes differing in prefrontally mediated cognitive performance are of major interest. Eighty healthy individuals (54 men, 26 women; mean age 23.3 years) performed an overt semantic verbal fluency task while brain activation was measured with functional magnetic resonance imaging (fMRI). COMT val(158)met genotype was determined and correlated with brain activation measured with fMRI during the task. Although there were no differences in performance, brain activation in the left inferior frontal gyrus [Brodmann area 10] was positively correlated with the number of val alleles in the COMT gene. COMT val(158)met status modulates brain activation during the language production on a semantic level in an area related to executive functions.

Brain Connectivity and Functional Recovery in Patients With Ischemic Stroke.

PubMed

Almeida, Sara Regina Meira; Vicentini, Jessica; Bonilha, Leonardo; De Campos, Brunno M; Casseb, Raphael F; Min, Li Li

2017-01-01

Brain mapping studies have demonstrated that functional poststroke brain reorganization is associated with recovery of motor function. Nonetheless, the specific mechanisms associated with functional reorganization leading to motor recovery are still partly unknown. In this study, we performed a cross-sectional evaluation of poststroke subjects with the following goals: (1) To assess intra- and interhemispheric functional brain activation patterns associated with motor function in poststroke patients with variable degrees of recovery; (2) to investigate the involvement of other nonmotor functional networks in relationship with recovery. We studied 59 individuals: 13 patients with function Rankin > 1 and Barthel < 100; 19 patients with preserved function with Rankin 0-1 and Barthel = 100; and 27 healthy controls. All subjects underwent structural and functional magnetic resonance imaging (3T Philips Achieva, Holland) using the same protocol (TR = 2 seconds, TE = 30 ms, FOV = 240 × 240 × 117, slice = 39). Resting state functional connectivity was used by in-house software, based on SPM12. Among patients with and without preserved function, the functional connectivity between the primary motor region (M1) and the contralateral hemisphere was increased compared with controls. Nonetheless, only patients with decreased function exhibited decreased functional connectivity between executive control, sensorimotor and visuospatial networks. Functional recovery after stroke is associated with preserved functional connectivity of motor to nonmotor networks. Copyright © 2016 by the American Society of Neuroimaging.

Higher-order Brain Areas Associated with Real-time Functional MRI Neurofeedback Training of the Somato-motor Cortex.

PubMed

Auer, Tibor; Dewiputri, Wan Ilma; Frahm, Jens; Schweizer, Renate

2018-05-15

Neurofeedback (NFB) allows subjects to learn self-regulation of neuronal brain activation based on information about the ongoing activation. The implementation of real-time functional magnetic resonance imaging (rt-fMRI) for NFB training now facilitates the investigation into underlying processes. Our study involved 16 control and 16 training right-handed subjects, the latter performing an extensive rt-fMRI NFB training using motor imagery. A previous analysis focused on the targeted primary somato-motor cortex (SMC). The present study extends the analysis to the supplementary motor area (SMA), the next higher brain area within the hierarchy of the motor system. We also examined transfer-related functional connectivity using a whole-volume psycho-physiological interaction (PPI) analysis to reveal brain areas associated with learning. The ROI analysis of the pre- and post-training fMRI data for motor imagery without NFB (transfer) resulted in a significant training-specific increase in the SMA. It could also be shown that the contralateral SMA exhibited a larger increase than the ipsilateral SMA in the training and the transfer runs, and that the right-hand training elicited a larger increase in the transfer runs than the left-hand training. The PPI analysis revealed a training-specific increase in transfer-related functional connectivity between the left SMA and frontal areas as well as the anterior midcingulate cortex (aMCC) for right- and left-hand trainings. Moreover, the transfer success was related with training-specific increase in functional connectivity between the left SMA and the target area SMC. Our study demonstrates that NFB training increases functional connectivity with non-targeted brain areas. These are associated with the training strategy (i.e., SMA) as well as with learning the NFB skill (i.e., aMCC and frontal areas). This detailed description of both the system to be trained and the areas involved in learning can provide valuable information for further optimization of NFB trainings. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Tracing Activity Across the Whole Brain Neural Network with Optogenetic Functional Magnetic Resonance Imaging

PubMed Central

Lee, Jin Hyung

2011-01-01

Despite the overwhelming need, there has been a relatively large gap in our ability to trace network level activity across the brain. The complex dense wiring of the brain makes it extremely challenging to understand cell-type specific activity and their communication beyond a few synapses. Recent development of the optogenetic functional magnetic resonance imaging (ofMRI) provides a new impetus for the study of brain circuits by enabling causal tracing of activities arising from defined cell types and firing patterns across the whole brain. Brain circuit elements can be selectively triggered based on their genetic identity, cell body location, and/or their axonal projection target with temporal precision while the resulting network response is monitored non-invasively with unprecedented spatial and temporal accuracy. With further studies including technological innovations to bring ofMRI to its full potential, ofMRI is expected to play an important role in our system-level understanding of the brain circuit mechanism. PMID:22046160

Brain basis of self: self-organization and lessons from dreaming

PubMed Central

Kahn, David

2013-01-01

Through dreaming, a different facet of the self is created as a result of a self-organizing process in the brain. Self-organization in biological systems often happens as an answer to an environmental change for which the existing system cannot cope; self-organization creates a system that can cope in the newly changed environment. In dreaming, self-organization serves the function of organizing disparate memories into a dream since the dreamer herself is not able to control how individual memories become weaved into a dream. The self-organized dream provides, thereby, a wide repertoire of experiences; this expanded repertoire of experience results in an expansion of the self beyond that obtainable when awake. Since expression of the self is associated with activity in specific areas of the brain, the article also discusses the brain basis of the self by reviewing studies of brain injured patients, discussing brain imaging studies in normal brain functioning when focused, when daydreaming and when asleep and dreaming. PMID:23882232

Fractionation of social brain circuits in autism spectrum disorders.

PubMed

Gotts, Stephen J; Simmons, W Kyle; Milbury, Lydia A; Wallace, Gregory L; Cox, Robert W; Martin, Alex

2012-09-01

Autism spectrum disorders are developmental disorders characterized by impairments in social and communication abilities and repetitive behaviours. Converging neuroscientific evidence has suggested that the neuropathology of autism spectrum disorders is widely distributed, involving impaired connectivity throughout the brain. Here, we evaluate the hypothesis that decreased connectivity in high-functioning adolescents with an autism spectrum disorder relative to typically developing adolescents is concentrated within domain-specific circuits that are specialized for social processing. Using a novel whole-brain connectivity approach in functional magnetic resonance imaging, we found that not only are decreases in connectivity most pronounced between regions of the social brain but also they are selective to connections between limbic-related brain regions involved in affective aspects of social processing from other parts of the social brain that support language and sensorimotor processes. This selective pattern was independently obtained for correlations with measures of social symptom severity, implying a fractionation of the social brain in autism spectrum disorders at the level of whole circuits.

Fractionation of social brain circuits in autism spectrum disorders

PubMed Central

Simmons, W. Kyle; Milbury, Lydia A.; Wallace, Gregory L.; Cox, Robert W.; Martin, Alex

2012-01-01

Autism spectrum disorders are developmental disorders characterized by impairments in social and communication abilities and repetitive behaviours. Converging neuroscientific evidence has suggested that the neuropathology of autism spectrum disorders is widely distributed, involving impaired connectivity throughout the brain. Here, we evaluate the hypothesis that decreased connectivity in high-functioning adolescents with an autism spectrum disorder relative to typically developing adolescents is concentrated within domain-specific circuits that are specialized for social processing. Using a novel whole-brain connectivity approach in functional magnetic resonance imaging, we found that not only are decreases in connectivity most pronounced between regions of the social brain but also they are selective to connections between limbic-related brain regions involved in affective aspects of social processing from other parts of the social brain that support language and sensorimotor processes. This selective pattern was independently obtained for correlations with measures of social symptom severity, implying a fractionation of the social brain in autism spectrum disorders at the level of whole circuits. PMID:22791801

Impairment in long-term memory formation and learning-dependent synaptic plasticity in mice lacking glycogen synthase in the brain

PubMed Central

Duran, Jordi; Saez, Isabel; Gruart, Agnès; Guinovart, Joan J; Delgado-García, José M

2013-01-01

Glycogen is the only carbohydrate reserve of the brain, but its overall contribution to brain functions remains unclear. Although it has traditionally been considered as an emergency energetic reservoir, increasing evidence points to a role of glycogen in the normal activity of the brain. To address this long-standing question, we generated a brain-specific Glycogen Synthase knockout (GYS1Nestin-KO) mouse and studied the functional consequences of the lack of glycogen in the brain under alert behaving conditions. These animals showed a significant deficiency in the acquisition of an associative learning task and in the concomitant activity-dependent changes in hippocampal synaptic strength. Long-term potentiation (LTP) evoked in the hippocampal CA3-CA1 synapse was also decreased in behaving GYS1Nestin-KO mice. These results unequivocally show a key role of brain glycogen in the proper acquisition of new motor and cognitive abilities and in the underlying changes in synaptic strength. PMID:23281428

Neurological soft signs are not "soft" in brain structure and functional networks: evidence from ALE meta-analysis.

PubMed

Zhao, Qing; Li, Zhi; Huang, Jia; Yan, Chao; Dazzan, Paola; Pantelis, Christos; Cheung, Eric F C; Lui, Simon S Y; Chan, Raymond C K

2014-05-01

Neurological soft signs (NSS) are associated with schizophrenia and related psychotic disorders. NSS have been conventionally considered as clinical neurological signs without localized brain regions. However, recent brain imaging studies suggest that NSS are partly localizable and may be associated with deficits in specific brain areas. We conducted an activation likelihood estimation meta-analysis to quantitatively review structural and functional imaging studies that evaluated the brain correlates of NSS in patients with schizophrenia and other psychotic disorders. Six structural magnetic resonance imaging (sMRI) and 15 functional magnetic resonance imaging (fMRI) studies were included. The results from meta-analysis of the sMRI studies indicated that NSS were associated with atrophy of the precentral gyrus, the cerebellum, the inferior frontal gyrus, and the thalamus. The results from meta-analysis of the fMRI studies demonstrated that the NSS-related task was significantly associated with altered brain activation in the inferior frontal gyrus, bilateral putamen, the cerebellum, and the superior temporal gyrus. Our findings from both sMRI and fMRI meta-analyses further support the conceptualization of NSS as a manifestation of the "cerebello-thalamo-prefrontal" brain network model of schizophrenia and related psychotic disorders.

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

PubMed

Wilson, Benjamin; Petkov, Christopher I

2011-04-01

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

Decoding brain responses to pixelized images in the primary visual cortex: implications for visual cortical prostheses

PubMed Central

Guo, Bing-bing; Zheng, Xiao-lin; Lu, Zhen-gang; Wang, Xing; Yin, Zheng-qin; Hou, Wen-sheng; Meng, Ming

2015-01-01

Visual cortical prostheses have the potential to restore partial vision. Still limited by the low-resolution visual percepts provided by visual cortical prostheses, implant wearers can currently only “see” pixelized images, and how to obtain the specific brain responses to different pixelized images in the primary visual cortex (the implant area) is still unknown. We conducted a functional magnetic resonance imaging experiment on normal human participants to investigate the brain activation patterns in response to 18 different pixelized images. There were 100 voxels in the brain activation pattern that were selected from the primary visual cortex, and voxel size was 4 mm × 4 mm × 4 mm. Multi-voxel pattern analysis was used to test if these 18 different brain activation patterns were specific. We chose a Linear Support Vector Machine (LSVM) as the classifier in this study. The results showed that the classification accuracies of different brain activation patterns were significantly above chance level, which suggests that the classifier can successfully distinguish the brain activation patterns. Our results suggest that the specific brain activation patterns to different pixelized images can be obtained in the primary visual cortex using a 4 mm × 4 mm × 4 mm voxel size and a 100-voxel pattern. PMID:26692860

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-01-01

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

Disruption to functional networks in neonates with perinatal brain injury predicts motor skills at 8 months.

PubMed

Linke, Annika C; Wild, Conor; Zubiaurre-Elorza, Leire; Herzmann, Charlotte; Duffy, Hester; Han, Victor K; Lee, David S C; Cusack, Rhodri

2018-01-01

Functional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries. Infants ( n  = 65, included in final analyses: n  = 53) were recruited from the neonatal intensive care unit (NICU) and were stratified based on their age at birth (premature vs. term), and on whether neuropathology was diagnosed from structural MRI. Functional brain networks and a measure of disruption to functional connectivity were obtained from 14 min of fcMRI acquired during natural sleep at term-equivalent age. Disruption to connectivity of the somatomotor and frontoparietal executive networks predicted motor impairment at 4 and 8 months. This disruption in functional connectivity was not found to be driven by differences between clinical groups, or by any of the specific measures we captured to describe the clinical course. fcMRI was predictive over and above other clinical measures available at discharge from the NICU, including structural MRI. Motor learning was affected by disruption to somatomotor networks, but also frontoparietal executive networks, which supports the functional importance of these networks in early development. Disruption to these two networks might be best addressed by distinct intervention strategies.

Direct electrical stimulation as an input gate into brain functional networks: principles, advantages and limitations.

PubMed

Mandonnet, Emmanuel; Winkler, Peter A; Duffau, Hugues

2010-02-01

While the fundamental and clinical contribution of direct electrical stimulation (DES) of the brain is now well acknowledged, its advantages and limitations have not been re-evaluated for a long time. Here, we critically review exactly what DES can tell us about cerebral function. First, we show that DES is highly sensitive for detecting the cortical and axonal eloquent structures. Moreover, DES also provides a unique opportunity to study brain connectivity, since each area responsive to stimulation is in fact an input gate into a large-scale network rather than an isolated discrete functional site. DES, however, also has a limitation: its specificity is suboptimal. Indeed, DES may lead to interpretations that a structure is crucial because of the induction of a transient functional response when stimulated, whereas (1) this effect is caused by the backward spreading of the electro-stimulation along the network to an essential area and/or (2) the stimulated region can be functionally compensated owing to long-term brain plasticity mechanisms. In brief, although DES is still the gold standard for brain mapping, its combination with new methods such as perioperative neurofunctional imaging and biomathematical modeling is now mandatory, in order to clearly differentiate those networks that are actually indispensable to function from those that can be compensated.

Sharing self-related information is associated with intrinsic functional connectivity of cortical midline brain regions

PubMed Central

Meshi, Dar; Mamerow, Loreen; Kirilina, Evgeniya; Morawetz, Carmen; Margulies, Daniel S.; Heekeren, Hauke R.

2016-01-01

Human beings are social animals and they vary in the degree to which they share information about themselves with others. Although brain networks involved in self-related cognition have been identified, especially via the use of resting-state experiments, the neural circuitry underlying individual differences in the sharing of self-related information is currently unknown. Therefore, we investigated the intrinsic functional organization of the brain with respect to participants’ degree of self-related information sharing using resting state functional magnetic resonance imaging and self-reported social media use. We conducted seed-based correlation analyses in cortical midline regions previously shown in meta-analyses to be involved in self-referential cognition: the medial prefrontal cortex (MPFC), central precuneus (CP), and caudal anterior cingulate cortex (CACC). We examined whether and how functional connectivity between these regions and the rest of the brain was associated with participants’ degree of self-related information sharing. Analyses revealed associations between the MPFC and right dorsolateral prefrontal cortex (DLPFC), as well as the CP with the right DLPFC, the left lateral orbitofrontal cortex and left anterior temporal pole. These findings extend our present knowledge of functional brain connectivity, specifically demonstrating how the brain’s intrinsic functional organization relates to individual differences in the sharing of self-related information. PMID:26948055

Heterozygous deletion of the LRFN2 gene is associated with working memory deficits

PubMed Central

Thevenon, Julien; Souchay, Céline; Seabold, Gail K; Dygai-Cochet, Inna; Callier, Patrick; Gay, Sébastien; Corbin, Lucie; Duplomb, Laurence; Thauvin-Robinet, Christel; Masurel-Paulet, Alice; El Chehadeh, Salima; Avila, Magali; Minot, Delphine; Guedj, Eric; Chancenotte, Sophie; Bonnet, Marlène; Lehalle, Daphne; Wang, Ya-Xian; Kuentz, Paul; Huet, Frédéric; Mosca-Boidron, Anne-Laure; Marle, Nathalie; Petralia, Ronald S; Faivre, Laurence

2016-01-01

Learning disabilities (LDs) are a clinically and genetically heterogeneous group of diseases. Array-CGH and high-throughput sequencing have dramatically expanded the number of genes implicated in isolated intellectual disabilities and LDs, highlighting the implication of neuron-specific post-mitotic transcription factors and synaptic proteins as candidate genes. We report a unique family diagnosed with autosomal dominant learning disability and a 6p21 microdeletion segregating in three patients. The 870 kb microdeletion encompassed the brain-expressed gene LRFN2, which encodes for a synaptic cell adhesion molecule. Neuropsychological assessment identified selective working memory deficits, with borderline intellectual functioning. Further investigations identified a defect in executive function, and auditory-verbal processes. These data were consistent with brain MRI and FDG-PET functional brain imaging, which, when compared with controls, revealed abnormal brain volume and hypometabolism of gray matter structures implicated in working memory. We performed electron microscopy immunogold labeling demonstrating the localization of LRFN2 at synapses of cerebellar and hippocampal rat neurons, often associated with the NR1 subunit of N-methyl-D-aspartate receptors (NMDARs). Altogether, the combined approaches imply a role for LRFN2 in LD, specifically for working memory processes and executive function. In conclusion, the identification of familial cases of clinically homogeneous endophenotypes of LD might help in both the management of patients and genetic counseling for families. PMID:26486473

Visual attention in preterm born adults: specifically impaired attentional sub-mechanisms that link with altered intrinsic brain networks in a compensation-like mode.

PubMed

Finke, Kathrin; Neitzel, Julia; Bäuml, Josef G; Redel, Petra; Müller, Hermann J; Meng, Chun; Jaekel, Julia; Daamen, Marcel; Scheef, Lukas; Busch, Barbara; Baumann, Nicole; Boecker, Henning; Bartmann, Peter; Habekost, Thomas; Wolke, Dieter; Wohlschläger, Afra; Sorg, Christian

2015-02-15

Although pronounced and lasting deficits in selective attention have been observed for preterm born individuals it is unknown which specific attentional sub-mechanisms are affected and how they relate to brain networks. We used the computationally specified 'Theory of Visual Attention' together with whole- and partial-report paradigms to compare attentional sub-mechanisms of pre- (n=33) and full-term (n=32) born adults. Resting-state fMRI was used to evaluate both between-group differences and inter-individual variance in changed functional connectivity of intrinsic brain networks relevant for visual attention. In preterm born adults, we found specific impairments of visual short-term memory (vSTM) storage capacity while other sub-mechanisms such as processing speed or attentional weighting were unchanged. Furthermore, changed functional connectivity was found in unimodal visual and supramodal attention-related intrinsic networks. Among preterm born adults, the individual pattern of changed connectivity in occipital and parietal cortices was systematically associated with vSTM in such a way that the more distinct the connectivity differences, the better the preterm adults' storage capacity. These findings provide first evidence for selectively changed attentional sub-mechanisms in preterm born adults and their relation to altered intrinsic brain networks. In particular, data suggest that cortical changes in intrinsic functional connectivity may compensate adverse developmental consequences of prematurity on visual short-term storage capacity. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2012-08-15

Riboflavin is an important water soluble vitamin (B2) required for metabolic reactions, normal cellular growth, differentiation and function. Mammalian brain cells cannot synthesize riboflavin and must import from systemic circulation. However, the uptake mechanism, cellular translocation and intracellular trafficking of riboflavin in brain capillary endothelial cells are poorly understood. The primary objective of this study is to investigate the existence of a riboflavin-specific transport system and delineate the uptake and intracellular regulation of riboflavin in immortalized rat brain capillary endothelial cells (RBE4). The uptake of [3H]-riboflavin is sodium, temperature and energy dependent but pH independent. [3H]-Riboflavin uptake is saturable with K(m) and V(max) values of 19 ± 3 μM and 0.235 ± 0.012 pmol/min/mg protein, respectively. The uptake process is inhibited by unlabelled structural analogs (lumiflavin, lumichrome) but not by structurally unrelated vitamins. Ca(++)/calmodulin and protein kinase A (PKA) pathways are found to play an important role in the intracellular regulation of [3H]-riboflavin. Apical and baso-lateral uptake of [3H]-riboflavin clearly indicates that a riboflavin specific transport system is predominantly localized on the apical side of RBE4 cells. A 628 bp band corresponding to a riboflavin transporter is revealed in RT-PCR analysis. These findings, for the first time report the existence of a specialized and high affinity transport system for riboflavin in RBE4 cells. The blood-brain barrier (BBB) is a major obstacle limiting drug transport inside the brain as it regulates drug permeation from systemic circulation. This transporter can be utilized for targeted delivery in enhancing brain permeation of highly potent drugs on systemic administration. Copyright © 2012 Elsevier B.V. All rights reserved.

Salience network-based classification and prediction of symptom severity in children with autism.

PubMed

Uddin, Lucina Q; Supekar, Kaustubh; Lynch, Charles J; Khouzam, Amirah; Phillips, Jennifer; Feinstein, Carl; Ryali, Srikanth; Menon, Vinod

2013-08-01

Autism spectrum disorder (ASD) affects 1 in 88 children and is characterized by a complex phenotype, including social, communicative, and sensorimotor deficits. Autism spectrum disorder has been linked with atypical connectivity across multiple brain systems, yet the nature of these differences in young children with the disorder is not well understood. To examine connectivity of large-scale brain networks and determine whether specific networks can distinguish children with ASD from typically developing (TD) children and predict symptom severity in children with ASD. Case-control study performed at Stanford University School of Medicine of 20 children 7 to 12 years old with ASD and 20 age-, sex-, and IQ-matched TD children. Between-group differences in intrinsic functional connectivity of large-scale brain networks, performance of a classifier built to discriminate children with ASD from TD children based on specific brain networks, and correlations between brain networks and core symptoms of ASD. We observed stronger functional connectivity within several large-scale brain networks in children with ASD compared with TD children. This hyperconnectivity in ASD encompassed salience, default mode, frontotemporal, motor, and visual networks. This hyperconnectivity result was replicated in an independent cohort obtained from publicly available databases. Using maps of each individual's salience network, children with ASD could be discriminated from TD children with a classification accuracy of 78%, with 75% sensitivity and 80% specificity. The salience network showed the highest classification accuracy among all networks examined, and the blood oxygen-level dependent signal in this network predicted restricted and repetitive behavior scores. The classifier discriminated ASD from TD in the independent sample with 83% accuracy, 67% sensitivity, and 100% specificity. Salience network hyperconnectivity may be a distinguishing feature in children with ASD. Quantification of brain network connectivity is a step toward developing biomarkers for objectively identifying children with ASD.

Salience Network–Based Classification and Prediction of Symptom Severity in Children With Autism

PubMed Central

Uddin, Lucina Q.; Supekar, Kaustubh; Lynch, Charles J.; Khouzam, Amirah; Phillips, Jennifer; Feinstein, Carl; Ryali, Srikanth; Menon, Vinod

2014-01-01

IMPORTANCE Autism spectrum disorder (ASD) affects 1 in 88 children and is characterized by a complex phenotype, including social, communicative, and sensorimotor deficits. Autism spectrum disorder has been linked with atypical connectivity across multiple brain systems, yet the nature of these differences in young children with the disorder is not well understood. OBJECTIVES To examine connectivity of large-scale brain networks and determine whether specific networks can distinguish children with ASD from typically developing (TD) children and predict symptom severity in children with ASD. DESIGN, SETTING, AND PARTICIPANTS Case-control study performed at Stanford University School of Medicine of 20 children 7 to 12 years old with ASD and 20 age-, sex-, and IQ-matched TD children. MAIN OUTCOMES AND MEASURES Between-group differences in intrinsic functional connectivity of large-scale brain networks, performance of a classifier built to discriminate children with ASD from TD children based on specific brain networks, and correlations between brain networks and core symptoms of ASD. RESULTS We observed stronger functional connectivity within several large-scale brain networks in children with ASD compared with TD children. This hyperconnectivity in ASD encompassed salience, default mode, frontotemporal, motor, and visual networks. This hyperconnectivity result was replicated in an independent cohort obtained from publicly available databases. Using maps of each individual’s salience network, children with ASD could be discriminated from TD children with a classification accuracy of 78%, with 75% sensitivity and 80% specificity. The salience network showed the highest classification accuracy among all networks examined, and the blood oxygen–level dependent signal in this network predicted restricted and repetitive behavior scores. The classifier discriminated ASD from TD in the independent sample with 83% accuracy, 67% sensitivity, and 100% specificity. CONCLUSIONS AND RELEVANCE Salience network hyperconnectivity may be a distinguishing feature in children with ASD. Quantification of brain network connectivity is a step toward developing biomarkers for objectively identifying children with ASD. PMID:23803651

Brain responses in 4-month-old infants are already language specific.

PubMed

Friederici, Angela D; Friedrich, Manuela; Christophe, Anne

2007-07-17

Language is the most important faculty that distinguishes humans from other animals. Infants learn their native language fast and effortlessly during the first years of life, as a function of the linguistic input in their environment. Behavioral studies reported the discrimination of melodic contours [1] and stress patterns [2, 3] in 1-4-month-olds. Behavioral [4, 5] and brain measures [6-8] have shown language-independent discrimination of phonetic contrasts at that age. Language-specific discrimination, however, has been reported for phonetic contrasts only for 6-12-month-olds [9-12]. Here we demonstrate language-specific discrimination of stress patterns in 4-month-old German and French infants by using electrophysiological brain measures. We compare the processing of disyllabic words differing in their rhythmic structure, mimicking German words being stressed on the first syllable, e.g., pápa/daddy[13], and French ones being stressed on the second syllable, e.g., papá/daddy. Event-related brain potentials reveal that experience with German and French differentially affects the brain responses of 4-month-old infants, with each language group displaying a processing advantage for the rhythmic structure typical in its native language. These data indicate language-specific neural representations of word forms in the infant brain as early as 4 months of age.

[Eating disorders].

PubMed

Miyake, Yoshie; Okamoto, Yuri; Jinnin, Ran; Shishida, Kazuhiro; Okamoto, Yasumasa

2015-02-01

Eating disorders are characterized by aberrant patterns of eating behavior, including such symptoms as extreme restriction of food intake or binge eating, and severe disturbances in the perception of body shape and weight, as well as a drive for thinness and obsessive fears of becoming fat. Eating disorder is an important cause for physical and psychosocial morbidity in young women. Patients with eating disorders have a deficit in the cognitive process and functional abnormalities in the brain system. Recently, brain-imaging techniques have been used to identify specific brain areas that function abnormally in patients with eating disorders. We have discussed the clinical and cognitive aspects of eating disorders and summarized neuroimaging studies of eating disorders.

Luria revisited: cognitive research in schizophrenia, past implications and future challenges.

PubMed

Zaytseva, Yuliya; Chan, Raymond C K; Pöppel, Ernst; Heinz, Andreas

2015-02-27

Contemporary psychiatry is becoming more biologically oriented in the attempt to elicit a biological rationale of mental diseases. Although mental disorders comprise mostly functional abnormalities, there is a substantial overlap between neurology and psychiatry in addressing cognitive disturbances. In schizophrenia, the presence of cognitive impairment prior to the onset of psychosis and early after its manifestation suggests that some neurocognitive abnormalities precede the onset of psychosis and may represent a trait marker. These cognitive alterations may arise from functional disconnectivity, as no significant brain damage has been found. In this review we aim to revise A.R. Luria's systematic approach used in the neuropsychological evaluation of cognitive functions, which was primarily applied in patients with neurological disorders and in the cognitive evaluation in schizophrenia and other related disorders. As proposed by Luria, cognitive processes, associated with higher cortical functions, may represent functional systems that are not localized in narrow, circumscribed areas of the brain, but occur among groups of concertedly working brain structures, each of which makes its own particular contribution to the organization of the functional system. Current developments in neuroscience provide evidence of functional connectivity in the brain. Therefore, Luria's approach may serve as a frame of reference for the analysis and interpretation of cognitive functions in general and their abnormalities in schizophrenia in particular. Having said that, modern technology, as well as experimental evidence, may help us to understand the brain better and lead us towards creating a new classification of cognitive functions. In schizophrenia research, multidisciplinary approaches must be utilized to address specific cognitive alterations. The relationships among the components of cognitive functions derived from the functional connectivity of the brain may provide an insight into cognitive machinery.

The construction of MRI brain/head templates for Chinese children from 7 to 16 years of age

PubMed Central

Xie, Wanze; Richards, John E.; Lei, Du; Zhu, Hongyan; Lee, Kang; Gong, Qiyong

2015-01-01

Population-specific brain templates that provide detailed brain information are beneficial to both structural and functional neuroimaging research. However, age-specific MRI templates have not been constructed for Chinese or any Asian developmental populations. This study developed novel T1-weighted average brain and head templates for Chinese children from 7 to 16 years of age in two-year increments using high quality magnetic resonance imaging (MRI) and well-validated image analysis techniques. A total of 138 Chinese children (51 F/87 M) were included in this study. The internally and externally validated registrations show that these Chinese age-specific templates fit Chinese children’s MR images significantly better than age-specific templates created from U.S. children, or adult templates based on either Chinese or North American adults. It implies that age-inappropriate (e.g., the Chinese56 template, the US20–24 template) and nationality-inappropriate brain templates (e.g., U.S. children’s templates, the US20–24 template) do not provide optimal reference MRIs for processing MR brain images of Chinese pediatric populations. Thus, our age-specific MRI templates are the first of the kind and should be useful in neuroimaging studies with children from Chinese or other Asian populations. These templates can also serve as the foundations for the construction of more comprehensive sets of nationality-specific templates for Asian developmental populations. These templates are available for use in our database. PMID:26343862

Sex differences in the neural substrates of spatial working memory during adolescence are not mediated by endogenous testosterone

PubMed Central

Alarcón, Gabriela; Cservenka, Anita; Fair, Damien A.; Nagel, Bonnie J.

2014-01-01

Adolescence is a developmental period characterized by notable changes in behavior, physical attributes, and an increase in endogenous sex steroid hormones, which may impact cognitive functioning. Moreover, sex differences in brain structure are present, leading to differences in neural function and cognition. Here, we examine sex differences in performance and blood oxygen level-dependent (BOLD) activation in a sample of adolescents during a spatial working memory (SWM) task. We also examine whether endogenous testosterone levels mediate differential brain activity between the sexes. Adolescents between ages 10 and 16 completed a SWM functional magnetic resonance imaging (fMRI) task, and serum hormone levels were assessed within seven days of scanning. While there were no sex differences in task performance (accuracy and reaction time), differences in BOLD response between girls and boys emerged, with girls deactivating brain regions in the default mode network and boys showing increased response in SWM-related brain regions of the frontal cortex. These results suggest that adolescent boys and girls adopted distinct neural strategies, while maintaining spatial cognitive strategies that facilitated comparable cognitive performance of a SWM task. A nonparametric bootstrapping procedure revealed that testosterone did not mediate sex-specific brain activity, suggesting that sex differences in BOLD activation during SWM may be better explained by other factors, such as early organizational effects of sex steroids or environmental influences. Elucidating sex differences in neural function and the influence of gonadal hormones can serve as a basis of comparison for understanding sexually dimorphic neurodevelopment and inform sex-specific psychopathology that emerges in adolescence. PMID:25312831

Changes of intranetwork and internetwork functional connectivity in Alzheimer’s disease and mild cognitive impairment

NASA Astrophysics Data System (ADS)

Zhu, Haoze; Zhou, Peng; Alcauter, Sarael; Chen, Yuanyuan; Cao, Hongbao; Tian, Miao; Ming, Dong; Qi, Hongzhi; Wang, Xuemin; Zhao, Xin; He, Feng; Ni, Hongyan; Gao, Wei

2016-08-01

Objective. Alzheimer’s disease (AD) is a serious neurodegenerative disorder characterized by deficits of working memory, attention, language and many other cognitive functions. Although different stages of the disease are relatively well characterized by clinical criteria, stage-specific pathological changes in the brain remain relatively poorly understood, especially at the level of large-scale functional networks. In this study, we aimed to characterize the potential disruptions of large-scale functional brain networks based on a sample including amnestic mild cognition impairment (aMCI) and AD patients to help delineate the underlying stage-dependent AD pathology. Approach. We sought to identify the neural connectivity mechanisms of aMCI and AD through examination of both intranetwork and internetwork interactions among four of the brain’s key networks, namely dorsal attention network (DAN), default mode network (DMN), executive control network (ECN) and salience network (SAL). We analyzed functional connectivity based on resting-state functional magnetic resonance imaging (rs-fMRI) data from 25 Alzheimer’s disease patients, 20 aMCI patients and 35 elderly normal controls (NC). Main results. Intranetwork functional disruptions within the DAN and ECN were detected in both aMCI and AD patients. Disrupted intranetwork connectivity of DMN and anti-correlation between DAN and DMN were observed in AD patients. Moreover, aMCI-specific alterations in the internetwork functional connectivity of SAL were observed. Significance. Our results confirmed previous findings that AD pathology was related to dysconnectivity both within and between resting-state networks but revealed more spatial details. Moreover, the SAL network, reportedly flexibly coupling either with the DAN or DMN networks during different brain states, demonstrated interesting alterations specifically in the early stage of the disease.

Frequency specific brain networks in Parkinson's disease and comorbid depression.

PubMed

Qian, Long; Zhang, Yi; Zheng, Li; Fu, Xuemei; Liu, Weiguo; Shang, Yuqing; Zhang, Yaoyu; Xu, Yuanyuan; Liu, Yijun; Zhu, Huaiqiu; Gao, Jia-Hong

2017-02-01

The topological organization underlying the human brain was extensively investigated using resting-state functional magnetic resonance imaging, focusing on a low frequency of signal oscillation from 0.01 to 0.1 Hz. However, the frequency specificities with regard to the topological properties of the brain networks have not been fully revealed. In this study, a novel complementary ensemble empirical mode decomposition (CEEMD) method was used to separate the fMRI time series into five characteristic oscillations with distinct frequencies. Then, the small world properties of brain networks were analyzed for each of these five oscillations in patients (n = 67) with depressed Parkinson's disease (DPD, n = 20) , non-depressed Parkinson's disease (NDPD, n = 47) and healthy controls (HC, n = 46). Compared with HC, the results showed decreased network efficiency in characteristic oscillations from 0.05 to 0.12 Hz and from 0.02 to 0.05 Hz for the DPD and NDPD patients, respectively. Furthermore, compared with HC, the most significant inter-group difference across five brain oscillations was found in the basal ganglia (0.01 to 0.05 Hz) and paralimbic-limbic network (0.02 to 0.22 Hz) for the DPD patients, and in the visual cortex (0.02 to 0.05 Hz) for the NDPD patients. Compared with NDPD, the DPD patients showed reduced efficiency of nodes in the basal ganglia network (0.01 to 0.05 Hz). Our results demonstrated that DPD is characterized by a disrupted topological organization in large-scale brain functional networks. Moreover, the CEEMD analysis suggested a prominent dissociation in the topological organization of brain networks between DPD and NDPD in both space and frequency domains. Our findings indicated that these characteristic oscillatory activities in different functional circuits may contribute to distinct motor and non-motor components of clinical impairments in Parkinson's disease.

Trends and Challenges in Neuroengineering: Toward "Intelligent" Neuroprostheses through Brain-"Brain Inspired Systems" Communication.

PubMed

Vassanelli, Stefano; Mahmud, Mufti

2016-01-01

Future technologies aiming at restoring and enhancing organs function will intimately rely on near-physiological and energy-efficient communication between living and artificial biomimetic systems. Interfacing brain-inspired devices with the real brain is at the forefront of such emerging field, with the term "neurobiohybrids" indicating all those systems where such interaction is established. We argue that achieving a "high-level" communication and functional synergy between natural and artificial neuronal networks in vivo , will allow the development of a heterogeneous world of neurobiohybrids, which will include "living robots" but will also embrace "intelligent" neuroprostheses for augmentation of brain function. The societal and economical impact of intelligent neuroprostheses is likely to be potentially strong, as they will offer novel therapeutic perspectives for a number of diseases, and going beyond classical pharmaceutical schemes. However, they will unavoidably raise fundamental ethical questions on the intermingling between man and machine and more specifically, on how deeply it should be allowed that brain processing is affected by implanted "intelligent" artificial systems. Following this perspective, we provide the reader with insights on ongoing developments and trends in the field of neurobiohybrids. We address the topic also from a "community building" perspective, showing through a quantitative bibliographic analysis, how scientists working on the engineering of brain-inspired devices and brain-machine interfaces are increasing their interactions. We foresee that such trend preludes to a formidable technological and scientific revolution in brain-machine communication and to the opening of new avenues for restoring or even augmenting brain function for therapeutic purposes.

Trends and Challenges in Neuroengineering: Toward “Intelligent” Neuroprostheses through Brain-“Brain Inspired Systems” Communication

PubMed Central

Vassanelli, Stefano; Mahmud, Mufti

2016-01-01

Future technologies aiming at restoring and enhancing organs function will intimately rely on near-physiological and energy-efficient communication between living and artificial biomimetic systems. Interfacing brain-inspired devices with the real brain is at the forefront of such emerging field, with the term “neurobiohybrids” indicating all those systems where such interaction is established. We argue that achieving a “high-level” communication and functional synergy between natural and artificial neuronal networks in vivo, will allow the development of a heterogeneous world of neurobiohybrids, which will include “living robots” but will also embrace “intelligent” neuroprostheses for augmentation of brain function. The societal and economical impact of intelligent neuroprostheses is likely to be potentially strong, as they will offer novel therapeutic perspectives for a number of diseases, and going beyond classical pharmaceutical schemes. However, they will unavoidably raise fundamental ethical questions on the intermingling between man and machine and more specifically, on how deeply it should be allowed that brain processing is affected by implanted “intelligent” artificial systems. Following this perspective, we provide the reader with insights on ongoing developments and trends in the field of neurobiohybrids. We address the topic also from a “community building” perspective, showing through a quantitative bibliographic analysis, how scientists working on the engineering of brain-inspired devices and brain-machine interfaces are increasing their interactions. We foresee that such trend preludes to a formidable technological and scientific revolution in brain-machine communication and to the opening of new avenues for restoring or even augmenting brain function for therapeutic purposes. PMID:27721741

[Cerebral metabolism and permeability of the hemato-encephalic barrier in an experimental model for brain radiotherapy].

PubMed

Cicciarello, R; Russi, E; Albiero, F; Mesiti, M; Torre, E; D'Aquino, A; Raffaele, L; Bertolani, S; D'Avella, D

1990-11-01

Whole brain irradiation (WBR) can produce acute and chronic neurological adverse effects, which are usually divided into acute, early delayed and late delayed reactions according to the time of onset. To assess the impact of WBR on brain functional parameters during the early-delayed phase, we employed the [14C]-2-deoxyglucose (2-DG) and the [14C]-alfa-aminoisobutyric (AIB) acid quantitative autoradiographic techniques to study local cerebral glucose utilization and blood-brain barrier permeability, respectively. Sprague-Dowley albino rats were exposed to conventional fractionation (200 Gy/day 5 days a week) for a total dose of 4000 Gy. Experiments were made 3 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased following irradiation. As a rule, brain areas with the highest basal metabolic rates showed the highest percentage drop in glucose utilization. Changes in blood-brain barrier function, as assessed by an increased transcapillary transport of AIB, were also demonstrated in specific brain regions. This study illustrates how moderate doses of WBR induce well-defined changes in brain metabolism and BBB function, which are possibly involved in the pathogenesis of the early-delayed radiation-induced cerebral dysfunction in humans.

Subjective cognitive impairment and brain structural networks in Chinese gynaecological cancer survivors compared with age-matched controls: a cross-sectional study.

PubMed

Zeng, Yingchun; Cheng, Andy S K; Song, Ting; Sheng, Xiujie; Zhang, Yang; Liu, Xiangyu; Chan, Chetwyn C H

2017-11-28

Subjective cognitive impairment can be a significant and prevalent problem for gynaecological cancer survivors. The aims of this study were to assess subjective cognitive functioning in gynaecological cancer survivors after primary cancer treatment, and to investigate the impact of cancer treatment on brain structural networks and its association with subjective cognitive impairment. This was a cross-sectional survey using a self-reported questionnaire by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) to assess subjective cognitive functioning, and applying DTI (diffusion tensor imaging) and graph theoretical analyses to investigate brain structural networks after primary cancer treatment. A total of 158 patients with gynaecological cancer (mean age, 45.86 years) and 130 age-matched non-cancer controls (mean age, 44.55 years) were assessed. Patients reported significantly greater subjective cognitive functioning on the FACT-Cog total score and two subscales of perceived cognitive impairment and perceived cognitive ability (all p values <0.001). Compared with patients who had received surgery only and non-cancer controls, patients treated with chemotherapy indicated the most altered global brain structural networks, especially in one of properties of small-worldness (p = 0.004). Reduced small-worldness was significantly associated with a lower FACT-Cog total score (r = 0.412, p = 0.024). Increased characteristic path length was also significantly associated with more subjective cognitive impairment (r = -0.388, p = 0.034). When compared with non-cancer controls, a considerable proportion of gynaecological cancer survivors may exhibit subjective cognitive impairment. This study provides the first evidence of brain structural network alteration in gynaecological cancer patients at post-treatment, and offers novel insights regarding the possible neurobiological mechanism of cancer-related cognitive impairment (CRCI) in gynaecological cancer patients. As primary cancer treatment can result in a more random organisation of structural brain networks, this may reduce brain functional specificity and segregation, and have implications for cognitive impairment. Future prospective and longitudinal studies are needed to build upon the study findings in order to assess potentially relevant clinical and psychosocial variables and brain network measures, so as to more accurately understand the specific risk factors related to subjective cognitive impairment in the gynaecological cancer population. Such knowledge could inform the development of appropriate treatment and rehabilitation efforts to ameliorate cognitive impairment in gynaecological cancer survivors.

Contributions of Memory Circuits to Language: The Declarative/Procedural Model

ERIC Educational Resources Information Center

Ullman, Michael T.

2004-01-01

The structure of the brain and the nature of evolution suggest that, despite its uniqueness, language likely depends on brain systems that also subserve other functions. The declarative/procedural (DP) model claims that the mental lexicon of memorized word-specific knowledge depends on the largely temporal-lobe substrates of declarative memory,…

Dose-volume metrics and their relation to memory performance in pediatric brain tumor patients: A preliminary study.

PubMed

Raghubar, Kimberly P; Lamba, Michael; Cecil, Kim M; Yeates, Keith Owen; Mahone, E Mark; Limke, Christina; Grosshans, David; Beckwith, Travis J; Ris, M Douglas

2018-06-01

Advances in radiation treatment (RT), specifically volumetric planning with detailed dose and volumetric data for specific brain structures, have provided new opportunities to study neurobehavioral outcomes of RT in children treated for brain tumor. The present study examined the relationship between biophysical and physical dose metrics and neurocognitive ability, namely learning and memory, 2 years post-RT in pediatric brain tumor patients. The sample consisted of 26 pediatric patients with brain tumor, 14 of whom completed neuropsychological evaluations on average 24 months post-RT. Prescribed dose and dose-volume metrics for specific brain regions were calculated including physical metrics (i.e., mean dose and maximum dose) and biophysical metrics (i.e., integral biological effective dose and generalized equivalent uniform dose). We examined the associations between dose-volume metrics (whole brain, right and left hippocampus), and performance on measures of learning and memory (Children's Memory Scale). Biophysical dose metrics were highly correlated with the physical metric of mean dose but not with prescribed dose. Biophysical metrics and mean dose, but not prescribed dose, correlated with measures of learning and memory. These preliminary findings call into question the value of prescribed dose for characterizing treatment intensity; they also suggest that biophysical dose has only a limited advantage compared to physical dose when calculated for specific regions of the brain. We discuss the implications of the findings for evaluating and understanding the relation between RT and neurocognitive functioning. © 2018 Wiley Periodicals, Inc.

Structural and functional plasticity specific to musical training with wind instruments.

PubMed

Choi, Uk-Su; Sung, Yul-Wan; Hong, Sujin; Chung, Jun-Young; Ogawa, Seiji

2015-01-01

Numerous neuroimaging studies have shown structural and functional changes resulting from musical training. Among these studies, changes in primary sensory areas are mostly related to motor functions. In this study, we looked for some similar functional and structural changes in other functional modalities, such as somatosensory function, by examining the effects of musical training with wind instruments. We found significant changes in two aspects of neuroplasticity, cortical thickness, and resting-state neuronal networks. A group of subjects with several years of continuous musical training and who are currently playing in university wind ensembles showed differences in cortical thickness in lip- and tongue-related brain areas vs. non-music playing subjects. Cortical thickness in lip-related brain areas was significantly thicker and that in tongue-related areas was significantly thinner in the music playing group compared with that in the non-music playing group. Association analysis of lip-related areas in the music playing group showed that the increase in cortical thickness was caused by musical training. In addition, seed-based correlation analysis showed differential activation in the precentral gyrus and supplementary motor areas (SMA) between the music and non-music playing groups. These results suggest that high-intensity training with specific musical instruments could induce structural changes in related anatomical areas and could also generate a new functional neuronal network in the brain.

Structural and functional plasticity specific to musical training with wind instruments

PubMed Central

Choi, Uk-Su; Sung, Yul-Wan; Hong, Sujin; Chung, Jun-Young; Ogawa, Seiji

2015-01-01

Numerous neuroimaging studies have shown structural and functional changes resulting from musical training. Among these studies, changes in primary sensory areas are mostly related to motor functions. In this study, we looked for some similar functional and structural changes in other functional modalities, such as somatosensory function, by examining the effects of musical training with wind instruments. We found significant changes in two aspects of neuroplasticity, cortical thickness, and resting-state neuronal networks. A group of subjects with several years of continuous musical training and who are currently playing in university wind ensembles showed differences in cortical thickness in lip- and tongue-related brain areas vs. non-music playing subjects. Cortical thickness in lip-related brain areas was significantly thicker and that in tongue-related areas was significantly thinner in the music playing group compared with that in the non-music playing group. Association analysis of lip-related areas in the music playing group showed that the increase in cortical thickness was caused by musical training. In addition, seed-based correlation analysis showed differential activation in the precentral gyrus and supplementary motor areas (SMA) between the music and non-music playing groups. These results suggest that high-intensity training with specific musical instruments could induce structural changes in related anatomical areas and could also generate a new functional neuronal network in the brain. PMID:26578939

Identifying with fictive characters: structural brain correlates of the personality trait ‘fantasy’

PubMed Central

Hänggi, Jürgen; Jancke, Lutz

2014-01-01

The perception of oneself as absorbed in the thoughts, feelings and happenings of a fictive character (e.g. in a novel or film) as if the character’s experiences were one’s own is referred to as identification. We investigated whether individual variation in the personality trait of identification is associated with individual variation in the structure of specific brain regions, using surface and volume-based morphometry. The hypothesized regions of interest were selected on the basis of their functional role in subserving the cognitive processing domains considered important for identification (i.e. mental imagery, empathy, theory of mind and merging) and for the immersive experience called ‘presence’. Controlling for age, sex, whole-brain volume and other traits, identification covaried significantly with the left hippocampal volume, cortical thickness in the right anterior insula and the left dorsal medial prefrontal cortex, and with gray matter volume in the dorsolateral prefrontal cortex. These findings show that trait identification is associated with structural variation in specific brain regions. The findings are discussed in relation to the potential functional contribution of these regions to identification. PMID:24464847

The Revised Neurobehavioral Severity Scale (NSS-R) for Rodents.

PubMed

Yarnell, Angela M; Barry, Erin S; Mountney, Andrea; Shear, Deborah; Tortella, Frank; Grunberg, Neil E

2016-04-08

Motor and sensory deficits are common following traumatic brain injury (TBI). Although rodent models provide valuable insight into the biological and functional outcomes of TBI, the success of translational research is critically dependent upon proper selection of sensitive, reliable, and reproducible assessments. Published literature includes various observational scales designed to evaluate post-injury functionality; however, the heterogeneity in TBI location, severity, and symptomology can complicate behavioral assessments. The importance of choosing behavioral outcomes that can be reliably and objectively quantified in an efficient manner is becoming increasingly important. The Revised Neurobehavioral Severity Scale (NSS-R) is a continuous series of specific, sensitive, and standardized observational tests that evaluate balance, motor coordination, and sensorimotor reflexes in rodents. The tasks follow a specific order designed to minimize interference: balance, landing, tail raise, dragging, righting reflex, ear reflex, eye reflex, sound reflex, tail pinch, and hindpaw pinch. The NSS-R has proven to be a reliable method differentiating brain-injured rodents from non-brain-injured rodents across many brain injury models. Copyright © 2016 John Wiley & Sons, Inc.

Construction of population-specific Indian MRI brain template: Morphometric comparison with Chinese and Caucasian templates.

PubMed

Bhalerao, Gaurav Vivek; Parlikar, Rujuta; Agrawal, Rimjhim; Shivakumar, Venkataram; Kalmady, Sunil V; Rao, Naren P; Agarwal, Sri Mahavir; Narayanaswamy, Janardhanan C; Reddy, Y C Janardhan; Venkatasubramanian, Ganesan

2018-06-01

Spatial normalization of brain MR images is highly dependent on the choice of target brain template. Morphological differences caused by factors like genetic and environmental exposures, generates a necessity to construct population specific brain templates. Brain image analysis performed using brain templates from Caucasian population may not be appropriate for non-Caucasian population. In this study, our objective was to construct an Indian brain template from a large population (N = 157 subjects) and compare the morphometric parameters of this template with that of Chinese-56 and MNI-152 templates. In addition, using an independent MRI data of 15 Indian subjects, we also evaluated the potential registration accuracy differences using these three templates. Indian brain template was constructed using iterative routines as per established procedures. We compared our Indian template with standard MNI-152 template and Chinese template by measuring global brain features. We also examined accuracy of registration by aligning 15 new Indian brains to Indian, Chinese and MNI templates. Furthermore, we supported our measurement protocol with inter-rater and intra-rater reliability analysis. Our results showed that there were significant differences in global brain features of Indian template in comparison with Chinese and MNI brain templates. The results of registration accuracy analysis revealed that fewer deformations are required when Indian brains are registered to Indian template as compared to Chinese and MNI templates. This study concludes that population specific Indian template is likely to be more appropriate for structural and functional image analysis of Indian population. Copyright © 2018 Elsevier B.V. All rights reserved.

Adolescent binge drinking linked to abnormal spatial working memory brain activation: differential gender effects.

PubMed

Squeglia, Lindsay M; Schweinsburg, Alecia Dager; Pulido, Carmen; Tapert, Susan F

2011-10-01

Binge drinking is prevalent during adolescence, and its effect on neurocognitive development is of concern. In adult and adolescent populations, heavy substance use has been associated with decrements in cognitive functioning, particularly on tasks of spatial working memory (SWM). Characterizing the gender-specific influences of heavy episodic drinking on SWM may help elucidate the early functional consequences of drinking on adolescent brain functioning. Forty binge drinkers (13 females, 27 males) and 55 controls (24 females, 31 males), aged 16 to 19 years, completed neuropsychological testing, substance use interviews, and an SWM task during functional magnetic resonance imaging. Significant binge drinking status × gender interactions were found (p < 0.05) in 8 brain regions spanning bilateral frontal, anterior cingulate, temporal, and cerebellar cortices. In all regions, female binge drinkers showed less SWM activation than female controls, while male bingers exhibited greater SWM response than male controls. For female binge drinkers, less activation was associated with poorer sustained attention and working memory performances (p < 0.025). For male binge drinkers, greater activation was linked to better spatial performance (p < 0.025). Binge drinking during adolescence is associated with gender-specific differences in frontal, temporal, and cerebellar brain activation during an SWM task, which in turn relate to cognitive performance. Activation correlates with neuropsychological performance, strengthening the argument that blood oxygen level-dependent activation is affected by alcohol use and is an important indicator of behavioral functioning. Females may be more vulnerable to the neurotoxic effects of heavy alcohol use during adolescence, while males may be more resilient to the deleterious effects of binge drinking. Future longitudinal research will examine the significance of SWM brain activation as an early neurocognitive marker of alcohol impact to the brain on future behaviors, such as driving safety, academic performance, and neuropsychological performance. Copyright © 2011 by the Research Society on Alcoholism.

The Grass Might Be Greener: Medical Marijuana Patients Exhibit Altered Brain Activity and Improved Executive Function after 3 Months of Treatment

PubMed Central

Gruber, Staci A.; Sagar, Kelly A.; Dahlgren, Mary K.; Gonenc, Atilla; Smith, Rosemary T.; Lambros, Ashley M.; Cabrera, Korine B.; Lukas, Scott E.

2018-01-01

The vast majority of states have enacted full or partial medical marijuana (MMJ) programs, causing the number of patients seeking certification for MMJ use to increase dramatically in recent years. Despite increased use of MMJ across the nation, no studies thus far have examined the specific impact of MMJ on cognitive function and related brain activation. In the present study, MMJ patients seeking treatment for a variety of documented medical conditions were assessed prior to initiating MMJ treatment and after 3 months of treatment as part of a larger longitudinal study. In order to examine the effect of MMJ treatment on task-related brain activation, MMJ patients completed the Multi-Source Interference Test (MSIT) while undergoing functional magnetic resonance imaging (fMRI). We also collected data regarding conventional medication use, clinical state, and health-related measures at each visit. Following 3 months of treatment, MMJ patients demonstrated improved task performance accompanied by changes in brain activation patterns within the cingulate cortex and frontal regions. Interestingly, after MMJ treatment, brain activation patterns appeared more similar to those exhibited by healthy controls from previous studies than at pre-treatment, suggestive of a potential normalization of brain function relative to baseline. These findings suggest that MMJ use may result in different effects relative to recreational marijuana (MJ) use, as recreational consumers have been shown to exhibit decrements in task performance accompanied by altered brain activation. Moreover, patients in the current study also reported improvements in clinical state and health-related measures as well as notable decreases in prescription medication use, particularly opioids and benzodiapezines after 3 months of treatment. Further research is needed to clarify the specific neurobiologic impact, clinical efficacy, and unique effects of MMJ for a range of indications and how it compares to recreational MJ use. PMID:29387010

The Grass Might Be Greener: Medical Marijuana Patients Exhibit Altered Brain Activity and Improved Executive Function after 3 Months of Treatment.

PubMed

Gruber, Staci A; Sagar, Kelly A; Dahlgren, Mary K; Gonenc, Atilla; Smith, Rosemary T; Lambros, Ashley M; Cabrera, Korine B; Lukas, Scott E

2017-01-01

The vast majority of states have enacted full or partial medical marijuana (MMJ) programs, causing the number of patients seeking certification for MMJ use to increase dramatically in recent years. Despite increased use of MMJ across the nation, no studies thus far have examined the specific impact of MMJ on cognitive function and related brain activation. In the present study, MMJ patients seeking treatment for a variety of documented medical conditions were assessed prior to initiating MMJ treatment and after 3 months of treatment as part of a larger longitudinal study. In order to examine the effect of MMJ treatment on task-related brain activation, MMJ patients completed the Multi-Source Interference Test (MSIT) while undergoing functional magnetic resonance imaging (fMRI). We also collected data regarding conventional medication use, clinical state, and health-related measures at each visit. Following 3 months of treatment, MMJ patients demonstrated improved task performance accompanied by changes in brain activation patterns within the cingulate cortex and frontal regions. Interestingly, after MMJ treatment, brain activation patterns appeared more similar to those exhibited by healthy controls from previous studies than at pre-treatment, suggestive of a potential normalization of brain function relative to baseline. These findings suggest that MMJ use may result in different effects relative to recreational marijuana (MJ) use, as recreational consumers have been shown to exhibit decrements in task performance accompanied by altered brain activation. Moreover, patients in the current study also reported improvements in clinical state and health-related measures as well as notable decreases in prescription medication use, particularly opioids and benzodiapezines after 3 months of treatment. Further research is needed to clarify the specific neurobiologic impact, clinical efficacy, and unique effects of MMJ for a range of indications and how it compares to recreational MJ use.

Unfolding dimension and the search for functional markers in the human electroencephalogram

NASA Astrophysics Data System (ADS)

Dünki, Rudolf M.; Schmid, Gary Bruno

1998-02-01

A biparametric approach to dimensional analysis in terms of a so-called ``unfolding dimension'' is introduced to explore the extent to which the human EEG can be described by stable features characteristic of an individual despite the well-known problems of intraindividual variability. Our analysis comprises an EEG data set recorded from healthy individuals over a time span of 5 years. The outcome is shown to be comparable to advanced linear methods of spectral analysis with regard to intraindividual specificity and stability over time. Such linear methods have not yet proven to be specific to the EEG of different brain states. Thus we have also investigated the specificity of our biparametric approach by comparing the mental states schizophrenic psychosis and remission, i.e., illness versus full recovery. A difference between EEG in psychosis and remission became apparent within recordings taken at rest with eyes closed and no stimulated or requested mental activity. Hence our approach distinguishes these functional brain states even in the absence of an active or intentional stimulus. This sheds a different light upon theories of schizophrenia as an information-processing disturbance of the brain.

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

PubMed

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

2011-08-22

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

The blind brain: how (lack of) vision shapes the morphological and functional architecture of the human brain.

PubMed

Ricciardi, Emiliano; Handjaras, Giacomo; Pietrini, Pietro

2014-11-01

Since the early days, how we represent the world around us has been a matter of philosophical speculation. Over the last few decades, modern neuroscience, and specifically the development of methodologies for the structural and the functional exploration of the brain have made it possible to investigate old questions with an innovative approach. In this brief review, we discuss the main findings from a series of brain anatomical and functional studies conducted in sighted and congenitally blind individuals by our's and others' laboratories. Historically, research on the 'blind brain' has focused mainly on the cross-modal plastic changes that follow sensory deprivation. More recently, a novel line of research has been developed to determine to what extent visual experience is truly required to achieve a representation of the surrounding environment. Overall, the results of these studies indicate that most of the brain fine morphological and functional architecture is programmed to develop and function independently from any visual experience. Distinct cortical areas are able to process information in a supramodal fashion, that is, independently from the sensory modality that carries that information to the brain. These observations strongly support the hypothesis of a modality-independent, i.e. more abstract, cortical organization, and may contribute to explain how congenitally blind individuals may interact efficiently with an external world that they have never seen. © 2014 by the Society for Experimental Biology and Medicine.

Short desynchronization episodes prevail in synchronous dynamics of human brain rhythms.

PubMed

Ahn, Sungwoo; Rubchinsky, Leonid L

2013-03-01

Neural synchronization is believed to be critical for many brain functions. It frequently exhibits temporal variability, but it is not known if this variability has a specific temporal patterning. This study explores these synchronization/desynchronization patterns. We employ recently developed techniques to analyze the fine temporal structure of phase-locking to study the temporal patterning of synchrony of the human brain rhythms. We study neural oscillations recorded by electroencephalograms in α and β frequency bands in healthy human subjects at rest and during the execution of a task. While the phase-locking strength depends on many factors, dynamics of synchrony has a very specific temporal pattern: synchronous states are interrupted by frequent, but short desynchronization episodes. The probability for a desynchronization episode to occur decreased with its duration. The transition matrix between synchronized and desynchronized states has eigenvalues close to 0 and 1 where eigenvalue 1 has multiplicity 1, and therefore if the stationary distribution between these states is perturbed, the system converges back to the stationary distribution very fast. The qualitative similarity of this patterning across different subjects, brain states and electrode locations suggests that this may be a general type of dynamics for the brain. Earlier studies indicate that not all oscillatory networks have this kind of patterning of synchronization/desynchronization dynamics. Thus, the observed prevalence of short (but potentially frequent) desynchronization events (length of one cycle of oscillations) may have important functional implications for the brain. Numerous short desynchronizations (as opposed to infrequent, but long desynchronizations) may allow for a quick and efficient formation and break-up of functionally significant neuronal assemblies.

Neuropsychology of humor: an introduction. Part II. Humor and the brain.

PubMed

Derouesné, Christian

2016-09-01

Impairment of the perception or comprehension of humor is observed in patients with focal brain lesions in both hemispheres, but mainly in the right frontal lobe. Studies by functional magnetic resonance imaging in healthy subjects show that humor is associated with activation of two main neural systems in both hemispheres. The detection and resolution of incongruity, cognitive groundings of humor, are associated with activation of the medial prefrontal and temporoparietal cortex, and the humor appreciation with activation of the orbito-frontal and insular cortex, amygdala and the brain reward system. However, activation of these areas is not humor-specific and can be observed in various cognitive or emotional processes. Event-related potential studies confirm the involvement of both hemispheres in humor processing, and suggest that left prefrontal area is associated with joke comprehension and right prefrontal area with the resolution stage. Humor thus appears to be a complex and dynamic functional process involving, on one hand, two specialized but not specific neural systems linked to humor apprehension and appreciation, and, on the other hand, multiple interconnected functional brain networks including neural patterns underlying the moral framework and belief system, acquired by conditioning or imitation during the cognitive development and social interactions of the individual, and more distributed systems associated with the analysis of the current context of humor occurrence. Disturbances of the sense of humor could then result from focal brain alterations localized in one or two of the specialized areas underlying the comprehension or appreciation of humor, or from perturbations of the network interconnectivity in non-focal brain disorders such as Alzheimer's disease or schizophrenia.

Short desynchronization episodes prevail in synchronous dynamics of human brain rhythms

NASA Astrophysics Data System (ADS)

Ahn, Sungwoo; Rubchinsky, Leonid L.

2013-03-01

Neural synchronization is believed to be critical for many brain functions. It frequently exhibits temporal variability, but it is not known if this variability has a specific temporal patterning. This study explores these synchronization/desynchronization patterns. We employ recently developed techniques to analyze the fine temporal structure of phase-locking to study the temporal patterning of synchrony of the human brain rhythms. We study neural oscillations recorded by electroencephalograms in α and β frequency bands in healthy human subjects at rest and during the execution of a task. While the phase-locking strength depends on many factors, dynamics of synchrony has a very specific temporal pattern: synchronous states are interrupted by frequent, but short desynchronization episodes. The probability for a desynchronization episode to occur decreased with its duration. The transition matrix between synchronized and desynchronized states has eigenvalues close to 0 and 1 where eigenvalue 1 has multiplicity 1, and therefore if the stationary distribution between these states is perturbed, the system converges back to the stationary distribution very fast. The qualitative similarity of this patterning across different subjects, brain states and electrode locations suggests that this may be a general type of dynamics for the brain. Earlier studies indicate that not all oscillatory networks have this kind of patterning of synchronization/desynchronization dynamics. Thus, the observed prevalence of short (but potentially frequent) desynchronization events (length of one cycle of oscillations) may have important functional implications for the brain. Numerous short desynchronizations (as opposed to infrequent, but long desynchronizations) may allow for a quick and efficient formation and break-up of functionally significant neuronal assemblies.

Do anesthetics harm the developing human brain? An integrative analysis of animal and human studies.

PubMed

Lin, Erica P; Lee, Jeong-Rim; Lee, Christopher S; Deng, Meng; Loepke, Andreas W

Anesthetics that permit surgical procedures and stressful interventions have been found to cause structural brain abnormalities and functional impairment in immature animals, generating extensive concerns among clinicians, parents, and government regulators regarding the safe use of these drugs in young children. Critically important questions remain, such as the exact age at which the developing brain is most vulnerable to the effects of anesthetic exposure, whether a particular age exists beyond which anesthetics are devoid of long-term effects on the brain, and whether any specific exposure duration exists that does not lead to deleterious effects. Accordingly, the present analysis attempts to put the growing body of animal studies, which we identified to include >440 laboratory studies to date, into a translational context, by integrating the preclinical data on brain structure and function with clinical results attained from human neurocognitive studies, which currently exceed 30 studies. Our analysis demonstrated no clear exposure duration threshold below which no structural injury or subsequent cognitive abnormalities occurred. Animal data did not clearly identify a specific age beyond which anesthetic exposure did not cause any structural or functional abnormalities. Several potential mitigating strategies were found, however, no general anesthetic was identified that consistently lacked neurodegenerative properties and could be recommended over other anesthetics. It therefore is imperative, to expand efforts to devise safer anesthetic techniques and mitigating strategies, even before long-term alterations in brain development are unequivocally confirmed to occur in millions of young children undergoing anesthesia every year. Copyright © 2016 Elsevier Inc. All rights reserved.

Electrical engram: how deep brain stimulation affects memory.

PubMed

Lee, Hweeling; Fell, Jürgen; Axmacher, Nikolai

2013-11-01

Deep brain stimulation (DBS) is a surgical procedure involving implantation of a pacemaker that sends electric impulses to specific brain regions. DBS has been applied in patients with Parkinson's disease, depression, and obsessive-compulsive disorder (among others), and more recently in patients with Alzheimer's disease to improve memory functions. Current DBS approaches are based on the concept that high-frequency stimulation inhibits or excites specific brain regions. However, because DBS entails the application of repetitive electrical stimuli, it primarily exerts an effect on extracellular field-potential oscillations similar to those recorded with electroencephalography. Here, we suggest a new perspective on how DBS may ameliorate memory dysfunction: it may enhance normal electrophysiological patterns underlying long-term memory processes within the medial temporal lobe. Copyright © 2013 Elsevier Ltd. All rights reserved.

Brain Structure-Function Couplings: Year 2 Accomplishments and Programmatic Plans

DTIC Science & Technology

2013-06-01

performance through individual-specific neurotechnologies and enhance Soldier protection technologies to minimize neural injury. The long-term vision of this...envision pathways that enable our basic science accomplishments to foster development of revolutionary Soldier neurotechnologies and Soldier protection...improve Soldier-system performance with Soldier-specific neurotechnologies . We expect mid-term impact with models linking structure and function that can

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

PubMed

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

2000-01-29

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

The Anatomical Distance of Functional Connections Predicts Brain Network Topology in Health and Schizophrenia

PubMed Central

Vértes, Petra E.; Stidd, Reva; Lalonde, François; Clasen, Liv; Rapoport, Judith; Giedd, Jay; Bullmore, Edward T.; Gogtay, Nitin

2013-01-01

The human brain is a topologically complex network embedded in anatomical space. Here, we systematically explored relationships between functional connectivity, complex network topology, and anatomical (Euclidean) distance between connected brain regions, in the resting-state functional magnetic resonance imaging brain networks of 20 healthy volunteers and 19 patients with childhood-onset schizophrenia (COS). Normal between-subject differences in average distance of connected edges in brain graphs were strongly associated with variation in topological properties of functional networks. In addition, a club or subset of connector hubs was identified, in lateral temporal, parietal, dorsal prefrontal, and medial prefrontal/cingulate cortical regions. In COS, there was reduced strength of functional connectivity over short distances especially, and therefore, global mean connection distance of thresholded graphs was significantly greater than normal. As predicted from relationships between spatial and topological properties of normal networks, this disorder-related proportional increase in connection distance was associated with reduced clustering and modularity and increased global efficiency of COS networks. Between-group differences in connection distance were localized specifically to connector hubs of multimodal association cortex. In relation to the neurodevelopmental pathogenesis of schizophrenia, we argue that the data are consistent with the interpretation that spatial and topological disturbances of functional network organization could arise from excessive “pruning” of short-distance functional connections in schizophrenia. PMID:22275481

Differences in Brain Activity during a Verbal Associative Memory Encoding Task in High- and Low-fit Adolescents

PubMed Central

Herting, Megan M.; Nagel, Bonnie J.

2013-01-01

Aerobic fitness is associated with better memory performance as well as larger volumes in memory-related brain regions in children, adolescents, and elderly. It is unclear if aerobic exercise also influences learning and memory functional neural circuitry. Here, we examine brain activity in 17 high-fit (HF) and 17 low-fit (LF) adolescents during a subsequent memory encoding paradigm using fMRI. Despite similar memory performance, HF and LF youth displayed a number of differences in memory-related and default mode (DMN) brain regions during encoding later remembered versus forgotten word pairs. Specifically, HF youth displayed robust deactivation in DMN areas, including the ventral medial PFC and posterior cingulate cortex, whereas LF youth did not show this pattern. Furthermore, LF youth showed greater bilateral hippocampal and right superior frontal gyrus activation during encoding of later remembered versus forgotten word pairs. Follow-up task-dependent functional correlational analyses showed differences in hippocampus and DMN activity coupling during successful encoding between the groups, suggesting aerobic fitness during adolescents may impact functional connectivity of the hippocampus and DMN during memory encoding. To our knowledge, this study is the first to examine the influence of aerobic fitness on hippocampal function and memory-related neural circuitry using fMRI. Taken together with previous research, these findings suggest aerobic fitness can influence not only memory-related brain structure, but also brain function. PMID:23249350

Cocaine-Induced Neurodevelopmental Deficits and Underlying Mechanisms

PubMed Central

Martin, Melissa M.; Graham, Devon L.; McCarthy, Deirdre M.; Bhide, Pradeep G.; Stanwood, Gregg D.

2017-01-01

Exposure to drugs early in life has complex and long-lasting implications for brain structure and function. This review summarizes work to date on the immediate and long-term effects of prenatal exposure to cocaine. In utero cocaine exposure produces disruptions in brain monoamines, particularly dopamine, during sensitive periods of brain development, and leads to permanent changes in specific brain circuits, molecules, and behavior. Here, we integrate clinical studies and significance with mechanistic preclinical studies, to define our current knowledge base and identify gaps for future investigation. PMID:27345015

Alterations in blood-brain barrier function following acute hypertension: comparison of the blood-to-brain transfer of horseradish peroxidase with that of alpha-aminisobutyric acid

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

Ellison, M.D.B.

The blood-brain barrier (BBB) selectively restricts the blood-to-brain passage of many solutes owing to unique properties of cerebrovascular endothelial cell membranes. To date, experimental study of the BBB has been accomplished primarily through the use of two different methodological approaches. Morphological studies have mostly employed large molecular weight (MW) tracers to detect morphological alterations underlying increased permeability. Physiological studies, employing smaller, more physiologic tracers have successfully described, quantitatively, certain functional aspects of blood-to-brain transfer. The current work attempts to merge these two approaches and to consider barrier function/dysfunction from both a morphological and a functional perspective. Specifically, the study comparesmore » in rats, following acute hypertension, the cerebrovascular passage of /sup 14/C-alpha-aminoisobutyric acid (AIB) and that of horseradish peroxidase (HRP). The blood-to-brain passage of AIB and HRP were compared following acute hypertension, with regard to both the distributions of the tracer extravasation patterns and the magnitude of tracer extravasation. The results of this study suggest that traditional morphological barrier studies alone do not reveal all aspects of altered barrier status and that multiple mechanisms underlying increased BBB permeability may operate simultaneously during BBB dysfunction.« less

Neuroimaging studies towards understanding the central effects of pharmacological cannabis products on patients with epilepsy.

PubMed

Allendorfer, Jane B; Szaflarski, Jerzy P

2017-05-01

Recent interest for the use of cannabis-derived products as therapeutic agents in the treatment of epilepsies has necessitated a reevaluation of their effects on brain and behavior. Overall, prolonged cannabis use is thought to result in functional and structural brain alterations. These effects may be dependent on a number of factors: e.g., which phytocannabinoid is used (e.g., cannabidiol (CBD) vs. tetrahyrocannabinol (THC)), the frequency of use (occasional vs. heavy), and at what age (prenatal, childhood, adulthood) the use began. However, due to the fact that there are over seven hundred constituents that make up the Cannabis sativa plant, it is difficult to determine which compound or combination of compounds is responsible for specific effects when studying recreational users. Therefore, this review focuses only on the functional MRI studies investigating the effects of specific pharmacological preparations of cannabis compounds, specifically THC, tetrahydrocannabivarin (THCV), and CBD, on brain function in healthy individuals and persons with epilepsy with references to non-epilepsy studies only to underline the gaps in research that need to be filled before cannabis-derived products are considered for a wide use in the treatment of epilepsy. This article is part of a Special Issue entitled "Cannabinoids and Epilepsy". Copyright © 2016 Elsevier Inc. All rights reserved.

Deciphering the functions of O-GlcNAc glycosylation in the brain: The role of site-specific quantitative O-GlcNAcomics.

PubMed

Thompson, John W; Sorum, Alexander W; Hsieh-Wilson, Linda C

2018-06-23

The dynamic posttranslational modification O-linked β-N-acetylglucosamine glycosylation (O-GlcNAcylation) is present on thousands of intracellular proteins in the brain. Like phosphorylation, O-GlcNAcylation is inducible and plays important functional roles in both physiology and disease. Recent advances in mass spectrometry (MS) and bioconjugation methods are now enabling the mapping of O-GlcNAcylation events to individual sites in proteins. However, our understanding of which glycosylation events are necessary for regulating protein function and controlling specific processes, phenotypes, or diseases remains in its infancy. Given the sheer number of O-GlcNAc sites, methods are greatly needed to identify promising sites and prioritize them for time- and resource-intensive functional studies. Revealing sites that are dynamically altered by different stimuli or disease states will likely to go a long way in this regard. Here, we describe advanced methods for identifying O-GlcNAc sites on individual proteins and across the proteome, and for determining their stoichiometry in vivo. We also highlight emerging technologies for quantitative, site-specific MS-based O-GlcNAc proteomics (O-GlcNAcomics), which allow proteome-wide tracking of O-GlcNAcylation dynamics at individual sites. These cutting-edge technologies are beginning to bridge the gap between the high-throughput cataloging of O-GlcNAcylated proteins and the relatively low-throughput study of individual proteins. By uncovering the O-GlcNAcylation events that change in specific physiological and disease contexts, these new approaches are providing key insights into the regulatory functions of O-GlcNAc in the brain, including their roles in neuroprotection, neuronal signaling, learning and memory, and neurodegenerative diseases.

Anti–IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus

PubMed Central

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

2015-01-01

Impaired blood-brain barrier function represents an important component of hypoxic-ischemic brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-brain barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-brain barrier abnormalities have not been examined in the immature brain in vivo. We generated pharmacologic quantities of ovine-specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal sheep at 126 days of gestation after exposure to brain ischemia. Anti–IL-6 mAbs were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid, blood-brain barrier permeability was quantified using the blood-to-brain transfer constant in brain regions, and IL-6, tight junction proteins, and plasmalemma vesicle protein (PLVAP) were detected by Western immunoblot. Anti–IL-6 mAb infusions resulted in increases in mAb (P < 0.05) in plasma, brain parenchyma, and cerebrospinal fluid and decreases in brain IL-6 protein. Twenty-four hours after ischemia, anti–IL-6 mAb infusions attenuated ischemia-related increases in blood-brain barrier permeability and modulated tight junction and PLVAP protein expression in fetal brain. We conclude that inhibiting the effects of IL-6 protein with systemic infusions of neutralizing antibodies attenuates ischemia-related increases in blood-brain barrier permeability by inhibiting IL-6 and modulates tight junction proteins after ischemia.—Zhang, J., Sadowska, G. B., Chen, X., Park, S. Y., Kim, J.-E., Bodge, C. A., Cummings, E., Lim, Y.-P., Makeyev, O., Besio, W. G., Gaitanis, J., Banks, W. A., Stonestreet, B. S. Anti–IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus. PMID:25609424

Rapid and minimum invasive functional brain mapping by real-time visualization of high gamma activity during awake craniotomy.

PubMed

Ogawa, Hiroshi; Kamada, Kyousuke; Kapeller, Christoph; Hiroshima, Satoru; Prueckl, Robert; Guger, Christoph

2014-11-01

Electrocortical stimulation (ECS) is the gold standard for functional brain mapping during an awake craniotomy. The critical issue is to set aside enough time to identify eloquent cortices by ECS. High gamma activity (HGA) ranging between 80 and 120 Hz on electrocorticogram is assumed to reflect localized cortical processing. In this report, we used real-time HGA mapping and functional neuronavigation integrated with functional magnetic resonance imaging (fMRI) for rapid and reliable identification of motor and language functions. Four patients with intra-axial tumors in their dominant hemisphere underwent preoperative fMRI and lesion resection with an awake craniotomy. All patients showed significant fMRI activation evoked by motor and language tasks. During the craniotomy, we recorded electrocorticogram activity by placing subdural grids directly on the exposed brain surface. Each patient performed motor and language tasks and demonstrated real-time HGA dynamics in hand motor areas and parts of the inferior frontal gyrus. Sensitivity and specificity of HGA mapping were 100% compared with ECS mapping in the frontal lobe, which suggested HGA mapping precisely indicated eloquent cortices. We found different HGA dynamics of language tasks in frontal and temporal regions. Specificities of the motor and language-fMRI did not reach 85%. The results of HGA mapping was mostly consistent with those of ECS mapping, although fMRI tended to overestimate functional areas. This novel technique enables rapid and accurate identification of motor and frontal language areas. Furthermore, real-time HGA mapping sheds light on underlying physiological mechanisms related to human brain functions. Copyright © 2014 Elsevier Inc. All rights reserved.

In vivo Visuotopic Brain Mapping with Manganese-Enhanced MRI and Resting-State Functional Connectivity MRI

PubMed Central

Chan, Kevin C.; Fan, Shu-Juan; Chan, Russell W.; Cheng, Joe S.; Zhou, Iris Y.; Wu, Ed X.

2014-01-01

The rodents are an increasingly important model for understanding the mechanisms of development, plasticity, functional specialization and disease in the visual system. However, limited tools have been available for assessing the structural and functional connectivity of the visual brain network globally, in vivo and longitudinally. There are also ongoing debates on whether functional brain connectivity directly reflects structural brain connectivity. In this study, we explored the feasibility of manganese-enhanced MRI (MEMRI) via 3 different routes of Mn2+ administration for visuotopic brain mapping and understanding of physiological transport in normal and visually deprived adult rats. In addition, resting-state functional connectivity MRI (RSfcMRI) was performed to evaluate the intrinsic functional network and structural-functional relationships in the corresponding anatomical visual brain connections traced by MEMRI. Upon intravitreal, subcortical, and intracortical Mn2+ injection, different topographic and layer-specific Mn enhancement patterns could be revealed in the visual cortex and subcortical visual nuclei along retinal, callosal, cortico-subcortical, transsynaptic and intracortical horizontal connections. Loss of visual input upon monocular enucleation to adult rats appeared to reduce interhemispheric polysynaptic Mn2+ transfer but not intra- or inter-hemispheric monosynaptic Mn2+ transport after Mn2+ injection into visual cortex. In normal adults, both structural and functional connectivity by MEMRI and RSfcMRI was stronger interhemispherically between bilateral primary/secondary visual cortex (V1/V2) transition zones (TZ) than between V1/V2 TZ and other cortical nuclei. Intrahemispherically, structural and functional connectivity was stronger between visual cortex and subcortical visual nuclei than between visual cortex and other subcortical nuclei. The current results demonstrated the sensitivity of MEMRI and RSfcMRI for assessing the neuroarchitecture, neurophysiology and structural-functional relationships of the visual brains in vivo. These may possess great potentials for effective monitoring and understanding of the basic anatomical and functional connections in the visual system during development, plasticity, disease, pharmacological interventions and genetic modifications in future studies. PMID:24394694

Altered resting-state functional connectivity in patients with chronic bilateral vestibular failure.

PubMed

Göttlich, Martin; Jandl, Nico M; Wojak, Jann F; Sprenger, Andreas; von der Gablentz, Janina; Münte, Thomas F; Krämer, Ulrike M; Helmchen, Christoph

2014-01-01

Patients with bilateral vestibular failure (BVF) suffer from gait unsteadiness, oscillopsia and impaired spatial orientation. Brain imaging studies applying caloric irrigation to patients with BVF have shown altered neural activity of cortical visual-vestibular interaction: decreased bilateral neural activity in the posterior insula and parietal operculum and decreased deactivations in the visual cortex. It is unknown how this affects functional connectivity in the resting brain and how changes in connectivity are related to vestibular impairment. We applied a novel data driven approach based on graph theory to investigate altered whole-brain resting-state functional connectivity in BVF patients (n= 22) compared to age- and gender-matched healthy controls (n= 25) using resting-state fMRI. Changes in functional connectivity were related to subjective (vestibular scores) and objective functional parameters of vestibular impairment, specifically, the adaptive changes during active (self-guided) and passive (investigator driven) head impulse test (HIT) which reflects the integrity of the vestibulo-ocular reflex (VOR). BVF patients showed lower bilateral connectivity in the posterior insula and parietal operculum but higher connectivity in the posterior cerebellum compared to controls. Seed-based analysis revealed stronger connectivity from the right posterior insula to the precuneus, anterior insula, anterior cingulate cortex and the middle frontal gyrus. Excitingly, functional connectivity in the supramarginal gyrus (SMG) of the inferior parietal lobe and posterior cerebellum correlated with the increase of VOR gain during active as compared to passive HIT, i.e., the larger the adaptive VOR changes the larger was the increase in regional functional connectivity. Using whole brain resting-state connectivity analysis in BVF patients we show that enduring bilateral deficient or missing vestibular input leads to changes in resting-state connectivity of the brain. These changes in the resting brain are robust and task-independent as they were found in the absence of sensory stimulation and without a region-related a priori hypothesis. Therefore they may indicate a fundamental disease-related change in the resting brain. They may account for the patients' persistent deficits in visuo-spatial attention, spatial orientation and unsteadiness. The relation of increasing connectivity in the inferior parietal lobe, specifically SMG, to improvement of VOR during active head movements reflects cortical plasticity in BVF and may play a clinical role in vestibular rehabilitation.

Detecting large-scale networks in the human brain using high-density electroencephalography.

PubMed

Liu, Quanying; Farahibozorg, Seyedehrezvan; Porcaro, Camillo; Wenderoth, Nicole; Mantini, Dante

2017-09-01

High-density electroencephalography (hdEEG) is an emerging brain imaging technique that can be used to investigate fast dynamics of electrical activity in the healthy and the diseased human brain. Its applications are however currently limited by a number of methodological issues, among which the difficulty in obtaining accurate source localizations. In particular, these issues have so far prevented EEG studies from reporting brain networks similar to those previously detected by functional magnetic resonance imaging (fMRI). Here, we report for the first time a robust detection of brain networks from resting state (256-channel) hdEEG recordings. Specifically, we obtained 14 networks previously described in fMRI studies by means of realistic 12-layer head models and exact low-resolution brain electromagnetic tomography (eLORETA) source localization, together with independent component analysis (ICA) for functional connectivity analysis. Our analyses revealed three important methodological aspects. First, brain network reconstruction can be improved by performing source localization using the gray matter as source space, instead of the whole brain. Second, conducting EEG connectivity analyses in individual space rather than on concatenated datasets may be preferable, as it permits to incorporate realistic information on head modeling and electrode positioning. Third, the use of a wide frequency band leads to an unbiased and generally accurate reconstruction of several network maps, whereas filtering data in a narrow frequency band may enhance the detection of specific networks and penalize that of others. We hope that our methodological work will contribute to rise of hdEEG as a powerful tool for brain research. Hum Brain Mapp 38:4631-4643, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Connectomics and other novel methods for examining neural systems.

PubMed

Wurtman, Richard J

2017-04-01

Novel approaches for studying the brain and relating its activities to mental phenomena have come into use during the past decade (Bargmann, 2015). These include both new laboratory methods - involving, among others, generation of isolated cells which retain neuronal characteristics in vivo; the selective stimulation of neurons by light in vivo; and direct electrical stimulation of specific brain regions to restore a system's balance of excitation and inhibition - and a new organizing principle, "connectomics", which recognizes that networks, and not simply a key nucleus or region, underlie most brain functions and malfunctions. Its application has already improved our comprehension of how the brain normally functions and our ability to help patients with such poorly treated neurologic and psychiatric diseases as Alzheimer's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Following the crowd: Brain Substrates of Long-Term Memory Conformity

PubMed Central

Edelson, Micah; Sharot, Tali; Dolan, Raymond J; Dudai, Yadin

2012-01-01

Human memory is strikingly susceptible to social influences, yet we know little about the underlying mechanisms. We examined how socially induced memory errors are generated in the brain by studying the memory of individuals exposed to recollections of others. Participants exhibited a strong tendency to conform to erroneous recollections of the group, producing both long-lasting and temporary errors, even when their initial memory was strong and accurate. Functional brain imaging revealed that social influence modified the neuronal representation of memory. Specifically, a particular brain signature of enhanced amygdala activity and enhanced amygdala-hippocampus connectivity predicted long-lasting, but not temporary memory alterations. Our findings reveal how social manipulation can alter memory and extend the known functions of the amygdala to encompass socially-mediated memory distortions. PMID:21719681

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?

Light-sensitive brain pathways and aging.

PubMed

Daneault, V; Dumont, M; Massé, É; Vandewalle, G; Carrier, J

2016-03-15

Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460-480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary constriction and cognitive brain sensitivity to light in the course of aging. Whereas the impact of light on cognitive brain responses appears to decrease substantially, pupillary constriction seems to remain more intact over the lifespan. Altogether, these results demonstrate that aging research should take into account the diversity of the pathways underlying the effects of light on specific NIF functions which may explain their differences in light sensitivity.

Disrupted topological organization of resting-state functional brain network in subcortical vascular mild cognitive impairment.

PubMed

Yi, Li-Ye; Liang, Xia; Liu, Da-Ming; Sun, Bo; Ying, Sun; Yang, Dong-Bo; Li, Qing-Bin; Jiang, Chuan-Lu; Han, Ying

2015-10-01

Neuroimaging studies have demonstrated both structural and functional abnormalities in widespread brain regions in patients with subcortical vascular mild cognitive impairment (svMCI). However, whether and how these changes alter functional brain network organization remains largely unknown. We recruited 21 patients with svMCI and 26 healthy control (HC) subjects who underwent resting-state functional magnetic resonance imaging scans. Graph theory-based network analyses were used to investigate alterations in the topological organization of functional brain networks. Compared with the HC individuals, the patients with svMCI showed disrupted global network topology with significantly increased path length and modularity. Modular structure was also impaired in the svMCI patients with a notable rearrangement of the executive control module, where the parietal regions were split out and grouped as a separate module. The svMCI patients also revealed deficits in the intra- and/or intermodule connectivity of several brain regions. Specifically, the within-module degree was decreased in the middle cingulate gyrus while it was increased in the left anterior insula, medial prefrontal cortex and cuneus. Additionally, increased intermodule connectivity was observed in the inferior and superior parietal gyrus, which was associated with worse cognitive performance in the svMCI patients. Together, our results indicate that svMCI patients exhibit dysregulation of the topological organization of functional brain networks, which has important implications for understanding the pathophysiological mechanism of svMCI. © 2015 John Wiley & Sons Ltd.

Regional homogeneity, resting-state functional connectivity and amplitude of low frequency fluctuation associated with creativity measured by divergent thinking in a sex-specific manner.

PubMed

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

2017-05-15

Brain connectivity is traditionally thought to be important for creativity. Here we investigated the associations of creativity measured by divergent thinking (CMDT) with resting-state functional magnetic imaging (fMRI) measures and their sex differences. We examined these relationships in the brains of 1277 healthy young adults. Whole-brain analyses revealed a significant interaction between verbal CMDT and sex on (a) regional homogeneity within an area from the left anterior temporal lobe (b) on the resting state functional connectivity (RSFC) between the mPFC and the left inferior frontal gyrus and (c) on fractional amplitude of low frequency fluctuations (fALFF) in several distinct areas, including the precuneus and middle cingulate gyrus, left middle temporal gyrus, right middle frontal gyrus, and cerebellum. These interactions were mediated by positive correlations in females and negative correlations in males. These findings suggest that greater CMDT in females is reflected by (a) regional coherence (regional homogeneity) of brain areas responsible for representing and combining concepts as well as (b) the efficient functional connection (RSFC) between the key areas for the default state of cognitive activity and speech production, and (c) greater spontaneous neural activity (fALFF) during the resting of brain areas involved in frontal lobe functions, default cognitive activities, and language functions. Furthermore, these findings suggest that the associations between creativity and resting state brain connectivity patterns are different between males and females. Copyright © 2017 Elsevier Inc. All rights reserved.

A combinatorial optogenetic approach to medial habenula function

NASA Astrophysics Data System (ADS)

Turner, Eric E.; Hsu, Yun-Wei; Wang, Si; Morton, Glenn; Zeng, Hongkui

2013-03-01

The habenula is a brain region found in all vertebrate species. It consists of medial and lateral subnuclei which make complex descending connections to the brainstem. Although the medial habenula (MHb) and its projection, the fasciculus retroflexus (FR), have been recognized for decades, their function remains obscure. The small size of the MHb in rodents, and the cellular and molecular complexity of this region, have made it difficult to study the function of this region with high specificity. Here we describe a Cre-mediated genetic system for expressing the microbial opsin channelrhodopsin (ChR2) specifically in the dorsal (dMHb) and ventral (vMHb) medial habenula. Genetically targeted expression of ChR2 allows MHb neurons to be selectively activated with light in acute brain slices with electrophysiological readouts, and in vivo by means of custom-built fiber optic cannulas. These tools will allow highly specific studies of MHb circuitry and the role of the MHb in behaviors related to addiction and mood regulation.

"Decoding versus comprehension": Brain responses underlying reading comprehension in children with autism.

PubMed

Bednarz, Haley M; Maximo, Jose O; Murdaugh, Donna L; O'Kelley, Sarah; Kana, Rajesh K

2017-06-01

Despite intact decoding ability, deficits in reading comprehension are relatively common in children with autism spectrum disorders (ASD). However, few neuroimaging studies have tested the neural bases of this specific profile of reading deficit in ASD. This fMRI study examined activation and synchronization of the brain's reading network in children with ASD with specific reading comprehension deficits during a word similarities task. Thirteen typically developing children and 18 children with ASD performed the task in the MRI scanner. No statistically significant group differences in functional activation were observed; however, children with ASD showed decreased functional connectivity between the left inferior frontal gyrus (LIFG) and the left inferior occipital gyrus (LIOG). In addition, reading comprehension ability significantly positively predicted functional connectivity between the LIFG and left thalamus (LTHAL) among all subjects. The results of this study provide evidence for altered recruitment of reading-related neural resources in ASD children and suggest specific weaknesses in top-down modulation of semantic processing. Copyright © 2017 Elsevier Inc. All rights reserved.

Distinct patterns of functional brain connectivity correlate with objective performance and subjective beliefs

PubMed Central

Barttfeld, Pablo; Wicker, Bruno; McAleer, Phil; Belin, Pascal; Cojan, Yann; Graziano, Martín; Leiguarda, Ramón; Sigman, Mariano

2013-01-01

The degree of correspondence between objective performance and subjective beliefs varies widely across individuals. Here we demonstrate that functional brain network connectivity measured before exposure to a perceptual decision task covaries with individual objective (type-I performance) and subjective (type-II performance) accuracy. Increases in connectivity with type-II performance were observed in networks measured while participants directed attention inward (focus on respiration), but not in networks measured during states of neutral (resting state) or exogenous attention. Measures of type-I performance were less sensitive to the subjects’ specific attentional states from which the networks were derived. These results suggest the existence of functional brain networks indexing objective performance and accuracy of subjective beliefs distinctively expressed in a set of stable mental states. PMID:23801762

Understanding the evolution of Mammalian brain structures; the need for a (new) cerebrotype approach.

PubMed

Willemet, Romain

2012-05-18

The mammalian brain varies in size by a factor of 100,000 and is composed of anatomically and functionally distinct structures. Theoretically, the manner in which brain composition can evolve is limited, ranging from highly modular ("mosaic evolution") to coordinated changes in brain structure size ("concerted evolution") or anything between these two extremes. There is a debate about the relative importance of these distinct evolutionary trends. It is shown here that the presence of taxa-specific allometric relationships between brain structures makes a taxa-specific approach obligatory. In some taxa, the evolution of the size of brain structures follows a unique, coordinated pattern, which, in addition to other characteristics at different anatomical levels, defines what has been called here a "taxon cerebrotype". In other taxa, no clear pattern is found, reflecting heterogeneity of the species' lifestyles. These results suggest that the evolution of brain size and composition depends on the complex interplay between selection pressures and constraints that have changed constantly during mammalian evolution. Therefore the variability in brain composition between species should not be considered as deviations from the normal, concerted mammalian trend, but in taxa and species-specific versions of the mammalian brain. Because it forms homogenous groups of species within this complex "space" of constraints and selection pressures, the cerebrotype approach developed here could constitute an adequate level of analysis for evo-devo studies, and by extension, for a wide range of disciplines related to brain evolution.

Understanding the Evolution of Mammalian Brain Structures; the Need for a (New) Cerebrotype Approach

PubMed Central

Willemet, Romain

2012-01-01

The mammalian brain varies in size by a factor of 100,000 and is composed of anatomically and functionally distinct structures. Theoretically, the manner in which brain composition can evolve is limited, ranging from highly modular (“mosaic evolution”) to coordinated changes in brain structure size (“concerted evolution”) or anything between these two extremes. There is a debate about the relative importance of these distinct evolutionary trends. It is shown here that the presence of taxa-specific allometric relationships between brain structures makes a taxa-specific approach obligatory. In some taxa, the evolution of the size of brain structures follows a unique, coordinated pattern, which, in addition to other characteristics at different anatomical levels, defines what has been called here a “taxon cerebrotype”. In other taxa, no clear pattern is found, reflecting heterogeneity of the species’ lifestyles. These results suggest that the evolution of brain size and composition depends on the complex interplay between selection pressures and constraints that have changed constantly during mammalian evolution. Therefore the variability in brain composition between species should not be considered as deviations from the normal, concerted mammalian trend, but in taxa and species-specific versions of the mammalian brain. Because it forms homogenous groups of species within this complex “space” of constraints and selection pressures, the cerebrotype approach developed here could constitute an adequate level of analysis for evo-devo studies, and by extension, for a wide range of disciplines related to brain evolution. PMID:24962772

Abnormal small-world brain functional networks in obsessive-compulsive disorder patients with poor insight.

PubMed

Lei, Hui; Cui, Yan; Fan, Jie; Zhang, Xiaocui; Zhong, Mingtian; Yi, Jinyao; Cai, Lin; Yao, Dezhong; Zhu, Xiongzhao

2017-09-01

There are limited data on neurobiological correlates of poor insight in obsessive-compulsive disorder (OCD). This study explored whether specific changes occur in small-world network (SWN) properties in the brain functional network of OCD patients with poor insight. Resting-state electroencephalograms (EEGs) were recorded for 12 medication-free OCD patients with poor insight, 50 medication-free OCD patients with good insight, and 36 healthy controls. Both of the OCD groups exhibited topological alterations in the brain functional network characterized by abnormal small-world parameters at the beta band. However, the alterations at the theta band only existed in the OCD patients with poor insight. A relatively small sample size. Subjects were naïve to medications and those with Axis I comorbidity were excluded, perhaps limiting generalizability. Disrupted functional integrity at the beta bands of the brain functional network may be related to OCD, while disrupted functional integrity at the theta band may be associated with poor insight in OCD patients, thus this study might provide novel insight into our understanding of the pathophysiology of OCD. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2012-03-01

We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. Copyright © 2011 Elsevier Inc. All rights reserved.

Designing Homework to Mediate Executive Functioning Deficits in Students with Disabilities

ERIC Educational Resources Information Center

Stockall, Nancy

2017-01-01

Designing homework to mediate executive functioning disorders of students with disabilities is critical to their future academic success. The article explains and defines different executive functions of the brain and how these impact students' ability to benefit from homework assignments. Specific strategies are provided for designing…

Developing a clinical translational neuroscience taxonomy for anxiety and mood disorder: protocol for the baseline-follow up Research domain criteria Anxiety and Depression ("RAD") project.

PubMed

Williams, Leanne M; Goldstein-Piekarski, Andrea N; Chowdhry, Nowreen; Grisanzio, Katherine A; Haug, Nancy A; Samara, Zoe; Etkin, Amit; O'Hara, Ruth; Schatzberg, Alan F; Suppes, Trisha; Yesavage, Jerome

2016-03-15

Understanding how brain circuit dysfunctions relate to specific symptoms offers promise for developing a brain-based taxonomy for classifying psychopathology, identifying targets for mechanistic studies and ultimately for guiding treatment choice. The goal of the Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health is to accelerate the development of such neurobiological models of mental disorder independent of traditional diagnostic criteria. In our RDoC Anxiety and Depression ("RAD") project we focus trans-diagnostically on the spectrum of depression and anxiety psychopathology. Our aims are a) to use brain imaging to define cohesive dimensions defined by dysfunction of circuits involved in reactivity to and regulation of negatively valenced emotional stimulation and in cognitive control, b) to assess the relationships between these dimension and specific symptoms, behavioral performance and the real world capacity to function socially and at work and c) to assess the stability of brain-symptom-behavior-function relationships over time. Here we present the protocol for the "RAD" project, one of the first RDoC studies to use brain circuit functioning to define new dimensions of psychopathology. The RAD project follows baseline-follow up design. In line with RDoC principles we use a strategy for recruiting all clients who "walk through the door" of a large community mental health clinic as well as the surrounding community. The clinic attends to a broad spectrum of anxiety and mood-related symptoms. Participants are unmedicated and studied at baseline using a standardized battery of functional brain imaging, structural brain imaging and behavioral probes that assay constructs of threat reactivity, threat regulation and cognitive control. The battery also includes self-report measures of anxiety and mood symptoms, and social and occupational functioning. After baseline assessments, therapists in the clinic apply treatment planning as usual. Follow-up assessments are undertaken at 3 months, to establish the reliability of brain-based subgroups over time and to assess whether these subgroups predict real-world functional capacity over time. First enrollment was August 2013, and is ongoing. This project is designed to advance knowledge toward a neural circuit taxonomy for mental disorder. Data will be shared via the RDoC database for dissemination to the scientific community. The clinical translational neuroscience goals of the project are to develop brain-behavior profile reports for each individual participant and to refine these reports with therapist feedback. Reporting of results is expected from December 2016 onward. ClinicalTrials.gov Identifier: NCT02220309 . Registered: August 13, 2014.

Brain structure and function correlates of cognitive subtypes in schizophrenia.

PubMed

Geisler, Daniel; Walton, Esther; Naylor, Melissa; Roessner, Veit; Lim, Kelvin O; Charles Schulz, S; Gollub, Randy L; Calhoun, Vince D; Sponheim, Scott R; Ehrlich, Stefan

2015-10-30

Stable neuropsychological deficits may provide a reliable basis for identifying etiological subtypes of schizophrenia. The aim of this study was to identify clusters of individuals with schizophrenia based on dimensions of neuropsychological performance, and to characterize their neural correlates. We acquired neuropsychological data as well as structural and functional magnetic resonance imaging from 129 patients with schizophrenia and 165 healthy controls. We derived eight cognitive dimensions and subsequently applied a cluster analysis to identify possible schizophrenia subtypes. Analyses suggested the following four cognitive clusters of schizophrenia: (1) Diminished Verbal Fluency, (2) Diminished Verbal Memory and Poor Motor Control, (3) Diminished Face Memory and Slowed Processing, and (4) Diminished Intellectual Function. The clusters were characterized by a specific pattern of structural brain changes in areas such as Wernicke's area, lingual gyrus and occipital face area, and hippocampus as well as differences in working memory-elicited neural activity in several fronto-parietal brain regions. Separable measures of cognitive function appear to provide a method for deriving cognitive subtypes meaningfully related to brain structure and function. Because the present study identified brain-based neural correlates of the cognitive clusters, the proposed groups of individuals with schizophrenia have some external validity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Functional Brain Imaging

PubMed Central

2006-01-01

Executive Summary Objective The objective of this analysis is to review a spectrum of functional brain imaging technologies to identify whether there are any imaging modalities that are more effective than others for various brain pathology conditions. This evidence-based analysis reviews magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI) for the diagnosis or surgical management of the following conditions: Alzheimer’s disease (AD), brain tumours, epilepsy, multiple sclerosis (MS), and Parkinson’s disease (PD). Clinical Need: Target Population and Condition Alzheimer’s disease is a progressive, degenerative, neurologic condition characterized by cognitive impairment and memory loss. The Canadian Study on Health and Aging estimated that there will be 97,000 incident cases (about 60,000 women) of dementia (including AD) in Canada in 2006. In Ontario, there will be an estimated 950 new cases and 580 deaths due to brain cancer in 2006. Treatments for brain tumours include surgery and radiation therapy. However, one of the limitations of radiation therapy is that it damages tissue though necrosis and scarring. Computed tomography (CT) and magnetic resonance imaging (MRI) may not distinguish between radiation effects and resistant tissue, creating a potential role for functional brain imaging. Epilepsy is a chronic disorder that provokes repetitive seizures. In Ontario, the rate of epilepsy is estimated to be 5 cases per 1,000 people. Most people with epilepsy are effectively managed with drug therapy; but about 50% do not respond to drug therapy. Surgical resection of the seizure foci may be considered in these patients, and functional brain imaging may play a role in localizing the seizure foci. Multiple sclerosis is a progressive, inflammatory, demyelinating disease of the central nervous system (CNS). The cause of MS is unknown; however, it is thought to be due to a combination of etiologies, including genetic and environmental components. The prevalence of MS in Canada is 240 cases per 100,000 people. Parkinson’s disease is the most prevalent movement disorder; it affects an estimated 100,000 Canadians. Currently, the standard for measuring disease progression is through the use of scales, which are subjective measures of disease progression. Functional brain imaging may provide an objective measure of disease progression, differentiation between parkinsonian syndromes, and response to therapy. The Technology Being Reviewed Functional Brain Imaging Functional brain imaging technologies measure blood flow and metabolism. The results of these tests are often used in conjunction with structural imaging (e.g., MRI or CT). Positron emission tomography and MRS identify abnormalities in brain tissues. The former measures abnormalities through uptake of radiotracers in the brain, while the latter measures chemical shifts in metabolite ratios to identify abnormalities. The potential role of functional MRI (fMRI) is to identify the areas of the brain responsible for language, sensory and motor function (sensorimotor cortex), rather than identifying abnormalities in tissues. Magnetoencephalography measures magnetic fields of the electric currents in the brain, identifying aberrant activity. Magnetoencephalography may have the potential to localize seizure foci and to identify the sensorimotor cortex, visual cortex and auditory cortex. In terms of regulatory status, MEG and PET are licensed by Health Canada. Both MRS and fMRI use a MRI platform; thus, they do not have a separate licence from Health Canada. The radiotracers used in PET scanning are not licensed by Health Canada for general use but can be used through a Clinical Trials Application. Review Strategy The literature published up to September 2006 was searched in the following databases: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, and International Network of Agencies for Health Technology Assessment (INAHTA). The database search was supplemented with a search of relevant Web sites and a review of the bibliographies of selected papers. General inclusion criteria were applied to all conditions. Those criteria included the following: Full reports of systematic reviews, randomized controlled trials (RCTs), cohort-control studies, prospective cohort studies (PCS’), and retrospective studies. Sample sizes of at least 20 patients (≥ 10 with condition being reviewed). English-language studies. Human studies. Any age. Studying at least one of the following: fMRI, PET, MRS, or MEG. Functional brain imaging modality must be compared with a clearly defined reference standard. Must report at least one of the following outcomes: sensitivity, specificity, accuracy, positive predictive value (PPV), receiver operating characteristic curve, outcome measuring impact on diagnostic testing, treatment, patient health, or cost. Summary of Findings There is evidence to indicate that PET can accurately diagnose AD; however, at this time, there is no evidence to suggest that a diagnosis of AD with PET alters the clinical outcomes of patients. The addition of MRS or O-(2-18F-Fluoroethyl)-L-Tyrosine (FET)-PET to gadolinium (Gd)-enhanced MRI for distinguishing malignant from benign tumours during primary diagnosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients to distinguish malignant from benign tumours is unclear, because patients with a suspected brain tumour will likely undergo a biopsy despite additional imaging results. The addition of MRS, FET-PET, or MRI T2 to Gd-enhanced MRI for the differentiation of recurrence from radiation necrosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients with a suspected recurrence is in the monitoring of patients. Based on the evidence available, it is unclear if one of the imaging modalities (MRS, FET-PET, or MRI T2) offers significantly improved specificity over another. There may be a role for fMRI in the identification of surgical candidates for tumour resection; however, this requires further research. Based on the studies available, it is unclear if MEG has similar accuracy in localizing seizure foci to intracranial electroencephalogram (ICEEG). More high-quality research is needed to establish whether there is a difference in accuracy between MEG and ICEEG. The results of the studies comparing PET to noninvasive electroencephalogram (EEG) did not demonstrate that PET was more accurate at localizing seizure foci; however, there may be some specific conditions, such as tuberous sclerosis, where PET may be more accurate than noninvasive EEG. There may be some clinical utility for MEG or fMRI in presurgical functional mapping; however, this needs further investigation involving comparisons with other modalities. The clinical utility of MRS has yet to be established for patients with epilepsy. Positron emission tomography has high sensitivity and specificity in the diagnosis of PD and the differential diagnosis of parkinsonian syndromes; however, it is unclear at this time if the addition of PET in the diagnosis of these conditions contributes to the treatment and clinical outcomes of patients. There is limited clinical utility of functional brain imaging in the management of patients with MS at this time. Diagnosis of MS is established through clinical history, evoked potentials, and MRI. Magnetic resonance imaging can identify the multifocal white lesions and other structural characteristics of MS. PMID:23074493

Functional brain imaging: an evidence-based analysis.

PubMed

2006-01-01

The objective of this analysis is to review a spectrum of functional brain imaging technologies to identify whether there are any imaging modalities that are more effective than others for various brain pathology conditions. This evidence-based analysis reviews magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI) for the diagnosis or surgical management of the following conditions: Alzheimer's disease (AD), brain tumours, epilepsy, multiple sclerosis (MS), and Parkinson's disease (PD). TARGET POPULATION AND CONDITION Alzheimer's disease is a progressive, degenerative, neurologic condition characterized by cognitive impairment and memory loss. The Canadian Study on Health and Aging estimated that there will be 97,000 incident cases (about 60,000 women) of dementia (including AD) in Canada in 2006. In Ontario, there will be an estimated 950 new cases and 580 deaths due to brain cancer in 2006. Treatments for brain tumours include surgery and radiation therapy. However, one of the limitations of radiation therapy is that it damages tissue though necrosis and scarring. Computed tomography (CT) and magnetic resonance imaging (MRI) may not distinguish between radiation effects and resistant tissue, creating a potential role for functional brain imaging. Epilepsy is a chronic disorder that provokes repetitive seizures. In Ontario, the rate of epilepsy is estimated to be 5 cases per 1,000 people. Most people with epilepsy are effectively managed with drug therapy; but about 50% do not respond to drug therapy. Surgical resection of the seizure foci may be considered in these patients, and functional brain imaging may play a role in localizing the seizure foci. Multiple sclerosis is a progressive, inflammatory, demyelinating disease of the central nervous system (CNS). The cause of MS is unknown; however, it is thought to be due to a combination of etiologies, including genetic and environmental components. The prevalence of MS in Canada is 240 cases per 100,000 people. Parkinson's disease is the most prevalent movement disorder; it affects an estimated 100,000 Canadians. Currently, the standard for measuring disease progression is through the use of scales, which are subjective measures of disease progression. Functional brain imaging may provide an objective measure of disease progression, differentiation between parkinsonian syndromes, and response to therapy. FUNCTIONAL BRAIN IMAGING: Functional brain imaging technologies measure blood flow and metabolism. The results of these tests are often used in conjunction with structural imaging (e.g., MRI or CT). Positron emission tomography and MRS identify abnormalities in brain tissues. The former measures abnormalities through uptake of radiotracers in the brain, while the latter measures chemical shifts in metabolite ratios to identify abnormalities. The potential role of functional MRI (fMRI) is to identify the areas of the brain responsible for language, sensory and motor function (sensorimotor cortex), rather than identifying abnormalities in tissues. Magnetoencephalography measures magnetic fields of the electric currents in the brain, identifying aberrant activity. Magnetoencephalography may have the potential to localize seizure foci and to identify the sensorimotor cortex, visual cortex and auditory cortex. In terms of regulatory status, MEG and PET are licensed by Health Canada. Both MRS and fMRI use a MRI platform; thus, they do not have a separate licence from Health Canada. The radiotracers used in PET scanning are not licensed by Health Canada for general use but can be used through a Clinical Trials Application. The literature published up to September 2006 was searched in the following databases: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, and International Network of Agencies for Health Technology Assessment (INAHTA). The database search was supplemented with a search of relevant Web sites and a review of the bibliographies of selected papers. General inclusion criteria were applied to all conditions. Those criteria included the following: Full reports of systematic reviews, randomized controlled trials (RCTs), cohort-control studies, prospective cohort studies (PCS'), and retrospective studies.Sample sizes of at least 20 patients (≥ 10 with condition being reviewed).English-language studies.Human studies.Any age.STUDYING AT LEAST ONE OF THE FOLLOWING: fMRI, PET, MRS, or MEG.Functional brain imaging modality must be compared with a clearly defined reference standard.MUST REPORT AT LEAST ONE OF THE FOLLOWING OUTCOMES: sensitivity, specificity, accuracy, positive predictive value (PPV), receiver operating characteristic curve, outcome measuring impact on diagnostic testing, treatment, patient health, or cost. There is evidence to indicate that PET can accurately diagnose AD; however, at this time, there is no evidence to suggest that a diagnosis of AD with PET alters the clinical outcomes of patients. The addition of MRS or O-(2-(18)F-Fluoroethyl)-L-Tyrosine (FET)-PET to gadolinium (Gd)-enhanced MRI for distinguishing malignant from benign tumours during primary diagnosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients to distinguish malignant from benign tumours is unclear, because patients with a suspected brain tumour will likely undergo a biopsy despite additional imaging results. The addition of MRS, FET-PET, or MRI T2 to Gd-enhanced MRI for the differentiation of recurrence from radiation necrosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients with a suspected recurrence is in the monitoring of patients. Based on the evidence available, it is unclear if one of the imaging modalities (MRS, FET-PET, or MRI T2) offers significantly improved specificity over another. There may be a role for fMRI in the identification of surgical candidates for tumour resection; however, this requires further research. Based on the studies available, it is unclear if MEG has similar accuracy in localizing seizure foci to intracranial electroencephalogram (ICEEG). More high-quality research is needed to establish whether there is a difference in accuracy between MEG and ICEEG. The results of the studies comparing PET to noninvasive electroencephalogram (EEG) did not demonstrate that PET was more accurate at localizing seizure foci; however, there may be some specific conditions, such as tuberous sclerosis, where PET may be more accurate than noninvasive EEG. There may be some clinical utility for MEG or fMRI in presurgical functional mapping; however, this needs further investigation involving comparisons with other modalities. The clinical utility of MRS has yet to be established for patients with epilepsy. Positron emission tomography has high sensitivity and specificity in the diagnosis of PD and the differential diagnosis of parkinsonian syndromes; however, it is unclear at this time if the addition of PET in the diagnosis of these conditions contributes to the treatment and clinical outcomes of patients. There is limited clinical utility of functional brain imaging in the management of patients with MS at this time. Diagnosis of MS is established through clinical history, evoked potentials, and MRI. Magnetic resonance imaging can identify the multifocal white lesions and other structural characteristics of MS.

Temporal and Spatial Effects of Blast Overpressure on Blood-Brain Barrier Permeability in Traumatic Brain Injury.

PubMed

Kuriakose, Matthew; Rama Rao, Kakulavarapu V; Younger, Daniel; Chandra, Namas

2018-06-06

Blast-induced traumatic brain injury (bTBI) is a "signature wound" in soldiers during training and in combat and has also become a major cause of morbidity in civilians due to increased insurgency. This work examines the role of blood-brain barrier (BBB) disruption as a result of both primary biomechanical and secondary biochemical injury mechanisms in bTBI. Extravasation of sodium fluorescein (NaF) and Evans blue (EB) tracers were used to demonstrate that compromise of the BBB occurs immediately following shock loading, increases in intensity up to 4 hours and returns back to normal in 24 hours. This BBB compromise occurs in multiple regions of the brain in the anterior-posterior direction of the shock wave, with maximum extravasation seen in the frontal cortex. Compromise of the BBB is confirmed by (a) extravasation of tracers into the brain, (b) quantification of tight-junction proteins (TJPs) in the brain and the blood, and (c) tracking specific blood-borne molecules into the brain and brain-specific proteins into the blood. Taken together, this work demonstrates that the BBB compromise occurs as a part of initial biomechanical loading and is a function of increasing blast overpressures.

Studies on regeneration of central nervous system and social ability of the earthworm Eudrilus eugeniae.

PubMed

Gopi Daisy, Nino; Subramanian, Elaiya Raja; Selvan Christyraj, Jackson Durairaj; Sudalai Mani, Dinesh Kumar; Selvan Christyraj, Johnson Retnaraj Samuel; Ramamoorthy, Kalidas; Arumugaswami, Vaithilingaraja; Sivasubramaniam, Sudhakar

2016-09-01

Earthworms are segmented invertebrates that belong to the phylum Annelida. The segments can be divided into the anterior, clitellar and posterior parts. If the anterior part of the earthworm, which includes the brain, is amputated, the worm would essentially survive even in the absence of the brain. In these brain amputee-derived worms, the nerve cord serves as the primary control center for neurological function. In this current work, we studied changes in the expression levels of anti-acetylated tubulin and serotonin as the indicators of neuro-regenerative processes. The data reveal that the blastemal tissues express the acetylated tubulin and serotonin from day four and that the worm amputated at the 7th segment takes 30 days to complete the regeneration of brain. The ability of self-assemblage is one of the specific functions of the earthworm's brain. The brain amputee restored the ability of self-assemblage on the eighth day.

Network effects of deep brain stimulation

PubMed Central

Alhourani, Ahmad; McDowell, Michael M.; Randazzo, Michael J.; Wozny, Thomas A.; Kondylis, Efstathios D.; Lipski, Witold J.; Beck, Sarah; Karp, Jordan F.; Ghuman, Avniel S.

2015-01-01

The ability to differentially alter specific brain functions via deep brain stimulation (DBS) represents a monumental advance in clinical neuroscience, as well as within medicine as a whole. Despite the efficacy of DBS in the treatment of movement disorders, for which it is often the gold-standard therapy when medical management becomes inadequate, the mechanisms through which DBS in various brain targets produces therapeutic effects is still not well understood. This limited knowledge is a barrier to improving efficacy and reducing side effects in clinical brain stimulation. A field of study related to assessing the network effects of DBS is gradually emerging that promises to reveal aspects of the underlying pathophysiology of various brain disorders and their response to DBS that will be critical to advancing the field. This review summarizes the nascent literature related to network effects of DBS measured by cerebral blood flow and metabolic imaging, functional imaging, and electrophysiology (scalp and intracranial electroencephalography and magnetoencephalography) in order to establish a framework for future studies. PMID:26269552

Inter-hemispheric language functional reorganization in low-grade glioma patients after tumour surgery.

PubMed

Kristo, Gert; Raemaekers, Mathijs; Rutten, Geert-Jan; de Gelder, Beatrice; Ramsey, Nick F

2015-03-01

Despite many claims of functional reorganization following tumour surgery, empirical studies that investigate changes in functional activation patterns are rare. This study investigates whether functional recovery following surgical treatment in patients with a low-grade glioma in the left hemisphere is linked to inter-hemispheric reorganization. Based on literature, we hypothesized that reorganization would induce changes in the spatial pattern of activation specifically in tumour homologue brain areas in the healthy right hemisphere. An experimental group (EG) of 14 patients with a glioma in the left hemisphere near language related brain areas, and a control group of 6 patients with a glioma in the right, non-language dominant hemisphere were scanned before and after resection. In addition, an age and gender matched second control group of 18 healthy volunteers was scanned twice. A verb generation task was used to map language related areas and a novel technique was used for data analysis. Contrary to our hypothesis, we found that functional recovery following surgery of low-grade gliomas cannot be linked to functional reorganization in language homologue brain areas in the healthy, right hemisphere. Although elevated changes in the activation pattern were found in patients after surgery, these were largest in brain areas in proximity to the surgical resection, and were very similar to the spatial pattern of the brain shift following surgery. This suggests that the apparent perilesional functional reorganization is mostly caused by the brain shift as a consequence of surgery. Perilesional functional reorganization can however not be excluded. The study suggests that language recovery after transient post-surgical language deficits involves recovery of functioning of the presurgical language system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Insulin receptor in the brain: Mechanisms of activation and the role in the CNS pathology and treatment.

PubMed

Pomytkin, Igor; Costa-Nunes, João P; Kasatkin, Vladimir; Veniaminova, Ekaterina; Demchenko, Anna; Lyundup, Alexey; Lesch, Klaus-Peter; Ponomarev, Eugene D; Strekalova, Tatyana

2018-04-24

While the insulin receptor (IR) was found in the CNS decades ago, the brain was long considered to be an insulin-insensitive organ. This view is currently revisited, given emerging evidence of critical roles of IR-mediated signaling in development, neuroprotection, metabolism, and plasticity in the brain. These diverse cellular and physiological IR activities are distinct from metabolic IR functions in peripheral tissues, thus highlighting region specificity of IR properties. This particularly concerns the fact that two IR isoforms, A and B, are predominantly expressed in either the brain or peripheral tissues, respectively, and neurons express exclusively IR-A. Intriguingly, in comparison with IR-B, IR-A displays high binding affinity and is also activated by low concentrations of insulin-like growth factor-2 (IGF-2), a regulator of neuronal plasticity, whose dysregulation is associated with neuropathologic processes. Deficiencies in IR activation, insulin availability, and downstream IR-related mechanisms may result in aberrant IR-mediated functions and, subsequently, a broad range of brain disorders, including neurodevelopmental syndromes, neoplasms, neurodegenerative conditions, and depression. Here, we discuss findings on the brain-specific features of IR-mediated signaling with focus on mechanisms of primary receptor activation and their roles in the neuropathology. We aimed to uncover the remaining gaps in current knowledge on IR physiology and highlight new therapies targeting IR, such as IR sensitizers. © 2018 John Wiley & Sons Ltd.

Roles of HAUSP-mediated p53 regulation in central nervous system development.

PubMed

Kon, N; Zhong, J; Kobayashi, Y; Li, M; Szabolcs, M; Ludwig, T; Canoll, P D; Gu, W

2011-08-01

The deubiquitinase HAUSP (herpesvirus-associated ubiquitin-specific protease; also called USP7) has a critical role in regulating the p53-Mdm2 (murine double minute 2) pathway. By using the conventional knockout approach, we previously showed that hausp inactivation leads to early embryonic lethality. To fully understand the physiological functions of hausp, we have generated mice lacking hausp specifically in the brain and examined the impacts of this manipulation on brain development. We found that deletion of hausp in neural cells resulted in neonatal lethality. The brains from these mice displayed hypoplasia and deficiencies in development, which were mainly caused by p53-mediated apoptosis. Detailed analysis also showed an increase of both p53 levels and p53-dependent transcriptional activation in hausp knockout brains. Notably, neural cell survival and brain development of hausp-mutant mice can largely be restored in the p53-null background. Nevertheless, in contrast to the case of mdm2- and mdm4 (murine double minute 4)-mutant mice, inactivation of p53 failed to completely rescue the neonatal lethality of these hausp-mutant mice. These results indicate that HAUSP-mediated p53 regulation is crucial for brain development, and also suggest that both the p53-dependent and the p53-independent functions of HAUSP contribute to the neonatal lethality of hausp-mutant mice.

Expression pattern of the type 1 sigma receptor in the brain and identity of critical anionic amino acid residues in the ligand-binding domain of the receptor.

PubMed

Seth, P; Ganapathy, M E; Conway, S J; Bridges, C D; Smith, S B; Casellas, P; Ganapathy, V

2001-07-25

The type 1 sigma receptor (sigmaR1) has been shown to participate in a variety of functions in the central nervous system. To identify the specific regions of the brain that are involved in sigmaR1 function, we analyzed the expression pattern of the receptor mRNA in the mouse brain by in situ hybridization. SigmaR1 mRNA was detectable primarily in the cerebral cortex, hippocampus, and Purkinje cells of cerebellum. To identify the critical anionic amino acid residues in the ligand-binding domain of sigmaR1, we employed two different approaches: chemical modification of anionic amino acid residues and site-directed mutagenesis. Chemical modification of anionic amino acids in sigmaR1 with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide reduced the ligand-binding activity markedly. Since it is known that a splice variant of this receptor which lacks exon 3 does not have the ability to bind sigma ligands, the ligand-binding domain with its critical anionic amino acid residues is likely to be present in or around the region coded by exon 3. Therefore, each of the anionic amino acids in this region was mutated individually and the influence of each mutation on ligand binding was assessed. These studies have identified two anionic amino acids, D126 and E172, that are obligatory for ligand binding. Even though the ligand-binding function was abolished by these two mutations, the expression of these mutants was normal at the protein level. These results show that sigmaR1 is expressed at high levels in specific areas of the brain that are involved in memory, emotion and motor functions. The results also provide important information on the chemical nature of the ligand-binding site of sigmaR1 that may be of use in the design of sigmaR1-specific ligands with potential for modulation of sigmaR1-related brain functions.

Indications for quantum computation requirements from comparative brain analysis

NASA Astrophysics Data System (ADS)

Bernroider, Gustav; Baer, Wolfgang

2010-04-01

Whether or not neuronal signal properties can engage 'non-trivial', i.e. functionally significant, quantum properties, is the subject of an ongoing debate. Here we provide evidence that quantum coherence dynamics can play a functional role in ion conduction mechanism with consequences on the shape and associative character of classical membrane signals. In particular, these new perspectives predict that a specific neuronal topology (e.g. the connectivity pattern of cortical columns in the primate brain) is less important and not really required to explain abilities in perception and sensory-motor integration. Instead, this evidence is suggestive for a decisive role of the number and functional segregation of ion channel proteins that can be engaged in a particular neuronal constellation. We provide evidence from comparative brain studies and estimates of computational capacity behind visual flight functions suggestive for a possible role of quantum computation in biological systems.

Brain plasticity and functional losses in the aged: scientific bases for a novel intervention.

PubMed

Mahncke, Henry W; Bronstone, Amy; Merzenich, Michael M

2006-01-01

Aging is associated with progressive losses in function across multiple systems, including sensation, cognition, memory, motor control, and affect. The traditional view has been that functional decline in aging is unavoidable because it is a direct consequence of brain machinery wearing down over time. In recent years, an alternative perspective has emerged, which elaborates on this traditional view of age-related functional decline. This new viewpoint--based upon decades of research in neuroscience, experimental psychology, and other related fields--argues that as people age, brain plasticity processes with negative consequences begin to dominate brain functioning. Four core factors--reduced schedules of brain activity, noisy processing, weakened neuromodulatory control, and negative learning--interact to create a self-reinforcing downward spiral of degraded brain function in older adults. This downward spiral might begin from reduced brain activity due to behavioral change, from a loss in brain function driven by aging brain machinery, or more likely from both. In aggregate, these interrelated factors promote plastic changes in the brain that result in age-related functional decline. This new viewpoint on the root causes of functional decline immediately suggests a remedial approach. Studies of adult brain plasticity have shown that substantial improvement in function and/or recovery from losses in sensation, cognition, memory, motor control, and affect should be possible, using appropriately designed behavioral training paradigms. Driving brain plasticity with positive outcomes requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis, in a behavioral context designed to re-engage and strengthen the neuromodulatory systems that control learning in adults, with the goal of increasing the fidelity, reliability, and power of cortical representations. Such a training program would serve a substantial unmet need in aging adults. Current treatments directed at age-related functional losses are limited in important ways. Pharmacological therapies can target only a limited number of the many changes believed to underlie functional decline. Behavioral approaches focus on teaching specific strategies to aid higher order cognitive functions, and do not usually aspire to fundamentally change brain function. A brain-plasticity-based training program would potentially be applicable to all aging adults with the promise of improving their operational capabilities. We have constructed such a brain-plasticity-based training program and conducted an initial randomized controlled pilot study to evaluate the feasibility of its use by older adults. A main objective of this initial study was to estimate the effect size on standardized neuropsychological measures of memory. We found that older adults could learn the training program quickly, and could use it entirely unsupervised for the majority of the time required. Pre- and posttesting documented a significant improvement in memory within the training group (effect size 0.41, p<0.0005), with no significant within-group changes in a time-matched computer using active control group, or in a no-contact control group. Thus, a brain-plasticity-based intervention targeting normal age-related cognitive decline may potentially offer benefit to a broad population of older adults.

Abnormal functional lateralization and activity of language brain areas in typical specific language impairment (developmental dysphasia)

PubMed Central

De Guibert, Clément; Maumet, Camille; Jannin, Pierre; Ferré, Jean-Christophe; Tréguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

2011-01-01

Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting structural language (n=21), to a matched group of typically-developing children using a panel of four language tasks neither requiring reading nor metalinguistic skills, including two auditory lexico-semantic tasks (category fluency and responsive naming) and two visual phonological tasks based on picture naming. Data processing involved normalizing the data with respect to a matched pairs pediatric template, groups and between-groups analysis, and laterality indexes assessment within regions of interest using single and combined task analysis. Children with specific language impairment exhibited a significant lack of left lateralization in all core language regions (inferior frontal gyrus-opercularis, inferior frontal gyrus-triangularis, supramarginal gyrus, superior temporal gyrus), across single or combined task analysis, but no difference of lateralization for the rest of the brain. Between-group comparisons revealed a left hypoactivation of Wernicke’s area at the posterior superior temporal/supramarginal junction during the responsive naming task, and a right hyperactivation encompassing the anterior insula with adjacent inferior frontal gyrus and the head of the caudate nucleus during the first phonological task. This study thus provides evidence that this specific subtype of specific language impairment is associated with atypical lateralization and functioning of core language areas. PMID:21719430

Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function.

PubMed

Piwecka, Monika; Glažar, Petar; Hernandez-Miranda, Luis R; Memczak, Sebastian; Wolf, Susanne A; Rybak-Wolf, Agnieszka; Filipchyk, Andrei; Klironomos, Filippos; Cerda Jara, Cledi Alicia; Fenske, Pascal; Trimbuch, Thorsten; Zywitza, Vera; Plass, Mireya; Schreyer, Luisa; Ayoub, Salah; Kocks, Christine; Kühn, Ralf; Rosenmund, Christian; Birchmeier, Carmen; Rajewsky, Nikolaus

2017-09-22

Hundreds of circular RNAs (circRNAs) are highly abundant in the mammalian brain, often with conserved expression. Here we show that the circRNA Cdr1as is massively bound by the microRNAs (miRNAs) miR-7 and miR-671 in human and mouse brains. When the Cdr1as locus was removed from the mouse genome, knockout animals displayed impaired sensorimotor gating-a deficit in the ability to filter out unnecessary information-which is associated with neuropsychiatric disorders. Electrophysiological recordings revealed dysfunctional synaptic transmission. Expression of miR-7 and miR-671 was specifically and posttranscriptionally misregulated in all brain regions analyzed. Expression of immediate early genes such as Fos , a direct miR-7 target, was enhanced in Cdr1as -deficient brains, providing a possible molecular link to the behavioral phenotype. Our data indicate an in vivo loss-of-function circRNA phenotype and suggest that interactions between Cdr1as and miRNAs are important for normal brain function. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

DHA Effects in Brain Development and Function

PubMed Central

Lauritzen, Lotte; Brambilla, Paolo; Mazzocchi, Alessandra; Harsløf, Laurine B. S.; Ciappolino, Valentina; Agostoni, Carlo

2016-01-01

Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Its accumulation in the fetal brain takes place mainly during the last trimester of pregnancy and continues at very high rates up to the end of the second year of life. Since the endogenous formation of DHA seems to be relatively low, DHA intake may contribute to optimal conditions for brain development. We performed a narrative review on research on the associations between DHA levels and brain development and function throughout the lifespan. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling. Most data from human studies concern the contribution of DHA to optimal visual acuity development. Accumulating data indicate that DHA may have effects on the brain in infancy, and recent studies indicate that the effect of DHA may depend on gender and genotype of genes involved in the endogenous synthesis of DHA. While DHA levels may affect early development, potential effects are also increasingly recognized during childhood and adult life, suggesting a role of DHA in cognitive decline and in relation to major psychiatric disorders. PMID:26742060

DHA Effects in Brain Development and Function.

PubMed

Lauritzen, Lotte; Brambilla, Paolo; Mazzocchi, Alessandra; Harsløf, Laurine B S; Ciappolino, Valentina; Agostoni, Carlo

2016-01-04

Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Its accumulation in the fetal brain takes place mainly during the last trimester of pregnancy and continues at very high rates up to the end of the second year of life. Since the endogenous formation of DHA seems to be relatively low, DHA intake may contribute to optimal conditions for brain development. We performed a narrative review on research on the associations between DHA levels and brain development and function throughout the lifespan. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling. Most data from human studies concern the contribution of DHA to optimal visual acuity development. Accumulating data indicate that DHA may have effects on the brain in infancy, and recent studies indicate that the effect of DHA may depend on gender and genotype of genes involved in the endogenous synthesis of DHA. While DHA levels may affect early development, potential effects are also increasingly recognized during childhood and adult life, suggesting a role of DHA in cognitive decline and in relation to major psychiatric disorders.

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

PubMed

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

2018-06-01

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

Motor and cortico-striatal-thalamic connectivity alterations in intrauterine growth restriction.

PubMed

Eixarch, Elisenda; Muñoz-Moreno, Emma; Bargallo, Nuria; Batalle, Dafnis; Gratacos, Eduard

2016-06-01

Intrauterine growth restriction is associated with short- and long-term neurodevelopmental problems. Structural brain changes underlying these alterations have been described with the use of different magnetic resonance-based methods that include changes in whole structural brain networks. However, evaluation of specific brain circuits and its correlation with related functions has not been investigated in intrauterine growth restriction. In this study, we aimed to investigate differences in tractography-related metrics in cortico-striatal-thalamic and motor networks in intrauterine growth restricted children and whether these parameters were related with their specific function in order to explore its potential use as an imaging biomarker of altered neurodevelopment. We included a group of 24 intrauterine growth restriction subjects and 27 control subjects that were scanned at 1 year old; we acquired T1-weighted and 30 directions diffusion magnetic resonance images. Each subject brain was segmented in 93 regions with the use of anatomical automatic labeling atlas, and deterministic tractography was performed. Brain regions included in motor and cortico-striatal-thalamic networks were defined based in functional and anatomic criteria. Within the streamlines that resulted from the whole brain tractography, those belonging to each specific circuit were selected and tractography-related metrics that included number of streamlines, fractional anisotropy, and integrity were calculated for each network. We evaluated differences between both groups and further explored the correlation of these parameters with the results of socioemotional, cognitive, and motor scales from Bayley Scale at 2 years of age. Reduced fractional anisotropy (cortico-striatal-thalamic, 0.319 ± 0.018 vs 0.315 ± 0.015; P = .010; motor, 0.322 ± 0.019 vs 0.319 ± 0.020; P = .019) and integrity cortico-striatal-thalamic (0.407 ± 0.040 vs 0.399 ± 0.034; P = .018; motor, 0.417 ± 0.044 vs 0.409 ± 0.046; P = .016) in both networks were observed in the intrauterine growth restriction group, with no differences in number of streamlines. More importantly, strong specific correlation was found between tractography-related metrics and its relative function in both networks in intrauterine growth restricted children. Motor network metrics were correlated specifically with motor scale results (fractional anisotropy: rho = 0.857; integrity: rho = 0.740); cortico-striatal-thalamic network metrics were correlated with cognitive (fractional anisotropy: rho = 0.793; integrity, rho = 0.762) and socioemotional scale (fractional anisotropy: rho = 0.850; integrity: rho = 0.877). These results support the existence of altered brain connectivity in intrauterine growth restriction demonstrated by altered connectivity in motor and cortico-striatal-thalamic networks, with reduced fractional anisotropy and integrity. The specific correlation between tractography-related metrics and neurodevelopmental outcomes in intrauterine growth restriction shows the potential to use this approach to develop imaging biomarkers to predict specific neurodevelopmental outcome in infants who are at risk because of intrauterine growth restriction and other prenatal diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Assessing dynamics, spatial scale, and uncertainty in task-related brain network analyses

PubMed Central

Stephen, Emily P.; Lepage, Kyle Q.; Eden, Uri T.; Brunner, Peter; Schalk, Gerwin; Brumberg, Jonathan S.; Guenther, Frank H.; Kramer, Mark A.

2014-01-01

The brain is a complex network of interconnected elements, whose interactions evolve dynamically in time to cooperatively perform specific functions. A common technique to probe these interactions involves multi-sensor recordings of brain activity during a repeated task. Many techniques exist to characterize the resulting task-related activity, including establishing functional networks, which represent the statistical associations between brain areas. Although functional network inference is commonly employed to analyze neural time series data, techniques to assess the uncertainty—both in the functional network edges and the corresponding aggregate measures of network topology—are lacking. To address this, we describe a statistically principled approach for computing uncertainty in functional networks and aggregate network measures in task-related data. The approach is based on a resampling procedure that utilizes the trial structure common in experimental recordings. We show in simulations that this approach successfully identifies functional networks and associated measures of confidence emergent during a task in a variety of scenarios, including dynamically evolving networks. In addition, we describe a principled technique for establishing functional networks based on predetermined regions of interest using canonical correlation. Doing so provides additional robustness to the functional network inference. Finally, we illustrate the use of these methods on example invasive brain voltage recordings collected during an overt speech task. The general strategy described here—appropriate for static and dynamic network inference and different statistical measures of coupling—permits the evaluation of confidence in network measures in a variety of settings common to neuroscience. PMID:24678295

Assessing dynamics, spatial scale, and uncertainty in task-related brain network analyses.

PubMed

Stephen, Emily P; Lepage, Kyle Q; Eden, Uri T; Brunner, Peter; Schalk, Gerwin; Brumberg, Jonathan S; Guenther, Frank H; Kramer, Mark A

2014-01-01

The brain is a complex network of interconnected elements, whose interactions evolve dynamically in time to cooperatively perform specific functions. A common technique to probe these interactions involves multi-sensor recordings of brain activity during a repeated task. Many techniques exist to characterize the resulting task-related activity, including establishing functional networks, which represent the statistical associations between brain areas. Although functional network inference is commonly employed to analyze neural time series data, techniques to assess the uncertainty-both in the functional network edges and the corresponding aggregate measures of network topology-are lacking. To address this, we describe a statistically principled approach for computing uncertainty in functional networks and aggregate network measures in task-related data. The approach is based on a resampling procedure that utilizes the trial structure common in experimental recordings. We show in simulations that this approach successfully identifies functional networks and associated measures of confidence emergent during a task in a variety of scenarios, including dynamically evolving networks. In addition, we describe a principled technique for establishing functional networks based on predetermined regions of interest using canonical correlation. Doing so provides additional robustness to the functional network inference. Finally, we illustrate the use of these methods on example invasive brain voltage recordings collected during an overt speech task. The general strategy described here-appropriate for static and dynamic network inference and different statistical measures of coupling-permits the evaluation of confidence in network measures in a variety of settings common to neuroscience.

Anomalous Development of Brain Structure and Function in Spina Bifida Myelomeningocele

ERIC Educational Resources Information Center

Juranek, Jenifer; Salman, Michael S.

2010-01-01

Spina bifida myelomeningocele (SBM) is a specific type of neural tube defect whereby the open neural tube at the level of the spinal cord alters brain development during early stages of gestation. Some structural anomalies are virtually unique to individuals with SBM, including a complex pattern of cerebellar dysplasia known as the Chiari II…

Localization and functional analysis of the insect-specific RabX4 in the brain of Bombyx mori.

PubMed

Uno, Tomohide; Furutani, Masayuki; Sakamoto, Katsuhiko; Uno, Yuichi; Kanamaru, Kengo; Mizoguchi, Akira; Hiragaki, Susumu; Takeda, Makio

2017-09-01

Rab proteins are small monomeric GTPases/GTP-binding proteins, which form the largest branch of the Ras superfamily. The different Rab GTPases are localized to the cytosolic face of specific intracellular membranes, where they function as regulators of distinct steps in membrane trafficking. RabX4 is an insect-specific Rab protein that has no close homolog in vertebrates. There is little information about insect-specific Rab proteins. RabX4 was expressed in Escherichia coli and subsequently purified. Antibodies against Bombyx mori RabX4 were produced in rabbits for western immunoblotting and immunohistochemistry. Western blotting of neural tissues revealed a single band, at approximately 26 kD. RabX4-like immunohistochemical reactivity was restricted to neurons of the pars intercerebralis and dorsolateral protocerebrum in the brain. Further immunohistochemical analysis revealed that RabX4 colocalized with Rab6 and bombyxin in the corpus allatum, a neuronal organ that secretes neuropeptides synthesized in the brain into the hemolymph. RabX4 expression in the frontal ganglion, part of the insect stomatogastric nervous system that is found in most insect orders, was restricted to two neurons on the outer region and did not colocalize with allatotropin or Rab6. Furthermore, RNA interference of RabX4 decreased bombyxin expression levels in the brain. These findings suggest that RabX4 is involved in the neurosecretion of a secretory organ in Bombyx mori. © 2017 Wiley Periodicals, Inc.

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-01-01

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

The Effects of Long-term Abacus Training on Topological Properties of Brain Functional Networks.

PubMed

Weng, Jian; Xie, Ye; Wang, Chunjie; Chen, Feiyan

2017-08-18

Previous studies in the field of abacus-based mental calculation (AMC) training have shown that this training has the potential to enhance a wide variety of cognitive abilities. It can also generate specific changes in brain structure and function. However, there is lack of studies investigating the impact of AMC training on the characteristics of brain networks. In this study, utilizing graph-based network analysis, we compared topological properties of brain functional networks between an AMC group and a matched control group. Relative to the control group, the AMC group exhibited higher nodal degrees in bilateral calcarine sulcus and increased local efficiency in bilateral superior occipital gyrus and right cuneus. The AMC group also showed higher nodal local efficiency in right fusiform gyrus, which was associated with better math ability. However, no relationship was significant in the control group. These findings provide evidence that long-term AMC training may improve information processing efficiency in visual-spatial related regions, which extend our understanding of training plasticity at the brain network level.

Hierarchical organization of functional connectivity in the mouse brain: a complex network approach.

PubMed

Bardella, Giampiero; Bifone, Angelo; Gabrielli, Andrea; Gozzi, Alessandro; Squartini, Tiziano

2016-08-18

This paper represents a contribution to the study of the brain functional connectivity from the perspective of complex networks theory. More specifically, we apply graph theoretical analyses to provide evidence of the modular structure of the mouse brain and to shed light on its hierarchical organization. We propose a novel percolation analysis and we apply our approach to the analysis of a resting-state functional MRI data set from 41 mice. This approach reveals a robust hierarchical structure of modules persistent across different subjects. Importantly, we test this approach against a statistical benchmark (or null model) which constrains only the distributions of empirical correlations. Our results unambiguously show that the hierarchical character of the mouse brain modular structure is not trivially encoded into this lower-order constraint. Finally, we investigate the modular structure of the mouse brain by computing the Minimal Spanning Forest, a technique that identifies subnetworks characterized by the strongest internal correlations. This approach represents a faster alternative to other community detection methods and provides a means to rank modules on the basis of the strength of their internal edges.

Hierarchical organization of functional connectivity in the mouse brain: a complex network approach

NASA Astrophysics Data System (ADS)

Bardella, Giampiero; Bifone, Angelo; Gabrielli, Andrea; Gozzi, Alessandro; Squartini, Tiziano

2016-08-01

This paper represents a contribution to the study of the brain functional connectivity from the perspective of complex networks theory. More specifically, we apply graph theoretical analyses to provide evidence of the modular structure of the mouse brain and to shed light on its hierarchical organization. We propose a novel percolation analysis and we apply our approach to the analysis of a resting-state functional MRI data set from 41 mice. This approach reveals a robust hierarchical structure of modules persistent across different subjects. Importantly, we test this approach against a statistical benchmark (or null model) which constrains only the distributions of empirical correlations. Our results unambiguously show that the hierarchical character of the mouse brain modular structure is not trivially encoded into this lower-order constraint. Finally, we investigate the modular structure of the mouse brain by computing the Minimal Spanning Forest, a technique that identifies subnetworks characterized by the strongest internal correlations. This approach represents a faster alternative to other community detection methods and provides a means to rank modules on the basis of the strength of their internal edges.

ErbB4 in Laminated Brain Structures: A Neurodevelopmental Approach to Schizophrenia

PubMed Central

Perez-Garcia, Carlos G.

2015-01-01

The susceptibility genes for schizophrenia Neuregulin-1 (NRG1) and ErbB4 have critical functions during brain development and in the adult. Alterations in the ErbB4 signaling pathway cause a variety of neurodevelopmental defects including deficiencies in neuronal migration, synaptic plasticity, and myelination. I have used the ErbB4-/- HER4heart KO mice to study the neurodevelopmental insults associated to deficiencies in the NRG1-ErbB4 signaling pathway and their potential implication with brain disorders such as schizophrenia, a chronic psychiatric disease affecting 1% of the population worldwide. ErbB4 deletion results in an array of neurodevelopmental deficits that are consistent with a schizophrenic model. First, similar defects appear in multiple brain structures, from the cortex to the cerebellum. Second, these defects affect multiple aspects of brain development, from deficits in neuronal migration to impairments in excitatory/inhibitory systems, including reductions in brain volume, cortical and cerebellar heterotopias, alterations in number and distribution of specific subpopulations of interneurons, deficiencies in the astrocytic and oligodendrocytic lineages, and additional insults in major brain structures. This suggests that alterations in specific neurodevelopmental genes that play similar functions in multiple neuroanatomical structures might account for some of the symptomatology observed in schizophrenic patients, such as defects in cognition. ErbB4 mutation uncovers flaws in brain development that are compatible with a neurodevelopmental model of schizophrenia, and it establishes a comprehensive model to study the basis of the disorder before symptoms are detected in the adult. PMID:26733804

Physiological Exploration of the Long Term Evolutionary Selection against Expression of N-Glycolylneuraminic Acid in the Brain*♦

PubMed Central

Naito-Matsui, Yuko; Davies, Leela R. L.; Takematsu, Hiromu; Chou, Hsun-Hua; Tangvoranuntakul, Pam; Carlin, Aaron F.; Verhagen, Andrea; Heyser, Charles J.; Yoo, Seung-Wan; Choudhury, Biswa; Paton, James C.; Paton, Adrienne W.; Varki, Nissi M.; Schnaar, Ronald L.; Varki, Ajit

2017-01-01

All vertebrate cell surfaces display a dense glycan layer often terminated with sialic acids, which have multiple functions due to their location and diverse modifications. The major sialic acids in most mammalian tissues are N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), the latter being derived from Neu5Ac via addition of one oxygen atom at the sugar nucleotide level by CMP-Neu5Ac hydroxylase (Cmah). Contrasting with other organs that express various ratios of Neu5Ac and Neu5Gc depending on the variable expression of Cmah, Neu5Gc expression in the brain is extremely low in all vertebrates studied to date, suggesting that neural expression is detrimental to animals. However, physiological exploration of the reasons for this long term evolutionary selection has been lacking. To explore the consequences of forced expression of Neu5Gc in the brain, we have established brain-specific Cmah transgenic mice. Such Neu5Gc overexpression in the brain resulted in abnormal locomotor activity, impaired object recognition memory, and abnormal axon myelination. Brain-specific Cmah transgenic mice were also lethally sensitive to a Neu5Gc-preferring bacterial toxin, even though Neu5Gc was overexpressed only in the brain and other organs maintained endogenous Neu5Gc expression, as in wild-type mice. Therefore, the unusually strict evolutionary suppression of Neu5Gc expression in the vertebrate brain may be explained by evasion of negative effects on neural functions and by selection against pathogens. PMID:28049733

Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia.

PubMed

Li, Tao; Wang, Qiang; Zhang, Jie; Rolls, Edmund T; Yang, Wei; Palaniyappan, Lena; Zhang, Lu; Cheng, Wei; Yao, Ye; Liu, Zhaowen; Gong, Xiaohong; Luo, Qiang; Tang, Yanqing; Crow, Timothy J; Broome, Matthew R; Xu, Ke; Li, Chunbo; Wang, Jijun; Liu, Zhening; Lu, Guangming; Wang, Fei; Feng, Jianfeng

2017-03-01

Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functional-connectivity involving the inferior frontal gyri (Broca's area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca's area, and these changes were correlated with delusions/blunted affect. For chronic patients, functional-connectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Structural plasticity of the social brain: Differential change after socio-affective and cognitive mental training.

PubMed

Valk, Sofie L; Bernhardt, Boris C; Trautwein, Fynn-Mathis; Böckler, Anne; Kanske, Philipp; Guizard, Nicolas; Collins, D Louis; Singer, Tania

2017-10-01

Although neuroscientific research has revealed experience-dependent brain changes across the life span in sensory, motor, and cognitive domains, plasticity relating to social capacities remains largely unknown. To investigate whether the targeted mental training of different cognitive and social skills can induce specific changes in brain morphology, we collected longitudinal magnetic resonance imaging (MRI) data throughout a 9-month mental training intervention from a large sample of adults between 20 and 55 years of age. By means of various daily mental exercises and weekly instructed group sessions, training protocols specifically addressed three functional domains: (i) mindfulness-based attention and interoception, (ii) socio-affective skills (compassion, dealing with difficult emotions, and prosocial motivation), and (iii) socio-cognitive skills (cognitive perspective-taking on self and others and metacognition). MRI-based cortical thickness analyses, contrasting the different training modules against each other, indicated spatially diverging changes in cortical morphology. Training of present-moment focused attention mostly led to increases in cortical thickness in prefrontal regions, socio-affective training induced plasticity in frontoinsular regions, and socio-cognitive training included change in inferior frontal and lateral temporal cortices. Module-specific structural brain changes correlated with training-induced behavioral improvements in the same individuals in domain-specific measures of attention, compassion, and cognitive perspective-taking, respectively, and overlapped with task-relevant functional networks. Our longitudinal findings indicate structural plasticity in well-known socio-affective and socio-cognitive brain networks in healthy adults based on targeted short daily mental practices. These findings could promote the development of evidence-based mental training interventions in clinical, educational, and corporate settings aimed at cultivating social intelligence, prosocial motivation, and cooperation.

Structural plasticity of the social brain: Differential change after socio-affective and cognitive mental training

PubMed Central

Valk, Sofie L.; Bernhardt, Boris C.; Trautwein, Fynn-Mathis; Böckler, Anne; Kanske, Philipp; Guizard, Nicolas; Collins, D. Louis; Singer, Tania

2017-01-01

Although neuroscientific research has revealed experience-dependent brain changes across the life span in sensory, motor, and cognitive domains, plasticity relating to social capacities remains largely unknown. To investigate whether the targeted mental training of different cognitive and social skills can induce specific changes in brain morphology, we collected longitudinal magnetic resonance imaging (MRI) data throughout a 9-month mental training intervention from a large sample of adults between 20 and 55 years of age. By means of various daily mental exercises and weekly instructed group sessions, training protocols specifically addressed three functional domains: (i) mindfulness-based attention and interoception, (ii) socio-affective skills (compassion, dealing with difficult emotions, and prosocial motivation), and (iii) socio-cognitive skills (cognitive perspective-taking on self and others and metacognition). MRI-based cortical thickness analyses, contrasting the different training modules against each other, indicated spatially diverging changes in cortical morphology. Training of present-moment focused attention mostly led to increases in cortical thickness in prefrontal regions, socio-affective training induced plasticity in frontoinsular regions, and socio-cognitive training included change in inferior frontal and lateral temporal cortices. Module-specific structural brain changes correlated with training-induced behavioral improvements in the same individuals in domain-specific measures of attention, compassion, and cognitive perspective-taking, respectively, and overlapped with task-relevant functional networks. Our longitudinal findings indicate structural plasticity in well-known socio-affective and socio-cognitive brain networks in healthy adults based on targeted short daily mental practices. These findings could promote the development of evidence-based mental training interventions in clinical, educational, and corporate settings aimed at cultivating social intelligence, prosocial motivation, and cooperation. PMID:28983507

[Immune dysfunction and cognitive deficit in stress and physiological aging. Part II: New approaches to cognitive disorder prevention and treatment ].

PubMed

Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

2014-01-01

Long-term stress as well as physiological aging result in similar immunological and hormonal disturbances including hypothalamic-pituitary-adrenal) axis depletion, aberrant immune response (regulatory T-cells, Tregs, and T(h17)-lymphocyte accumulation) and decreased dehydroepian-drosterone synthesis both in the brain and in the adrenal glands. Since the main mechanisms of inflammation control, "prompt" (stress hormones) and "delayed" (Tregs), are broken, serum cytokine levels increase and become sufficient for blood-brain-barrier disruption. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Structural and functional alterations of blood-brain-barrier as well as stress- (or age-) induced neuroinflammation promote influx of bone marrow derived dendritic cells and lymphocyte effectors into the brain parenchyma. Thereafter, mass intrusion ofpro-inflammatory mediators and immune cells having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets: 1) reduction of excessive Treg accumulation; 2) supporting hypothalamic-pituitary-adrenal axis and inflammatory reaction attenuation; 3) recovery of dehydroepiandrosterone level; 4) improvement of blood-brain-barrier function.

Perinatal asphyxia exerts lifelong effects on neuronal responsiveness to stress in specific brain regions in the rat.

PubMed

Salchner, Peter; Engidawork, Ephrem; Hoeger, Harald; Lubec, Barbara; Singewald, Nicolas

2003-09-01

Perinatal asphyxia (PA) causes irreversible damage to the brain of newborns and can produce neurologic and behavioral changes later in life. To identify neuronal substrates underlying the effects of PA, we investigated whether and how neuronal responsiveness to an established stress challenge is affected. We used Fos expression as a marker of neuronal activation and examined the pattern of Fos expression in response to acute swim stress in 24-month-old rats exposed to a 20-minute PA insult. Swim stress produced a similar pattern of Fos expression in control and asphyxiated rats in 34 brain areas. Asphyxiated rats displayed a higher number of stress-induced Fos-positive cells in the nucleus of the solitary tract, parabrachial nucleus, periaqueductal gray, paraventricular hypothalamic nucleus, nucleus accumbens, caudate-putamen, and prelimbic cortex. No differences in the Fos response to stress were observed in other regions, including the locus ceruleus, amygdala, hippocampus, or septum. These data provide functional anatomic evidence that PA has lifelong effects on neuronal communication and leads to an abnormal, augmented neuronal responsiveness to stress in specific brain areas, particularly in the main telencephalic target regions of the mesencephalic dopamine projections, as well as in a functionally related set of brain regions associated with autonomic and neuroendocrine regulation.

Cognitive Screening in Brain Tumors: Short but Sensitive Enough?

PubMed Central

Robinson, Gail A.; Biggs, Vivien; Walker, David G.

2015-01-01

Cognitive deficits in brain tumors are generally thought to be relatively mild and non-specific, although recent evidence challenges this notion. One possibility is that cognitive screening tools are being used to assess cognitive functions but their sensitivity to detect cognitive impairment may be limited. For improved sensitivity to recognize mild and/or focal cognitive deficits in brain tumors, neuropsychological evaluation tailored to detect specific impairments has been thought crucial. This study investigates the sensitivity of a cognitive screening tool, the Montreal Cognitive Assessment (MoCA), compared to a brief but tailored cognitive assessment (CA) for identifying cognitive deficits in an unselected primary brain tumor sample (i.e., low/high-grade gliomas, meningiomas). Performance is compared on broad measures of impairment: (a) number of patients impaired on the global screening measure or in any cognitive domain; and (b) number of cognitive domains impaired and specific analyses of MoCA-Intact and MoCA-Impaired patients on specific cognitive tests. The MoCA-Impaired group obtained lower naming and word fluency scores than the MoCA-Intact group, but otherwise performed comparably on cognitive tests. Overall, based on our results from patients with brain tumor, the MoCA has extremely poor sensitivity for detecting cognitive impairments and a brief but tailored CA is necessary. These findings will be discussed in relation to broader issues for clinical management and planning, as well as specific considerations for neuropsychological assessment of brain tumor patients. PMID:25815273

Physiology and molecular biology of barrier mechanisms in the fetal and neonatal brain.

PubMed

Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld; Habgood, Mark D

2018-05-17

Properties of the local internal environment of the adult brain are tightly controlled providing a stable milieu essential for its normal function. The mechanisms involved in this complex control are structural, molecular and physiological (influx and efflux transporters) frequently referred to as the "blood-brain barrier". These mechanisms include regulation of ion levels in brain interstitial fluid essential for normal neuronal function, supply of nutrients, removal of metabolic products and prevention of entry or elimination of toxic agents. A key feature is cerebrospinal fluid secretion and turnover. This is much less during development, allowing greater accumulation of permeating molecules. The overall effect of these mechanisms is to tightly control the exchange of molecules into and out of the brain. This review presents experimental evidence currently available on the status of these mechanisms in developing brain. It has been frequently stated for over nearly a century that the blood-brain barrier is not present or at least is functionally deficient in the embryo, fetus and newborn. We suggest the alternative hypothesis that the barrier mechanisms in developing brain are likely to be appropriately matched to each stage of its development. The contributions of different barrier mechanisms, such as changes in constituents of cerebrospinal fluid in relation to specific features of brain development, for example neurogenesis, are only beginning to be studied. The evidence on this previously neglected aspect of brain barrier function is outlined. We also suggest future directions this field could follow with special emphasis on potential applications in a clinical setting. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Mitochondrial accumulation of APP and Aβ: significance for Alzheimer disease pathogenesis

PubMed Central

Pavlov, Pavel F; Petersen, Camilla Hansson; Glaser, Elzbieta; Ankarcrona, Maria

2009-01-01

Accumulating evidence suggest that alterations in energy metabolism are among the earliest events that occur in the Alzheimer disease (AD) affected brain. Energy consumption is drastically decreased in the AD-affected regions of cerebral cortex and hippocampus pointing towards compromised mitochondrial function of neurons within specific brain regions. This is accompanied by an elevated production of reactive oxygen species contributing to increased rates of neuronal loss in the AD-affected brain regions. In this review, we will discuss the role of mitochondrial function and dysfunction in AD. We will focus on the consequences of amyloid precursor protein and amyloid-β peptide accumulation in mitochondria and their involvement in AD pathogenesis. PMID:19725915

PRANAYAMA AND BRAIN CORRELATES

PubMed Central

Srinivasan, T. M.

1991-01-01

Many yogic methods emphasis control and suspension of breath as important components of the path to transcendence. However, the Pranayamas are varied and their role of both improve the physical aspects of breathing and for calming the mind, the latter being very important in the management of many phycosomatic disorders. Different types of Pranayama seem to influence the brain functioning in specific ways. Since the breath seems to link the body and the mind, it is possible to study this link by studying the effect of Pranayama on some brain functioning. This report document some of the recent observations of EEG changes during different types of Pranayama and their significance in health and diseases. PMID:22556548

Mirror neuron system as the joint from action to language.

PubMed

Chen, Wei; Yuan, Ti-Fei

2008-08-01

Mirror neuron system (MNS) represents one of the most important discoveries of cognitive neuroscience in the past decade, and it has been found to involve in multiple aspects of brain functions including action understanding, imitation, language understanding, empathy, action prediction and speech evolution. This manuscript reviewed the function of MNS in action understanding as well as language evolution, and specifically assessed its roles as the bridge from body language to fluent speeches. Then we discussed the speech defects of autism patients due to the disruption of MNS. Finally, given that MNS is plastic in adult brain, we proposed MNS targeted therapy provides an efficient rehabilitation approach for brain damages conditions as well as autism patients.

Simple wavefront correction framework for two-photon microscopy of in-vivo brain

PubMed Central

Galwaduge, P. T.; Kim, S. H.; Grosberg, L. E.; Hillman, E. M. C.

2015-01-01

We present an easily implemented wavefront correction scheme that has been specifically designed for in-vivo brain imaging. The system can be implemented with a single liquid crystal spatial light modulator (LCSLM), which makes it compatible with existing patterned illumination setups, and provides measurable signal improvements even after a few seconds of optimization. The optimization scheme is signal-based and does not require exogenous guide-stars, repeated image acquisition or beam constraint. The unconstrained beam approach allows the use of Zernike functions for aberration correction and Hadamard functions for scattering correction. Low order corrections performed in mouse brain were found to be valid up to hundreds of microns away from the correction location. PMID:26309763

Double Dissociation in the Anatomy of Socioemotional Disinhibition and Executive Functioning in Dementia

PubMed Central

Krueger, Casey E.; Laluz, Victor; Rosen, Howard J.; Neuhaus, John M.; Miller, Bruce L.; Kramer, Joel H.

2010-01-01

Objective To determine if socioemotional disinhibition and executive dysfunction are related to dissociable patterns of brain atrophy in neurodegenerative disease. Previous studies have indicated that behavioral and cognitive dysfunction in neurodegenerative disease are linked to atrophy in different parts of the frontal lobe, but these prior studies did not establish that these relationships were specific, which would best be demonstrated by a double dissociation. Method Subjects included 157 patients with neurodegenerative disease. A semi-automated parcellation program (Freesurfer) was used to generate regional cortical volumes from structural MRI scans. Regions of interest (ROIs) included anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), middle frontal gyrus (MFG) and inferior frontal gyrus (IFG). Socioemotional disinhibition was measured using the Neuropsychiatric Inventory. Principal component analysis including three tasks of executive function (EF; verbal fluency, Stroop Interference, modified Trails) was used to generate a single factor score to represent EF. Results Partial correlations between ROIs, disinhibition, and EF were computed after controlling for total intracranial volume, MMSE, diagnosis, age, and education. Brain regions significantly correlated with disinhibition (ACC, OFC, IFG, and temporal lobes) and EF (MFG) were entered into separate hierarchical regressions to determine which brain regions predicted disinhibition and EF. OFC was the only brain region to significantly predict disinhibition and MFG significantly predicted executive functioning performance. A multivariate general linear model demonstrated a significant interaction between ROIs and cognitive-behavioral functions. Conclusions These results support a specific association between orbitofrontal areas and behavioral management as compared to dorsolateral areas and EF. PMID:21381829

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

Neurobiology of Schizophrenia: Search for the Elusive Correlation with Symptoms

PubMed Central

Mathalon, Daniel H.; Ford, Judith M.

2012-01-01

In the last half-century, human neuroscience methods provided a way to study schizophrenia in vivo, and established that it is associated with subtle abnormalities in brain structure and function. However, efforts to understand the neurobiological bases of the clinical symptoms that the diagnosis is based on have been largely unsuccessful. In this paper, we provide an overview of the conceptual and methodological obstacles that undermine efforts to link the severity of specific symptoms to specific neurobiological measures. These obstacles include small samples, questionable reliability and validity of measurements, medication confounds, failure to distinguish state and trait effects, correlation–causation ambiguity, and the absence of compelling animal models of specific symptoms to test mechanistic hypotheses derived from brain-symptom correlations. We conclude with recommendations to promote progress in establishing brain-symptom relationships. PMID:22654745

Differential Hemispheric Predilection of Microstructural White Matter and Functional Connectivity Abnormalities between Respectively Semantic and Behavioral Variant Frontotemporal Dementia.

PubMed

Meijboom, Rozanna; Steketee, Rebecca M E; Ham, Leontine S; van der Lugt, Aad; van Swieten, John C; Smits, Marion

2017-01-01

Semantic dementia (SD) and behavioral variant frontotemporal dementia (bvFTD), subtypes of frontotemporal dementia, are characterized by distinct clinical symptoms and neuroimaging features, with predominant left temporal grey matter (GM) atrophy in SD and bilateral or right frontal GM atrophy in bvFTD. Such differential hemispheric predilection may also be reflected by other neuroimaging features, such as brain connectivity. This study investigated white matter (WM) microstructure and functional connectivity differences between SD and bvFTD, focusing on the hemispheric predilection of these differences. Eight SD and 12 bvFTD patients, and 17 controls underwent diffusion tensor imaging and resting state functional MRI at 3T. Whole-brain WM microstructure was assessed to determine distinct WM tracts affected in SD and bvFTD. For these tracts, diffusivity measures and lateralization indices were calculated. Functional connectivity was established for GM regions affected in early stage SD or bvFTD. Results of a direct comparison between SD and bvFTD are reported. Whole-brain WM microstructure abnormalities were more pronounced in the left hemisphere in SD and bilaterally- with a slight predilection for the right- in bvFTD. Lateralization of tract-specific abnormalities was seen in SD only, toward the left hemisphere. Functional connectivity of disease-specific regions was mainly decreased bilaterally in SD and in the right hemisphere in bvFTD. SD and bvFTD show WM microstructure and functional connectivity abnormalities in different regions, that are respectively more pronounced in the left hemisphere in SD and in the right hemisphere in bvFTD. This indicates differential hemispheric predilection of brain connectivity abnormalities between SD and bvFTD.

Comparison of continuously acquired resting state and extracted analogues from active tasks

PubMed Central

Ganger, Sebastian; Hahn, Andreas; Küblböck, Martin; Kranz, Georg S.; Spies, Marie; Vanicek, Thomas; Seiger, René; Sladky, Ronald; Windischberger, Christian; Kasper, Siegfried

2015-01-01

Abstract Functional connectivity analysis of brain networks has become an important tool for investigation of human brain function. Although functional connectivity computations are usually based on resting‐state data, the application to task‐specific fMRI has received growing attention. Three major methods for extraction of resting‐state data from task‐related signal have been proposed (1) usage of unmanipulated task data for functional connectivity; (2) regression against task effects, subsequently using the residuals; and (3) concatenation of baseline blocks located in‐between task blocks. Despite widespread application in current research, consensus on which method best resembles resting‐state seems to be missing. We, therefore, evaluated these techniques in a sample of 26 healthy controls measured at 7 Tesla. In addition to continuous resting‐state, two different task paradigms were assessed (emotion discrimination and right finger‐tapping) and five well‐described networks were analyzed (default mode, thalamus, cuneus, sensorimotor, and auditory). Investigating the similarity to continuous resting‐state (Dice, Intraclass correlation coefficient (ICC), R 2) showed that regression against task effects yields functional connectivity networks most alike to resting‐state. However, all methods exhibited significant differences when compared to continuous resting‐state and similarity metrics were lower than test‐retest of two resting‐state scans. Omitting global signal regression did not change these findings. Visually, the networks are highly similar, but through further investigation marked differences can be found. Therefore, our data does not support referring to resting‐state when extracting signals from task designs, although functional connectivity computed from task‐specific data may indeed yield interesting information. Hum Brain Mapp 36:4053–4063, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26178250

Sex differences in the neural substrates of spatial working memory during adolescence are not mediated by endogenous testosterone.

PubMed

Alarcón, Gabriela; Cservenka, Anita; Fair, Damien A; Nagel, Bonnie J

2014-12-17

Adolescence is a developmental period characterized by notable changes in behavior, physical attributes, and an increase in endogenous sex steroid hormones, which may impact cognitive functioning. Moreover, sex differences in brain structure are present, leading to differences in neural function and cognition. Here, we examine sex differences in performance and blood oxygen level-dependent (BOLD) activation in a sample of adolescents during a spatial working memory (SWM) task. We also examine whether endogenous testosterone levels mediate differential brain activity between the sexes. Adolescents between ages 10 and 16 years completed a SWM functional magnetic resonance imaging (fMRI) task, and serum hormone levels were assessed within seven days of scanning. While there were no sex differences in task performance (accuracy and reaction time), differences in BOLD response between girls and boys emerged, with girls deactivating brain regions in the default mode network and boys showing increased response in SWM-related brain regions of the frontal cortex. These results suggest that adolescent boys and girls adopted distinct neural strategies, while maintaining spatial cognitive strategies that facilitated comparable cognitive performance of a SWM task. A nonparametric bootstrapping procedure revealed that testosterone did not mediate sex-specific brain activity, suggesting that sex differences in BOLD activation during SWM may be better explained by other factors, such as early organizational effects of sex steroids or environmental influences. Elucidating sex differences in neural function and the influence of gonadal hormones can serve as a basis of comparison for understanding sexually dimorphic neurodevelopment and inform sex-specific psychopathology that emerges in adolescence. Copyright © 2014 Elsevier B.V. All rights reserved.

The hippocampal response to psychosocial stress varies with salivary uric acid level

PubMed Central

Goodman, Adam M.; Wheelock, Muriah D.; Harnett, Nathaniel G.; Mrug, Sylvie; Granger, Douglas A.; Knight, David C.

2016-01-01

Uric acid is a naturally occurring, endogenous compound that impacts mental health. In particular, uric acid levels are associated with emotion-related psychopathology (e.g., anxiety and depression). Therefore, understanding uric acid’s impact on the brain would provide valuable new knowledge regarding neural mechanisms that mediate the relationship between uric acid and mental health. Brain regions including the prefrontal cortex, amygdala, and hippocampus underlie stress reactivity and emotion regulation. Thus, uric acid may impact emotion by modifying the function of these brain regions. The present study used functional magnetic resonance imaging (fMRI) during a psychosocial stress task to investigate the relationship between baseline uric acid levels (in saliva) and brain function. Results demonstrate that activity within the bilateral hippocampal complex varied with uric acid concentrations. Specifically, activity within the hippocampus and surrounding cortex increased as a function of uric acid level. The current findings suggest that uric acid levels modulate stress-related hippocampal activity. Given that the hippocampus has been implicated in emotion regulation during psychosocial stress, the present findings offer a potential mechanism by which uric acid impacts mental health. PMID:27725214

Activating Developmental Reserve Capacity Via Cognitive Training or Non-invasive Brain Stimulation: Potentials for Promoting Fronto-Parietal and Hippocampal-Striatal Network Functions in Old Age

PubMed Central

Passow, Susanne; Thurm, Franka; Li, Shu-Chen

2017-01-01

Existing neurocomputational and empirical data link deficient neuromodulation of the fronto-parietal and hippocampal-striatal circuitries with aging-related increase in processing noise and declines in various cognitive functions. Specifically, the theory of aging neuronal gain control postulates that aging-related suboptimal neuromodulation may attenuate neuronal gain control, which yields computational consequences on reducing the signal-to-noise-ratio of synaptic signal transmission and hampering information processing within and between cortical networks. Intervention methods such as cognitive training and non-invasive brain stimulation, e.g., transcranial direct current stimulation (tDCS), have been considered as means to buffer cognitive functions or delay cognitive decline in old age. However, to date the reported effect sizes of immediate training gains and maintenance effects of a variety of cognitive trainings are small to moderate at best; moreover, training-related transfer effects to non-trained but closely related (i.e., near-transfer) or other (i.e., far-transfer) cognitive functions are inconsistent or lacking. Similarly, although applying different tDCS protocols to reduce aging-related cognitive impairments by inducing temporary changes in cortical excitability seem somewhat promising, evidence of effects on short- and long-term plasticity is still equivocal. In this article, we will review and critically discuss existing findings of cognitive training- and stimulation-related behavioral and neural plasticity effects in the context of cognitive aging, focusing specifically on working memory and episodic memory functions, which are subserved by the fronto-parietal and hippocampal-striatal networks, respectively. Furthermore, in line with the theory of aging neuronal gain control we will highlight that developing age-specific brain stimulation protocols and the concurrent applications of tDCS during cognitive training may potentially facilitate short- and long-term cognitive and brain plasticity in old age. PMID:28280465

Aerobic Exercise Intervention, Cognitive Performance, and Brain Structure: Results from the Physical Influences on Brain in Aging (PHIBRA) Study.

PubMed

Jonasson, Lars S; Nyberg, Lars; Kramer, Arthur F; Lundquist, Anders; Riklund, Katrine; Boraxbekk, Carl-Johan

2016-01-01

Studies have shown that aerobic exercise has the potential to improve cognition and reduce brain atrophy in older adults. However, the literature is equivocal with regards to the specificity or generality of these effects. To this end, we report results on cognitive function and brain structure from a 6-month training intervention with 60 sedentary adults (64-78 years) randomized to either aerobic training or stretching and toning control training. Cognitive functions were assessed with a neuropsychological test battery in which cognitive constructs were measured using several different tests. Freesurfer was used to estimate cortical thickness in frontal regions and hippocampus volume. Results showed that aerobic exercisers, compared to controls, exhibited a broad, rather than specific, improvement in cognition as indexed by a higher "Cognitive score," a composite including episodic memory, processing speed, updating, and executive function tasks ( p = 0.01). There were no group differences in cortical thickness, but additional analyses revealed that aerobic fitness at baseline was specifically related to larger thickness in dorsolateral prefrontal cortex (dlPFC), and hippocampus volume was positively associated with increased aerobic fitness over time. Moreover, "Cognitive score" was related to dlPFC thickness at baseline, but changes in "Cognitive score" and dlPFC thickness were associated over time in the aerobic group only. However, aerobic fitness did not predict dlPFC change, despite the improvement in "Cognitive score" in aerobic exercisers. Our interpretation of these observations is that potential exercise-induced changes in thickness are slow, and may be undetectable within 6-months, in contrast to change in hippocampus volume which in fact was predicted by the change in aerobic fitness. To conclude, our results add to a growing literature suggesting that aerobic exercise has a broad influence on cognitive functioning, which may aid in explaining why studies focusing on a narrower range of functions have sometimes reported mixed results.

Aerobic Exercise Intervention, Cognitive Performance, and Brain Structure: Results from the Physical Influences on Brain in Aging (PHIBRA) Study

PubMed Central

Jonasson, Lars S.; Nyberg, Lars; Kramer, Arthur F.; Lundquist, Anders; Riklund, Katrine; Boraxbekk, Carl-Johan

2017-01-01

Studies have shown that aerobic exercise has the potential to improve cognition and reduce brain atrophy in older adults. However, the literature is equivocal with regards to the specificity or generality of these effects. To this end, we report results on cognitive function and brain structure from a 6-month training intervention with 60 sedentary adults (64–78 years) randomized to either aerobic training or stretching and toning control training. Cognitive functions were assessed with a neuropsychological test battery in which cognitive constructs were measured using several different tests. Freesurfer was used to estimate cortical thickness in frontal regions and hippocampus volume. Results showed that aerobic exercisers, compared to controls, exhibited a broad, rather than specific, improvement in cognition as indexed by a higher “Cognitive score,” a composite including episodic memory, processing speed, updating, and executive function tasks (p = 0.01). There were no group differences in cortical thickness, but additional analyses revealed that aerobic fitness at baseline was specifically related to larger thickness in dorsolateral prefrontal cortex (dlPFC), and hippocampus volume was positively associated with increased aerobic fitness over time. Moreover, “Cognitive score” was related to dlPFC thickness at baseline, but changes in “Cognitive score” and dlPFC thickness were associated over time in the aerobic group only. However, aerobic fitness did not predict dlPFC change, despite the improvement in “Cognitive score” in aerobic exercisers. Our interpretation of these observations is that potential exercise-induced changes in thickness are slow, and may be undetectable within 6-months, in contrast to change in hippocampus volume which in fact was predicted by the change in aerobic fitness. To conclude, our results add to a growing literature suggesting that aerobic exercise has a broad influence on cognitive functioning, which may aid in explaining why studies focusing on a narrower range of functions have sometimes reported mixed results. PMID:28149277

Heart and brain interaction in patients with heart failure: overview and proposal for a taxonomy. A position paper from the Study Group on Heart and Brain Interaction of the Heart Failure Association.

PubMed

Doehner, Wolfram; Ural, Dilek; Haeusler, Karl Georg; Čelutkienė, Jelena; Bestetti, Reinaldo; Cavusoglu, Yuksel; Peña-Duque, Marco A; Glavas, Duska; Iacoviello, Massimo; Laufs, Ulrich; Alvear, Ricardo Marmol; Mbakwem, Amam; Piepoli, Massimo F; Rosen, Stuart D; Tsivgoulis, Georgios; Vitale, Cristiana; Yilmaz, M Birhan; Anker, Stefan D; Filippatos, Gerasimos; Seferovic, Petar; Coats, Andrew J S; Ruschitzka, Frank

2018-02-01

Heart failure (HF) is a complex clinical syndrome with multiple interactions between the failing myocardium and cerebral (dys-)functions. Bi-directional feedback interactions between the heart and the brain are inherent in the pathophysiology of HF: (i) the impaired cardiac function affects cerebral structure and functional capacity, and (ii) neuronal signals impact on the cardiovascular continuum. These interactions contribute to the symptomatic presentation of HF patients and affect many co-morbidities of HF. Moreover, neuro-cardiac feedback signals significantly promote aggravation and further progression of HF and are causal in the poor prognosis of HF. The diversity and complexity of heart and brain interactions make it difficult to develop a comprehensive overview. In this paper a systematic approach is proposed to develop a comprehensive atlas of related conditions, signals and disease mechanisms of the interactions between the heart and the brain in HF. The proposed taxonomy is based on pathophysiological principles. Impaired perfusion of the brain may represent one major category, with acute (cardio-embolic) or chronic (haemodynamic failure) low perfusion being sub-categories with mostly different consequences (i.e. ischaemic stroke or cognitive impairment, respectively). Further categories include impairment of higher cortical function (mood, cognition), of brain stem function (sympathetic over-activation, neuro-cardiac reflexes). Treatment-related interactions could be categorized as medical, interventional and device-related interactions. Also interactions due to specific diseases are categorized. A methodical approach to categorize the interdependency of heart and brain may help to integrate individual research areas into an overall picture. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Relations between brain volumes, neuropsychological assessment and parental questionnaire in prematurely born children.

PubMed

Lind, Annika; Haataja, Leena; Rautava, Liisi; Väliaho, Anniina; Lehtonen, Liisa; Lapinleimu, Helena; Parkkola, Riitta; Korkman, Marit

2010-05-01

The objective of this study is to assess the relationship between brain volumes at term equivalent age and neuropsychological functions at 5 years of age in very low birth weight (VLBW) children, and to compare the results from a neuropsychological assessment and a parental questionnaire at 5 years of age. The study group included a regional cohort of 97 VLBW children and a control group of 161 children born at term. At term equivalent age, brain magnetic resonance imaging (MRI) was performed on the VLBW children, and analysed for total and regional brain volumes. At 5 years of age, a psychologist assessed the neuropsychological performance with NEPSY II, and parents completed the Five to fifteen (FTF) questionnaire on development and behaviour. The results of the control group were used to give the age-specific reference values. No significant associations were found between the brain volumes and the NEPSY II domains. As for the FTF, significant associations were found between a smaller total brain tissue volume and poorer executive functions, between a smaller cerebellar volume and both poorer executive functions and motor skills, and, surprisingly, between a larger volume of brainstem and poorer language functions. Even after adjustment for total brain tissue volume, the two associations between the cerebellar volume and the FTF domains remained borderline significant (P = 0.05). The NEPSY II domains Executive Functioning, Language and Motor Skills were significantly associated with the corresponding FTF domains. In conclusion, altered brain volumes at term equivalent age appear to affect development still at 5 years of age. The FTF seems to be a good instrument when used in combination with other neuropsychological assessment.

Investigating the Predictive Value of Functional MRI to Appetitive and Aversive Stimuli: A Pattern Classification Approach.

PubMed

McCabe, Ciara; Rocha-Rego, Vanessa

2016-01-01

Dysfunctional neural responses to appetitive and aversive stimuli have been investigated as possible biomarkers for psychiatric disorders. However it is not clear to what degree these are separate processes across the brain or in fact overlapping systems. To help clarify this issue we used Gaussian process classifier (GPC) analysis to examine appetitive and aversive processing in the brain. 25 healthy controls underwent functional MRI whilst seeing pictures and receiving tastes of pleasant and unpleasant food. We applied GPCs to discriminate between the appetitive and aversive sights and tastes using functional activity patterns. The diagnostic accuracy of the GPC for the accuracy to discriminate appetitive taste from neutral condition was 86.5% (specificity = 81%, sensitivity = 92%, p = 0.001). If a participant experienced neutral taste stimuli the probability of correct classification was 92. The accuracy to discriminate aversive from neutral taste stimuli was 82.5% (specificity = 73%, sensitivity = 92%, p = 0.001) and appetitive from aversive taste stimuli was 73% (specificity = 77%, sensitivity = 69%, p = 0.001). In the sight modality, the accuracy to discriminate appetitive from neutral condition was 88.5% (specificity = 85%, sensitivity = 92%, p = 0.001), to discriminate aversive from neutral sight stimuli was 92% (specificity = 92%, sensitivity = 92%, p = 0.001), and to discriminate aversive from appetitive sight stimuli was 63.5% (specificity = 73%, sensitivity = 54%, p = 0.009). Our results demonstrate the predictive value of neurofunctional data in discriminating emotional and neutral networks of activity in the healthy human brain. It would be of interest to use pattern recognition techniques and fMRI to examine network dysfunction in the processing of appetitive, aversive and neutral stimuli in psychiatric disorders. Especially where problems with reward and punishment processing have been implicated in the pathophysiology of the disorder.

Community structure in networks of functional connectivity: resolving functional organization in the rat brain with pharmacological MRI.

PubMed

Schwarz, Adam J; Gozzi, Alessandro; Bifone, Angelo

2009-08-01

In the study of functional connectivity, fMRI data can be represented mathematically as a network of nodes and links, where image voxels represent the nodes and the connections between them reflect a degree of correlation or similarity in their response. Here we show that, within this framework, functional imaging data can be partitioned into 'communities' of tightly interconnected voxels corresponding to maximum modularity within the overall network. We evaluated this approach systematically in application to networks constructed from pharmacological MRI (phMRI) of the rat brain in response to acute challenge with three different compounds with distinct mechanisms of action (d-amphetamine, fluoxetine, and nicotine) as well as vehicle (physiological saline). This approach resulted in bilaterally symmetric sub-networks corresponding to meaningful anatomical and functional connectivity pathways consistent with the purported mechanism of action of each drug. Interestingly, common features across all three networks revealed two groups of tightly coupled brain structures that responded as functional units independent of the specific neurotransmitter systems stimulated by the drug challenge, including a network involving the prefrontal cortex and sub-cortical regions extending from the striatum to the amygdala. This finding suggests that each of these networks includes general underlying features of the functional organization of the rat brain.

Disconnected aging: cerebral white matter integrity and age-related differences in cognition.

PubMed

Bennett, I J; Madden, D J

2014-09-12

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Disconnected Aging: Cerebral White Matter Integrity and Age-Related Differences in Cognition

PubMed Central

Bennett, Ilana J.; Madden, David J.

2013-01-01

Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. PMID:24280637

Neuroimaging and Neuromodulation: Complementary Approaches for Identifying the Neuronal Correlates of Tinnitus

PubMed Central

Langguth, Berthold; Schecklmann, Martin; Lehner, Astrid; Landgrebe, Michael; Poeppl, Timm Benjamin; Kreuzer, Peter Michal; Schlee, Winfried; Weisz, Nathan; Vanneste, Sven; De Ridder, Dirk

2012-01-01

An inherent limitation of functional imaging studies is their correlational approach. More information about critical contributions of specific brain regions can be gained by focal transient perturbation of neural activity in specific regions with non-invasive focal brain stimulation methods. Functional imaging studies have revealed that tinnitus is related to alterations in neuronal activity of central auditory pathways. Modulation of neuronal activity in auditory cortical areas by repetitive transcranial magnetic stimulation (rTMS) can reduce tinnitus loudness and, if applied repeatedly, exerts therapeutic effects, confirming the relevance of auditory cortex activation for tinnitus generation and persistence. Measurements of oscillatory brain activity before and after rTMS demonstrate that the same stimulation protocol has different effects on brain activity in different patients, presumably related to interindividual differences in baseline activity in the clinically heterogeneous study cohort. In addition to alterations in auditory pathways, imaging techniques also indicate the involvement of non-auditory brain areas, such as the fronto-parietal “awareness” network and the non-tinnitus-specific distress network consisting of the anterior cingulate cortex, anterior insula, and amygdale. Involvement of the hippocampus and the parahippocampal region putatively reflects the relevance of memory mechanisms in the persistence of the phantom percept and the associated distress. Preliminary studies targeting the dorsolateral prefrontal cortex, the dorsal anterior cingulate cortex, and the parietal cortex with rTMS and with transcranial direct current stimulation confirm the relevance of the mentioned non-auditory networks. Available data indicate the important value added by brain stimulation as a complementary approach to neuroimaging for identifying the neuronal correlates of the various clinical aspects of tinnitus. PMID:22509155

Influence of maternal thyroid hormones during gestation on fetal brain development

PubMed Central

Moog, Nora K.; Entringer, Sonja; Heim, Christine; Wadhwa, Pathik D.; Kathmann, Norbert; Buss, Claudia

2015-01-01

Thyroid hormones (TH) play an obligatory role in many fundamental processes underlying brain development and maturation. The developing embryo/fetus is dependent on maternal supply of TH. The fetal thyroid gland does not commence THs synthesis until mid gestation, and the adverse consequences of severe maternal TH deficiency on offspring neurodevelopment are well established. Recent evidence suggests that even more moderate forms of maternal thyroid dysfunction, particularly during early gestation, may have a long-lasting influence on child cognitive development and risk of neurodevelopmental disorders. Moreover, these observed alterations appear to be largely irreversible after birth. It is, therefore, important to gain a better understanding of the role of maternal thyroid dysfunction on offspring neurodevelopment in terms of the nature, magnitude, time-specificity, and context-specificity of its effects. With respect to the issue of context specificity, it is possible that maternal stress and stress-related biological processes during pregnancy may modulate maternal thyroid function. The possibility of an interaction between the thyroid and stress systems in the context of fetal brain development has, however, not been addressed to date. We begin this review with a brief overview of TH biology during pregnancy and a summary of the literature on its effect on the developing brain. Next, we consider and discuss whether and how processes related to maternal stress and stress biology may interact with and modify the effects of maternal thyroid function on offspring brain development. We synthesize several research areas and identify important knowledge gaps that may warrant further study. The scientific and public health relevance of this review relates to achieving a better understanding of the timing, mechanisms and contexts of thyroid programming of brain development, with implications for early identification of risk, primary prevention and intervention. PMID:26434624

A Protocol for the Administration of Real-Time fMRI Neurofeedback Training

PubMed Central

Sherwood, Matthew S.; Diller, Emily E.; Ey, Elizabeth; Ganapathy, Subhashini; Nelson, Jeremy T.; Parker, Jason G.

2017-01-01

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control neuroplastic processes and correct abnormal function, or even shift functions from damaged tissue to physiologically healthy brain regions, hold the potential to dramatically improve overall health. Of the current neuroplastic interventions in development, neurofeedback training (NFT) from functional Magnetic Resonance Imaging (fMRI) has the advantages of being completely non-invasive, non-pharmacologic, and spatially localized to target brain regions, as well as having no known side effects. Furthermore, NFT techniques, initially developed using fMRI, can often be translated to exercises that can be performed outside of the scanner without the aid of medical professionals or sophisticated medical equipment. In fMRI NFT, the fMRI signal is measured from specific regions of the brain, processed, and presented to the participant in real-time. Through training, self-directed mental processing techniques, that regulate this signal and its underlying neurophysiologic correlates, are developed. FMRI NFT has been used to train volitional control over a wide range of brain regions with implications for several different cognitive, behavioral, and motor systems. Additionally, fMRI NFT has shown promise in a broad range of applications such as the treatment of neurologic disorders and the augmentation of baseline human performance. In this article, we present an fMRI NFT protocol developed at our institution for modulation of both healthy and abnormal brain function, as well as examples of using the method to target both cognitive and auditory regions of the brain. PMID:28872110

A Protocol for the Administration of Real-Time fMRI Neurofeedback Training.

PubMed

Sherwood, Matthew S; Diller, Emily E; Ey, Elizabeth; Ganapathy, Subhashini; Nelson, Jeremy T; Parker, Jason G

2017-08-24

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control neuroplastic processes and correct abnormal function, or even shift functions from damaged tissue to physiologically healthy brain regions, hold the potential to dramatically improve overall health. Of the current neuroplastic interventions in development, neurofeedback training (NFT) from functional Magnetic Resonance Imaging (fMRI) has the advantages of being completely non-invasive, non-pharmacologic, and spatially localized to target brain regions, as well as having no known side effects. Furthermore, NFT techniques, initially developed using fMRI, can often be translated to exercises that can be performed outside of the scanner without the aid of medical professionals or sophisticated medical equipment. In fMRI NFT, the fMRI signal is measured from specific regions of the brain, processed, and presented to the participant in real-time. Through training, self-directed mental processing techniques, that regulate this signal and its underlying neurophysiologic correlates, are developed. FMRI NFT has been used to train volitional control over a wide range of brain regions with implications for several different cognitive, behavioral, and motor systems. Additionally, fMRI NFT has shown promise in a broad range of applications such as the treatment of neurologic disorders and the augmentation of baseline human performance. In this article, we present an fMRI NFT protocol developed at our institution for modulation of both healthy and abnormal brain function, as well as examples of using the method to target both cognitive and auditory regions of the brain.

Does the regulation of local excitation-inhibition balance aid in recovery of functional connectivity? A computational account.

PubMed

Vattikonda, Anirudh; Surampudi, Bapi Raju; Banerjee, Arpan; Deco, Gustavo; Roy, Dipanjan

2016-08-01

Computational modeling of the spontaneous dynamics over the whole brain provides critical insight into the spatiotemporal organization of brain dynamics at multiple resolutions and their alteration to changes in brain structure (e.g. in diseased states, aging, across individuals). Recent experimental evidence further suggests that the adverse effect of lesions is visible on spontaneous dynamics characterized by changes in resting state functional connectivity and its graph theoretical properties (e.g. modularity). These changes originate from altered neural dynamics in individual brain areas that are otherwise poised towards a homeostatic equilibrium to maintain a stable excitatory and inhibitory activity. In this work, we employ a homeostatic inhibitory mechanism, balancing excitation and inhibition in the local brain areas of the entire cortex under neurological impairments like lesions to understand global functional recovery (across brain networks and individuals). Previous computational and empirical studies have demonstrated that the resting state functional connectivity varies primarily due to the location and specific topological characteristics of the lesion. We show that local homeostatic balance provides a functional recovery by re-establishing excitation-inhibition balance in all areas that are affected by lesion. We systematically compare the extent of recovery in the primary hub areas (e.g. default mode network (DMN), medial temporal lobe, medial prefrontal cortex) as well as other sensory areas like primary motor area, supplementary motor area, fronto-parietal and temporo-parietal networks. Our findings suggest that stability and richness similar to the normal brain dynamics at rest are achievable by re-establishment of balance. Copyright © 2016 Elsevier Inc. All rights reserved.

Dynamic Reorganization of Functional Connectivity Reveals Abnormal Temporal Efficiency in Schizophrenia.

PubMed

Sun, Yu; Collinson, Simon L; Suckling, John; Sim, Kang

2018-06-07

Emerging evidence suggests that schizophrenia is associated with brain dysconnectivity. Nonetheless, the implicit assumption of stationary functional connectivity (FC) adopted in most previous resting-state functional magnetic resonance imaging (fMRI) studies raises an open question of schizophrenia-related aberrations in dynamic properties of resting-state FC. This study introduces an empirical method to examine the dynamic functional dysconnectivity in patients with schizophrenia. Temporal brain networks were estimated from resting-state fMRI of 2 independent datasets (patients/controls = 18/19 and 53/57 for self-recorded dataset and a publicly available replication dataset, respectively) by the correlation of sliding time-windowed time courses among regions of a predefined atlas. Through the newly introduced temporal efficiency approach and temporal random network models, we examined, for the first time, the 3D spatiotemporal architecture of the temporal brain network. We found that although prominent temporal small-world properties were revealed in both groups, temporal brain networks of patients with schizophrenia in both datasets showed a significantly higher temporal global efficiency, which cannot be simply attributable to head motion and sampling error. Specifically, we found localized changes of temporal nodal properties in the left frontal, right medial parietal, and subcortical areas that were associated with clinical features of schizophrenia. Our findings demonstrate that altered dynamic FC may underlie abnormal brain function and clinical symptoms observed in schizophrenia. Moreover, we provide new evidence to extend the dysconnectivity hypothesis in schizophrenia from static to dynamic brain network and highlight the potential of aberrant brain dynamic FC in unraveling the pathophysiologic mechanisms of the disease.

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

PubMed Central

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

2012-01-01

Most of what is known about the reorganization of functional brain networks that accompanies normal aging is based on neuroimaging studies in which participants perform specific tasks. In these studies, reorganization is defined by the differences in task activation between young and old adults. However, task activation differences could be the result of differences in task performance, strategy, or motivation, and not necessarily reflect reorganization. Resting-state fMRI provides a method of investigating functional brain networks without such confounds. Here, a support vector machine (SVM) classifier was used in an attempt to differentiate older adults from younger adults based on their resting-state functional connectivity. In addition, the information used by the SVM was investigated to see what functional connections best differentiated younger adult brains from older adult brains. Three separate resting-state scans from 26 younger adults (18-35 yrs) and 26 older adults (55-85) were obtained from the International Consortium for Brain Mapping (ICBM) dataset made publically available in the 1000 Functional Connectomes project www.nitrc.org/projects/fcon_1000. 100 seed-regions from four functional networks with 5 mm3 radius were defined based on a recent study using machine learning classifiers on adolescent brains. Time-series for every seed-region were averaged and three matrices of z-transformed correlation coefficients were created for each subject corresponding to each individual’s three resting-state scans. SVM was then applied using leave-one-out cross-validation. The SVM classifier was 84% accurate in classifying older and younger adult brains. The majority of the connections used by the classifier to distinguish subjects by age came from seed-regions belonging to the sensorimotor and cingulo-opercular networks. These results suggest that age-related decreases in positive correlations within the cingulo-opercular and default networks, and decreases in negative correlations between the default and sensorimotor networks, are the distinguishing characteristics of age-related reorganization. PMID:22227886

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

PubMed

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

2012-03-01

Most of what is known about the reorganization of functional brain networks that accompanies normal aging is based on neuroimaging studies in which participants perform specific tasks. In these studies, reorganization is defined by the differences in task activation between young and old adults. However, task activation differences could be the result of differences in task performance, strategy, or motivation, and not necessarily reflect reorganization. Resting-state fMRI provides a method of investigating functional brain networks without such confounds. Here, a support vector machine (SVM) classifier was used in an attempt to differentiate older adults from younger adults based on their resting-state functional connectivity. In addition, the information used by the SVM was investigated to see what functional connections best differentiated younger adult brains from older adult brains. Three separate resting-state scans from 26 younger adults (18-35 yrs) and 26 older adults (55-85) were obtained from the International Consortium for Brain Mapping (ICBM) dataset made publically available in the 1000 Functional Connectomes project www.nitrc.org/projects/fcon_1000. 100 seed-regions from four functional networks with 5mm(3) radius were defined based on a recent study using machine learning classifiers on adolescent brains. Time-series for every seed-region were averaged and three matrices of z-transformed correlation coefficients were created for each subject corresponding to each individual's three resting-state scans. SVM was then applied using leave-one-out cross-validation. The SVM classifier was 84% accurate in classifying older and younger adult brains. The majority of the connections used by the classifier to distinguish subjects by age came from seed-regions belonging to the sensorimotor and cingulo-opercular networks. These results suggest that age-related decreases in positive correlations within the cingulo-opercular and default networks, and decreases in negative correlations between the default and sensorimotor networks, are the distinguishing characteristics of age-related reorganization. Copyright © 2011 Elsevier Inc. All rights reserved.

Estrogen synthesis and signaling pathways during ageing: from periphery to brain

PubMed Central

Cui, Jie; Shen, Yong; Li, Rena

2012-01-01

Estrogens are the primary female sex hormones and play important roles in both reproductive and non-reproductive systems. Estrogens can be synthesized in non-reproductive tissue as liver, heart, muscle, bone and brain. The tissue-specific estrogen synthesis is consistent with a diversity of estrogen actions. Here, we will focus on tissue and cell-specific estrogen synthesis and estrogen receptor signaling. This review will include three parts: (I) tissue and cell-specific estrogen synthesis and metabolism, (II) tissue and cell-specific distribution of estrogen receptors and signaling and (III) tissue-specific estrogen function and related disorders, including cardiovascular diseases, osteoporosis, Alzheimer's disease and Parkinson disease. This comprehensive review provides new insights into estrogens by giving a better understanding of the tissue-specific estrogen effects and their roles in various diseases. PMID:23348042