Sample records for influences brain function

  1. Separate effects of sex hormones and sex chromosomes on brain structure and function revealed by high-resolution magnetic resonance imaging and spatial navigation assessment of the Four Core Genotype mouse model.

    PubMed

    Corre, Christina; Friedel, Miriam; Vousden, Dulcie A; Metcalf, Ariane; Spring, Shoshana; Qiu, Lily R; Lerch, Jason P; Palmert, Mark R

    2016-03-01

    Males and females exhibit several differences in brain structure and function. To examine the basis for these sex differences, we investigated the influences of sex hormones and sex chromosomes on brain structure and function in mice. We used the Four Core Genotype (4CG) mice, which can generate both male and female mice with XX or XY sex chromosome complement, allowing the decoupling of sex chromosomes from hormonal milieu. To examine whole brain structure, high-resolution ex vivo MRI was performed, and to assess differences in cognitive function, mice were trained on a radial arm maze. Voxel-wise and volumetric analyses of MRI data uncovered a striking independence of hormonal versus chromosomal influences in 30 sexually dimorphic brain regions. For example, the bed nucleus of the stria terminalis and the parieto-temporal lobe of the cerebral cortex displayed steroid-dependence while the cerebellar cortex, corpus callosum, and olfactory bulbs were influenced by sex chromosomes. Spatial learning and memory demonstrated strict hormone-dependency with no apparent influence of sex chromosomes. Understanding the influences of chromosomes and hormones on brain structure and function is important for understanding sex differences in brain structure and function, an endeavor that has eventual implications for understanding sex biases observed in the prevalence of psychiatric disorders.

  2. How hormones influence composition and physiological function of the brain-blood barrier.

    PubMed

    Hampl, R; Bičíková, M; Sosvorová, L

    2015-01-01

    Hormones exert many actions in the brain. Their access and effects in the brain are regulated by the blood-brain barrier (BBB). Hormones as other substances may enter the brain and vice versa either by paracellular way requiring breaching tight junctions stitching the endothelial cells composing the BBB, or by passage through the cells (transcellular way). Hormones influence both ways through their receptors, both membrane and intracellular, present on/in the BBB. In the review the main examples are outlined how hormones influence the expression and function of proteins forming the tight junctions, as well as how they regulate expression and function of major protein transporters mediating transport of various substances including hormone themselves.

  3. 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

  4. 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

  5. The Influence of Frontal Lobe Tumors and Surgical Treatment on Advanced Cognitive Functions.

    PubMed

    Fang, Shengyu; Wang, Yinyan; Jiang, Tao

    2016-07-01

    Brain cognitive functions affect patient quality of life. The frontal lobe plays a crucial role in advanced cognitive functions, including executive function, meta-cognition, decision-making, memory, emotion, and language. Therefore, frontal tumors can lead to serious cognitive impairments. Currently, neurosurgical treatment is the primary method to treat brain tumors; however, the effects of the surgical treatments are difficult to predict or control. The treatment may both resolve the effects of the tumor to improve cognitive function or cause permanent disabilities resulting from damage to healthy functional brain tissue. Previous studies have focused on the influence of frontal lesions and surgical treatments on patient cognitive function. Here, we review cognitive impairment caused by frontal lobe brain tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Thermodynamic laws apply to brain function.

    PubMed

    Salerian, Alen J

    2010-02-01

    Thermodynamic laws and complex system dynamics govern brain function. Thus, any change in brain homeostasis by an alteration in brain temperature, neurotransmission or content may cause region-specific brain dysfunction. This is the premise for the Salerian Theory of Brain built upon a new paradigm for neuropsychiatric disorders: the governing influence of neuroanatomy, neurophysiology, thermodynamic laws. The principles of region-specific brain function thermodynamics are reviewed. The clinical and supporting evidence including the paradoxical effects of various agents that alter brain homeostasis is demonstrated.

  7. Leptin and the brain: influences on brain development, cognitive functioning and psychiatric disorders.

    PubMed

    Farr, Olivia M; Tsoukas, Michael A; Mantzoros, Christos S

    2015-01-01

    Receptors of leptin, the prototypical adipokine, are expressed throughout the cortex and several other areas of the brain. Although typically studied for its role in energy intake and expenditure, leptin plays a critical role in many other neurocognitive processes and interacts with various other hormones and neurotransmitters to perform these functions. Here, we review the literature on how leptin influences brain development, neural degradation, Alzheimer's disease, psychiatric disorders, and more complicated cognitive functioning and feeding behaviors. We also discuss modulators of leptin and the leptin receptor as they relate to normal cognitive functioning and may mediate some of the actions of leptin in the brain. Although we are beginning to better understand the critical role leptin plays in normal cognitive functioning, there is much to be discovered. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Finding language in the matter of the brain: origins of the clinical aphasia examination.

    PubMed

    Roth, Heidi L

    2002-12-01

    The origins of the aphasia examination can be traced back to the 19th century when physicians and scientists began to understand how higher mental functions such as language could be localized in the brain. Paul Broca, Carl Wernicke, and Hughlings Jackson developed different models of brain function, and each contributed important insights to the study of aphasia. Broca's contributions were influenced by the fundamental question of whether higher mental function could be localized in the brain at all; Wernicke's contributions were influenced by an attempt to unite more mechanistic and physiological principles to a model of higher brain functions; and Jackson's contributions were influenced by British association psychology. In addition to reviewing the origins of the aphasia examination, this article reviews the historical context in which these contributors worked, the factors that affected the reception of their views, and the manner in which their views have affected the aphasia examination and understanding of aphasia today.

  9. More than a drainage fluid: the role of CSF in signaling in the brain and other effects on brain tissue.

    PubMed

    Illes, Sebastian

    2017-01-01

    Current progress in neuroscience demonstrates that the brain is not an isolated organ and is influenced by the systemic environment and extracerebral processes within the body. In view of this new concept, blood and cerebrospinal fluid (CSF) are important body fluids linking extracerebral and intracerebral processes. For decades, substantial evidence has been accumulated indicating that CSF modulates brain states and influences behavior as well as cognition. This chapter provides an overview of how CSF directly modulates the function of different types of brain cells, such as neurons, neural stem cells, and CSF-contacting cells. Alterations in CSF content occur in most pathologic central nervous system (CNS) conditions. In a classic view, the function of CSF is to drain waste products and detrimental factors derived from diseased brain parenchyma. This chapter presents examples for how intra- and extracerebral pathologic processes lead to alterations in the CSF content. Current knowledge about how pathologically altered CSF influences the functionality of brain cells will be presented. Thereby, it becomes evident that CSF has more than a drainage function and has a causal role for the etiology and pathogenesis of different CNS diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Evaluation of the factors influencing brain language laterality in presurgical planning.

    PubMed

    Batouli, Seyed Amir Hossein; Hasani, Nafiseh; Gheisari, Sara; Behzad, Ebrahim; Oghabian, Mohammad Ali

    2016-10-01

    Brain lesions cause functional deficits, and one treatment for this condition is lesion resection. In most cases, presurgical planning (PSP) and the information from laterality indices are necessary for maximum preservation of the critical functions after surgery. Language laterality index (LI) is reliably estimated using functional magnetic resonance imaging (fMRI); however, this measure is under the influence of some external factors. In this study, we investigated the influence of a number of factors on language LI, using data from 120 patients (mean age=35.65 (±13.4) years) who underwent fMRI for PSP. Using two proposed language tasks from our previous works, brain left hemisphere was showed to be dominant for the language function, although a higher LI was obtained using the "Word Generation" task, compared to the "Reverse Word Reading". In addition, decline of LIs with age, and lower LI when the lesion invaded brain language area were observed. Meanwhile, gender, lesion side (affected hemisphere), LI calculation strategy, and fMRI analysis Z-values did not statistically show any influences on the LIs. Although fMRI is widely used to estimate language LI, it is shown here that in order to present a reliable language LI and to correctly select the dominant hemisphere of the brain, the influence of external factors should be carefully considered. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  11. 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

  12. Effects of the diet on brain function

    NASA Technical Reports Server (NTRS)

    Fernstrom, J. D.

    1981-01-01

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

  13. The stomach-brain axis.

    PubMed

    Holtmann, Gerald; Talley, Nicholas J

    2014-12-01

    The stomach has distinct functions in relation to the ingestion and handling of solids and liquids. These functions include storage of the food before it is gradually emptied into the duodenum, mechanical crushing of larger food particles to increase the surface area, secretion of an acidic enzyme rich gastric juice and mixing the ingested food with the gastric juice. In addition, the stomach 'senses' the composition of the gastric content and this information is passed via the vagal nerve to the lateral hypothalamus and the limbic system, most likely as palatability signals that influence eating behaviour. Other sensory qualities related to the stimulation of gastric tension receptors are satiety and fullness. Receptors that respond to macronutrient content or gastric wall tension influence appetite and meal related hormone responses. The ingestion of food - in contrast to an infusion of nutrients into the stomach - has distinct effects on the activation of specific brain regions. Brain areas such as thalamus, amygdala, putamen and praecuneus are activated by the ingestion of food. Gastric nutrient infusion evokes greater activation in the hippocampus and anterior cingulate. The brain integrates these interrelated neural and hormonal signals arising from the stomach as well as visual, olfactory and anticipatory stimuli that ultimately influence eating and other behavioural patterns. Furthermore, there is now good evidence from experimental studies that gastric afferents influence mood, and animal studies point towards the possibility that gastric dysfunction may be a risk factor for mood disorders such as anxiety and depression. The stomach is also not only colonised by Helicobacter pylori but a large array of bacteria. While there is sufficient evidence to suggest that H. pylori may alter caloric intake and mood, the role of other gastric microbiome for the brain function is unknown. To address this appropriate targeted gastric microbiome studies would be required instead of widely utilised opportunistic stool microbiome studies. In summary, it is now well established that there are important links between the brain and the stomach that have significant effects on gastric function. However, the stomach also influences the brain. Disturbances in the crosstalk between the stomach and the brain may manifest as functional GI disorders while disturbances in the stomach-brain communication may also result in an altered regulation of satiety and as a consequence may affect eating behaviour and mood. These observations may enable the identification of novel therapies targeted at the gastroduodenum that positively alter brain function and treat or prevent conditions such as obesity or functional gastrointestinal disorders. Copyright © 2014. Published by Elsevier Ltd.

  14. 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

  15. The Learning Hippocampus: Education and Experience-Dependent Plasticity

    ERIC Educational Resources Information Center

    Wenger, Elisabeth; Lövdén, Martin

    2016-01-01

    The hippocampal formation of the brain plays a crucial role in declarative learning and memory while at the same time being particularly susceptible to environmental influences. Education requires a well-functioning hippocampus, but may also influence the development of this brain structure. Understanding these bidirectional influences may have…

  16. 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.

  17. [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.

  18. A half-truth is a whole lie: on the necessity of investigating sex influences on the brain.

    PubMed

    Cahill, Larry

    2012-06-01

    Sex influences are proving to be extremely widespread on brain function, including the human brain. Ample evidence now proves that the sex of subjects can influence, ever reverse, findings, hence conclusions, at all levels of brain science, down to the molecular level, often in completely unanticipated ways. Thus the still-prominent assumption that sex influences may be safely ignored by neurobiologists is invalid and must be abandoned. The failure to properly consider the issue fills the literature with conclusions tenuous at best, false at worst. The continuing, widespread resistance to investigating sex influences among brain scientists, a resistance largely rooted in deeply entrenched biases against the topic, is becoming increasingly scientifically indefensible and strongly retards progress in our field.

  19. Diet and Gender Influences on Processing and Discrimination of Speech Sounds in 3- and 6-Month-Old Infants: A Developmental ERP Study

    ERIC Educational Resources Information Center

    Pivik, R. T.; Andres, Aline; Badger, Thomas M.

    2011-01-01

    Early post-natal nutrition influences later development, but there are no studies comparing brain function in healthy infants as a function of dietary intake even though the major infant diets differ significantly in nutrient composition. We studied brain responses (event-related potentials; ERPs) to speech sounds for infants who were fed either…

  20. Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis.

    PubMed

    Jenkins, Trisha A; Nguyen, Jason C D; Polglaze, Kate E; Bertrand, Paul P

    2016-01-20

    The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi-directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis.

  1. 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.

  2. Brain imaging in the context of food perception and eating.

    PubMed

    Hollmann, Maurice; Pleger, Burkhard; Villringer, Arno; Horstmann, Annette

    2013-02-01

    Eating behavior depends heavily on brain function. In recent years, brain imaging has proved to be a powerful tool to elucidate brain function and brain structure in the context of eating. In this review, we summarize recent findings in the fast growing body of literature in the field and provide an overview of technical aspects as well as the basic brain mechanisms identified with imaging. Furthermore, we highlight findings linking neural processing of eating-related stimuli with obesity. The consumption of food is based on a complex interplay between homeostatic and hedonic mechanisms. Several hormones influence brain activity to regulate food intake and interact with the brain's reward circuitry, which is partly mediated by dopamine signaling. Additionally, it was shown that food stimuli trigger cognitive control mechanisms that incorporate internal goals into food choice. The brain mechanisms observed in this context are strongly influenced by genetic factors, sex and personality traits. Overall, a complex picture arises from brain-imaging findings, because a multitude of factors influence human food choice. Although several key mechanisms have been identified, there is no comprehensive model that is able to explain the behavioral observations to date. Especially a careful characterization of patients according to genotypes and phenotypes could help to better understand the current and future findings in neuroimaging studies.

  3. 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.

  4. Disrupted resting-state functional architecture of the brain after 45-day simulated microgravity

    PubMed Central

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

    2014-01-01

    Long-term spaceflight induces both physiological and psychological changes in astronauts. To understand the neural mechanisms underlying these physiological and psychological changes, it is critical to investigate the effects of microgravity on the functional architecture of the brain. In this study, we used resting-state functional MRI (rs-fMRI) to study whether the functional architecture of the brain is altered after 45 days of −6° head-down tilt (HDT) bed rest, which is a reliable model for the simulation of microgravity. Sixteen healthy male volunteers underwent rs-fMRI scans before and after 45 days of −6° HDT bed rest. Specifically, we used a commonly employed graph-based measure of network organization, i.e., degree centrality (DC), to perform a full-brain exploration of the regions that were influenced by simulated microgravity. We subsequently examined the functional connectivities of these regions using a seed-based resting-state functional connectivity (RSFC) analysis. We found decreased DC in two regions, the left anterior insula (aINS) and the anterior part of the middle cingulate cortex (MCC; also called the dorsal anterior cingulate cortex in many studies), in the male volunteers after 45 days of −6° HDT bed rest. Furthermore, seed-based RSFC analyses revealed that a functional network anchored in the aINS and MCC was particularly influenced by simulated microgravity. These results provide evidence that simulated microgravity alters the resting-state functional architecture of the brains of males and suggest that the processing of salience information, which is primarily subserved by the aINS–MCC functional network, is particularly influenced by spaceflight. The current findings provide a new perspective for understanding the relationships between microgravity, cognitive function, autonomic neural function, and central neural activity. PMID:24926242

  5. Cerebral Low-Molecular Metabolites Influenced by Intestinal Microbiota: A Pilot Study

    PubMed Central

    Matsumoto, Mitsuharu; Kibe, Ryoko; Ooga, Takushi; Aiba, Yuji; Sawaki, Emiko; Koga, Yasuhiro; Benno, Yoshimi

    2013-01-01

    Recent studies suggest that intestinal microbiota influences gut-brain communication. In this study, we aimed to clarify the influence of intestinal microbiota on cerebral metabolism. We analyzed the cerebral metabolome of germ-free (GF) mice and Ex-GF mice, which were inoculated with suspension of feces obtained from specific pathogen-free mice, using capillary electrophoresis with time-of-flight mass spectrometry (CE-TOFMS). CE-TOFMS identified 196 metabolites from the cerebral metabolome in both GF and Ex-GF mice. The concentrations of 38 metabolites differed significantly (p < 0.05) between GF and Ex-GF mice. Approximately 10 of these metabolites are known to be involved in brain function, whilst the functions of the remainder are unclear. Furthermore, we observed a novel association between cerebral glycolytic metabolism and intestinal microbiota. Our work shows that cerebral metabolites are influenced by normal intestinal microbiota through the microbiota-gut-brain axis, and indicates that normal intestinal microbiota closely connected with brain health and disease, development, attenuation, learning, memory, and behavior. PMID:23630473

  6. Developmental imaging genetics: linking dopamine function to adolescent behavior.

    PubMed

    Padmanabhan, Aarthi; Luna, Beatriz

    2014-08-01

    Adolescence is a period of development characterized by numerous neurobiological changes that significantly influence behavior and brain function. Adolescence is of particular interest due to the alarming statistics indicating that mortality rates increase two to three-fold during this time compared to childhood, due largely to a peak in risk-taking behaviors resulting from increased impulsivity and sensation seeking. Furthermore, there exists large unexplained variability in these behaviors that are in part mediated by biological factors. Recent advances in molecular genetics and functional neuroimaging have provided a unique and exciting opportunity to non-invasively study the influence of genetic factors on brain function in humans. While genes do not code for specific behaviors, they do determine the structure and function of proteins that are essential to the neuronal processes that underlie behavior. Therefore, studying the interaction of genotype with measures of brain function over development could shed light on critical time points when biologically mediated individual differences in complex behaviors emerge. Here we review animal and human literature examining the neurobiological basis of adolescent development related to dopamine neurotransmission. Dopamine is of critical importance because of (1) its role in cognitive and affective behaviors, (2) its role in the pathogenesis of major psychopathology, and (3) the protracted development of dopamine signaling pathways over adolescence. We will then focus on current research examining the role of dopamine-related genes on brain function. We propose the use of imaging genetics to examine the influence of genetically mediated dopamine variability on brain function during adolescence, keeping in mind the limitations of this approach. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. 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.

  8. Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis

    PubMed Central

    Jenkins, Trisha A.; Nguyen, Jason C. D.; Polglaze, Kate E.; Bertrand, Paul P.

    2016-01-01

    The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi-directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis. PMID:26805875

  9. Degree centrality and fractional amplitude of low-frequency oscillations associated with Stroop interference.

    PubMed

    Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Sekiguchi, Atsushi; Hashizume, Hiroshi; Sassa, Yuko; Kotozaki, Yuka; Miyauchi, Carlos Makoto; Yokoyama, Ryoichi; Iizuka, Kunio; Nakagawa, Seishu; Nagase, Tomomi; Kunitoki, Keiko; Kawashima, Ryuta

    2015-10-01

    Stroop paradigms are commonly used as an index of attention deficits and a tool for investigating functions of the frontal lobes and other associated structures. Here we investigated the correlation between resting-state functional magnetic imaging (fMRI) measures [degree centrality (DC)/fractional amplitude of low frequency fluctuations (fALFFs)] and Stroop interference. We examined this relationship in the brains of 958 healthy young adults. DC reflects the number of instantaneous functional connections between a region and the rest of the brain within the entire connectivity matrix of the brain (connectome), and thus how much of the node influences the entire brain areas, while fALFF is an indicator of the intensity of regional brain spontaneous activity. Reduced Stroop interference was associated with larger DC in the left lateral prefrontal cortex, left IFJ, and left inferior parietal lobule as well as larger fALFF in the areas of the dorsal attention network and the precuneus. These findings suggest that Stroop performance is reflected in resting state functional properties of these areas and the network. In addition, default brain activity of the dorsal attention network and precuneus as well as higher cognitive processes represented there, and default stronger global influence of the areas critical in executive functioning underlie better Stroop performance. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Kynurenine pathway metabolism and the microbiota-gut-brain axis.

    PubMed

    Kennedy, P J; Cryan, J F; Dinan, T G; Clarke, G

    2017-01-01

    It has become increasingly clear that the gut microbiota influences not only gastrointestinal physiology but also central nervous system (CNS) function by modulating signalling pathways of the microbiota-gut-brain axis. Understanding the neurobiological mechanisms underpinning the influence exerted by the gut microbiota on brain function and behaviour has become a key research priority. Microbial regulation of tryptophan metabolism has become a focal point in this regard, with dual emphasis on the regulation of serotonin synthesis and the control of kynurenine pathway metabolism. Here, we focus in detail on the latter pathway and begin by outlining the structural and functional dynamics of the gut microbiota and the signalling pathways of the brain-gut axis. We summarise preclinical and clinical investigations demonstrating that the gut microbiota influences CNS physiology, anxiety, depression, social behaviour, cognition and visceral pain. Pertinent studies are drawn from neurogastroenterology demonstrating the importance of tryptophan and its metabolites in CNS and gastrointestinal function. We outline how kynurenine pathway metabolism may be regulated by microbial control of neuroendocrine function and components of the immune system. Finally, preclinical evidence demonstrating direct and indirect mechanisms by which the gut microbiota can regulate tryptophan availability for kynurenine pathway metabolism, with downstream effects on CNS function, is reviewed. Targeting the gut microbiota represents a tractable target to modulate kynurenine pathway metabolism. Efforts to develop this approach will markedly increase our understanding of how the gut microbiota shapes brain and behaviour and provide new insights towards successful translation of microbiota-gut-brain axis research from bench to bedside. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Understanding the broad influence of sex hormones and sex differences in the brain.

    PubMed

    McEwen, Bruce S; Milner, Teresa A

    2017-01-02

    Sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Sex hormones can act through many cellular and molecular processes that alter structure and function of neural systems and influence behavior as well as providing neuroprotection. Within neurons, sex hormone receptors are found in nuclei and are also located near membranes, where they are associated with presynaptic terminals, mitochondria, spine apparatus, and postsynaptic densities. Sex hormone receptors also are found in glial cells. Hormonal regulation of a variety of signaling pathways as well as direct and indirect effects on gene expression induce spine synapses, up- or downregulate and alter the distribution of neurotransmitter receptors, and regulate neuropeptide expression and cholinergic and GABAergic activity as well as calcium sequestration and oxidative stress. Many neural and behavioral functions are affected, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences and responses to sex hormones in brain regions, which influence functions not previously regarded as subject to such differences, indicate that we are entering a new era of our ability to understand and appreciate the diversity of gender-related behaviors and brain functions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Omega-3 fatty acids and brain resistance to ageing and stress: body of evidence and possible mechanisms.

    PubMed

    Denis, I; Potier, B; Vancassel, S; Heberden, C; Lavialle, M

    2013-03-01

    The increasing life expectancy in the populations of rich countries raises the pressing question of how the elderly can maintain their cognitive function. Cognitive decline is characterised by the loss of short-term memory due to a progressive impairment of the underlying brain cell processes. Age-related brain damage has many causes, some of which may be influenced by diet. An optimal diet may therefore be a practical way of delaying the onset of age-related cognitive decline. Nutritional investigations indicate that the ω-3 poyunsaturated fatty acid (PUFA) content of western diets is too low to provide the brain with an optimal supply of docosahexaenoic acid (DHA), the main ω-3 PUFA in cell membranes. Insufficient brain DHA has been associated with memory impairment, emotional disturbances and altered brain processes in rodents. Human studies suggest that an adequate dietary intake of ω-3 PUFA can slow the age-related cognitive decline and may also protect against the risk of senile dementia. However, despite the many studies in this domain, the beneficial impact of ω-3 PUFA on brain function has only recently been linked to specific mechanisms. This review examines the hypothesis that an optimal brain DHA status, conferred by an adequate ω-3 PUFA intake, limits age-related brain damage by optimizing endogenous brain repair mechanisms. Our analysis of the abundant literature indicates that an adequate amount of DHA in the brain may limit the impact of stress, an important age-aggravating factor, and influences the neuronal and astroglial functions that govern and protect synaptic transmission. This transmission, particularly glutamatergic neurotransmission in the hippocampus, underlies memory formation. The brain DHA status also influences neurogenesis, nested in the hippocampus, which helps maintain cognitive function throughout life. Although there are still gaps in our knowledge of the way ω-3 PUFA act, the mechanistic studies reviewed here indicate that ω-3 PUFA may be a promising tool for preventing age-related brain deterioration. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    PubMed

    Yan, Chaogan; He, Yong

    2011-01-01

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

  14. 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

  15. Effects of mechanical ventilation on gene expression profiles in renal allografts from brain dead rats.

    PubMed

    Hottenrott, Maximilia C; Krebs, Joerg; Pelosi, Paolo; Luecke, Thomas; Rocco, Patricia R M; Sticht, Carsten; Breedijk, Annette; Yard, Benito; Tsagogiorgas, Charalambos

    2017-12-01

    Pathophysiological changes of brain death (BD) are impairing distal organ function and harming potential renal allografts. Whether ventilation strategies influence the quality of renal allografts from BD donors has not been thoroughly studied. 28 adult male Wistar rats were randomly assigned to four groups: 1) no brain death (NBD) with low tidal volume/low positive endexpiratory pressure (PEEP) titrated to minimal static elastance of the respiratory system (LVT/OLPEEP); 2) NBD with high tidal volume/low PEEP (HVT/LPEEP); 3) brain death (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP. We hypothesized that HVT/LPEEP in BD leads to increased interleukin 6 (IL-6) gene expression and impairs potential renal allografts after six hours of mechanical ventilation. We assessed inflammatory cytokines in serum, genome wide gene expression profiles and quantitative PCR (qPCR) in kidney tissue. The influence of BD on renal gene-expression profiles was greater than the influence of the ventilation strategy. In BD, LVT ventilation did not influence the inflammatory parameters or kidney function in our experimental model. Copyright © 2017. Published by Elsevier B.V.

  16. Experience-Dependent Neural Plasticity in the Adult Damaged Brain

    ERIC Educational Resources Information Center

    Kerr, Abigail L.; Cheng, Shao-Ying; Jones, Theresa A.

    2011-01-01

    Behavioral experience is at work modifying the structure and function of the brain throughout the lifespan, but it has a particularly dramatic influence after brain injury. This review summarizes recent findings on the role of experience in reorganizing the adult damaged brain, with a focus on findings from rodent stroke models of chronic upper…

  17. Epilepsy, behavior, and art (Epilepsy, Brain, and Mind, part 1).

    PubMed

    Rektor, Ivan; Schachter, Steven C; Arzy, Shahar; Baloyannis, Stavros J; Bazil, Carl; Brázdil, Milan; Engel, Jerome; Helmstaedter, Gerhard; Hesdorffer, Dale C; Jones-Gotman, Marilyn; Kesner, Ladislav; Komárek, Vladimír; Krämer, Günter; Leppik, Ilo E; Mann, Michael W; Mula, Marco; Risse, Gail L; Stoker, Guy W; Kasteleijn-Nolst Trenité, Dorothée G A; Trimble, Michael; Tyrliková, Ivana; Korczyn, Amos D

    2013-08-01

    Epilepsy is both a disease of the brain and the mind. Brain diseases, structural and/or functional, underlie the appearance of epilepsy, but the notion of epilepsy is larger and cannot be reduced exclusively to the brain. We can therefore look at epilepsy from two angles. The first perspective is intrinsic: the etiology and pathophysiology, problems of therapy, impact on the brain networks, and the "mind" aspects of brain functions - cognitive, emotional, and affective. The second perspective is extrinsic: the social interactions of the person with epilepsy, the influence of the surrounding environment, and the influences of epilepsy on society. All these aspects reaching far beyond the pure biological nature of epilepsy have been the topics of two International Congresses of Epilepsy, Brain, and Mind that were held in Prague, Czech Republic, in 2010 and 2012 (the third Congress will be held in Brno, Czech Republic on April 3-5, 2014; www.epilepsy-brain-mind2014.eu). Here, we present the first of two papers with extended summaries of selected presentations of the 2012 Congress that focused on epilepsy, behavior, and art. Copyright © 2013. Published by Elsevier Inc.

  18. 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

  19. Turner Syndrome: Neuroimaging Findings--Structural and Functional

    ERIC Educational Resources Information Center

    Mullaney, Ronan; Murphy, Declan

    2009-01-01

    Neuroimaging studies of Turner syndrome can advance our understanding of the X chromosome in brain development, and the modulatory influence of endocrine factors. There is increasing evidence from neuroimaging studies that TX individuals have significant differences in the anatomy, function, and metabolism of a number of brain regions; including…

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

    PubMed

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

    2009-05-01

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

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

    PubMed

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

    2016-01-01

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

  2. The independent influences of age and education on functional brain networks and cognition in healthy older adults.

    PubMed

    Perry, Alistair; Wen, Wei; Kochan, Nicole A; Thalamuthu, Anbupalam; Sachdev, Perminder S; Breakspear, Michael

    2017-10-01

    Healthy aging is accompanied by a constellation of changes in cognitive processes and alterations in functional brain networks. The relationships between brain networks and cognition during aging in later life are moderated by demographic and environmental factors, such as prior education, in a poorly understood manner. Using multivariate analyses, we identified three latent patterns (or modes) linking resting-state functional connectivity to demographic and cognitive measures in 101 cognitively normal elders. The first mode (P = 0.00043) captures an opposing association between age and core cognitive processes such as attention and processing speed on functional connectivity patterns. The functional subnetwork expressed by this mode links bilateral sensorimotor and visual regions through key areas such as the parietal operculum. A strong, independent association between years of education and functional connectivity loads onto a second mode (P = 0.012), characterized by the involvement of key hub regions. A third mode (P = 0.041) captures weak, residual brain-behavior relations. Our findings suggest that circuits supporting lower level cognitive processes are most sensitive to the influence of age in healthy older adults. Education, and to a lesser extent, executive functions, load independently onto functional networks-suggesting that the moderating effect of education acts upon networks distinct from those vulnerable with aging. This has important implications in understanding the contribution of education to cognitive reserve during healthy aging. Hum Brain Mapp 38:5094-5114, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits

    PubMed Central

    Niwa, Minae; Kamiya, Atsushi; Murai, Rina; Kubo, Ken-ichiro; Gruber, Aaron J; Tomita, Kenji; Lu, Lingling; Tomisato, Shuta; Jaaro-Peled, Hanna; Seshadri, Saurav; Hiyama, Hideki; Huang, Beverly; Kohda, Kazuhisa; Noda, Yukihiro; O’Donnell, Patricio; Nakajima, Kazunori; Sawa, Akira; Nabeshima, Toshitaka

    2011-01-01

    SUMMARY Adult brain function and behavior are influenced by neuronal network formation during development. Genetic susceptibility factors for adult psychiatric illnesses, such as Neuregulin-1 and Disrupted-in-Schizophrenia-1 (DISC1), influence adult high brain functions, including cognition and information processing. These factors have roles during neurodevelopment and are likely to cooperate, forming “pathways” or “signalosomes.” Here we report the potential to generate an animal model via in utero gene transfer in order to address an important question of how nonlethal deficits in early development may affect postnatal brain maturation and high brain functions in adulthood, which are impaired in various psychiatric illnesses, such as schizophrenia. We show that transient knockdown of DISC1 in the pre- and peri-natal stages, specifically in a lineage of pyramidal neurons mainly in the prefrontal cortex, leads to selective abnormalities in postnatal mesocortical dopaminergic maturation and behavioral abnormalities associated with disturbed cortical neurocircuitry after puberty. PMID:20188653

  4. Functional organization of intrinsic connectivity networks in Chinese-chess experts.

    PubMed

    Duan, Xujun; Long, Zhiliang; Chen, Huafu; Liang, Dongmei; Qiu, Lihua; Huang, Xiaoqi; Liu, Timon Cheng-Yi; Gong, Qiyong

    2014-04-16

    The functional architecture of the human brain has been extensively described in terms of functional connectivity networks, detected from the low-frequency coherent neuronal fluctuations during a resting state condition. Accumulating evidence suggests that the overall organization of functional connectivity networks is associated with individual differences in cognitive performance and prior experience. Such an association raises the question of how cognitive expertise exerts an influence on the topological properties of large-scale functional networks. To address this question, we examined the overall organization of brain functional networks in 20 grandmaster and master level Chinese-chess players (GM/M) and twenty novice players, by means of resting-state functional connectivity and graph theoretical analyses. We found that, relative to novices, functional connectivity was increased in GM/Ms between basal ganglia, thalamus, hippocampus, and several parietal and temporal areas, suggesting the influence of cognitive expertise on intrinsic connectivity networks associated with learning and memory. Furthermore, we observed economical small-world topology in the whole-brain functional connectivity networks in both groups, but GM/Ms exhibited significantly increased values of normalized clustering coefficient which resulted in increased small-world topology. These findings suggest an association between the functional organization of brain networks and individual differences in cognitive expertise, which might provide further evidence of the mechanisms underlying expert behavior. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    ERIC Educational Resources Information Center

    Belsky, Jay; de Haan, Michelle

    2011-01-01

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

  6. Midsagittal Brain Shape Correlation with Intelligence and Cognitive Performance

    ERIC Educational Resources Information Center

    Bruner, Emiliano; Martin-Loeches, Manuel; Burgaleta, Miguel; Colom, Roberto

    2011-01-01

    Brain shape might influence cognitive performance because of the relationships between functions, spatial organization, and differential volumetric development of cortical areas. Here we analyze the relationships between midsagittal brain shape variation and a set of basic psychological measures. Coordinates in 2D from 102 MRI-scanned young adult…

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

    PubMed

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

    2018-04-28

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

  8. Lack of sex effect on brain activity during a visuomotor response task: functional MR imaging study.

    PubMed

    Mikhelashvili-Browner, Nina; Yousem, David M; Wu, Colin; Kraut, Michael A; Vaughan, Christina L; Oguz, Kader Karli; Calhoun, Vince D

    2003-03-01

    As more individuals are enrolled in clinical functional MR imaging (fMRI) studies, an understanding of how sex may influence fMRI-measured brain activation is critical. We used fixed- and random-effects models to study the influence of sex on fMRI patterns of brain activation during a simple visuomotor reaction time task in the group of 26 age-matched men and women. We evaluated the right visual, left visual, left primary motor, left supplementary motor, and left anterior cingulate areas. Volumes of activations did not significantly differ between the groups in any defined regions. Analysis of variance failed to show any significant correlations between sex and volumes of brain activation in any location studied. Mean percentage signal-intensity changes for all locations were similar between men and women. A two-way t test of brain activation in men and women, performed as a part of random-effects modeling, showed no significant difference at any site. Our results suggest that sex seems to have little influence on fMRI brain activation when we compared performance on the simple reaction-time task. The need to control for sex effects is not critical in the analysis of this task with fMRI.

  9. Prolonged fasting impairs neural reactivity to visual stimulation.

    PubMed

    Kohn, N; Wassenberg, A; Toygar, T; Kellermann, T; Weidenfeld, C; Berthold-Losleben, M; Chechko, N; Orfanos, S; Vocke, S; Laoutidis, Z G; Schneider, F; Karges, W; Habel, U

    2016-01-01

    Previous literature has shown that hypoglycemia influences the intensity of the BOLD signal. A similar but smaller effect may also be elicited by low normal blood glucose levels in healthy individuals. This may not only confound the BOLD signal measured in fMRI, but also more generally interact with cognitive processing, and thus indirectly influence fMRI results. Here we show in a placebo-controlled, crossover, double-blind study on 40 healthy subjects, that overnight fasting and low normal levels of glucose contrasted to an activated, elevated glucose condition have an impact on brain activation during basal visual stimulation. Additionally, functional connectivity of the visual cortex shows a strengthened association with higher-order attention-related brain areas in an elevated blood glucose condition compared to the fasting condition. In a fasting state visual brain areas show stronger coupling to the inferior temporal gyrus. Results demonstrate that prolonged overnight fasting leads to a diminished BOLD signal in higher-order occipital processing areas when compared to an elevated blood glucose condition. Additionally, functional connectivity patterns underscore the modulatory influence of fasting on visual brain networks. Patterns of brain activation and functional connectivity associated with a broad range of attentional processes are affected by maturation and aging and associated with psychiatric disease and intoxication. Thus, we conclude that prolonged fasting may decrease fMRI design sensitivity in any task involving attentional processes when fasting status or blood glucose is not controlled.

  10. Genetic influences on individual differences in longitudinal changes in global and subcortical brain volumes: Results of the ENIGMA plasticity working group.

    PubMed

    Brouwer, Rachel M; Panizzon, Matthew S; Glahn, David C; Hibar, Derrek P; Hua, Xue; Jahanshad, Neda; Abramovic, Lucija; de Zubicaray, Greig I; Franz, Carol E; Hansell, Narelle K; Hickie, Ian B; Koenis, Marinka M G; Martin, Nicholas G; Mather, Karen A; McMahon, Katie L; Schnack, Hugo G; Strike, Lachlan T; Swagerman, Suzanne C; Thalamuthu, Anbupalam; Wen, Wei; Gilmore, John H; Gogtay, Nitin; Kahn, René S; Sachdev, Perminder S; Wright, Margaret J; Boomsma, Dorret I; Kremen, William S; Thompson, Paul M; Hulshoff Pol, Hilleke E

    2017-09-01

    Structural brain changes that occur during development and ageing are related to mental health and general cognitive functioning. Individuals differ in the extent to which their brain volumes change over time, but whether these differences can be attributed to differences in their genotypes has not been widely studied. Here we estimate heritability (h 2 ) of changes in global and subcortical brain volumes in five longitudinal twin cohorts from across the world and in different stages of the lifespan (N = 861). Heritability estimates of brain changes were significant and ranged from 16% (caudate) to 42% (cerebellar gray matter) for all global and most subcortical volumes (with the exception of thalamus and pallidum). Heritability estimates of change rates were generally higher in adults than in children suggesting an increasing influence of genetic factors explaining individual differences in brain structural changes with age. In children, environmental influences in part explained individual differences in developmental changes in brain structure. Multivariate genetic modeling showed that genetic influences of change rates and baseline volume significantly overlapped for many structures. The genetic influences explaining individual differences in the change rate for cerebellum, cerebellar gray matter and lateral ventricles were independent of the genetic influences explaining differences in their baseline volumes. These results imply the existence of genetic variants that are specific for brain plasticity, rather than brain volume itself. Identifying these genes may increase our understanding of brain development and ageing and possibly have implications for diseases that are characterized by deviant developmental trajectories of brain structure. Hum Brain Mapp 38:4444-4458, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. A centric/non-centric impact protocol and finite element model methodology for the evaluation of American football helmets to evaluate risk of concussion.

    PubMed

    Post, Andrew; Oeur, Anna; Walsh, Evan; Hoshizaki, Blaine; Gilchrist, Michael D

    2014-01-01

    American football reports high incidences of head injuries, in particular, concussion. Research has described concussion as primarily a rotation dominant injury affecting the diffuse areas of brain tissue. Current standards do not measure how helmets manage rotational acceleration or how acceleration loading curves influence brain deformation from an impact and thus are missing important information in terms of how concussions occur. The purpose of this study was to investigate a proposed three-dimensional impact protocol for use in evaluating football helmets. The dynamic responses resulting from centric and non-centric impact conditions were examined to ascertain the influence they have on brain deformations in different functional regions of the brain that are linked to concussive symptoms. A centric and non-centric protocol was used to impact an American football helmet; the resulting dynamic response data was used in conjunction with a three-dimensional finite element analysis of the human brain to calculate brain tissue deformation. The direction of impact created unique loading conditions, resulting in peaks in different regions of the brain associated with concussive symptoms. The linear and rotational accelerations were not predictive of the brain deformation metrics used in this study. In conclusion, the test protocol used in this study revealed that impact conditions influences the region of loading in functional regions of brain tissue that are associated with the symptoms of concussion. The protocol also demonstrated that using brain deformation metrics may be more appropriate when evaluating risk of concussion than using dynamic response data alone.

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

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

    Welzel, Grit; Fleckenstein, Katharina; Department of Radiation Oncology, Duke University Medical Center, Durham, NC

    2008-12-01

    Purpose: To prospectively compare the effect of prophylactic and therapeutic whole brain radiotherapy (WBRT) on memory function in patients with and without brain metastases. Methods and Materials: Adult patients with and without brain metastases (n = 44) were prospectively evaluated with serial cognitive testing, before RT (T0), after starting RT (T1), at the end of RT (T2), and 6-8 weeks (T3) after RT completion. Data were obtained from small-cell lung cancer patients treated with prophylactic cranial irradiation, patients with brain metastases treated with therapeutic cranial irradiation (TCI), and breast cancer patients treated with RT to the breast. Results: Before therapy,more » prophylactic cranial irradiation patients performed worse than TCI patients or than controls on most test scores. During and after WBRT, verbal memory function was influenced by pretreatment cognitive status (p < 0.001) and to a lesser extent by WBRT. Acute (T1) radiation effects on verbal memory function were only observed in TCI patients (p = 0.031). Subacute (T3) radiation effects on verbal memory function were observed in both TCI and prophylactic cranial irradiation patients (p = 0.006). These effects were more pronounced in patients with above-average performance at baseline. Visual memory and attention were not influenced by WBRT. Conclusions: The results of our study have shown that WBRT causes cognitive dysfunction immediately after the beginning of RT in patients with brain metastases only. At 6-8 weeks after the end of WBRT, cognitive dysfunction was seen in patients with and without brain metastases. Because cognitive dysfunction after WBRT is restricted to verbal memory, patients should not avoid WBRT because of a fear of neurocognitive side effects.« less

  13. Gait and Glasgow Coma Scale scores can predict functional recovery in patients with traumatic brain injury☆

    PubMed Central

    Bilgin, Sevil; Guclu-Gunduz, Arzu; Oruckaptan, Hakan; Kose, Nezire; Celik, Bülent

    2012-01-01

    Fifty-one patients with mild (n = 14), moderate (n = 10) and severe traumatic brain injury (n = 27) received early rehabilitation. Level of consciousness was evaluated using the Glasgow Coma Score. Functional level was determined using the Glasgow Outcome Score, whilst mobility was evaluated using the Mobility Scale for Acute Stroke. Activities of daily living were assessed using the Barthel Index. Following Bobath neurodevelopmental therapy, the level of consciousness was significantly improved in patients with moderate and severe traumatic brain injury, but was not greatly influenced in patients with mild traumatic brain injury. Mobility and functional level were significantly improved in patients with mild, moderate and severe traumatic brain injury. Gait recovery was more obvious in patients with mild traumatic brain injury than in patients with moderate and severe traumatic brain injury. Activities of daily living showed an improvement but this was insignificant except for patients with severe traumatic brain injury. Nevertheless, complete recovery was not acquired at discharge. Multiple regression analysis showed that gait and Glasgow Coma Scale scores can be considered predictors of functional outcomes following traumatic brain injury. PMID:25624828

  14. Testosterone affects language areas of the adult human brain.

    PubMed

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

    2016-05-01

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

  15. [Influence of factors on independence of patients after stroke in early rehabilitation stage].

    PubMed

    Petruseviciene, Daiva; Krisciūnas, Aleksandras

    2005-01-01

    Brain stroke is the main cause of disability starting from age of 40 years. Due to this disability, a person loses his ability to work because of long-lasting disorders of biosocial functions. According to literature, occupational therapy for such patients, taking regard to their social, cultural and economic background, significantly increases their self-care and independence and helps to educate working skills. OBJECTIVE. To evaluate conditional disorders of patients with stroke under rehabilitation and to establish the influence of extent of brain damage, localization, age and gender on effectiveness of occupational therapy. Study included 47 men and 53 women diagnosed with brain ischemia or hemorrhage (ischemic or hemorrhagic stroke). Out of them, 30 were of working age (18-59 years old) and 70 of non-working age (more than 60 years old). The mean age was 63.4+/-1.2 years. In order to assess the functional status of patients, they were tested using the Functional Independence Measure (FIM). At the start of rehabilitation, the mean FIM score was 47.4+/-16.1 (48.9+/-15.6 for men and 46.3+/-16.6 for women, p>0.05). At the end of early rehabilitation, the mean FIM score reached up to 89.9+/-22.3 (94.7+/-18.9 for men and 85.7+/-24.3 for women, p<0.05). Evaluation of functional status showed that at the start of rehabilitation functional status was worse in women than men, nevertheless, women's functional status improved during rehabilitation, though the difference between men and women still remained. Occupational therapy was less effective for patients who suffered from hemiplegia than for patients with hemiparesis (p<0.01). Older patients (more than 60 years) had more expressed functional disorders, and worse functional recovery comparing with younger, working age patients (18-59 years old). Evaluation of occupational therapy effectiveness at the end of early rehabilitation showed that extent of brain damage influences independence of patients suffering from brain stroke (p<0.01).

  16. The Neural Basis of Social Influence in a Dictator Decision.

    PubMed

    Wei, Zhenyu; Zhao, Zhiying; Zheng, Yong

    2017-01-01

    Humans tend to reduce inequitable distributions. Previous neuroimaging studies have shown that inequitable decisions are related to brain regions that associated with negative emotion and signaling conflict. In the highly complex human social environment, our opinions and behaviors can be affected by social information. In current study, we used a modified dictator game to investigate the effect of social influence on making an equitable decision. We found that the choices of participants in present task was influenced by the choices of peers. However, participants' decisions were influenced by equitable rather than inequitable group choices. fMRI results showed that brain regions that related to norm violation and social conflict were related to the inequitable social influence. The neural responses in the dorsomedial prefrontal cortex, rostral cingulate zone, and insula predicted subsequent conforming behavior in individuals. Additionally, psychophysiological interaction analysis revealed that the interconnectivity between the dorsal striatum and insula was elevated in advantageous inequity influence versus no-social influence conditions. We found decreased functional connectivity between the medial prefrontal cortex and insula, supplementary motor area, posterior cingulate gyrus and dorsal anterior cingulate cortex in the disadvantageous inequity influence versus no-social influence conditions. This suggests that a disadvantageous inequity influence may decrease the functional connectivity among brain regions that are related to reward processes. Thus, the neural mechanisms underlying social influence in an equitable decision may be similar to those implicated in social norms and reward processing.

  17. Application and validation of the barrow neurological institute screen for higher cerebral functions in a control population and in patient groups commonly seen in neurorehabilitation.

    PubMed

    Hofgren, Caisa; Esbjörnsson, Eva; Aniansson, Hans; Sunnerhagen, Katharina Stibrant

    2007-09-01

    To determine whether the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) can differentiate brain-dysfunctional patients from controls. A case-control study. A total of 92 controls and 120 patients from a neuro-rehabilitation clinic with a diagnosis of: right and left hemisphere stroke, traumatic brain injury, Parkinson's disease or anoxic brain damage. The BNIS has a maximum total score of 50 points, < 47 indicates cognitive dysfunction. Group comparisons and exploration of variables influencing the BNIS total score were made. A significant difference was found between the control group and the total patient group for the BNIS total score and for the subscales (p < 0.0005). Sensitivity was 88% and specificity 78%. Presence of disease and educational level had the greatest influence on the results of the BNIS. Patients with Parkinson's disease were shown to be the least cognitively affected and those with anoxic brain damage the most affected. The BNIS has potential value as a screening instrument for cognitive functions and is sufficiently sensitive to differentiate brain-dysfunctional patients from a control population. It appears to be applicable in a neurological rehabilitation setting, and can be used early in the process, giving a baseline cognitive functional level.

  18. Observed Measures of Negative Parenting Predict Brain Development during Adolescence.

    PubMed

    Whittle, Sarah; Vijayakumar, Nandita; Dennison, Meg; Schwartz, Orli; Simmons, Julian G; Sheeber, Lisa; Allen, Nicholas B

    2016-01-01

    Limited attention has been directed toward the influence of non-abusive parenting behaviour on brain structure in adolescents. It has been suggested that environmental influences during this period are likely to impact the way that the brain develops over time. The aim of this study was to investigate the association between aggressive and positive parenting behaviors on brain development from early to late adolescence, and in turn, psychological and academic functioning during late adolescence, using a multi-wave longitudinal design. Three hundred and sixty seven magnetic resonance imaging (MRI) scans were obtained over three time points from 166 adolescents (11-20 years). At the first time point, observed measures of maternal aggressive and positive behaviors were obtained. At the final time point, measures of psychological and academic functioning were obtained. Results indicated that a higher frequency of maternal aggressive behavior was associated with alterations in the development of right superior frontal and lateral parietal cortical thickness, and of nucleus accumbens volume, in males. Development of the superior frontal cortex in males mediated the relationship between maternal aggressive behaviour and measures of late adolescent functioning. We suggest that our results support an association between negative parenting and adolescent functioning, which may be mediated by immature or delayed brain maturation.

  19. Observed Measures of Negative Parenting Predict Brain Development during Adolescence

    PubMed Central

    Whittle, Sarah; Vijayakumar, Nandita; Dennison, Meg; Schwartz, Orli; Simmons, Julian G.; Sheeber, Lisa; Allen, Nicholas B.

    2016-01-01

    Limited attention has been directed toward the influence of non-abusive parenting behaviour on brain structure in adolescents. It has been suggested that environmental influences during this period are likely to impact the way that the brain develops over time. The aim of this study was to investigate the association between aggressive and positive parenting behaviors on brain development from early to late adolescence, and in turn, psychological and academic functioning during late adolescence, using a multi-wave longitudinal design. Three hundred and sixty seven magnetic resonance imaging (MRI) scans were obtained over three time points from 166 adolescents (11–20 years). At the first time point, observed measures of maternal aggressive and positive behaviors were obtained. At the final time point, measures of psychological and academic functioning were obtained. Results indicated that a higher frequency of maternal aggressive behavior was associated with alterations in the development of right superior frontal and lateral parietal cortical thickness, and of nucleus accumbens volume, in males. Development of the superior frontal cortex in males mediated the relationship between maternal aggressive behaviour and measures of late adolescent functioning. We suggest that our results support an association between negative parenting and adolescent functioning, which may be mediated by immature or delayed brain maturation. PMID:26824348

  20. Motor programme activating therapy influences adaptive brain functions in multiple sclerosis: clinical and MRI study.

    PubMed

    Rasova, Kamila; Prochazkova, Marie; Tintera, Jaroslav; Ibrahim, Ibrahim; Zimova, Denisa; Stetkarova, Ivana

    2015-03-01

    There is still little scientific evidence for the efficacy of neurofacilitation approaches and their possible influence on brain plasticity and adaptability. In this study, the outcome of a new kind of neurofacilitation approach, motor programme activating therapy (MPAT), was evaluated on the basis of a set of clinical functions and with MRI. Eighteen patients were examined four times with standardized clinical tests and diffusion tensor imaging to monitor changes without therapy, immediately after therapy and 1 month after therapy. Moreover, the strength of effective connectivity was analysed before and after therapy. Patients underwent a 1-h session of MPAT twice a week for 2 months. The data were analysed by nonparametric tests of association and were subsequently statistically evaluated. The therapy led to significant improvement in clinical functions, significant increment of fractional anisotropy and significant decrement of mean diffusivity, and decrement of effective connectivity at supplementary motor areas was observed immediately after the therapy. Changes in clinical functions and diffusion tensor images persisted 1 month after completing the programme. No statistically significant changes in clinical functions and no differences in MRI-diffusion tensor images were observed without physiotherapy. Positive immediate and long-term effects of MPAT on clinical and brain functions, as well as brain microstructure, were confirmed.

  1. The influence of intravenous laser irradiation of blood on some metabolic and functional parameters in intact rabbits and experimental cerebral ischaemia

    NASA Astrophysics Data System (ADS)

    Nechipurenko, N.; Vasilevskaya, L.; Musienko, J.; Maslova, G.

    2007-07-01

    It has been studied the intravenous laser irradiation of blood (ILIB) influence with helium-neon laser (HNL) of 630 nm wavelength on some of lipid peroxidation (LPO) and antioxidant system (AOS) findings, aside-base status (ABS) and blood oxygen transport (BOT), state of dermal microhaemodynamics (MGD) in the intact rabbits and after modeling of local ischemia of brain (LIB). Depending on conditions of organism functioning (norm or brain ischaemia) ILIB has resulted in stimulating or normalizing effects on the whole metabolic and microhaemocirculation processes which had been studied during our investigation. It is discussed the mechanisms of pathogenetic directivity of ILIB influence in cerebral ischaemia

  2. Dependency Network Analysis (DEPNA) Reveals Context Related Influence of Brain Network Nodes

    PubMed Central

    Jacob, Yael; Winetraub, Yonatan; Raz, Gal; Ben-Simon, Eti; Okon-Singer, Hadas; Rosenberg-Katz, Keren; Hendler, Talma; Ben-Jacob, Eshel

    2016-01-01

    Communication between and within brain regions is essential for information processing within functional networks. The current methods to determine the influence of one region on another are either based on temporal resolution, or require a predefined model for the connectivity direction. However these requirements are not always achieved, especially in fMRI studies, which have poor temporal resolution. We thus propose a new graph theory approach that focuses on the correlation influence between selected brain regions, entitled Dependency Network Analysis (DEPNA). Partial correlations are used to quantify the level of influence of each node during task performance. As a proof of concept, we conducted the DEPNA on simulated datasets and on two empirical motor and working memory fMRI tasks. The simulations revealed that the DEPNA correctly captures the network’s hierarchy of influence. Applying DEPNA to the functional tasks reveals the dynamics between specific nodes as would be expected from prior knowledge. To conclude, we demonstrate that DEPNA can capture the most influencing nodes in the network, as they emerge during specific cognitive processes. This ability opens a new horizon for example in delineating critical nodes for specific clinical interventions. PMID:27271458

  3. Altered Whole-Brain and Network-Based Functional Connectivity in Parkinson's Disease.

    PubMed

    de Schipper, Laura J; Hafkemeijer, Anne; van der Grond, Jeroen; Marinus, Johan; Henselmans, Johanna M L; van Hilten, Jacobus J

    2018-01-01

    Background: Functional imaging methods, such as resting-state functional magnetic resonance imaging, reflect changes in neural connectivity and may help to assess the widespread consequences of disease-specific network changes in Parkinson's disease. In this study we used a relatively new graph analysis approach in functional imaging: eigenvector centrality mapping. This model-free method, applied to all voxels in the brain, identifies prominent regions in the brain network hierarchy and detects localized differences between patient populations. In other neurological disorders, eigenvector centrality mapping has been linked to changes in functional connectivity in certain nodes of brain networks. Objectives: Examining changes in functional brain connectivity architecture on a whole brain and network level in patients with Parkinson's disease. Methods: Whole brain resting-state functional architecture was studied with a recently introduced graph analysis approach (eigenvector centrality mapping). Functional connectivity was further investigated in relation to eight known resting-state networks. Cross-sectional analyses included group comparison of functional connectivity measures of Parkinson's disease patients ( n = 107) with control subjects ( n = 58) and correlations with clinical data, including motor and cognitive impairment and a composite measure of predominantly non-dopaminergic symptoms. Results: Eigenvector centrality mapping revealed that frontoparietal regions were more prominent in the whole-brain network function in patients compared to control subjects, while frontal and occipital brain areas were less prominent in patients. Using standard resting-state networks, we found predominantly increased functional connectivity, namely within sensorimotor system and visual networks in patients. Regional group differences in functional connectivity of both techniques between patients and control subjects partly overlapped for highly connected posterior brain regions, in particular in the posterior cingulate cortex and precuneus. Clinico-functional imaging relations were not found. Conclusions: Changes on the level of functional brain connectivity architecture might provide a different perspective of pathological consequences of Parkinson's disease. The involvement of specific, highly connected (hub) brain regions may influence whole brain functional network architecture in Parkinson's disease.

  4. Studying variability in human brain aging in a population-based German cohort-rationale and design of 1000BRAINS.

    PubMed

    Caspers, Svenja; Moebus, Susanne; Lux, Silke; Pundt, Noreen; Schütz, Holger; Mühleisen, Thomas W; Gras, Vincent; Eickhoff, Simon B; Romanzetti, Sandro; Stöcker, Tony; Stirnberg, Rüdiger; Kirlangic, Mehmet E; Minnerop, Martina; Pieperhoff, Peter; Mödder, Ulrich; Das, Samir; Evans, Alan C; Jöckel, Karl-Heinz; Erbel, Raimund; Cichon, Sven; Nöthen, Markus M; Sturma, Dieter; Bauer, Andreas; Jon Shah, N; Zilles, Karl; Amunts, Katrin

    2014-01-01

    The ongoing 1000 brains study (1000BRAINS) is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR) Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45-75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions and language; examination of motor skills; ratings of personality, life quality, mood and daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3 Tesla) of the brain. The latter includes (i) 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii) three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fiber tracking and for diffusion kurtosis imaging; (iii) resting-state and task-based functional MRI; and (iv) fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i) comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii) identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates.

  5. 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.

  6. From structure to function, via dynamics

    NASA Astrophysics Data System (ADS)

    Stetter, O.; Soriano, J.; Geisel, T.; Battaglia, D.

    2013-01-01

    Neurons in the brain are wired into a synaptic network that spans multiple scales, from local circuits within cortical columns to fiber tracts interconnecting distant areas. However, brain function require the dynamic control of inter-circuit interactions on time-scales faster than synaptic changes. In particular, strength and direction of causal influences between neural populations (described by the so-called directed functional connectivity) must be reconfigurable even when the underlying structural connectivity is fixed. Such directed functional influences can be quantified resorting to causal analysis of time-series based on tools like Granger Causality or Transfer Entropy. The ability to quickly reorganize inter-areal interactions is a chief requirement for performance in a changing natural environment. But how can manifold functional networks stem "on demand" from an essentially fixed structure? We explore the hypothesis that the self-organization of neuronal synchronous activity underlies the control of brain functional connectivity. Based on simulated and real recordings of critical neuronal cultures in vitro, as well as on mean-field and spiking network models of interacting brain areas, we have found that "function follows dynamics", rather than structure. Different dynamic states of a same structural network, characterized by different synchronization properties, are indeed associated to different functional digraphs (functional multiplicity). We also highlight the crucial role of dynamics in establishing a structure-to-function link, by showing that whenever different structural topologies lead to similar dynamical states, than the associated functional connectivities are also very similar (structural degeneracy).

  7. Iron and Mechanisms of Emotional Behavior

    PubMed Central

    Kim, Jonghan; Wessling-Resnick, Marianne

    2014-01-01

    Iron is required for appropriate behavioral organization. Iron deficiency results in poor brain myelination and impaired monoamine metabolism. Glutamate and GABA homeostasis is modified by changes in brain iron status. Such changes not only produce deficits in memory/learning capacity and motor skills, but also emotional and psychological problems. An accumulating body of evidence indicates that both energy metabolism and neurotransmitter homeostasis influence emotional behavior, and both functions are influenced by brain iron status. Like other neurobehavioral aspects, the influence of iron metabolism on mechanisms of emotional behavior are multifactorial: brain region-specific control of behavior, regulation of neurotransmitters and associated proteins, temporal and regional differences in iron requirements, oxidative stress responses to excess iron, sex differences in metabolism, and interactions between iron and other metals. To better understand the role that brain iron plays in emotional behavior and mental health, this review discusses the pathologies associated with anxiety and other emotional disorders with respect to body iron status. PMID:25154570

  8. Does Aerobic Exercise Influence Intrinsic Brain Activity? An Aerobic Exercise Intervention among Healthy Old Adults

    PubMed Central

    Flodin, Pär; Jonasson, Lars S.; Riklund, Katrin; Nyberg, Lars; Boraxbekk, C. J.

    2017-01-01

    Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64–78 years) were randomized into either an aerobic exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). Additionally, a comprehensive battery of cognitive tasks assessing, e.g., executive function and episodic memory was administered. Both the aerobic and the control group improved in aerobic capacity (VO2-peak) over 6 months, but a significant group by time interaction confirmed that the aerobic group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings. At baseline, VO2-peak was negativly related to BOLD-signal fluctuations (BOLDSTD) in mid temporal areas. Over 6 months, improvements in aerobic capacity were associated with decreased connectivity between left hippocampus and contralateral precentral gyrus, and positively to connectivity between right mid-temporal areas and frontal and parietal regions. Independent component analysis identified a VO2-related increase in coupling between the default mode network and left orbitofrontal cortex, as well as a decreased connectivity between the sensorimotor network and thalamus. Extensive exploratory data analyses of global efficiency, connectome wide multivariate pattern analysis (connectome-MVPA), as well as ASL, did not reveal any relationships between aerobic fitness and intrinsic brain activity. Moreover, fitness-predicted changes in functional connectivity did not relate to changes in cognition, which is likely due to absent cross-sectional or longitudinal relationships between VO2-peak and cognition. We conclude that the aerobic exercise intervention had limited influence on patterns of intrinsic brain activity, although post hoc analyses indicated that individual changes in aerobic capacity preferentially influenced mid-temporal brain areas. PMID:28848424

  9. Does Aerobic Exercise Influence Intrinsic Brain Activity? An Aerobic Exercise Intervention among Healthy Old Adults.

    PubMed

    Flodin, Pär; Jonasson, Lars S; Riklund, Katrin; Nyberg, Lars; Boraxbekk, C J

    2017-01-01

    Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64-78 years) were randomized into either an aerobic exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). Additionally, a comprehensive battery of cognitive tasks assessing, e.g., executive function and episodic memory was administered. Both the aerobic and the control group improved in aerobic capacity (VO 2 -peak) over 6 months, but a significant group by time interaction confirmed that the aerobic group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings. At baseline, VO 2 -peak was negativly related to BOLD-signal fluctuations (BOLD STD ) in mid temporal areas. Over 6 months, improvements in aerobic capacity were associated with decreased connectivity between left hippocampus and contralateral precentral gyrus, and positively to connectivity between right mid-temporal areas and frontal and parietal regions. Independent component analysis identified a VO 2 -related increase in coupling between the default mode network and left orbitofrontal cortex, as well as a decreased connectivity between the sensorimotor network and thalamus. Extensive exploratory data analyses of global efficiency, connectome wide multivariate pattern analysis (connectome-MVPA), as well as ASL, did not reveal any relationships between aerobic fitness and intrinsic brain activity. Moreover, fitness-predicted changes in functional connectivity did not relate to changes in cognition, which is likely due to absent cross-sectional or longitudinal relationships between VO 2 -peak and cognition. We conclude that the aerobic exercise intervention had limited influence on patterns of intrinsic brain activity, although post hoc analyses indicated that individual changes in aerobic capacity preferentially influenced mid-temporal brain areas.

  10. Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases.

    PubMed

    Sun, Bao-Liang; Wang, Li-Hua; Yang, Tuo; Sun, Jing-Yi; Mao, Lei-Lei; Yang, Ming-Feng; Yuan, Hui; Colvin, Robert A; Yang, Xiao-Yi

    2017-09-10

    The belief that the vertebrate brain functions normally without classical lymphatic drainage vessels has been held for many decades. On the contrary, new findings show that functional lymphatic drainage does exist in the brain. The brain lymphatic drainage system is composed of basement membrane-based perivascular pathway, a brain-wide glymphatic pathway, and cerebrospinal fluid (CSF) drainage routes including sinus-associated meningeal lymphatic vessels and olfactory/cervical lymphatic routes. The brain lymphatic systems function physiological as a route of drainage for interstitial fluid (ISF) from brain parenchyma to nearby lymph nodes. Brain lymphatic drainage helps maintain water and ion balance of the ISF, waste clearance, and reabsorption of macromolecular solutes. A second physiological function includes communication with the immune system modulating immune surveillance and responses of the brain. These physiological functions are influenced by aging, genetic phenotypes, sleep-wake cycle, and body posture. The impairment and dysfunction of the brain lymphatic system has crucial roles in age-related changes of brain function and the pathogenesis of neurovascular, neurodegenerative, and neuroinflammatory diseases, as well as brain injury and tumors. In this review, we summarize the key component elements (regions, cells, and water transporters) of the brain lymphatic system and their regulators as potential therapeutic targets in the treatment of neurologic diseases and their resulting complications. Finally, we highlight the clinical importance of ependymal route-based targeted gene therapy and intranasal drug administration in the brain by taking advantage of the unique role played by brain lymphatic pathways in the regulation of CSF flow and ISF/CSF exchange. Copyright © 2017. Published by Elsevier Ltd.

  11. Social connectedness, mental health and the adolescent brain.

    PubMed

    Lamblin, M; Murawski, C; Whittle, S; Fornito, A

    2017-09-01

    Social relationships promote health and wellbeing. Brain regions regulating social behavior continue to develop throughout adolescence, as teens learn to navigate their social environment with increasing sophistication. Adolescence is also a time of increased risk for the development of psychiatric disorders, many of which are characteristically associated with social dysfunction. In this review, we consider the links between adolescent brain development and the broader social environment. We examine evidence that individual differences in social ability, partly determined by genetic influences on brain structure and function, impact the quality and quantity of social ties during adolescence and that, conversely, the structure of one's social network exerts complex yet profound influences on individual behavior and mental health. In this way, the brain and social environment sculpt each other throughout the teenage years to influence one's social standing amongst peers. Reciprocal interactions between brain maturation and the social environment at this critical developmental stage may augment risk or promote resilience for mental illness and other health outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Compensatory recruitment of neural resources in chronic alcoholism.

    PubMed

    Chanraud, Sandra; Sullivan, Edith V

    2014-01-01

    Functional recovery occurs with sustained sobriety, but the neural mechanisms enabling recovery are only now emerging. Theories about promising mechanisms involve concepts of neuroadaptation, where excessive alcohol consumption results in untoward structural and functional brain changes which are subsequently candidates for reversal with sobriety. Views on functional adaptation in chronic alcoholism have expanded with results from neuroimaging studies. Here, we first describe and define the concept of neuroadaptation according to emerging theories based on the growing literature in aging-related cognitive functioning. Then we describe findings as they apply to chronic alcoholism and factors that could influence compensation, such as functional brain reserve and the integrity of brain structure. Finally, we review brain plasticity based on physiologic mechanisms that could underlie mechanisms of neural compensation. Where possible, we provide operational criteria to define functional and neural compensation. © 2014 Elsevier B.V. All rights reserved.

  13. The influence of sex chromosome aneuploidy on brain asymmetry.

    PubMed

    Rezaie, Roozbeh; Daly, Eileen M; Cutter, William J; Murphy, Declan G M; Robertson, Dene M W; DeLisi, Lynn E; Mackay, Clare E; Barrick, Thomas R; Crow, Timothy J; Roberts, Neil

    2009-01-05

    The cognitive deficits present in individuals with sex chromosome aneuploidies suggest that hemispheric differentiation of function is determined by an X-Y homologous gene [Crow (1993); Lancet 342:594-598]. In particular, females with Turner's syndrome (TS) who have only one X-chromosome exhibit deficits of spatial ability whereas males with Klinefelter's syndrome (KS) who possess a supernumerary X-chromosome are delayed in acquiring words. Since spatial and verbal abilities are generally associated with right and left hemispheric function, such deficits may relate to anomalies of cerebral asymmetry. We therefore applied a novel image analysis technique to investigate the relationship between sex chromosome dosage and structural brain asymmetry. Specifically, we tested Crow's prediction that the magnitude of the brain torque (i.e., a combination of rightward frontal and leftward occipital asymmetry) would, as a function of sex chromosome dosage, be respectively decreased in TS women and increased in KS men, relative to genotypically normal controls. We found that brain torque was not significantly different in TS women and KS men, in comparison to controls. However, TS women exhibited significantly increased leftward brain asymmetry, restricted to the posterior of the brain and focused on the superior temporal and parietal-occipital association cortex, while KS men showed a trend for decreased brain asymmetry throughout the frontal lobes. The findings suggest that the number of sex chromosomes influences the development of brain asymmetry not simply to modify the torque but in a complex pattern along the antero-posterior axis. 2008 Wiley-Liss, Inc.

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2012-01-01

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

  16. Impacts of stress and sex hormones on dopamine neurotransmission in the adolescent brain.

    PubMed

    Sinclair, Duncan; Purves-Tyson, Tertia D; Allen, Katherine M; Weickert, Cynthia Shannon

    2014-04-01

    Adolescence is a developmental period of complex neurobiological change and heightened vulnerability to psychiatric illness. As a result, understanding factors such as sex and stress hormones which drive brain changes in adolescence, and how these factors may influence key neurotransmitter systems implicated in psychiatric illness, is paramount. In this review, we outline the impact of sex and stress hormones at adolescence on dopamine neurotransmission, a signaling pathway which is critical to healthy brain function and has been implicated in psychiatric illness. We review normative developmental changes in dopamine, sex hormone, and stress hormone signaling during adolescence and throughout postnatal life, then highlight the interaction of sex and stress hormones and review their impacts on dopamine neurotransmission in the adolescent brain. Adolescence is a time of increased responsiveness to sex and stress hormones, during which the maturing dopaminergic neural circuitry is profoundly influenced by these factors. Testosterone, estrogen, and glucocorticoids interact with each other and have distinct, brain region-specific impacts on dopamine neurotransmission in the adolescent brain, shaping brain maturation and cognitive function in adolescence and adulthood. Some effects of stress/sex hormones on cortical and subcortical dopamine parameters bear similarities with dopaminergic abnormalities seen in schizophrenia, suggesting a possible role for sex/stress hormones at adolescence in influencing risk for psychiatric illness via modulation of dopamine neurotransmission. Stress and sex hormones may prove useful targets in future strategies for modifying risk for psychiatric illness.

  17. Control channels in the brain and their influence on brain executive functions

    NASA Astrophysics Data System (ADS)

    Meng, Qinglei; Choa, Fow-Sen; Hong, Elliot; Wang, Zhiguang; Islam, Mohammad

    2014-05-01

    In a computer network there are distinct data channels and control channels where massive amount of visual information are transported through data channels but the information streams are routed and controlled by intelligent algorithm through "control channels". Recent studies on cognition and consciousness have shown that the brain control channels are closely related to the brainwave beta (14-40 Hz) and alpha (7-13 Hz) oscillations. The high-beta wave is used by brain to synchronize local neural activities and the alpha oscillation is for desynchronization. When two sensory inputs are simultaneously presented to a person, the high-beta is used to select one of the inputs and the alpha is used to deselect the other so that only one input will get the attention. In this work we demonstrated that we can scan a person's brain using binaural beats technique and identify the individual's preferred control channels. The identified control channels can then be used to influence the subject's brain executive functions. In the experiment, an EEG measurement system was used to record and identify a subject's control channels. After these channels were identified, the subject was asked to do Stroop tests. Binaural beats was again used to produce these control-channel frequencies on the subject's brain when we recorded the completion time of each test. We found that the high-beta signal indeed speeded up the subject's executive function performance and reduced the time to complete incongruent tests, while the alpha signal didn't seem to be able to slow down the executive function performance.

  18. 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.

  19. Model of brain activation predicts the neural collective influence map of the brain

    PubMed Central

    Morone, Flaviano; Roth, Kevin; Min, Byungjoon; Makse, Hernán A.

    2017-01-01

    Efficient complex systems have a modular structure, but modularity does not guarantee robustness, because efficiency also requires an ingenious interplay of the interacting modular components. The human brain is the elemental paradigm of an efficient robust modular system interconnected as a network of networks (NoN). Understanding the emergence of robustness in such modular architectures from the interconnections of its parts is a longstanding challenge that has concerned many scientists. Current models of dependencies in NoN inspired by the power grid express interactions among modules with fragile couplings that amplify even small shocks, thus preventing functionality. Therefore, we introduce a model of NoN to shape the pattern of brain activations to form a modular environment that is robust. The model predicts the map of neural collective influencers (NCIs) in the brain, through the optimization of the influence of the minimal set of essential nodes responsible for broadcasting information to the whole-brain NoN. Our results suggest intervention protocols to control brain activity by targeting influential neural nodes predicted by network theory. PMID:28351973

  20. Role of mitochondrial calcium uptake homeostasis in resting state fMRI brain networks.

    PubMed

    Kannurpatti, Sridhar S; Sanganahalli, Basavaraju G; Herman, Peter; Hyder, Fahmeed

    2015-11-01

    Mitochondrial Ca(2+) uptake influences both brain energy metabolism and neural signaling. Given that brain mitochondrial organelles are distributed in relation to vascular density, which varies considerably across brain regions, we hypothesized different physiological impacts of mitochondrial Ca(2+) uptake across brain regions. We tested the hypothesis by monitoring brain "intrinsic activity" derived from the resting state functional MRI (fMRI) blood oxygen level dependent (BOLD) fluctuations in different functional networks spanning the somatosensory cortex, caudate putamen, hippocampus and thalamus, in normal and perturbed mitochondrial Ca(2+) uptake states. In anesthetized rats at 11.7 T, mitochondrial Ca(2+) uptake was inhibited or enhanced respectively by treatments with Ru360 or kaempferol. Surprisingly, mitochondrial Ca(2+) uptake inhibition by Ru360 and enhancement by kaempferol led to similar dose-dependent decreases in brain-wide intrinsic activities in both the frequency domain (spectral amplitude) and temporal domain (resting state functional connectivity; RSFC). The fact that there were similar dose-dependent decreases in the frequency and temporal domains of the resting state fMRI-BOLD fluctuations during mitochondrial Ca(2+) uptake inhibition or enhancement indicated that mitochondrial Ca(2+) uptake and its homeostasis may strongly influence the brain's functional organization at rest. Interestingly, the resting state fMRI-derived intrinsic activities in the caudate putamen and thalamic regions saturated much faster with increasing dosage of either drug treatment than the drug-induced trends observed in cortical and hippocampal regions. Regional differences in how the spectral amplitude and RSFC changed with treatment indicate distinct mitochondrion-mediated spontaneous neuronal activity coupling within the various RSFC networks determined by resting state fMRI. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Effects of geomagnetic activity variations on the physiological and psychological state of functionally healthy humans: Some results of Azerbaijani studies

    NASA Astrophysics Data System (ADS)

    Babayev, Elchin S.; Allahverdiyeva, Aysel A.

    There are collaborative and cross-disciplinary space weather studies in the Azerbaijan National Academy of Sciences conducted with purposes of revealing possible effects of solar, geomagnetic and cosmic ray variability on certain technological, biological and ecological systems. This paper describes some results of the experimental studies of influence of the periodical and aperiodical changes of geomagnetic activity upon human brain, human health and psycho-emotional state. It also covers the conclusions of studies on influence of violent solar events and severe geomagnetic storms of the solar cycle 23 on the mentioned systems in middle-latitude location. It is experimentally established that weak and moderate geomagnetic storms do not cause significant changes in the brain's bioelectrical activity and exert only stimulating influence while severe disturbances of geomagnetic conditions cause negative influence, seriously disintegrate brain's functionality, activate braking processes and amplify the negative emotional background of an individual. It is concluded that geomagnetic disturbances affect mainly emotional and vegetative spheres of human beings while characteristics reflecting personality properties do not undergo significant changes.

  2. Imaging brain development: the adolescent brain.

    PubMed

    Blakemore, Sarah-Jayne

    2012-06-01

    The past 15 years have seen a rapid expansion in the number of studies using neuroimaging techniques to investigate maturational changes in the human brain. In this paper, I review MRI studies on structural changes in the developing brain, and fMRI studies on functional changes in the social brain during adolescence. Both MRI and fMRI studies point to adolescence as a period of continued neural development. In the final section, I discuss a number of areas of research that are just beginning and may be the subject of developmental neuroimaging in the next twenty years. Future studies might focus on complex questions including the development of functional connectivity; how gender and puberty influence adolescent brain development; the effects of genes, environment and culture on the adolescent brain; development of the atypical adolescent brain; and implications for policy of the study of the adolescent brain. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. The Neural Basis of Social Influence in a Dictator Decision

    PubMed Central

    Wei, Zhenyu; Zhao, Zhiying; Zheng, Yong

    2017-01-01

    Humans tend to reduce inequitable distributions. Previous neuroimaging studies have shown that inequitable decisions are related to brain regions that associated with negative emotion and signaling conflict. In the highly complex human social environment, our opinions and behaviors can be affected by social information. In current study, we used a modified dictator game to investigate the effect of social influence on making an equitable decision. We found that the choices of participants in present task was influenced by the choices of peers. However, participants’ decisions were influenced by equitable rather than inequitable group choices. fMRI results showed that brain regions that related to norm violation and social conflict were related to the inequitable social influence. The neural responses in the dorsomedial prefrontal cortex, rostral cingulate zone, and insula predicted subsequent conforming behavior in individuals. Additionally, psychophysiological interaction analysis revealed that the interconnectivity between the dorsal striatum and insula was elevated in advantageous inequity influence versus no-social influence conditions. We found decreased functional connectivity between the medial prefrontal cortex and insula, supplementary motor area, posterior cingulate gyrus and dorsal anterior cingulate cortex in the disadvantageous inequity influence versus no-social influence conditions. This suggests that a disadvantageous inequity influence may decrease the functional connectivity among brain regions that are related to reward processes. Thus, the neural mechanisms underlying social influence in an equitable decision may be similar to those implicated in social norms and reward processing. PMID:29375412

  4. A review of structural and functional brain networks: small world and atlas.

    PubMed

    Yao, Zhijun; Hu, Bin; Xie, Yuanwei; Moore, Philip; Zheng, Jiaxiang

    2015-03-01

    Brain networks can be divided into two categories: structural and functional networks. Many studies of neuroscience have reported that the complex brain networks are characterized by small-world or scale-free properties. The identification of nodes is the key factor in studying the properties of networks on the macro-, micro- or mesoscale in both structural and functional networks. In the study of brain networks, nodes are always determined by atlases. Therefore, the selection of atlases is critical, and appropriate atlases are helpful to combine the analyses of structural and functional networks. Currently, some problems still exist in the establishment or usage of atlases, which are often caused by the segmentation or the parcellation of the brain. We suggest that quantification of brain networks might be affected by the selection of atlases to a large extent. In the process of building atlases, the influences of single subjects and groups should be balanced. In this article, we focused on the effects of atlases on the analysis of brain networks and the improved divisions based on the tractography or connectivity in the parcellation of atlases.

  5. Factors influencing executive function by physical activity level among young adults: a near-infrared spectroscopy study.

    PubMed

    Matsuda, Kensuke; Ikeda, Shou; Mitsutake, Tsubasa; Nakahara, Masami; Nagai, Yoshiharu; Ikeda, Takuro; Horikawa, Etsuo

    2017-03-01

    [Purpose] Prevention of dementia requires early intervention against it. To ensure that early interventions are effective it is crucial to study the cognitive functions related to dementia in young adulthood. Moreover, it is needed not only to verify the cognitive function test but also to elucidate the actual brain activity and the influence of related factors on the brain activity. To investigate the factors influencing cognitive function among young adults and examine the differences in executive function by physical activity level. [Subjects and Methods] Forty healthy university students (mean age, 20.4 years) were classified into two groups by cognitive function score (HIGH and LOW), determined according to Trail Making Test performance and Stroop task processing time. We then assessed what factors were related to cognitive function by logistic regression analysis. Executive function was determined by brain blood flow using near-infrared spectroscopy during the Stroop task, and was then compared by physical activity levels (determined according to number of steps per hour). [Results] Full-scale Intelligence Quotient according to the 3rd Wechsler Adult Intelligent Scale and number of steps per hour influenced cognitive function score, with odds ratios of 1.104 and 1.012, respectively. Oxy-hemoglobin concentrations in areas related to executive function during the Stroop task were significantly higher among those in the high physical activity group than among those in the low physical activity group. [Conclusion] The study revealed that Full-scale Intelligence Quotient and a number of steps per hour are factors associated with the cognitive functions in young adulthood. In addition, activity in execution function related area was found to be significantly higher in the high physical activity group than in the low physical activity group, suggesting the importance of physical activity for enhancing young adulthood cognitive functions.

  6. Cortisol Excess and the Brain.

    PubMed

    Resmini, Eugenia; Santos, Alicia; Webb, Susan M

    2016-01-01

    Until the last decade, little was known about the effects of chronic hypercortisolism on the brain. In the last few years, new data have arisen thanks to advances in imaging techniques; therefore, it is now possible to investigate brain activity in vivo. Memory impairments are present in patients with Cushing's syndrome (CS) and are related to hippocampal damage; functional dysfunctions would precede structural abnormalities as detected by brain imaging. Earlier diagnosis and rapid normalization of hypercortisolism could stop the progression of hippocampal damage and memory impairments. Impairments of executive functions (including decision-making) and other functions such as visuoconstructive skills, language, motor functions and information processing speed are also present in CS patients. There is controversy concerning the reversibility of brain impairment. It seems that longer disease duration and older age are associated with less recovery of brain functioning. Conversely, earlier diagnosis and rapid normalization of hypercortisolism appear to stop progression of brain damage and functional impairments. Moreover, brain tissue functioning and neuroplasticity can be influenced by many factors. Currently available studies appear to be complementary, evaluating the same phenomenon from different points of view, but are often not directly comparable. Finally, CS patients have a high prevalence of psychopathology, such as depression and anxiety which do not completely revert after cure. Thus, psychological or psychiatric evaluation could be recommended in CS patients, so that treatment may be prescribed if required. © 2016 S. Karger AG, Basel.

  7. Testosterone affects language areas of the adult human brain

    PubMed Central

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

    2016-01-01

    Abstract Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high‐dose hormone application in adult female‐to‐male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel‐based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting‐state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone‐dependent neuroplastic adaptations in adulthood within language‐specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738–1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  8. Understanding the Broad Influence of Sex Hormones and Sex Differences in the Brain

    PubMed Central

    McEwen, Bruce S.; Milner, Teresa A.

    2016-01-01

    Sex hormones act throughout the entire brain of both males and females via both genomic and non-genomic receptors. Sex hormones can act through many cellular and molecular processes that alter structure and function of neural systems and influence behavior as well as providing neuroprotection. Within neurons, sex hormone receptors are found in nuclei and are also located near membranes where they are associated with presynaptic terminals, mitochondria, spine apparatus, post-synaptic densities. Sex hormone receptors also are found in glial cells. Hormonal regulation of a variety of signaling pathways as well as direct and indirect effects upon gene expression induce spine synapses, up- or down-regulate and alter the distribution of neurotransmitter receptors, regulate neuropeptide expression and cholinergic and GABAergic activity as well as calcium sequestration and oxidative stress. Many neural and behavioral functions are affected, including mood, cognitive function, blood pressure regulation, motor coordination, pain and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not-yet-precisely-defined genetic factors including the mitochondrial genome. These sex differences and responses to sex hormones in brain regions, and upon functions not previously regarded as subject to such differences, indicates that we are entering a new era of our ability to understand and appreciate the diversity of gender-related behaviors and brain functions. PMID:27870427

  9. Adolescent Cannabis Use: What is the Evidence for Functional Brain Alteration?

    PubMed

    Lorenzetti, Valentina; Alonso-Lana, Silvia; Youssef, George J; Verdejo-Garcia, Antonio; Suo, Chao; Cousijn, Janna; Takagi, Michael; Yücel, Murat; Solowij, Nadia

    2016-01-01

    Cannabis use typically commences during adolescence, a period during which the brain undergoes profound remodeling in areas that are high in cannabinoid receptors and that mediate cognitive control and emotion regulation. It is therefore important to determine the impact of adolescent cannabis use on brain function. We investigate the impact of adolescent cannabis use on brain function by reviewing the functional magnetic resonance imaging studies in adolescent samples. We systematically reviewed the literature and identified 13 functional neuroimaging studies in adolescent cannabis users (aged 13 to 18 years) performing working memory, inhibition and reward processing tasks. The majority of the studies found altered brain function, but intact behavioural task performance in adolescent cannabis users versus controls. The most consistently reported differences were in the frontal-parietal network, which mediates cognitive control. Heavier use was associated with abnormal brain function in most samples. A minority of studies controlled for the influence of confounders that can also undermine brain function, such as tobacco and alcohol use, psychopathology symptoms, family history of psychiatric disorders and substance use. Emerging evidence shows abnormal frontal-parietal network activity in adolescent cannabis users, particularly in heavier users. Brain functional alterations may reflect a compensatory neural mechanism that enables normal behavioural performance. It remains unclear if cannabis exposure drives these alterations, as substance use and mental health confounders have not been systematically examined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Measuring Second Language Proficiency with EEG Synchronization: How Functional Cortical Networks and Hemispheric Involvement Differ as a Function of Proficiency Level in Second Language Speakers

    ERIC Educational Resources Information Center

    Reiterer, Susanne; Pereda, Ernesto; Bhattacharya, Joydeep

    2009-01-01

    This article examines the question of whether university-based high-level foreign language and linguistic training can influence brain activation and whether different L2 proficiency groups have different brain activation in terms of lateralization and hemispheric involvement. The traditional and prevailing theory of hemispheric involvement in…

  11. Maturation of Sensori-Motor Functional Responses in the Preterm Brain.

    PubMed

    Allievi, Alessandro G; Arichi, Tomoki; Tusor, Nora; Kimpton, Jessica; Arulkumaran, Sophie; Counsell, Serena J; Edwards, A David; Burdet, Etienne

    2016-01-01

    Preterm birth engenders an increased risk of conditions like cerebral palsy and therefore this time may be crucial for the brain's developing sensori-motor system. However, little is known about how cortical sensori-motor function matures at this time, whether development is influenced by experience, and about its role in spontaneous motor behavior. We aimed to systematically characterize spatial and temporal maturation of sensori-motor functional brain activity across this period using functional MRI and a custom-made robotic stimulation device. We studied 57 infants aged from 30 + 2 to 43 + 2 weeks postmenstrual age. Following both induced and spontaneous right wrist movements, we saw consistent positive blood oxygen level-dependent functional responses in the contralateral (left) primary somatosensory and motor cortices. In addition, we saw a maturational trend toward faster, higher amplitude, and more spatially dispersed functional responses; and increasing integration of the ipsilateral hemisphere and sensori-motor associative areas. We also found that interhemispheric functional connectivity was significantly related to ex-utero exposure, suggesting the influence of experience-dependent mechanisms. At term equivalent age, we saw a decrease in both response amplitude and interhemispheric functional connectivity, and an increase in spatial specificity, culminating in the establishment of a sensori-motor functional response similar to that seen in adults. © The Author 2015. Published by Oxford University Press.

  12. Influence of P-Glycoprotein Inhibition or Deficiency at the Blood-Brain Barrier on (18)F-2-Fluoro-2-Deoxy-D-glucose ( (18)F-FDG) Brain Kinetics.

    PubMed

    Tournier, Nicolas; Saba, Wadad; Goutal, Sébastien; Gervais, Philippe; Valette, Héric; Scherrmann, Jean-Michel; Bottlaender, Michel; Cisternino, Salvatore

    2015-05-01

    The fluorinated D-glucose analog (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) is the most prevalent radiopharmaceutical for positron emission tomography (PET) imaging. P-Glycoprotein's (P-gp, MDR1, and ABCB1) function in various cancer cell lines and tumors was shown to impact (18)F-FDG incorporation, suggesting that P-gp function at the blood-brain barrier may also modulate (18)F-FDG brain kinetics. We tested the influence of P-gp inhibition using the cyclosporine analog valspodar (PSC833; 5 μM) on the uptake of (18)F-FDG in standardized human P-gp-overexpressing cells (MDCKII-MDR1). Consequences for (18)F-FDG brain kinetics were then assessed using (i) (18)F-FDG PET imaging and suitable kinetic modelling in baboons without or with P-gp inhibition by intravenous cyclosporine infusion (15 mg kg(-1) h(-1)) and (ii) in situ brain perfusion in wild-type and P-gp/Bcrp (breast cancer resistance protein) knockout mice and controlled D-glucose exposure to the brain. In vitro, the time course of (18)F-FDG uptake in MDR1 cells was influenced by the presence of valspodar in the absence of D-glucose but not in the presence of high D-glucose concentration. PET analysis revealed that P-gp inhibition had no significant impact on estimated brain kinetics parameters K 1, k 2, k 3, V T , and CMRGlc. The lack of P-gp effect on in vivo (18)F-FDG brain distribution was confirmed in P-gp/Bcrp-deficient mice. P-gp inhibition indirectly modulates (18)F-FDG uptake into P-gp-overexpressing cells, possibly through differences in the energetic cell level state. (18)F-FDG is not a P-gp substrate at the BBB and (18)F-FDG brain kinetics as well as estimated brain glucose metabolism are influenced by neither P-gp inhibition nor P-gp/Bcrp deficiencies in baboon and mice, respectively.

  13. Neurocognitive and Family Functioning and Quality of Life Among Young Adult Survivors of Childhood Brain Tumors

    PubMed Central

    Hocking, Matthew C.; Hobbie, Wendy L.; Deatrick, Janet A.; Lucas, Matthew S.; Szabo, Margo M.; Volpe, Ellen M.; Barakat, Lamia P.

    2012-01-01

    Many childhood brain tumor survivors experience significant neurocognitive late effects across multiple domains that negatively affect quality of life. A theoretical model of survivorship suggests that family functioning and survivor neurocognitive functioning interact to affect survivor and family outcomes. This paper reviews the types of neurocognitive late effects experienced by survivors of pediatric brain tumors. Quantitative and qualitative data from three case reports of young adult survivors and their mothers are analyzed according to the theoretical model and presented in this paper to illustrate the importance of key factors presented in the model. The influence of age at brain tumor diagnosis, family functioning, and family adaptation to illness on survivor quality of life and family outcomes are highlighted. Future directions for research and clinical care for this vulnerable group of survivors are discussed. PMID:21722062

  14. The Vertebrate Brain, Evidence of Its Modular Organization and Operating System: Insights into the Brain's Basic Units of Structure, Function, and Operation and How They Influence Neuronal Signaling and Behavior.

    PubMed

    Baslow, Morris H

    2011-01-01

    The human brain is a complex organ made up of neurons and several other cell types, and whose role is processing information for use in eliciting behaviors. However, the composition of its repeating cellular units for both structure and function are unresolved. Based on recent descriptions of the brain's physiological "operating system", a function of the tri-cellular metabolism of N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) for supply of energy, and on the nature of "neuronal words and languages" for intercellular communication, insights into the brain's modular structural and functional units have been gained. In this article, it is proposed that the basic structural unit in brain is defined by its physiological operating system, and that it consists of a single neuron, and one or more astrocytes, oligodendrocytes, and vascular system endothelial cells. It is also proposed that the basic functional unit in the brain is defined by how neurons communicate, and consists of two neurons and their interconnecting dendritic-synaptic-dendritic field. Since a functional unit is composed of two neurons, it requires two structural units to form a functional unit. Thus, the brain can be envisioned as being made up of the three-dimensional stacking and intertwining of myriad structural units which results not only in its gross structure, but also in producing a uniform distribution of binary functional units. Since the physiological NAA-NAAG operating system for supply of energy is repeated in every structural unit, it is positioned to control global brain function.

  15. Musical expertise and second language learning.

    PubMed

    Chobert, Julie; Besson, Mireille

    2013-06-06

    Increasing evidence suggests that musical expertise influences brain organization and brain functions. Moreover, results at the behavioral and neurophysiological levels reveal that musical expertise positively influences several aspects of speech processing, from auditory perception to speech production. In this review, we focus on the main results of the literature that led to the idea that musical expertise may benefit second language acquisition. We discuss several interpretations that may account for the influence of musical expertise on speech processing in native and foreign languages, and we propose new directions for future research.

  16. Musical Expertise and Second Language Learning

    PubMed Central

    Chobert, Julie; Besson, Mireille

    2013-01-01

    Increasing evidence suggests that musical expertise influences brain organization and brain functions. Moreover, results at the behavioral and neurophysiological levels reveal that musical expertise positively influences several aspects of speech processing, from auditory perception to speech production. In this review, we focus on the main results of the literature that led to the idea that musical expertise may benefit second language acquisition. We discuss several interpretations that may account for the influence of musical expertise on speech processing in native and foreign languages, and we propose new directions for future research. PMID:24961431

  17. The Affective Neuroscience of Aging

    PubMed Central

    Mather, Mara

    2018-01-01

    While aging is associated with clear declines in physical and cognitive processes, emotional functioning fares relatively well. Consistent with this behavioral profile, two core emotional brain regions, the amygdala and ventromedial prefrontal cortex, show little structural and functional decline in aging, compared with other regions. However, emotional processes depend on interacting systems of neurotransmitters and brain regions that go beyond these structures. This review examines how age-related brain changes influence processes such as attending to and remembering emotional stimuli, regulating emotion, recognizing emotional expressions, empathy, risk taking, impulsivity, behavior change and attentional focus. PMID:26436717

  18. The Affective Neuroscience of Aging.

    PubMed

    Mather, Mara

    2016-01-01

    Although aging is associated with clear declines in physical and cognitive processes, emotional functioning fares relatively well. Consistent with this behavioral profile, two core emotional brain regions, the amygdala and ventromedial prefrontal cortex, show little structural and functional decline in aging, compared with other regions. However, emotional processes depend on interacting systems of neurotransmitters and brain regions that go beyond these structures. This review examines how age-related brain changes influence processes such as attending to and remembering emotional stimuli, regulating emotion, and recognizing emotional expressions, as well as empathy, risk taking, impulsivity, behavior change, and attentional focus.

  19. Toward reliable characterization of functional homogeneity in the human brain: Preprocessing, scan duration, imaging resolution and computational space

    PubMed Central

    Zuo, Xi-Nian; Xu, Ting; Jiang, Lili; Yang, Zhi; Cao, Xiao-Yan; He, Yong; Zang, Yu-Feng; Castellanos, F. Xavier; Milham, Michael P.

    2013-01-01

    While researchers have extensively characterized functional connectivity between brain regions, the characterization of functional homogeneity within a region of the brain connectome is in early stages of development. Several functional homogeneity measures were proposed previously, among which regional homogeneity (ReHo) was most widely used as a measure to characterize functional homogeneity of resting state fMRI (R-fMRI) signals within a small region (Zang et al., 2004). Despite a burgeoning literature on ReHo in the field of neuroimaging brain disorders, its test–retest (TRT) reliability remains unestablished. Using two sets of public R-fMRI TRT data, we systematically evaluated the ReHo’s TRT reliability and further investigated the various factors influencing its reliability and found: 1) nuisance (head motion, white matter, and cerebrospinal fluid) correction of R-fMRI time series can significantly improve the TRT reliability of ReHo while additional removal of global brain signal reduces its reliability, 2) spatial smoothing of R-fMRI time series artificially enhances ReHo intensity and influences its reliability, 3) surface-based R-fMRI computation largely improves the TRT reliability of ReHo, 4) a scan duration of 5 min can achieve reliable estimates of ReHo, and 5) fast sampling rates of R-fMRI dramatically increase the reliability of ReHo. Inspired by these findings and seeking a highly reliable approach to exploratory analysis of the human functional connectome, we established an R-fMRI pipeline to conduct ReHo computations in both 3-dimensions (volume) and 2-dimensions (surface). PMID:23085497

  20. Choline: Dietary Requirements and Role in Brain Development.

    PubMed

    Sanders, Lisa M; Zeisel, Steven H

    2007-01-01

    Choline is needed for the maintenance of the structural integrity and signaling functions of cell membranes, for neurotransmission, and for transport of lipids and as a source of methyl groups. Choline can be made de novo in the body, but some individuals must also obtain choline in the diet to prevent deficiency symptoms. A number of environmental and genetic factors influence dietary requirements for choline, and average intakes in the population vary widely. Therefore, certain individuals may be at greater risk of choline deficiency. Choline is critical during fetal development, particularly during the development of the brain, where it can influence neural tube closure and lifelong memory and learning functions.

  1. Effects of Beta-Alanine Supplementation on Brain Homocarnosine/Carnosine Signal and Cognitive Function: An Exploratory Study

    PubMed Central

    Hobson, Ruth M; Artioli, Guilherme G.; Otaduy, Maria C.; Roschel, Hamilton; Robertson, Jacques; Martin, Daniel; S. Painelli, Vitor; Harris, Roger C.; Gualano, Bruno

    2015-01-01

    Objectives Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P<0.05), although there was no effect (P>0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists. PMID:25875297

  2. Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study.

    PubMed

    Solis, Marina Yazigi; Cooper, Simon; Hobson, Ruth M; Artioli, Guilherme G; Otaduy, Maria C; Roschel, Hamilton; Robertson, Jacques; Martin, Daniel; S Painelli, Vitor; Harris, Roger C; Gualano, Bruno; Sale, Craig

    2015-01-01

    Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d(-1) on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P < 0.05), although there was no effect (P>0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. 28 d of beta-alanine supplementation at 6.4 g d(-1) appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists.

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

    PubMed Central

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

    2015-01-01

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

  4. Attentional Modulation of Brain Responses to Primary Appetitive and Aversive Stimuli

    PubMed Central

    Field, Brent A.; Buck, Cara L.; McClure, Samuel M.; Nystrom, Leigh E.; Kahneman, Daniel; Cohen, Jonathan D.

    2015-01-01

    Studies of subjective well-being have conventionally relied upon self-report, which directs subjects’ attention to their emotional experiences. This method presumes that attention itself does not influence emotional processes, which could bias sampling. We tested whether attention influences experienced utility (the moment-by-moment experience of pleasure) by using functional magnetic resonance imaging (fMRI) to measure the activity of brain systems thought to represent hedonic value while manipulating attentional load. Subjects received appetitive or aversive solutions orally while alternatively executing a low or high attentional load task. Brain regions associated with hedonic processing, including the ventral striatum, showed a response to both juice and quinine. This response decreased during the high-load task relative to the low-load task. Thus, attentional allocation may influence experienced utility by modulating (either directly or indirectly) the activity of brain mechanisms thought to represent hedonic value. PMID:26158468

  5. A novel approach to analyzing fMRI and SNP data via parallel independent component analysis

    NASA Astrophysics Data System (ADS)

    Liu, Jingyu; Pearlson, Godfrey; Calhoun, Vince; Windemuth, Andreas

    2007-03-01

    There is current interest in understanding genetic influences on brain function in both the healthy and the disordered brain. Parallel independent component analysis, a new method for analyzing multimodal data, is proposed in this paper and applied to functional magnetic resonance imaging (fMRI) and a single nucleotide polymorphism (SNP) array. The method aims to identify the independent components of each modality and the relationship between the two modalities. We analyzed 92 participants, including 29 schizophrenia (SZ) patients, 13 unaffected SZ relatives, and 50 healthy controls. We found a correlation of 0.79 between one fMRI component and one SNP component. The fMRI component consists of activations in cingulate gyrus, multiple frontal gyri, and superior temporal gyrus. The related SNP component is contributed to significantly by 9 SNPs located in sets of genes, including those coding for apolipoprotein A-I, and C-III, malate dehydrogenase 1 and the gamma-aminobutyric acid alpha-2 receptor. A significant difference in the presences of this SNP component is found between the SZ group (SZ patients and their relatives) and the control group. In summary, we constructed a framework to identify the interactions between brain functional and genetic information; our findings provide new insight into understanding genetic influences on brain function in a common mental disorder.

  6. The role of polyhalogenated aromatic hydrocarbons on thyroid hormone disruption and cognitive function: a review.

    PubMed

    Builee, T L; Hatherill, J R

    2004-11-01

    Thyroid hormones (TH) are essential to normal brain development, influencing behavior and cognitive function in both adult and children. It is suggested that conditions found in TH abnormalities such as hypothyroidism, hyperthyroidism and generalized resistance to thyroid hormone (GRTH) share symptomatic behavioral impulses found in cases of attention deficit hyperactivity disorder (ADHD) and other cognitive disorders. Disrupters of TH are various and prevalent in the environment. This paper reviews the mechanisms of TH disruption caused by the general class of polyhalogenated aromatic hydrocarbons (PHAH)'s acting as thyroid disrupters (TD). PHAHs influence the hypothalamus-pituitary-thyroid (HPT) axis, as mimicry agents affecting synthesis and secretion of TH. Exposure to PHAH induces liver microsomal enzymes UDP-glucuronosyltransferase (UGT) resulting in accelerated clearance of TH. PHAHs can compromise function of transport and receptor binding proteins such as transthyretin and aryl hydrocarbon receptors (Ahr). Glucose metabolism and catecholamine synthesis are disrupted in the brain by the presence of PHAH. Further, PHAH can alter brain growth and development by perturbing cytoskeletal formation, thereby affecting neuronal migration, elongation and branching. The complex relationships between PHAH and cognitive function are examined in regard to the disruption of T4 regulation in the hypothalamus-pituitary-thyroid axis, blood, brain, neurons, liver and pre and postnatal development.

  7. Malondialdehyde Suppresses Cerebral Function by Breaking Homeostasis between Excitation and Inhibition in Turtle Trachemys scripta

    PubMed Central

    Li, Fangxu; Yang, Zhilai; Lu, Yang; Wei, Yan; Wang, Jinhui; Yin, Dazhong; He, Rongqiao

    2010-01-01

    The levels of malondialdehyde (MDA) are high in the brain during carbonyl stress, such as following daily activities and sleep deprivation. To examine our hypothesis that MDA is one of the major substances in the brain leading to fatigue, the influences of MDA on brain functions and neuronal encodings in red-eared turtle (Trachemys scripta) were studied. The intrathecal injections of MDA brought about sleep-like EEG and fatigue-like behaviors in a dose-dependent manner. These changes were found associated with the deterioration of encoding action potentials in cortical neurons. In addition, MDA increased the ratio of γ-aminobutyric acid to glutamate in turtle's brain, as well as the sensitivity of GABAergic neurons to inputs compared to excitatory neurons. Therefore, MDA, as a metabolic product in the brain, may weaken cerebral function during carbonyl stress through breaking the homeostasis between excitatory and inhibitory neurons. PMID:21203547

  8. The role of psychosocial factors and psychiatric disorders in functional dyspepsia.

    PubMed

    Van Oudenhove, Lukas; Aziz, Qasim

    2013-03-01

    In this Review, after a brief historical introduction, we first provide an overview of epidemiological studies that demonstrate an association between functional dyspepsia and psychological traits, states or psychiatric disorders. These studies suggest an important intrinsic role for psychosocial factors and psychiatric disorders, especially anxiety and depression, in the aetiopathogenesis of functional dyspepsia, in addition to their putative influence on health-care-seeking behaviour. Second, we describe pathophysiological evidence on how psychosocial factors and psychiatric disorders might exert their role in functional dyspepsia. Novel insights from functional brain imaging studies regarding the integration of gut-brain signals, processed in homeostatic-interoceptive brain regions, with input from the exteroceptive system, the reward system and affective and cognitive circuits, help to clarify the important role of psychological processes and psychiatric morbidity. We therefore propose an integrated model of functional dyspepsia as a disorder of gut-brain signalling, supporting a biopsychosocial approach to the diagnosis and management of this disorder.

  9. Stimulus-Elicited Connectivity Influences Resting-State Connectivity Years Later in Human Development: A Prospective Study.

    PubMed

    Gabard-Durnam, Laurel Joy; Gee, Dylan Grace; Goff, Bonnie; Flannery, Jessica; Telzer, Eva; Humphreys, Kathryn Leigh; Lumian, Daniel Stephen; Fareri, Dominic Stephen; Caldera, Christina; Tottenham, Nim

    2016-04-27

    Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is currently known about the mechanisms through which these networks assemble into stable mature patterns. The current study posits and tests the long-term phasic molding hypothesis that resting-state networks are gradually shaped by recurring stimulus-elicited connectivity across development by examining how both stimulus-elicited and resting-state functional connections of the human brain emerge over development at the systems level. Using a sequential design following 4- to 18-year-olds over a 2 year period, we examined the predictive associations between stimulus-elicited and resting-state connectivity in amygdala-cortical circuitry as an exemplar case (given this network's protracted development across these ages). Age-related changes in amygdala functional connectivity converged on the same regions of medial prefrontal cortex (mPFC) and inferior frontal gyrus when elicited by emotional stimuli and when measured at rest. Consistent with the long-term phasic molding hypothesis, prospective analyses for both connections showed that the magnitude of an individual's stimulus-elicited connectivity unidirectionally predicted resting-state functional connectivity 2 years later. For the amygdala-mPFC connection, only stimulus-elicited connectivity during childhood and the transition to adolescence shaped future resting-state connectivity, consistent with a sensitive period ending with adolescence for the amygdala-mPFC circuit. Together, these findings suggest that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited by environmental stimuli over the course of development on the order of years. A fundamental issue in understanding the ontogeny of brain function is how resting-state (intrinsic) functional networks emerge and relate to stimulus-elicited functional connectivity. Here, we posit and test the long-term phasic molding hypothesis that resting-state network development is influenced by recurring stimulus-elicited connectivity through prospective examination of the developing human amygdala-cortical functional connections. Our results provide critical insight into how early environmental events sculpt functional network architecture across development and highlight childhood as a potential developmental period of heightened malleability for the amygdala-medial prefrontal cortex circuit. These findings have implications for how both positive and adverse experiences influence the developing brain and motivate future investigations of whether this molding mechanism reflects a general phenomenon of brain development. Copyright © 2016 the authors 0270-6474/16/364772-14$15.00/0.

  10. Stimulus-Elicited Connectivity Influences Resting-State Connectivity Years Later in Human Development: A Prospective Study

    PubMed Central

    Gee, Dylan Grace; Goff, Bonnie; Flannery, Jessica; Telzer, Eva; Humphreys, Kathryn Leigh; Lumian, Daniel Stephen; Fareri, Dominic Stephen; Caldera, Christina; Tottenham, Nim

    2016-01-01

    Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is currently known about the mechanisms through which these networks assemble into stable mature patterns. The current study posits and tests the long-term phasic molding hypothesis that resting-state networks are gradually shaped by recurring stimulus-elicited connectivity across development by examining how both stimulus-elicited and resting-state functional connections of the human brain emerge over development at the systems level. Using a sequential design following 4- to 18-year-olds over a 2 year period, we examined the predictive associations between stimulus-elicited and resting-state connectivity in amygdala-cortical circuitry as an exemplar case (given this network's protracted development across these ages). Age-related changes in amygdala functional connectivity converged on the same regions of medial prefrontal cortex (mPFC) and inferior frontal gyrus when elicited by emotional stimuli and when measured at rest. Consistent with the long-term phasic molding hypothesis, prospective analyses for both connections showed that the magnitude of an individual's stimulus-elicited connectivity unidirectionally predicted resting-state functional connectivity 2 years later. For the amygdala-mPFC connection, only stimulus-elicited connectivity during childhood and the transition to adolescence shaped future resting-state connectivity, consistent with a sensitive period ending with adolescence for the amygdala-mPFC circuit. Together, these findings suggest that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited by environmental stimuli over the course of development on the order of years. SIGNIFICANCE STATEMENT A fundamental issue in understanding the ontogeny of brain function is how resting-state (intrinsic) functional networks emerge and relate to stimulus-elicited functional connectivity. Here, we posit and test the long-term phasic molding hypothesis that resting-state network development is influenced by recurring stimulus-elicited connectivity through prospective examination of the developing human amygdala-cortical functional connections. Our results provide critical insight into how early environmental events sculpt functional network architecture across development and highlight childhood as a potential developmental period of heightened malleability for the amygdala-medial prefrontal cortex circuit. These findings have implications for how both positive and adverse experiences influence the developing brain and motivate future investigations of whether this molding mechanism reflects a general phenomenon of brain development. PMID:27122035

  11. How environment and genes shape the adolescent brain.

    PubMed

    Paus, Tomáš

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". This review provides a conceptual framework for the study of factors--in our genes and environment--that shape the adolescent brain. I start by pointing out that brain phenotypes obtained with magnetic resonance imaging are complex traits reflecting the interplay of genes and the environment. In some cases, variations in the structural phenotypes observed during adolescence have their origin in the pre-natal or early post-natal periods. I then emphasize the bidirectional nature of brain-behavior relationships observed during this period of human development, where function may be more likely to influence structure rather than vice versa. In the main part of this article, I review our ongoing work on the influence of gonadal hormones on the adolescent brain. I also discuss the importance of social context and brain plasticity on shaping the relevant neural circuits. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Family functioning in severe brain injuries: correlations with caregivers' burden, perceived social support and quality of life.

    PubMed

    Tramonti, Francesco; Bonfiglio, Luca; Di Bernardo, Carolina; Ulivi, Chiara; Virgillito, Alessandra; Rossi, Bruno; Carboncini, Maria Chiara

    2015-01-01

    Severe brain injuries have long-term consequences on functional status and psychosocial functioning. Family life can be greatly influenced as well, and features of high caregiver burden can emerge. Although the data on caregivers' distress are constantly increasing, less information is available about the role of family functioning. Thirty caregivers of hospitalised patients with severe brain injuries received questionnaires for the evaluation of caregiver burden, family functioning and perceived social support. A semi-structured interview was performed for the evaluation of quality of life. Family cohesion and adaptability positively correlated with caregivers' quality of life and perceived social support. Partner caregivers' scores were significantly higher on the time-dependent burden than those of sons and daughters, whereas the latter scored higher on the emotional burden.

  13. 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

  14. The Cerebellum, Sensitive Periods, and Autism

    PubMed Central

    Wang, Samuel S.-H.; Kloth, Alexander D.; Badura, Aleksandra

    2014-01-01

    Cerebellar research has focused principally on adult motor function. However, the cerebellum also maintains abundant connections with nonmotor brain regions throughout postnatal life. Here we review evidence that the cerebellum may guide the maturation of remote nonmotor neural circuitry and influence cognitive development, with a focus on its relationship with autism. Specific cerebellar zones influence neocortical substrates for social interaction, and we propose that sensitive-period disruption of such internal brain communication can account for autism's key features. PMID:25102558

  15. Dissociable effects of local inhibitory and excitatory theta-burst stimulation on large-scale brain dynamics

    PubMed Central

    Sale, Martin V.; Lord, Anton; Zalesky, Andrew; Breakspear, Michael; Mattingley, Jason B.

    2015-01-01

    Normal brain function depends on a dynamic balance between local specialization and large-scale integration. It remains unclear, however, how local changes in functionally specialized areas can influence integrated activity across larger brain networks. By combining transcranial magnetic stimulation with resting-state functional magnetic resonance imaging, we tested for changes in large-scale integration following the application of excitatory or inhibitory stimulation on the human motor cortex. After local inhibitory stimulation, regions encompassing the sensorimotor module concurrently increased their internal integration and decreased their communication with other modules of the brain. There were no such changes in modular dynamics following excitatory stimulation of the same area of motor cortex nor were there changes in the configuration and interactions between core brain hubs after excitatory or inhibitory stimulation of the same area. These results suggest the existence of selective mechanisms that integrate local changes in neural activity, while preserving ongoing communication between brain hubs. PMID:25717162

  16. The Vertebrate Brain, Evidence of Its Modular Organization and Operating System: Insights into the Brain's Basic Units of Structure, Function, and Operation and How They Influence Neuronal Signaling and Behavior

    PubMed Central

    Baslow, Morris H.

    2011-01-01

    The human brain is a complex organ made up of neurons and several other cell types, and whose role is processing information for use in eliciting behaviors. However, the composition of its repeating cellular units for both structure and function are unresolved. Based on recent descriptions of the brain's physiological “operating system”, a function of the tri-cellular metabolism of N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) for supply of energy, and on the nature of “neuronal words and languages” for intercellular communication, insights into the brain's modular structural and functional units have been gained. In this article, it is proposed that the basic structural unit in brain is defined by its physiological operating system, and that it consists of a single neuron, and one or more astrocytes, oligodendrocytes, and vascular system endothelial cells. It is also proposed that the basic functional unit in the brain is defined by how neurons communicate, and consists of two neurons and their interconnecting dendritic–synaptic–dendritic field. Since a functional unit is composed of two neurons, it requires two structural units to form a functional unit. Thus, the brain can be envisioned as being made up of the three-dimensional stacking and intertwining of myriad structural units which results not only in its gross structure, but also in producing a uniform distribution of binary functional units. Since the physiological NAA–NAAG operating system for supply of energy is repeated in every structural unit, it is positioned to control global brain function. PMID:21720525

  17. How Oral Contraceptives Impact Social-Emotional Behavior and Brain Function.

    PubMed

    Montoya, Estrella R; Bos, Peter A

    2017-02-01

    Millions of women worldwide use oral contraceptives ('the pill'; OCs), often starting at a pubertal age when their brains are in a crucial developmental stage. Research into the social-emotional effects of OCs is of utmost importance. In this review, we provide an overview of studies that have emerged over the past decade investigating how OCs, and their main ingredients estradiol (E) and progesterone (P), influence social-emotional behaviors and underlying brain functions. Based on this overview, we present a heuristic model that postulates that OCs modulate core social-emotional behaviors and brain systems. Research domains and challenges for the future, as well as implications, are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Definition of Traumatic Brain Injury, Neurosurgery, Trauma Orthopedics, Neuroimaging, Psychology, and Psychiatry in Mild Traumatic Brain Injury.

    PubMed

    Pervez, Mubashir; Kitagawa, Ryan S; Chang, Tiffany R

    2018-02-01

    Traumatic brain injury (TBI) disrupts the normal function of the brain. This condition can adversely affect a person's quality of life with cognitive, behavioral, emotional, and physical symptoms that limit interpersonal, social, and occupational functioning. Although many systems exist, the simplest classification includes mild, moderate, and severe TBI depending on the nature of injury and the impact on the patient's clinical status. Patients with TBI require prompt evaluation and multidisciplinary management. Aside from the type and severity of the TBI, recovery is influenced by individual patient characteristics, social and environmental factors, and access to medical and rehabilitation services. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Cerebral Glucose Metabolism and Sedation in Brain-injured Patients: A Microdialysis Study.

    PubMed

    Hertle, Daniel N; Santos, Edgar; Hagenston, Anna M; Jungk, Christine; Haux, Daniel; Unterberg, Andreas W; Sakowitz, Oliver W

    2015-07-01

    Disturbed brain metabolism is a signature of primary damage and/or precipitates secondary injury processes after severe brain injury. Sedatives and analgesics target electrophysiological functioning and are as such well-known modulators of brain energy metabolism. Still unclear, however, is how sedatives impact glucose metabolism and whether they differentially influence brain metabolism in normally active, healthy brain and critically impaired, injured brain. We therefore examined and compared the effects of anesthetic drugs under both critical (<1 mmol/L) and noncritical (>1 mmol/L) extracellular brain glucose levels. We performed an explorative, retrospective analysis of anesthetic drug administration and brain glucose concentrations, obtained by bedside microdialysis, in 19 brain-injured patients. Our investigations revealed an inverse linear correlation between brain glucose and both the concentration of extracellular glutamate (Pearson r=-0.58, P=0.01) and the lactate/glucose ratio (Pearson r=-0.55, P=0.01). For noncritical brain glucose levels, we observed a positive linear correlation between midazolam dose and brain glucose (P<0.05). For critical brain glucose levels, extracellular brain glucose was unaffected by any type of sedative. These findings suggest that the use of anesthetic drugs may be of limited value in attempts to influence brain glucose metabolism in injured brain tissue.

  20. Illness as a source of variation of laterality in lions (Panthera leo).

    PubMed

    Zucca, Paolo; Baciadonna, Luigi; Masci, Stefano; Mariscoli, Massimo

    2011-05-01

    Brain asymmetry--i.e. the specialisation of each cerebral hemisphere for sensorimotor processing mechanisms and for specific cognitive functions-is widely distributed among vertebrates. Several factors, such as embryological manipulations, sex, age, and breeds, can influence the maintenance, strength, and direction of laterality within a certain vertebrate species. Brain lateralisation is a universal phenomenon characterising not only cerebral control of cognitive or emotion-related functions but also cerebral regulation of somatic processes, and its evolution is strongly influenced by social selection pressure. Diseases are well known to be a cost of sociality but their role in influencing behaviour has received very little attention. The present study investigates the influence of illness conditions as a source of variation on laterality in a social keystone vertebrate predator model, the lion. In a preliminary stage, the clinical conditions of 24 adult lions were assessed. The same animals were scored for forelimb preference when in the quadrupedal standing position. Lions show a marked forelimb preference with a population bias towards the use of the right forelimb. Illness conditions strongly influenced the strength of laterality bias, with a significant difference between clinically healthy and sick lions. According to these results, health conditions should be recognised as an important source of variation in brain lateralisation.

  1. Modelling of pathologies of the nervous system by the example of computational and electronic models of elementary nervous systems

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

    Shumilov, V. N., E-mail: vnshumilov@rambler.ru; Syryamkin, V. I., E-mail: maximus70sir@gmail.com; Syryamkin, M. V., E-mail: maximus70sir@gmail.com

    The paper puts forward principles of action of devices operating similarly to the nervous system and the brain of biological systems. We propose an alternative method of studying diseases of the nervous system, which may significantly influence prevention, medical treatment, or at least retardation of development of these diseases. This alternative is to use computational and electronic models of the nervous system. Within this approach, we represent the brain in the form of a huge electrical circuit composed of active units, namely, neuron-like units and connections between them. As a result, we created computational and electronic models of elementary nervousmore » systems, which are based on the principles of functioning of biological nervous systems that we have put forward. Our models demonstrate reactions to external stimuli and their change similarly to the behavior of simplest biological organisms. The models possess the ability of self-training and retraining in real time without human intervention and switching operation/training modes. In our models, training and memorization take place constantly under the influence of stimuli on the organism. Training is without any interruption and switching operation modes. Training and formation of new reflexes occur by means of formation of new connections between excited neurons, between which formation of connections is physically possible. Connections are formed without external influence. They are formed under the influence of local causes. Connections are formed between outputs and inputs of two neurons, when the difference between output and input potentials of excited neurons exceeds a value sufficient to form a new connection. On these grounds, we suggest that the proposed principles truly reflect mechanisms of functioning of biological nervous systems and the brain. In order to confirm the correspondence of the proposed principles to biological nature, we carry out experiments for the study of processes of formation of connections between neurons in simplest biological objects. Based on the correspondence of function of the created models to function of biological nervous systems we suggest the use of computational and electronic models of the brain for the study of its function under normal and pathological conditions, because operating principles of the models are built on principles imitating the function of biological nervous systems and the brain.« less

  2. Modelling of pathologies of the nervous system by the example of computational and electronic models of elementary nervous systems

    NASA Astrophysics Data System (ADS)

    Shumilov, V. N.; Syryamkin, V. I.; Syryamkin, M. V.

    2015-11-01

    The paper puts forward principles of action of devices operating similarly to the nervous system and the brain of biological systems. We propose an alternative method of studying diseases of the nervous system, which may significantly influence prevention, medical treatment, or at least retardation of development of these diseases. This alternative is to use computational and electronic models of the nervous system. Within this approach, we represent the brain in the form of a huge electrical circuit composed of active units, namely, neuron-like units and connections between them. As a result, we created computational and electronic models of elementary nervous systems, which are based on the principles of functioning of biological nervous systems that we have put forward. Our models demonstrate reactions to external stimuli and their change similarly to the behavior of simplest biological organisms. The models possess the ability of self-training and retraining in real time without human intervention and switching operation/training modes. In our models, training and memorization take place constantly under the influence of stimuli on the organism. Training is without any interruption and switching operation modes. Training and formation of new reflexes occur by means of formation of new connections between excited neurons, between which formation of connections is physically possible. Connections are formed without external influence. They are formed under the influence of local causes. Connections are formed between outputs and inputs of two neurons, when the difference between output and input potentials of excited neurons exceeds a value sufficient to form a new connection. On these grounds, we suggest that the proposed principles truly reflect mechanisms of functioning of biological nervous systems and the brain. In order to confirm the correspondence of the proposed principles to biological nature, we carry out experiments for the study of processes of formation of connections between neurons in simplest biological objects. Based on the correspondence of function of the created models to function of biological nervous systems we suggest the use of computational and electronic models of the brain for the study of its function under normal and pathological conditions, because operating principles of the models are built on principles imitating the function of biological nervous systems and the brain.

  3. Influence of paravertebral muscles training on brain plasticity and postural control in chronic low back pain.

    PubMed

    Massé-Alarie, Hugo; Beaulieu, Louis-David; Preuss, Richard; Schneider, Cyril

    2016-07-01

    Isometric activation (ISOM) of deep multifidi muscles (MF) can influence postural adjustments and primary motor cortex (M1) function in chronic low back pain (CLBP). In order to better understand how ISOM impacts on CLBP condition, the present study contrasted ISOM after-effects on M1 function, MF postural activation and pain with another training, the global activation of paravertebral muscles (GLOB, hip extension). The main objective of this study was to compare the effects of ISOM and GLOB (3-week training each) on MF postural activation and M1 function in a CLBP population. Twenty-four people with CLBP were randomly allocated to ISOM and GLOB groups for a 3-week daily practice. Pre/post-training after-effects were assessed by the onset of superficial MF (MF-S) activation during ballistic limb movements (bilateral shoulder flexion in standing; unilateral hip extension in prine lying), MF-S corticomotor control tested by transcranial magnetic stimulation of M1, and assessment of pain, kinesiophobia and disability by standardized questionnaires. Both ISOM and GLOB improved pain and disability. However, only ISOM influenced M1 function (decreased corticospinal excitability and increased intracortical inhibition), fastened MF-S postural activation and decreased kinesiophobia. Changes of corticospinal excitability and of MF-S postural adjustments suggest that ISOM better influenced brain plasticity. Future studies should further test whether our novel findings relate to an influence of the exercises on the lumbopelvic control of different muscles and on cognitive function. Clinically, individual's evaluation remains warranted before prescribing one or the other of these two conventional exercises for reducing pain. This original study presents how motor control exercises can influence brain plasticity and postural control in chronic low back pain. This knowledge will impact on the decision of clinicians to prescribe specific exercises with a view of improving motor control in this musculoskeletal condition. Copyright © 2016 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  4. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis.

    PubMed

    O'Mahony, S M; Clarke, G; Borre, Y E; Dinan, T G; Cryan, J F

    2015-01-15

    The brain-gut axis is a bidirectional communication system between the central nervous system and the gastrointestinal tract. Serotonin functions as a key neurotransmitter at both terminals of this network. Accumulating evidence points to a critical role for the gut microbiome in regulating normal functioning of this axis. In particular, it is becoming clear that the microbial influence on tryptophan metabolism and the serotonergic system may be an important node in such regulation. There is also substantial overlap between behaviours influenced by the gut microbiota and those which rely on intact serotonergic neurotransmission. The developing serotonergic system may be vulnerable to differential microbial colonisation patterns prior to the emergence of a stable adult-like gut microbiota. At the other extreme of life, the decreased diversity and stability of the gut microbiota may dictate serotonin-related health problems in the elderly. The mechanisms underpinning this crosstalk require further elaboration but may be related to the ability of the gut microbiota to control host tryptophan metabolism along the kynurenine pathway, thereby simultaneously reducing the fraction available for serotonin synthesis and increasing the production of neuroactive metabolites. The enzymes of this pathway are immune and stress-responsive, both systems which buttress the brain-gut axis. In addition, there are neural processes in the gastrointestinal tract which can be influenced by local alterations in serotonin concentrations with subsequent relay of signals along the scaffolding of the brain-gut axis to influence CNS neurotransmission. Therapeutic targeting of the gut microbiota might be a viable treatment strategy for serotonin-related brain-gut axis disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Estrogens of multiple classes and their role in mental health disease mechanisms.

    PubMed

    Watson, Cheryl S; Alyea, Rebecca A; Cunningham, Kathryn A; Jeng, Yow-Jiun

    2010-08-09

    Gender and sex hormones can influence a variety of mental health states, including mood, cognitive development and function, and vulnerability to neurodegenerative diseases and brain damage. Functions of neuronal cells may be altered by estrogens depending upon the availability of different physiological estrogenic ligands; these ligands and their effects vary with life stages, the genetic or postgenetic regulation of receptor levels in specific tissues, or the intercession of competing nonphysiological ligands (either intentional or unintentional, beneficial to health or not). Here we review evidence for how different estrogens (physiological and environmental/dietary), acting via different estrogen receptor subtypes residing in alternative subcellular locations, influence brain functions and behavior. We also discuss the families of receptors and transporters for monoamine neurotransmitters and how they may interact with the estrogenic signaling pathways.

  6. Toward reliable characterization of functional homogeneity in the human brain: preprocessing, scan duration, imaging resolution and computational space.

    PubMed

    Zuo, Xi-Nian; Xu, Ting; Jiang, Lili; Yang, Zhi; Cao, Xiao-Yan; He, Yong; Zang, Yu-Feng; Castellanos, F Xavier; Milham, Michael P

    2013-01-15

    While researchers have extensively characterized functional connectivity between brain regions, the characterization of functional homogeneity within a region of the brain connectome is in early stages of development. Several functional homogeneity measures were proposed previously, among which regional homogeneity (ReHo) was most widely used as a measure to characterize functional homogeneity of resting state fMRI (R-fMRI) signals within a small region (Zang et al., 2004). Despite a burgeoning literature on ReHo in the field of neuroimaging brain disorders, its test-retest (TRT) reliability remains unestablished. Using two sets of public R-fMRI TRT data, we systematically evaluated the ReHo's TRT reliability and further investigated the various factors influencing its reliability and found: 1) nuisance (head motion, white matter, and cerebrospinal fluid) correction of R-fMRI time series can significantly improve the TRT reliability of ReHo while additional removal of global brain signal reduces its reliability, 2) spatial smoothing of R-fMRI time series artificially enhances ReHo intensity and influences its reliability, 3) surface-based R-fMRI computation largely improves the TRT reliability of ReHo, 4) a scan duration of 5 min can achieve reliable estimates of ReHo, and 5) fast sampling rates of R-fMRI dramatically increase the reliability of ReHo. Inspired by these findings and seeking a highly reliable approach to exploratory analysis of the human functional connectome, we established an R-fMRI pipeline to conduct ReHo computations in both 3-dimensions (volume) and 2-dimensions (surface). Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Gut-Brain Glucose Signaling in Energy Homeostasis.

    PubMed

    Soty, Maud; Gautier-Stein, Amandine; Rajas, Fabienne; Mithieux, Gilles

    2017-06-06

    Intestinal gluconeogenesis is a recently identified function influencing energy homeostasis. Intestinal gluconeogenesis induced by specific nutrients releases glucose, which is sensed by the nervous system surrounding the portal vein. This initiates a signal positively influencing parameters involved in glucose control and energy management controlled by the brain. This knowledge has extended our vision of the gut-brain axis, classically ascribed to gastrointestinal hormones. Our work raises several questions relating to the conditions under which intestinal gluconeogenesis proceeds and may provide its metabolic benefits. It also leads to questions on the advantage conferred by its conservation through a process of natural selection. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Effect of Sex Differences on Brain Mitochondrial Function and Its Suppression by Ovariectomy and in Aged Mice.

    PubMed

    Gaignard, Pauline; Savouroux, Stéphane; Liere, Philippe; Pianos, Antoine; Thérond, Patrice; Schumacher, Michael; Slama, Abdelhamid; Guennoun, Rachida

    2015-08-01

    Sex steroids regulate brain function in both normal and pathological states. Mitochondria are an essential target of steroids, as demonstrated by the experimental administration of 17β-estradiol or progesterone (PROG) to ovariectomized female rodents, but the influence of endogenous sex steroids remains understudied. To address this issue, mitochondrial oxidative stress, the oxidative phosphorylation system, and brain steroid levels were analyzed under 3 different experimental sets of endocrine conditions. The first set was designed to study steroid-mediated sex differences in young male and female mice, intact and after gonadectomy. The second set concerned young female mice at 3 time points of the estrous cycle in order to analyze the influence of transient variations in steroid levels. The third set involved the evaluation of the effects of a permanent decrease in gonadal steroids in aged male and female mice. Our results show that young adult females have lower oxidative stress and a higher reduced nicotinamide adenine dinucleotide (NADH)-linked respiration rate, which is related to a higher pyruvate dehydrogenase complex activity as compared with young adult males. This sex difference did not depend on phases of the estrous cycle, was suppressed by ovariectomy but not by orchidectomy, and no longer existed in aged mice. Concomitant analysis of brain steroids showed that pregnenolone and PROG brain levels were higher in females during the reproductive period than in males and decreased with aging in females. These findings suggest that the major male/female differences in brain pregnenolone and PROG levels may contribute to the sex differences observed in brain mitochondrial function.

  9. Housing conditions influence motor functions and exploratory behavior following focal damage of the rat brain.

    PubMed

    Gornicka-Pawlak, Elzbieta; Jabłońska, Anna; Chyliński, Andrzej; Domańska-Janik, Krystyna

    2009-01-01

    The present study investigated influence of housing conditions on motor functions recovery and exploratory behavior following ouabain focal brain lesion in the rat. During 30 days post-surgery period rats were housed individually in standard cages (IS) or in groups in enriched environment (EE) and behaviorally tested. The EE lesioned rats showed enhanced recovery from motor impairments in walking beam task, comparing with IS animals. Contrarily, in the open field IS rats (both lesioned and control) traveled a longer distance, showed less habituation and spent less time resting at the home base than the EE animals. Unlike the EE lesioned animals, the lesioned IS rats, presented a tendency to hyperactivity in postinjury period. Turning tendency was significantly affected by unilateral brain lesion only in the EE rats. We can conclude that housing conditions distinctly affected the rat's behavior in classical laboratory tests.

  10. Seizure Control and Memory Impairment Are Related to Disrupted Brain Functional Integration in Temporal Lobe Epilepsy.

    PubMed

    Park, Chang-Hyun; Choi, Yun Seo; Jung, A-Reum; Chung, Hwa-Kyoung; Kim, Hyeon Jin; Yoo, Jeong Hyun; Lee, Hyang Woon

    2017-01-01

    Brain functional integration can be disrupted in patients with temporal lobe epilepsy (TLE), but the clinical relevance of this disruption is not completely understood. The authors hypothesized that disrupted functional integration over brain regions remote from, as well as adjacent to, the seizure focus could be related to clinical severity in terms of seizure control and memory impairment. Using resting-state functional MRI data acquired from 48 TLE patients and 45 healthy controls, the authors mapped functional brain networks and assessed changes in a network parameter of brain functional integration, efficiency, to examine the distribution of disrupted functional integration within and between brain regions. The authors assessed whether the extent of altered efficiency was influenced by seizure control status and whether the degree of altered efficiency was associated with the severity of memory impairment. Alterations in the efficiency were observed primarily near the subcortical region ipsilateral to the seizure focus in TLE patients. The extent of regional involvement was greater in patients with poor seizure control: it reached the frontal, temporal, occipital, and insular cortices in TLE patients with poor seizure control, whereas it was limited to the limbic and parietal cortices in TLE patients with good seizure control. Furthermore, TLE patients with poor seizure control experienced more severe memory impairment, and this was associated with lower efficiency in the brain regions with altered efficiency. These findings indicate that the distribution of disrupted brain functional integration is clinically relevant, as it is associated with seizure control status and comorbid memory impairment.

  11. Branched-chain amino acids and brain function.

    PubMed

    Fernstrom, John D

    2005-06-01

    Branched-chain amino acids (BCAAs) influence brain function by modifying large, neutral amino acid (LNAA) transport at the blood-brain barrier. Transport is shared by several LNAAs, notably the BCAAs and the aromatic amino acids (ArAAs), and is competitive. Consequently, when plasma BCAA concentrations rise, which can occur in response to food ingestion or BCAA administration, or with the onset of certain metabolic diseases (e.g., uncontrolled diabetes), brain BCAA concentrations rise, and ArAA concentrations decline. Such effects occur acutely and chronically. Such reductions in brain ArAA concentrations have functional consequences: biochemically, they reduce the synthesis and the release of neurotransmitters derived from ArAAs, notably serotonin (from tryptophan) and catecholamines (from tyrosine and phenylalanine). The functional effects of such neurochemical changes include altered hormonal function, blood pressure, and affective state. Although the BCAAs thus have biochemical and functional effects in the brain, few attempts have been made to characterize time-course or dose-response relations for such effects. And, no studies have attempted to identify levels of BCAA intake that might produce adverse effects on the brain. The only "model" of very high BCAA exposure is a very rare genetic disorder, maple syrup urine disease, a feature of which is substantial brain dysfunction but that probably cannot serve as a useful model for excessive BCAA intake by normal individuals. Given the known biochemical and functional effects of the BCAAs, it should be a straightforward exercise to design studies to assess dose-response relations for biochemical and functional effects and, in this context, to explore for adverse effect thresholds.

  12. 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.

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

    PubMed

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

    2018-03-12

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

  14. At risk of being risky: The relationship between "brain age" under emotional states and risk preference.

    PubMed

    Rudolph, Marc D; Miranda-Domínguez, Oscar; Cohen, Alexandra O; Breiner, Kaitlyn; Steinberg, Laurence; Bonnie, Richard J; Scott, Elizabeth S; Taylor-Thompson, Kim; Chein, Jason; Fettich, Karla C; Richeson, Jennifer A; Dellarco, Danielle V; Galván, Adriana; Casey, B J; Fair, Damien A

    2017-04-01

    Developmental differences regarding decision making are often reported in the absence of emotional stimuli and without context, failing to explain why some individuals are more likely to have a greater inclination toward risk. The current study (N=212; 10-25y) examined the influence of emotional context on underlying functional brain connectivity over development and its impact on risk preference. Using functional imaging data in a neutral brain-state we first identify the "brain age" of a given individual then validate it with an independent measure of cortical thickness. We then show, on average, that "brain age" across the group during the teen years has the propensity to look younger in emotional contexts. Further, we show this phenotype (i.e. a younger brain age in emotional contexts) relates to a group mean difference in risk perception - a pattern exemplified greatest in young-adults (ages 18-21). The results are suggestive of a specified functional brain phenotype that relates to being at "risk to be risky." Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. At risk of being risky: the relationship between “brain age” under emotional states and risk preference

    PubMed Central

    Rudolph, Marc D.; Miranda-Dominguez, Oscar; Cohen, Alexandra O.; Breiner, Kaitlyn; Steinberg, Laurence; Bonnie, Richard J.; Scott, Elizabeth S.; Taylor-Thompson, Kim A.; Chein, Jason; Fettich, Karla C.; Richeson, Jennifer A.; Dellarco, Danielle V.; Galván, Adriana; Casey, BJ; Fair, Damien A.

    2017-01-01

    Developmental differences regarding decision making are often reported in the absence of emotional stimuli and without context, failing to explain why some individuals are more likely to have a greater inclination toward risk. The current study (N=212; 10–25y) examined the influence of emotional context on underlying functional brain connectivity over development and its impact on risk preference. Using functional imaging data in a neutral brain-state we first identify the “brain age” of a given individual then validate it with an independent measure of cortical thickness. We then show, on average, that “brain age” across the group during the teen years has the propensity to look younger in emotional contexts. Further, we show this phenotype (i.e. a younger brain age in emotional contexts) relates to a group mean difference in risk perception – a pattern exemplified greatest in young-adults (ages 18–21). The results are suggestive of a specified functional brain phenotype that relates to being at “risk to be risky.” PMID:28279917

  16. Executive Functions in Adolescence: Inferences from Brain and Behavior

    ERIC Educational Resources Information Center

    Crone, Eveline A.

    2009-01-01

    Despite the advances in understanding cognitive improvements in executive function in adolescence, much less is known about the influence of affective and social modulators on executive function and the biological underpinnings of these functions and sensitivities. Here, recent behavioral and neuroscientific studies are summarized that have used…

  17. Microglia in the developing brain: a potential target with lifetime effects

    PubMed Central

    Harry, G. Jean; Kraft, Andrew D.

    2012-01-01

    Microglia are a heterogeneous group of monocyte-derived cells serving multiple roles within the brain, many of which are associated with immune and macrophage like properties. These cells are known to serve a critical role during brain injury and to maintain homeostasis; yet, their defined roles during development have yet to be elucidated. Microglial actions appear to influence events associated with neuronal proliferation and differentiation during development, as well as, contribute to processes associated with the removal of dying neurons or cellular debris and management of synaptic connections. These long-lived cells display changes during injury and with aging that are critical to the maintenance of the neuronal environment over the lifespan of the organism. These processes may be altered by changes in the colonization of the brain or by inflammatory events during development. This review addresses the role of microglia during brain development, both structurally and functionally, as well as the inherent vulnerability of the developing nervous system. A framework is presented considering microglia as a critical nervous system-specific cell that can influence multiple aspects of brain development (e.g., vascularization, synaptogenesis, and myelination) and have a long term impact on the functional vulnerability of the nervous system to a subsequent insult, whether environmental, physical, age-related, or disease-related. PMID:22322212

  18. Influences on the Test-Retest Reliability of Functional Connectivity MRI and its Relationship with Behavioral Utility.

    PubMed

    Noble, Stephanie; Spann, Marisa N; Tokoglu, Fuyuze; Shen, Xilin; Constable, R Todd; Scheinost, Dustin

    2017-11-01

    Best practices are currently being developed for the acquisition and processing of resting-state magnetic resonance imaging data used to estimate brain functional organization-or "functional connectivity." Standards have been proposed based on test-retest reliability, but open questions remain. These include how amount of data per subject influences whole-brain reliability, the influence of increasing runs versus sessions, the spatial distribution of reliability, the reliability of multivariate methods, and, crucially, how reliability maps onto prediction of behavior. We collected a dataset of 12 extensively sampled individuals (144 min data each across 2 identically configured scanners) to assess test-retest reliability of whole-brain connectivity within the generalizability theory framework. We used Human Connectome Project data to replicate these analyses and relate reliability to behavioral prediction. Overall, the historical 5-min scan produced poor reliability averaged across connections. Increasing the number of sessions was more beneficial than increasing runs. Reliability was lowest for subcortical connections and highest for within-network cortical connections. Multivariate reliability was greater than univariate. Finally, reliability could not be used to improve prediction; these findings are among the first to underscore this distinction for functional connectivity. A comprehensive understanding of test-retest reliability, including its limitations, supports the development of best practices in the field. © The Author 2017. Published by Oxford University Press.

  19. Thinking, Walking, Talking: Integratory Motor and Cognitive Brain Function

    PubMed Central

    Leisman, Gerry; Moustafa, Ahmed A.; Shafir, Tal

    2016-01-01

    In this article, we argue that motor and cognitive processes are functionally related and most likely share a similar evolutionary history. This is supported by clinical and neural data showing that some brain regions integrate both motor and cognitive functions. In addition, we also argue that cognitive processes coincide with complex motor output. Further, we also review data that support the converse notion that motor processes can contribute to cognitive function, as found by many rehabilitation and aerobic exercise training programs. Support is provided for motor and cognitive processes possessing dynamic bidirectional influences on each other. PMID:27252937

  20. Structure and function of the healthy pre-adolescent pediatric gut microbiome

    USDA-ARS?s Scientific Manuscript database

    The gut microbiome influences myriad host functions, including nutrient acquisition, immune modulation, brain development, and behavior. Although human gut microbiota are recognized to change as we age, information regarding the structure and function of the gut microbiome during childhood is limite...

  1. [Testosterone and psyche].

    PubMed

    Leiber, C; Wetterauer, U; Berner, M

    2010-01-01

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

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

    PubMed

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

    2013-07-01

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

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

    PubMed

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

    2014-09-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2017-04-01

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

  5. Family environment influences emotion recognition following paediatric traumatic brain injury.

    PubMed

    Schmidt, Adam T; Orsten, Kimberley D; Hanten, Gerri R; Li, Xiaoqi; Levin, Harvey S

    2010-01-01

    This study investigated the relationship between family functioning and performance on two tasks of emotion recognition (emotional prosody and face emotion recognition) and a cognitive control procedure (the Flanker task) following paediatric traumatic brain injury (TBI) or orthopaedic injury (OI). A total of 142 children (75 TBI, 67 OI) were assessed on three occasions: baseline, 3 months and 1 year post-injury on the two emotion recognition tasks and the Flanker task. Caregivers also completed the Life Stressors and Resources Scale (LISRES) on each occasion. Growth curve analysis was used to analyse the data. Results indicated that family functioning influenced performance on the emotional prosody and Flanker tasks but not on the face emotion recognition task. Findings on both the emotional prosody and Flanker tasks were generally similar across groups. However, financial resources emerged as significantly related to emotional prosody performance in the TBI group only (p = 0.0123). Findings suggest family functioning variables--especially financial resources--can influence performance on an emotional processing task following TBI in children.

  6. Study of heart-brain interactions through EEG, ECG, and emotions

    NASA Astrophysics Data System (ADS)

    Ramasamy, Mouli; Varadan, Vijay K.

    2017-04-01

    Neurocardiology is the exploration of neurophysiological, neurological and neuroanatomical facets of neuroscience's influence in cardiology. The paraphernalia of emotions on the heart and brain are premeditated because of the interaction between the central and peripheral nervous system. This is an investigative attempt to study emotion based neurocardiology and the factors that influence this phenomenon. The factors include: interaction between sleep EEG (electroencephalogram) and ECG (electrocardiogram), relationship between emotion and music, psychophysiological coherence between the heart and brain, emotion recognition techniques, and biofeedback mechanisms. Emotions contribute vitally to the mundane life and are quintessential to a numerous biological and everyday-functional modality of a human being. Emotions are best represented through EEG signals, and to a certain extent, can be observed through ECG and body temperature. Confluence of medical and engineering science has enabled the monitoring and discrimination of emotions influenced by happiness, anxiety, distress, excitement and several other factors that influence the thinking patterns and the electrical activity of the brain. Similarly, HRV (Heart Rate Variability) widely investigated for its provision and discerning characteristics towards EEG and the perception in neurocardiology.

  7. From the Bottom-Up: Chemotherapy and Gut-Brain Axis Dysregulation.

    PubMed

    Bajic, Juliana E; Johnston, Ian N; Howarth, Gordon S; Hutchinson, Mark R

    2018-01-01

    The central nervous system and gastrointestinal tract form the primary targets of chemotherapy-induced toxicities. Symptoms associated with damage to these regions have been clinically termed chemotherapy-induced cognitive impairment and mucositis. Whilst extensive literature outlines the complex etiology of each pathology, to date neither chemotherapy-induced side-effect has considered the potential impact of one on the pathogenesis of the other disorder. This is surprising considering the close bidirectional relationship shared between each organ; the gut-brain axis. There are complex multiple pathways linking the gut to the brain and vice versa in both normal physiological function and disease. For instance, psychological and social factors influence motility and digestive function, symptom perception, and behaviors associated with illness and pathological outcomes. On the other hand, visceral pain affects central nociception pathways, mood and behavior. Recent interest highlights the influence of functional gut disorders, such as inflammatory bowel diseases and irritable bowel syndrome in the development of central comorbidities. Gut-brain axis dysfunction and microbiota dysbiosis have served as key portals in understanding the potential mechanisms associated with these functional gut disorders and their effects on cognition. In this review we will present the role gut-brain axis dysregulation plays in the chemotherapy setting, highlighting peripheral-to-central immune signaling mechanisms and their contribution to neuroimmunological changes associated with chemotherapy exposure. Here, we hypothesize that dysregulation of the gut-brain axis plays a major role in the intestinal, psychological and neurological complications following chemotherapy. We pay particular attention to evidence surrounding microbiota dysbiosis, the role of intestinal permeability, damage to nerves of the enteric and peripheral nervous systems and vagal and humoral mediated changes.

  8. Using the virtual brain to reveal the role of oscillations and plasticity in shaping brain's dynamical landscape.

    PubMed

    Roy, Dipanjan; Sigala, Rodrigo; Breakspear, Michael; McIntosh, Anthony Randal; Jirsa, Viktor K; Deco, Gustavo; Ritter, Petra

    2014-12-01

    Spontaneous brain activity, that is, activity in the absence of controlled stimulus input or an explicit active task, is topologically organized in multiple functional networks (FNs) maintaining a high degree of coherence. These "resting state networks" are constrained by the underlying anatomical connectivity between brain areas. They are also influenced by the history of task-related activation. The precise rules that link plastic changes and ongoing dynamics of resting-state functional connectivity (rs-FC) remain unclear. Using the framework of the open source neuroinformatics platform "The Virtual Brain," we identify potential computational mechanisms that alter the dynamical landscape, leading to reconfigurations of FNs. Using a spiking neuron model, we first demonstrate that network activity in the absence of plasticity is characterized by irregular oscillations between low-amplitude asynchronous states and high-amplitude synchronous states. We then demonstrate the capability of spike-timing-dependent plasticity (STDP) combined with intrinsic alpha (8-12 Hz) oscillations to efficiently influence learning. Further, we show how alpha-state-dependent STDP alters the local area dynamics from an irregular to a highly periodic alpha-like state. This is an important finding, as the cortical input from the thalamus is at the rate of alpha. We demonstrate how resulting rhythmic cortical output in this frequency range acts as a neuronal tuner and, hence, leads to synchronization or de-synchronization between brain areas. Finally, we demonstrate that locally restricted structural connectivity changes influence local as well as global dynamics and lead to altered rs-FC.

  9. How the Timing and Quality of Early Experiences Influence the Development of Brain Architecture

    PubMed Central

    Fox, Sharon E.; Levitt, Pat; Nelson, Charles A.

    2009-01-01

    Early life events can exert a powerful influence on both the pattern of brain architecture and behavioral development. In this paper a conceptual framework is provided for considering how the structure of early experience gets “under the skin.” The paper begins with a description of the genetic framework that lays the foundation for brain development, and then to the ways experience interacts with and modifies the structures and functions of the developing brain. Much of the attention is focused on early experience and sensitive periods, although it is made clear that later experience also plays an important role in maintaining and elaborating this early wiring diagram, which is critical to establishing a solid footing for development beyond the early years. PMID:20331653

  10. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof-of-concept and roadmap for future studies

    PubMed Central

    Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Shugart, Yin Yao; Ho, Yvonne YW; Martin, Nicholas G; Wright, Margaret J

    2016-01-01

    Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between schizophrenia cases and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. The current study provides proof-of-concept (albeit based on a limited set of structural brain measures), and defines a roadmap for future studies investigating the genetic covariance between structural/functional brain phenotypes and risk for psychiatric disorders. PMID:26854805

  11. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept.

    PubMed

    Franke, Barbara; Stein, Jason L; Ripke, Stephan; Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Shugart, Yin Yao; Ho, Yvonne Yw; Martin, Nicholas G; Wright, Margaret J; O'Donovan, Michael C; Thompson, Paul M; Neale, Benjamin M; Medland, Sarah E; Sullivan, Patrick F

    2016-03-01

    Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.

  12. [Physical activity: positive impact on brain plasticity].

    PubMed

    Achiron, Anat; Kalron, Alon

    2008-03-01

    The central nervous system has a unique capability of plasticity that enables a single neuron or a group of neurons to undergo functional and constructional changes that are important to learning processes and for compensation of brain damage. The current review aims to summarize recent data related to the effects of physical activity on brain plasticity. In the last decade it was reported that physical activity can affect and manipulate neuronal connections, synaptic activity and adaptation to new neuronal environment following brain injury. One of the most significant neurotrophic factors that is critical for synaptic re-organization and is influenced by physical activity is brain-derived neurotrophic factor (BDNF). The frequency of physical activity and the intensity of exercises are of importance to brain remodeling, support neuronal survival and positively affect rehabilitation therapy. Physical activity should be employed as a tool to improve neural function in healthy subjects and in patients suffering from neurological damage.

  13. EEG functional connectivity is partially predicted by underlying white matter connectivity

    PubMed Central

    Chu, CJ; Tanaka, N; Diaz, J; Edlow, BL; Wu, O; Hämäläinen, M; Stufflebeam, S; Cash, SS; Kramer, MA.

    2015-01-01

    Over the past decade, networks have become a leading model to illustrate both the anatomical relationships (structural networks) and the coupling of dynamic physiology (functional networks) linking separate brain regions. The relationship between these two levels of description remains incompletely understood and an area of intense research interest. In particular, it is unclear how cortical currents relate to underlying brain structural architecture. In addition, although theory suggests that brain communication is highly frequency dependent, how structural connections influence overlying functional connectivity in different frequency bands has not been previously explored. Here we relate functional networks inferred from statistical associations between source imaging of EEG activity and underlying cortico-cortical structural brain connectivity determined by probabilistic white matter tractography. We evaluate spontaneous fluctuating cortical brain activity over a long time scale (minutes) and relate inferred functional networks to underlying structural connectivity for broadband signals, as well as in seven distinct frequency bands. We find that cortical networks derived from source EEG estimates partially reflect both direct and indirect underlying white matter connectivity in all frequency bands evaluated. In addition, we find that when structural support is absent, functional connectivity is significantly reduced for high frequency bands compared to low frequency bands. The association between cortical currents and underlying white matter connectivity highlights the obligatory interdependence of functional and structural networks in the human brain. The increased dependence on structural support for the coupling of higher frequency brain rhythms provides new evidence for how underlying anatomy directly shapes emergent brain dynamics at fast time scales. PMID:25534110

  14. How emotional abilities modulate the influence of early life stress on hippocampal functioning.

    PubMed

    Aust, Sabine; Alkan Härtwig, Elif; Koelsch, Stefan; Heekeren, Hauke R; Heuser, Isabella; Bajbouj, Malek

    2014-07-01

    Early life stress (ELS) is known to have considerable influence on brain development, mental health and affective functioning. Previous investigations have shown that alexithymia, a prevalent personality trait associated with difficulties experiencing and verbalizing emotions, is particularly related to ELS. The aim of the present study was to investigate how neural correlates of emotional experiences in alexithymia are altered in the presence and absence of ELS. Therefore, 50 healthy individuals with different levels of alexithymia were matched regarding ELS and investigated with respect to neural correlates of audio-visually induced emotional experiences via functional magnetic resonance imaging. The main finding was that ELS modulated hippocampal responses to pleasant (>neutral) stimuli in high-alexithymic individuals, whereas there was no such modulation in low-alexithymic individuals matched for ELS. Behavioral and psychophysiological results followed a similar pattern. When considered independent of ELS, alexithymia was associated with decreased responses in insula (pleasant > neutral) and temporal pole (unpleasant > neutral). Our results show that the influence of ELS on emotional brain responses seems to be modulated by an individual's degree of alexithymia. Potentially, protective and adverse effects of emotional abilities on brain responses to emotional experiences are discussed. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  15. Estradiol modulates functional brain organization during the menstrual cycle: an analysis of interhemispheric inhibition.

    PubMed

    Weis, Susanne; Hausmann, Markus; Stoffers, Barbara; Vohn, René; Kellermann, Thilo; Sturm, Walter

    2008-12-10

    According to the hypothesis of progesterone-mediated interhemispheric decoupling (Hausmann and Güntürkün, 2000), functional cerebral asymmetries (FCAs), which are stable in men and change during the menstrual cycle in women, are generated by interhemispheric inhibition of the dominant on the nondominant hemisphere. The change of lateralization during the menstrual cycle in women might indicate that sex hormones play an important role in modulating FCAs. We used functional magnetic resonance imaging to examine the role of estradiol in determining cyclic changes of interhemispheric inhibition. Women performed a word-matching task, while they were scanned twice during the cycle, once during the menstrual and once during the follicular phase. By use of a connectivity analysis we found that the inhibitory influence of left-hemispheric language areas on homotopic areas of the right hemisphere is strongest during the menses, resulting in a pronounced lateralization. During the follicular phase, due to rising estradiol levels, inhibition and thus functional cerebral asymmetries are reduced. These results reveal a powerful neuromodulatory action of estradiol on the dynamics of functional brain organization in the female brain. They may further contribute to the ongoing discussion of sex differences in brain function in that they help explain the dynamic part of functional brain organization in which the female differs from the male brain.

  16. Mapping the Regional Influence of Genetics on Brain Structure Variability - A Tensor-Based Morphometry Study

    PubMed Central

    Brun, Caroline; Leporé, Natasha; Pennec, Xavier; Lee, Agatha D.; Barysheva, Marina; Madsen, Sarah K.; Avedissian, Christina; Chou, Yi-Yu; de Zubicaray, Greig I.; McMahon, Katie; Wright, Margaret; Toga, Arthur W.; Thompson, Paul M.

    2010-01-01

    Genetic and environmental factors influence brain structure and function profoundly The search for heritable anatomical features and their influencing genes would be accelerated with detailed 3D maps showing the degree to which brain morphometry is genetically determined. As part of an MRI study that will scan 1150 twins, we applied Tensor-Based Morphometry to compute morphometric differences in 23 pairs of identical twins and 23 pairs of same-sex fraternal twins (mean age: 23.8 ± 1.8 SD years). All 92 twins’ 3D brain MRI scans were nonlinearly registered to a common space using a Riemannian fluid-based warping approach to compute volumetric differences across subjects. A multi-template method was used to improve volume quantification. Vector fields driving each subject’s anatomy onto the common template were analyzed to create maps of local volumetric excesses and deficits relative to the standard template. Using a new structural equation modeling method, we computed the voxelwise proportion of variance in volumes attributable to additive (A) or dominant (D) genetic factors versus shared environmental (C) or unique environmental factors (E). The method was also applied to various anatomical regions of interest (ROIs). As hypothesized, the overall volumes of the brain, basal ganglia, thalamus, and each lobe were under strong genetic control; local white matter volumes were mostly controlled by common environment. After adjusting for individual differences in overall brain scale, genetic influences were still relatively high in the corpus callosum and in early-maturing brain regions such as the occipital lobes, while environmental influences were greater in frontal brain regions which have a more protracted maturational time-course. PMID:19446645

  17. Influence of BDNF Genotype and Exercise on BDNF Serum Levels and VO2 Max after Acute Exercise and Post Training

    DTIC Science & Technology

    2017-07-29

    exercise prescription and training. 15. SUBJECT TERMS cognitive, physical training, BDNF, Val66Val, Val66Met, VO2Max 16. SECURITY CLASSIFICATION...Key Words: Functional agility training, physical training, cognitive upregulation, brain-derived neurotrophic factor, BDNF, Val66Val, Val66Met...cognitive output [21,29,30]. Met carriers may also experience better physical function recovery post-brain injury event [31]. Importantly, exercise may

  18. Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future "Non-Cognitive" Outcomes of Alzheimer's Disease.

    PubMed

    Ingber, Adam P; Hassenstab, Jason; Fagan, Anne M; Benzinger, Tammie L S; Grant, Elizabeth A; Holtzman, David M; Morris, John C; Roe, Catherine M

    2016-01-01

    The influence of reserve variables and Alzheimer's disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on "non-cognitive" outcomes, including functional abilities and mood. We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior. Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants. Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers. The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD.

  19. Cerebral motor function in very premature-at-birth adolescents: a brain stimulation exploration of kangaroo mother care effects.

    PubMed

    Schneider, Cyril; Charpak, Nathalie; Ruiz-Peláez, Juan G; Tessier, Réjean

    2012-10-01

      Given that prematurity has deleterious effects on brain networking development beyond childhood, the study explored whether an early intervention such as Kangaroo Mother Care (KMC) in very preterm preemies could have influenced brain motor function up to adolescence.   Transcranial magnetic stimulation (TMS) was applied over the primary motor cortex (M1) of 39 adolescents born very prematurely (<33 weeks' gestational age, 21 having received KMC after birth, 18 Controls with no KMC) and nine adolescents born at term (>37 weeks' gestational age, >2500 g) to assess the functional integrity of motor circuits in each hemisphere (motor planning) and between hemispheres (callosal function).   All TMS outcomes were similar between KMC and term adolescents, with typical values as in healthy adults, and better than in Controls. KMC adolescents presented faster conduction times revealing more efficient M1 cell synchronization (p < 0.05) and interhemispheric transfer time (p < 0.0001), more frequent inhibitory processes with a better control between hemispheres (p < 0.0001).   The enhanced synchronization, conduction times and connectivity of cerebral motor pathways in the KMC group suggests that the Kangaroo Mother Care positively influenced the premature brain networks and synaptic efficacy up to adolescence. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

  20. Trigeminal, Visceral and Vestibular Inputs May Improve Cognitive Functions by Acting through the Locus Coeruleus and the Ascending Reticular Activating System: A New Hypothesis

    PubMed Central

    De Cicco, Vincenzo; Tramonti Fantozzi, Maria P.; Cataldo, Enrico; Barresi, Massimo; Bruschini, Luca; Faraguna, Ugo; Manzoni, Diego

    2018-01-01

    It is known that sensory signals sustain the background discharge of the ascending reticular activating system (ARAS) which includes the noradrenergic locus coeruleus (LC) neurons and controls the level of attention and alertness. Moreover, LC neurons influence brain metabolic activity, gene expression and brain inflammatory processes. As a consequence of the sensory control of ARAS/LC, stimulation of a sensory channel may potential influence neuronal activity and trophic state all over the brain, supporting cognitive functions and exerting a neuroprotective action. On the other hand, an imbalance of the same input on the two sides may lead to an asymmetric hemispheric excitability, leading to an impairment in cognitive functions. Among the inputs that may drive LC neurons and ARAS, those arising from the trigeminal region, from visceral organs and, possibly, from the vestibular system seem to be particularly relevant in regulating their activity. The trigeminal, visceral and vestibular control of ARAS/LC activity may explain why these input signals: (1) affect sensorimotor and cognitive functions which are not directly related to their specific informational content; and (2) are effective in relieving the symptoms of some brain pathologies, thus prompting peripheral activation of these input systems as a complementary approach for the treatment of cognitive impairments and neurodegenerative disorders. PMID:29358907

  1. Genetic and environmental influences on the size of specific brain regions in midlife: the VETSA MRI study.

    PubMed

    Kremen, William S; Prom-Wormley, Elizabeth; Panizzon, Matthew S; Eyler, Lisa T; Fischl, Bruce; Neale, Michael C; Franz, Carol E; Lyons, Michael J; Pacheco, Jennifer; Perry, Michele E; Stevens, Allison; Schmitt, J Eric; Grant, Michael D; Seidman, Larry J; Thermenos, Heidi W; Tsuang, Ming T; Eisen, Seth A; Dale, Anders M; Fennema-Notestine, Christine

    2010-01-15

    The impact of genetic and environmental factors on human brain structure is of great importance for understanding normative cognitive and brain aging as well as neuropsychiatric disorders. However, most studies of genetic and environmental influences on human brain structure have either focused on global measures or have had samples that were too small for reliable estimates. Using the classical twin design, we assessed genetic, shared environmental, and individual-specific environmental influences on individual differences in the size of 96 brain regions of interest (ROIs). Participants were 474 middle-aged male twins (202 pairs; 70 unpaired) in the Vietnam Era Twin Study of Aging (VETSA). They were 51-59 years old, and were similar to U.S. men in their age range in terms of sociodemographic and health characteristics. We measured thickness of cortical ROIs and volume of other ROIs. On average, genetic influences accounted for approximately 70% of the variance in the volume of global, subcortical, and ventricular ROIs and approximately 45% of the variance in the thickness of cortical ROIs. There was greater variability in the heritability of cortical ROIs (0.00-0.75) as compared with subcortical and ventricular ROIs (0.48-0.85). The results did not indicate lateralized heritability differences or greater genetic influences on the size of regions underlying higher cognitive functions. The findings provide key information for imaging genetic studies and other studies of brain phenotypes and endophenotypes. Longitudinal analysis will be needed to determine whether the degree of genetic and environmental influences changes for different ROIs from midlife to later life.

  2. The role of sex and gender in neuropsychiatric disorders.

    PubMed

    Thibaut, Florence

    2016-12-01

    The prevalence, age of onset, and clinical symptoms of many neuropsychiatric diseases substantially differ between males and females. Factors influencing the relationships between brain development and function and sex or gender may help us understand the differences between males and females in terms of risk or resilience factors in brain diseases.

  3. Eating breakfast enhances the efficiency of neural networks engaged during mental arithmetic in school-aged children

    USDA-ARS?s Scientific Manuscript database

    Are there effects of morning nutrition on brain functions important for learning and performance in children? We used time-frequency analyses of EEG activity recorded while children solved simple math problems to study how brain processes were influenced by eating or skipping breakfast. Participants...

  4. Sleep and Psychiatric Disorders in Persons With Mild Traumatic Brain Injury.

    PubMed

    Mollayeva, Tatyana; D'Souza, Andrea; Mollayeva, Shirin

    2017-08-01

    Mild traumatic brain injury (mTBI) frequently challenges the integrity of sleep function by affecting multiple brain areas implicated in controlling the switch between wakefulness and sleep and those involved in circadian and homeostatic processes; the malfunction of each causes a variety of disorders. In this review, we discuss recent data on the dynamics between disorders of sleep and mental/psychiatric disorders in persons with mTBI. This analysis sets the stage for understanding how a variety of physiological, emotional and environmental influences affect sleep and mental activities after injury to the brain. Consideration of the intricate links between sleep and mental functions in future research can increase understanding on the underlying mechanisms of sleep-related and psychiatric comorbidity in mTBI.

  5. 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

  6. Bridging animal and human models of exercise-induced brain plasticity

    PubMed Central

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

    2015-01-01

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

  7. 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.

  8. Speech-induced striatal dopamine release is left lateralized and coupled to functional striatal circuits in healthy humans: A combined PET, fMRI and DTI study

    PubMed Central

    Simonyan, Kristina; Herscovitch, Peter; Horwitz, Barry

    2013-01-01

    Considerable progress has been recently made in understanding the brain mechanisms underlying speech and language control. However, the neurochemical underpinnings of normal speech production remain largely unknown. We investigated the extent of striatal endogenous dopamine release and its influences on the organization of functional striatal speech networks during production of meaningful English sentences using a combination of positron emission tomography (PET) with the dopamine D2/D3 receptor radioligand [11C]raclopride and functional MRI (fMRI). In addition, we used diffusion tensor tractography (DTI) to examine the extent of dopaminergic modulatory influences on striatal structural network organization. We found that, during sentence production, endogenous dopamine was released in the ventromedial portion of the dorsal striatum, in its both associative and sensorimotor functional divisions. In the associative striatum, speech-induced dopamine release established a significant relationship with neural activity and influenced the left-hemispheric lateralization of striatal functional networks. In contrast, there were no significant effects of endogenous dopamine release on the lateralization of striatal structural networks. Our data provide the first evidence for endogenous dopamine release in the dorsal striatum during normal speaking and point to the possible mechanisms behind the modulatory influences of dopamine on the organization of functional brain circuits controlling normal human speech. PMID:23277111

  9. Do (epi)genetics impact the brain in functional neurologic disorders?

    PubMed

    Frodl, T

    2016-01-01

    Advances in neuropsychiatric research are supposed to lead to significant improvements in understanding functional neurologic disorders and their diagnosis. However, epigenetic and genetic research on conversion disorders and somatoform disorders is only at its start. This review demonstrates the current state within this field and tries to bridge a gap from what is known on gene-stress interactions in other psychiatric disorders like depression. The etiology of conversion disorders is hypothesized to be multifactorial. These considerations also suggest that potential etiologic factors lead to alterations in brain function, either episodically or chronically, eventually leading to structural brain changes. In particular, the knowledge of how the environment influences brain structure and function, e.g., via epigenetic regulation, may be interesting for future research in functional neurologic disorders. Reviewing the literature results in evidence that childhood adversities play a role in the development of functional neurologic disorders, whereby at present no reports exist about the interactive effect between childhood adversity and genetic factors or about the impact of epigenetics. © 2016 Elsevier B.V. All rights reserved.

  10. Regional autonomy changes in resting-state functional MRI in patients with HIV associated neurocognitive disorder

    NASA Astrophysics Data System (ADS)

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

    2018-03-01

    In this study, we investigate whether there are discernable changes in influence that brain regions have on themselves once patients show symptoms of HIV Associated Neurocognitive Disorder (HAND) using functional MRI (fMRI). Simple functional connectivity measures, such as correlation cannot reveal such information. To this end, we use mutual connectivity analysis (MCA) with Local Models (LM), which reveals a measure of influence in terms of predictability. Once such measures of interaction are obtained, we train two classifiers to characterize difference in patterns of regional self-influence between healthy subjects and subjects presenting with HAND symptoms. The two classifiers we use are Support Vector Machines (SVM) and Localized Generalized Matrix Learning Vector Quantization (LGMLVQ). Performing machine learning on fMRI connectivity measures is popularly known as multi-voxel pattern analysis (MVPA). By performing such an analysis, we are interested in studying the impact HIV infection has on an individual's brain. The high area under receiver operating curve (AUC) and accuracy values for 100 different train/test separations using MCA-LM self-influence measures (SVM: mean AUC=0.86, LGMLVQ: mean AUC=0.88, SVM and LGMLVQ: mean accuracy=0.78) compared with standard MVPA analysis using cross-correlation between fMRI time-series (SVM: mean AUC=0.58, LGMLVQ: mean AUC=0.57), demonstrates that self-influence features can be more discriminative than measures of interaction between time-series pairs. Furthermore, our results suggest that incorporating measures of self-influence in MVPA analysis used commonly in fMRI analysis has the potential to provide a performance boost and indicate important changes in dynamics of regions in the brain as a consequence of HIV infection.

  11. The Network Architecture of Cortical Processing in Visuo-spatial Reasoning

    PubMed Central

    Shokri-Kojori, Ehsan; Motes, Michael A.; Rypma, Bart; Krawczyk, Daniel C.

    2012-01-01

    Reasoning processes have been closely associated with prefrontal cortex (PFC), but specifically emerge from interactions among networks of brain regions. Yet it remains a challenge to integrate these brain-wide interactions in identifying the flow of processing emerging from sensory brain regions to abstract processing regions, particularly within PFC. Functional magnetic resonance imaging data were collected while participants performed a visuo-spatial reasoning task. We found increasing involvement of occipital and parietal regions together with caudal-rostral recruitment of PFC as stimulus dimensions increased. Brain-wide connectivity analysis revealed that interactions between primary visual and parietal regions predominantly influenced activity in frontal lobes. Caudal-to-rostral influences were found within left-PFC. Right-PFC showed evidence of rostral-to-caudal connectivity in addition to relatively independent influences from occipito-parietal cortices. In the context of hierarchical views of PFC organization, our results suggest that a caudal-to-rostral flow of processing may emerge within PFC in reasoning tasks with minimal top-down deductive requirements. PMID:22624092

  12. The network architecture of cortical processing in visuo-spatial reasoning.

    PubMed

    Shokri-Kojori, Ehsan; Motes, Michael A; Rypma, Bart; Krawczyk, Daniel C

    2012-01-01

    Reasoning processes have been closely associated with prefrontal cortex (PFC), but specifically emerge from interactions among networks of brain regions. Yet it remains a challenge to integrate these brain-wide interactions in identifying the flow of processing emerging from sensory brain regions to abstract processing regions, particularly within PFC. Functional magnetic resonance imaging data were collected while participants performed a visuo-spatial reasoning task. We found increasing involvement of occipital and parietal regions together with caudal-rostral recruitment of PFC as stimulus dimensions increased. Brain-wide connectivity analysis revealed that interactions between primary visual and parietal regions predominantly influenced activity in frontal lobes. Caudal-to-rostral influences were found within left-PFC. Right-PFC showed evidence of rostral-to-caudal connectivity in addition to relatively independent influences from occipito-parietal cortices. In the context of hierarchical views of PFC organization, our results suggest that a caudal-to-rostral flow of processing may emerge within PFC in reasoning tasks with minimal top-down deductive requirements.

  13. Influence of strain rate on indentation response of porcine brain.

    PubMed

    Qian, Long; Zhao, Hongwei; Guo, Yue; Li, Yuanshang; Zhou, Mingxing; Yang, Liguo; Wang, Zhiwei; Sun, Yifan

    2018-06-01

    Knowledge of brain tissue mechanical properties may be critical for formulating hypotheses about some specific diseases mechanisms and its accurate simulations such as traumatic brain injury (TBI) and tumor growth. Compared to traditional tests (e.g. tensile and compression), indentation shows superiority by virtue of its pinpoint and nondestructive/quasi-nondestructive. As a viscoelastic material, the properties of brain tissue depend on the strain rate by definition. However most efforts focus on the aspect of velocity in the field of brain indentation, rather than strain rate. The influence of strain rate on indentation response of brain tissue is taken little attention. Further, by comparing different results from literatures, it is also obvious that strain rate rather than velocity is more appropriate to characterize mechanical properties of brain. In this paper, to systematically characterize the influence of strain rate, a series of indentation-relaxation tests n = 210) are performed on the cortex of porcine brain using a custom-designed indentation device. The mechanical response that correlates with indenter diameters, depths of indentation and velocities, is revealed for the indentation portion, and elastic behavior of brain tissue is analyzed as the function of strain rate. Similarly, a linear viscoelastic model with a Prony series is employed for the indentation-relaxation portion, wherein the brain tissue shows more viscous and responds more quickly with increasing strain rate. Understanding the effect of strain rate on mechanical properties of brain indentation may be far-reaching for brain injury biomechanics and accurate simulations, but be important for bridging between indentation results of different literatures. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Vitamins and neural and cognitive developmental outcomes in children.

    PubMed

    Benton, David

    2012-02-01

    The role of vitamin status in the development of the brain and the subsequent functioning of the brain was considered. There are data with a range of vitamins, from animal studies and human studies in developing countries, suggesting that a clinical deficiency during the critical period when the brain is developing causes permanent damage. To date there is, however, with the exception of cases of clinical deficiency such as those that might be associated with a vegan diet, little evidence that variations in the diet of those living in industrialised countries have a lasting developmental influence. Similarly, later in life clinical deficiencies of various vitamins disrupt cognition although there is to date limited evidence that variations in the intake of single vitamins in industrialised societies influence functioning. It may well be, however, unreasonable to expect that vitamins examined in isolation will be associated with differences in cognitive functioning. The output of the brain reflects millions of metabolic processes, each potentially susceptible to any of a range of vitamins. A diet poor in one respect is likely to be poor in other respects as well. As such, the preliminary reports in double-blind placebo-controlled trials that aspects of cognition and behaviour respond to supplementation with multi-micronutrients may indicate the way forward.

  15. 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

  16. Decrease in fMRI brain activation during working memory performed after sleeping under 10 lux light.

    PubMed

    Kang, Seung-Gul; Yoon, Ho-Kyoung; Cho, Chul-Hyun; Kwon, Soonwook; Kang, June; Park, Young-Min; Lee, Eunil; Kim, Leen; Lee, Heon-Jeong

    2016-11-09

    The aim of this study was to investigate the effect of exposure to dim light at night (dLAN) when sleeping on functional brain activation during a working-memory tasks. We conducted the brain functional magnetic resonance imaging (fMRI) analysis on 20 healthy male subjects. All participants slept in a polysomnography laboratory without light exposure on the first and second nights and under a dim-light condition of either 5 or 10 lux on the third night. The fMRI scanning was conducted during n-back tasks after second and third nights. Statistical parametric maps revealed less activation in the right inferior frontal gyrus (IFG) after exposure to 10-lux light. The brain activity in the right and left IFG areas decreased more during the 2-back task than during the 1- or 0-back task in the 10-lux group. The exposure to 5-lux light had no significant effect on brain activities. The exposure to dLAN might influence the brain function which is related to the cognition.

  17. Molecular Imaging Provides Novel Insights on Estrogen Receptor Activity in Mouse Brain

    PubMed Central

    Stell, Alessia; Belcredito, Silvia; Ciana, Paolo; Maggi, Adriana

    2009-01-01

    Estrogen receptors have long been known to be expressed in several brain areas in addition to those directly involved in the control of reproductive functions. Investigations in humans and in animal models suggest a strong influence of estrogens on limbic and motor functions, yet the complexity and heterogeneity of neural tissue have limited our approaches to the full understanding of estrogen activity in the central nervous system. The aim of this study was to examine the transcriptional activity of estrogen receptors in the brain of male and female mice. Exploiting the ERE-Luc reporter mouse, we set up a novel, bioluminescence-based technique to study brain estrogen receptor transcriptional activity. Here we show, for the first time, that estrogen receptors are similarly active in male and female brains and that the estrous cycle affects estrogen receptor activity in regions of the central nervous system not known to be associated with reproductive functions. Because of its reproducibility and sensitivity, this novel bioluminescence application candidates as an innovative methodology for the study and development of drugs targeting brain estrogen receptors. PMID:19123998

  18. Molecular imaging provides novel insights on estrogen receptor activity in mouse brain.

    PubMed

    Stell, Alessia; Belcredito, Silvia; Ciana, Paolo; Maggi, Adriana

    2008-01-01

    Estrogen receptors have long been known to be expressed in several brain areas in addition to those directly involved in the control of reproductive functions. Investigations in humans and in animal models suggest a strong influence of estrogens on limbic and motor functions, yet the complexity and heterogeneity of neural tissue have limited our approaches to the full understanding of estrogen activity in the central nervous system. The aim of this study was to examine the transcriptional activity of estrogen receptors in the brain of male and female mice. Exploiting the ERE-Luc reporter mouse, we set up a novel, bioluminescence-based technique to study brain estrogen receptor transcriptional activity. Here we show, for the first time, that estrogen receptors are similarly active in male and female brains and that the estrous cycle affects estrogen receptor activity in regions of the central nervous system not known to be associated with reproductive functions. Because of its reproducibility and sensitivity, this novel bioluminescence application stands as a candidate as an innovative methodology for the study and development of drugs targeting brain estrogen receptors.

  19. Income change alters default mode network connectivity for adolescents in poverty.

    PubMed

    Weissman, David G; Conger, Rand D; Robins, Richard W; Hastings, Paul D; Guyer, Amanda E

    2018-04-01

    Experiencing poverty during childhood and adolescence may affect brain function. However, income is dynamic, and studies have not addressed whether income change relates to brain function. In the present study, we investigated whether intrinsic functional connectivity of default mode network (DMN) regions was influenced by mean family income and family income change. Parents of 68 Mexican-origin adolescents (35 females) reported family income annually when adolescents were 10-16 years old. Intercept and slope of income at each of these ages were calculated for each participant. At age 16 years, adolescents completed a resting state functional neuroimaging scan. Adolescents from high and low income families did not differ in their functional connectivity, but for adolescents in families with lower incomes, their connectivity patterns depended on their income slope. Low-income adolescents whose income increased demonstrated greater connectivity between the posterior cingulate cortex (PCC) and the medial prefrontal cortex (mPFC), both DMN regions, and between the PCC and the right inferior frontal gyrus. Increases in income were associated with greater connectivity of the mPFC with the right inferior frontal gyrus and the left superior parietal lobule regardless of mean income. Increases in income, especially among adolescents in poverty, may alleviate stressors, influencing the development of brain networks. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Reduced cognitive function, increased blood-brain-barrier transport and inflammatory responses, and altered brain metabolites in LDLr -/-and C57BL/6 mice fed a western diet

    PubMed Central

    Lee, Linda L.; Puchowicz, Michelle; Golub, Mari S.; Befroy, Douglas E.; Wilson, Dennis W.; Anderson, Steven; Cline, Gary; Bini, Jason; Borkowski, Kamil; Knotts, Trina A.; Rutledge, John C.

    2018-01-01

    Recent work suggests that diet affects brain metabolism thereby impacting cognitive function. Our objective was to determine if a western diet altered brain metabolism, increased blood-brain barrier (BBB) transport and inflammation, and induced cognitive impairment in C57BL/6 (WT) mice and low-density lipoprotein receptor null (LDLr -/-) mice, a model of hyperlipidemia and cognitive decline. We show that a western diet and LDLr -/- moderately influence cognitive processes as assessed by Y-maze and radial arm water maze. Also, western diet significantly increased BBB transport, as well as microvessel factor VIII in LDLr -/- and microglia IBA1 staining in WT, both indicators of activation and neuroinflammation. Interestingly, LDLr -/- mice had a significant increase in 18F- fluorodeoxyglucose uptake irrespective of diet and brain 1H-magnetic resonance spectroscopy showed increased lactate and lipid moieties. Metabolic assessments of whole mouse brain by GC/MS and LC/MS/MS showed that a western diet altered brain TCA cycle and β-oxidation intermediates, levels of amino acids, and complex lipid levels and elevated proinflammatory lipid mediators. Our study reveals that the western diet has multiple impacts on brain metabolism, physiology, and altered cognitive function that likely manifest via multiple cellular pathways. PMID:29444171

  1. The Alzheimer's Disease Mitochondrial Cascade Hypothesis: Progress and Perspectives

    PubMed Central

    Swerdlow, Russell H.; Burns, Jeffrey M.; Khan, Shaharyar M.

    2013-01-01

    Ten years ago we first proposed the Alzheimer's disease (AD) mitochondrial cascade hypothesis. This hypothesis maintains gene inheritance defines an individual's baseline mitochondrial function; inherited and environmental factors determine rates at which mitochondrial function changes over time; and baseline mitochondrial function and mitochondrial change rates influence AD chronology. Our hypothesis unequivocally states in sporadic, late-onset AD, mitochondrial function affects amyloid precursor protein (APP) expression, APP processing, or beta amyloid (Aβ) accumulation and argues if an amyloid cascade truly exists, mitochondrial function triggers it. We now review the state of the mitochondrial cascade hypothesis, and discuss it in the context of recent AD biomarker studies, diagnostic criteria, and clinical trials. Our hypothesis predicts biomarker changes reflect brain aging, new AD definitions clinically stage brain aging, and removing brain Aβ at any point will marginally impact cognitive trajectories. Our hypothesis, therefore, offers unique perspective into what sporadic, late-onset AD is and how to best treat it. PMID:24071439

  2. Functional Interplay between Small Non-Coding RNAs and RNA Modification in the Brain.

    PubMed

    Leighton, Laura J; Bredy, Timothy W

    2018-06-07

    Small non-coding RNAs are essential for transcription, translation and gene regulation in all cell types, but are particularly important in neurons, with known roles in neurodevelopment, neuroplasticity and neurological disease. Many small non-coding RNAs are directly involved in the post-transcriptional modification of other RNA species, while others are themselves substrates for modification, or are functionally modulated by modification of their target RNAs. In this review, we explore the known and potential functions of several distinct classes of small non-coding RNAs in the mammalian brain, focusing on the newly recognised interplay between the epitranscriptome and the activity of small RNAs. We discuss the potential for this relationship to influence the spatial and temporal dynamics of gene activation in the brain, and predict that further research in the field of epitranscriptomics will identify interactions between small RNAs and RNA modifications which are essential for higher order brain functions such as learning and memory.

  3. Brain and language: evidence for neural multifunctionality.

    PubMed

    Cahana-Amitay, Dalia; Albert, Martin L

    2014-01-01

    This review paper presents converging evidence from studies of brain damage and longitudinal studies of language in aging which supports the following thesis: the neural basis of language can best be understood by the concept of neural multifunctionality. In this paper the term "neural multifunctionality" refers to incorporation of nonlinguistic functions into language models of the intact brain, reflecting a multifunctional perspective whereby a constant and dynamic interaction exists among neural networks subserving cognitive, affective, and praxic functions with neural networks specialized for lexical retrieval, sentence comprehension, and discourse processing, giving rise to language as we know it. By way of example, we consider effects of executive system functions on aspects of semantic processing among persons with and without aphasia, as well as the interaction of executive and language functions among older adults. We conclude by indicating how this multifunctional view of brain-language relations extends to the realm of language recovery from aphasia, where evidence of the influence of nonlinguistic factors on the reshaping of neural circuitry for aphasia rehabilitation is clearly emerging.

  4. Shiga Toxin 1 Induces on Lipopolysaccharide-Treated Astrocytes the Release of Tumor Necrosis Factor-alpha that Alter Brain-Like Endothelium Integrity

    PubMed Central

    Landoni, Verónica I.; Schierloh, Pablo; de Campos Nebel, Marcelo; Fernández, Gabriela C.; Calatayud, Cecilia; Lapponi, María J.; Isturiz, Martín A.

    2012-01-01

    The hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia and renal dysfunction. The typical form of HUS is generally associated with infections by Gram-negative Shiga toxin (Stx)-producing Escherichia coli (STEC). Endothelial dysfunction induced by Stx is central, but bacterial lipopolysaccharide (LPS) and neutrophils (PMN) contribute to the pathophysiology. Although renal failure is characteristic of this syndrome, neurological complications occur in severe cases and is usually associated with death. Impaired blood-brain barrier (BBB) is associated with damage to cerebral endothelial cells (ECs) that comprise the BBB. Astrocytes (ASTs) are inflammatory cells in the brain and determine the BBB function. ASTs are in close proximity to ECs, hence the study of the effects of Stx1 and LPS on ASTs, and the influence of their response on ECs is essential. We have previously demonstrated that Stx1 and LPS induced activation of rat ASTs and the release of inflammatory factors such as TNF-α, nitric oxide and chemokines. Here, we demonstrate that rat ASTs-derived factors alter permeability of ECs with brain properties (HUVECd); suggesting that functional properties of BBB could also be affected. Additionally, these factors activate HUVECd and render them into a proagregant state promoting PMN and platelets adhesion. Moreover, these effects were dependent on ASTs secreted-TNF-α. Stx1 and LPS-induced ASTs response could influence brain ECs integrity and BBB function once Stx and factors associated to the STEC infection reach the brain parenchyma and therefore contribute to the development of the neuropathology observed in HUS. PMID:22479186

  5. Pharmacological Tools to Study the Role of Astrocytes in Neural Network Functions.

    PubMed

    Peña-Ortega, Fernando; Rivera-Angulo, Ana Julia; Lorea-Hernández, Jonathan Julio

    2016-01-01

    Despite that astrocytes and microglia do not communicate by electrical impulses, they can efficiently communicate among them, with each other and with neurons, to participate in complex neural functions requiring broad cell-communication and long-lasting regulation of brain function. Glial cells express many receptors in common with neurons; secrete gliotransmitters as well as neurotrophic and neuroinflammatory factors, which allow them to modulate synaptic transmission and neural excitability. All these properties allow glial cells to influence the activity of neuronal networks. Thus, the incorporation of glial cell function into the understanding of nervous system dynamics will provide a more accurate view of brain function. Our current knowledge of glial cell biology is providing us with experimental tools to explore their participation in neural network modulation. In this chapter, we review some of the classical, as well as some recent, pharmacological tools developed for the study of astrocyte's influence in neural function. We also provide some examples of the use of these pharmacological agents to understand the role of astrocytes in neural network function and dysfunction.

  6. Pharmacologic approaches to cerebral aging and neuroplasticity: insights from the stroke model.

    PubMed

    Chollet, François

    2013-03-01

    Brain plasticity is an intrinsic characteristic of the nervous system that allows continuous remodeling of brain functions in pathophysiological conditions. Although normal aging is associated with morphological modifications and decline of cerebral functions, brain plasticity is at least partially preserved in elderly individuals. A growing body of evidence supports the notion that cognitive enrichment and aerobic training induce a dynamic reorganization of higher cerebral functions, thereby helping to maintain operational skills in the elderly and reducing the incidence of dementia. The stroke model clearly shows that spontaneous brain plasticity exists after a lesion, even in old patients, and that it can be modulated through external factors like rehabilitation and drugs. Whether drugs can be used with the aim of modulating the effects of physical training or cognitive stimulation in healthy aged people has not been addressed until now. The risk:benefit ratio will be the key question with regard to the ethical aspect of this challenge. We review in this article the main aspects of human brain plasticity as shown in patients with stroke, the drug modulation of brain plasticity and its consequences on recovery, and finally we address the question of the influence of aging on brain plasticity.

  7. Richness in Functional Connectivity Depends on the Neuronal Integrity within the Posterior Cingulate Cortex

    PubMed Central

    Lord, Anton R.; Li, Meng; Demenescu, Liliana R.; van den Meer, Johan; Borchardt, Viola; Krause, Anna Linda; Heinze, Hans-Jochen; Breakspear, Michael; Walter, Martin

    2017-01-01

    The brain's connectivity skeleton—a rich club of strongly interconnected members—was initially shown to exist in human structural networks, but recent evidence suggests a functional counterpart. This rich club typically includes key regions (or hubs) from multiple canonical networks, reducing the cost of inter-network communication. The posterior cingulate cortex (PCC), a hub node embedded within the default mode network, is known to facilitate communication between brain networks and is a key member of the “rich club.” Here, we assessed how metabolic signatures of neuronal integrity and cortical thickness influence the global extent of a functional rich club as measured using the functional rich club coefficient (fRCC). Rich club estimation was performed on functional connectivity of resting state brain signals acquired at 3T in 48 healthy adult subjects. Magnetic resonance spectroscopy was measured in the same session using a point resolved spectroscopy sequence. We confirmed convergence of functional rich club with a previously established structural rich club. N-acetyl aspartate (NAA) in the PCC is significantly correlated with age (p = 0.001), while the rich club coefficient showed no effect of age (p = 0.106). In addition, we found a significant quadratic relationship between fRCC and NAA concentration in PCC (p = 0.009). Furthermore, cortical thinning in the PCC was correlated with a reduced rich club coefficient after accounting for age and NAA. In conclusion, we found that the fRCC is related to a marker of neuronal integrity in a key region of the cingulate cortex. Furthermore, cortical thinning in the same area was observed, suggesting that both cortical thinning and neuronal integrity in the hub regions influence functional integration of at a whole brain level. PMID:28439224

  8. Richness in Functional Connectivity Depends on the Neuronal Integrity within the Posterior Cingulate Cortex.

    PubMed

    Lord, Anton R; Li, Meng; Demenescu, Liliana R; van den Meer, Johan; Borchardt, Viola; Krause, Anna Linda; Heinze, Hans-Jochen; Breakspear, Michael; Walter, Martin

    2017-01-01

    The brain's connectivity skeleton-a rich club of strongly interconnected members-was initially shown to exist in human structural networks, but recent evidence suggests a functional counterpart. This rich club typically includes key regions (or hubs) from multiple canonical networks, reducing the cost of inter-network communication. The posterior cingulate cortex (PCC), a hub node embedded within the default mode network, is known to facilitate communication between brain networks and is a key member of the "rich club." Here, we assessed how metabolic signatures of neuronal integrity and cortical thickness influence the global extent of a functional rich club as measured using the functional rich club coefficient (fRCC). Rich club estimation was performed on functional connectivity of resting state brain signals acquired at 3T in 48 healthy adult subjects. Magnetic resonance spectroscopy was measured in the same session using a point resolved spectroscopy sequence. We confirmed convergence of functional rich club with a previously established structural rich club. N-acetyl aspartate (NAA) in the PCC is significantly correlated with age ( p = 0.001), while the rich club coefficient showed no effect of age (p = 0.106). In addition, we found a significant quadratic relationship between fRCC and NAA concentration in PCC ( p = 0.009). Furthermore, cortical thinning in the PCC was correlated with a reduced rich club coefficient after accounting for age and NAA. In conclusion, we found that the fRCC is related to a marker of neuronal integrity in a key region of the cingulate cortex. Furthermore, cortical thinning in the same area was observed, suggesting that both cortical thinning and neuronal integrity in the hub regions influence functional integration of at a whole brain level.

  9. Critical Periods of Brain Growth and Cognitive Function in Children

    ERIC Educational Resources Information Center

    Gale, Catharine R.; O'Callaghan, Finbar J.; Godfrey, Keith M.; Law, Catherine M.; Martyn, Christopher N.

    2004-01-01

    There is evidence that IQ tends to be higher in those who were heavier at birth or who grew taller in childhood and adolescence. Although these findings imply that growth in both foetal and postnatal life influences cognitive performance, little is known about the relative importance of brain growth during different periods of development. We…

  10. The developing brain in a multitasking world.

    PubMed

    Rothbart, Mary K; Posner, Michael I

    2015-03-01

    To understand the problem of multitasking, it is necessary to examine the brain's attention networks that underlie the ability to switch attention between stimuli and tasks and to maintain a single focus among distractors. In this paper we discuss the development of brain networks related to the functions of achieving the alert state, orienting to sensory events, and developing self-control. These brain networks are common to everyone, but their efficiency varies among individuals and reflects both genes and experience. Training can alter brain networks. We consider two forms of training: (1) practice in tasks that involve particular networks, and (2) changes in brain state through such practices as meditation that may influence many networks. Playing action video games and multitasking are themselves methods of training the brain that can lead to improved performance but also to overdependence on media activity. We consider both of these outcomes and ideas about how to resist overdependence on media. Overall, our paper seeks to inform the reader about what has been learned about attention that can influence multitasking over the course of development.

  11. Large-scale Granger causality analysis on resting-state functional MRI

    NASA Astrophysics Data System (ADS)

    D'Souza, Adora M.; Abidin, Anas Zainul; Leistritz, Lutz; Wismüller, Axel

    2016-03-01

    We demonstrate an approach to measure the information flow between each pair of time series in resting-state functional MRI (fMRI) data of the human brain and subsequently recover its underlying network structure. By integrating dimensionality reduction into predictive time series modeling, large-scale Granger Causality (lsGC) analysis method can reveal directed information flow suggestive of causal influence at an individual voxel level, unlike other multivariate approaches. This method quantifies the influence each voxel time series has on every other voxel time series in a multivariate sense and hence contains information about the underlying dynamics of the whole system, which can be used to reveal functionally connected networks within the brain. To identify such networks, we perform non-metric network clustering, such as accomplished by the Louvain method. We demonstrate the effectiveness of our approach to recover the motor and visual cortex from resting state human brain fMRI data and compare it with the network recovered from a visuomotor stimulation experiment, where the similarity is measured by the Dice Coefficient (DC). The best DC obtained was 0.59 implying a strong agreement between the two networks. In addition, we thoroughly study the effect of dimensionality reduction in lsGC analysis on network recovery. We conclude that our approach is capable of detecting causal influence between time series in a multivariate sense, which can be used to segment functionally connected networks in the resting-state fMRI.

  12. 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.

  13. Pointwise influence matrices for functional-response regression.

    PubMed

    Reiss, Philip T; Huang, Lei; Wu, Pei-Shien; Chen, Huaihou; Colcombe, Stan

    2017-12-01

    We extend the notion of an influence or hat matrix to regression with functional responses and scalar predictors. For responses depending linearly on a set of predictors, our definition is shown to reduce to the conventional influence matrix for linear models. The pointwise degrees of freedom, the trace of the pointwise influence matrix, are shown to have an adaptivity property that motivates a two-step bivariate smoother for modeling nonlinear dependence on a single predictor. This procedure adapts to varying complexity of the nonlinear model at different locations along the function, and thereby achieves better performance than competing tensor product smoothers in an analysis of the development of white matter microstructure in the brain. © 2017, The International Biometric Society.

  14. Quantitative electroencephalograms and neuro-optometry: a case study that explores changes in electrophysiology while wearing therapeutic eyeglasses

    PubMed Central

    Zelinsky, Deborah; Feinberg, Corey

    2017-01-01

    Abstract. The brain is equipped with a complex system for processing sensory information, including retinal circuitry comprising part of the central nervous system. Retinal stimulation can influence brain function via customized eyeglasses at both subcortical and cortical levels. We investigated cortical effects from wearing therapeutic eyeglasses, hypothesizing that they can create measureable changes in electroencephalogram (EEG) tracings. A Z-BellSM test was performed on a participant to select optimal lenses. An EEG measurement was recorded before and after the participant wore the eyeglasses. Equivalent quantitative electroencephalography (QEEG) analyses (statistical analysis on raw EEG recordings) were performed and compared with baseline findings. With glasses on, the participant’s readings were found to be closer to the normed database. The original objective of our investigation was met, and additional findings were revealed. The Z-bellSM test identified lenses to influence neurotypical brain activity, supporting the paradigm that eyeglasses can be utilized as a therapeutic intervention. Also, EEG analysis demonstrated that encephalographic techniques can be used to identify channels through which neuro-optomertric treatments work. This case study’s preliminary exploration illustrates the potential role of QEEG analysis and EEG-derived brain imaging in neuro-optometric research endeavors to affect brain function. PMID:28386574

  15. Mother-caregiver expectations for function among survivors of childhood brain tumors

    PubMed Central

    Barakat, Lamia P.; Ulrich, Connie M.; Jones, Nora L.; Deatrick, Janet A.

    2015-01-01

    Purpose Children diagnosed with brain tumors increasingly survive to adulthood, although they do so with needs often requiring continued parental caregiving. We sought to describe the nature of caregivers’ expectations about survivors’ function and how expectations connect to ongoing management and decision-making. Methods Forty-five qualitative interviews with mother-caregivers were conducted and coded for themes related to expectations for their adolescent/young adult children living post-childhood brain tumors. Results Five main themes emerged as integral to mother-caregiver expectations: realizing a difference in the survivor, noticing limitations to independence in the survivor, memories of learning about clinical prognoses as understood from consent meetings and education, managing these realizations, and acknowledging unresolved challenges. Conclusions Caregiver expectations are influenced by both initial clinical interactions and contemporary family dynamics and require individual- and family-specific survivorship planning. As caregiver expectations can influence management behaviors that impact outcomes and possibly independence, implications for clinician-caregiver shared decision-making are substantial. PMID:26556212

  16. Plasticity-related genes in brain development and amygdala-dependent learning.

    PubMed

    Ehrlich, D E; Josselyn, S A

    2016-01-01

    Learning about motivationally important stimuli involves plasticity in the amygdala, a temporal lobe structure. Amygdala-dependent learning involves a growing number of plasticity-related signaling pathways also implicated in brain development, suggesting that learning-related signaling in juveniles may simultaneously influence development. Here, we review the pleiotropic functions in nervous system development and amygdala-dependent learning of a signaling pathway that includes brain-derived neurotrophic factor (BDNF), extracellular signaling-related kinases (ERKs) and cyclic AMP-response element binding protein (CREB). Using these canonical, plasticity-related genes as an example, we discuss the intersection of learning-related and developmental plasticity in the immature amygdala, when aversive and appetitive learning may influence the developmental trajectory of amygdala function. We propose that learning-dependent activation of BDNF, ERK and CREB signaling in the immature amygdala exaggerates and accelerates neural development, promoting amygdala excitability and environmental sensitivity later in life. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  17. Influence of anesthesia on cerebral blood flow, cerebral metabolic rate, and brain functional connectivity.

    PubMed

    Bonhomme, Vincent; Boveroux, Pierre; Hans, Pol; Brichant, Jean François; Vanhaudenhuyse, Audrey; Boly, Melanie; Laureys, Steven

    2011-10-01

    To describe recent studies exploring brain function under the influence of hypnotic anesthetic agents, and their implications on the understanding of consciousness physiology and anesthesia-induced alteration of consciousness. Cerebral cortex is the primary target of the hypnotic effect of anesthetic agents, and higher-order association areas are more sensitive to this effect than lower-order processing regions. Increasing concentration of anesthetic agents progressively attenuates connectivity in the consciousness networks, while connectivity in lower-order sensory and motor networks is preserved. Alteration of thalamic sub-cortical regulation could compromise the cortical integration of information despite preserved thalamic activation by external stimuli. At concentrations producing unresponsiveness, the activity of consciousness networks becomes anticorrelated with thalamic activity, while connectivity in lower-order sensory networks persists, although with cross-modal interaction alterations. Accumulating evidence suggests that hypnotic anesthetic agents disrupt large-scale cerebral connectivity. This would result in an inability of the brain to generate and integrate information, while external sensory information is still processed at a lower order of complexity.

  18. Hygiene and other early childhood influences on the subsequent function of the immune system.

    PubMed

    Rook, Graham A W; Lowry, Christopher A; Raison, Charles L

    2015-08-18

    The immune system influences brain development and function. Hygiene and other early childhood influences impact the subsequent function of the immune system during adulthood, with consequences for vulnerability to neurodevelopmental and psychiatric disorders. Inflammatory events during pregnancy can act directly to cause developmental problems in the central nervous system (CNS) that have been implicated in schizophrenia and autism. The immune system also acts indirectly by "farming" the intestinal microbiota, which then influences brain development and function via the multiple pathways that constitute the gut-brain axis. The gut microbiota also regulates the immune system. Regulation of the immune system is crucial because inflammatory states in pregnancy need to be limited, and throughout life inflammation needs to be terminated completely when not required; for example, persistently raised levels of background inflammation during adulthood (in the presence or absence of a clinically apparent inflammatory stimulus) correlate with an increased risk of depression. A number of factors in the perinatal period, notably immigration from rural low-income to rich developed settings, caesarean delivery, breastfeeding and antibiotic abuse have profound effects on the microbiota and on immunoregulation during early life that persist into adulthood. Many aspects of the modern western environment deprive the infant of the immunoregulatory organisms with which humans co-evolved, while encouraging exposure to non-immunoregulatory organisms, associated with more recently evolved "crowd" infections. Finally, there are complex interactions between perinatal psychosocial stressors, the microbiota, and the immune system that have significant additional effects on both physical and psychiatric wellbeing in subsequent adulthood. This article is part of a Special Issue entitled Neuroimmunology in Health And Disease. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  19. A Complex Interplay of Vitamin B1 and B6 Metabolism with Cognition, Brain Structure, and Functional Connectivity in Older Adults.

    PubMed

    Jannusch, Kai; Jockwitz, Christiane; Bidmon, Hans-Jürgen; Moebus, Susanne; Amunts, Katrin; Caspers, Svenja

    2017-01-01

    Aging is associated with brain atrophy, functional brain network reorganization and decline of cognitive performance, albeit characterized by high interindividual variability. Among environmental influencing factors accounting for this variability, nutrition and particularly vitamin supply is thought to play an important role. While evidence exists that supplementation of vitamins B6 and B1 might be beneficial for cognition and brain structure, at least in deficient states and neurodegenerative diseases, little is known about this relation during healthy aging and in relation to reorganization of functional brain networks. We thus assessed the relation between blood levels of vitamins B1 and B6 and cognitive performance, cortical folding, and functional resting-state connectivity in a large sample of older adults ( N > 600; age: 55-85 years), drawn from the population-based 1000BRAINS study. In addition to blood sampling, subjects underwent structural and functional resting-state neuroimaging as well as extensive neuropsychological testing in the domains of executive functions, (working) memory, attention, and language. Brain regions showing changes in the local gyrification index as calculated using FreeSurfer in relation to vitamin levels were used for subsequent seed-based resting-state functional connectivity analysis. For B6, a positive correlation with local cortical folding was found throughout the brain, while only slight changes in functional connectivity were observed. Contrarily, for B1, a negative correlation with cortical folding as well as problem solving and visuo-spatial working memory performance was found, which was accompanied by pronounced increases of interhemispheric and decreases of intrahemispheric functional connectivity. While the effects for B6 expand previous knowledge on beneficial effects of B6 supplementation on brain structure, they also showed that additional effects on cognition might not be recognizable in healthy older subjects with normal B6 blood levels. The cortical atrophy and pronounced functional reorganization associated with B1, contrarily, was more in line with the theory of a disturbed B1 metabolism in older adults, leading to B1 utilization deficits, and thus, an effective B1 deficiency in the brain, despite normal to high-normal blood levels.

  20. A Complex Interplay of Vitamin B1 and B6 Metabolism with Cognition, Brain Structure, and Functional Connectivity in Older Adults

    PubMed Central

    Jannusch, Kai; Jockwitz, Christiane; Bidmon, Hans-Jürgen; Moebus, Susanne; Amunts, Katrin; Caspers, Svenja

    2017-01-01

    Aging is associated with brain atrophy, functional brain network reorganization and decline of cognitive performance, albeit characterized by high interindividual variability. Among environmental influencing factors accounting for this variability, nutrition and particularly vitamin supply is thought to play an important role. While evidence exists that supplementation of vitamins B6 and B1 might be beneficial for cognition and brain structure, at least in deficient states and neurodegenerative diseases, little is known about this relation during healthy aging and in relation to reorganization of functional brain networks. We thus assessed the relation between blood levels of vitamins B1 and B6 and cognitive performance, cortical folding, and functional resting-state connectivity in a large sample of older adults (N > 600; age: 55–85 years), drawn from the population-based 1000BRAINS study. In addition to blood sampling, subjects underwent structural and functional resting-state neuroimaging as well as extensive neuropsychological testing in the domains of executive functions, (working) memory, attention, and language. Brain regions showing changes in the local gyrification index as calculated using FreeSurfer in relation to vitamin levels were used for subsequent seed-based resting-state functional connectivity analysis. For B6, a positive correlation with local cortical folding was found throughout the brain, while only slight changes in functional connectivity were observed. Contrarily, for B1, a negative correlation with cortical folding as well as problem solving and visuo-spatial working memory performance was found, which was accompanied by pronounced increases of interhemispheric and decreases of intrahemispheric functional connectivity. While the effects for B6 expand previous knowledge on beneficial effects of B6 supplementation on brain structure, they also showed that additional effects on cognition might not be recognizable in healthy older subjects with normal B6 blood levels. The cortical atrophy and pronounced functional reorganization associated with B1, contrarily, was more in line with the theory of a disturbed B1 metabolism in older adults, leading to B1 utilization deficits, and thus, an effective B1 deficiency in the brain, despite normal to high-normal blood levels. PMID:29163003

  1. Differential attentional responding in caesarean versus vaginally delivered infants.

    PubMed

    Adler, Scott A; Wong-Kee-You, Audrey M B

    2015-11-01

    Little is known about the role that the birth experience plays in brain and cognitive development. Recent research has suggested that birth experience influences the development of the somatosensory cortex, an area involved in spatial attention to sensory information. In this study, we explored whether differences in spatial attention would occur in infants who had different birth experiences, as occurs for caesarean versus vaginal delivery. Three-month-old infants performed either a spatial cueing task or a visual expectation task. We showed that caesarean-delivered infants' stimulus-driven, reflexive attention was slowed relative to vaginally delivered infants', whereas their cognitively driven, voluntary attention was unaffected. Thus, types of birth experience influence at least one form of infants' attention, and possibly any cognitive process that relies on spatial attention. This study also suggests that birth experience influences the initial state of brain functioning and, consequently, should be considered in our understanding of brain development.

  2. Corticostriatal Connectivity in Antisocial Personality Disorder by MAO-A Genotype and Its Relationship to Aggressive Behavior.

    PubMed

    Kolla, Nathan J; Dunlop, Katharine; Meyer, Jeffrey H; Downar, Jonathan

    2018-05-09

    The influence of genetic variation on resting-state neural networks represents a burgeoning line of inquiry in psychiatric research. Monoamine oxidase A, an X-linked gene, is one example of a molecular target linked to brain activity in psychiatric illness. Monoamine oxidase A genetic variants, including the high and low variable nucleotide tandem repeat polymorphisms, have been shown to differentially affect brain functional connectivity in healthy humans. However, it is currently unknown whether these same polymorphisms influence resting-state brain activity in clinical conditions. Given its high burden on society and strong connection to violent behavior, antisocial personality disorder is a logical condition to study, since in vivo markers of monoamine oxidase A brain enzyme are reduced in key affect-modulating regions, and striatal levels of monoamine oxidase A show a relation with the functional connectivity of this same region. We utilized monoamine oxidase A genotyping and seed-to-voxel-based functional connectivity to investigate the relationship between genotype and corticostriatal connectivity in 21 male participants with severe antisocial personality disorder and 19 male healthy controls. Dorsal striatal connectivity to the frontal pole and anterior cingulate gyrus differentiated antisocial personality disorder subjects and healthy controls by monoamine oxidase A genotype. Furthermore, the linear relationship of proactive aggression to superior ventral striatal-angular gyrus functional connectivity differed by monoamine oxidase A genotype in the antisocial personality disorder groups. These results suggest that monoamine oxidase A genotype may affect corticostriatal connectivity in antisocial personality disorder and that these functional connections may also underlie use of proactive aggression in a genotype-specific manner.

  3. Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future “Non-Cognitive” Outcomes of Alzheimer’s Disease

    PubMed Central

    Ingber, Adam P.; Hassenstab, Jason; Fagan, Anne M.; Benzinger, Tammie L.S.; Grant, Elizabeth A.; Holtzman, David M.; Morris, John C.; Roe, Catherine M.

    2016-01-01

    Background The influence of reserve variables and Alzheimer’s disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on “non-cognitive” outcomes, including functional abilities and mood. Objective We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior. Methods Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants. Results Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers. Conclusions The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD. PMID:27104893

  4. Volume transmission-mediated encephalopathies: a possible new concept?

    PubMed

    Hartung, Hans-Peter; Dihné, Marcel

    2012-03-01

    There is strong evidence that the composition of cerebrospinal fluid (CSF) influences brain development, neurogenesis, and behavior. The bidirectional exchange of CSF and interstitial fluid (ISF) across the ependymal and pia-glial membranes is required for these phenomena to occur. Because ISF surrounds the parenchymal compartment, neuroactive substances in the CSF and ISF can influence neuronal activity. Functionally important neuroactive substances are distributed to distant sites of the central nervous system by the convection and diffusion of CSF and ISF, a process known as volume transmission. It has recently been shown that pathologically altered CSF from patients with acute traumatic brain injury suppresses in vitro neuronal network activity (ivNNA) recorded by multielectrode arrays measuring synchronously bursting neural populations. Functionally relevant substances in pathologically altered CSF have been biochemically identified, and ivNNA has been partially recovered by pharmacologic intervention. It remains unclear whether the in vivo parenchymal compartment remains unaffected by pathologically altered CSF that significantly impairs ivNNA. We hypothesize that pathologic CSF alterations are not just passive indicators of brain diseases but that they actively and directly evoke functional disturbances in global brain activity through the distribution of neuroactive substances, for instance, secondary to focal neurologic disease. For this mechanism, we propose the new term volume transmission-mediated encephalopathies (VTE). Recording ivNNA in the presence of pure human CSF could help to identify and monitor functionally relevant CSF alterations that directly result in VTEs, and the collected data might point to therapeutic ways to antagonize these alterations.

  5. Glucose, Lactate, and Shuttling of Metabolites in Vertebrate Retinas

    PubMed Central

    Hurley, James B.; Lindsay, Kenneth J.; Du, Jianhai

    2016-01-01

    The vertebrate retina has specific functions and structures that give it a unique set of constraints on the way in which it can produce and use metabolic energy. The retina’s response to illumination influences its energy requirements, and the retina’s laminated structure influences the extent to which neurons and glia can access metabolic fuels. There are fundamental differences between energy metabolism in retina and that in brain. The retina relies on aerobic glycolysis much more than the brain does, and morphological differences between retina and brain limit the types of metabolic relationships that are possible between neurons and glia. This Mini-Review summarizes the unique metabolic features of the retina with a focus on the role of lactate shuttling. PMID:25801286

  6. Neural and mental hierarchies.

    PubMed

    Wiest, Gerald

    2012-01-01

    The history of the sciences of the human brain and mind has been characterized from the beginning by two parallel traditions. The prevailing theory that still influences the way current neuroimaging techniques interpret brain function, can be traced back to classical localizational theories, which in turn go back to early phrenological theories. The other approach has its origins in the hierarchical neurological theories of Hughlings-Jackson, which have been influenced by the philosophical conceptions of Herbert Spencer. Another hallmark of the hierarchical tradition, which is also inherent to psychoanalytic metapsychology, is its deeply evolutionary perspective by taking both ontogenetic and phylogenetic trajectories into consideration. This article provides an outline on hierarchical concepts in brain and mind sciences, which contrast with current cognitivistic and non-hierarchical theories in the neurosciences.

  7. Neural and Mental Hierarchies

    PubMed Central

    Wiest, Gerald

    2012-01-01

    The history of the sciences of the human brain and mind has been characterized from the beginning by two parallel traditions. The prevailing theory that still influences the way current neuroimaging techniques interpret brain function, can be traced back to classical localizational theories, which in turn go back to early phrenological theories. The other approach has its origins in the hierarchical neurological theories of Hughlings-Jackson, which have been influenced by the philosophical conceptions of Herbert Spencer. Another hallmark of the hierarchical tradition, which is also inherent to psychoanalytic metapsychology, is its deeply evolutionary perspective by taking both ontogenetic and phylogenetic trajectories into consideration. This article provides an outline on hierarchical concepts in brain and mind sciences, which contrast with current cognitivistic and non-hierarchical theories in the neurosciences. PMID:23189066

  8. Psychoneuroimmunology - psyche and autoimmunity.

    PubMed

    Ziemssen, Tjalf

    2012-01-01

    Psychoneuroimmunology is a relatively young field of research that investigates interactions between central nervous and immune system. The brain modulates the immune system by the endocrine and autonomic nervous system. Vice versa, the immune system modulates brain activity including sleep and body temperature. Based on a close functional and anatomical link, the immune and nervous systems act in a highly reciprocal manner. From fever to stress, the influence of one system on the other has evolved in an intricate manner to help sense danger and to mount an appropriate adaptive response. Over recent decades, reasonable evidence has emerged that these brain-to-immune interactions are highly modulated by psychological factors which influence immunity and autoimmune disease. For several diseases, the relevance of psychoneuroimmunological findings has already been demonstrated.

  9. Brain aromatase (Cyp19A2) and estrogen receptors, in larvae and adult pejerrey fish Odontesthes bonariensis: Neuroanatomical and functional relations

    USGS Publications Warehouse

    Strobl-Mazzulla, P. H.; Lethimonier, C.; Gueguen, M.M.; Karube, M.; Fernandino, J.I.; Yoshizaki, G.; Patino, R.; Strussmann, C.A.; Kah, O.; Somoza, G.M.

    2008-01-01

    Although estrogens exert many functions on vertebrate brains, there is little information on the relationship between brain aromatase and estrogen receptors. Here, we report the cloning and characterization of two estrogen receptors, ?? and ??, in pejerrey. Both receptors' mRNAs largely overlap and were predominantly expressed in the brain, pituitary, liver, and gonads. Also brain aromatase and estrogen receptors were up-regulated in the brain of estradiol-treated males. In situ hybridization was performed to study in more detail, the distribution of the two receptors in comparison with brain aromatase mRNA in the brain of adult pejerrey. The estrogen receptors' mRNAs exhibited distinct but partially overlapping patterns of expression in the preoptic area and the mediobasal hypothalamus, as well as in the pituitary gland. Moreover, the estrogen receptor ??, but not ??, were found to be expressed in cells lining the preoptic recess, similarly as observed for brain aromatase. Finally, it was shown that the onset expression of brain aromatase and both estrogen receptors in the head of larvae preceded the morphological differentiation of the gonads. Because pejerrey sex differentiation is strongly influenced by temperature, brain aromatase expression was measured during the temperature-sensitive window and was found to be significantly higher at male-promoting temperature. Taken together these results suggest close neuroanatomical and functional relationships between brain aromatase and estrogen receptors, probably involved in the sexual differentiation of the brain and raising interesting questions on the origin (central or peripheral) of the brain aromatase substrate. ?? 2008 Elsevier Inc.

  10. 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

  11. Microstructural and functional connectivity in the developing preterm brain

    PubMed Central

    Lubsen, Julia; Vohr, Betty; Myers, Eliza; Hampson, Michelle; Lacadie, Cheryl; Schneider, Karen C.; Katz, Karol H.; Constable, R. Todd; Ment, Laura R.

    2011-01-01

    Prematurely born children are at increased risk for cognitive deficits, but the neurobiological basis of these findings remains poorly understood. Since variations in neural circuitry may influence performance on cognitive tasks, recent investigations have explored the impact of preterm birth on connectivity in the developing brain. Diffusion tensor imaging studies demonstrate widespread alterations in fractional anisotropy, a measure of axonal integrity and microstructural connectivity, throughout the developing preterm brain. Functional connectivity studies report that preterm neonates, children and adolescents exhibit alterations in both resting state and task-based connectivity when compared to term control subjects. Taken together, these data suggest that neurodevelopmental impairment following preterm birth may represent a disease of neural connectivity. PMID:21255705

  12. The social brain in adolescence: Evidence from functional magnetic resonance imaging and behavioural studies

    PubMed Central

    Burnett, Stephanie; Sebastian, Catherine; Kadosh, Kathrin Cohen; Blakemore, Sarah-Jayne

    2015-01-01

    Social cognition is the collection of cognitive processes required to understand and interact with others. The term ‘social brain’ refers to the network of brain regions that underlies these processes. Recent evidence suggests that a number of social cognitive functions continue to develop during adolescence, resulting in age differences in tasks that assess cognitive domains including face processing, mental state inference and responding to peer influence and social evaluation. Concurrently, functional and structural magnetic resonance imaging (MRI) studies show differences between adolescent and adult groups within parts of the social brain. Understanding the relationship between these neural and behavioural observations is a challenge. This review discusses current research findings on adolescent social cognitive development and its functional MRI correlates, then integrates and interprets these findings in the context of hypothesised developmental neurocognitive and neurophysiological mechanisms. PMID:21036192

  13. Manipulating motor performance and memory through real-time fMRI neurofeedback.

    PubMed

    Scharnowski, Frank; Veit, Ralf; Zopf, Regine; Studer, Petra; Bock, Simon; Diedrichsen, Jörn; Goebel, Rainer; Mathiak, Klaus; Birbaumer, Niels; Weiskopf, Nikolaus

    2015-05-01

    Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Manipulating motor performance and memory through real-time fMRI neurofeedback

    PubMed Central

    Scharnowski, Frank; Veit, Ralf; Zopf, Regine; Studer, Petra; Bock, Simon; Diedrichsen, Jörn; Goebel, Rainer; Mathiak, Klaus; Birbaumer, Niels; Weiskopf, Nikolaus

    2015-01-01

    Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects. PMID:25796342

  15. 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.

  16. Family environment influences emotion recognition following paediatric traumatic brain injury

    PubMed Central

    SCHMIDT, ADAM T.; ORSTEN, KIMBERLEY D.; HANTEN, GERRI R.; LI, XIAOQI; LEVIN, HARVEY S.

    2011-01-01

    Objective This study investigated the relationship between family functioning and performance on two tasks of emotion recognition (emotional prosody and face emotion recognition) and a cognitive control procedure (the Flanker task) following paediatric traumatic brain injury (TBI) or orthopaedic injury (OI). Methods A total of 142 children (75 TBI, 67 OI) were assessed on three occasions: baseline, 3 months and 1 year post-injury on the two emotion recognition tasks and the Flanker task. Caregivers also completed the Life Stressors and Resources Scale (LISRES) on each occasion. Growth curve analysis was used to analyse the data. Results Results indicated that family functioning influenced performance on the emotional prosody and Flanker tasks but not on the face emotion recognition task. Findings on both the emotional prosody and Flanker tasks were generally similar across groups. However, financial resources emerged as significantly related to emotional prosody performance in the TBI group only (p = 0.0123). Conclusions Findings suggest family functioning variables—especially financial resources—can influence performance on an emotional processing task following TBI in children. PMID:21058900

  17. Image formation of brain function in patients suffering from knee osteoarthritis treated with moxibustion.

    PubMed

    Xie, Hongwu; Xu, Fangming; Chen, Rixin; Luo, Tianyou; Chen, Mingren; Fang, Weidong; Lü, Fajin; Wu, Fei; Song, Yune; Xiong, Jun

    2013-04-01

    Functional magnetic resonance imaging (fMRI) technology was used to study changes to the resting state blood flow in the brains of patients with knee osteoarthritis (KOA) before and after treatment with moxibustion at the acupoint of the left Dubi (ST 35) and to probe the cerebral mechanism underlying the effect of moxibustion. The resting state brain function of 30 patients with left KOA was scanned with fMRI before and after treatment with moxibustion. The analytic methods of fractional amplitude of low frequency fluctuation (fALFF) and regional homogeneity (ReHo) were used to observe changes in resting state brain function. The fALFF values of the right cerebrum, extra-nucleus, left cerebellum, left cerebrum and white matter of patients after moxibustion treatment were higher than before treatment, and the fALFF values of the precentral gyrus, frontal lobe and occipital lobe were lower than before treatment (P < 0.05, K > or = 85). The ReHo values of the thalamus, extra-nucleus and parietal lobe of patients were much higher than those before moxibustion treatment, and the ReHo values of the right cerebrum, left cerebrum and frontal lobe were lower than before treatment (P < 0.05, K > or = 85). The influence of moxibustion on obvious changes in brain regions basically conforms to the way that pain and warmth is transmitted in the body, and the activation of sensitive systems in the body may be objective evidence of channel transmission. The regulation of brain function by moxibustion is not in a single brain region but rather in a network of many brain regions.

  18. Mechanism of action of ionizing radiation on hexokinase and cholinesterase activity in the rat brain, in the presence of altered function of M-cholinergic structures. [X radiation

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

    Khripchenko, I.P.; Kukulyanskaya, M.F.; Markina, V.L.

    1977-01-01

    Data are submitted on activity of hexokinase and isozymes thereof, and cholinesterase in subcellular fractions of the brain in the case of inhibition and stimulation of M-cholinoreactive structures under the influence of a relatively small dose, 40 R, of ionizing radiation.

  19. Adolescent Neurobiological Susceptibility to Social Context

    PubMed Central

    Schriber, Roberta A.; Guyer, Amanda E.

    2016-01-01

    Adolescence has been characterized as a period of heightened sensitivity to social contexts. However, adolescents vary in how their social contexts affect them. According to neurobiological susceptibility models, endogenous, biological factors confer some individuals, relative to others, with greater susceptibility to environmental influences, whereby more susceptible individuals fare the best or worst of all individuals, depending on the environment they encounter (e.g., high vs. low parental warmth). Until recently, research guided by these theoretical frameworks has not incorporated direct measures of brain structure or function to index this sensitivity. Drawing on prevailing models of adolescent neurodevelopment and a growing number of neuroimaging studies on the interrelations among social contexts, the brain, and developmental outcomes, we review research that supports the idea of adolescent neurobiological susceptibility to social context for understanding why and how adolescents differ in development and well-being. We propose that adolescent development is shaped in part by brain-based individual differences in sensitivity to social contexts – be they positive or negative – such as those created through relationships with parents/caregivers and peers. As such, we recommend that future research measure brain function and structure to operationalize susceptibility factors that moderate the influence of social contexts on developmental outcomes. PMID:26773514

  20. Non-synaptic receptors and transporters involved in brain functions and targets of drug treatment.

    PubMed

    Vizi, E S; Fekete, A; Karoly, R; Mike, A

    2010-06-01

    Beyond direct synaptic communication, neurons are able to talk to each other without making synapses. They are able to send chemical messages by means of diffusion to target cells via the extracellular space, provided that the target neurons are equipped with high-affinity receptors. While synaptic transmission is responsible for the 'what' of brain function, the 'how' of brain function (mood, attention, level of arousal, general excitability, etc.) is mainly controlled non-synaptically using the extracellular space as communication channel. It is principally the 'how' that can be modulated by medicine. In this paper, we discuss different forms of non-synaptic transmission, localized spillover of synaptic transmitters, local presynaptic modulation and tonic influence of ambient transmitter levels on the activity of vast neuronal populations. We consider different aspects of non-synaptic transmission, such as synaptic-extrasynaptic receptor trafficking, neuron-glia communication and retrograde signalling. We review structural and functional aspects of non-synaptic transmission, including (i) anatomical arrangement of non-synaptic release sites, receptors and transporters, (ii) intravesicular, intra- and extracellular concentrations of neurotransmitters, as well as the spatiotemporal pattern of transmitter diffusion. We propose that an effective general strategy for efficient pharmacological intervention could include the identification of specific non-synaptic targets and the subsequent development of selective pharmacological tools to influence them.

  1. The impact of junk foods on the adolescent brain.

    PubMed

    Reichelt, Amy C; Rank, Michelle M

    2017-12-01

    Adolescence is a significant period of physical, social, and emotional development, and is characterized by prominent neurobiological changes in the brain. The maturational processes that occur in brain regions responsible for cognitive control and reward seeking may underpin excessive consumption of palatable high fat and high sugar "junk" foods during adolescence. Recent studies have highlighted the negative impact of these foods on brain function, resulting in cognitive impairments and altered reward processing. The increased neuroplasticity during adolescence may render the brain vulnerable to the negative effects of these foods on cognition and behavior. In this review, we describe the mechanisms by which junk food diets influence neurodevelopment during adolescence. Diet can lead to alterations in dopamine-mediated reward signaling, and inhibitory neurotransmission controlled by γ-aminobutyric acid (GABA), two major neurotransmitter systems that are under construction across adolescence. We propose that poor dietary choices may derail the normal adolescent maturation process and influence neurodevelopmental trajectories, which can predispose individuals to dysregulated eating and impulsive behaviors. © 2017 Wiley Periodicals, Inc.

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

    PubMed Central

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

    2016-01-01

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

  3. Intranasal oxytocin modulates neural functional connectivity during human social interaction.

    PubMed

    Rilling, James K; Chen, Xiangchuan; Chen, Xu; Haroon, Ebrahim

    2018-02-10

    Oxytocin (OT) modulates social behavior in primates and many other vertebrate species. Studies in non-primate animals have demonstrated that, in addition to influencing activity within individual brain areas, OT influences functional connectivity across networks of areas involved in social behavior. Previously, we used fMRI to image brain function in human subjects during a dyadic social interaction task following administration of either intranasal oxytocin (INOT) or placebo, and analyzed the data with a standard general linear model. Here, we conduct an extensive re-analysis of these data to explore how OT modulates functional connectivity across a neural network that animal studies implicate in social behavior. OT induced widespread increases in functional connectivity in response to positive social interactions among men and widespread decreases in functional connectivity in response to negative social interactions among women. Nucleus basalis of Meynert, an important regulator of selective attention and motivation with a particularly high density of OT receptors, had the largest number of OT-modulated connections. Regions known to receive mesolimbic dopamine projections such as the nucleus accumbens and lateral septum were also hubs for OT effects on functional connectivity. Our results suggest that the neural mechanism by which OT influences primate social cognition may include changes in patterns of activity across neural networks that regulate social behavior in other animals. © 2018 Wiley Periodicals, Inc.

  4. 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.

  5. Bike Desks in the Classroom: Energy Expenditure, Physical Health, Cognitive Performance, Brain Functioning, and Academic Performance.

    PubMed

    Torbeyns, Tine; de Geus, Bas; Bailey, Stephen; Decroix, Lieselot; Van Cutsem, Jeroen; De Pauw, Kevin; Meeusen, Romain

    2017-06-01

    Physical activity is positively associated with physical health, cognitive performance, brain functioning and academic performance. The aim of this study is to investigate the influence of bike desks in the classroom on adolescents' energy expenditure, physical health, cognitive performance, brain functioning and academic performance. Forty-four adolescents were randomly assigned to control group (CG) or intervention group (IG). During 5 months, the IG used a bike desk for 4 class hours/week. Energy expenditure was measured during 6 consecutive days. Anthropometric parameters, aerobic fitness, academic performance, cognitive performance and brain functioning were assessed before (T0) and after (T1) the intervention. Energy expenditure of the IG was significantly higher during the class hours in which they used the bike desks relative to normal class hours. The CG had a significantly higher BMI at T1 relative to T0 while this was not significantly different for the IG. Aerobic fitness was significantly better in the IG at T1 relative to T0. No significant effects on academic performance cognitive performance and brain functioning were observed. As the implementation of bike desks in the classroom did not interfere with adolescents' academic performance, this can be seen as an effective means of reducing in-class sedentary time and improving adolescents' physical health.

  6. Functional Connectivity in Brain Networks Underlying Cognitive Control in Chronic Cannabis Users

    PubMed Central

    Harding, Ian H; Solowij, Nadia; Harrison, Ben J; Takagi, Michael; Lorenzetti, Valentina; Lubman, Dan I; Seal, Marc L; Pantelis, Christos; Yücel, Murat

    2012-01-01

    The long-term effect of regular cannabis use on brain function underlying cognitive control remains equivocal. Cognitive control abilities are thought to have a major role in everyday functioning, and their dysfunction has been implicated in the maintenance of maladaptive drug-taking patterns. In this study, the Multi-Source Interference Task was employed alongside functional magnetic resonance imaging and psychophysiological interaction methods to investigate functional interactions between brain regions underlying cognitive control. Current cannabis users with a history of greater than 10 years of daily or near-daily cannabis smoking (n=21) were compared with age, gender, and IQ-matched non-using controls (n=21). No differences in behavioral performance or magnitude of task-related brain activations were evident between the groups. However, greater connectivity between the prefrontal cortex and the occipitoparietal cortex was evident in cannabis users, as compared with controls, as cognitive control demands increased. The magnitude of this connectivity was positively associated with age of onset and lifetime exposure to cannabis. These findings suggest that brain regions responsible for coordinating behavioral control have an increased influence on the direction and switching of attention in cannabis users, and that these changes may have a compensatory role in mitigating cannabis-related impairments in cognitive control or perceptual processes. PMID:22534625

  7. Functional anatomy of visuo-spatial working memory during mental rotation is influenced by sex, menstrual cycle, and sex steroid hormones.

    PubMed

    Schöning, S; Engelien, A; Kugel, H; Schäfer, S; Schiffbauer, H; Zwitserlood, P; Pletziger, E; Beizai, P; Kersting, A; Ohrmann, P; Greb, R R; Lehmann, W; Heindel, W; Arolt, V; Konrad, C

    2007-11-05

    Recent observations indicate that sex and level of steroid hormones may influence cortical networks associated with specific cognitive functions, in particular visuo-spatial abilities. The present study probed the influence of sex, menstrual cycle, and sex steroid hormones on 3D mental rotation and brain function using 3-T fMRI. Twelve healthy women and 12 men were investigated. Menstrual cycle and hormone levels were assessed. The early follicular and midluteal phase of the menstrual cycle were chosen to examine short-term cyclical changes. Parietal and frontal areas were activated during mental rotation in both sexes. Significant differences between men and women were revealed in both phases of menstrual cycle. In men we observed a significant correlation of activation levels with testosterone levels in the left parietal lobe (BA 40). In women, a cycle-dependent correlation pattern was observed for testosterone: brain activation correlated with this male hormone only during the early follicular phase. In both cycle phases females' brain activation was significantly correlated with estradiol in frontal and parietal areas. Our study provides evidence that fMRI-related activity during performance of cognitive tasks varies across sex and phases of the menstrual cycle. The variation might be partly explained by better task performance in men, but our results indicate that further explanations like basic neuronal or neurovascular effects modulated by steroid hormones must be considered. Both estradiol and testosterone levels may influence fMRI signals of cognitive tasks, which should affect selection of subjects for future fMRI studies.

  8. Severe Urban Outdoor Air Pollution and Children's Structural and Functional Brain Development, From Evidence to Precautionary Strategic Action.

    PubMed

    D'Angiulli, Amedeo

    2018-01-01

    According to the latest estimates, about 2 billion children around the world are exposed to severe urban outdoor air pollution. Transdisciplinary, multi-method findings from epidemiology, developmental neuroscience, psychology, and pediatrics, show detrimental outcomes associated with pre- and postnatal exposure are found at all ages. Affected brain-related functions include perceptual and sensory information processing, intellectual and cognitive development, memory and executive functions, emotion and self-regulation, and academic achievement. Correspondingly, with the breakdown of natural barriers against entry and translocation of toxic particles in the brain, the most common structural changes are responses promoting neuroinflammation and indicating early neurodegenerative processes. In spite of the gaps in current scientific knowledge and the challenges posed by non-scientific issues that influence policy, the evidence invites the conclusion that urban outdoor air pollution is a serious threat to healthy brain development which may set the conditions for neurodegenerative diseases. Such evidence supports the perspective that urgent strategic precautionary actions, minimizing exposure and attenuating its effects, are needed to protect children and their brain development.

  9. Severe Urban Outdoor Air Pollution and Children’s Structural and Functional Brain Development, From Evidence to Precautionary Strategic Action

    PubMed Central

    D’Angiulli, Amedeo

    2018-01-01

    According to the latest estimates, about 2 billion children around the world are exposed to severe urban outdoor air pollution. Transdisciplinary, multi-method findings from epidemiology, developmental neuroscience, psychology, and pediatrics, show detrimental outcomes associated with pre- and postnatal exposure are found at all ages. Affected brain-related functions include perceptual and sensory information processing, intellectual and cognitive development, memory and executive functions, emotion and self-regulation, and academic achievement. Correspondingly, with the breakdown of natural barriers against entry and translocation of toxic particles in the brain, the most common structural changes are responses promoting neuroinflammation and indicating early neurodegenerative processes. In spite of the gaps in current scientific knowledge and the challenges posed by non-scientific issues that influence policy, the evidence invites the conclusion that urban outdoor air pollution is a serious threat to healthy brain development which may set the conditions for neurodegenerative diseases. Such evidence supports the perspective that urgent strategic precautionary actions, minimizing exposure and attenuating its effects, are needed to protect children and their brain development. PMID:29670873

  10. Functional Plasticity in Childhood Brain Disorders: When, What, How, and Whom to Assess

    PubMed Central

    Dennis, Maureen; Spiegler, Brenda J.; Simic, Nevena; Sinopoli, Katia J.; Wilkinson, Amy; Yeates, Keith Owen; Taylor, H. Gerry; Bigler, Erin D.; Fletcher, Jack M.

    2014-01-01

    At every point in the lifespan, the brain balances malleable processes representing neural plasticity that promote change with homeostatic processes that promote stability. Whether a child develops typically or with brain injury, his or her neural and behavioral outcome is constructed through transactions between plastic and homeostatic processes and the environment. In clinical research with children in whom the developing brain has been malformed or injured, behavioral outcomes provide an index of the result of plasticity, homeostasis, and environmental transactions. When should we assess outcome in relation to age at brain insult, time since brain insult, and age of the child at testing? What should we measure? Functions involving reacting to the past and predicting the future, as well as social-affective skills, are important. How should we assess outcome? Information from performance variability, direct measures and informants, overt and covert measures, and laboratory and ecological measures should be considered. In whom are we assessing outcome? Assessment should be cognizant of individual differences in gene, socio-economic status (SES), parenting, nutrition, and interpersonal supports, which are moderators that interact with other factors influencing functional outcome. PMID:24821533

  11. The developing brain in a multitasking world

    PubMed Central

    Rothbart, Mary K.; Posner, Michael I.

    2015-01-01

    To understand the problem of multitasking, it is necessary to examine the brain’s attention networks that underlie the ability to switch attention between stimuli and tasks and to maintain a single focus among distractors. In this paper we discuss the development of brain networks related to the functions of achieving the alert state, orienting to sensory events, and developing self-control. These brain networks are common to everyone, but their efficiency varies among individuals and reflects both genes and experience. Training can alter brain networks. We consider two forms of training: (1) practice in tasks that involve particular networks, and (2) changes in brain state through such practices as meditation that may influence many networks. Playing action video games and multitasking are themselves methods of training the brain that can lead to improved performance but also to overdependence on media activity. We consider both of these outcomes and ideas about how to resist overdependence on media. Overall, our paper seeks to inform the reader about what has been learned about attention that can influence multitasking over the course of development. PMID:25821335

  12. The Influence of Adipose Tissue on Brain Development, Cognition, and Risk of Neurodegenerative Disorders.

    PubMed

    Letra, Liliana; Santana, Isabel

    2017-01-01

    The brain is a highly metabolic organ and thus especially vulnerable to changes in peripheral metabolism, including those induced by obesity-associated adipose tissue dysfunction. In this context, it is likely that the development and maturation of neurocognitive circuits may also be affected and modulated by metabolic environmental factors, beginning in utero. It is currently recognized that maternal obesity, either pre-gestational or gestational, negatively influences fetal brain development and elevates the risk of cognitive impairment and neuropsychiatric disorders in the offspring. During infancy and adolescence, obesity remains a limiting factor for healthy neurodevelopment, especially affecting executive functions but also attention, visuospatial ability, and motor skills. In middle age, obesity seems to induce an accelerated brain aging and thus may increase the risk of age-related neurodegenerative diseases such as Alzheimer's disease. In this chapter we review and discuss experimental and clinical evidence focusing on the influence of adipose tissue dysfunction on neurodevelopment and cognition across lifespan, as well as some possible mechanistic links, namely the role of the most well studied adipokines.

  13. Brain functional connectivity changes in children that differ in impulsivity temperamental trait

    PubMed Central

    Inuggi, Alberto; Sanz-Arigita, Ernesto; González-Salinas, Carmen; Valero-García, Ana V.; García-Santos, Jose M.; Fuentes, Luis J.

    2014-01-01

    Impulsivity is a core personality trait forming part of normal behavior and contributing to adaptive functioning. However, in typically developing children, altered patterns of impulsivity constitute a risk factor for the development of behavioral problems. Since both pathological and non-pathological states are commonly characterized by continuous transitions, we used a correlative approach to investigate the potential link between personality and brain dynamics. We related brain functional connectivity of typically developing children, measured with magnetic resonance imaging at rest, with their impulsivity scores obtained from a questionnaire completed by their parents. We first looked for areas within the default mode network (DMN) whose functional connectivity might be modulated by trait impulsivity. Then, we calculated the functional connectivity among these regions and the rest of the brain in order to assess if impulsivity trait altered their relationships. We found two DMN clusters located at the posterior cingulate cortex and the right angular gyrus which were negatively correlated with impulsivity scores. The whole-brain correlation analysis revealed the classic network of correlating and anti-correlating areas with respect to the DMN. The impulsivity trait modulated such pattern showing that the canonical anti-phasic relation between DMN and action-related network was reduced in high impulsive children. These results represent the first evidence that the impulsivity, measured as personality trait assessed through parents' report, exerts a modulatory influence over the functional connectivity of resting state brain networks in typically developing children. The present study goes further to connect developmental approaches, mainly based on data collected through the use of questionnaires, and behavioral neuroscience, interested in how differences in brain structure and functions reflect in differences in behavior. PMID:24834038

  14. Brain functional connectivity changes in children that differ in impulsivity temperamental trait.

    PubMed

    Inuggi, Alberto; Sanz-Arigita, Ernesto; González-Salinas, Carmen; Valero-García, Ana V; García-Santos, Jose M; Fuentes, Luis J

    2014-01-01

    Impulsivity is a core personality trait forming part of normal behavior and contributing to adaptive functioning. However, in typically developing children, altered patterns of impulsivity constitute a risk factor for the development of behavioral problems. Since both pathological and non-pathological states are commonly characterized by continuous transitions, we used a correlative approach to investigate the potential link between personality and brain dynamics. We related brain functional connectivity of typically developing children, measured with magnetic resonance imaging at rest, with their impulsivity scores obtained from a questionnaire completed by their parents. We first looked for areas within the default mode network (DMN) whose functional connectivity might be modulated by trait impulsivity. Then, we calculated the functional connectivity among these regions and the rest of the brain in order to assess if impulsivity trait altered their relationships. We found two DMN clusters located at the posterior cingulate cortex and the right angular gyrus which were negatively correlated with impulsivity scores. The whole-brain correlation analysis revealed the classic network of correlating and anti-correlating areas with respect to the DMN. The impulsivity trait modulated such pattern showing that the canonical anti-phasic relation between DMN and action-related network was reduced in high impulsive children. These results represent the first evidence that the impulsivity, measured as personality trait assessed through parents' report, exerts a modulatory influence over the functional connectivity of resting state brain networks in typically developing children. The present study goes further to connect developmental approaches, mainly based on data collected through the use of questionnaires, and behavioral neuroscience, interested in how differences in brain structure and functions reflect in differences in behavior.

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

    PubMed Central

    Sowndhararajan, Kandhasamy; Kim, Songmun

    2016-01-01

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

  16. Brain and Language: Evidence for Neural Multifunctionality

    PubMed Central

    Cahana-Amitay, Dalia; Albert, Martin L.

    2014-01-01

    This review paper presents converging evidence from studies of brain damage and longitudinal studies of language in aging which supports the following thesis: the neural basis of language can best be understood by the concept of neural multifunctionality. In this paper the term “neural multifunctionality” refers to incorporation of nonlinguistic functions into language models of the intact brain, reflecting a multifunctional perspective whereby a constant and dynamic interaction exists among neural networks subserving cognitive, affective, and praxic functions with neural networks specialized for lexical retrieval, sentence comprehension, and discourse processing, giving rise to language as we know it. By way of example, we consider effects of executive system functions on aspects of semantic processing among persons with and without aphasia, as well as the interaction of executive and language functions among older adults. We conclude by indicating how this multifunctional view of brain-language relations extends to the realm of language recovery from aphasia, where evidence of the influence of nonlinguistic factors on the reshaping of neural circuitry for aphasia rehabilitation is clearly emerging. PMID:25009368

  17. Genetic influences on functional connectivity associated with feedback processing and prediction error: Phase coupling of theta-band oscillations in twins.

    PubMed

    Demiral, Şükrü Barış; Golosheykin, Simon; Anokhin, Andrey P

    2017-05-01

    Detection and evaluation of the mismatch between the intended and actually obtained result of an action (reward prediction error) is an integral component of adaptive self-regulation of behavior. Extensive human and animal research has shown that evaluation of action outcome is supported by a distributed network of brain regions in which the anterior cingulate cortex (ACC) plays a central role, and the integration of distant brain regions into a unified feedback-processing network is enabled by long-range phase synchronization of cortical oscillations in the theta band. Neural correlates of feedback processing are associated with individual differences in normal and abnormal behavior, however, little is known about the role of genetic factors in the cerebral mechanisms of feedback processing. Here we examined genetic influences on functional cortical connectivity related to prediction error in young adult twins (age 18, n=399) using event-related EEG phase coherence analysis in a monetary gambling task. To identify prediction error-specific connectivity pattern, we compared responses to loss and gain feedback. Monetary loss produced a significant increase of theta-band synchronization between the frontal midline region and widespread areas of the scalp, particularly parietal areas, whereas gain resulted in increased synchrony primarily within the posterior regions. Genetic analyses showed significant heritability of frontoparietal theta phase synchronization (24 to 46%), suggesting that individual differences in large-scale network dynamics are under substantial genetic control. We conclude that theta-band synchronization of brain oscillations related to negative feedback reflects genetically transmitted differences in the neural mechanisms of feedback processing. To our knowledge, this is the first evidence for genetic influences on task-related functional brain connectivity assessed using direct real-time measures of neuronal synchronization. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. A Parallel Independent Component Analysis Approach to Investigate Genomic Influence on Brain Function

    PubMed Central

    Liu, Jingyu; Demirci, Oguz; Calhoun, Vince D.

    2009-01-01

    Relationships between genomic data and functional brain images are of great interest but require new analysis approaches to integrate the high-dimensional data types. This letter presents an extension of a technique called parallel independent component analysis (paraICA), which enables the joint analysis of multiple modalities including interconnections between them. We extend our earlier work by allowing for multiple interconnections and by providing important overfitting controls. Performance was assessed by simulations under different conditions, and indicated reliable results can be extracted by properly balancing overfitting and underfitting. An application to functional magnetic resonance images and single nucleotide polymorphism array produced interesting findings. PMID:19834575

  19. A Parallel Independent Component Analysis Approach to Investigate Genomic Influence on Brain Function.

    PubMed

    Liu, Jingyu; Demirci, Oguz; Calhoun, Vince D

    2008-01-01

    Relationships between genomic data and functional brain images are of great interest but require new analysis approaches to integrate the high-dimensional data types. This letter presents an extension of a technique called parallel independent component analysis (paraICA), which enables the joint analysis of multiple modalities including interconnections between them. We extend our earlier work by allowing for multiple interconnections and by providing important overfitting controls. Performance was assessed by simulations under different conditions, and indicated reliable results can be extracted by properly balancing overfitting and underfitting. An application to functional magnetic resonance images and single nucleotide polymorphism array produced interesting findings.

  20. Sex Influences on the Neurobiology of Learning and Memory

    ERIC Educational Resources Information Center

    Andreano, Joseph M.; Cahill, Larry

    2009-01-01

    In essentially every domain of neuroscience, the generally implicit assumption that few, if any, meaningful differences exist between male and female brain function is being challenged. Here we address how this development is influencing studies of the neurobiology of learning and memory. While it has been commonly held that males show an…

  1. The Influence of Daily Structured Physical Activity on Academic Progress of Elementary Students with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Everhart, Brett; Dimon, Chelsea; Stone, Danielle; Desmond, Deborah; Casilio, Mary

    2012-01-01

    Recent evidence suggests regular physical activity can positively influence academic performance. Although, little has been published on physical activity's impact on academic performance of students with intellectual disabilities, research shows the impact on brain and cognitive function of movement and physical activity. In this study, seven…

  2. A functional neuroimaging review of obesity, appetitive hormones and ingestive behavior.

    PubMed

    Burger, Kyle S; Berner, Laura A

    2014-09-01

    Adequate energy intake is vital for the survival of humans and is regulated by complex homeostatic and hedonic mechanisms. Supported by functional MRI (fMRI) studies that consistently demonstrate differences in brain response as a function of weight status during exposure to appetizing food stimuli, it has been posited that hedonically driven food intake contributes to weight gain and obesity maintenance. These food reward theories of obesity are reliant on the notion that the aberrant brain response to food stimuli relates directly to ingestive behavior, specifically, excess food intake. Importantly, functioning of homeostatic neuroendocrine regulators of food intake, such as leptin and ghrelin, are impacted by weight status. Thus, data from studies that evaluate the effect on weight status on brain response to food may be a result of differences in neuroendocrine functioning and/or behavior. In the present review, we examine the influence of weight and weight change, exogenous administration of appetitive hormones, and ingestive behavior on BOLD response to food stimuli. Published by Elsevier Inc.

  3. Flexible establishment of functional brain networks supports attentional modulation of unconscious cognition.

    PubMed

    Ulrich, Martin; Adams, Sarah C; Kiefer, Markus

    2014-11-01

    In classical theories of attention, unconscious automatic processes are thought to be independent of higher-level attentional influences. Here, we propose that unconscious processing depends on attentional enhancement of task-congruent processing pathways implemented by a dynamic modulation of the functional communication between brain regions. Using functional magnetic resonance imaging, we tested our model with a subliminally primed lexical decision task preceded by an induction task preparing either a semantic or a perceptual task set. Subliminal semantic priming was significantly greater after semantic compared to perceptual induction in ventral occipito-temporal (vOT) and inferior frontal cortex, brain areas known to be involved in semantic processing. The functional connectivity pattern of vOT varied depending on the induction task and successfully predicted the magnitude of behavioral and neural priming. Together, these findings support the proposal that dynamic establishment of functional networks by task sets is an important mechanism in the attentional control of unconscious processing. © 2014 Wiley Periodicals, Inc.

  4. 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

  5. A combination of lipidomics, MS imaging, and PET scan imaging reveals differences in cerebral activity in rat pups according to the lipid quality of infant formulas.

    PubMed

    Aidoud, Nacima; Delplanque, Bernadette; Baudry, Charlotte; Garcia, Cyrielle; Moyon, Anais; Balasse, Laure; Guillet, Benjamin; Antona, Claudine; Darmaun, Dominique; Fraser, Karl; Ndiaye, Sega; Leruyet, Pascale; Martin, Jean-Charles

    2018-03-22

    We evaluated the effect of adding docosahexaenoic:arachidonic acids (3:2) (DHA+ARA) to 2 representative commercial infant formulas on brain activity and brain and eye lipids in an artificially reared rat pup model. The formula lipid background was either a pure plant oil blend, or dairy fat with a plant oil blend (1:1). Results at weaning were compared to breast milk-fed pups. Brain functional activity was determined by positron emission tomography scan imaging, the brain and eye fatty acid and lipid composition by targeted and untargeted lipidomics, and DHA brain regional location by mass-spectrometry imaging. The brain functional activity was normalized to controls with DHA+ARA added to the formulas. DHA in both brain and eyes was influenced by formula intake, but more than two-thirds of tissue DHA-glycerolipids remained insensitive to the dietary challenge. However, the DHA lipidome correlated better with brain function than sole DHA content ( r = 0.70 vs. r = 0.48; P < 0.05). Brain DHA regional distribution was more affected by the formula lipid background than the provision of PUFAs. Adding DHA+ARA to formulas alters the DHA content and lipidome of nervous tissue in the neonate, making it closer to dam milk-fed controls, and normalizes brain functional activity.-Aidoud, N., Delplanque, B., Baudry, C., Garcia, C., Moyon, A., Balasse, L., Guillet, B., Antona, C., Darmaun, D., Fraser, K., Ndiaye, S., Leruyet, P., Martin, J.-C. A combination of lipidomics, MS imaging, and PET scan imaging reveals differences in cerebral activity in rat pups according to the lipid quality of infant formulas.

  6. The heritability of the functional connectome is robust to common nonlinear registration methods

    NASA Astrophysics Data System (ADS)

    Hafzalla, George W.; Prasad, Gautam; Baboyan, Vatche G.; Faskowitz, Joshua; Jahanshad, Neda; McMahon, Katie L.; de Zubicaray, Greig I.; Wright, Margaret J.; Braskie, Meredith N.; Thompson, Paul M.

    2016-03-01

    Nonlinear registration algorithms are routinely used in brain imaging, to align data for inter-subject and group comparisons, and for voxelwise statistical analyses. To understand how the choice of registration method affects maps of functional brain connectivity in a sample of 611 twins, we evaluated three popular nonlinear registration methods: Advanced Normalization Tools (ANTs), Automatic Registration Toolbox (ART), and FMRIB's Nonlinear Image Registration Tool (FNIRT). Using both structural and functional MRI, we used each of the three methods to align the MNI152 brain template, and 80 regions of interest (ROIs), to each subject's T1-weighted (T1w) anatomical image. We then transformed each subject's ROIs onto the associated resting state functional MRI (rs-fMRI) scans and computed a connectivity network or functional connectome for each subject. Given the different degrees of genetic similarity between pairs of monozygotic (MZ) and same-sex dizygotic (DZ) twins, we used structural equation modeling to estimate the additive genetic influences on the elements of the function networks, or their heritability. The functional connectome and derived statistics were relatively robust to nonlinear registration effects.

  7. Clinical and Biochemical Characteristics of Brain-Dead Donors as Predictors of Early- and Long-Term Renal Function After Transplant.

    PubMed

    Kwiatkowska, Ewa; Domański, Leszek; Bober, Joanna; Safranow, Krzysztof; Pawlik, Andrzej; Ciechanowski, Kazimierz; Wiśniewska, Magda; Kędzierska, Karolina

    2017-08-01

    Organs from brain-dead donors are the main source of allografts for transplant. Comparisons between living-donor and brain-dead donor kidneys show that the latter are more likely to demonstrate delayed graft function and lower long-term survival. This study aimed to assess the effects of various clinical and biochemical factors of donors on early- and long-term renal function after transplant. We analyzed data from kidney recipients treated between 2006 and 2008 who received organs from brain-dead donors. Data from 54 donors and 89 recipients were analyzed. No relation was observed between donor sodium concentration and the presence of delayed graft function. Donor height was positively correlated with creatinine clearance in recipients in the 1 to 3 months after renal transplant. Donor diastolic blood pressure was negatively correlated with estimated glomerular filtration rate throughout the observation period. Donor age was negatively correlated with the allograft recipient's estimated glomerular filtration rate throughout 4 years of observation. Donor estimated glomerular filtration rate was positively correlated with that of the recipient throughout 3 years of observation. The results of this study indicate that various factors associated with allograft donors may influence graft function.

  8. Circadian misalignment, reward-related brain function, and adolescent alcohol involvement.

    PubMed

    Hasler, Brant P; Clark, Duncan B

    2013-04-01

    Developmental changes in sleep and circadian rhythms that occur during adolescence may contribute to reward-related brain dysfunction, and consequently increase the risk of alcohol use disorders (AUDs). This review (i) describes marked changes in circadian rhythms, reward-related behavior and brain function, and alcohol involvement that occur during adolescence, (ii) offers evidence that these parallel developmental changes are associated, and (iii) posits a conceptual model by which misalignment between sleep-wake timing and endogenous circadian timing may increase the risk of adolescent AUDs by altering reward-related brain function. The timing of sleep shifts later throughout adolescence, in part due to developmental changes in endogenous circadian rhythms, which tend to become more delayed. This tendency for delayed sleep and circadian rhythms is at odds with early school start times during secondary education, leading to misalignment between many adolescents' sleep-wake schedules and their internal circadian timing. Circadian misalignment is associated with increased alcohol use and other risk-taking behaviors, as well as sleep loss and sleep disturbance. Growing evidence indicates that circadian rhythms modulate the reward system, suggesting that circadian misalignment may impact adolescent alcohol involvement by altering reward-related brain function. Neurocognitive function is also subject to sleep and circadian influence, and thus circadian misalignment may also impair inhibitory control and other cognitive processes relevant to alcohol use. Specifically, circadian misalignment may further exacerbate the cortical-subcortical imbalance within the reward circuit, an imbalance thought to explain increased risk-taking and sensation-seeking during adolescence. Adolescent alcohol use is highly contextualized, however, and thus studies testing this model will also need to consider factors that may influence both circadian misalignment and alcohol use. This review highlights growing evidence supporting a path by which circadian misalignment may disrupt reward mechanisms, which may in turn accelerate the transition from alcohol use to AUDs in vulnerable adolescents. Copyright © 2013 by the Research Society on Alcoholism.

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

    PubMed Central

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

    2016-01-01

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

  10. Brain activity monitoring by compressed spectral array during deep hypothermic circulatory arrest in acute aortic dissection surgery.

    PubMed

    Urbanowicz, Tomasz K; Budniak, Wiktor; Buczkowski, Piotr; Perek, Bartłomiej; Walczak, Maciej; Tomczyk, Jadwiga; Katarzyński, Sławomir; Jemielity, Marek

    2014-12-01

    Monitoring the central nervous system during aortic dissection repair may improve the understanding of the intraoperative changes related to its bioactivity. The aim of the study was to evaluate the influence of deep hypothermia on intraoperative brain bioactivity measured by the compressed spectral array (CSA) method and to assess the influence of the operations on postoperative cognitive function. The study enrolled 40 patients (31 men and 9 women) at the mean age of 60.2 ± 8.6 years, diagnosed with acute aortic dissection. They underwent emergency operations in deep hypothermic circulatory arrest (DHCA). During the operations, brain bioactivity was monitored with the compressed spectral array method. There were no intraoperative deaths. Electrocerebral silence during DHCA was observed in 31 patients (74%). The lowest activity was observed during DHCA: it was 0.01 ± 0.05 nW in the left hemisphere and 0.01 ± 0.03 nW in the right hemisphere. The postoperative results of neurological tests deteriorated statistically significantly (26.9 ± 1.7 points vs. 22.0 ± 1.7 points; p < 0.001), especially among patients who exhibited brain activity during DHCA. The compressed spectral array method is clinically useful in monitoring brain bioactivity during emergency operations of acute aortic dissections. Electrocerebral silence occurs in 75% of patients during DHCA. The cognitive function of patients deteriorates significantly after operations with DHCA.

  11. fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease

    PubMed Central

    Bondi, Mark W.; Houston, Wes S.; Eyler, Lisa T.; Brown, Gregory G.

    2006-01-01

    Objective To determine whether APOE genotype influences brain response and whether nonverbal stimuli generate findings comparable with those of previous studies that used verbal stimuli. The relationship between APOE genotype and blood oxygenation level dependent (BOLD) brain response was examined during a picture-encoding task in nondemented older adults. Methods Twenty nondemented participants with normal episodic memory function were divided into two groups based on the presence (n = 10) or absence (n = 10) of the APOE ε4 allele. Picture learning was completed during functional MRI in a blocked design alternating between experimental (novel pictures) and control (repeated picture) conditions. Results Nondemented older adults with an APOE ε4 allele showed greater magnitude and extent of BOLD brain response during learning of new pictures relative to their matched ε3 counterparts. Different patterns and directions of association between hippocampal activity and learning and memory performance were also demonstrated. Conclusions The results suggest that brain response differences are not due to poorer general memory abilities, differential atrophy, or brain response during control conditions, but instead appear to be directly influenced by APOE genotype. Results are consistent with a compensatory hypothesis wherein older adults at genetic risk for Alzheimer disease by virtue of the APOE ε4 allele appear to require additional cognitive effort to achieve comparable performance levels on tests of episodic memory encoding. PMID:15699382

  12. New Therapeutic Drugs from Bioactive Natural Molecules: the Role of Gut Microbiota Metabolism in Neurodegenerative Diseases.

    PubMed

    Di Meo, Francesco; Donato, Stella; Di Pardo, Alba; Maglione, Vittorio; Filosa, Stefania; Crispi, Stefania

    2018-04-03

    The gut-brain axis is considered a neuroendocrine system, which connects brain and gastrointestinal tract and plays an important role in stress response. The homeostasis of gut-brain axis is important for healthy conditions and its alterations are associated to neurological disorders and neurodegenerative diseases. Gut microbiota is a dynamic ecosystem that can be altered by external factors such as diet composition, antibiotics or xenobiotics. Recent advances in gut microbiota analyses indicate that the gut bacterial community plays a key role in maintaining normal brain functions. Recent metagenomic analyses have elucidated that the relationship between gut and brain, either in normal or in pathological conditions, reflects the existence of a "microbiota-gut-brain" axis. Gut microbiota composition can be influenced by dietary ingestion of probiotics or natural bioactive molecules such as prebiotics and polyphenols. Their derivatives coming from microbiota metabolism can affect both gut bacterial composition and brain biochemistry. Modifications of microbiota composition by natural bioactive molecules could be used to restore the altered brain functions, which characterize neurodegenerative diseases, leading to consider these compounds as novel therapeutic strategies for the treatment of neuropathologies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Gut-Brain Axis and Behavior.

    PubMed

    Martin, Clair R; Mayer, Emeran A

    2017-01-01

    In the last 5 years, interest in the interactions among the gut microbiome, brain, and behavior has exploded. Preclinical evidence supports a role of the gut microbiome in behavioral responses associated with pain, emotion, social interactions, and food intake. Limited, but growing, clinical evidence comes primarily from associations of gut microbial composition and function to behavioral and clinical features and brain structure and function. Converging evidence suggests that the brain and the gut microbiota are in bidirectional communication. Observed dysbiotic states in depression, chronic stress, and autism may reflect altered brain signaling to the gut, while altered gut microbial signaling to the brain may play a role in reinforcing brain alterations. On the other hand, primary dysbiotic states due to Western diets may signal to the brain, altering ingestive behavior. While studies performed in patients with depression and rodent models generated by fecal microbial transfer from such patients suggest causation, evidence for an influence of acute gut microbial alterations on human behavioral and clinical parameters is lacking. Only recently has an open-label microbial transfer therapy in children with autism tentatively validated the gut microbiota as a therapeutic target. The translational potential of preclinical findings remains unclear without further clinical investigation. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

  14. 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.

  15. Fractality of sensations and the brain health: the theory linking neurodegenerative disorder with distortion of spatial and temporal scale-invariance and fractal complexity of the visible world

    PubMed Central

    Zueva, Marina V.

    2015-01-01

    The theory that ties normal functioning and pathology of the brain and visual system with the spatial–temporal structure of the visual and other sensory stimuli is described for the first time in the present study. The deficit of fractal complexity of environmental influences can lead to the distortion of fractal complexity in the visual pathways of the brain and abnormalities of development or aging. The use of fractal light stimuli and fractal stimuli of other modalities can help to restore the functions of the brain, particularly in the elderly and in patients with neurodegenerative disorders or amblyopia. Non-linear dynamics of these physiological processes have a strong base of evidence, which is seen in the impaired fractal regulation of rhythmic activity in aged and diseased brains. From birth to old age, we live in a non-linear world, in which objects and processes with the properties of fractality and non-linearity surround us. Against this background, the evolution of man took place and all periods of life unfolded. Works of art created by man may also have fractal properties. The positive influence of music on cognitive functions is well-known. Insufficiency of sensory experience is believed to play a crucial role in the pathogenesis of amblyopia and age-dependent diseases. The brain is very plastic in its early development, and the plasticity decreases throughout life. However, several studies showed the possibility to reactivate the adult’s neuroplasticity in a variety of ways. We propose that a non-linear structure of sensory information on many spatial and temporal scales is crucial to the brain health and fractal regulation of physiological rhythms. Theoretical substantiation of the author’s theory is presented. Possible applications and the future research that can experimentally confirm or refute the theoretical concept are considered. PMID:26236232

  16. Consciousness, brain, neuroplasticity

    PubMed Central

    Askenasy, Jean; Lehmann, Joseph

    2013-01-01

    Subjectivity, intentionality, self-awareness and will are major components of consciousness in human beings. Changes in consciousness and its content following different brain processes and malfunction have long been studied. Cognitive sciences assume that brain activities have an infrastructure, but there is also evidence that consciousness itself may change this infrastructure. The two-way influence between brain and consciousness has been at the center of philosophy and less so, of science. This so-called bottom-up and top-down interrelationship is controversial and is the subject of our article. We would like to ask: how does it happen that consciousness may provoke structural changes in the brain? The living brain means continuous changes at the synaptic level with every new experience, with every new process of learning, memorizing or mastering new and existing skills. Synapses are generated and dissolved, while others are preserved, in an ever-changing process of so-called neuroplasticity. Ongoing processes of synaptic reinforcements and decay occur during wakefulness when consciousness is present, but also during sleep when it is mostly absent. We suggest that consciousness influences brain neuroplasticity both during wakefulness as well as sleep in a top-down way. This means that consciousness really activates synaptic flow and changes brain structures and functional organization. The dynamic impact of consciousness on brain never stops despite the relative stationary structure of the brain. Such a process can be a target for medical intervention, e.g., by cognitive training. PMID:23847580

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

    PubMed

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

    2017-02-01

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

  18. Dysbindin modulates brain function during visual processing in children.

    PubMed

    Mechelli, A; Viding, E; Kumar, A; Pettersson-Yeo, W; Fusar-Poli, P; Tognin, S; O'Donovan, M C; McGuire, P

    2010-01-01

    Schizophrenia is a neurodevelopmental disorder, and risk genes are thought to act through disruption of brain development. Several genetic studies have identified dystrobrevin binding protein 1 (DTNBP1, also known as dysbindin) as a potential susceptibility gene for schizophrenia, but its impact on brain function is poorly understood. It has been proposed that DTNBP1 may be associated with differences in visual processing. To test this, we examined the impact on visual processing in 61 healthy children aged 10-12 years of a genetic variant in DTNBP1 (rs2619538) that was common to all schizophrenia associated haplotypes in an earlier UK-Irish study. We tested the hypothesis that carriers of the risk allele would show altered occipital cortical function relative to noncarriers. Functional Magnetic Resonance Imaging (fMRI) was used to measure brain responses during a visual matching task. The data were analysed using statistical parametric mapping and statistical inferences were made at p<0.05 (corrected for multiple comparisons). Relative to noncarriers, carriers of the risk allele had greater activation in the lingual, fusiform gyrus and inferior occipital gyri. In these regions DTNBP1 genotype accounted for 19%, 20% and 14% of the inter-individual variance, respectively. Our results suggest that that genetic variation in DTNBP1 is associated with differences in the function of brain areas that mediate visual processing, and that these effects are evident in young children. These findings are consistent with the notion that the DTNBP1 gene influences brain development and can thereby modulate vulnerability to schizophrenia.

  19. Study of emotion-based neurocardiology through wearable systems

    NASA Astrophysics Data System (ADS)

    Ramasamy, Mouli; Varadan, Vijay

    2016-04-01

    Neurocardiology is the exploration of neurophysiological, neurological and neuroanatomical facets of neuroscience's influence in cardiology. The paraphernalia of emotions on the heart and brain are premeditated because of the interaction between the central and peripheral nervous system. This is an investigative attempt to study emotion based neurocardiology and the factors that influence this phenomena. The factors include: interaction between sleep EEG (electroencephalogram) and ECG (electrocardiogram), relationship between emotion and music, psychophysiological coherence between the heart and brain, emotion recognition techniques, and biofeedback mechanisms. Emotions contribute vitally to the mundane life and are quintessential to a numerous biological and everyday-functional modalities of a human being. Emotions are best represented through EEG signals, and to a certain extent, can be observed through ECG and body temperature. Confluence of medical and engineering science has enabled the monitoring and discrimination of emotions influenced by happiness, anxiety, distress, excitement and several other factors that influence the thinking patterns and the electrical activity of the brain. Similarly, HRV (Heart Rate Variability) widely investigated for its provision and discerning characteristics towards EEG and the perception in neurocardiology.

  20. Brain networks involved in tactile speed classification of moving dot patterns: the effects of speed and dot periodicity

    PubMed Central

    Yang, Jiajia; Kitada, Ryo; Kochiyama, Takanori; Yu, Yinghua; Makita, Kai; Araki, Yuta; Wu, Jinglong; Sadato, Norihiro

    2017-01-01

    Humans are able to judge the speed of an object’s motion by touch. Research has suggested that tactile judgment of speed is influenced by physical properties of the moving object, though the neural mechanisms underlying this process remain poorly understood. In the present study, functional magnetic resonance imaging was used to investigate brain networks that may be involved in tactile speed classification and how such networks may be affected by an object’s texture. Participants were asked to classify the speed of 2-D raised dot patterns passing under their right middle finger. Activity in the parietal operculum, insula, and inferior and superior frontal gyri was positively related to the motion speed of dot patterns. Activity in the postcentral gyrus and superior parietal lobule was sensitive to dot periodicity. Psycho-physiological interaction (PPI) analysis revealed that dot periodicity modulated functional connectivity between the parietal operculum (related to speed) and postcentral gyrus (related to dot periodicity). These results suggest that texture-sensitive activity in the primary somatosensory cortex and superior parietal lobule influences brain networks associated with tactually-extracted motion speed. Such effects may be related to the influence of surface texture on tactile speed judgment. PMID:28145505

  1. Brain Morphology Links Systemic Inflammation to Cognitive Function in Midlife Adults

    PubMed Central

    Marsland, Anna L.; Gianaros, Peter J.; Kuan, Dora C-H.; Sheu, Lei K.; Krajina, Katarina; Manuck, Stephen B.

    2015-01-01

    Background Inflammation is linked to cognitive decline in midlife, but the neural basis for this link is unclear. One possibility is that inflammation associates with adverse changes in brain morphology, which accelerates cognitive aging and later dementia risk. Clear evidence is lacking, however, regarding whether inflammation relates to cognition in midlife via changes in brain morphology. Accordingly, the current study examines whether associations of inflammation with cognitive function are mediated by variation in cortical gray matter volume among midlife adults. Methods Plasma levels of interleukin (IL)-6 and C-reactive protein (CRP), relatively stable markers of peripheral systemic inflammation, were assessed in 408 community volunteers aged 30–54 years. All participants underwent structural neuroimaging to assess global and regional brain morphology and completed neuropsychological tests sensitive to early changes in cognitive function. Measurements of brain morphology (regional tissue volumes and cortical thickness and surface area) were derived using Freesurfer. Results Higher peripheral inflammation was associated with poorer spatial reasoning, short term memory, verbal proficiency, learning and memory, and executive function, as well as lower cortical gray and white matter volumes, hippocampal volume and cortical surface area. Mediation models with age, sex and intracranial volume as covariates showed cortical gray matter volume to partially mediate the association of inflammation with cognitive performance. Exploratory analyses of body mass suggested that adiposity may be a source of the inflammation linking brain morphology to cognition. Conclusions Inflammation and adiposity might relate to cognitive decline via influences on brain morphology. PMID:25882911

  2. Lifestyle Shapes the Dialogue between Environment, Microglia, and Adult Neurogenesis.

    PubMed

    Valero, Jorge; Paris, Iñaki; Sierra, Amanda

    2016-04-20

    Lifestyle modulates brain function. Diet, stress levels, and physical exercise among other factors influence the "brain cognitive reserve", that is, the capacity of the brain to maintain a normal function when confronting neurodegenerative diseases, injury, and/or aging. This cognitive reserve relays on several cellular and molecular elements that contribute to brain plasticity allowing adaptive responses to cognitive demands, and one of its key components is the hippocampal neurogenic reserve. Hippocampal neural stem cells give rise to new neurons that integrate into the local circuitry and contribute to hippocampal functions such as memory and learning. Importantly, adult hippocampal neurogenesis is well-known to be modulated by the demands of the environment and lifestyle factors. Diet, stress, and physical exercise directly act on neural stem cells and/or their progeny, but, in addition, they may also indirectly affect neurogenesis by acting on microglia. Microglia, the guardians of the brain, rapidly sense changes in the brain milieu, and it has been recently shown that their function is affected by lifestyle factors. However, few studies have analyzed the modulatory effect of microglia on adult neurogenesis in these conditions. Here, we review the current knowledge about the dialogue maintained between microglia and the hippocampal neurogenic cascade. Understanding how the communication between microglia and hippocampal neurogenesis is affected by lifestyle choices is crucial to maintain the brain cognitive reserve and prevent the maladaptive responses that emerge during disease or injury through adulthood and aging.

  3. Influence of posterior dental arch length on brain activity during chewing in patients with mandibular distal extension removable partial dentures.

    PubMed

    Shoi, K; Fueki, K; Usui, N; Taira, M; Wakabayashi, N

    2014-07-01

    It is well known that shortened dental arch decreases masticatory function. However, its potential to change brain activity during mastication is unknown. The present study investigates the effect of a shortened posterior dental arch with mandibular removable partial dentures (RPDs) on brain activity during gum chewing. Eleven subjects with missing mandibular molars (mean age, 66.1 years) on both sides received experimental RPDs with interchangeable artificial molars in a crossover trial design. Brain activity during gum chewing with RPDs containing (full dental arch) and lacking artificial molars (shortened dental arch) was measured using functional magnetic resonance imaging. Additionally, masticatory function was evaluated for each dental arch type. Food comminuting and mixing ability and the perceived chewing ability were significantly lower in subjects with a shortened dental arch than those with a full dental arch (P < 0.05). Brain activation during gum chewing with the full dental arch occurred in the middle frontal gyrus, primary sensorimotor cortex extending to the pre-central gyrus, supplementary motor area, putamen, insula and cerebellum. However, middle frontal gyrus activation was not observed during gum chewing with the shortened dental arch. These results suggest that shortened dental arch affects human brain activity in the middle frontal gyrus during gum chewing, and the decreased middle frontal gyrus activation may be associated with decreased masticatory function. © 2014 John Wiley & Sons Ltd.

  4. Evolution and the neurosciences down-under.

    PubMed

    Macmillan, Malcolm

    2009-01-01

    At the end of the nineteenth and the beginning of the twentieth century three Australians made notable contributions to founding the neurosciences: Alfred Walter Campbell (1868-1937) conducted the first extensive histological studies of the human brain; Grafton Elliot Smith (1871-1937) studied the monotreme brain and established the basis for understanding the mammalian brain; and Stanley David Porteus (1883-1972) extended his studies of intellectual disability to encompass the relation between brain size and intelligence. The work of each was decisively influenced by important members of the Edinburgh medical school or by Edinburgh medical graduates: William Turner (1832-1916) and William Rutherford (1839-1899) Professors of Anatomy and Physiology respectively at Edinburgh; James Thomas Wilson (1861-1945) Professor of Anatomy at the University of Sydney; and Richard James Arthur Berry (1867-1962) Professor of Anatomy at the University of Melbourne. An important aspect of the influence on the Australians was a materialist view of brain function but the work of all was most important for a theory even more central held by the Scots who had influenced them: Darwin's theory of evolution. The importance of the work of Campbell and especially that of Smith for Darwinism is contrasted with Darwin's own indifference to the peculiarities of the Australian fauna he observed when he visited Australia during HMS Beagle's voyage of discovery in 1836.

  5. Large-scale imaging in small brains

    PubMed Central

    Ahrens, Misha B.; Engert, Florian

    2016-01-01

    The dense connectivity in the brain and arrangements of cells into circuits means that one neuron’s activity can influence many others. To observe this interconnected system comprehensively, an aspiration within neuroscience is to record from as many neurons as possible at the same time. There are two useful routes toward this goal: one is to expand the spatial extent of functional imaging techniques, and the second is to use animals with small brains. Here we review recent progress toward imaging many neurons and complete populations of identified neurons in small vertebrates and invertebrates. PMID:25636154

  6. Large-scale imaging in small brains.

    PubMed

    Ahrens, Misha B; Engert, Florian

    2015-06-01

    The dense connectivity in the brain means that one neuron's activity can influence many others. To observe this interconnected system comprehensively, an aspiration within neuroscience is to record from as many neurons as possible at the same time. There are two useful routes toward this goal: one is to expand the spatial extent of functional imaging techniques, and the second is to use animals with small brains. Here we review recent progress toward imaging many neurons and complete populations of identified neurons in small vertebrates and invertebrates. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Musical training, neuroplasticity and cognition.

    PubMed

    Rodrigues, Ana Carolina; Loureiro, Maurício Alves; Caramelli, Paulo

    2010-01-01

    The influence of music on the human brain has been recently investigated in numerous studies. Several investigations have shown that structural and functional cerebral neuroplastic processes emerge as a result of long-term musical training, which in turn may produce cognitive differences between musicians and non-musicians. Musicians can be considered ideal cases for studies on brain adaptation, due to their unique and intensive training experiences. This article presents a review of recent findings showing positive effects of musical training on non-musical cognitive abilities, which probably reflect plastic changes in brains of musicians.

  8. Effect of Experimental Thyrotoxicosis on Brain Gray Matter: A Voxel-Based Morphometry Study.

    PubMed

    Göbel, Anna; Heldmann, Marcus; Göttlich, Martin; Dirk, Anna-Luise; Brabant, Georg; Münte, Thomas F

    2015-09-01

    Hyper-as well hypothyroidism have an effect on behavior and brain function. Moreover, during development thyroid hormones influence brain structure. This study aimed to demonstrate an effect of experimentally induced hyperthyroidism on brain gray matter in healthy adult humans. High-resolution 3D T1-weighted images were acquired in 29 healthy young subjects prior to as well as after receiving 250 µg of T4 per day for 8 weeks. Voxel-based morphometry analysis was performed using Statistical Parametric Mapping 8 (SPM8). Laboratory testing confirmed the induction of hyperthyroidism. In the hyperthyroid condition, gray matter volumes were increased in the right posterior cerebellum (lobule VI) and decreased in the bilateral visual cortex and anterior cerebellum (lobules I-IV) compared to the euthyroid condition. Our study provides evidence that short periods of hyperthyroidism induce distinct alterations in brain structures of cerebellar regions that have been associated with sensorimotor functions as well as working memory in the literature.

  9. Brain network disturbance related to posttraumatic stress and traumatic brain injury in veterans.

    PubMed

    Spielberg, Jeffrey M; McGlinchey, Regina E; Milberg, William P; Salat, David H

    2015-08-01

    Understanding the neural causes and consequences of posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) is a high research priority, given the high rates of associated disability and suicide. Despite remarkable progress in elucidating the brain mechanisms of PTSD and mTBI, a comprehensive understanding of these conditions at the level of brain networks has yet to be achieved. The present study sought to identify functional brain networks and topological properties (measures of network organization and function) related to current PTSD severity and mTBI. Graph theoretic tools were used to analyze resting-state functional magnetic resonance imaging data from 208 veterans of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn, all of whom had experienced a traumatic event qualifying for PTSD criterion A. Analyses identified brain networks and topological network properties linked to current PTSD symptom severity, mTBI, and the interaction between PTSD and mTBI. Two brain networks were identified in which weaker connectivity was linked to higher PTSD re-experiencing symptoms, one of which was present only in veterans with comorbid mTBI. Re-experiencing was also linked to worse functional segregation (necessary for specialized processing) and diminished influence of key regions on the network, including the hippocampus. Findings of this study demonstrate that PTSD re-experiencing symptoms are linked to weakened connectivity in a network involved in providing contextual information. A similar relationship was found in a separate network typically engaged in the gating of working memory, but only in veterans with mTBI. Published by Elsevier Inc.

  10. Chaos in the heart: the interaction between body and mind

    NASA Astrophysics Data System (ADS)

    Redington, Dana

    1993-11-01

    A number of factors influence the chaotic dynamics of heart function. Genetics, age, sex, disease, the environment, experience, and of course the mind, play roles in influencing cardiovascular dynamics. The mind is of particular interest because it is an emergent phenomenon of the body admittedly seated and co-occurrent in the brain. The brain serves as the body's controller, and commands the heart through complex multipathway feedback loops. Structures deep within the brain, the hypothalamus and other centers in the brainstem, modulate heart function, partially as a result of afferent input from the body but also a result of higher mental processes. What can chaos in the body, i.e., the nonlinear dynamics of the heart, tell of the mind? This paper presents a brief overview of the spectral structure of heart rate activity followed by a summary of experimental results based on phase space analysis of data from semi-structured interviews. This paper then describes preliminary quantification of cardiovascular dynamics during different stressor conditions in an effort to apply more quantitative methods to clinical data.

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

    PubMed

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

    2017-05-22

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

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

    PubMed Central

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

    2017-01-01

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

  13. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior.

    PubMed

    Patrick, Rhonda P; Ames, Bruce N

    2015-06-01

    Serotonin regulates a wide variety of brain functions and behaviors. Here, we synthesize previous findings that serotonin regulates executive function, sensory gating, and social behavior and that attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior all share in common defects in these functions. It has remained unclear why supplementation with omega-3 fatty acids and vitamin D improve cognitive function and behavior in these brain disorders. Here, we propose mechanisms by which serotonin synthesis, release, and function in the brain are modulated by vitamin D and the 2 marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Brain serotonin is synthesized from tryptophan by tryptophan hydroxylase 2, which is transcriptionally activated by vitamin D hormone. Inadequate levels of vitamin D (∼70% of the population) and omega-3 fatty acids are common, suggesting that brain serotonin synthesis is not optimal. We propose mechanisms by which EPA increases serotonin release from presynaptic neurons by reducing E2 series prostaglandins and DHA influences serotonin receptor action by increasing cell membrane fluidity in postsynaptic neurons. We propose a model whereby insufficient levels of vitamin D, EPA, or DHA, in combination with genetic factors and at key periods during development, would lead to dysfunctional serotonin activation and function and may be one underlying mechanism that contributes to neuropsychiatric disorders and depression. This model suggests that optimizing vitamin D and marine omega-3 fatty acid intake may help prevent and modulate the severity of brain dysfunction. © FASEB.

  14. Functional analysis and intervention for perseverative verbal behaviour of an older adult with traumatic brain injury.

    PubMed

    Quearry, Amy Garcia; Lundervold, Duane A

    2016-01-01

    A functional analysis of behaviour was conducted to determine the controlling variables related to the perseverative verbal behaviour (PBV) of a 60-year-old female with a long-standing traumatic brain injury receiving educational assistance. Functional analyses (FA) of antecedent and consequent conditions related to PCB were conducted to determine controlling influence of: (a) content of verbal interaction and, (b) social reinforcement. After isolating the controlling variables, the functioned-based intervention was implemented in 60 minute tutoring sessions. A reversal condition was used to demonstrate experimental control of the behavior during tutoring sessions. PVB which occurred in the context of tutoring for an undergraduate course significantly interfered with the delivery of instruction. Multiple replications of the functional relation between social reinforcement and PVB duration was demonstrated using an A-B-A-B reversal design during functional analysis and tutoring conditions. PVB markedly declined, but did not extinguish over the course of weekly tutoring (extinction) sessions, most likely due to 'bootleg reinforcement' occurring in other situations. Results indicate that perseverative verbal behaviour following closed head injury may be strongly influenced by the social contingencies operating in various contexts and is amenable to applied behaviour analysis interventions.

  15. Genetic Mapping of Brain Plasticity Across Development in Williams Syndrome: ERP Markers of Face and Language Processing

    PubMed Central

    Mills, D. L.; Dai, L.; Fishman, I.; Yam, A.; Appelbaum, L. G.; Galaburda, A.; Bellugi, U.; Korenberg, J. R.

    2014-01-01

    In Williams Syndrome (WS), a known genetic deletion results in atypical brain function with strengths in face and language processing. We examined how genetic influences on brain activity change with development. In three studies, ERPs from large samples of children, adolescents, and adults with the full genetic deletion for WS were compared to typically developing controls, and two adults with partial deletions for WS. Studies 1 and 2 identified ERP markers of brain plasticity in WS across development. Study 3 suggested that in adults with partial deletions for WS, specific genes may be differentially implicated in face and language processing. PMID:24219698

  16. The self-regulating brain and neurofeedback: Experimental science and clinical promise.

    PubMed

    Thibault, Robert T; Lifshitz, Michael; Raz, Amir

    2016-01-01

    Neurofeedback, one of the primary examples of self-regulation, designates a collection of techniques that train the brain and help to improve its function. Since coming on the scene in the 1960s, electroencephalography-neurofeedback has become a treatment vehicle for a host of mental disorders; however, its clinical effectiveness remains controversial. Modern imaging technologies of the living human brain (e.g., real-time functional magnetic resonance imaging) and increasingly rigorous research protocols that utilize such methodologies begin to shed light on the underlying mechanisms that may facilitate more effective clinical applications. In this paper we focus on recent technological advances in the field of human brain imaging and discuss how these modern methods may influence the field of neurofeedback. Toward this end, we outline the state of the evidence and sketch out future directions to further explore the potential merits of this contentious therapeutic prospect. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. [Gut microbiome and psyche: paradigm shift in the concept of brain-gut axis].

    PubMed

    Konturek, Peter C; Zopf, Yurdagül

    2016-05-25

    The concept of the brain-gut axis describes the communication between the central and enteric nervous system. The exchange of information takes place in both directions. The great advances in molecular medicine in recent years led to the discovery of an enormous number of microorganisms in the intestine (gut microbiome), which greatly affect the function of the brain-gut axis. Overview Numerous studies indicate that the dysfunction of the brain-gut axis could lead to both inflammatory and functional diseases of the gastrointestinal tract. Moreover, it was shown that a faulty composition of the gut microbiota in childhood influences the maturation of the central nervous system and thus may favor the development of mental disorders such as autism, depression, or other. An exact causal relationship between psyche and microbiome must be clarified by further studies in order to find new therapeutic options.

  18. Diet and gender influences on processing and discrimination of speech sounds in 3 and 6 month-old infants: A developmental ERP study

    USDA-ARS?s Scientific Manuscript database

    Although early post-natal nutrition influences later development, there are no studies comparing brain function in healthy infants fed the three major infant diets (breast milk, milk-based and soy-based formula) even though these diets differ significantly in nutrient composition. We have studied br...

  19. How does dysautonomia influence the outcome of traumatic brain injured patients admitted in a neurorehabilitation unit?

    PubMed

    Laxe, Sara; Terré, Rosa; León, Daniel; Bernabeu, Montserrat

    2013-01-01

    Patients surviving severe traumatic brain injury (TBI) may suffer from symptoms presumed to be related to an excessive sympathetic production known as paroxysmal sympathetic hyperactivity (PSH). While this condition is more common in the acute phase, prognosis is less clear in rehabilitation settings. The goal of this study is to describe the functional status of patients with PSH admitted in a rehabilitation hospital and to determine its prognostic influence during rehabilitation. A cohort study was undertaken of all the patients admitted in a neurorehabilitation hospital suffering from PSH. Functional outcomes were reported according to the Glasgow outcome scale-extended (GOSE), the Disability Rating Scale (DRS) and the Functional Independence Measure (FIM). Thirteen out of 39 patients suffered symptoms compatible with PSH. Neuroimaging of PSH patients showed more diffuse lesions. The FIM at admission was lower in the PSH group who was transferred for rehabilitation at an earlier stage. At discharge no differences were seen using the FIM, DRS and GOS-E. Functional status is similar and PSH does not appear to influence recovery during the rehabilitation, although PSH patients are more likely to undergo psychoactive medications and special care is needed to approach their caregivers that perceive PSH as a complication for rehabilitation.

  20. White Matter Connectivity of the Thalamus Delineates the Functional Architecture of Competing Thalamocortical Systems

    PubMed Central

    O'Muircheartaigh, Jonathan; Keller, Simon S.; Barker, Gareth J.; Richardson, Mark P.

    2015-01-01

    There is an increasing awareness of the involvement of thalamic connectivity on higher level cortical functioning in the human brain. This is reflected by the influence of thalamic stimulation on cortical activity and behavior as well as apparently cortical lesion syndromes occurring as a function of small thalamic insults. Here, we attempt to noninvasively test the correspondence of structural and functional connectivity of the human thalamus using diffusion-weighted and resting-state functional MRI. Using a large sample of 102 adults, we apply tensor independent component analysis to diffusion MRI tractography data to blindly parcellate bilateral thalamus according to diffusion tractography-defined structural connectivity. Using resting-state functional MRI collected in the same subjects, we show that the resulting structurally defined thalamic regions map to spatially distinct, and anatomically predictable, whole-brain functional networks in the same subjects. Although there was significant variability in the functional connectivity patterns, the resulting 51 structural and functional patterns could broadly be reduced to a subset of 7 similar core network types. These networks were distinct from typical cortical resting-state networks. Importantly, these networks were distributed across the brain and, in a subset, map extremely well to known thalamocortico-basal-ganglial loops. PMID:25899706

  1. Traumatic brain injury shows better functional recovery than brain tumor: a rehabilitative perspective.

    PubMed

    Bilgin, S; Kose, N; Karakaya, J; Mut, M

    2014-02-01

    The similar symptoms seen in the brain tumor (BT) and traumatic brain injury (TBI) population. However, functional comparisons between these two diagnostic groups have been limited. To compare functional outcomes in patients with supratentorial BT and TBI after early rehabilitation. This was a retrospective database analysis. Setting. Patients admitted to an Acute Care Unit as inpatient (Hacettepe Hospital, Ankara-Turkey). Population. The population included patients with BT and TBI. Thirty-four patients with BT and TBI were matched one-to-one by lesion side and sex. The Barthel Index was used to assess functional status at the pre- and postrehabilitation. The change rate and efficiency in BI were also calculated. The time between injury onset and admission to rehabilitation (the onset to admission interval, OAI) and length of stay in rehabilitation (LOS rehab) were recorded. In addition, the influence of lesion side (left and right) and age on functional outcome were analyzed. The functional level was significantly lower in TBI patients than in patients BT before rehabilitation (P<0.05). The post-rehabilitation BI score was similar in patients with BT and TBI (P>0.05). Patients with TBI had greater the change rate and efficiency in BI (P<0.05). The OAI and LOS rehab was longer in patients with TBI (P<0.05). In terms of lesion side comparisons, no differences were found (P>0.05). The age had no effect on functional outcome in patients with TBI and BT (P>0.05), expect the age group 45-59 (P<0.05). The early rehabilitation program improved functional ability of patients with brain tumors, as well as patients with traumatic brain injury. Despite the lower functional status, patients with TBI displayed better functional recovery than patients with BT. Lesion side had no effect on functional outcome in patients with TBI and BT. Differences in functional status begin to appear even in patients with TBI between 45 and 59 years. Further investigations with more detailed outcome instruments are required to better understand the qualitative limitations of a patient's recovery. Patients with TBI will make functional gains comparable with patients with brain tumors in a similar rehabilitation setting.

  2. Fumarate decreases edema volume and improves functional outcome after experimental stroke.

    PubMed

    Clausen, Bettina Hjelm; Lundberg, Louise; Yli-Karjanmaa, Minna; Martin, Nellie Anne; Svensson, Martina; Alfsen, Maria Zeiler; Flæng, Simon Bertram; Lyngsø, Kristina; Boza-Serrano, Antonio; Nielsen, Helle H; Hansen, Pernille B; Finsen, Bente; Deierborg, Tomas; Illes, Zsolt; Lambertsen, Kate Lykke

    2017-09-01

    Oxidative stress and inflammation exacerbate tissue damage in the brain after ischemic stroke. Dimethyl-fumarate (DMF) and its metabolite monomethyl-fumarate (MMF) are known to stimulate anti-oxidant pathways and modulate inflammatory responses. Considering these dual effects of fumarates, we examined the effect of MMF treatment after ischemic stroke in mice. Permanent middle cerebral artery occlusion (pMCAO) was performed using adult, male C57BL/6 mice. Thirty minutes after pMCAO, 20mg/kg MMF was administered intravenously. Outcomes were evaluated 6, 24 and 48h after pMCAO. First, we examined whether a bolus of MMF was capable of changing expression of kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor (Nrf)2 in the infarcted brain. Next, we studied the effect of MMF on functional recovery. To explore mechanisms potentially influencing functional changes, we examined infarct volumes, edema formation, the expression of heat shock protein (Hsp)72, hydroxycarboxylic acid receptor 2 (Hcar2), and inducible nitric oxide synthase (iNOS) in the infarcted brain using real-time PCR and Western blotting. Concentrations of a panel of pro- and anti-inflammatory cytokines (IFNγ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, TNF) were examined in both the infarcted brain tissue and plasma samples 6, 24 and 48h after pMCAO using multiplex electrochemoluminiscence analysis. Administration of MMF increased the protein level of Nrf2 6h after pMCAO, and improved functional outcome at 24 and 48h after pMCAO. MMF treatment did not influence infarct size, however reduced edema volume at both 24 and 48h after pMCAO. MMF treatment resulted in increased Hsp72 expression in the brain 6h after pMCAO. Hcar2 mRNA levels increased significantly 24h after pMCAO, but were not different between saline- and MMF-treated mice. MMF treatment also increased the level of the anti-inflammatory cytokine IL-10 in the brain and plasma 6h after pMCAO, and additionally reduced the level of the pro-inflammatory cytokine IL-12p70 in the brain at 24 and 48h after pMCAO. A single intravenous bolus of MMF improved sensory-motor function after ischemic stroke, reduced edema formation, and increased the levels of the neuroprotective protein Hsp72 in the brain. The early increase in IL-10 and reduction in IL-12p70 in the brain combined with changes in systemic cytokine levels may also contribute to the functional recovery after pMCAO. Copyright © 2017. Published by Elsevier Inc.

  3. Non-synaptic receptors and transporters involved in brain functions and targets of drug treatment

    PubMed Central

    Vizi, ES; Fekete, A; Karoly, R; Mike, A

    2010-01-01

    Beyond direct synaptic communication, neurons are able to talk to each other without making synapses. They are able to send chemical messages by means of diffusion to target cells via the extracellular space, provided that the target neurons are equipped with high-affinity receptors. While synaptic transmission is responsible for the ‘what’ of brain function, the ‘how’ of brain function (mood, attention, level of arousal, general excitability, etc.) is mainly controlled non-synaptically using the extracellular space as communication channel. It is principally the ‘how’ that can be modulated by medicine. In this paper, we discuss different forms of non-synaptic transmission, localized spillover of synaptic transmitters, local presynaptic modulation and tonic influence of ambient transmitter levels on the activity of vast neuronal populations. We consider different aspects of non-synaptic transmission, such as synaptic–extrasynaptic receptor trafficking, neuron–glia communication and retrograde signalling. We review structural and functional aspects of non-synaptic transmission, including (i) anatomical arrangement of non-synaptic release sites, receptors and transporters, (ii) intravesicular, intra- and extracellular concentrations of neurotransmitters, as well as the spatiotemporal pattern of transmitter diffusion. We propose that an effective general strategy for efficient pharmacological intervention could include the identification of specific non-synaptic targets and the subsequent development of selective pharmacological tools to influence them. PMID:20136842

  4. SOCIAL: an integrative framework for the development of social skills.

    PubMed

    Beauchamp, Miriam H; Anderson, Vicki

    2010-01-01

    Despite significant advances in the field of social neuroscience, much remains to be understood regarding the development and maintenance of social skills across the life span. Few comprehensive models exist that integrate multidisciplinary perspectives and explain the multitude of factors that influence the emergence and expression of social skills. Here, a developmental biopsychosocial model (SOCIAL) is offered that incorporates the biological underpinnings and socio-cognitive skills that underlie social function (attention/executive function, communication, socio-emotional skills), as well as the internal and external (environmental) factors that mediate these skills. The components of the model are discussed in the context of the social brain network and are supported by evidence from 3 conditions known to affect social functioning (autism spectrum disorders, schizophrenia, and traumatic brain injury). This integrative model is intended to provide a theoretical structure for understanding the origins of social dysfunction and the factors that influence the emergence of social skills through childhood and adolescence in both healthy and clinical populations.

  5. 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.

  6. Genetic Psychophysiology: advances, problems, and future directions

    PubMed Central

    Anokhin, Andrey P.

    2014-01-01

    This paper presents an overview of historical advances and the current state of genetic psychophysiology, a rapidly developing interdisciplinary research linking genetics, brain, and human behavior, discusses methodological problems, and outlines future directions of research. The main goals of genetic psychophysiology are to elucidate the neural pathways and mechanisms mediating genetic influences on cognition and emotion, identify intermediate brain-based phenotypes for psychopathology, and provide a functional characterization of genes being discovered by large association studies of behavioral phenotypes. Since the initiation of this neurogenetic approach to human individual differences in the 1970s, numerous twin and family studies have provided strong evidence for heritability of diverse aspects of brain function including resting-state brain oscillations, functional connectivity, and event-related neural activity in a variety of cognitive and emotion processing tasks, as well as peripheral psychophysiological responses. These data indicate large differences in the presence and strength of genetic influences across measures and domains, permitting the selection of heritable characteristics for gene finding studies. More recently, candidate gene association studies began to implicate specific genetic variants in different aspects of neurocognition. However, great caution is needed in pursuing this line of research due to its demonstrated proneness to generate false-positive findings. Recent developments in methods for physiological signal analysis, hemodynamic imaging, and genomic technologies offer new exciting opportunities for the investigation of the interplay between genetic and environmental factors in the development of individual differences in behavior, both normal and abnormal. PMID:24739435

  7. Special issue on the teenage brain: Sensitivity to social evaluation

    PubMed Central

    Somerville, Leah H.

    2013-01-01

    Relative to childhood, peer relationships take on a heightened importance during adolescence. Might adolescents be highly attuned to information that concerns when and how they are being evaluated, and what their peers think of them? This review evaluates how continuing brain development - which influences brain function - partially explains or reflects adolescents’ attunement to social evaluation. Though preliminary, evidence is mounting to suggest that while processing information relevant to social evaluation and the internal states of other people, adolescents respond with greater emotional intensity and corresponding nonlinear recruitment of socioaffective brain circuitry. This review highlights research findings that relate trajectories of brain development and social behavior, and discusses promising avenues of future research that will inform how brain development might lead adolescents sensitized to social evaluation. PMID:24761055

  8. Adaptive Capacity: An Evolutionary Neuroscience Model Linking Exercise, Cognition, and Brain Health.

    PubMed

    Raichlen, David A; Alexander, Gene E

    2017-07-01

    The field of cognitive neuroscience was transformed by the discovery that exercise induces neurogenesis in the adult brain, with the potential to improve brain health and stave off the effects of neurodegenerative disease. However, the basic mechanisms underlying exercise-brain connections are not well understood. We use an evolutionary neuroscience approach to develop the adaptive capacity model (ACM), detailing how and why physical activity improves brain function based on an energy-minimizing strategy. Building on studies showing a combined benefit of exercise and cognitive challenge to enhance neuroplasticity, our ACM addresses two fundamental questions: (i) what are the proximate and ultimate mechanisms underlying age-related brain atrophy, and (ii) how do lifestyle changes influence the trajectory of healthy and pathological aging? Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. The cognitive neuroscience of ageing.

    PubMed

    Grady, Cheryl

    2012-06-20

    The availability of neuroimaging technology has spurred a marked increase in the human cognitive neuroscience literature, including the study of cognitive ageing. Although there is a growing consensus that the ageing brain retains considerable plasticity of function, currently measured primarily by means of functional MRI, it is less clear how age differences in brain activity relate to cognitive performance. The field is also hampered by the complexity of the ageing process itself and the large number of factors that are influenced by age. In this Review, current trends and unresolved issues in the cognitive neuroscience of ageing are discussed.

  10. 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.

  11. Short-Term Variations in Response Distribution to Cortical Stimulation

    ERIC Educational Resources Information Center

    Lesser, Ronald P.; Lee, Hyang Woon; Webber, W. R. S.; Prince, Barry; Crone, Nathan E.; Miglioretti, Diana L.

    2008-01-01

    Patterns of responses in the cerebral cortex can vary, and are influenced by pre-existing cortical function, but it is not known how rapidly these variations can occur in humans. We investigated how rapidly response patterns to electrical stimulation can vary in intact human brain. We also investigated whether the type of functional change…

  12. Stimulation through Simulation? Motor Imagery and Functional Reorganization in Hemiplegic Stroke Patients

    ERIC Educational Resources Information Center

    Johnson-Frey, Scott H.

    2004-01-01

    A key factor influencing reorganization of function in damaged neural networks of the adult brain is stimulation. How to stimulate motor areas of patients with paralyses is a formidable challenge. One possibility is to use internal movement simulations, or motor imagery, as an alternative to conventional therapeutic interventions that require…

  13. Differential impact of thalamic versus subthalamic deep brain stimulation on lexical processing.

    PubMed

    Krugel, Lea K; Ehlen, Felicitas; Tiedt, Hannes O; Kühn, Andrea A; Klostermann, Fabian

    2014-10-01

    Roles of subcortical structures in language processing are vague, but, interestingly, basal ganglia and thalamic Deep Brain Stimulation can go along with reduced lexical capacities. To deepen the understanding of this impact, we assessed word processing as a function of thalamic versus subthalamic Deep Brain Stimulation. Ten essential tremor patients treated with thalamic and 14 Parkinson׳s disease patients with subthalamic Deep Brain Stimulation performed an acoustic Lexical Decision Task ON and OFF stimulation. Combined analysis of task performance and event-related potentials allowed the determination of processing speed, priming effects, and N400 as neurophysiological correlate of lexical stimulus processing. 12 age-matched healthy participants acted as control subjects. Thalamic Deep Brain Stimulation prolonged word decisions and reduced N400 potentials. No comparable ON-OFF effects were present in patients with subthalamic Deep Brain Stimulation. In the latter group of patients with Parkinson' disease, N400 amplitudes were, however, abnormally low, whether under active or inactive Deep Brain Stimulation. In conclusion, performance speed and N400 appear to be influenced by state functions, modulated by thalamic, but not subthalamic Deep Brain Stimulation, compatible with concepts of thalamo-cortical engagement in word processing. Clinically, these findings specify cognitive sequels of Deep Brain Stimulation in a target-specific way. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Causal influence in neural systems: Reconciling mechanistic-reductionist and statistical perspectives. Comment on "Foundational perspectives on causality in large-scale brain networks" by M. Mannino & S.L. Bressler

    NASA Astrophysics Data System (ADS)

    Griffiths, John D.

    2015-12-01

    The modern understanding of the brain as a large, complex network of interacting elements is a natural consequence of the Neuron Doctrine [1,2] that has been bolstered in recent years by the tools and concepts of connectomics. In this abstracted, network-centric view, the essence of neural and cognitive function derives from the flows between network elements of activity and information - or, more generally, causal influence. The appropriate characterization of causality in neural systems, therefore, is a question at the very heart of systems neuroscience.

  15. Regional expression of the MAPT gene is associated with loss of hubs in brain networks and cognitive impairment in Parkinson disease and progressive supranuclear palsy.

    PubMed

    Rittman, Timothy; Rubinov, Mikail; Vértes, Petra E; Patel, Ameera X; Ginestet, Cedric E; Ghosh, Boyd C P; Barker, Roger A; Spillantini, Maria Grazia; Bullmore, Edward T; Rowe, James B

    2016-12-01

    Abnormalities of tau protein are central to the pathogenesis of progressive supranuclear palsy, whereas haplotype variation of the tau gene MAPT influences the risk of Parkinson disease and Parkinson's disease dementia. We assessed whether regional MAPT expression might be associated with selective vulnerability of global brain networks to neurodegenerative pathology. Using task-free functional magnetic resonance imaging in progressive supranuclear palsy, Parkinson disease, and healthy subjects (n = 128), we examined functional brain networks and measured the connection strength between 471 gray matter regions. We obtained MAPT and SNCA microarray expression data in healthy subjects from the Allen brain atlas. Regional connectivity varied according to the normal expression of MAPT. The regional expression of MAPT correlated with the proportionate loss of regional connectivity in Parkinson's disease. Executive cognition was impaired in proportion to the loss of hub connectivity. These effects were not seen with SNCA, suggesting that alpha-synuclein pathology is not mediated through global network properties. The results establish a link between regional MAPT expression and selective vulnerability of functional brain networks to neurodegeneration. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. How does a specific learning and memory system in the mammalian brain gain control of behavior?

    PubMed

    McDonald, Robert J; Hong, Nancy S

    2013-11-01

    This review addresses a fundamental, yet poorly understood set of issues in systems neuroscience. The issues revolve around conceptualizations of the organization of learning and memory in the mammalian brain. One intriguing, and somewhat popular, conceptualization is the idea that there are multiple learning and memory systems in the mammalian brain and they interact in different ways to influence and/or control behavior. This approach has generated interesting empirical and theoretical work supporting this view. One issue that needs to be addressed is how these systems influence or gain control of voluntary behavior. To address this issue, we clearly specify what we mean by a learning and memory system. We then review two types of processes that might influence which memory system gains control of behavior. One set of processes are external factors that can affect which system controls behavior in a given situation including task parameters like the kind of information available to the subject, types of training experience, and amount of training. The second set of processes are brain mechanisms that might influence what memory system controls behavior in a given situation including executive functions mediated by the prefrontal cortex; switching mechanisms mediated by ascending neurotransmitter systems, the unique role of the hippocampus during learning. The issue of trait differences in control of different learning and memory systems will also be considered in which trait differences in learning and memory function are thought to potentially emerge from differences in level of prefrontal influence, differences in plasticity processes, differences in ascending neurotransmitter control, differential access to effector systems like motivational and motor systems. Finally, we present scenarios in which different mechanisms might interact. This review was conceived to become a jumping off point for new work directed at understanding these issues. The outcome of this work, in combination with other approaches, might improve understanding of the mechanisms of volition in human and non-human animals. Copyright © 2013 Wiley Periodicals, Inc.

  17. Current Strategies for Brain Drug Delivery

    PubMed Central

    Dong, Xiaowei

    2018-01-01

    The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature. PMID:29556336

  18. Interictal epileptiform discharges have an independent association with cognitive impairment in children with lesional epilepsy.

    PubMed

    Glennon, Jennifer M; Weiss-Croft, Louise; Harrison, Sue; Cross, J Helen; Boyd, Stewart G; Baldeweg, Torsten

    2016-09-01

    The relative contribution of interictal epileptiform discharges (IEDs) to cognitive dysfunction in comparison with the underlying brain pathology is not yet understood in children with lesional focal epilepsy. The current study investigated the association of IEDs with intellectual functioning in 103 children with medication-resistant focal epilepsy. Hierarchical multiple regression analyses were used to determine the independent contribution of IED features on intellectual functioning, after controlling for effects of lesional pathology, epilepsy duration, and medication. Exploratory analyses were conducted for language and memory scores as well as academic skills available in a subset of participants. The results reveal that IEDs have a negative association with IQ with independent, additive effects documented for frequent and bilaterally distributed IEDs as well as discharge enhancement in sleep. Left-lateralized IEDs had a prominent effect on verbal intelligence, in excess of the influence of left-sided brain pathology. These effects extended to other cognitive functions, most prominently for sleep-enhanced IEDs to be associated with deficits in expressive and receptive language, reading, spelling and numerical skills. Overall, IED effects on cognition were of a magnitude similar to lesional influences or drug effects (topiramate use). This study demonstrates an association between IEDs and cognitive dysfunction, independent of the underlying focal brain pathology. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  19. No significant brain volume decreases or increases in adults with high-functioning autism spectrum disorder and above average intelligence: a voxel-based morphometric study.

    PubMed

    Riedel, Andreas; Maier, Simon; Ulbrich, Melanie; Biscaldi, Monica; Ebert, Dieter; Fangmeier, Thomas; Perlov, Evgeniy; Tebartz van Elst, Ludger

    2014-08-30

    Autism spectrum disorder (ASD) is increasingly being recognized as an important issue in adult psychiatry and psychotherapy. High intelligence indicates overall good brain functioning and might thus present a particularly good opportunity to study possible cerebral correlates of core autistic features in terms of impaired social cognition, communication skills, the need for routines, and circumscribed interests. Anatomical MRI data sets for 30 highly intelligent patients with high-functioning autism and 30 pairwise-matched control subjects were acquired and analyzed with voxel-based morphometry. The gray matter volume of the pairwise-matched patients and the controls did not differ significantly. When correcting for total brain volume influences, the patients with ASD exhibited smaller left superior frontal volumes on a trend level. Heterogeneous volumetric findings in earlier studies might partly be explained by study samples biased by a high inclusion rate of secondary forms of ASD, which often go along with neuronal abnormalities. Including only patients with high IQ scores might have decreased the influence of secondary forms of ASD and might explain the absence of significant volumetric differences between the patients and the controls in this study. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson's Disease.

    PubMed

    Caputi, Valentina; Giron, Maria Cecilia

    2018-06-06

    Parkinson’s disease (PD) is a progressively debilitating neurodegenerative disease characterized by α-synucleinopathy, which involves all districts of the brain-gut axis, including the central, autonomic and enteric nervous systems. The highly bidirectional communication between the brain and the gut is markedly influenced by the microbiome through integrated immunological, neuroendocrine and neurological processes. The gut microbiota and its relevant metabolites interact with the host via a series of biochemical and functional inputs, thereby affecting host homeostasis and health. Indeed, a dysregulated microbiota-gut-brain axis in PD might lie at the basis of gastrointestinal dysfunctions which predominantly emerge many years prior to the diagnosis, corroborating the theory that the pathological process is spread from the gut to the brain. Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing conserved motifs primarily found in microorganisms and a dysregulation in their signaling may be implicated in α-synucleinopathy, such as PD. An overstimulation of the innate immune system due to gut dysbiosis and/or small intestinal bacterial overgrowth, together with higher intestinal barrier permeability, may provoke local and systemic inflammation as well as enteric neuroglial activation, ultimately triggering the development of alpha-synuclein pathology. In this review, we provide the current knowledge regarding the relationship between the microbiota-gut⁻brain axis and TLRs in PD. A better understanding of the dialogue sustained by the microbiota-gut-brain axis and innate immunity via TLR signaling should bring interesting insights in the pathophysiology of PD and provide novel dietary and/or therapeutic measures aimed at shaping the gut microbiota composition, improving the intestinal epithelial barrier function and balancing the innate immune response in PD patients, in order to influence the early phases of the following neurodegenerative cascade.

  1. Influence of Inflammation on Poststroke Plasticity

    PubMed Central

    Kossut, Malgorzata

    2013-01-01

    Age-related brain injuries including stroke are a leading cause of morbidity and mental disability worldwide. Most patients who survive stroke experience some degree of recovery. The restoration of lost functions can be explained by neuronal plasticity, understood as brain ability to reorganize and remodel itself in response to changed environmental requirements. However, stroke triggers a cascade of events which may prevent the normal development of the plastic changes. One of them may be inflammatory response initiated immediately after stroke, which has been found to contribute to neuronal injury. Some recent evidence though has suggested that inflammatory reaction can be also neuroprotective. This paper attempts to discuss the influence of poststroke inflammatory response on brain plasticity and stroke outcome. We also describe the recent anti-inflammatory strategies that have been effective for recovery in experimental stroke. PMID:23533818

  2. Protecting Neural Structures and Cognitive Function During Prolonged Space Flight by Targeting the Brain Derived Neurotrophic Factor Molecular Network

    NASA Technical Reports Server (NTRS)

    Schmidt, M. A.; Goodwin, T. J.

    2014-01-01

    Brain derived neurotrophic factor (BDNF) is the main activity-dependent neurotrophin in the human nervous system. BDNF is implicated in production of new neurons from dentate gyrus stem cells (hippocampal neurogenesis), synapse formation, sprouting of new axons, growth of new axons, sprouting of new dendrites, and neuron survival. Alterations in the amount or activity of BDNF can produce significant detrimental changes to cortical function and synaptic transmission in the human brain. This can result in glial and neuronal dysfunction, which may contribute to a range of clinical conditions, spanning a number of learning, behavioral, and neurological disorders. There is an extensive body of work surrounding the BDNF molecular network, including BDNF gene polymorphisms, methylated BDNF gene promoters, multiple gene transcripts, varied BDNF functional proteins, and different BDNF receptors (whose activation differentially drive the neuron to neurogenesis or apoptosis). BDNF is also closely linked to mitochondrial biogenesis through PGC-1alpha, which can influence brain and muscle metabolic efficiency. BDNF AS A HUMAN SPACE FLIGHT COUNTERMEASURE TARGET Earth-based studies reveal that BDNF is negatively impacted by many of the conditions encountered in the space environment, including oxidative stress, radiation, psychological stressors, sleep deprivation, and many others. A growing body of work suggests that the BDNF network is responsive to a range of diet, nutrition, exercise, drug, and other types of influences. This section explores the BDNF network in the context of 1) protecting the brain and nervous system in the space environment, 2) optimizing neurobehavioral performance in space, and 3) reducing the residual effects of space flight on the nervous system on return to Earth

  3. Vertex Stimulation as a Control Site for Transcranial Magnetic Stimulation: A Concurrent TMS/fMRI Study.

    PubMed

    Jung, JeYoung; Bungert, Andreas; Bowtell, Richard; Jackson, Stephen R

    2016-01-01

    A common control condition for transcranial magnetic stimulation (TMS) studies is to apply stimulation at the vertex. An assumption of vertex stimulation is that it has relatively little influence over on-going brain processes involved in most experimental tasks, however there has been little attempt to measure neural changes linked to vertex TMS. Here we directly test this assumption by using a concurrent TMS/fMRI paradigm in which we investigate fMRI blood-oxygenation-level-dependent (BOLD) signal changes across the whole brain linked to vertex stimulation. Thirty-two healthy participants to part in this study. Twenty-one were stimulated at the vertex, at 120% of resting motor threshold (RMT), with short bursts of 1 Hz TMS, while functional magnetic resonance imaging (fMRI) BOLD images were acquired. As a control condition, we delivered TMS pulses over the left primary motor cortex using identical parameters to 11 other participants. Vertex stimulation did not evoke increased BOLD activation at the stimulated site. By contrast we observed widespread BOLD deactivations across the brain, including regions within the default mode network (DMN). To examine the effects of vertex stimulation a functional connectivity analysis was conducted. The results demonstrated that stimulating the vertex with suprathreshold TMS reduced neural activity in brain regions related to the DMN but did not influence the functional connectivity of this network. Our findings provide brain imaging evidence in support of the use of vertex simulation as a control condition in TMS but confirm that vertex TMS induces regional widespread decreases in BOLD activation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Serotonergic Psychedelics Temporarily Modify Information Transfer in Humans

    PubMed Central

    Alonso, Joan Francesc; Romero, Sergio; Mañanas, Miquel Àngel

    2015-01-01

    Background: Psychedelics induce intense modifications in the sensorium, the sense of “self,” and the experience of reality. Despite advances in our understanding of the molecular and cellular level mechanisms of these drugs, knowledge of their actions on global brain dynamics is still incomplete. Recent imaging studies have found changes in functional coupling between frontal and parietal brain structures, suggesting a modification in information flow between brain regions during acute effects. Methods: Here we assessed the psychedelic-induced changes in directionality of information flow during the acute effects of a psychedelic in humans. We measured modifications in connectivity of brain oscillations using transfer entropy, a nonlinear measure of directed functional connectivity based on information theory. Ten healthy male volunteers with prior experience with psychedelics participated in 2 experimental sessions. They received a placebo or a dose of ayahuasca, a psychedelic preparation containing the serotonergic 5-HT2A agonist N,N-dimethyltryptamine. Results: The analysis showed significant changes in the coupling of brain oscillations between anterior and posterior recording sites. Transfer entropy analysis showed that frontal sources decreased their influence over central, parietal, and occipital sites. Conversely, sources in posterior locations increased their influence over signals measured at anterior locations. Exploratory correlations found that anterior-to-posterior transfer entropy decreases were correlated with the intensity of subjective effects, while the imbalance between anterior-to-posterior and posterior-to-anterior transfer entropy correlated with the degree of incapacitation experienced. Conclusions: These results suggest that psychedelics induce a temporary disruption of neural hierarchies by reducing top-down control and increasing bottom-up information transfer in the human brain. PMID:25820842

  5. Prenatal and pubertal testosterone affect brain lateralization.

    PubMed

    Beking, T; Geuze, R H; van Faassen, M; Kema, I P; Kreukels, B P C; Groothuis, T G G

    2018-02-01

    After decades of research, the influence of prenatal testosterone on brain lateralization is still elusive, whereas the influence of pubertal testosterone on functional brain lateralization has not been investigated, although there is increasing evidence that testosterone affects the brain in puberty. We performed a longitudinal study, investigating the relationship between prenatal testosterone concentrations in amniotic fluid, pubertal testosterone concentrations in saliva, and brain lateralization (measured with functional Transcranial Doppler ultrasonography (fTCD)) of the Mental Rotation, Chimeric Faces and Word Generation tasks. Thirty boys and 30 girls participated in this study at the age of 15 years. For boys, we found a significant interaction effect between prenatal and pubertal testosterone on lateralization of Mental Rotation and Chimeric Faces. In the boys with low prenatal testosterone levels, pubertal testosterone was positively related to the strength of lateralization in the right hemisphere, while in the boys with high prenatal testosterone levels, pubertal testosterone was negatively related to the strength of lateralization. For Word Generation, pubertal testosterone was negatively related to the strength of lateralization in the left hemisphere in boys. For girls, we did not find any significant effects, possibly because their pubertal testosterone levels were in many cases below quantification limit. To conclude, prenatal and pubertal testosterone affect lateralization in a task-specific way. Our findings cannot be explained by simple models of prenatal testosterone affecting brain lateralization in a similar way for all tasks. We discuss alternative models involving age dependent effects of testosterone, with a role for androgen receptor distribution and efficiency. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Disrupted Structural and Functional Networks and Their Correlation with Alertness in Right Temporal Lobe Epilepsy: A Graph Theory Study.

    PubMed

    Jiang, Wenyu; Li, Jianping; Chen, Xuemei; Ye, Wei; Zheng, Jinou

    2017-01-01

    Previous studies have shown that temporal lobe epilepsy (TLE) involves abnormal structural or functional connectivity in specific brain areas. However, limited comprehensive studies have been conducted on TLE associated changes in the topological organization of structural and functional networks. Additionally, epilepsy is associated with impairment in alertness, a fundamental component of attention. In this study, structural networks were constructed using diffusion tensor imaging tractography, and functional networks were obtained from resting-state functional MRI temporal series correlations in 20 right temporal lobe epilepsy (rTLE) patients and 19 healthy controls. Global network properties were computed by graph theoretical analysis, and correlations were assessed between global network properties and alertness. The results from these analyses showed that rTLE patients exhibit abnormal small-world attributes in structural and functional networks. Structural networks shifted toward more regular attributes, but functional networks trended toward more random attributes. After controlling for the influence of the disease duration, negative correlations were found between alertness, small-worldness, and the cluster coefficient. However, alertness did not correlate with either the characteristic path length or global efficiency in rTLE patients. Our findings show that disruptions of the topological construction of brain structural and functional networks as well as small-world property bias are associated with deficits in alertness in rTLE patients. These data suggest that reorganization of brain networks develops as a mechanism to compensate for altered structural and functional brain function during disease progression.

  7. The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study.

    PubMed

    Samaras, Katherine; Lutgers, Helen L; Kochan, Nicole A; Crawford, John D; Campbell, Lesley V; Wen, Wei; Slavin, Melissa J; Baune, Bernard T; Lipnicki, Darren M; Brodaty, Henry; Trollor, Julian N; Sachdev, Perminder S

    2014-04-01

    Type 2 diabetes predicts accelerated cognitive decline and brain atrophy. We hypothesized that impaired fasting glucose (IFG) and incident glucose disorders have detrimental effects on global cognition and brain volume. We further hypothesized that metabolic and inflammatory derangements accompanying hyperglycaemia contribute to change in brain structure and function. This was a longitudinal study of a community-dwelling elderly cohort with neuropsychological testing (n = 880) and brain volumes by magnetic resonance imaging (n = 312) measured at baseline and 2 years. Primary outcomes were global cognition and total brain volume. Secondary outcomes were cognitive domains (processing speed, memory, language, visuospatial and executive function) and brain volumes (hippocampal, parahippocampal, precuneus and frontal lobe). Participants were categorised as normal, impaired fasting glucose at both assessments (stable IFG), baseline diabetes or incident glucose disorders (incident diabetes or IFG at 2 years). Measures included inflammatory cytokines and oxidative metabolites. Covariates were age, sex, education, non-English speaking background, smoking, blood pressure, lipid-lowering or antihypertensive medications, mood score, apolipoprotein E genotype and baseline cognition or brain volume. Participants with incident glucose disorders had greater decline in global cognition and visuospatial function compared to normal, similar to that observed in baseline diabetes. Homocysteine was independently associated with the observed effect of diabetes on executive function. Apolipoprotein E genotype did not influence the observed effects of diabetes on cognition. Incident glucose disorders and diabetes were also associated with greater 2-year decline in total brain volume, compared to normal (40.0 ± 4.2 vs. 46.7 ± 5.7 mm(3) vs. 18.1 ± 6.2, respectively, p < 0.005). Stable IFG did not show greater decline in global cognition or brain volumes compared to normal. Incident glucose disorders, like diabetes, are associated with accelerated decline in global cognition and brain volumes in non-demented elderly, whereas stable IFG is not. Preventing deterioration in glucose metabolism in the elderly may help preserve brain structure and function.

  8. Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex.

    PubMed

    Guadalupe, Tulio; Mathias, Samuel R; vanErp, Theo G M; Whelan, Christopher D; Zwiers, Marcel P; Abe, Yoshinari; Abramovic, Lucija; Agartz, Ingrid; Andreassen, Ole A; Arias-Vásquez, Alejandro; Aribisala, Benjamin S; Armstrong, Nicola J; Arolt, Volker; Artiges, Eric; Ayesa-Arriola, Rosa; Baboyan, Vatche G; Banaschewski, Tobias; Barker, Gareth; Bastin, Mark E; Baune, Bernhard T; Blangero, John; Bokde, Arun L W; Boedhoe, Premika S W; Bose, Anushree; Brem, Silvia; Brodaty, Henry; Bromberg, Uli; Brooks, Samantha; Büchel, Christian; Buitelaar, Jan; Calhoun, Vince D; Cannon, Dara M; Cattrell, Anna; Cheng, Yuqi; Conrod, Patricia J; Conzelmann, Annette; Corvin, Aiden; Crespo-Facorro, Benedicto; Crivello, Fabrice; Dannlowski, Udo; de Zubicaray, Greig I; de Zwarte, Sonja M C; Deary, Ian J; Desrivières, Sylvane; Doan, Nhat Trung; Donohoe, Gary; Dørum, Erlend S; Ehrlich, Stefan; Espeseth, Thomas; Fernández, Guillén; Flor, Herta; Fouche, Jean-Paul; Frouin, Vincent; Fukunaga, Masaki; Gallinat, Jürgen; Garavan, Hugh; Gill, Michael; Suarez, Andrea Gonzalez; Gowland, Penny; Grabe, Hans J; Grotegerd, Dominik; Gruber, Oliver; Hagenaars, Saskia; Hashimoto, Ryota; Hauser, Tobias U; Heinz, Andreas; Hibar, Derrek P; Hoekstra, Pieter J; Hoogman, Martine; Howells, Fleur M; Hu, Hao; Hulshoff Pol, Hilleke E; Huyser, Chaim; Ittermann, Bernd; Jahanshad, Neda; Jönsson, Erik G; Jurk, Sarah; Kahn, Rene S; Kelly, Sinead; Kraemer, Bernd; Kugel, Harald; Kwon, Jun Soo; Lemaitre, Herve; Lesch, Klaus-Peter; Lochner, Christine; Luciano, Michelle; Marquand, Andre F; Martin, Nicholas G; Martínez-Zalacaín, Ignacio; Martinot, Jean-Luc; Mataix-Cols, David; Mather, Karen; McDonald, Colm; McMahon, Katie L; Medland, Sarah E; Menchón, José M; Morris, Derek W; Mothersill, Omar; Maniega, Susana Munoz; Mwangi, Benson; Nakamae, Takashi; Nakao, Tomohiro; Narayanaswaamy, Janardhanan C; Nees, Frauke; Nordvik, Jan E; Onnink, A Marten H; Opel, Nils; Ophoff, Roel; Paillère Martinot, Marie-Laure; Papadopoulos Orfanos, Dimitri; Pauli, Paul; Paus, Tomáš; Poustka, Luise; Reddy, Janardhan Yc; Renteria, Miguel E; Roiz-Santiáñez, Roberto; Roos, Annerine; Royle, Natalie A; Sachdev, Perminder; Sánchez-Juan, Pascual; Schmaal, Lianne; Schumann, Gunter; Shumskaya, Elena; Smolka, Michael N; Soares, Jair C; Soriano-Mas, Carles; Stein, Dan J; Strike, Lachlan T; Toro, Roberto; Turner, Jessica A; Tzourio-Mazoyer, Nathalie; Uhlmann, Anne; Hernández, Maria Valdés; van den Heuvel, Odile A; van der Meer, Dennis; van Haren, Neeltje E M; Veltman, Dick J; Venkatasubramanian, Ganesan; Vetter, Nora C; Vuletic, Daniella; Walitza, Susanne; Walter, Henrik; Walton, Esther; Wang, Zhen; Wardlaw, Joanna; Wen, Wei; Westlye, Lars T; Whelan, Robert; Wittfeld, Katharina; Wolfers, Thomas; Wright, Margaret J; Xu, Jian; Xu, Xiufeng; Yun, Je-Yeon; Zhao, JingJing; Franke, Barbara; Thompson, Paul M; Glahn, David C; Mazoyer, Bernard; Fisher, Simon E; Francks, Clyde

    2017-10-01

    The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.

  9. The effects of physical activity on functional MRI activation associated with cognitive control in children: a randomized controlled intervention

    PubMed Central

    Chaddock-Heyman, Laura; Erickson, Kirk I.; Voss, Michelle W.; Knecht, Anya M.; Pontifex, Matthew B.; Castelli, Darla M.; Hillman, Charles H.; Kramer, Arthur F.

    2013-01-01

    This study used functional magnetic resonance imaging (fMRI) to examine the influence of a 9-month physical activity program on task-evoked brain activation during childhood. The results demonstrated that 8- to 9-year-old children who participated in 60+ min of physical activity, 5 days per week, for 9 months, showed decreases in fMRI brain activation in the right anterior prefrontal cortex coupled with within-group improvements in performance on a task of attentional and interference control. Children assigned to a wait-list control group did not show changes in brain function. Furthermore, at post-test, children in the physical activity group showed similar anterior frontal brain patterns and incongruent accuracy rates to a group of college-aged young adults. Children in the wait-list control group still differed from the young adults in terms of anterior prefrontal activation and performance at post-test. There were no significant changes in fMRI activation in the anterior cingulate cortex (ACC) for either group. These results suggest that physical activity during childhood may enhance specific elements of prefrontal cortex function involved in cognitive control. PMID:23487583

  10. Amino Acids That Centrally Influence Blood Pressure and Regional Blood Flow in Conscious Rats

    PubMed Central

    Takemoto, Yumi

    2012-01-01

    Functional roles of amino acids have increasingly become the focus of research. This paper summarizes amino acids that influence cardiovascular system via the brain of conscious rats. This paper firstly describes why amino acids are selected and outlines how the brain regulates blood pressure and regional blood flow. This section includes a concise history of amino acid neurotransmitters in cardiovascular research and summarizes brain areas where chemical stimulations produce blood pressure changes mainly in anesthetized animals. This is followed by comments about findings regarding several newly examined amino acids with intracisternal stimulation in conscious rats that produce changes in blood pressure. The same pressor or depressor response to central amino acid stimulations can be produced by distinct mechanisms at central and peripheral levels, which will be briefly explained. Thereafter, cardiovascular actions of some of amino acids at the mechanism level will be discussed based upon findings of pharmacological and regional blood flow measurements. Several examined amino acids in addition to the established neurotransmitter amino acids appear to differentially activate brain structures to produce changes in blood pressure and regional blood flows. They may have physiological roles in the healthy brain, but pathological roles in the brain with cerebral vascular diseases such as stroke where the blood-brain barrier is broken. PMID:22690328

  11. Loss of T cells influences sex differences in behavior and brain structure.

    PubMed

    Rilett, Kelly C; Friedel, Miriam; Ellegood, Jacob; MacKenzie, Robyn N; Lerch, Jason P; Foster, Jane A

    2015-05-01

    Clinical and animal studies demonstrate that immune-brain communication influences behavior and brain function. Mice lacking T cell receptor β and δ chains were tested in the elevated plus maze, open field, and light-dark test and showed reduced anxiety-like behavior compared to wild type. Interestingly sex differences were observed in the behavioural phenotype of TCRβ-/-δ- mice. Specifically, female TCRβ-/-δ- mice spent more time in the light chamber compared to wild type females, whereas male TCRβ-/-δ- spent more time in the center of the open field compared to wild type males. In addition, TCRβ-/-δ- mice did not show sex differences in activity-related behaviors observed in WT mice. Ex vivo brain imaging (7 Tesla MRI) revealed volume changes in hippocampus, hypothalamus, amygdala, periaqueductal gray, and dorsal raphe and other brain regions between wild type and T cell receptor knockout mice. There was also a loss of sexual dimorphism in brain volume in the bed nucleus of the stria terminalis, normally the most sexually dimorphic region in the brain, in immune compromised mice. These data demonstrate the presence of T cells is important in the development of sex differences in CNS circuitry and behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Preserved local but disrupted contextual figure-ground influences in an individual with abnormal function of intermediate visual areas

    PubMed Central

    Brooks, Joseph L.; Gilaie-Dotan, Sharon; Rees, Geraint; Bentin, Shlomo; Driver, Jon

    2012-01-01

    Visual perception depends not only on local stimulus features but also on their relationship to the surrounding stimulus context, as evident in both local and contextual influences on figure-ground segmentation. Intermediate visual areas may play a role in such contextual influences, as we tested here by examining LG, a rare case of developmental visual agnosia. LG has no evident abnormality of brain structure and functional neuroimaging showed relatively normal V1 function, but his intermediate visual areas (V2/V3) function abnormally. We found that contextual influences on figure-ground organization were selectively disrupted in LG, while local sources of figure-ground influences were preserved. Effects of object knowledge and familiarity on figure-ground organization were also significantly diminished. Our results suggest that the mechanisms mediating contextual and familiarity influences on figure-ground organization are dissociable from those mediating local influences on figure-ground assignment. The disruption of contextual processing in intermediate visual areas may play a role in the substantial object recognition difficulties experienced by LG. PMID:22947116

  13. The effects of cholesterol on learning and memory.

    PubMed

    Schreurs, Bernard G

    2010-07-01

    Cholesterol is vital to normal brain function including learning and memory but that involvement is as complex as the synthesis, metabolism and excretion of cholesterol itself. Dietary cholesterol influences learning tasks from water maze to fear conditioning even though cholesterol does not cross the blood brain barrier. Excess cholesterol has many consequences including peripheral pathology that can signal brain via cholesterol metabolites, pro-inflammatory mediators and antioxidant processes. Manipulations of cholesterol within the central nervous system through genetic, pharmacological, or metabolic means circumvent the blood brain barrier and affect learning and memory but often in animals already otherwise compromised. The human literature is no less complex. Cholesterol reduction using statins improves memory in some cases but not others. There is also controversy over statin use to alleviate memory problems in Alzheimer's disease. Correlations of cholesterol and cognitive function are mixed and association studies find some genetic polymorphisms are related to cognitive function but others are not. In sum, the field is in flux with a number of seemingly contradictory results and many complexities. Nevertheless, understanding cholesterol effects on learning and memory is too important to ignore.

  14. Probiotics drive gut microbiome triggering emotional brain signatures.

    PubMed

    Bagga, Deepika; Reichert, Johanna Louise; Koschutnig, Karl; Aigner, Christoph Stefan; Holzer, Peter; Koskinen, Kaisa; Eichinger, Christine Moissl; Schöpf, Veronika

    2018-05-03

    Experimental manipulation of the gut microbiome was found to modify emotional and cognitive behavior, neurotransmitter expression and brain function in rodents, but corresponding human data remain scarce. The present double-blind, placebo-controlled randomised study aimed at investigating the effects of 4 weeks' probiotic administration on behavior, brain function and gut microbial composition in healthy volunteers. Forty-five healthy participants divided equally into three groups (probiotic, placebo and no intervention) underwent functional MRI (emotional decision-making and emotional recognition memory tasks). In addition, stool samples were collected to investigate the gut microbial composition. Probiotic administration for 4 weeks was associated with changes in brain activation patterns in response to emotional memory and emotional decision-making tasks, which were also accompanied by subtle shifts in gut microbiome profile. Microbiome composition mirrored self-reported behavioral measures and memory performance. This is the first study reporting a distinct influence of probiotic administration at behavioral, neural, and microbiome levels at the same time in healthy volunteers. The findings provide a basis for future investigations into the role of the gut microbiota and potential therapeutic application of probiotics.

  15. Usual and virtual reality video game-based physiotherapy for children and youth with acquired brain injuries.

    PubMed

    Levac, Danielle; Miller, Patricia; Missiuna, Cheryl

    2012-05-01

    Little is known about how therapists promote learning of functional motor skills for children with acquired brain injuries. This study explores physiotherapists' description of these interventions in comparison to virtual reality (VR) video game-based therapy. Six physiotherapists employed at a children's rehabilitation center participated in semi-structured interviews, which were transcribed and analyzed using thematic analysis. Physiotherapists describe using interventions that motivate children to challenge performance quality and optimize real-life functioning. Intervention strategies are influenced by characteristics of the child, parent availability to practice skills outside therapy, and therapist experience. VR use motivates children to participate, but can influence therapist use of verbal strategies and complicate interventions. Physiotherapists consider unique characteristics of this population when providing interventions that promote learning of motor skills. The VR technology has advantageous features but its use with this population can be challenging; further research is recommended.

  16. SIRT1/PGC-1α Signaling Promotes Mitochondrial Functional Recovery and Reduces Apoptosis after Intracerebral Hemorrhage in Rats

    PubMed Central

    Zhou, Yang; Wang, Shaohua; Li, Yixin; Yu, Shanshan; Zhao, Yong

    2018-01-01

    Silent information regulator 1 (SIRT1) exerts neuroprotection in many neurodegenerative diseases. However, it is not clear if SIRT1 has protective effects after intracerebral hemorrhage (ICH)-induced brain injury in rats. Thus, our goal was to examine the influence of SIRT1 on ICH injuries and any underlying mechanisms of this influence. Brain injury was induced by autologous arterial blood (60 μL) injection into rat brains, and data show that activation of SIRT1 with SRT1720 (5 mg/kg) restored nuclear SIRT1, deacetylation of PGC-1α, and mitochondrial biogenesis and decreased mortality, behavioral deficits, and brain water content without significant changes in phosphorylated AMP-activated protein kinase (pAMPK) induced by ICH. Activation of SIRT1 with SRT1720 also restored mitochondrial electron transport chain proteins and decreased apoptotic proteins in ICH; however, these changes were reversed after ICH. In contrast, treatment with PGC-1α siRNA yielded opposite effects. To explore the protective effects of SIRT1 after ICH, siRNAs were used to knockdown SIRT1. Treatment with SIRT1 siRNA increased mortality, behavioral deficits, brain water content, mitochondrial dysfunction, and neurocyte apoptosis after ICH. Thus, activation of SIRT1 promotes recovery of mitochondrial protein and function by increasing mitochondrial biogenesis and reduces apoptosis after ICH via the PGC-1α mitochondrial pathway. These data may suggest a new therapeutic approach for ICH injuries. PMID:29375306

  17. [On factors that effect the variability of central mechanisms of bilingualism].

    PubMed

    Kruchinina, O V; Gal'perina, E I; Kats, E É; Shepoval'nikov, A N

    2012-01-01

    The article discusses the probable role of many factors that determine the individual variety of neurophysiological mechanisms, which provide the opportunity to learn and free use two or more languages. The formation of a speech functions is affected by both the general factors for bilinguals and monolinguals, as well as the specific characteristic of the situation of bilingualism. The general factors include genetic and environmental impact of explaining the diversity of individual options for the development of morphofunctional organization of speech functions. A bilinguals, obviously, have even more wide variance of the central maintenance of speech activity, due to the combination of different conditions that influence the language environment, which include the age of the second language acquisition, the language proficiency, linguistic closeness of the languages, the method of their acquisition, intensity of use and the scope of application of each of the languages. The influence of these factors can mediates in different ways by the individual characteristics of the bilingual's brain. Being exposed to two languages from the first days of life, the child uses for the development of speech skills of the unique features of the brain, which are available only in the initial stages of postnatal ontogenesis. In older age mastering a second language requires much more effort, when, as maturation, the brain acquires new additional possibilities, but permanently lose that special "bonus", which nature gives a small child only in the first months of life. Large individual variability patterns of activation of the cortex when verbal activity in late bilingual" compared with the "early", allows to assume, that the brain of "late bilingual", mastering a new language, forced to operate a large number of backup mechanisms, and this is reflected in the increase of variation in the cerebral processes, responsible for providing of speech functions. In addition, there is serious reason to believe that learning a second language contributes to the expansion of the functional capabilities of the brain and creates the basis for a successful cognitive activity.

  18. When brain neuroscience meets hydrology: timeseries analysis methods for capturing structural and functional aspects of hydrologic connectivity

    NASA Astrophysics Data System (ADS)

    Ali, G.; Rinderer, M.

    2016-12-01

    In hydrology, several connectivity definitions exist that hinder intercomparison between different studies. Yet, consensus exists on the distinction between structural connectivity (i.e., physical adjacency of landscape elements that is thought to influence material transfer) and functional or effective connectivity (i.e., interaction or causality between spatial adjacency characteristics and temporally varying factors, leading to the connected flow of material). While hydrologists have succeeded in deriving measures of structural connectivity (SC), the quantification of functional (FC) or effective connectivity (EC) is elusive. Here we borrowed timeseries analysis methods from brain neuroscience to quantify EC and FC among groundwater (n = 34) and stream discharge (n = 1) monitoring sites in a 20-ha Swiss catchment where topography is assumed to be a major driver of connectivity. Influence maps created from elevation data were used to assess SC. FC was assessed by cross-correlation, total and partial mutual information and EC quantified via total and partial entropy, Granger causality and a phase slope index. Results show that generally, a fair percentage of structural connections were also expressed as functional or effective connections. Some FC and EC measures had clear advantages over others, for instance in terms of making a distinction between Darcian fluxes of water and pressure wave-driven processes. False-positive estimations, i.e., the detection of FC and EC despite the absence of SC, were also encountered and used to invalidate the applicability of some brain-connectivity measures in a hydrological context. While our goal was not to identify the best measure of FC or EC, our study showed that the application of brain neuroscience methods for assessing FC and EC in hydrology was possible as long as SC measures were used as constraints for (or prior beliefs about) the establishment of FC and EC.

  19. INTERDISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Influence of Blurred Ways on Pattern Recognition of a Scale-Free Hopfield Neural Network

    NASA Astrophysics Data System (ADS)

    Chang, Wen-Li

    2010-01-01

    We investigate the influence of blurred ways on pattern recognition of a Barabási-Albert scale-free Hopfield neural network (SFHN) with a small amount of errors. Pattern recognition is an important function of information processing in brain. Due to heterogeneous degree of scale-free network, different blurred ways have different influences on pattern recognition with same errors. Simulation shows that among partial recognition, the larger loading ratio (the number of patterns to average degree P/langlekrangle) is, the smaller the overlap of SFHN is. The influence of directed (large) way is largest and the directed (small) way is smallest while random way is intermediate between them. Under the ratio of the numbers of stored patterns to the size of the network P/N is less than 0. 1 conditions, there are three families curves of the overlap corresponding to directed (small), random and directed (large) blurred ways of patterns and these curves are not associated with the size of network and the number of patterns. This phenomenon only occurs in the SFHN. These conclusions are benefit for understanding the relation between neural network structure and brain function.

  20. Effects of HIV and childhood trauma on brain morphometry and neurocognitive function.

    PubMed

    Spies, Georgina; Ahmed-Leitao, Fatima; Fennema-Notestine, Christine; Cherner, Mariana; Seedat, Soraya

    2016-04-01

    A wide spectrum of neurocognitive deficits characterises HIV infection in adults. HIV infection is additionally associated with morphological brain abnormalities affecting neural substrates that subserve neurocognitive function. Early life stress (ELS) also has a direct influence on brain morphology. However, the combined impact of ELS and HIV on brain structure and neurocognitive function has not been examined in an all-female sample with advanced HIV disease. The present study examined the effects of HIV and childhood trauma on brain morphometry and neurocognitive function. Structural data were acquired using a 3T Magnetom MRI scanner, and a battery of neurocognitive tests was administered to 124 women: HIV-positive with ELS (n = 32), HIV-positive without ELS (n = 30), HIV-negative with ELS (n = 31) and HIV-negative without ELS (n = 31). Results revealed significant group volumetric differences for right anterior cingulate cortex (ACC), bilateral hippocampi, corpus callosum, left and right caudate and left and right putamen. Mean regional volumes were lowest in HIV-positive women with ELS compared to all other groups. Although causality cannot be inferred, findings also suggest that alterations in the left frontal lobe, right ACC, left hippocampus, corpus callosum, left and right amygdala and left caudate may be associated with poorer neurocognitive performance in the domains of processing speed, attention/working memory, abstraction/executive functions, motor skills, learning and language/fluency with these effects more pronounced in women living with both HIV and childhood trauma. This study highlights the potential contributory role of childhood trauma to brain alterations and neurocognitive decline in HIV-infected individuals.

  1. Inverse association between BMI and prefrontal metabolic activity in healthy adults.

    PubMed

    Volkow, Nora D; Wang, Gene-Jack; Telang, Frank; Fowler, Joanna S; Goldstein, Rita Z; Alia-Klein, Nelly; Logan, Jean; Wong, Christopher; Thanos, Panayotis K; Ma, Yemine; Pradhan, Kith

    2009-01-01

    Obesity has been associated with a higher risk for impaired cognitive function, which most likely reflects associated medical complications (i.e., cerebrovascular pathology). However, there is also evidence that in healthy individuals excess weight may adversely affect cognition (executive function, attention, and memory). Here, we measured regional brain glucose metabolism (using positron emission tomography (PET) and 2-deoxy-2[(18)F]fluoro-D-glucose (FDG)) to assess the relationship between BMI and brain metabolism (marker of brain function) in 21 healthy controls (BMI range 19-37 kg/m(2)) studied during baseline (no stimulation) and during cognitive stimulation (numerical calculations). Statistical parametric mapping (SPM) revealed a significant negative correlation between BMI and metabolic activity in prefrontal cortex (Brodmann areas 8, 9, 10, 11, 44) and cingulate gyrus (Brodmann area 32) but not in other regions. Moreover, baseline metabolism in these prefrontal regions was positively associated with performance on tests of memory (California Verbal Learning Test) and executive function (Stroop Interference and Symbol Digit Modality tests). In contrast, the regional brain changes during cognitive stimulation were not associated with BMI nor with neuropsychological performance. The observed association between higher BMI and lower baseline prefrontal metabolism may underlie the impaired performance reported in healthy obese individuals on some cognitive tests of executive function. On the other hand, the lack of an association between BMI and brain metabolic activation during cognitive stimulation indicates that BMI does not influence brain glucose utilization during cognitive performance. These results further highlight the urgency to institute public health interventions to prevent obesity.

  2. Brain functional connectivity network studies of acupuncture: a systematic review on resting-state fMRI.

    PubMed

    Cai, Rong-Lin; Shen, Guo-Ming; Wang, Hao; Guan, Yuan-Yuan

    2018-01-01

    Functional magnetic resonance imaging (fMRI) is a novel method for studying the changes of brain networks due to acupuncture treatment. In recent years, more and more studies have focused on the brain functional connectivity network of acupuncture stimulation. To offer an overview of the different influences of acupuncture on the brain functional connectivity network from studies using resting-state fMRI. The authors performed a systematic search according to PRISMA guidelines. The database PubMed was searched from January 1, 2006 to December 31, 2016 with restriction to human studies in English language. Electronic searches were conducted in PubMed using the keywords "acupuncture" and "neuroimaging" or "resting-state fMRI" or "functional connectivity". Selection of included articles, data extraction and methodological quality assessments were respectively conducted by two review authors. Forty-four resting-state fMRI studies were included in this systematic review according to inclusion criteria. Thirteen studies applied manual acupuncture vs. sham, four studies applied electro-acupuncture vs. sham, two studies also compared transcutaneous electrical acupoint stimulation vs. sham, and nine applied sham acupoint as control. Nineteen studies with a total number of 574 healthy subjects selected to perform fMRI only considered healthy adult volunteers. The brain functional connectivity of the patients had varying degrees of change. Compared with sham acupuncture, verum acupuncture could increase default mode network and sensorimotor network connectivity with pain-, affective- and memory-related brain areas. It has significantly greater connectivity of genuine acupuncture between the periaqueductal gray, anterior cingulate cortex, left posterior cingulate cortex, right anterior insula, limbic/paralimbic and precuneus compared with sham acupuncture. Some research had also shown that acupuncture could adjust the limbic-paralimbic-neocortical network, brainstem, cerebellum, subcortical and hippocampus brain areas. It can be presumed that the functional connectivity network is closely related to the mechanism of acupuncture, and central integration plays a critical role in the acupuncture mechanism. Copyright © 2017 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

  3. Nutritional strategies to optimise cognitive function in the aging brain.

    PubMed

    Wahl, Devin; Cogger, Victoria C; Solon-Biet, Samantha M; Waern, Rosilene V R; Gokarn, Rahul; Pulpitel, Tamara; Cabo, Rafael de; Mattson, Mark P; Raubenheimer, David; Simpson, Stephen J; Le Couteur, David G

    2016-11-01

    Old age is the greatest risk factor for most neurodegenerative diseases. During recent decades there have been major advances in understanding the biology of aging, and the development of nutritional interventions that delay aging including calorie restriction (CR) and intermittent fasting (IF), and chemicals that influence pathways linking nutrition and aging processes. CR influences brain aging in many animal models and recent findings suggest that dietary interventions can influence brain health and dementia in older humans. The role of individual macronutrients in brain aging also has been studied, with conflicting results about the effects of dietary protein and carbohydrates. A new approach known as the Geometric Framework (GF) has been used to unravel the complex interactions between macronutrients (protein, fat, and carbohydrate) and total energy on outcomes such as aging. These studies have shown that low-protein, high-carbohydrate (LPHC) diets are optimal for lifespan in ad libitum fed animals, while total calories have minimal effect once macronutrients are taken into account. One of the primary purposes of this review is to explore the notion that macronutrients may have a more translational potential than CR and IF in humans, and therefore there is a pressing need to use GF to study the impact of diet on brain aging. Furthermore, given the growing recognition of the role of aging biology in dementia, such studies might provide a new approach for dietary interventions for optimizing brain health and preventing dementia in older people. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. The hidden side of drug action: Brain temperature changes induced by neuroactive drugs

    PubMed Central

    Kiyatkin, Eugene A.

    2013-01-01

    Rationale Most neuroactive drugs affect brain metabolism as well as systemic and cerebral blood flow, thus altering brain temperature. Although this aspect of drug action usually remains in the shadows, drug-induced alterations in brain temperature reflect their metabolic neural effects and affect neural activity and neural functions. Objectives Here, I review brain temperature changes induced by neuroactive drugs, which are used therapeutically (general anesthetics), as a research tool (dopamine agonists and antagonists), and self-administered to induce desired psychic effects (cocaine, methamphetamine, ecstasy). I consider the mechanisms underlying these temperature fluctuations and their influence on neural, physiological, and behavioral effects of these drugs. Results By interacting with neural mechanisms regulating metabolic activity and heat exchange between the brain and the rest of the body, neuroactive drugs either increase or decrease brain temperatures both within (35-39°C) and exceeding the range of physiological fluctuations. These temperature effects differ drastically depending upon the environmental conditions and activity state during drug administration. This state-dependence is especially important for drugs of abuse that are usually taken by humans during psycho-physiological activation and in environments that prevent proper heat dissipation from the brain. Under these conditions, amphetamine-like stimulants induce pathological brain hyperthermia (>40°C) associated with leakage of the blood-brain barrier and structural abnormalities of brain cells. Conclusions The knowledge on brain temperature fluctuations induced by neuroactive drugs provides new information to understand how they influence metabolic neural activity, why their effects depend upon the behavioral context of administration, and the mechanisms underlying adverse drug effects including neurotoxicity PMID:23274506

  5. Source-based neurofeedback methods using EEG recordings: training altered brain activity in a functional brain source derived from blind source separation

    PubMed Central

    White, David J.; Congedo, Marco; Ciorciari, Joseph

    2014-01-01

    A developing literature explores the use of neurofeedback in the treatment of a range of clinical conditions, particularly ADHD and epilepsy, whilst neurofeedback also provides an experimental tool for studying the functional significance of endogenous brain activity. A critical component of any neurofeedback method is the underlying physiological signal which forms the basis for the feedback. While the past decade has seen the emergence of fMRI-based protocols training spatially confined BOLD activity, traditional neurofeedback has utilized a small number of electrode sites on the scalp. As scalp EEG at a given electrode site reflects a linear mixture of activity from multiple brain sources and artifacts, efforts to successfully acquire some level of control over the signal may be confounded by these extraneous sources. Further, in the event of successful training, these traditional neurofeedback methods are likely influencing multiple brain regions and processes. The present work describes the use of source-based signal processing methods in EEG neurofeedback. The feasibility and potential utility of such methods were explored in an experiment training increased theta oscillatory activity in a source derived from Blind Source Separation (BSS) of EEG data obtained during completion of a complex cognitive task (spatial navigation). Learned increases in theta activity were observed in two of the four participants to complete 20 sessions of neurofeedback targeting this individually defined functional brain source. Source-based EEG neurofeedback methods using BSS may offer important advantages over traditional neurofeedback, by targeting the desired physiological signal in a more functionally and spatially specific manner. Having provided preliminary evidence of the feasibility of these methods, future work may study a range of clinically and experimentally relevant brain processes where individual brain sources may be targeted by source-based EEG neurofeedback. PMID:25374520

  6. Endothelial LRP1 - A Potential Target for the Treatment of Alzheimer's Disease : Theme: Drug Discovery, Development and Delivery in Alzheimer's Disease Guest Editor: Davide Brambilla.

    PubMed

    Storck, Steffen E; Pietrzik, Claus U

    2017-12-01

    The accumulation of the neurotoxin beta-amyloid (Aβ) is a major hallmark in Alzheimer's disease (AD). Aβ homeostasis in the brain is governed by its production and various clearance mechanisms. Both pathways are influenced by the ubiquitously expressed low-density lipoprotein receptor-related protein 1 (LRP1). In cerebral blood vessels, LRP1 is an important mediator for the rapid removal of Aβ from brain via transport across the blood-brain barrier (BBB). Here, we summarize recent findings on LRP1 function and discuss the targeting of LRP1 as a modulator for AD pathology and drug delivery into the brain.

  7. Are rapid changes in brain elasticity possible?

    NASA Astrophysics Data System (ADS)

    Parker, K. J.

    2017-09-01

    Elastography of the brain is a topic of clinical and preclinical research, motivated by the potential for viscoelastic measures of the brain to provide sensitive indicators of pathological processes, and to assist in early diagnosis. To date, studies of the normal brain and of those with confirmed neurological disorders have reported a wide range of shear stiffness and shear wave speeds, even within similar categories. A range of factors including the shear wave frequency, and the age of the individual are thought to have a possible influence. However, it may be that short term dynamics within the brain may have an influence on the measured stiffness. This hypothesis is addressed quantitatively using the framework of the microchannel flow model, which derives the tissue stiffness, complex modulus, and shear wave speed as a function of the vascular and fluid network in combination with the elastic matrix that comprise the brain. Transformation rules are applied so that any changes in the fluid channels or the elastic matrix can be mapped to changes in observed elastic properties on a macroscopic scale. The results are preliminary but demonstrate that measureable, time varying changes in brain stiffness are possible simply by accounting for vasodynamic or electrochemical changes in the state of any region of the brain. The value of this preliminary exploration is to identify possible mechanisms and order-of-magnitude changes that may be testable in vivo by specialized protocols.

  8. 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.

  9. Sleep spindles and cognitive performance across adolescence: A meta-analytic review.

    PubMed

    Reynolds, C M; Short, M A; Gradisar, M

    2018-07-01

    Higher sleep spindle activity generally relates to better cognitive performance in adults, while studies in children often show the opposite. As children become young adults, there is rapid brain maturation and development of higher-order cognitive functions, and therefore investigations within this age group may elucidate the relationship between spindles and cognition in this developmental period. Twelve studies published between 2009 and 2016 were identified. Meta-analyses revealed a positive relationship between spindles and cognition overall (r = 0.27), however effects varied depending on cognitive domain. Moderate positive relationships were seen for fluid IQ (r = 0.44), working memory/executive function (r = 0.40) and speed/accuracy (r = 0.33), while full IQ/verbal IQ was not significantly associated (r = -0.05). Meta-regressions indicated cognitive domain and spindle characteristic had a small influence over effect sizes, while age and gender did not have a significant influence. The relationship between spindles and cognition in adolescents is likely influenced by individual neural makeup and brain maturation. Copyright © 2018 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  10. When Neuroscience 'Touches' Architecture: From Hapticity to a Supramodal Functioning of the Human Brain.

    PubMed

    Papale, Paolo; Chiesi, Leonardo; Rampinini, Alessandra C; Pietrini, Pietro; Ricciardi, Emiliano

    2016-01-01

    In the last decades, the rapid growth of functional brain imaging methodologies allowed cognitive neuroscience to address open questions in philosophy and social sciences. At the same time, novel insights from cognitive neuroscience research have begun to influence various disciplines, leading to a turn to cognition and emotion in the fields of planning and architectural design. Since 2003, the Academy of Neuroscience for Architecture has been supporting 'neuro-architecture' as a way to connect neuroscience and the study of behavioral responses to the built environment. Among the many topics related to multisensory perceptual integration and embodiment, the concept of hapticity was recently introduced, suggesting a pivotal role of tactile perception and haptic imagery in architectural appraisal. Arguments have thus risen in favor of the existence of shared cognitive foundations between hapticity and the supramodal functional architecture of the human brain. Precisely, supramodality refers to the functional feature of defined brain regions to process and represent specific information content in a more abstract way, independently of the sensory modality conveying such information to the brain. Here, we highlight some commonalities and differences between the concepts of hapticity and supramodality according to the distinctive perspectives of architecture and cognitive neuroscience. This comparison and connection between these two different approaches may lead to novel observations in regard to people-environment relationships, and even provide empirical foundations for a renewed evidence-based design theory.

  11. The psyche and gastric functions.

    PubMed

    Nardone, Gerardo; Compare, Debora

    2014-01-01

    Although the idea that gastric problems are in some way related to mental activity dates back to the beginning of the last century, until now it has received scant attention by physiologists, general practitioners and gastroenterologists. The major breakthrough in understanding the interactions between the central nervous system and the gut was the discovery of the enteric nervous system (ENS) in the 19th century. ENS (also called 'little brain') plays a crucial role in the regulation of the physiological gut functions. Furthermore, the identification of corticotropin-releasing factor (CRF) and the development of specific CRF receptor antagonists have permitted to characterize the neurochemical basis of the stress response. The neurobiological response to stress in mammals involves three key mechanisms: (1) stress is perceived and processed by higher brain centers; (2) the brain mounts a neuroendocrine response by way of the hypothalamic-pituitary-adrenal axis (HPA) and the autonomic nervous system (ANS), and (3) the brain triggers feedback mechanisms by HPA and ANS stimulation to restore homeostasis. Various stressors such as anger, fear, painful stimuli, as well as life or social learning experiences affect both the individual's physiologic and gastric function, revealing a two-way interaction between brain and stomach. There is overwhelming experimental and clinical evidence that stress influences gastric function, thereby outlining the pathogenesis of gastric diseases such as functional dyspepsia, gastroesophageal reflux disease and peptic ulcer disease. A better understanding of the role of pathological stressors in the modulation of disease activity may have important pathogenetic and therapeutic implications. © 2014 S. Karger AG, Basel.

  12. Perinatal programming of emotional brain circuits: an integrative view from systems to molecules

    PubMed Central

    Bock, Jörg; Rether, Kathy; Gröger, Nicole; Xie, Lan; Braun, Katharina

    2014-01-01

    Environmental influences such as perinatal stress have been shown to program the developing organism to adapt brain and behavioral functions to cope with daily life challenges. Evidence is now accumulating that the specific and individual effects of early life adversity on the functional development of brain and behavior emerge as a function of the type, intensity, timing and the duration of the adverse environment, and that early life stress (ELS) is a major risk factor for developing behavioral dysfunctions and mental disorders. Results from clinical as well as experimental studies in animal models support the hypothesis that ELS can induce functional “scars” in prefrontal and limbic brain areas, regions that are essential for emotional control, learning and memory functions. On the other hand, the concept of “stress inoculation” is emerging from more recent research, which revealed positive functional adaptations in response to ELS resulting in resilience against stress and other adversities later in life. Moreover, recent studies indicate that early life experiences and the resulting behavioral consequences can be transmitted to the next generation, leading to a transgenerational cycle of adverse or positive adaptations of brain function and behavior. In this review we propose a unifying view of stress vulnerability and resilience by connecting genetic predisposition and programming sensitivity to the context of experience-expectancy and transgenerational epigenetic traits. The adaptive maturation of stress responsive neural and endocrine systems requires environmental challenges to optimize their functions. Repeated environmental challenges can be viewed within the framework of the match/mismatch hypothesis, the outcome, psychopathology or resilience, depends on the respective predisposition and on the context later in life. PMID:24550772

  13. The neurogenetic frontier--lessons from misbehaving zebrafish.

    PubMed

    Burgess, Harold A; Granato, Michael

    2008-11-01

    One of the central questions in neuroscience is how refined patterns of connectivity in the brain generate and monitor behavior. Genetic mutations can influence neural circuits by disrupting differentiation or maintenance of component neuronal cells or by altering functional patterns of nervous system connectivity. Mutagenesis screens therefore have the potential to reveal not only the molecular underpinnings of brain development and function, but to illuminate the cellular basis of behavior. Practical considerations make the zebrafish an organism of choice for undertaking forward genetic analysis of behavior. The powerful array of experimental tools at the disposal of the zebrafish researcher makes it possible to link molecular function to neuronal properties that underlie behavior. This review focuses on specific challenges to isolating and analyzing behavioral mutants in zebrafish.

  14. The neurogenetic frontier—lessons from misbehaving zebrafish

    PubMed Central

    Granato, Michael

    2008-01-01

    One of the central questions in neuroscience is how refined patterns of connectivity in the brain generate and monitor behavior. Genetic mutations can influence neural circuits by disrupting differentiation or maintenance of component neuronal cells or by altering functional patterns of nervous system connectivity. Mutagenesis screens therefore have the potential to reveal not only the molecular underpinnings of brain development and function, but to illuminate the cellular basis of behavior. Practical considerations make the zebrafish an organism of choice for undertaking forward genetic analysis of behavior. The powerful array of experimental tools at the disposal of the zebrafish researcher makes it possible to link molecular function to neuronal properties that underlie behavior. This review focuses on specific challenges to isolating and analyzing behavioral mutants in zebrafish. PMID:18836206

  15. Alterations of functional connectivities from early to middle adulthood: Clues from multivariate pattern analysis of resting-state fMRI data.

    PubMed

    Tian, Lixia; Ma, Lin; Wang, Linlin

    2016-04-01

    In contrast to extended research interests in the maturation and aging of human brain, alterations of brain structure and function from early to middle adulthood have been much less studied. The aim of the present study was to investigate the extent and pattern of the alterations of functional interactions between brain regions from early to middle adulthood. We carried out the study by multivariate pattern analysis of resting-state fMRI (RS-fMRI) data of 63 adults aged 18 to 45 years. Specifically, using elastic net, we performed brain age estimation and age-group classification (young adults aged 18-28 years vs. middle-aged adults aged 35-45 years) based on the resting-state functional connectivities (RSFCs) between 160 regions of interest (ROIs) evaluated on the RS-fMRI data of each subject. The results indicate that the estimated brain ages were significantly correlated with the chronological age (R=0.78, MAE=4.81), and a classification rate of 94.44% and area under the receiver operating characteristic curve (AUC) of 0.99 were obtained when classifying the young and middle-aged adults. These results provide strong evidence that functional interactions between brain regions undergo notable alterations from early to middle adulthood. By analyzing the RSFCs that contribute to brain age estimation/age-group classification, we found that a majority of the RSFCs were inter-network, and we speculate that inter-network RSFCs might mature late but age early as compared to intra-network ones. In addition, the strengthening/weakening of the RSFCs associated with the left/right hemispheric ROIs, the weakening of cortico-cerebellar RSFCs and the strengthening of the RSFCs between the default mode network and other networks contributed much to both brain age estimation and age-group classification. All these alterations might reflect that aging of brain function is already in progress in middle adulthood. Overall, the present study indicated that the RSFCs undergo notable alterations from early to middle adulthood and highlighted the necessity of careful considerations of possible influences of these alterations in related studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. MicroRNAs in neuronal function and dysfunction

    PubMed Central

    Im, Heh-In; Kenny, Paul J.

    2012-01-01

    MicroRNAs (miRNAs) are small noncoding RNA transcripts expressed throughout the brain that can regulate neuronal gene expression at the post-transcriptional level. Here, we provide an overview of the role for miRNAs in brain development and function, and review evidence suggesting that dysfunction in miRNA signaling contributes to neurodevelopment disorders such as Rett and fragile X syndromes, as well as complex behavioral disorders including schizophrenia, depression and drug addiction. A better understanding of how miRNAs influence the development of neuropsychiatric disorders may reveal fundamental insights into the causes of these devastating illnesses and offer novel targets for therapeutic development. PMID:22436491

  17. Neuroimaging the interaction of mind and metabolism in humans

    PubMed Central

    D’Agostino, Alexandra E.; Small, Dana M.

    2012-01-01

    Hormonal and metabolic signals interact with neural circuits orchestrating behavior to guide food intake. Neuroimaging techniques such as functional magnetic resonance imaging (fMRI) enable the identification of where in the brain particular mental processes like desire, satiety and pleasure occur. Once these neural circuits are described it then becomes possible to determine how metabolic and hormonal signals can alter brain response to influence psychological states and decision-making processes to guide intake. Here, we provide an overview of the contributions of functional neuroimaging to the understanding of how subjective and neural responses to food and food cues interact with metabolic/hormonal factors. PMID:24024114

  18. The evolving neurobiology of gut feelings.

    PubMed

    Mayer, E A; Naliboff, B; Munakata, J

    2000-01-01

    The bi-directional communication between limbic regions and the viscera play a central role in the generation and expression of emotional responses and associated emotional feelings. The response of different viscera to distinct, emotion-specific patterns of autonomic output is fed back to the brain, in particular to the cingulofrontal convergence region. Even though this process unfolds largely without conscious awareness, it plays an important role in emotional function and may influence rational decision making in the healthy individual. Alterations in this bi-directional process such as peripheral pathologies within the gut or alterations at the brain level may explain the close association between certain affective disorders and functional visceral syndromes.

  19. IV. The cognitive implications of obesity and nutrition in childhood.

    PubMed

    Khan, Naiman A; Raine, Lauren B; Donovan, Sharon M; Hillman, Charles H

    2014-12-01

    The prevalence of childhood obesity in the United States has tripled since the 1980s and is strongly linked to the early onset of several metabolic diseases. Recent studies indicate that lower cognitive function may be another complication of childhood obesity. This review considers the research to date on the role of obesity and nutrition on childhood cognition and brain health. Although a handful of studies point to a maladaptive relationship between obesity and aspects of cognitive control, remarkably little is known regarding the impact of fat mass on brain development and cognitive function. Further, missing from the literature is the role of nutrition in the obesity-cognition interaction. Nutrition may directly or indirectly influence cognitive performance via several pathways including provision of key substrates for optimal brain health, modulation of gut microbiota, and alterations in systemic energy balance. However, in the absence of malnutrition, the functional benefits of specific nutrient intake on particular cognitive domains are not well characterized. Here, we examine the literature linking childhood obesity and cognition while considering the effects of nutritional intake. Possible mechanisms for these relationships are discussed and suggestions are made for future study topics. Although childhood obesity prevalence rates in some developed countries have recently stabilized, significant disparities remain among groups based on sex and socioeconomic status. Given that the elevated prevalence of pediatric overweight and obesity may persist for the foreseeable future, it is crucial to develop a comprehensive understanding of the influence of obesity and nutrition on cognition and brain health in the pediatric population. © 2014 The Society for Research in Child Development, Inc.

  20. Relationship of a common OXTR gene variant to brain structure and default mode network function in healthy humans.

    PubMed

    Wang, Junping; Braskie, Meredith N; Hafzalla, George W; Faskowitz, Joshua; McMahon, Katie L; de Zubicaray, Greig I; Wright, Margaret J; Yu, Chunshui; Thompson, Paul M

    2017-02-15

    A large body of research suggests that oxytocin receptor (OXTR) gene polymorphisms may influence both social behaviors and psychiatric conditions related to social deficits, such as autism spectrum disorders (ASDs), schizophrenia, and mood and anxiety disorders. However, the neural mechanism underlying these associations is still unclear. Relative to controls, patients with these psychiatric conditions show differences in brain structure, and in resting state fMRI (rs-fMRI) signal synchronicity among default mode network (DMN) regions (also known as functional connectivity). We used a stepwise imaging genetics approach in 328 healthy young adults to test the hypothesis that 10 SNPs in OXTR are associated with differences in DMN synchronicity and structure of some of the associated brain regions. As OXTR effects may be sex-dependent, we also tested whether our findings were modulated by sex. OXTR rs2254298 A allele carriers had significantly lower rsFC with PCC in a cluster extending from the right fronto-insular cortex to the putamen and globus pallidus, and in bilateral dorsal anterior cingulate cortex (dACC) compared to individuals with the GG genotype; all observed effects were found only in males. Moreover, compared to the male individuals with GG genotype ofrs2254298, the male A allele carriers demonstrated significantly thinner cortical gray matter in the bilateral dACC. Our findings suggest that there may be sexually dimorphic mechanisms by which a naturally occurring variation of the OXTR gene may influence brain structure and function in DMN-related regions implicated in neuropsychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Neuroimaging of response interference in twins concordant or discordant for inattention and hyperactivity symptoms

    PubMed Central

    van ’t Ent, D.; van Beijsterveldt, C.E.M.; Derks, E.M.; Hudziak, J.J.; Veltman, D.J.; Todd, R.D.; Boomsma, D.I.; De Geus, E.J.C.

    2009-01-01

    Attention deficit hyperactivity disorder (ADHD) is to a large extent influenced by genetic factors, but environmental influences are considered important as well. To distinguish between functional brain changes underlying primarily genetically and environmentally mediated ADHD, we used functional MRI to compare response interference in monozygotic twins highly concordant or discordant for attention problems (AP). AP scores were assessed longitudinally with the Child Behavior Check List attention problem scale (CBCL-AP). Response interference was measured during two executive function paradigms; a color-word Stroop and a flanker task. The neuroimaging results indicated that, across the entire sample, children with high CBCL-AP scores, relative to children with low CBCL-AP scores, showed decreased activation to response interference in dorsolateral prefrontal, parietal and temporal brain regions. Increased activation was noted in the premotor cortex and regions associated with visual selective attention processing, possibly reflecting compensatory mechanisms to maintain task performance. Specific comparisons of high and low scoring concordant twin pairs suggest that AP of genetic origin was characterized by decreased activation of the left dorsolateral prefrontal cortex during the Stroop task and right parietal lobe during the flanker task. In contrast, comparison of twins from discordant monozygotic pairs, suggest that AP of environmental origin was characterized by decreased activation in left and right temporal lobe areas, but only during Stroop interference. The finding of distinct brain activation changes to response interference in inattention/hyperactivity of ‘genetic’ versus ‘environmental’ origin, indicate that genetic and environmental risk factors for attention/hyperactivity problems affect the brain in different ways. PMID:19409224

  2. Influence of the partial volume correction method on 18F-fluorodeoxyglucose brain kinetic modelling from dynamic PET images reconstructed with resolution model based OSEM

    PubMed Central

    Bowen, Spencer L.; Byars, Larry G.; Michel, Christian J.; Chonde, Daniel B.; Catana, Ciprian

    2014-01-01

    Kinetic parameters estimated from dynamic 18F-fluorodeoxyglucose PET acquisitions have been used frequently to assess brain function in humans. Neglecting partial volume correction (PVC) for a dynamic series has been shown to produce significant bias in model estimates. Accurate PVC requires a space-variant model describing the reconstructed image spatial point spread function (PSF) that accounts for resolution limitations, including non-uniformities across the field of view due to the parallax effect. For OSEM, image resolution convergence is local and influenced significantly by the number of iterations, the count density, and background-to-target ratio. As both count density and background-to-target values for a brain structure can change during a dynamic scan, the local image resolution may also concurrently vary. When PVC is applied post-reconstruction the kinetic parameter estimates may be biased when neglecting the frame-dependent resolution. We explored the influence of the PVC method and implementation on kinetic parameters estimated by fitting 18F-fluorodeoxyglucose dynamic data acquired on a dedicated brain PET scanner and reconstructed with and without PSF modelling in the OSEM algorithm. The performance of several PVC algorithms was quantified with a phantom experiment, an anthropomorphic Monte Carlo simulation, and a patient scan. Using the last frame reconstructed image only for regional spread function (RSF) generation, as opposed to computing RSFs for each frame independently, and applying perturbation GTM PVC with PSF based OSEM produced the lowest magnitude bias kinetic parameter estimates in most instances, although at the cost of increased noise compared to the PVC methods utilizing conventional OSEM. Use of the last frame RSFs for PVC with no PSF modelling in the OSEM algorithm produced the lowest bias in CMRGlc estimates, although by less than 5% in most cases compared to the other PVC methods. The results indicate that the PVC implementation and choice of PSF modelling in the reconstruction can significantly impact model parameters. PMID:24052021

  3. What is special about the adolescent (JME) brain?

    PubMed

    Craiu, Dana

    2013-07-01

    Juvenile myoclonic epilepsy (JME) involves cortico-thalamo-cortical networks. Thalamic, frontal gray matter, connectivity, and neurotransmitter disturbances have been demonstrated by structural/functional imaging studies. Few patients with JME show mutations in genes coding ion channels or GABAA (gamma-aminobutyric acid) receptor subunits. Recent research points to EFHC1 gene mutations leading to microdysgenesis and possible aberrant circuitry. Imaging studies have shown massive structural/functional changes of normally developing adolescent brain structures maturing at strikingly different rates and times. Gray matter (GM) volume diminishes in cortical areas (frontal and parietal) and deep structures (anterior thalamus, putamen, and caudate). Diffusion tensor imaging (DTI) findings support continued microstructural change in WM (white matter) during late adolescence with robust developmental changes in thalamocortical connectivity. The GABAA receptor distribution and specific receptor subunits' expression patterns change with age from neonate to adolescent/adult, contributing to age-related changes in brain excitability. Hormonal influence on brain structure development during adolescence is presented. Possible implications of brain changes during adolescence on the course of JME are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. A review on neuroimaging studies of genetic and environmental influences on early brain development.

    PubMed

    Gao, Wei; Grewen, Karen; Knickmeyer, Rebecca C; Qiu, Anqi; Salzwedel, Andrew; Lin, Weili; Gilmore, John H

    2018-04-16

    The past decades witnessed a surge of interest in neuroimaging study of normal and abnormal early brain development. Structural and functional studies of normal early brain development revealed massive structural maturation as well as sequential, coordinated, and hierarchical emergence of functional networks during the infancy period, providing a great foundation for the investigation of abnormal early brain development mechanisms. Indeed, studies of altered brain development associated with either genetic or environmental risks emerged and thrived. In this paper, we will review selected studies of genetic and environmental risks that have been relatively more extensively investigated-familial risks, candidate risk genes, and genome-wide association studies (GWAS) on the genetic side; maternal mood disorders and prenatal drug exposures on the environmental side. Emerging studies on environment-gene interactions will also be reviewed. Our goal was not to perform an exhaustive review of all studies in the field but to leverage some representative ones to summarize the current state, point out potential limitations, and elicit discussions on important future directions. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Apollo’s gift: new aspects of neurologic music therapy

    PubMed Central

    Altenmüller, Eckart; Schlaug, Gottfried

    2015-01-01

    Music listening and music making activities are powerful tools to engage multisensory and motor networks, induce changes within these networks, and foster links between distant, but functionally related brain regions with continued and life-long musical practice. These multimodal effects of music together with music’s ability to tap into the emotion and reward system in the brain can be used to facilitate and enhance therapeutic approaches geared toward rehabilitating and restoring neurological dysfunctions and impairments of an acquired or congenital brain disorder. In this article, we review plastic changes in functional networks and structural components of the brain in response to short- and long-term music listening and music making activities. The specific influence of music on the developing brain is emphasized and possible transfer effects on emotional and cognitive processes are discussed. Furthermore, we present data on the potential of using musical tools and activities to support and facilitate neurorehabilitation. We will focus on interventions such as melodic intonation therapy and music-supported motor rehabilitation to showcase the effects of neurologic music therapies and discuss their underlying neural mechanisms. PMID:25725918

  6. Of Microbes and Minds: A Narrative Review on the Second Brain Aging.

    PubMed

    Calvani, Riccardo; Picca, Anna; Lo Monaco, Maria Rita; Landi, Francesco; Bernabei, Roberto; Marzetti, Emanuele

    2018-01-01

    In recent years, an extensive body of literature focused on the gut-brain axis and the possible role played by the gut microbiota in modulating brain morphology and function from birth to old age. Gut microbiota has been proposed as a relevant player during the early phases of neurodevelopment, with possible long-standing effects in later life. The reduction in gut microbiota diversity has also become one of the hallmarks of aging, and disturbances in its composition are associated with several (age-related) neurological conditions, including depression, Alzheimer's disease, and Parkinson's disease. Several pathways have been evoked for gut microbiota-brain communication, including neural connections (vagus nerve), circulating mediators derived by host-bacteria cometabolism, as well as the influence exerted by gut microbiota on host gut function, metabolism, and immune system. Although the most provoking data emerged from animal studies and despite the huge debate around the possible epiphenomenal nature of those findings, the gut microbiota-brain axis still remains a fascinating target to be exploited to attenuate some of the most burdensome consequences of aging.

  7. Apollo's gift: new aspects of neurologic music therapy.

    PubMed

    Altenmüller, Eckart; Schlaug, Gottfried

    2015-01-01

    Music listening and music making activities are powerful tools to engage multisensory and motor networks, induce changes within these networks, and foster links between distant, but functionally related brain regions with continued and life-long musical practice. These multimodal effects of music together with music's ability to tap into the emotion and reward system in the brain can be used to facilitate and enhance therapeutic approaches geared toward rehabilitating and restoring neurological dysfunctions and impairments of an acquired or congenital brain disorder. In this article, we review plastic changes in functional networks and structural components of the brain in response to short- and long-term music listening and music making activities. The specific influence of music on the developing brain is emphasized and possible transfer effects on emotional and cognitive processes are discussed. Furthermore, we present data on the potential of using musical tools and activities to support and facilitate neurorehabilitation. We will focus on interventions such as melodic intonation therapy and music-supported motor rehabilitation to showcase the effects of neurologic music therapies and discuss their underlying neural mechanisms. © 2015 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2014-04-01

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

  9. Left-right asymmetry is required for the habenulae to respond to both visual and olfactory stimuli.

    PubMed

    Dreosti, Elena; Vendrell Llopis, Nuria; Carl, Matthias; Yaksi, Emre; Wilson, Stephen W

    2014-02-17

    Left-right asymmetries are most likely a universal feature of bilaterian nervous systems and may serve to increase neural capacity by specializing equivalent structures on left and right sides for distinct roles. However, little is known about how asymmetries are encoded within vertebrate neural circuits and how lateralization influences processing of information in the brain. Consequently, it remains unclear the extent to which lateralization of the nervous system is important for normal cognitive and other brain functions and whether defects in lateralization contribute to neurological deficits. Here we show that sensory responses to light and odor are lateralized in larval zebrafish habenulae and that loss of brain asymmetry leads to concomitant loss of responsiveness to either visual or olfactory stimuli. We find that in wild-type zebrafish, most habenular neurons responding to light are present on the left, whereas neurons responding to odor are more frequent on the right. Manipulations that reverse the direction of brain asymmetry reverse the functional properties of habenular neurons, whereas manipulations that generate either double-left- or double-right-sided brains lead to loss of habenular responsiveness to either odor or light, respectively. Our results indicate that loss of brain lateralization has significant consequences upon sensory processing and circuit function. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Brain corticostriatal systems and the major clinical symptom dimensions of obsessive-compulsive disorder.

    PubMed

    Harrison, Ben J; Pujol, Jesus; Cardoner, Narcis; Deus, Joan; Alonso, Pino; López-Solà, Marina; Contreras-Rodríguez, Oren; Real, Eva; Segalàs, Cinto; Blanco-Hinojo, Laura; Menchon, José M; Soriano-Mas, Carles

    2013-02-15

    Functional neuroimaging studies have provided consistent support for the idea that obsessive-compulsive disorder (OCD) is associated with disturbances of brain corticostriatal systems. However, in general, these studies have not sought to account for the disorder's prominent clinical heterogeneity. To address these concerns, we investigated the influence of major OCD symptom dimensions on brain corticostriatal functional systems in a large sample of OCD patients (n = 74) and control participants (n = 74) examined with resting-state functional magnetic resonance imaging. We employed a valid method for mapping ventral and dorsal striatal functional connectivity, which supported both standard group comparisons and linear regression analyses with patients' scores on the Dimensional Yale-Brown Obsessive-Compulsive Scale. Consistent with past findings, patients demonstrated a common connectivity alteration involving the ventral striatum and orbitofrontal cortex that predicted overall illness severity levels. This common alteration was independent of the effect of particular symptom dimensions. Instead, we observed distinct anatomical relationships between the severity of symptom dimensions and striatal functional connectivity. Aggression symptoms modulated connectivity between the ventral striatum, amygdala, and ventromedial frontal cortex, while sexual/religious symptoms had a specific influence on ventral striatal-insular connectivity. Hoarding modulated the strength of ventral and dorsal striatal connectivity with distributed frontal regions. Taken together, these results suggest that pathophysiological changes among orbitofrontal-striatal regions may be common to all forms of OCD. They suggest that a further examination of certain dimensional relationships will also be relevant for advancing current neurobiological models of the disorder. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Emotional and cognitive functional imaging of estrogen and progesterone effects in the female human brain: a systematic review.

    PubMed

    Toffoletto, Simone; Lanzenberger, Rupert; Gingnell, Malin; Sundström-Poromaa, Inger; Comasco, Erika

    2014-12-01

    Ovarian hormones are pivotal for the physiological maintenance of the brain function as well as its response to environmental stimuli. There is mounting evidence attesting the relevance of endogenous ovarian hormones as well as exogenous estradiol and progesterone for emotional and cognitive processing. The present review systematically summarized current knowledge on sex steroid hormonal modulation of neural substrates of emotion and cognition revealed by functional magnetic resonance imaging (fMRI). Twenty-four studies of healthy naturally cycling and combined oral contraceptives (COC) user women, or women undergoing experimental manipulations, during their reproductive age, were included. Furthermore, six studies of premenstrual dysphoric disorder (PMDD), a hormonally based mood disorder, and three of gender dysphoria (GD), which provides an intriguing opportunity to examine the effect of high-dose cross-sex hormone therapy (CSHT) on brain functioning, were included. Globally, low (early follicular and the entire follicular phase for estrogen and progesterone, respectively) and high (COC, CSHT, late follicular and luteal phase for estrogen; COC, mid- and late-luteal phase for progesterone) hormonal milieu diversely affected the response of several brain regions including the amygdala, anterior cingulate cortex, and inferior frontal gyrus, but their functional recruitment across groups and domains was scattered. The constellation of findings provides initial evidence of the influence of sex steroid hormones on cortical and subcortical regions implicated in emotional and cognitive processing. Further well-powered and multimodal neuroimaging studies will be needed to identify the neural mechanism of functional brain alterations induced by sex steroid hormones. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed

    Spetter, Maartje S; Hallschmid, Manfred

    2015-08-03

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

  13. Zinc in Gut-Brain Interaction in Autism and Neurological Disorders

    PubMed Central

    Vela, Guillermo; Stark, Peter; Socha, Michael; Sauer, Ann Katrin; Hagmeyer, Simone; Grabrucker, Andreas M.

    2015-01-01

    A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life. PMID:25878905

  14. Zinc in gut-brain interaction in autism and neurological disorders.

    PubMed

    Vela, Guillermo; Stark, Peter; Socha, Michael; Sauer, Ann Katrin; Hagmeyer, Simone; Grabrucker, Andreas M

    2015-01-01

    A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life.

  15. Analytical modelling of temperature effects on an AMPA-type synapse.

    PubMed

    Kufel, Dominik S; Wojcik, Grzegorz M

    2018-05-11

    It was previously reported, that temperature may significantly influence neural dynamics on the different levels of brain function. Thus, in computational neuroscience, it would be useful to make models scalable for a wide range of various brain temperatures. However, lack of experimental data and an absence of temperature-dependent analytical models of synaptic conductance does not allow to include temperature effects at the multi-neuron modeling level. In this paper, we propose a first step to deal with this problem: A new analytical model of AMPA-type synaptic conductance, which is able to incorporate temperature effects in low-frequency stimulations. It was constructed based on Markov model description of AMPA receptor kinetics using the set of coupled ODEs. The closed-form solution for the set of differential equations was found using uncoupling assumption (introduced in the paper) with few simplifications motivated both from experimental data and from Monte Carlo simulation of synaptic transmission. The model may be used for computationally efficient and biologically accurate implementation of temperature effects on AMPA receptor conductance in large-scale neural network simulations. As a result, it may open a wide range of new possibilities for researching the influence of temperature on certain aspects of brain functioning.

  16. [Effects of shortened mandibular dental arch on human brain activity during chewing: an fMRI study].

    PubMed

    Shoi, Kazuhito

    2014-03-01

    According to the shortened dental arch concept, missing molars should not always be restored with prosthetic treatment. A shortened dental arch with missing molars is associated with a decrease in masticatory function. However, it is not known whether a shortened dental arch influences brain activity during chewing. This study aimed to clarify the effect of posterior arch length of mandibular bilateral distal extension removable partial dentures (RPDs) on brain activity during chewing. Eleven subjects with bilaterally missing mandibular molars (mean age, 66.1 years) participated in the study. RPDs with full dental arch and shortened dental arch were fabricated and brain activity during gum chewing under each dental condition was measured using functional magnetic resonance imaging. Brain activation during gum chewing with the full dental arch was observed in the middle frontal gyrus, primary sensorimotor cortex extending to the premotor cortex, supplementary motor area, putamen, insula and cerebellum. However, activation of the middle frontal gyrus was not observed during gum chewing with the shortened dental arch. The results of this study suggest that human brain activity during chewing in the middle frontal gyrus may be associated with chewing in the presence of the molar region.

  17. Weighted and directed interactions in evolving large-scale epileptic brain networks

    NASA Astrophysics Data System (ADS)

    Dickten, Henning; Porz, Stephan; Elger, Christian E.; Lehnertz, Klaus

    2016-10-01

    Epilepsy can be regarded as a network phenomenon with functionally and/or structurally aberrant connections in the brain. Over the past years, concepts and methods from network theory substantially contributed to improve the characterization of structure and function of these epileptic networks and thus to advance understanding of the dynamical disease epilepsy. We extend this promising line of research and assess—with high spatial and temporal resolution and using complementary analysis approaches that capture different characteristics of the complex dynamics—both strength and direction of interactions in evolving large-scale epileptic brain networks of 35 patients that suffered from drug-resistant focal seizures with different anatomical onset locations. Despite this heterogeneity, we find that even during the seizure-free interval the seizure onset zone is a brain region that, when averaged over time, exerts strongest directed influences over other brain regions being part of a large-scale network. This crucial role, however, manifested by averaging on the population-sample level only - in more than one third of patients, strongest directed interactions can be observed between brain regions far off the seizure onset zone. This may guide new developments for individualized diagnosis, treatment and control.

  18. Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders

    PubMed Central

    Breit, Sigrid; Kupferberg, Aleksandra; Rogler, Gerhard; Hasler, Gregor

    2018-01-01

    The vagus nerve represents the main component of the parasympathetic nervous system, which oversees a vast array of crucial bodily functions, including control of mood, immune response, digestion, and heart rate. It establishes one of the connections between the brain and the gastrointestinal tract and sends information about the state of the inner organs to the brain via afferent fibers. In this review article, we discuss various functions of the vagus nerve which make it an attractive target in treating psychiatric and gastrointestinal disorders. There is preliminary evidence that vagus nerve stimulation is a promising add-on treatment for treatment-refractory depression, posttraumatic stress disorder, and inflammatory bowel disease. Treatments that target the vagus nerve increase the vagal tone and inhibit cytokine production. Both are important mechanism of resiliency. The stimulation of vagal afferent fibers in the gut influences monoaminergic brain systems in the brain stem that play crucial roles in major psychiatric conditions, such as mood and anxiety disorders. In line, there is preliminary evidence for gut bacteria to have beneficial effect on mood and anxiety, partly by affecting the activity of the vagus nerve. Since, the vagal tone is correlated with capacity to regulate stress responses and can be influenced by breathing, its increase through meditation and yoga likely contribute to resilience and the mitigation of mood and anxiety symptoms. PMID:29593576

  19. The effects of handwriting experience on functional brain development in pre-literate children

    PubMed Central

    James, Karin H.; Engelhardt, Laura

    2014-01-01

    In an age of increasing technology, the possibility that typing on a keyboard will replace handwriting raises questions about the future usefulness of handwriting skills. Here we present evidence that brain activation during letter perception is influenced in different, important ways by previous handwriting of letters versus previous typing or tracing of those same letters. Preliterate, five-year old children printed, typed, or traced letters and shapes, then were shown images of these stimuli while undergoing functional MRI scanning. A previously documented “reading circuit” was recruited during letter perception only after handwriting—not after typing or tracing experience. These findings demonstrate that handwriting is important for the early recruitment in letter processing of brain regions known to underlie successful reading. Handwriting therefore may facilitate reading acquisition in young children. PMID:25541600

  20. Developmental effects of androgens in the human brain.

    PubMed

    Nguyen, T-V

    2018-02-01

    Neuroendocrine theories of brain development posit that androgens play a crucial role in sex-specific cortical growth, although little is known about the differential effects of testosterone and dehydroepiandrosterone (DHEA) on cortico-limbic development and cognition during adolescence. In this context, the National Institutes of Health Study of Normal Brain Development, a longitudinal study of typically developing children and adolescents aged 4-24 years (n=433), offers a unique opportunity to examine the developmental effects of androgens on cortico-limbic maturation and cognition. Using data from this sample, our group found that higher testosterone levels were associated with left-sided decreases in cortical thickness (CTh) in post-pubertal boys, particularly in the prefrontal cortex, compared to right-sided increases in CTh in somatosensory areas in pre-pubertal girls. Prefrontal-amygdala and prefrontal-hippocampal structural covariance (considered to reflect structural connectivity) also varied according to testosterone levels, with the testosterone-related brain phenotype predicting higher aggression levels and lower executive function, particularly in boys. By contrast, DHEA was associated with a pre-pubertal increase in CTh of several regions involved in cognitive control in both boys and girls. Covariance within several cortico-amygdalar structural networks also varied as a function of DHEA levels, with the DHEA-related brain phenotype predicting improvements in visual attention in both boys and girls. DHEA-related cortico-hippocampal structural covariance, on the other hand, predicted higher scores on a test of working memory. Interestingly, there were significant interactions between testosterone and DHEA, such that DHEA tended to mitigate the anti-proliferative effects of testosterone on brain structure. In sum, testosterone-related effects on the developing brain may lead to detrimental effects on cortical functions (ie, higher aggression and lower executive function), whereas DHEA-related effects may optimise cortical functions (ie, better attention and working memory), perhaps by decreasing the influence of amygdalar and hippocampal afferents on cortical functions. © 2017 British Society for Neuroendocrinology.

  1. A brief primer on the mediational role of BDNF in the exercise-memory link.

    PubMed

    Loprinzi, Paul D; Frith, Emily

    2018-05-02

    One of the most amazing aspects of the human brain is its ability to learn information and use it to change behaviour. A key neurotrophin that influences memory function is brain-derived neurotrophic factor (BDNF). This review briefly discusses the mechanistic role that BDNF may play in facilitating learning and memory. We also describe the role of exercise on this relationship. As discussed herein, BDNF may influence memory via BDNF-induced alterations in membrane receptor expression and translocation, as well as activating several pathways (PLC-y, PI3K, ERK) that act together to facilitate cellular effects that influence synaptic plasticity. Exercise may help to facilitate BDNF expression and its downstream cellular pathways from both direct and indirect mechanisms. © 2018 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  2. Serotonergic psychedelics temporarily modify information transfer in humans.

    PubMed

    Alonso, Joan Francesc; Romero, Sergio; Mañanas, Miquel Àngel; Riba, Jordi

    2015-03-28

    Psychedelics induce intense modifications in the sensorium, the sense of "self," and the experience of reality. Despite advances in our understanding of the molecular and cellular level mechanisms of these drugs, knowledge of their actions on global brain dynamics is still incomplete. Recent imaging studies have found changes in functional coupling between frontal and parietal brain structures, suggesting a modification in information flow between brain regions during acute effects. Here we assessed the psychedelic-induced changes in directionality of information flow during the acute effects of a psychedelic in humans. We measured modifications in connectivity of brain oscillations using transfer entropy, a nonlinear measure of directed functional connectivity based on information theory. Ten healthy male volunteers with prior experience with psychedelics participated in 2 experimental sessions. They received a placebo or a dose of ayahuasca, a psychedelic preparation containing the serotonergic 5-HT2A agonist N,N-dimethyltryptamine. The analysis showed significant changes in the coupling of brain oscillations between anterior and posterior recording sites. Transfer entropy analysis showed that frontal sources decreased their influence over central, parietal, and occipital sites. Conversely, sources in posterior locations increased their influence over signals measured at anterior locations. Exploratory correlations found that anterior-to-posterior transfer entropy decreases were correlated with the intensity of subjective effects, while the imbalance between anterior-to-posterior and posterior-to-anterior transfer entropy correlated with the degree of incapacitation experienced. These results suggest that psychedelics induce a temporary disruption of neural hierarchies by reducing top-down control and increasing bottom-up information transfer in the human brain. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  3. Adenosine A1 receptors contribute to immune regulation after neonatal hypoxic ischemic brain injury.

    PubMed

    Winerdal, Max; Winerdal, Malin E; Wang, Ying-Qing; Fredholm, Bertil B; Winqvist, Ola; Ådén, Ulrika

    2016-03-01

    Neonatal brain hypoxic ischemia (HI) often results in long-term motor and cognitive impairments. Post-ischemic inflammation greatly effects outcome and adenosine receptor signaling modulates both HI and immune cell function. Here, we investigated the influence of adenosine A1 receptor deficiency (A1R(-/-)) on key immune cell populations in a neonatal brain HI model. Ten-day-old mice were subjected to HI. Functional outcome was assessed by open locomotion and beam walking test and infarction size evaluated. Flow cytometry was performed on brain-infiltrating cells, and semi-automated analysis of flow cytometric data was applied. A1R(-/-) mice displayed larger infarctions (+33%, p < 0.05) and performed worse in beam walking tests (44% more mistakes, p < 0.05) than wild-type (WT) mice. Myeloid cell activation after injury was enhanced in A1R(-/-) versus WT brains. Activated B lymphocytes expressing IL-10 infiltrated the brain after HI in WT, but were less activated and did not increase in relative frequency in A1R(-/-). Also, A1R(-/-) B lymphocytes expressed less IL-10 than their WT counterparts, the A1R antagonist DPCPX decreased IL-10 expression whereas the A1R agonist CPA increased it. CD4(+) T lymphocytes including FoxP3(+) T regulatory cells, were unaffected by genotype, whereas CD8(+) T lymphocyte responses were smaller in A1R(-/-) mice. Using PCA to characterize the immune profile, we could discriminate the A1R(-/-) and WT genotypes as well as sham operated from HI-subjected animals. We conclude that A1R signaling modulates IL-10 expression by immune cells, influences the activation of these cells in vivo, and affects outcome after HI.

  4. 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

  5. Short-term fructose ingestion affects the brain independently from establishment of metabolic syndrome.

    PubMed

    Jiménez-Maldonado, Alberto; Ying, Zhe; Byun, Hyae Ran; Gomez-Pinilla, Fernando

    2018-01-01

    Chronic fructose ingestion is linked to the global epidemic of metabolic syndrome (MetS), and poses a serious threat to brain function. We asked whether a short period (one week) of fructose ingestion potentially insufficient to establish peripheral metabolic disorder could impact brain function. We report that the fructose treatment had no effect on liver/body weight ratio, weight gain, glucose tolerance and insulin sensitivity, was sufficient to reduce several aspects of hippocampal plasticity. Fructose consumption reduced the levels of the neuronal nuclear protein NeuN, Myelin Basic Protein, and the axonal growth-associated protein 43, concomitant with a decline in hippocampal weight. A reduction in peroxisome proliferator-activated receptor gamma coactivator-1 alpha and Cytochrome c oxidase subunit II by fructose treatment is indicative of mitochondrial dysfunction. Furthermore, the GLUT5 fructose transporter was increased in the hippocampus after fructose ingestion suggesting that fructose may facilitate its own transport to brain. Fructose elevated levels of ketohexokinase in the liver but did not affect SIRT1 levels, suggesting that fructose is metabolized in the liver, without severely affecting liver function commensurable to an absence of metabolic syndrome condition. These results advocate that a short period of fructose can influence brain plasticity without a major peripheral metabolic dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Cholesterol as a modifying agent of the neurovascular unit structure and function under physiological and pathological conditions.

    PubMed

    Czuba, Ewelina; Steliga, Aleksandra; Lietzau, Grażyna; Kowiański, Przemysław

    2017-08-01

    The brain, demanding constant level of cholesterol, precisely controls its synthesis and homeostasis. The brain cholesterol pool is almost completely separated from the rest of the body by the functional blood-brain barrier (BBB). Only a part of cholesterol pool can be exchanged with the blood circulation in the form of the oxysterol metabolites such, as 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC). Not only neurons but also blood vessels and neuroglia, constituting neurovascular unit (NVU), are crucial for the brain cholesterol metabolism and undergo precise regulation by numerous modulators, metabolites and signal molecules. In physiological conditions maintaining the optimal cholesterol concentration is important for the energetic metabolism, composition of cell membranes and myelination. However, a growing body of evidence indicates the consequences of the cholesterol homeostasis dysregulation in several pathophysiological processes. There is a causal relationship between hypercholesterolemia and 1) development of type 2 diabetes due to long-term high-fat diet consumption, 2) significance of the oxidative stress consequences for cerebral amyloid angiopathy and neurodegenerative diseases, 3) insulin resistance on progression of the neurodegenerative brain diseases. In this review, we summarize the current state of knowledge concerning the cholesterol influence upon functioning of the NVU under physiological and pathological conditions.

  7. Segregation and persistence of form in the lateral occipital complex.

    PubMed

    Ferber, Susanne; Humphrey, G Keith; Vilis, Tutis

    2005-01-01

    While the lateral occipital complex (LOC) has been shown to be implicated in object recognition, it is unclear whether this brain area is responsive to low-level stimulus-driven features or high-level representational processes. We used scrambled shape-from-motion displays to disambiguate the presence of contours from figure-ground segregation and to measure the strength of the binding process for shapes without contours. We found persisting brain activation in the LOC for scrambled displays after the motion stopped indicating that this brain area subserves and maintains figure-ground segregation processes, a low-level function in the object processing hierarchy. In our second experiment, we found that the figure-ground segregation process has some form of spatial constancy indicating top-down influences. The persisting activation after the motion stops suggests an intermediate role in object recognition processes for this brain area and might provide further evidence for the idea that the lateral occipital complex subserves mnemonic functions mediating between iconic and short-term memory.

  8. The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease.

    PubMed

    Sundman, Mark H; Chen, Nan-Kuei; Subbian, Vignesh; Chou, Ying-Hui

    2017-11-01

    As head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Brain responses to sexual images in 46,XY women with complete androgen insensitivity syndrome are female-typical.

    PubMed

    Hamann, Stephan; Stevens, Jennifer; Vick, Janice Hassett; Bryk, Kristina; Quigley, Charmian A; Berenbaum, Sheri A; Wallen, Kim

    2014-11-01

    Androgens, estrogens, and sex chromosomes are the major influences guiding sex differences in brain development, yet their relative roles and importance remain unclear. Individuals with complete androgen insensitivity syndrome (CAIS) offer a unique opportunity to address these issues. Although women with CAIS have a Y chromosome, testes, and produce male-typical levels of androgens, they lack functional androgen receptors preventing responding to their androgens. Thus, they develop a female physical phenotype, are reared as girls, and develop into women. Because sexually differentiated brain development in primates is determined primarily by androgens, but may be affected by sex chromosome complement, it is currently unknown whether brain structure and function in women with CAIS is more like that of women or men. In the first functional neuroimaging study of (46,XY) women with CAIS, typical (46,XX) women, and typical (46, XY) men, we found that men showed greater amygdala activation to sexual images than did either typical women or women with CAIS. Typical women and women with CAIS had highly similar patterns of brain activation, indicating that a Y chromosome is insufficient for male-typical human brain responses. Because women with CAIS produce male-typical or elevated levels of testosterone which is aromatized to estradiol these results rule out aromatization of testosterone to estradiol as a determinate of sex differences in patterns of brain activation to sexual images. We cannot, however, rule out an effect of social experience on the brain responses of women with CAIS as all were raised as girls. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Prenatal Tobacco Exposure and Brain Morphology: A Prospective Study in Young Children

    PubMed Central

    El Marroun, Hanan; Schmidt, Marcus N; Franken, Ingmar H A; Jaddoe, Vincent W V; Hofman, Albert; van der Lugt, Aad; Verhulst, Frank C; Tiemeier, Henning; White, Tonya

    2014-01-01

    It is well known that smoking during pregnancy can affect offspring health. Prenatal tobacco exposure has been associated with negative behavioral and cognitive outcomes in childhood, adolescence, and young adulthood. These associations between prenatal tobacco exposure and psychopathology in offspring could possibly be explained by the influence of prenatal tobacco exposure on brain development. In this prospective study, we investigated the association between prenatal tobacco exposure, behavioral and emotional functioning and brain morphology in young children. On the basis of age and gender, we matched 113 children prenatally exposed to tobacco with 113 unexposed controls. These children were part of a population-based study in the Netherlands, the Generation R Study, and were followed from pregnancy onward. Behavioral and emotional functioning was assessed at age 6 with the Child Behavior Checklist. We assessed brain morphology using magnetic resonance imaging techniques in children aged 6–8 years. Children exposed to tobacco throughout pregnancy have smaller total brain volumes and smaller cortical gray matter volumes. Continued prenatal tobacco exposure was associated with cortical thinning, primarily in the superior frontal, superior parietal, and precentral cortices. These children also demonstrated increased scores of affective problems. In addition, thickness of the precentral and superior frontal cortices was associated with affective problems. Importantly, brain development in offspring of mothers who quit smoking during pregnancy resembled that of nonexposed controls (no smaller brain volumes and no thinning of the cortex). Our findings suggest an association between continued prenatal tobacco exposure and brain structure and function in school-aged children. PMID:24096296

  11. Pigment-Dispersing Factor-expressing neurons convey circadian information in the honey bee brain

    PubMed Central

    Beer, Katharina; Kolbe, Esther; Kahana, Noa B.; Yayon, Nadav; Weiss, Ron; Menegazzi, Pamela; Bloch, Guy

    2018-01-01

    Pigment-Dispersing Factor (PDF) is an important neuropeptide in the brain circadian network of Drosophila and other insects, but its role in bees in which the circadian clock influences complex behaviour is not well understood. We combined high-resolution neuroanatomical characterizations, quantification of PDF levels over the day and brain injections of synthetic PDF peptide to study the role of PDF in the honey bee Apis mellifera. We show that PDF co-localizes with the clock protein Period (PER) in a cluster of laterally located neurons and that the widespread arborizations of these PER/PDF neurons are in close vicinity to other PER-positive cells (neurons and glia). PDF-immunostaining intensity oscillates in a diurnal and circadian manner with possible influences for age or worker task on synchrony of oscillations in different brain areas. Finally, PDF injection into the area between optic lobes and the central brain at the end of the subjective day produced a consistent trend of phase-delayed circadian rhythms in locomotor activity. Altogether, these results are consistent with the hypothesis that PDF is a neuromodulator that conveys circadian information from pacemaker cells to brain centres involved in diverse functions including locomotion, time memory and sun-compass orientation. PMID:29321240

  12. Permeability of ergot alkaloids across the blood-brain barrier in vitro and influence on the barrier integrity

    PubMed Central

    Mulac, Dennis; Hüwel, Sabine; Galla, Hans-Joachim; Humpf, Hans-Ulrich

    2012-01-01

    Scope Ergot alkaloids are secondary metabolites of Claviceps spp. and they have been in the focus of research for many years. Experiments focusing on ergotamine as a former migraine drug referring to the ability to reach the brain revealed controversial results. The question to which extent ergot alkaloids are able to cross the blood-brain barrier is still not answered. Methods and results In order to answer this question we have studied the ability of ergot alkaloids to penetrate the blood-brain barrier in a well established in vitro model system using primary porcine brain endothelial cells. It could clearly be demonstrated that ergot alkaloids are able to cross the blood-brain barrier in high quantities in only a few hours. We could further identify an active transport for ergometrine as a substrate for the BCRP/ABCG2 transporter. Investigations concerning barrier integrity properties have identified ergocristinine as a potent substance to accumulate in these cells ultimately leading to a weakened barrier function. Conclusion For the first time we could show that the so far as biologically inactive described 8-(S) isomers of ergot alkaloids seem to have an influence on barrier integrity underlining the necessity for a risk assessment of ergot alkaloids in food and feed. PMID:22147614

  13. Available processing resources influence encoding-related brain activity before an event

    PubMed Central

    Galli, Giulia; Gebert, A. Dorothea; Otten, Leun J.

    2013-01-01

    Effective cognitive functioning not only relies on brain activity elicited by an event, but also on activity that precedes it. This has been demonstrated in a number of cognitive domains, including memory. Here, we show that brain activity that precedes the effective encoding of a word into long-term memory depends on the availability of sufficient processing resources. We recorded electrical brain activity from the scalps of healthy adult men and women while they memorized intermixed visual and auditory words for later recall. Each word was preceded by a cue that indicated the modality of the upcoming word. The degree to which processing resources were available before word onset was manipulated by asking participants to make an easy or difficult perceptual discrimination on the cue. Brain activity before word onset predicted later recall of the word, but only in the easy discrimination condition. These findings indicate that anticipatory influences on long-term memory are limited in capacity and sensitive to the degree to which attention is divided between tasks. Prestimulus activity that affects later encoding can only be engaged when the necessary cognitive resources can be allocated to the encoding process. PMID:23219383

  14. Feeding the microbiota-gut-brain axis: diet, microbiome, and neuropsychiatry.

    PubMed

    Sandhu, Kiran V; Sherwin, Eoin; Schellekens, Harriët; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

    2017-01-01

    The microbial population residing within the human gut represents one of the most densely populated microbial niche in the human body with growing evidence showing it playing a key role in the regulation of behavior and brain function. The bidirectional communication between the gut microbiota and the brain, the microbiota-gut-brain axis, occurs through various pathways including the vagus nerve, the immune system, neuroendocrine pathways, and bacteria-derived metabolites. This axis has been shown to influence neurotransmission and the behavior that are often associated with neuropsychiatric conditions. Therefore, research targeting the modulation of this gut microbiota as a novel therapy for the treatment of various neuropsychiatric conditions is gaining interest. Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth, and environment. However, it is diet composition and nutritional status that has repeatedly been shown to be one of the most critical modifiable factors regulating the gut microbiota at different time points across the lifespan and under various health conditions. Thus the microbiota is poised to play a key role in nutritional interventions for maintaining brain health. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Mechanisms and use of neural transplants for brain repair.

    PubMed

    Dunnett, Stephen B; Björklund, Anders

    2017-01-01

    Under appropriate conditions, neural tissues transplanted into the adult mammalian brain can survive, integrate, and function so as to influence the behavior of the host, opening the prospect of repairing neuronal damage, and alleviating symptoms associated with neuronal injury or neurodegenerative disease. Alternative mechanisms of action have been postulated: nonspecific effects of surgery; neurotrophic and neuroprotective influences on disease progression and host plasticity; diffuse or locally regulated pharmacological delivery of deficient neurochemicals, neurotransmitters, or neurohormones; restitution of the neuronal and glial environment necessary for proper host neuronal support and processing; promoting local and long-distance host and graft axon growth; formation of reciprocal connections and reconstruction of local circuits within the host brain; and up to full integration and reconstruction of fully functional host neuronal networks. Analysis of neural transplants in a broad range of anatomical systems and disease models, on simple and complex classes of behavioral function and information processing, have indicated that all of these alternative mechanisms are likely to contribute in different circumstances. Thus, there is not a single or typical mode of graft function; rather grafts can and do function in multiple ways, specific to each particular context. Consequently, to develop an effective cell-based therapy, multiple dimensions must be considered: the target disease pathogenesis; the neurodegenerative basis of each type of physiological dysfunction or behavioral symptom; the nature of the repair required to alleviate or remediate the functional impairments of particular clinical relevance; and identification of a suitable cell source or delivery system, along with the site and method of implantation, that can achieve the sought for repair and recovery. © 2017 Elsevier B.V. All rights reserved.

  16. Association of the brain-derived neurotrophic factor Val66Met polymorphism with negative symptoms severity, but not cognitive function, in first-episode schizophrenia spectrum disorders.

    PubMed

    Mezquida, G; Penadés, R; Cabrera, B; Savulich, G; Lobo, A; González-Pinto, A; Penzol, M J; Corripio, I; Fernandez-Egea, E; Gassó, P; Cuesta, M J; Bernardo, M

    2016-10-01

    A functional polymorphism of the brain-derived neurotrophic factor gene (BDNF) Val66Met has been associated with cognitive function and symptom severity in patients with schizophrenia. It has been suggested that the Val66Met polymorphism has a role as a modulator in a range of clinical features of the illness, including symptoms severity, therapeutic responsiveness, age of onset, brain morphology and cognitive function. However, little work has been done in first-episode schizophrenia (FES) spectrum disorders. The objective of this study is to investigate the association of the BDNF Val66Met polymorphism on cognitive function and clinical symptomatology in FES patients. Using a cross-sectional design in a cohort of 204 patients with FES or a schizophrenia spectrum disorder and 204 healthy matched controls, we performed BDNF Val66Met genotyping and tested its relationship with cognitive testing (attention, working memory, learning/verbal memory and reasoning/problem-solving) and assessment of clinical symptom severity. There was no significant influence of the BDNF allele frequency on cognitive factor scores in either patients or controls. An augmented severity of negative symptoms was found in FES patients that carried the Met allele. The results of this study suggest that in patients with a first-episode of schizophrenia or a schizophrenia spectrum disorder, the BDNF Val66Met polymorphism does not exert an influence on cognitive functioning, but is associated with negative symptoms severity. BDNF may serve as suitable marker of negative symptomatology severity in FES patients within the schizophrenia spectrum. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Sex and disease-related alterations of anterior insula functional connectivity in chronic abdominal pain.

    PubMed

    Hong, Jui-Yang; Kilpatrick, Lisa A; Labus, Jennifer S; Gupta, Arpana; Katibian, David; Ashe-McNalley, Cody; Stains, Jean; Heendeniya, Nuwanthi; Smith, Suzanne R; Tillisch, Kirsten; Naliboff, Bruce; Mayer, Emeran A

    2014-10-22

    Resting-state functional magnetic resonance imaging has been used to investigate intrinsic brain connectivity in healthy subjects and patients with chronic pain. Sex-related differences in the frequency power distribution within the human insula (INS), a brain region involved in the integration of interoceptive, affective, and cognitive influences, have been reported. Here we aimed to test sex and disease-related alterations in the intrinsic functional connectivity of the dorsal anterior INS. The anterior INS is engaged during goal-directed tasks and modulates the default mode and executive control networks. By comparing functional connectivity of the dorsal anterior INS in age-matched female and male healthy subjects and patients with irritable bowel syndrome (IBS), a common chronic abdominal pain condition, we show evidence for sex and disease-related alterations in the functional connectivity of this region: (1) male patients compared with female patients had increased positive connectivity of the dorsal anterior INS bilaterally with the medial prefrontal cortex (PFC) and dorsal posterior INS; (2) female patients compared with male patients had greater negative connectivity of the left dorsal anterior INS with the left precuneus; (3) disease-related differences in the connectivity between the bilateral dorsal anterior INS and the dorsal medial PFC were observed in female subjects; and (4) clinical characteristics were significantly correlated to the insular connectivity with the dorsal medial PFC in male IBS subjects and with the precuneus in female IBS subjects. These findings are consistent with the INS playing an important role in modulating the intrinsic functional connectivity of major networks in the resting brain and show that this role is influenced by sex and diagnosis. Copyright © 2014 the authors 0270-6474/14/3414252-08$15.00/0.

  18. 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.

  19. 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

  20. Enriched environment improves motor function and increases neurotrophins in hemicerebellar lesioned rats.

    PubMed

    Gelfo, Francesca; Cutuli, Debora; Foti, Francesca; Laricchiuta, Daniela; De Bartolo, Paola; Caltagirone, Carlo; Petrosini, Laura; Angelucci, Francesco

    2011-01-01

    Environmental enrichment (EE) defined as "a combination of complex inanimate and social stimulation" influences brain function and anatomy by enhancing sensory, cognitive, motor, and social stimulation. The beneficial effects of EE in the presence of brain damage have been partially attributed to upregulation of neurotrophins, proteins involved in neuronal survival and in activity-dependent plasticity. The authors tested the hypothesis that EE may have advantageous effects on recovery of motor function after cerebellar damage, associated with changes in local neurotrophin production. They performed a hemicerebellectomy in rats previously exposed to EE or reared in standard conditions. The time course of compensation of motor symptoms was analyzed in both lesioned groups. Then, the local production of the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the spared hemicerebellum and other extracerebellar regions was evaluated. Long-term exposure to EE accelerated the motor recovery in hemicerebellectomized rats and elicited an increase in NGF levels in the spared hemicerebellum, as compared with nonenriched lesioned and control rats. BDNF levels were higher in hemicerebellectomized rats but not influenced by EE. In the frontal cortex, both NGF and BDNF levels were upregulated in hemicerebellectomized enriched rats as compared with hemicerebellectomized nonenriched and control rats. This study suggests that the beneficial effects of EE on motor symptoms after cerebellar damage may be, at least partly, because of modulation of neurotrophic proteins involved in the regeneration processes.

  1. Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study.

    PubMed

    Merege-Filho, Carlos Alberto Abujabra; Otaduy, Maria Concepción Garcia; de Sá-Pinto, Ana Lúcia; de Oliveira, Maira Okada; de Souza Gonçalves, Lívia; Hayashi, Ana Paula Tanaka; Roschel, Hamilton; Pereira, Rosa Maria Rodrigues; Silva, Clovis Artur; Brucki, Sonia Maria Dozzi; da Costa Leite, Claudia; Gualano, Bruno

    2017-02-01

    It has been hypothesized that dietary creatine could influence cognitive performance by increasing brain creatine in developing individuals. This double-blind, randomized, placebo-controlled, proof-of-principle study aimed to investigate the effects of creatine supplementation on cognitive function and brain creatine content in healthy youth. The sample comprised 67 healthy participants aged 10 to 12 years. The participants were given creatine or placebo supplementation for 7 days. At baseline and after the intervention, participants undertook a battery of cognitive tests. In a random subsample of participants, brain creatine content was also assessed in the regions of left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe by proton magnetic resonance spectroscopy (1H-MRS) technique. The scores obtained from verbal learning and executive functions tests did not significantly differ between groups at baseline or after the intervention (all p > 0.05). Creatine content was not significantly different between groups in left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe (all p > 0.05). In conclusion, a 7-day creatine supplementation protocol did not elicit improvements in brain creatine content or cognitive performance in healthy youth, suggesting that this population mainly relies on brain creatine synthesis rather than exogenous creatine intake to maintain brain creatine homeostasis.

  2. Characteristics of voxel prediction power in full-brain Granger causality analysis of fMRI data

    NASA Astrophysics Data System (ADS)

    Garg, Rahul; Cecchi, Guillermo A.; Rao, A. Ravishankar

    2011-03-01

    Functional neuroimaging research is moving from the study of "activations" to the study of "interactions" among brain regions. Granger causality analysis provides a powerful technique to model spatio-temporal interactions among brain regions. We apply this technique to full-brain fMRI data without aggregating any voxel data into regions of interest (ROIs). We circumvent the problem of dimensionality using sparse regression from machine learning. On a simple finger-tapping experiment we found that (1) a small number of voxels in the brain have very high prediction power, explaining the future time course of other voxels in the brain; (2) these voxels occur in small sized clusters (of size 1-4 voxels) distributed throughout the brain; (3) albeit small, these clusters overlap with most of the clusters identified with the non-temporal General Linear Model (GLM); and (4) the method identifies clusters which, while not determined by the task and not detectable by GLM, still influence brain activity.

  3. Hierarchy of Information Processing in the Brain: A Novel 'Intrinsic Ignition' Framework.

    PubMed

    Deco, Gustavo; Kringelbach, Morten L

    2017-06-07

    A general theory of brain function has to be able to explain local and non-local network computations over space and time. We propose a new framework to capture the key principles of how local activity influences global computation, i.e., describing the propagation of information and thus the broadness of communication driven by local activity. More specifically, we consider the diversity in space (nodes or brain regions) over time using the concept of intrinsic ignition, which are naturally occurring intrinsic perturbations reflecting the capability of a given brain area to propagate neuronal activity to other regions in a given brain state. Characterizing the profile of intrinsic ignition for a given brain state provides insight into the precise nature of hierarchical information processing. Combining this data-driven method with a causal whole-brain computational model can provide novel insights into the imbalance of brain states found in neuropsychiatric disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Huntingtin-interacting protein 1 influences worm and mouse presynaptic function and protects Caenorhabditis elegans neurons against mutant polyglutamine toxicity.

    PubMed

    Parker, J Alex; Metzler, Martina; Georgiou, John; Mage, Marilyne; Roder, John C; Rose, Ann M; Hayden, Michael R; Néri, Christian

    2007-10-10

    Huntingtin-interacting protein 1 (HIP1) was identified through its interaction with htt (huntingtin), the Huntington's disease (HD) protein. HIP1 is an endocytic protein that influences transport and function of AMPA and NMDA receptors in the brain. However, little is known about its contribution to neuronal dysfunction in HD. We report that the Caenorhabditis elegans HIP1 homolog hipr-1 modulates presynaptic activity and the abundance of synaptobrevin, a protein involved in synaptic vesicle fusion. Presynaptic function was also altered in hippocampal brain slices of HIP1-/- mice demonstrating delayed recovery from synaptic depression and a reduction in paired-pulse facilitation, a form of presynaptic plasticity. Interestingly, neuronal dysfunction in transgenic nematodes expressing mutant N-terminal huntingtin was specifically enhanced by hipr-1 loss of function. A similar effect was observed with several other mutant proteins that are expressed at the synapse and involved in endocytosis, such as unc-11/AP180, unc-26/synaptojanin, and unc-57/endophilin. Thus, HIP1 is involved in presynaptic nerve terminal activity and modulation of mutant polyglutamine-induced neuronal dysfunction. Moreover, synaptic proteins involved in endocytosis may protect neurons against amino acid homopolymer expansion.

  5. Family function and its relationship to injury severity and psychiatric outcome in children with acquired brain injury: a systematized review.

    PubMed

    Lax Pericall, Maria Teresa; Taylor, Eric

    2014-01-01

    The psychological and psychiatric outcome of children with acquired brain injury is influenced by many variables. A review was undertaken to clarify the contribution of family function, how it relates to injury severity, and what particular aspects of family function influence psychological outcome in this group. A systematized review of the literature of studies published between 1970 and 2012 from OvidMedline, PsychoInfo, PsycARTICLES, and Cochrane was undertaken focusing on family function, injury severity, and psychiatric outcome. Thirty-six papers met the inclusion criteria. Injury severity was linked to the development of organic personality change. Family function before injury, measured by the Family Assessment Device or the Clinical Rating Scale, had a statistically significant effect on general psychological functioning in six out of eight studies. Family function had a significant effect for oppositional defiant disorder and secondary attention-deficit-hyperactivity disorder. The effects of family function may differ depending on the age of the child and the severity of the injury. Some styles of parenting moderated recovery. After injury, family function was related to the child's contemporaneous psychiatric symptoms. The level of evidence for these papers was 3 or 4 (Oxford Centre for Evidence-based Medicine criteria). Screening for some aspects of family functioning before injury and family function during the rehabilitation phase may identify children at risk of psychiatric disorders. © 2013 Mac Keith Press.

  6. In Utero Administration of Drugs Targeting Microglia Improves the Neurodevelopmental Outcome Following Cytomegalovirus Infection of the Rat Fetal Brain

    PubMed Central

    Cloarec, Robin; Bauer, Sylvian; Teissier, Natacha; Schaller, Fabienne; Luche, Hervé; Courtens, Sandra; Salmi, Manal; Pauly, Vanessa; Bois, Emilie; Pallesi-Pocachard, Emilie; Buhler, Emmanuelle; Michel, François J.; Gressens, Pierre; Malissen, Marie; Stamminger, Thomas; Streblow, Daniel N.; Bruneau, Nadine; Szepetowski, Pierre

    2018-01-01

    Congenital cytomegalovirus (CMV) infections represent one leading cause of neurodevelopmental disorders. Recently, we reported on a rat model of CMV infection of the developing brain in utero, characterized by early and prominent infection and alteration of microglia—the brain-resident mononuclear phagocytes. Besides their canonical function against pathogens, microglia are also pivotal to brain development. Here we show that CMV infection of the rat fetal brain recapitulated key postnatal phenotypes of human congenital CMV including increased mortality, sensorimotor impairment reminiscent of cerebral palsy, hearing defects, and epileptic seizures. The possible influence of early microglia alteration on those phenotypes was then questioned by pharmacological targeting of microglia during pregnancy. One single administration of clodronate liposomes in the embryonic brains at the time of CMV injection to deplete microglia, and maternal feeding with doxycyxline throughout pregnancy to modify microglia in the litters' brains, were both associated with dramatic improvements of survival, body weight gain, sensorimotor development and with decreased risk of epileptic seizures. Improvement of microglia activation status did not persist postnatally after doxycycline discontinuation; also, active brain infection remained unchanged by doxycycline. Altogether our data indicate that early microglia alteration, rather than brain CMV load per se, is instrumental in influencing survival and the neurological outcomes of CMV-infected rats, and suggest that microglia might participate in the neurological outcome of congenital CMV in humans. Furthermore this study represents a first proof-of-principle for the design of microglia-targeted preventive strategies in the context of congenital CMV infection of the brain. PMID:29559892

  7. Do you believe in brain training? A questionnaire about expectations of computerised cognitive training.

    PubMed

    Rabipour, Sheida; Davidson, Patrick S R

    2015-12-15

    "Brain training" (i.e., enhancing, rehabilitating, or simply maintaining cognitive function through deliberate cognitive exercise) is growing rapidly in popularity, yet remains highly controversial. Among the greatest problems in current research is the lack of a measure of participants' expectations, which can influence the degree to which they improve over training (i.e., the placebo effect). Here we created a questionnaire to measure the perceived effectiveness of brain-training software. Given the growth in advertising of these programmes, we sought to determine whether even a brief positive (or negative) message about brain training would increase (or decrease) the reported optimism of participants. We measured participants' expectations at baseline, and then following exposure to separate, brief messages that such programmes have either high or low effectiveness. Based on the knowledge they have gleaned from advertising and other real-world sources, people are relatively optimistic about brain training. However, brief messages can influence reported expectations about brain-training results: Reading a brief positive message can increase reported optimism, whereas reading a brief negative message can decrease it. Older adults appear more optimistic about brain training than young adults, especially when they report being knowledgeable about brain training and computers. These data indicate that perceptions of brain training are malleable to at least some extent, and may vary depending on age and other factors. Our questionnaire can serve as a simple, easily-incorporated tool to assess the face validity of brain training interventions and to create a covariate to account for expectations in statistical analyses. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Sex differences in the gut microbiome-brain axis across the lifespan.

    PubMed

    Jašarević, Eldin; Morrison, Kathleen E; Bale, Tracy L

    2016-02-19

    In recent years, the bidirectional communication between the gut microbiome and the brain has emerged as a factor that influences immunity, metabolism, neurodevelopment and behaviour. Cross-talk between the gut and brain begins early in life immediately following the transition from a sterile in utero environment to one that is exposed to a changing and complex microbial milieu over a lifetime. Once established, communication between the gut and brain integrates information from the autonomic and enteric nervous systems, neuroendocrine and neuroimmune signals, and peripheral immune and metabolic signals. Importantly, the composition and functional potential of the gut microbiome undergoes many transitions that parallel dynamic periods of brain development and maturation for which distinct sex differences have been identified. Here, we discuss the sexually dimorphic development, maturation and maintenance of the gut microbiome-brain axis, and the sex differences therein important in disease risk and resilience throughout the lifespan. © 2016 The Author(s).

  9. Brain transcriptome perturbations in the Hfe(-/-) mouse model of genetic iron loading.

    PubMed

    Johnstone, Daniel; Graham, Ross M; Trinder, Debbie; Delima, Roheeth D; Riveros, Carlos; Olynyk, John K; Scott, Rodney J; Moscato, Pablo; Milward, Elizabeth A

    2012-04-11

    Severe disruption of brain iron homeostasis can cause fatal neurodegenerative disease, however debate surrounds the neurologic effects of milder, more common iron loading disorders such as hereditary hemochromatosis, which is usually caused by loss-of-function polymorphisms in the HFE gene. There is evidence from both human and animal studies that HFE gene variants may affect brain function and modify risks of brain disease. To investigate how disruption of HFE influences brain transcript levels, we used microarray and real-time reverse transcription polymerase chain reaction to assess the brain transcriptome in Hfe(-/-) mice relative to wildtype AKR controls (age 10 weeks, n≥4/group). The Hfe(-/-) mouse brain showed numerous significant changes in transcript levels (p<0.05) although few of these related to proteins directly involved in iron homeostasis. There were robust changes of at least 2-fold in levels of transcripts for prominent genes relating to transcriptional regulation (FBJ osteosarcoma oncogene Fos, early growth response genes), neurotransmission (glutamate NMDA receptor Grin1, GABA receptor Gabbr1) and synaptic plasticity and memory (calcium/calmodulin-dependent protein kinase IIα Camk2a). As previously reported for dietary iron-supplemented mice, there were altered levels of transcripts for genes linked to neuronal ceroid lipofuscinosis, a disease characterized by excessive lipofuscin deposition. Labile iron is known to enhance lipofuscin generation which may accelerate brain aging. The findings provide evidence that iron loading disorders can considerably perturb levels of transcripts for genes essential for normal brain function and may help explain some of the neurologic signs and symptoms reported in hemochromatosis patients. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Factors Influencing Cerebral Plasticity in the Normal and Injured Brain

    PubMed Central

    Kolb, Bryan; Teskey, G. Campbell; Gibb, Robbin

    2010-01-01

    An important development in behavioral neuroscience in the past 20 years has been the demonstration that it is possible to stimulate functional recovery after cerebral injury in laboratory animals. Rodent models of cerebral injury provide an important tool for developing such rehabilitation programs. The models include analysis at different levels including detailed behavioral paradigms, electrophysiology, neuronal morphology, protein chemistry, and epigenetics. A significant challenge for the next 20 years will be the translation of this work to improve the outcome from brain injury and disease in humans. Our goal in the article will be to synthesize the multidisciplinary laboratory work on brain plasticity and behavior in the injured brain to inform the development of rehabilitation programs. PMID:21120136

  11. Exploring the motivational brain: effects of implicit power motivation on brain activation in response to facial expressions of emotion.

    PubMed

    Schultheiss, Oliver C; Wirth, Michelle M; Waugh, Christian E; Stanton, Steven J; Meier, Elizabeth A; Reuter-Lorenz, Patricia

    2008-12-01

    This study tested the hypothesis that implicit power motivation (nPower), in interaction with power incentives, influences activation of brain systems mediating motivation. Twelve individuals low (lowest quartile) and 12 individuals high (highest quartile) in nPower, as assessed per content coding of picture stories, were selected from a larger initial participant pool and participated in a functional magnetic resonance imaging study during which they viewed high-dominance (angry faces), low-dominance (surprised faces) and control stimuli (neutral faces, gray squares) under oddball-task conditions. Consistent with hypotheses, high-power participants showed stronger activation in response to emotional faces in brain structures involved in emotion and motivation (insula, dorsal striatum, orbitofrontal cortex) than low-power participants.

  12. Brain Reward Circuits in Morphine Addiction

    PubMed Central

    Kim, Juhwan; Ham, Suji; Hong, Heeok; Moon, Changjong; Im, Heh-In

    2016-01-01

    Morphine is the most potent analgesic for chronic pain, but its clinical use has been limited by the opiate’s innate tendency to produce tolerance, severe withdrawal symptoms and rewarding properties with a high risk of relapse. To understand the addictive properties of morphine, past studies have focused on relevant molecular and cellular changes in the brain, highlighting the functional roles of reward-related brain regions. Given the accumulated findings, a recent, emerging trend in morphine research is that of examining the dynamics of neuronal interactions in brain reward circuits under the influence of morphine action. In this review, we highlight recent findings on the roles of several reward circuits involved in morphine addiction based on pharmacological, molecular and physiological evidences. PMID:27506251

  13. Extrinsic and Intrinsic Brain Network Connectivity Maintains Cognition across the Lifespan Despite Accelerated Decay of Regional Brain Activation.

    PubMed

    Tsvetanov, Kamen A; Henson, Richard N A; Tyler, Lorraine K; Razi, Adeel; Geerligs, Linda; Ham, Timothy E; Rowe, James B

    2016-03-16

    The maintenance of wellbeing across the lifespan depends on the preservation of cognitive function. We propose that successful cognitive aging is determined by interactions both within and between large-scale functional brain networks. Such connectivity can be estimated from task-free functional magnetic resonance imaging (fMRI), also known as resting-state fMRI (rs-fMRI). However, common correlational methods are confounded by age-related changes in the neurovascular signaling. To estimate network interactions at the neuronal rather than vascular level, we used generative models that specified both the neural interactions and a flexible neurovascular forward model. The networks' parameters were optimized to explain the spectral dynamics of rs-fMRI data in 602 healthy human adults from population-based cohorts who were approximately uniformly distributed between 18 and 88 years (www.cam-can.com). We assessed directed connectivity within and between three key large-scale networks: the salience network, dorsal attention network, and default mode network. We found that age influences connectivity both within and between these networks, over and above the effects on neurovascular coupling. Canonical correlation analysis revealed that the relationship between network connectivity and cognitive function was age-dependent: cognitive performance relied on neural dynamics more strongly in older adults. These effects were driven partly by reduced stability of neural activity within all networks, as expressed by an accelerated decay of neural information. Our findings suggest that the balance of excitatory connectivity between networks, and the stability of intrinsic neural representations within networks, changes with age. The cognitive function of older adults becomes increasingly dependent on these factors. Maintaining cognitive function is critical to successful aging. To study the neural basis of cognitive function across the lifespan, we studied a large population-based cohort (n = 602, 18-88 years), separating neural connectivity from vascular components of fMRI signals. Cognitive ability was influenced by the strength of connection within and between functional brain networks, and this positive relationship increased with age. In older adults, there was more rapid decay of intrinsic neuronal activity in multiple regions of the brain networks, which related to cognitive performance. Our data demonstrate increased reliance on network flexibility to maintain cognitive function, in the presence of more rapid decay of neural activity. These insights will facilitate the development of new strategies to maintain cognitive ability. Copyright © 2016 Tsvetanov et al.

  14. Extrinsic and Intrinsic Brain Network Connectivity Maintains Cognition across the Lifespan Despite Accelerated Decay of Regional Brain Activation

    PubMed Central

    Henson, Richard N.A.; Tyler, Lorraine K.; Razi, Adeel; Geerligs, Linda; Ham, Timothy E.; Rowe, James B.

    2016-01-01

    The maintenance of wellbeing across the lifespan depends on the preservation of cognitive function. We propose that successful cognitive aging is determined by interactions both within and between large-scale functional brain networks. Such connectivity can be estimated from task-free functional magnetic resonance imaging (fMRI), also known as resting-state fMRI (rs-fMRI). However, common correlational methods are confounded by age-related changes in the neurovascular signaling. To estimate network interactions at the neuronal rather than vascular level, we used generative models that specified both the neural interactions and a flexible neurovascular forward model. The networks' parameters were optimized to explain the spectral dynamics of rs-fMRI data in 602 healthy human adults from population-based cohorts who were approximately uniformly distributed between 18 and 88 years (www.cam-can.com). We assessed directed connectivity within and between three key large-scale networks: the salience network, dorsal attention network, and default mode network. We found that age influences connectivity both within and between these networks, over and above the effects on neurovascular coupling. Canonical correlation analysis revealed that the relationship between network connectivity and cognitive function was age-dependent: cognitive performance relied on neural dynamics more strongly in older adults. These effects were driven partly by reduced stability of neural activity within all networks, as expressed by an accelerated decay of neural information. Our findings suggest that the balance of excitatory connectivity between networks, and the stability of intrinsic neural representations within networks, changes with age. The cognitive function of older adults becomes increasingly dependent on these factors. SIGNIFICANCE STATEMENT Maintaining cognitive function is critical to successful aging. To study the neural basis of cognitive function across the lifespan, we studied a large population-based cohort (n = 602, 18–88 years), separating neural connectivity from vascular components of fMRI signals. Cognitive ability was influenced by the strength of connection within and between functional brain networks, and this positive relationship increased with age. In older adults, there was more rapid decay of intrinsic neuronal activity in multiple regions of the brain networks, which related to cognitive performance. Our data demonstrate increased reliance on network flexibility to maintain cognitive function, in the presence of more rapid decay of neural activity. These insights will facilitate the development of new strategies to maintain cognitive ability. PMID:26985024

  15. Globally conditioned Granger causality in brain–brain and brain–heart interactions: a combined heart rate variability/ultra-high-field (7 T) functional magnetic resonance imaging study

    PubMed Central

    Passamonti, Luca; Wald, Lawrence L.; Barbieri, Riccardo

    2016-01-01

    The causal, directed interactions between brain regions at rest (brain–brain networks) and between resting-state brain activity and autonomic nervous system (ANS) outflow (brain–heart links) have not been completely elucidated. We collected 7 T resting-state functional magnetic resonance imaging (fMRI) data with simultaneous respiration and heartbeat recordings in nine healthy volunteers to investigate (i) the causal interactions between cortical and subcortical brain regions at rest and (ii) the causal interactions between resting-state brain activity and the ANS as quantified through a probabilistic, point-process-based heartbeat model which generates dynamical estimates for sympathetic and parasympathetic activity as well as sympathovagal balance. Given the high amount of information shared between brain-derived signals, we compared the results of traditional bivariate Granger causality (GC) with a globally conditioned approach which evaluated the additional influence of each brain region on the causal target while factoring out effects concomitantly mediated by other brain regions. The bivariate approach resulted in a large number of possibly spurious causal brain–brain links, while, using the globally conditioned approach, we demonstrated the existence of significant selective causal links between cortical/subcortical brain regions and sympathetic and parasympathetic modulation as well as sympathovagal balance. In particular, we demonstrated a causal role of the amygdala, hypothalamus, brainstem and, among others, medial, middle and superior frontal gyri, superior temporal pole, paracentral lobule and cerebellar regions in modulating the so-called central autonomic network (CAN). In summary, we show that, provided proper conditioning is employed to eliminate spurious causalities, ultra-high-field functional imaging coupled with physiological signal acquisition and GC analysis is able to quantify directed brain–brain and brain–heart interactions reflecting central modulation of ANS outflow. PMID:27044985

  16. ENDOCRINE DISRUPTORS AS A THREAT TO NEUROLOGICAL FUNCTION

    PubMed Central

    Weiss, Bernard

    2011-01-01

    Endocrine disruption is a concept and principle whose origins can be traced to the beginnings of the environmental movement in the 1960s. It began with puzzlement about and the flaring of research on the decline of wildlife, particularly avian species. The proposed causes accented pesticides, especially persistent organochlorines such as DDT. Its scope gradually widened beyond pesticides, and, as endocrine disruption offered an explanation for the wildlife phenomena, it seemed to explain, as well, changes in fertility and disorders of male reproduction such as testicular cancer. Once disturbed gonadal hormone function became the most likely explanation, it provoked other questions. The most challenging arose because of how critical gonadal hormones are to brain function, especially as determinants of brain sexual differentiation. Pursuit of such connections has generated a robust literature embracing a broad swath of chemical classes. How endocrine disrupting chemicals influence the adult and aging brain is a question, so far mostly ignored because of the emphasis on early development, that warrants vigorous investigation. Gonadal hormones are crucial to optimal brain function during maturity and even senescence. They are pivotal to the processes of neurogenesis. They exert protective actions against neurodegenerative disorders such as dementia and support smoothly functioning cognitive activities. The limited research conducted so far on endocrine disruptors, aging, and neurogenesis argues that they should be overlooked no longer. PMID:21474148

  17. Stress, Anxiety, and Immunomodulation: A Pharmacological Analysis.

    PubMed

    Ray, A; Gulati, K; Rai, N

    2017-01-01

    Stress and stressful events are common occurrences in our daily lives and such aversive situations bring about complex changes in the biological system. Such stress responses influence the brain and behavior, neuroendocrine and immune systems, and these responses orchestrate to increase or decrease the ability of the organism to cope with such stressors. The brain via expression of complex behavioral paradigms controls peripheral responses to stress and a bidirectional link exists in the modulation of stress effects. Anxiety is a common neurobehavioral correlate of a variety of stressors, and both acute and chronic stress exposure could precipitate anxiety disorders. Psychoneuroimmunology involves interactions between the brain and the immune system, and it is now being increasingly recognized that the immune system could contribute to the neurobehavioral responses to stress. Studies have shown that the brain and its complex neurotransmitter networks could influence immune function, and there could be a possible link between anxiogenesis and immunomodulation during stress. Physiological and pharmacological data have highlighted this concept, and the present review gives an overview of the relationship between stress, anxiety, and immune responsiveness. © 2017 Elsevier Inc. All rights reserved.

  18. Influence of metformin on mitochondrial subproteome in the brain of apoE knockout mice.

    PubMed

    Suski, Maciej; Olszanecki, Rafał; Chmura, Łukasz; Stachowicz, Aneta; Madej, Józef; Okoń, Krzysztof; Adamek, Dariusz; Korbut, Ryszard

    2016-02-05

    Neurodegenerative diseases are the set of progressive, age-related brain disorders, characterized by an excessive accumulation of mutant proteins in the certain regions of the brain. Such changes, collectively identified as causal factors of neurodegeneration, all impact mitochondria, imminently leading to their dysfunction. These observations predestine mitochondria as an attractive drug target for counteracting degenerative brain damage. The aim of this study was to use a differential proteomic approach to comprehensively assess the changes in mitochondrial protein expression in the brain of apoE-knockout mice (apoE(-/-)) and to investigate the influence of prolonged treatment with metformin - an indirect activator of AMP-activated protein kinase (AMPK) on the brain mitoproteome in apoE(-/-) mice. The quantitative assessment of the brain mitoproteome in apoE(-/-) revealed the changes in 10 proteins expression as compared to healthy C57BL/6J mice and 25 proteins expression in metformin-treated apoE(-/-) mice. Identified proteins mainly included apoptosis regulators, metabolic enzymes and structural proteins. In summary, our study provided proteomic characteristics suggesting the decrease of antioxidant defense and structural disturbances in the brain mitochondria of apoE(-/-) mice as compared to healthy controls. In this setting, the use of metformin changed the expression of several proteins primarily involved in metabolic processes, the regulation of apoptosis and the structural maintenance of mitochondria, what could potentially restore their native functionalities. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Effect of motor imagery in children with unilateral cerebral palsy: fMRI study.

    PubMed

    Chinier, Eva; N'Guyen, Sylvie; Lignon, Grégoire; Ter Minassian, Aram; Richard, Isabelle; Dinomais, Mickaël

    2014-01-01

    Motor imagery is considered as a promising therapeutic tool for rehabilitation of motor planning problems in patients with cerebral palsy. However motor planning problems may lead to poor motor imagery ability. The aim of this functional magnetic resonance imaging study was to examine and compare brain activation following motor imagery tasks in patients with hemiplegic cerebral palsy with left or right early brain lesions. We tested also the influence of the side of imagined hand movement. Twenty patients with clinical hemiplegic cerebral palsy (sixteen males, mean age 12 years and 10 months, aged 6 years 10 months to 20 years 10 months) participated in this study. Using block design, brain activations following motor imagery of a simple opening-closing hand movement performed by either the paretic or nonparetic hand was examined. During motor imagery tasks, patients with early right brain damages activated bilateral fronto-parietal network that comprise most of the nodes of the network well described in healthy subjects. Inversely, in patients with left early brain lesion brain activation following motor imagery tasks was reduced, compared to patients with right brain lesions. We found also a weak influence of the side of imagined hand movement. Decreased activations following motor imagery in patients with right unilateral cerebral palsy highlight the dominance of the left hemisphere during motor imagery tasks. This study gives neuronal substrate to propose motor imagery tasks in unilateral cerebral palsy rehabilitation at least for patients with right brain lesions.

  20. Reproducibility assessment of brain responses to visual food stimuli in adults with overweight and obesity.

    PubMed

    Drew Sayer, R; Tamer, Gregory G; Chen, Ningning; Tregellas, Jason R; Cornier, Marc-Andre; Kareken, David A; Talavage, Thomas M; McCrory, Megan A; Campbell, Wayne W

    2016-10-01

    The brain's reward system influences ingestive behavior and subsequently obesity risk. Functional magnetic resonance imaging (fMRI) is a common method for investigating brain reward function. This study sought to assess the reproducibility of fasting-state brain responses to visual food stimuli using BOLD fMRI. A priori brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fasting-state fMRI and appetite assessments were completed by 28 women (n = 16) and men (n = 12) with overweight or obesity on 2 days. Reproducibility was assessed by comparing mean fasting-state brain responses and measuring test-retest reliability of these responses on the two testing days. Mean fasting-state brain responses on day 2 were reduced compared with day 1 in the left insula and right amygdala, but mean day 1 and day 2 responses were not different in the other regions of interest. With the exception of the left orbitofrontal cortex response (fair reliability), test-retest reliabilities of brain responses were poor or unreliable. fMRI-measured responses to visual food cues in adults with overweight or obesity show relatively good mean-level reproducibility but considerable within-subject variability. Poor test-retest reliability reduces the likelihood of observing true correlations and increases the necessary sample sizes for studies. © 2016 The Obesity Society.

  1. The Relatives' Big Five Personality Influences the Trajectories of Recovery of Patients After Severe TBI: A Multilevel Analysis.

    PubMed

    Haller, Chiara S

    2017-08-01

    This study examines the influence of the personality of relatives on the trajectories of recovery of patients with severe traumatic brain injury (TBI). The present subsample (N = 376) of a larger population-based, prospective, 12-month multicenter cohort study in Switzerland (2007-2011) consists of patients with severe TBI (age ≥ 16) and their relatives. The predictors are the NEO Five-Factor Inventory and time (trajectory of functioning of the patient over time). The outcomes are the patients' (a) neurological functioning; (b) reported emotional, interpersonal, cognitive, and total functioning post-injury; and (c) health-related quality of life (HRQoL). The covariates included Abbreviated Injury Scale score of the head region and age. Results for patients > 50 are (a) relatives' Extraversion influenced patients' total, interpersonal, and cognitive functioning; (b) relatives' Agreeableness influenced patients' interpersonal functioning; and (c) relatives' Conscientiousness influenced patients' physical HRQoL (ps < .05). Results for patients ≤ 50 are (a) relatives' Neuroticism influenced patients' neurological and emotional functioning, and (b) relatives' Extraversion influenced patients' emotional functioning and psychological HRQoL (ps < .05). The personality traits of the relative covary with the functioning of the patient, and psychological adaptation to the loss of function may progress at a later stage after physical health improvements have been achieved. Thus, a biopsychosocial perspective on the rehabilitation process is needed. © 2016 Wiley Periodicals, Inc.

  2. Mosaic analysis of gene function in postnatal mouse brain development by using virus-based Cre recombination.

    PubMed

    Gibson, Daniel A; Ma, Le

    2011-08-01

    Normal brain function relies not only on embryonic development when major neuronal pathways are established, but also on postnatal development when neural circuits are matured and refined. Misregulation at this stage may lead to neurological and psychiatric disorders such as autism and schizophrenia. Many genes have been studied in the prenatal brain and found crucial to many developmental processes. However, their function in the postnatal brain is largely unknown, partly because their deletion in mice often leads to lethality during neonatal development, and partly because their requirement in early development hampers the postnatal analysis. To overcome these obstacles, floxed alleles of these genes are currently being generated in mice. When combined with transgenic alleles that express Cre recombinase in specific cell types, conditional deletion can be achieved to study gene function in the postnatal brain. However, this method requires additional alleles and extra time (3-6 months) to generate the mice with appropriate genotypes, thereby limiting the expansion of the genetic analysis to a large scale in the mouse brain. Here we demonstrate a complementary approach that uses virally-expressed Cre to study these floxed alleles rapidly and systematically in postnatal brain development. By injecting recombinant adeno-associated viruses (rAAVs) encoding Cre into the neonatal brain, we are able to delete the gene of interest in different regions of the brain. By controlling the viral titer and coexpressing a fluorescent protein marker, we can simultaneously achieve mosaic gene inactivation and sparse neuronal labeling. This method bypasses the requirement of many genes in early development, and allows us to study their cell autonomous function in many critical processes in postnatal brain development, including axonal and dendritic growth, branching, and tiling, as well as synapse formation and refinement. This method has been used successfully in our own lab (unpublished results) and others, and can be extended to other viruses, such as lentivirus, as well as to the expression of shRNA or dominant active proteins. Furthermore, by combining this technique with electrophysiology as well as recently-developed optical imaging tools, this method provides a new strategy to study how genetic pathways influence neural circuit development and function in mice and rats.

  3. Contralesional homotopic activity negatively influences functional recovery after stroke (Conference Presentation)

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

    Recent fcMRI studies examining spontaneous brain activity after stoke have revealed disrupted global patterns of functional connectivity (FC). Interestingly, acute interhemispheric homotopic FC has been shown to be predictive of recovery potential. While substantial indirect evidence also suggests that homotopic brain activity may directly impact recovery, results in humans are extremely varied. A better understanding of how activity within networks functionally-connected to lesioned tissue influences brain plasticity might improve therapeutic strategies. We combine cell-type specific optogenetic targeting with optical intrinsic signal (OIS) imaging to assess the effects of homotopic contralesional activity (specifically in excitatory CamKIIa pyramidal neurons) on FC, cortical remapping, and behavior after stroke. Thirty-one mice were housed in enriched cages for the experiment. OIS imaging was performed before, 1, and 4 weeks after photothrombosis of left forepaw somatosensory cortex (S1fp). On day 1 after stroke, 17 mice were subjected to chronic, intermittent optical stimulation of right S1fp for 10 min, 5 days/week for 4 weeks. New cortical representations of left S1fp appeared in non-stimulated mice at week 1, but not in stimulated mice (p=0.005). Evoked responses were comparable in both groups at week 4 (p=0.57). Homotopic FC between left and right S1fp regions was equally reduced in both groups (p=0.012) at week 1. However, in non-stimulated mice, behavioral performance and FC between right S1fp and left perilesional S1 cortex was significantly higher by 4 weeks compared to stimulated mice (p=0.009). Our results suggest that increased homotopic, contralesional activity in excitatory neurons negatively influences spontaneous recovery following ischemic stroke.

  4. Sex Differences in Brain-Derived Neurotrophic Factor Signaling and Functions

    PubMed Central

    Chan, Chi Bun; Ye, Keqiang

    2016-01-01

    Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family that plays a critical role in numerous neuronal activities. Recent studies report that some functions or action mechanisms of BDNF vary in a sex-dependent manner. In particular, BDNF content in some brain parts and the tendency of developing BDNF-deficient-related diseases like depression is higher in female animals. With the support of other relevant studies, it is suggested that sex hormones or steroids can modulate the activities of BDNF, which may account for its functional discrepancy in different sexes. Indeed, the cross-talk between BDNF and sex steroids has been detected for decades and some sex steroids like estrogen have a positive regulatory effect to BDNF expression and signaling. Thus, the sex of animal models used is critical when studying the functions of BDNF in vivo. In this review, we will summarize our current findings on the difference in expression, signaling, and functions of BDNF between sexes. We will also discuss the potential mechanisms in mediating these differential responses with a specific emphasis on sex steroids. By presenting and discussing these findings, we encourage taking sex influences into consideration when designing experiments, interpreting results and drawing conclusions. PMID:27870419

  5. Multi-subject hierarchical inverse covariance modelling improves estimation of functional brain networks.

    PubMed

    Colclough, Giles L; Woolrich, Mark W; Harrison, Samuel J; Rojas López, Pedro A; Valdes-Sosa, Pedro A; Smith, Stephen M

    2018-05-07

    A Bayesian model for sparse, hierarchical, inver-covariance estimation is presented, and applied to multi-subject functional connectivity estimation in the human brain. It enables simultaneous inference of the strength of connectivity between brain regions at both subject and population level, and is applicable to fMRI, MEG and EEG data. Two versions of the model can encourage sparse connectivity, either using continuous priors to suppress irrelevant connections, or using an explicit description of the network structure to estimate the connection probability between each pair of regions. A large evaluation of this model, and thirteen methods that represent the state of the art of inverse covariance modelling, is conducted using both simulated and resting-state functional imaging datasets. Our novel Bayesian approach has similar performance to the best extant alternative, Ng et al.'s Sparse Group Gaussian Graphical Model algorithm, which also is based on a hierarchical structure. Using data from the Human Connectome Project, we show that these hierarchical models are able to reduce the measurement error in MEG beta-band functional networks by 10%, producing concomitant increases in estimates of the genetic influence on functional connectivity. Copyright © 2018. Published by Elsevier Inc.

  6. Mapping cortical hubs in tinnitus

    PubMed Central

    2009-01-01

    Background Subjective tinnitus is the perception of a sound in the absence of any physical source. It has been shown that tinnitus is associated with hyperactivity of the auditory cortices. Accompanying this hyperactivity, changes in non-auditory brain structures have also been reported. However, there have been no studies on the long-range information flow between these regions. Results Using Magnetoencephalography, we investigated the long-range cortical networks of chronic tinnitus sufferers (n = 23) and healthy controls (n = 24) in the resting state. A beamforming technique was applied to reconstruct the brain activity at source level and the directed functional coupling between all voxels was analyzed by means of Partial Directed Coherence. Within a cortical network, hubs are brain structures that either influence a great number of other brain regions or that are influenced by a great number of other brain regions. By mapping the cortical hubs in tinnitus and controls we report fundamental group differences in the global networks, mainly in the gamma frequency range. The prefrontal cortex, the orbitofrontal cortex and the parieto-occipital region were core structures in this network. The information flow from the global network to the temporal cortex correlated positively with the strength of tinnitus distress. Conclusion With the present study we suggest that the hyperactivity of the temporal cortices in tinnitus is integrated in a global network of long-range cortical connectivity. Top-down influence from the global network on the temporal areas relates to the subjective strength of the tinnitus distress. PMID:19930625

  7. The influence of context on hemispheric recruitment during metaphor processing

    PubMed Central

    Diaz, Michele T.; Hogstrom, Larson J.

    2011-01-01

    Although the left hemisphere's prominence in language is well established, less emphasis has been placed on possible roles for the right hemisphere. Behavioral, patient, and neuroimaging research suggests that the right hemisphere may be involved in processing figurative language. Additionally, research has demonstrated that context can modify language processes and facilitate comprehension. Here we investigated how figurativeness and context influenced brain activation, with a specific interest in right hemisphere function. Previous work in our lab indicated that novel stimuli engaged right inferior frontal gyrus and that both novel and familiar metaphors engaged right inferior frontal gyrus and right temporal pole. The Graded Salience Hypothesis (GSH) proposes that context may lessen integration demands, increase the salience of metaphors, and thereby reduce right hemisphere recruitment for metaphors. In the present study, functional Magnetic Resonance Imaging was used to investigate brain function while participants read literal and metaphoric sentences that were preceded by either a congruent or an incongruent literal sentence. Consistent with prior research, all sentences engaged traditional left hemisphere regions. Differences between metaphors and literal sentences were observed, but only in the left hemisphere. In contrast, a main effect of congruence was found in right inferior frontal gyrus, right temporal pole, and dorsal medial prefrontal cortex. Partially consistent with the GSH, our results highlight the strong influence of context on language, demonstrate the importance of the right hemisphere in discourse, and suggest that in a wider discourse context congruence has a greater influence on right hemisphere recruitment than figurativeness. PMID:21568642

  8. The microbiota-gut-brain axis as a key regulator of neural function and the stress response: Implications for human and animal health.

    PubMed

    Wiley, N C; Dinan, T G; Ross, R P; Stanton, C; Clarke, G; Cryan, J F

    2017-07-01

    The brain-gut-microbiota axis comprises an extensive communication network between the brain, the gut, and the microbiota residing there. Development of a diverse gut microbiota is vital for multiple features of behavior and physiology, as well as many fundamental aspects of brain structure and function. Appropriate early-life assembly of the gut microbiota is also believed to play a role in subsequent emotional and cognitive development. If the composition, diversity, or assembly of the gut microbiota is impaired, this impairment can have a negative impact on host health and lead to disorders such as obesity, diabetes, inflammatory diseases, and even potentially neuropsychiatric illnesses, including anxiety and depression. Therefore, much research effort in recent years has focused on understanding the potential of targeting the intestinal microbiota to prevent and treat such disorders. This review aims to explore the influence of the gut microbiota on host neural function and behavior, particularly those of relevance to stress-related disorders. The involvement of microbiota in diverse neural functions such as myelination, microglia function, neuronal morphology, and blood-brain barrier integrity across the life span, from early life to adolescence to old age, will also be discussed. Nurturing an optimal gut microbiome may also prove beneficial in animal science as a means to manage stressful situations and to increase productivity of farm animals. The implications of these observations are manifold, and researchers are hopeful that this promising body of preclinical work can be successfully translated to the clinic and beyond.

  9. Functional and clinical neuroanatomy of morality.

    PubMed

    Fumagalli, Manuela; Priori, Alberto

    2012-07-01

    Morality is among the most sophisticated features of human judgement, behaviour and, ultimately, mind. An individual who behaves immorally may violate ethical rules and civil rights, and may threaten others' individual liberty, sometimes becoming violent and aggressive. In recent years, neuroscience has shown a growing interest in human morality, and has advanced our understanding of the cognitive and emotional processes involved in moral decisions, their anatomical substrates and the neurology of abnormal moral behaviour. In this article, we review research findings that have provided a key insight into the functional and clinical neuroanatomy of the brain areas involved in normal and abnormal moral behaviour. The 'moral brain' consists of a large functional network including both cortical and subcortical anatomical structures. Because morality is a complex process, some of these brain structures share their neural circuits with those controlling other behavioural processes, such as emotions and theory of mind. Among the anatomical structures implicated in morality are the frontal, temporal and cingulate cortices. The prefrontal cortex regulates activity in subcortical emotional centres, planning and supervising moral decisions, and when its functionality is altered may lead to impulsive aggression. The temporal lobe is involved in theory of mind and its dysfunction is often implicated in violent psychopathy. The cingulate cortex mediates the conflict between the emotional and the rational components of moral reasoning. Other important structures contributing to moral behaviour include the subcortical nuclei such as the amygdala, hippocampus and basal ganglia. Brain areas participating in moral processing can be influenced also by genetic, endocrine and environmental factors. Hormones can modulate moral behaviour through their effects on the brain. Finally, genetic polymorphisms can predispose to aggressivity and violence, arguing for a genetic-based predisposition to morality. Because abnormal moral behaviour can arise from both functional and structural brain abnormalities that should be diagnosed and treated, the neurology of moral behaviour has potential implications for clinical practice and raises ethical concerns. Last, since research has developed several neuromodulation techniques to improve brain dysfunction (deep brain stimulation, transcranial magnetic stimulation and transcranial direct current stimulation), knowing more about the 'moral brain' might help to develop novel therapeutic strategies for neurologically based abnormal moral behaviour.

  10. When Neuroscience ‘Touches’ Architecture: From Hapticity to a Supramodal Functioning of the Human Brain

    PubMed Central

    Papale, Paolo; Chiesi, Leonardo; Rampinini, Alessandra C.; Pietrini, Pietro; Ricciardi, Emiliano

    2016-01-01

    In the last decades, the rapid growth of functional brain imaging methodologies allowed cognitive neuroscience to address open questions in philosophy and social sciences. At the same time, novel insights from cognitive neuroscience research have begun to influence various disciplines, leading to a turn to cognition and emotion in the fields of planning and architectural design. Since 2003, the Academy of Neuroscience for Architecture has been supporting ‘neuro-architecture’ as a way to connect neuroscience and the study of behavioral responses to the built environment. Among the many topics related to multisensory perceptual integration and embodiment, the concept of hapticity was recently introduced, suggesting a pivotal role of tactile perception and haptic imagery in architectural appraisal. Arguments have thus risen in favor of the existence of shared cognitive foundations between hapticity and the supramodal functional architecture of the human brain. Precisely, supramodality refers to the functional feature of defined brain regions to process and represent specific information content in a more abstract way, independently of the sensory modality conveying such information to the brain. Here, we highlight some commonalities and differences between the concepts of hapticity and supramodality according to the distinctive perspectives of architecture and cognitive neuroscience. This comparison and connection between these two different approaches may lead to novel observations in regard to people–environment relationships, and even provide empirical foundations for a renewed evidence-based design theory. PMID:27375542

  11. Surveillance, Phagocytosis, and Inflammation: How Never-Resting Microglia Influence Adult Hippocampal Neurogenesis

    PubMed Central

    Sierra, Amanda; Beccari, Sol; Diaz-Aparicio, Irune; Encinas, Juan M.; Comeau, Samuel; Tremblay, Marie-Ève

    2014-01-01

    Microglia cells are the major orchestrator of the brain inflammatory response. As such, they are traditionally studied in various contexts of trauma, injury, and disease, where they are well-known for regulating a wide range of physiological processes by their release of proinflammatory cytokines, reactive oxygen species, and trophic factors, among other crucial mediators. In the last few years, however, this classical view of microglia was challenged by a series of discoveries showing their active and positive contribution to normal brain functions. In light of these discoveries, surveillant microglia are now emerging as an important effector of cellular plasticity in the healthy brain, alongside astrocytes and other types of inflammatory cells. Here, we will review the roles of microglia in adult hippocampal neurogenesis and their regulation by inflammation during chronic stress, aging, and neurodegenerative diseases, with a particular emphasis on their underlying molecular mechanisms and their functional consequences for learning and memory. PMID:24772353

  12. The Benefits of Exercise and Metabolic Interventions for the Prevention and Early Treatment of Alzheimer's Disease.

    PubMed

    Maliszewska-Cyna, Ewelina; Lynch, Madelaine; Oore, Jonathan Jordan; Nagy, Paul Michael; Aubert, Isabelle

    2017-01-01

    Alzheimer's disease (AD) is characterized by neuronal degeneration, vascular pathology and cognitive decline. Furthermore, deficits in cerebral glucose metabolism and insulin resistance are being increasingly recognized in AD. Many lifestyle-modifying approaches, including diet and exercise, have yielded promising results in modulating brain morphology and function for the prevention and early treatment of AD. This review focuses on the effects of physical exercise on rescuing cognition and limiting the progression of AD pathology. Specifically, the impact of exercise, in human and animal models of AD, on the stimulation and preservation of cognition, neurotransmission, neurogenesis, vasculature, glucose metabolism and insulin signaling is discussed. Studies have highlighted the potential of physical activity to improve overall brain health, which could delay or lessen AD-related cognitive deficits and pathology. Physical activity influences cognitive function, vascular health and brain metabolism, which taken together offers benefits for the aging population, including AD patients.

  13. p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development

    PubMed Central

    Contreras, Esteban G.; Sierralta, Jimena

    2018-01-01

    Background Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called ‘brain sparing’. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. Results Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. Conclusions Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals. PMID:29621246

  14. p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development.

    PubMed

    Contreras, Esteban G; Sierralta, Jimena; Glavic, Alvaro

    2018-01-01

    Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called 'brain sparing'. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals.

  15. Polygenic risk for depression and the neural correlates of working memory in healthy subjects.

    PubMed

    Yüksel, Dilara; Dietsche, Bruno; Forstner, Andreas J; Witt, Stephanie H; Maier, Robert; Rietschel, Marcella; Konrad, Carsten; Nöthen, Markus M; Dannlowski, Udo; Baune, Bernhard T; Kircher, Tilo; Krug, Axel

    2017-10-03

    Major depressive disorder (MDD) patients show impairments of cognitive functioning such as working memory (WM), and furthermore alterations during WM-fMRI tasks especially in frontal and parietal brain regions. The calculation of a polygenic risk score (PRS) can be used to describe the genetic influence on MDD, hence imaging genetic studies aspire to combine both genetics and neuroimaging data to identify the influence of genetic factors on brain functioning. We aimed to detect the effect of MDD-PRS on brain activation during a WM task measured with fMRI and expect healthy individuals with a higher PRS to be more resembling to MDD patients. In total, n=137 (80 men, 57 women, aged 34.5, SD=10.4years) healthy subjects performed a WM n-back task [0-back (baseline), 2-back and 3-back condition] in a 3T-MRI-tomograph. The sample was genotyped using the Infinium PsychArray BeadChip and a polygenic risk score was calculated for MDD using PGC MDD GWAS results. A lower MDD risk score was associated with increased activation in the bilateral middle occipital gyri (MOG), the bilateral middle frontal gyri (MFG) and the right precentral gyrus (PCG) during the 2-back vs. baseline condition. Moreover, a lower PRS was associated with increased brain activation during the 3-back vs. baseline condition in the bilateral cerebellum, the right MFG and the left inferior parietal lobule. A higher polygenic risk score was associated with hyperactivation in brain regions comprising the right MFG and the right supplementary motor area during the 3-back vs. 2-back condition. The results suggest that part of the WM-related brain activation patterns might be explained by genetic variants captured by the MDD-PRS. Furthermore we were able to detect MDD-associated activation patterns in healthy individuals depending on the MDD-PRS and the task complexity. Additional gene loci could contribute to these task-dependent brain activation patterns. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Identification of Genetic Loci Jointly Influencing Schizophrenia Risk and the Cognitive Traits of Verbal-Numerical Reasoning, Reaction Time, and General Cognitive Function.

    PubMed

    Smeland, Olav B; Frei, Oleksandr; Kauppi, Karolina; Hill, W David; Li, Wen; Wang, Yunpeng; Krull, Florian; Bettella, Francesco; Eriksen, Jon A; Witoelar, Aree; Davies, Gail; Fan, Chun C; Thompson, Wesley K; Lam, Max; Lencz, Todd; Chen, Chi-Hua; Ueland, Torill; Jönsson, Erik G; Djurovic, Srdjan; Deary, Ian J; Dale, Anders M; Andreassen, Ole A

    2017-10-01

    Schizophrenia is associated with widespread cognitive impairments. Although cognitive deficits are one of the factors most strongly associated with functional outcome in schizophrenia, current treatment strategies largely fail to ameliorate these impairments. To develop more efficient treatment strategies in patients with schizophrenia, a better understanding of the pathogenesis of these cognitive deficits is needed. Accumulating evidence indicates that genetic risk of schizophrenia may contribute to cognitive dysfunction. To identify genomic regions jointly influencing schizophrenia and the cognitive domains of reaction time and verbal-numerical reasoning, as well as general cognitive function, a phenotype that captures the shared variation in performance across cognitive domains. Combining data from genome-wide association studies from multiple phenotypes using conditional false discovery rate analysis provides increased power to discover genetic variants and could elucidate shared molecular genetic mechanisms. Data from the following genome-wide association studies, published from July 24, 2014, to January 17, 2017, were combined: schizophrenia in the Psychiatric Genomics Consortium cohort (n = 79 757 [cases, 34 486; controls, 45 271]); verbal-numerical reasoning (n = 36 035) and reaction time (n = 111 483) in the UK Biobank cohort; and general cognitive function in CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) (n = 53 949) and COGENT (Cognitive Genomics Consortium) (n = 27 888). Genetic loci identified by conditional false discovery rate analysis. Brain messenger RNA expression and brain expression quantitative trait locus functionality were determined. Among the participants in the genome-wide association studies, 21 loci jointly influencing schizophrenia and cognitive traits were identified: 2 loci shared between schizophrenia and verbal-numerical reasoning, 6 loci shared between schizophrenia and reaction time, and 14 loci shared between schizophrenia and general cognitive function. One locus was shared between schizophrenia and 2 cognitive traits and represented the strongest shared signal detected (nearest gene TCF20; chromosome 22q13.2), and was shared between schizophrenia (z score, 5.01; P = 5.53 × 10-7), general cognitive function (z score, -4.43; P = 9.42 × 10-6), and verbal-numerical reasoning (z score, -5.43; P = 5.64 × 10-8). For 18 loci, schizophrenia risk alleles were associated with poorer cognitive performance. The implicated genes are expressed in the developmental and adult human brain. Replicable expression quantitative trait locus functionality was identified for 4 loci in the adult human brain. The discovered loci improve the understanding of the common genetic basis underlying schizophrenia and cognitive function, suggesting novel molecular genetic mechanisms.

  17. Teaching About "Brain and Learning" in High School Biology Classes: Effects on Teachers' Knowledge and Students' Theory of Intelligence.

    PubMed

    Dekker, Sanne; Jolles, Jelle

    2015-01-01

    This study evaluated a new teaching module about "Brain and Learning" using a controlled design. The module was implemented in high school biology classes and comprised three lessons: (1) brain processes underlying learning; (2) neuropsychological development during adolescence; and (3) lifestyle factors that influence learning performance. Participants were 32 biology teachers who were interested in "Brain and Learning" and 1241 students in grades 8-9. Teachers' knowledge and students' beliefs about learning potential were examined using online questionnaires. Results indicated that before intervention, biology teachers were significantly less familiar with how the brain functions and develops than with its structure and with basic neuroscientific concepts (46 vs. 75% correct answers). After intervention, teachers' knowledge of "Brain and Learning" had significantly increased (64%), and more students believed that intelligence is malleable (incremental theory). This emphasizes the potential value of a short teaching module, both for improving biology teachers' insights into "Brain and Learning," and for changing students' beliefs about intelligence.

  18. Brain dynamics of post-task resting state are influenced by expertise: Insights from baseball players.

    PubMed

    Muraskin, Jordan; Dodhia, Sonam; Lieberman, Gregory; Garcia, Javier O; Verstynen, Timothy; Vettel, Jean M; Sherwin, Jason; Sajda, Paul

    2016-12-01

    Post-task resting state dynamics can be viewed as a task-driven state where behavioral performance is improved through endogenous, non-explicit learning. Tasks that have intrinsic value for individuals are hypothesized to produce post-task resting state dynamics that promote learning. We measured simultaneous fMRI/EEG and DTI in Division-1 collegiate baseball players and compared to a group of controls, examining differences in both functional and structural connectivity. Participants performed a surrogate baseball pitch Go/No-Go task before a resting state scan, and we compared post-task resting state connectivity using a seed-based analysis from the supplementary motor area (SMA), an area whose activity discriminated players and controls in our previous results using this task. Although both groups were equally trained on the task, the experts showed differential activity in their post-task resting state consistent with motor learning. Specifically, we found (1) differences in bilateral SMA-L Insula functional connectivity between experts and controls that may reflect group differences in motor learning, (2) differences in BOLD-alpha oscillation correlations between groups suggests variability in modulatory attention in the post-task state, and (3) group differences between BOLD-beta oscillations that may indicate cognitive processing of motor inhibition. Structural connectivity analysis identified group differences in portions of the functionally derived network, suggesting that functional differences may also partially arise from variability in the underlying white matter pathways. Generally, we find that brain dynamics in the post-task resting state differ as a function of subject expertise and potentially result from differences in both functional and structural connectivity. Hum Brain Mapp 37:4454-4471, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  19. Relationship between cardiac function and resting cerebral blood flow: MRI measurements in healthy elderly subjects.

    PubMed

    Henriksen, Otto M; Jensen, Lars T; Krabbe, Katja; Larsson, Henrik B W; Rostrup, Egill

    2014-11-01

    Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43.6 ml per 100 g min(-1), 5.5 l min(-1) and 2.7 l min(-1) m(-2), respectively, in males, and 53.4 ml per 100 g min(-1), 4.3 l min(-1) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender-related inverse association of increased low-to-high-frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender-related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  20. A call for comparative effectiveness research to learn whether routine clinical care decisions can protect from dementia and cognitive decline.

    PubMed

    Dacks, Penny A; Armstrong, Joshua J; Brannan, Stephen K; Carman, Aaron J; Green, Allan M; Kirkman, M Sue; Krakoff, Lawrence R; Kuller, Lewis H; Launer, Lenore J; Lovestone, Simon; Merikle, Elizabeth; Neumann, Peter J; Rockwood, Kenneth; Shineman, Diana W; Stefanacci, Richard G; Velentgas, Priscilla; Viswanathan, Anand; Whitmer, Rachel A; Williamson, Jeff D; Fillit, Howard M

    2016-08-20

    Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer's and other dementia. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer's Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia.

  1. Academic stress and personality interact to increase the neural response to high-calorie food cues.

    PubMed

    Neseliler, Selin; Tannenbaum, Beth; Zacchia, Maria; Larcher, Kevin; Coulter, Kirsty; Lamarche, Marie; Marliss, Errol B; Pruessner, Jens; Dagher, Alain

    2017-09-01

    Psychosocial stress is associated with an increased intake of palatable foods and weight gain in stress-reactive individuals. Personality traits have been shown to predict stress-reactivity. However, it is not known if personality traits influence brain activity in regions implicated in appetite control during psychosocial stress. The current study assessed whether Gray's Behavioural Inhibition System (BIS) scale, a measure of stress-reactivity, was related to the activity of brain regions implicated in appetite control during a stressful period. Twenty-two undergraduate students participated in a functional magnetic resonance imaging (fMRI) experiment once during a non-exam period and once during final exams in a counter-balanced order. In the scanner, they viewed food and scenery pictures. In the exam compared with the non-exam condition, BIS scores related to increased perceived stress and correlated with increased blood-oxygen-level dependent (BOLD) response to high-calorie food images in regions implicated in food reward and subjective value, such as the ventromedial prefrontal cortex, (vmPFC) and the amygdala. BIS scores negatively related to the functional connectivity between the vmPFC and the dorsolateral prefrontal cortex. The results demonstrate that the BIS trait influences stress reactivity. This is observed both as an increased activity in brain regions implicated in computing the value of food cues and decreased connectivity of these regions to prefrontal regions implicated in self-control. This suggests that the effects of real life stress on appetitive brain function and self-control is modulated by a personality trait. This may help to explain why stressful periods can lead to overeating in vulnerable individuals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. NOS1 ex1f-VNTR polymorphism influences prefrontal brain oxygenation during a working memory task.

    PubMed

    Kopf, Juliane; Schecklmann, Martin; Hahn, Tim; Dresler, Thomas; Dieler, Alica C; Herrmann, Martin J; Fallgatter, Andreas J; Reif, Andreas

    2011-08-15

    Nitric oxide (NO) synthase produces NO, which serves as first and second messenger in neurons, where the protein is encoded by the NOS1 gene. A functional variable number of tandem repeats (VNTR) polymorphism in the promoter region of the alternative first exon 1f of NOS1 is associated with various functions of human behavior, for example increased impulsivity, while another, non-functional variant was linked to decreased verbal working memory and a heightened risk for schizophrenia. We therefore investigated the influence of NOS1 ex 1f-VNTR on working memory function as reflected by both behavioral measures and prefrontal oxygenation. We hypothesized that homozygous short allele carriers exhibit altered brain oxygenation in task-related areas, namely the dorsolateral and ventrolateral prefrontal cortex and the parietal cortex. To this end, 56 healthy subjects were stratified into a homozygous long allele group and a homozygous short allele group comparable for age, sex and intelligence. All subjects completed a letter n-back task (one-, two-, and three-back), while concentration changes of oxygenated (O(2)Hb) hemoglobin in the prefrontal cortex were measured with functional near-infrared spectroscopy (fNIRS). We found load-associated O(2)Hb increases in the prefrontal and parts of the parietal cortex. Significant load-associated oxygenation differences between the two genotype groups could be shown for the dorsolateral prefrontal cortex and the parietal cortex. Specifically, short allele carriers showed a significantly larger increase in oxygenation in all three n-back tasks. This suggests a potential compensatory mechanism, with task-related brain regions being more active in short allele carriers to compensate for reduced NOS1 expression. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Brain Activation during Addition and Subtraction Tasks In-Noise and In-Quiet

    PubMed Central

    Abd Hamid, Aini Ismafairus; Yusoff, Ahmad Nazlim; Mukari, Siti Zamratol-Mai Sarah; Mohamad, Mazlyfarina

    2011-01-01

    Background: In spite of extensive research conducted to study how human brain works, little is known about a special function of the brain that stores and manipulates information—the working memory—and how noise influences this special ability. In this study, Functional magnetic resonance imaging (fMRI) was used to investigate brain responses to arithmetic problems solved in noisy and quiet backgrounds. Methods: Eighteen healthy young males performed simple arithmetic operations of addition and subtraction with in-quiet and in-noise backgrounds. The MATLAB-based Statistical Parametric Mapping (SPM8) was implemented on the fMRI datasets to generate and analyse the activated brain regions. Results: Group results showed that addition and subtraction operations evoked extended activation in the left inferior parietal lobe, left precentral gyrus, left superior parietal lobe, left supramarginal gyrus, and left middle temporal gyrus. This supported the hypothesis that the human brain relatively activates its left hemisphere more compared with the right hemisphere when solving arithmetic problems. The insula, middle cingulate cortex, and middle frontal gyrus, however, showed more extended right hemispheric activation, potentially due to the involvement of attention, executive processes, and working memory. For addition operations, there was extensive left hemispheric activation in the superior temporal gyrus, inferior frontal gyrus, and thalamus. In contrast, subtraction tasks evoked a greater activation of similar brain structures in the right hemisphere. For both addition and subtraction operations, the total number of activated voxels was higher for in-noise than in-quiet conditions. Conclusion: These findings suggest that when arithmetic operations were delivered auditorily, the auditory, attention, and working memory functions were required to accomplish the executive processing of the mathematical calculation. The respective brain activation patterns appear to be modulated by the noisy background condition. PMID:22135581

  4. Macrostructural and Microstructural Brain Lesions Relate to Gait Pathology in Children With Cerebral Palsy.

    PubMed

    Meyns, Pieter; Van Gestel, Leen; Leunissen, Inge; De Cock, Paul; Sunaert, Stefan; Feys, Hilde; Duysens, Jacques; Desloovere, Kaat; Ortibus, Els

    2016-10-01

    Background Even though lower-limb motor disorders are core features of spastic cerebral palsy (sCP), the relationship with brain lesions remains unclear. Unraveling the relation between gait pathology, lower-limb function, and brain lesions in sCP is complex for several reasons; wide heterogeneity in brain lesions, ongoing brain maturation, and gait depends on a number of primary motor functions/deficits (eg, muscle strength, spasticity). Objective To use a comprehensive approach combining conventional MRI and diffusion tensor imaging (DTI) in children with sCP above 3 years old to relate quantitative parameters of brain lesions in multiple brain areas to gait performance. Methods A total of 50 children with sCP (25 bilateral, 25 unilateral involvement) were enrolled. The investigated neuroradiological parameters included the following: (1) volumetric measures of the corpus callosum (CC) and lateral ventricles (LVs), and (2) DTI parameters of the corticospinal tract (CST). Gait pathology and primary motor deficits, including muscle strength and spasticity, were evaluated by 3D gait analysis and clinical examination. Results In bilateral sCP (n = 25), volume of the LV and the subparts of the CC connecting frontal, (pre)motor, and sensory areas were most related to lower-limb functioning and gait pathology. DTI measures of the CST revealed additional relations with the primary motor deficits (n = 13). In contrast, in unilateral sCP, volumetric (n = 25) and diffusion measures (n = 14) were only correlated to lower-limb strength. Conclusions These results indicate that the combined influence of multiple brain lesions and their impact on the primary motor deficits might explain a large part of the gait pathology in sCP. © The Author(s) 2016.

  5. An exercise-based randomized controlled trial on brain, cognition, physical health and mental health in overweight/obese children (ActiveBrains project): Rationale, design and methods.

    PubMed

    Cadenas-Sánchez, Cristina; Mora-González, José; Migueles, Jairo H; Martín-Matillas, Miguel; Gómez-Vida, José; Escolano-Margarit, María Victoria; Maldonado, José; Enriquez, Gala María; Pastor-Villaescusa, Belén; de Teresa, Carlos; Navarrete, Socorro; Lozano, Rosa María; de Dios Beas-Jiménez, Juan; Estévez-López, Fernando; Mena-Molina, Alejandra; Heras, María José; Chillón, Palma; Campoy, Cristina; Muñoz-Hernández, Victoria; Martínez-Ávila, Wendy Daniela; Merchan, María Elisa; Perales, José C; Gil, Ángel; Verdejo-García, Antonio; Aguilera, Concepción M; Ruiz, Jonatan R; Labayen, Idoia; Catena, Andrés; Ortega, Francisco B

    2016-03-01

    The new and recent advances in neuroelectric and neuroimaging technologies provide a new era for further exploring and understanding how brain and cognition function can be stimulated by environmental factors, such as exercise, and particularly to study whether physical exercise influences brain development in early ages. The present study, namely the ActiveBrains project, aims to examine the effects of a physical exercise programme on brain and cognition, as well as on selected physical and mental health outcomes in overweight/obese children. A total of 100 participants aged 8 to 11 years are randomized into an exercise group (N=50) or a control group (N=50). The intervention lasts 20-weeks, with 3-5 sessions per week of 90 min each, and is mainly focused on high-intensity aerobic exercise yet also includes muscle-strengthening exercises. The extent to what the intervention effect remains 8-months after the exercise programme finishes is also studied in a subsample. Brain structure and function and cognitive performance are assessed using structural and functional magnetic resonance imaging and electroencephalographic recordings. Secondary outcomes include physical health outcomes (e.g. physical fitness, body fatness, bone mass and lipid-metabolic factors) and mental health outcomes (e.g. chronic stress indicators and overall behavioural and personality measurements such as anxiety or depression). This project will substantially contribute to the existing knowledge and will have an impact on societies, since early stimulation of brain development might have long lasting consequences on cognitive performance, academic achievement and in the prevention of behavioural problems and the promotion of psychological adjustment and mental health. Clinical trials. Gov identifier: NCT02295072. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Disruptions in Functional Network Connectivity during Alcohol Intoxicated Driving

    PubMed Central

    Rzepecki-Smith, Catherine I.; Meda, Shashwath A.; Calhoun, Vince D.; Stevens, Michael C.; Jafri, Madiha J.; Astur, Robert S.; Pearlson, Godfrey D.

    2009-01-01

    Background: Driving while under the influence of alcohol is a major public health problem whose neural basis is not well understood. In a recently published fMRI study (Meda et al, 2009), our group identified five, independent critical driving-associated brain circuits whose inter-regional connectivity was disrupted by alcohol intoxication. However, the functional connectivity between these circuits has not yet been explored in order to determine how these networks communicate with each other during sober and alcohol-intoxicated states. Methods: In the current study, we explored such differences in connections between the above brain circuits and driving behavior, under the influence of alcohol versus placebo. Forty social drinkers who drove regularly underwent fMRI scans during virtual reality driving simulations following two alcohol doses, placebo and an individualized dose producing blood alcohol concentrations (BACs) of 0.10%. Results: At the active dose, we found specific disruptions of functional network connectivity between the frontal-temporal-basal ganglia and the cerebellar circuits. The temporal connectivity between these two circuits was found to be less correlated (p <0.05) when driving under the influence of alcohol. This disconnection was also associated with an abnormal driving behavior (unstable motor vehicle steering). Conclusions: Connections between frontal-temporal-basal ganglia and cerebellum have recently been explored; these may be responsible in part for maintaining normal motor behavior by integrating their overlapping motor control functions. These connections appear to be disrupted by alcohol intoxication, in turn associated with an explicit type of impaired driving behavior. PMID:20028354

  7. Mitigation of stress: new treatment alternatives.

    PubMed

    Subhani, Ahmad Rauf; Kamel, Nidal; Mohamad Saad, Mohamad Naufal; Nandagopal, Nanda; Kang, Kenneth; Malik, Aamir Saeed

    2018-02-01

    Complaints of stress are common in modern life. Psychological stress is a major cause of lifestyle-related issues, contributing to poor quality of life. Chronic stress impedes brain function, causing impairment of many executive functions, including working memory, decision making and attentional control. The current study sought to describe newly developed stress mitigation techniques, and their influence on autonomic and endocrine functions. The literature search revealed that the most frequently studied technique for stress mitigation was biofeedback (BFB). However, evidence suggests that neurofeedback (NFB) and noninvasive brain stimulation (NIBS) could potentially provide appropriate approaches. We found that recent studies of BFB methods have typically used measures of heart rate variability, respiration and skin conductance. In contrast, studies of NFB methods have typically utilized neurocomputation techniques employing electroencephalography, functional magnetic resonance imaging and near infrared spectroscopy. NIBS studies have typically utilized transcranial direct current stimulation methods. Mitigation of stress is a challenging but important research target for improving quality of life.

  8. Risk-Taking Behavior in a Computerized Driving Task: Brain Activation Correlates of Decision-Making, Outcome, and Peer Influence in Male Adolescents.

    PubMed

    Vorobyev, Victor; Kwon, Myoung Soo; Moe, Dagfinn; Parkkola, Riitta; Hämäläinen, Heikki

    2015-01-01

    Increased propensity for risky behavior in adolescents, particularly in peer groups, is thought to reflect maturational imbalance between reward processing and cognitive control systems that affect decision-making. We used functional magnetic resonance imaging (fMRI) to investigate brain functional correlates of risk-taking behavior and effects of peer influence in 18-19-year-old male adolescents. The subjects were divided into low and high risk-taking groups using either personality tests or risk-taking rates in a simulated driving task. The fMRI data were analyzed for decision-making (whether to take a risk at intersections) and outcome (pass or crash) phases, and for the influence of peer competition. Personality test-based groups showed no difference in the amount of risk-taking (similarly increased during peer competition) and brain activation. When groups were defined by actual task performance, risk-taking activated two areas in the left medial prefrontal cortex (PFC) significantly more in low than in high risk-takers. In the entire sample, risky decision-specific activation was found in the anterior and dorsal cingulate, superior parietal cortex, basal ganglia (including the nucleus accumbens), midbrain, thalamus, and hypothalamus. Peer competition increased outcome-related activation in the right caudate head and cerebellar vermis in the entire sample. Our results suggest that the activation of the medial (rather than lateral) PFC and striatum is most specific to risk-taking behavior of male adolescents in a simulated driving situation, and reflect a stronger conflict and thus increased cognitive effort to take risks in low risk-takers, and reward anticipation for risky decisions, respectively. The activation of the caudate nucleus, particularly for the positive outcome (pass) during peer competition, further suggests enhanced reward processing of risk-taking under peer influence.

  9. Neural Correlates of Social Influence Among Cannabis Users.

    PubMed

    Gilman, Jodi M

    2017-06-01

    Although peer influence is an important factor in the initiation and maintenance of cannabis use, few studies have investigated the neural correlates of peer influence among cannabis users. The current review summarizes research on the neuroscience of social influence in cannabis users, with the goal of highlighting gaps in the literature and the need for future research. Brain regions underlying peer influence may function differently in cannabis users. Compared to non-using controls, regions of the brain underlying reward, such as the striatum, show greater connectivity with frontal regions, and also show hyperactivity when participants are presented with peer information. Other subcortical regions, such as the insula, show hypoactivation during social exclusion in cannabis users, indicating that neural responses to peer interactions may be altered in cannabis users. Although neuroscience is increasingly being used to study social behavior, few studies have specifically focused on cannabis use, and therefore it is difficult to draw conclusions about social mechanisms that may differentiate cannabis users and controls. This area of research may be a promising avenue in which to explore a critical factor underlying cannabis use and addiction.

  10. Stem cells for brain repair in neonatal hypoxia-ischemia.

    PubMed

    Chicha, L; Smith, T; Guzman, R

    2014-01-01

    Neonatal hypoxic-ischemic insults are a significant cause of pediatric encephalopathy, developmental delays, and spastic cerebral palsy. Although the developing brain's plasticity allows for remarkable self-repair, severe disruption of normal myelination and cortical development upon neonatal brain injury are likely to generate life-persisting sensory-motor and cognitive deficits in the growing child. Currently, no treatments are available that can address the long-term consequences. Thus, regenerative medicine appears as a promising avenue to help restore normal developmental processes in affected infants. Stem cell therapy has proven effective in promoting functional recovery in animal models of neonatal hypoxic-ischemic injury and therefore represents a hopeful therapy for this unmet medical condition. Neural stem cells derived from pluripotent stem cells or fetal tissues as well as umbilical cord blood and mesenchymal stem cells have all shown initial success in improving functional outcomes. However, much still remains to be understood about how those stem cells can safely be administered to infants and what their repair mechanisms in the brain are. In this review, we discuss updated research into pathophysiological mechanisms of neonatal brain injury, the types of stem cell therapies currently being tested in this context, and the potential mechanisms through which exogenous stem cells might interact with and influence the developing brain.

  11. Healthy Aging Promotion through Neuroscientific Information-Based Strategies.

    PubMed

    Seinfeld, Sofia; Sanchez-Vives, Maria V

    2015-09-28

    To ensure the well-being of a rapidly growing elderly population, it is fundamental to find strategies to foster healthy brain aging. With this intention, we designed a program of scientific-based lectures aimed at dissemination by established neuroscientists about brain function, brain plasticity and how lifestyle influences the brain. We also carried out a pilot study on the impact of the lectures on attendees. The objective was to provide information to elderly people in order to encourage them to identify unhealthy and healthy daily habits, and more importantly, to promote behavioral changes towards healthy brain aging. Here we report on our experience. In order to determine the impact of the lectures in the daily routine of the attendees, we asked them to fill out questionnaires. Preliminary results indicate that neuroscientific information-based strategies can be a useful method to have a positive impact on the lives of elderly, increase their awareness on how to improve brain function and promote positive lifestyle modifications. Furthermore, based on self-reported data, we also found that through this strategy it is possible to promote behavioral changes related to nutrition, sleep, and realization of physical and cognitively stimulating activities. Finally, based on the results obtained, the importance of promoting self-efficacy and the empowerment of the older populations is highlighted.

  12. Healthy Aging Promotion through Neuroscientific Information-Based Strategies

    PubMed Central

    Seinfeld, Sofia; Sanchez-Vives, Maria V.

    2015-01-01

    To ensure the well-being of a rapidly growing elderly population, it is fundamental to find strategies to foster healthy brain aging. With this intention, we designed a program of scientific-based lectures aimed at dissemination by established neuroscientists about brain function, brain plasticity and how lifestyle influences the brain. We also carried out a pilot study on the impact of the lectures on attendees. The objective was to provide information to elderly people in order to encourage them to identify unhealthy and healthy daily habits, and more importantly, to promote behavioral changes towards healthy brain aging. Here we report on our experience. In order to determine the impact of the lectures in the daily routine of the attendees, we asked them to fill out questionnaires. Preliminary results indicate that neuroscientific information-based strategies can be a useful method to have a positive impact on the lives of elderly, increase their awareness on how to improve brain function and promote positive lifestyle modifications. Furthermore, based on self-reported data, we also found that through this strategy it is possible to promote behavioral changes related to nutrition, sleep, and realization of physical and cognitively stimulating activities. Finally, based on the results obtained, the importance of promoting self-efficacy and the empowerment of the older populations is highlighted. PMID:26426029

  13. Growing up in a Bubble: Using Germ-Free Animals to Assess the Influence of the Gut Microbiota on Brain and Behavior

    PubMed Central

    Luczynski, Pauline; McVey Neufeld, Karen-Anne; Oriach, Clara Seira; Clarke, Gerard; Dinan, Timothy G.

    2016-01-01

    There is a growing recognition of the importance of the commensal intestinal microbiota in the development and later function of the central nervous system. Research using germ-free mice (mice raised without any exposure to microorganisms) has provided some of the most persuasive evidence for a role of these bacteria in gut-brain signalling. Key findings show that the microbiota is necessary for normal stress responsivity, anxiety-like behaviors, sociability, and cognition. Furthermore, the microbiota maintains central nervous system homeostasis by regulating immune function and blood brain barrier integrity. Studies have also found that the gut microbiota influences neurotransmitter, synaptic, and neurotrophic signalling systems and neurogenesis. The principle advantage of the germ-free mouse model is in proof-of-principle studies and that a complete microbiota or defined consortiums of bacteria can be introduced at various developmental time points. However, a germ-free upbringing can induce permanent neurodevelopmental deficits that may deem the model unsuitable for specific scientific queries that do not involve early-life microbial deficiency. As such, alternatives and complementary strategies to the germ-free model are warranted and include antibiotic treatment to create microbiota-deficient animals at distinct time points across the lifespan. Increasing our understanding of the impact of the gut microbiota on brain and behavior has the potential to inform novel management strategies for stress-related gastrointestinal and neuropsychiatric disorders. PMID:26912607

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

    PubMed

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

    2016-08-01

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

  15. Alterations in Functional Cortical Hierarchy in Hemiparkinsonian Rats.

    PubMed

    Jávor-Duray, Borbála Nóra; Vinck, Martin; van der Roest, Marcel; Bezard, Erwan; Berendse, Henk W; Boraud, Thomas; Voorn, Pieter

    2017-08-09

    Parkinson's disease and experimentally induced hemiparkinsonism are characterized by increased beta synchronization between cortical and subcortical areas. This change in beta connectivity might reflect either a symmetric increase in interareal influences or asymmetric changes in directed influences among brain areas. We assessed patterns of functional and directed connectivity within and between striatum and six cortical sites in each hemisphere of the hemiparkinsonian rat model. LFPs were recorded in resting and walking states, before and after unilateral 6-hydroxydopamine lesion. The hemiparkinsonian state was characterized by increased oscillatory activity in the 20-40 Hz range in resting and walking states, and increased interhemispheric coupling (phase lag index) that was more widespread at rest than during walking. Spectral Granger-causality analysis revealed that the change in symmetric functional connectivity comprised profound reorganization of hierarchical organization and directed influence patterns. First, in the lesioned hemisphere, the more anterior, nonprimary motor areas located at the top of the cortical hierarchy (i.e., receiving many directed influences) tended to increase their directed influence onto the posterior primary motor and somatosensory areas. This enhanced influence of "higher" areas may be related to the loss of motor control due to the 6-OHDA lesion. Second, the drive from the nonlesioned toward the lesioned hemisphere (in particular to striatum) increased, most prominently during walking. The nature of these adaptations (disturbed signaling or compensation) is discussed. The present study demonstrates that hemiparkinsonism is associated with a profound reorganization of the hierarchical organization of directed influence patterns among brain areas, perhaps reflecting compensatory processes. SIGNIFICANCE STATEMENT Parkinson's disease classically first becomes manifest in one hemibody before affecting both sides, suggesting that degeneration is asymmetrical. Our results suggest that asymmetrical degeneration of the dopaminergic system induces an increased drive from the nonlesioned toward the lesioned hemisphere and a profound reorganization of functional cortical hierarchical organization, leading to a stronger directed influence of hierarchically higher placed cortical areas over primary motor and somatosensory cortices. These changes may represent a compensatory mechanism for loss of motor control as a consequence of dopamine depletion. Copyright © 2017 the authors 0270-6474/17/377669-13$15.00/0.

  16. Stimulation of functional vision in children with perinatal brain damage.

    PubMed

    Alimović, Sonja; Mejaski-Bosnjak, Vlatka

    2011-01-01

    Cerebral visual impairment (CVI) is one of the most common causes of bilateral visual loss, which frequently occurs due to perinatal brain injury. Vision in early life has great impact on acquisition of basic comprehensions which are fundamental for further development. Therefore, early detection of visual problems and early intervention is necessary. The aim of the present study is to determine specific visual functioning of children with perinatal brain damage and the influence of visual stimulation on development of functional vision at early age of life. We initially assessed 30 children with perinatal brain damage up to 3 years of age, who were reffered to our pediatric low vision cabinet in "Little house" from child neurologists, ophthalmologists Type and degree of visual impairment was determined according to functional vision assessment of each child. On the bases of those assessments different kind of visual stimulations were carried out with children who have been identified to have a certain visual impairment. Through visual stimulation program some of the children were stimulated with light stimulus, some with different materials under the ultraviolet (UV) light, and some with bright color and high contrast materials. Children were also involved in program of early stimulation of overall sensory motor development. Goals and methods of therapy were determined individually, based on observation of child's possibilities and need. After one year of program, reassessment was done. Results for visual functions and functional vision were compared to evaluate the improvement of the vision development. These results have shown that there was significant improvement in functional vision, especially in visual attention and visual communication.

  17. A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra.

    PubMed

    Rae, Caroline D

    2014-01-01

    The current knowledge of the normal biochemistry of compounds that give rise to resonances in human brain proton magnetic resonance spectra measureable at readily available field strengths (i.e. ≤3 T) is reviewed. Molecules covered include myo- and scyllo-inositol, glycerophospho- and phospho-choline and choline, creatine and phosphocreatine, N-acetylaspartate, N-acetylaspartylglutamate, glutamate, glutamine, γ-aminobutyrate, glucose, glutathione and lactate. The factors which influence changes in the levels of these compounds are discussed. As most proton resonances in the brain at low field are derived from a combination of moieties whose biochemistry is complex and interrelated, an understanding of the mechanisms underlying why these species change is crucial to meaningful interpretation of human brain spectra.

  18. The brain's Geppetto-microbes as puppeteers of neural function and behaviour?

    PubMed

    Stilling, Roman M; Dinan, Timothy G; Cryan, John F

    2016-02-01

    Research on the microbiome and its interaction with various host organs, including the brain, is increasingly gaining momentum. With more evidence establishing a comprehensive microbiota-gut-brain axis, questions have been raised as to the extent to which microbes influence brain physiology and behaviour. In parallel, there is a growing literature showing active behavioural manipulation in favour of the microbe for certain parasites. However, it seems unclear where the hidden majority of microbes are localised on the parasitism-mutualism spectrum. A long evolutionary history intimately connects host and microbiota, which complicates this classification. In this conceptual minireview, we discuss current hypotheses on host-microbe interaction and argue that novel experimental approaches and theoretical concepts, such as the hologenome theory, are necessary to incorporate transgenerational epigenetic inheritance of the microbiome into evolutionary theories.

  19. Somatic influences on subjective well-being and affective disorders: the convergence of thermosensory and central serotonergic systems

    PubMed Central

    Raison, Charles L.; Hale, Matthew W.; Williams, Lawrence E.; Wager, Tor D.; Lowry, Christopher A.

    2015-01-01

    Current theories suggest that the brain is the sole source of mental illness. However, affective disorders, and major depressive disorder (MDD) in particular, may be better conceptualized as brain-body disorders that involve peripheral systems as well. This perspective emphasizes the embodied, multifaceted physiology of well-being, and suggests that afferent signals from the body may contribute to cognitive and emotional states. In this review, we focus on evidence from preclinical and clinical studies suggesting that afferent thermosensory signals contribute to well-being and depression. Although thermoregulatory systems have traditionally been conceptualized as serving primarily homeostatic functions, increasing evidence suggests neural pathways responsible for regulating body temperature may be linked more closely with emotional states than previously recognized, an affective warmth hypothesis. Human studies indicate that increasing physical warmth activates brain circuits associated with cognitive and affective functions, promotes interpersonal warmth and prosocial behavior, and has antidepressant effects. Consistent with these effects, preclinical studies in rodents demonstrate that physical warmth activates brain serotonergic neurons implicated in antidepressant-like effects. Together, these studies suggest that (1) thermosensory pathways interact with brain systems that control affective function, (2) these pathways are dysregulated in affective disorders, and (3) activating warm thermosensory pathways promotes a sense of well-being and has therapeutic potential in the treatment of affective disorders. PMID:25628593

  20. Abnormalities in emotion processing within cortical and subcortical regions in criminal psychopaths: evidence from a functional magnetic resonance imaging study using pictures with emotional content.

    PubMed

    Müller, Jürgen L; Sommer, Monika; Wagner, Verena; Lange, Kirsten; Taschler, Heidrun; Röder, Christian H; Schuierer, Gerhardt; Klein, Helmfried E; Hajak, Göran

    2003-07-15

    Neurobiology of psychopathy is important for our understanding of current neuropsychiatric questions. Despite a growing interest in biological research in psychopathy, its neural underpinning remains obscure. We used functional magnetic resonance imaging to study the influence of affective contents on brain activation in psychopaths. Series containing positive and negative pictures from the International Affective Picture System were shown to six male psychopaths and six male control subjects while 100 whole-brain echo-planar-imaging measurements were acquired. Differences in brain activation were evaluated using BrainVoyager software 4.6. In psychopaths, increased activation through negative contents was found right-sided in prefrontal regions and amygdala. Activation was reduced right-sided in the subgenual cingulate and the temporal gyrus, and left-sided in the dorsal cingulate and the parahippocampal gyrus. Increased activation through positive contents was found left-sided in the orbitofrontal regions. Activation was reduced in right medial frontal and medial temporal regions. These findings underline the hypotheses that psychopathy is neurobiologically reflected by dysregulation and disturbed functional connectivity of emotion-related brain regions. These findings may be interpreted within a framework including prefrontal regions that provide top-down control to and regulate bottom-up signals from limbic areas. Because of the small sample size, the results of this study have to be regarded as preliminary.

  1. Right-hemispheric dominance of spatial memory in split-brain mice.

    PubMed

    Shinohara, Yoshiaki; Hosoya, Aki; Yamasaki, Nobuyuki; Ahmed, Hassan; Hattori, Satoko; Eguchi, Megumi; Yamaguchi, Shun; Miyakawa, Tsuyoshi; Hirase, Hajime; Shigemoto, Ryuichi

    2012-02-01

    Left-right asymmetry of human brain function has been known for a century, although much of molecular and cellular basis of brain laterality remains to be elusive. Recent studies suggest that hippocampal CA3-CA1 excitatory synapses are asymmetrically arranged, however, the functional implication of the asymmetrical circuitry has not been studied at the behavioral level. In order to address the left-right asymmetry of hippocampal function in behaving mice, we analyzed the performance of "split-brain" mice in the Barnes maze. The "split-brain" mice received ventral hippocampal commissure and corpus callosum transection in addition to deprivation of visual input from one eye. In such mice, the hippocampus in the side of visual deprivation receives sensory-driven input. Better spatial task performance was achieved by the mice which were forced to use the right hippocampus than those which were forced to use the left hippocampus. In two-choice spatial maze, forced usage of left hippocampus resulted in a comparable performance to the right counterpart, suggesting that both hippocampal hemispheres are capable of conducting spatial learning. Therefore, the results obtained from the Barnes maze suggest that the usage of the right hippocampus improves the accuracy of spatial memory. Performance of non-spatial yet hippocampus-dependent tasks (e.g. fear conditioning) was not influenced by the laterality of the hippocampus. Copyright © 2010 Wiley Periodicals, Inc.

  2. Association of ventral striatum monoamine oxidase-A binding and functional connectivity in antisocial personality disorder with high impulsivity: A positron emission tomography and functional magnetic resonance imaging study.

    PubMed

    Kolla, Nathan J; Dunlop, Katharine; Downar, Jonathan; Links, Paul; Bagby, R Michael; Wilson, Alan A; Houle, Sylvain; Rasquinha, Fawn; Simpson, Alexander I; Meyer, Jeffrey H

    2016-04-01

    Impulsivity is a core feature of antisocial personality disorder (ASPD) associated with abnormal brain function and neurochemical alterations. The ventral striatum (VS) is a key region of the neural circuitry mediating impulsive behavior, and low monoamine oxidase-A (MAO-A) level in the VS has shown a specific relationship to the impulsivity of ASPD. Because it is currently unknown whether phenotypic MAO-A markers can influence brain function in ASPD, we investigated VS MAO-A level and the functional connectivity (FC) of two seed regions, superior and inferior VS (VSs, VSi). Nineteen impulsive ASPD males underwent [(11)C] harmine positron emission tomography scanning to measure VS MAO-A VT, an index of MAO-A density, and resting-state functional magnetic resonance imaging that assessed the FC of bilateral seed regions in the VSi and VSs. Subjects also completed self-report impulsivity measures. Results revealed functional coupling of the VSs with bilateral dorsomedial prefrontal cortex (DMPFC) that was correlated with VS MAO-A VT (r=0.47, p=0.04), and functional coupling of the VSi with right hippocampus that was anti-correlated with VS MAO-A VT (r=-0.55, p=0.01). Additionally, VSs-DMPFC FC was negatively correlated with NEO Personality Inventory-Revised impulsivity (r=-0.49, p=0.03), as was VSi-hippocampus FC with Barratt Impulsiveness Scale-11 motor impulsiveness (r=-0.50, p=0.03). These preliminary results highlight an association of VS MAO-A level with the FC of striatal regions linked to impulsive behavior in ASPD and suggest that phenotype-based brain markers of ASPD have relevance to understanding brain function. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  3. Probiotics Improve Inflammation-Associated Sickness Behavior by Altering Communication between the Peripheral Immune System and the Brain.

    PubMed

    D'Mello, Charlotte; Ronaghan, Natalie; Zaheer, Raza; Dicay, Michael; Le, Tai; MacNaughton, Wallace K; Surrette, Michael G; Swain, Mark G

    2015-07-29

    Patients with systemic inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, chronic liver disease) commonly develop debilitating symptoms (i.e., sickness behaviors) that arise from changes in brain function. The microbiota-gut-brain axis alters brain function and probiotic ingestion can influence behavior. However, how probiotics do this remains unclear. We have previously described a novel periphery-to-brain communication pathway in the setting of peripheral organ inflammation whereby monocytes are recruited to the brain in response to systemic TNF-α signaling, leading to microglial activation and subsequently driving sickness behavior development. Therefore, we investigated whether probiotic ingestion (i.e., probiotic mixture VSL#3) alters this periphery-to-brain communication pathway, thereby reducing subsequent sickness behavior development. Using a well characterized mouse model of liver inflammation, we now show that probiotic (VSL#3) treatment attenuates sickness behavior development in mice with liver inflammation without affecting disease severity, gut microbiota composition, or gut permeability. Attenuation of sickness behavior development was associated with reductions in microglial activation and cerebral monocyte infiltration. These events were paralleled by changes in markers of systemic immune activation, including decreased circulating TNF-α levels. Our observations highlight a novel pathway through which probiotics mediate cerebral changes and alter behavior. These findings allow for the potential development of novel therapeutic interventions targeted at the gut microbiome to treat inflammation-associated sickness behaviors in patients with systemic inflammatory diseases. This research shows that probiotics, when eaten, can improve the abnormal behaviors (including social withdrawal and immobility) that are commonly associated with inflammation. Probiotics are able to cause this effect within the body by changing how the immune system signals the brain to alter brain function. These findings broaden our understanding of how probiotics may beneficially affect brain function in the context of inflammation occurring within the body and may open potential new therapeutic alternatives for the treatment of these alterations in behavior that can greatly affect patient quality of life. Copyright © 2015 the authors 0270-6474/15/3510822-10$15.00/0.

  4. Adult Onset-hypothyroidism has Minimal Effects on Synaptic Transmission in the Hippocampus of Rats Independent of Hypothermia

    EPA Science Inventory

    Introduction: Thyroid hormones (TH) influence central nervous system (CNS) function during development and in adulthood. The hippocampus, a brain area critical for learning and memory is sensitive to TH insufficiency. Synaptic transmission in the hippocampus is impaired following...

  5. Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition

    PubMed Central

    Pichora-Fuller, M. Kathleen; Mick, Paul; Reed, Marilyn

    2015-01-01

    Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging. PMID:27516713

  6. Influence of long-term Sahaja Yoga meditation practice on emotional processing in the brain: An ERP study.

    PubMed

    Reva, N V; Pavlov, S V; Loktev, K V; Korenyok, V V; Aftanas, L I

    2014-12-05

    Despite growing interest in meditation as a tool for alternative therapy of stress-related and psychosomatic diseases, brain mechanisms of beneficial influences of meditation practice on health and quality of life are still unclear. We propose that the key point is a persistent change in emotional functioning, specifically the modulation of the early appraisal of motivational significance of events. The main aim was to study the effects of long-term meditation practice on event-related brain potentials (ERPs) during affective picture viewing. ERPs were recorded in 20 long-term Sahaja Yoga meditators and 20 control subjects without prior experience in meditation. The meditators' mid-latency (140-400ms) ERPs were attenuated for both positive and negative pictures (i.e. there were no arousal-related increases in ERP positivity) and this effect was more prominent over the right hemisphere. However, we found no differences in the long latency (400-800ms) responses to emotional images, associated with meditation practice. In addition we found stronger ERP negativity in the time window 200-300ms for meditators compared to the controls, regardless of picture valence. We assume that long-term meditation practice enhances frontal top-down control over fast automatic salience detection, based on amygdala functions. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Hepato- and neuro-protective influences of biopropolis on thioacetamide-induced acute hepatic encephalopathy in rats.

    PubMed

    Mostafa, Rasha E; Salama, Abeer A A; Abdel-Rahman, Rehab F; Ogaly, Hanan A

    2017-05-01

    Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that ultimately occurs as a complication of acute or chronic liver failure; accompanied by hyperammonemia. This study aimed to evaluate the potential of biopropolis as a hepato- and neuro-protective agent using thioacetamide (TAA)-induced acute HE in rats as a model. Sixty Wistar rats were divided into 5 groups: Group 1 (normal control) received only saline and paraffin oil. Group 2 (hepatotoxic control) received TAA (300 mg/kg, once). Groups 3, 4, and 5 received TAA followed by vitamin E (100 mg/kg) and biopropolis (100 and 200 mg/kg), respectively, daily for 30 days. Evidences of HE were clearly detected in TAA-hepatotoxic group including significant elevation in the serum level of ammonia, liver functions, increased oxidative stress in liver and brain, apoptotic DNA fragmentation and overexpression of iNOS gene in brain tissue. The findings for groups administered biopropolis, highlighted its efficacy as a hepato- and neuro-protectant through improving the liver functions, oxidative status and DNA fragmentation as well as suppressing the brain expression of iNOS gene. In conclusion, biopropolis, at a dose of 200 mg/kg per day protected against TAA-induced HE through its antioxidant and antiapoptotic influence; therefore, it can be used as a protective natural product.

  8. Influence of peptide transporter 2 (PEPT2) on the distribution of cefadroxil in mouse brain: A microdialysis study.

    PubMed

    Chen, Xiaomei; Keep, Richard F; Liang, Yan; Zhu, Hao-Jie; Hammarlund-Udenaes, Margareta; Hu, Yongjun; Smith, David E

    2017-05-01

    Peptide transporter 2 (PEPT2) is a high-affinity low-capacity transporter belonging to the proton-coupled oligopeptide transporter family. Although many aspects of PEPT2 structure-function are known, including its localization in choroid plexus and neurons, its regional activity in brain, especially extracellular fluid (ECF), is uncertain. In this study, the pharmacokinetics and regional brain distribution of cefadroxil, a β-lactam antibiotic and PEPT2 substrate, were investigated in wildtype and Pept2 null mice using in vivo intracerebral microdialysis. Cefadroxil was infused intravenously over 4h at 0.15mg/min/kg, and samples obtained from plasma, brain ECF, cerebrospinal fluid (CSF) and brain tissue. A permeability-surface area experiment was also performed in which 0.15mg/min/kg cefadroxil was infused intravenously for 10min, and samples obtained from plasma and brain tissues. Our results showed that PEPT2 ablation significantly increased the brain ECF and CSF levels of cefadroxil (2- to 2.5-fold). In contrast, there were no significant differences between wildtype and Pept2 null mice in the amount of cefadroxil in brain cells. The unbound volume of distribution of cefadroxil in brain was 60% lower in Pept2 null mice indicating an uptake function for PEPT2 in brain cells. Finally, PEPT2 did not affect the influx clearance of cefadroxil, thereby, ruling out differences between the two genotypes in drug entry across the blood-brain barriers. These findings demonstrate, for the first time, the impact of PEPT2 on brain ECF as well as the known role of PEPT2 in removing peptide-like drugs, such as cefadroxil, from the CSF to blood. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Removing the effect of response time on brain activity reveals developmental differences in conflict processing in the posterior medial prefrontal cortex.

    PubMed

    Carp, Joshua; Fitzgerald, Kate Dimond; Taylor, Stephan F; Weissman, Daniel H

    2012-01-02

    In functional magnetic resonance imaging (fMRI) studies, researchers often attempt to ensure that group differences in brain activity are not confounded with group differences in mean reaction time (RT). However, even when groups are matched for performance, they may differ in terms of the RT-BOLD relationship: the degree to which brain activity varies with RT on a trial-by-trial basis. Group activation differences might therefore be influenced by group differences in the relationship between brain activity and time on task. Here, we investigated whether correcting for this potential confound alters group differences in brain activity. Specifically, we reanalyzed data from a functional MRI study of response conflict in children and adults, in which conventional analyses indicated that conflict-related activity did not differ between groups. We found that the RT-BOLD relationship was weaker in children than in adults. Consequently, after removing the effect of RT on brain activity, children exhibited greater conflict-related activity than adults in both the posterior medial prefrontal cortex and the right dorsolateral prefrontal cortex. These results identify the RT-BOLD relationship as an important potential confound in fMRI studies of group differences. They also suggest that the magnitude of the RT-BOLD relationship may be a useful biomarker of brain maturity. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Reproducibility assessment of brain responses to visual food stimuli in adults with overweight and obesity

    PubMed Central

    Sayer, R Drew; Tamer, Gregory G; Chen, Ningning; Tregellas, Jason R; Cornier, Marc-Andre; Kareken, David A; Talavage, Thomas M; McCrory, Megan A; Campbell, Wayne W

    2016-01-01

    Objective The brain’s reward system influences ingestive behavior and subsequently, obesity risk. Functional magnetic resonance imaging (fMRI) is a common method for investigating brain reward function. We sought to assess the reproducibility of fasting-state brain responses to visual food stimuli using BOLD fMRI. Methods A priori brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fasting-state fMRI and appetite assessments were completed by 28 women (n=16) and men (n=12) with overweight or obesity on 2 days. Reproducibility was assessed by comparing mean fasting-state brain responses and measuring test-retest reliability of these responses on the 2 testing days. Results Mean fasting-state brain responses on Day 2 were reduced compared to Day 1 in the left insula and right amygdala, but mean Day 1 and Day 2 responses were not different in the other regions of interest. With the exception of the left orbitofrontal cortex response (fair reliability), test-retest reliabilities of brain responses were poor or unreliable. Conclusion fMRI-measured responses to visual food cues in adults with overweight or obesity show relatively good mean-level reproducibility, but considerable within-subject variability. Poor test-retest reliability reduces the likelihood of observing true correlations and increases the necessary sample sizes for studies. PMID:27542906

  11. Influence of maternal hyperthyroidism in the rat on the expression of neuronal and astrocytic cytoskeletal proteins in fetal brain.

    PubMed

    Evans, I M; Pickard, M R; Sinha, A K; Leonard, A J; Sampson, D C; Ekins, R P

    2002-12-01

    Maternal hypothyroidism during pregnancy impairs brain function in human and rat offspring, but little is known regarding the influence of maternal hyperthyroidism on neurodevelopment. We have previously shown that the expression of neuronal and glial differentiation markers in fetal brain is compromised in hypothyroid rat dam pregnancies and have now therefore extended this investigation to hyperthyroid rat dams. Study groups comprised partially thyroidectomised dams, implanted with osmotic pumps infusing either vehicle (TX dams) or a supraphysiological dose of thyroxine (T4) (HYPER dams), and euthyroid dams infused with vehicle (N dams). Cytoskeletal protein abundance was determined in fetal brain at 21 days of gestation by immunoblot analysis. Relative to N dams, circulating total T4 levels were reduced to around one-third in TX dams but were doubled in HYPER dams. Fetal brain weight was increased in HYPER dams, whereas litter size and fetal body weight were reduced in TX dams. Glial fibrillary acidic protein expression was similar in HYPER and TX dams, being reduced in both cases relative to N dams. alpha-Internexin (INX) abundance was reduced in HYPER dams and increased in TX dams, whereas neurofilament 68 (NF68) exhibited increased abundance in HYPER dams. Furthermore, INX was inversely related to - and NF68 directly related to - maternal serum total T4 levels, independently of fetal brain weight. In conclusion, maternal hyperthyroidism compromises the expression of neuronal cytoskeletal proteins in late fetal brain, suggestive of a pattern of accelerated neuronal differentiation.

  12. Early cannabinoid exposure influences neuroendocrine and reproductive functions in male mice: I. Prenatal exposure.

    PubMed

    Dalterio, S; Steger, R; Mayfield, D; Bartke, A

    1984-01-01

    Maternal exposure to delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent in marihuana, or to the non-psychoactive cannabinol (CBN) or cannabidiol (CBD) alters endocrine functions and concentrations of brain biogenic amines in their male offspring. Prenatal CBN exposure on day 18 of gestation resulted in decreased plasma FSH levels, testicular testosterone (T) concentrations, and seminal vesicles weights, but increased plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) post-castration in adulthood. Prenatal exposure to THC significantly enhanced the responsiveness of the testes to intratesticular LH injection in vivo and tended to increase human chorionic gonadotropin (hCG)-stimulated T production by decapsulated testes in vitro. In the CBN-exposed mice, hCG-stimulated T production was enhanced, while CBD exposure had no effect. Prenatal THC exposure altered the negative feedback effects of exogenous gonadal steroids in castrated adults, with lower plasma T and FSH levels after 20 micrograms T than in castrated controls. In contrast, CBD-exposed mice had higher levels of LH in plasma post-castration. In CBN-exposed adults, two weeks post-castration the concentration of norepinephrine (NE) and dopamine (DA) in hypothalamus and remaining brain were reduced, while levels of serotonin (5-HT) and its metabolite, 5-HIAA, were elevated compared to that in castrated OIL-controls. Prenatal CBD-exposure also reduced NE and elevated 5-HT and 5-HIAA, but did not affect DA levels post-castration. Concentrations of brain biogenic amines were not influenced by prenatal THC exposure in the present study. A single prenatal exposure to psychoactive or non-psychoactive components of marihuana results in long term alterations in the function of the hypothalamo-pituitary-gonadal axis. Changes in the concentrations of brain biogenic amines may be related to these effects of prenatal cannabinoids on endocrine function in adult male mice.

  13. Green tea effects on cognition, mood and human brain function: A systematic review.

    PubMed

    Mancini, Edele; Beglinger, Christoph; Drewe, Jürgen; Zanchi, Davide; Lang, Undine E; Borgwardt, Stefan

    2017-10-15

    Green tea (Camellia sinensis) is a beverage consumed for thousands of years. Numerous claims about the benefits of its consumption were stated and investigated. As green tea is experiencing a surge in popularity in Western culture and as millions of people all over the world drink it every day, it is relevant to understand its effects on the human brain. To assess the current state of knowledge in the literature regarding the effects of green tea or green tea extracts, l-theanine and epigallocatechin gallate both components of green tea-on general neuropsychology, on the sub-category cognition and on brain functions in humans. We systematically searched on PubMed database and selected studies by predefined eligibility criteria. We then assessed their quality and extracted data. We structured our effort according to the PRISMA statement. We reviewed and assessed 21 studies, 4 of which were randomised controlled trials, 12 cross-over studies (both assessed with an adapted version of the DELPHI-list), 4 were cross-sectional studies and one was a cohort study (both assessed with an adapted version of the Newcastle-Ottawa assessment scale). The average study quality as appraised by means of the DELPHI-list was good (8.06/9); the studies evaluated with the Newcastle-Ottawa-scale were also good (6.7/9). The reviewed studies presented evidence that green tea influences psychopathological symptoms (e.g. reduction of anxiety), cognition (e.g. benefits in memory and attention) and brain function (e.g. activation of working memory seen in functional MRI). The effects of green tea cannot be attributed to a single constituent of the beverage. This is exemplified in the finding that beneficial green tea effects on cognition are observed under the combined influence of both caffeine and l-theanine, whereas separate administration of either substance was found to have a lesser impact. Copyright © 2017. Published by Elsevier GmbH.

  14. May the Force Be With You: The Light and Dark Sides of the Microbiota-Gut-Brain Axis in Neuropsychiatry.

    PubMed

    Sherwin, Eoin; Sandhu, Kiran V; Dinan, Timothy G; Cryan, John F

    2016-11-01

    The role of the gut microbiota in health and disease is becoming increasingly recognized. The microbiota-gut-brain axis is a bi-directional pathway between the brain and the gastrointestinal system. The bacterial commensals in our gut can signal to the brain through a variety of mechanisms, which are slowly being resolved. These include the vagus nerve, immune mediators and microbial metabolites, which influence central processes such as neurotransmission and behaviour. Dysregulation in the composition of the gut microbiota has been identified in several neuropsychiatric disorders, such as autism, schizophrenia and depression. Moreover, preclinical studies suggest that they may be the driving force behind the behavioural abnormalities observed in these conditions. Understanding how bacterial commensals are involved in regulating brain function may lead to novel strategies for development of microbiota-based therapies for these neuropsychiatric disorders.

  15. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour.

    PubMed

    Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Slava; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Olga; Kolb, Bryan

    2016-01-26

    Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model.Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.

  16. Microglia: new roles for the synaptic stripper.

    PubMed

    Kettenmann, Helmut; Kirchhoff, Frank; Verkhratsky, Alexei

    2013-01-09

    Any pathologic event in the brain leads to the activation of microglia, the immunocompetent cells of the central nervous system. In recent decades diverse molecular pathways have been identified by which microglial activation is controlled and by which the activated microglia affects neurons. In the normal brain microglia were considered "resting," but it has recently become evident that they constantly scan the brain environment and contact synapses. Activated microglia can remove damaged cells as well as dysfunctional synapses, a process termed "synaptic stripping." Here we summarize evidence that molecular pathways characterized in pathology are also utilized by microglia in the normal and developing brain to influence synaptic development and connectivity, and therefore should become targets of future research. Microglial dysfunction results in behavioral deficits, indicating that microglia are essential for proper brain function. This defines a new role for microglia beyond being a mere pathologic sensor. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Influence of dorsolateral prefrontal cortex and ventral striatum on risk avoidance in addiction: a mediation analysis.

    PubMed

    Yamamoto, Dorothy J; Woo, Choong-Wan; Wager, Tor D; Regner, Michael F; Tanabe, Jody

    2015-04-01

    Alterations in frontal and striatal function are hypothesized to underlie risky decision making in drug users, but how these regions interact to affect behavior is incompletely understood. We used mediation analysis to investigate how prefrontal cortex and ventral striatum together influence risk avoidance in abstinent drug users. Thirty-seven abstinent substance-dependent individuals (SDI) and 43 controls underwent fMRI while performing a decision-making task involving risk and reward. Analyses of a priori regions-of-interest tested whether activity in dorsolateral prefrontal cortex (DLPFC) and ventral striatum (VST) explained group differences in risk avoidance. Whole-brain analysis was conducted to identify brain regions influencing the negative VST-risk avoidance relationship. Right DLPFC (RDLPFC) positively mediated the group-risk avoidance relationship (p < 0.05); RDLPFC activity was higher in SDI and predicted higher risk avoidance across groups, controlling for SDI vs. Conversely, VST activity negatively influenced risk avoidance (p < 0.05); it was higher in SDI, and predicted lower risk avoidance. Whole-brain analysis revealed that, across group, RDLPFC and left temporal-parietal junction positively (p ≤ 0.001) while right thalamus and left middle frontal gyrus negatively (p < 0.005) mediated the VST activity-risk avoidance relationship. RDLPFC activity mediated less risky decision making while VST mediated more risky decision making across drug users and controls. These results suggest a dual pathway underlying decision making, which, if imbalanced, may adversely influence choices involving risk. Modeling contributions of multiple brain systems to behavior through mediation analysis could lead to a better understanding of mechanisms of behavior and suggest neuromodulatory treatments for addiction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Influence of dorsolateral prefrontal cortex and ventral striatum on risk avoidance in addiction: a mediation analysis*

    PubMed Central

    Yamamoto, Dorothy J.; Woo, Choong-Wan; Wager, Tor D.; Regner, Michael F.; Tanabe, Jody

    2015-01-01

    Background Alterations in frontal and striatal function are hypothesized to underlie risky decision-making in drug users, but how these regions interact to affect behavior is incompletely understood. We used mediation analysis to investigate how prefrontal cortex and ventral striatum together influence risk avoidance in abstinent drug users. Method Thirty-seven abstinent substance-dependent individuals (SDI) and 43 controls underwent fMRI while performing a decision-making task involving risk and reward. Analyses of a priori regions-of-interest tested whether activity in dorsolateral prefrontal cortex (DLPFC) and ventral striatum (VST) explained group differences in risk avoidance. Whole-brain analysis was conducted to identify brain regions influencing the negative VST-risk avoidance relationship. Results Right DLPFC (RDLPFC) positively mediated the group-risk avoidance relationship (p < 0.05); RDLPFC activity was higher in SDI and predicted higher risk avoidance across groups, controlling for SDI vs. controls. Conversely, VST activity negatively influenced risk avoidance (p < 0.05); it was higher in SDI, and predicted lower risk avoidance. Whole-brain analysis revealed that, across group, RDLPFC and left temporal-parietal junction positively (p ≤ 0.001) while right thalamus and left middle frontal gyrus negatively (p < 0.005) mediated the VST activity-risk avoidance relationship. Conclusion RDLPFC activity mediated less risky decision-making while VST mediated more risky decision-making across drug users and controls. These results suggest a dual pathway underlying decision-making, which, if imbalanced, may adversely influence choices involving risk. Modeling contributions of multiple brain systems to behavior through mediation analysis could lead to a better understanding of mechanisms of behavior and suggest neuromodulatory treatments for addiction. PMID:25736619

  19. Influences of Hunger, Satiety and Oral Glucose on Functional Brain Connectivity: A Multimethod Resting-State fMRI Study.

    PubMed

    Al-Zubaidi, Arkan; Heldmann, Marcus; Mertins, Alfred; Jauch-Chara, Kamila; Münte, Thomas F

    2018-07-01

    A major regulatory task of the organism is to keep brain functions relatively constant in spite of metabolic changes (e.g., hunger vs. satiety) or availability of energy (e.g., glucose administration). Resting-state functional magnetic resonance imaging (rs-fMRI) can reveal resulting changes in brain function but previous studies have focused mostly on the hypothalamus. Therefore, we took a whole-brain approach and examined 24 healthy normal-weight men once after 36 h of fasting and once in a satiated state (six meals over the course of 36 h). At the end of each treatment, rs-fMRI was recorded before and after the oral administration of 75 g of glucose. We calculated local connectivity (regional homogeneity [ReHo]), global connectivity (degree of centrality [DC]), and amplitude (fractional amplitude of low-frequency fluctuation [fALFF]) maps from the rs-fMRI data. We found that glucose administration reduced all measures selectively in the left supplementary motor area and increased ReHo and fALFF in the right middle and superior frontal gyri. For fALFF, we observed a significant interaction between metabolic states and glucose in the left thalamus. This interaction was driven by a fALFF increase after glucose treatment in the hunger relative to the satiety condition. Our results indicate that fALFF analysis is the most sensitive measure to detect effects of metabolic states on resting-state brain activity. Moreover, we show that multimethod rs-fMRI provides an unbiased approach to identify spontaneous brain activity associated with changes in homeostasis and caloric intake. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Study protocol: imaging brain development in the Childhood to Adolescence Transition Study (iCATS).

    PubMed

    Simmons, Julian G; Whittle, Sarah L; Patton, George C; Dudgeon, Paul; Olsson, Craig; Byrne, Michelle L; Mundy, Lisa K; Seal, Marc L; Allen, Nicholas B

    2014-04-30

    Puberty is a critical developmental phase in physical, reproductive and socio-emotional maturation that is associated with the period of peak onset for psychopathology. Puberty also drives significant changes in brain development and function. Research to date has focused on gonadarche, driven by the hypothalamic-pituitary-gonadal axis, and yet increasing evidence suggests that the earlier pubertal stage of adrenarche, driven by the hypothalamic-pituitary-adrenal axis, may play a critical role in both brain development and increased risk for disorder. We have established a unique cohort of children who differ in their exposure to adrenarcheal hormones. This presents a unique opportunity to examine the influence of adrenarcheal timing on brain structural and functional development, and subsequent health outcomes. The primary objective of the study is to explore the hypothesis that patterns of structural and functional brain development will mediate the relationship between adrenarcheal timing and indices of affect, self-regulation, and mental health symptoms collected across time (and therefore years of development). Children were recruited based upon earlier or later timing of adrenarche, from a larger cohort, with 128 children (68 female; M age 9.51 years) and one of their parents taking part. Children completed brain MRI structural and functional sequences, provided saliva samples for adrenarcheal hormones and immune biomarkers, hair for long-term cortisol levels, and completed questionnaires, anthropometric measures and an IQ test. Parents completed questionnaires reporting on child behaviour, development, health, traumatic events, and parental report of family environment and parenting style. This study, by examining the neurobiological and behavioural consequences of relatively early and late exposure to adrenarche, has the potential to significantly impact our understanding of pubertal risk processes.

  1. Speech networks at rest and in action: interactions between functional brain networks controlling speech production.

    PubMed

    Simonyan, Kristina; Fuertinger, Stefan

    2015-04-01

    Speech production is one of the most complex human behaviors. Although brain activation during speaking has been well investigated, our understanding of interactions between the brain regions and neural networks remains scarce. We combined seed-based interregional correlation analysis with graph theoretical analysis of functional MRI data during the resting state and sentence production in healthy subjects to investigate the interface and topology of functional networks originating from the key brain regions controlling speech, i.e., the laryngeal/orofacial motor cortex, inferior frontal and superior temporal gyri, supplementary motor area, cingulate cortex, putamen, and thalamus. During both resting and speaking, the interactions between these networks were bilaterally distributed and centered on the sensorimotor brain regions. However, speech production preferentially recruited the inferior parietal lobule (IPL) and cerebellum into the large-scale network, suggesting the importance of these regions in facilitation of the transition from the resting state to speaking. Furthermore, the cerebellum (lobule VI) was the most prominent region showing functional influences on speech-network integration and segregation. Although networks were bilaterally distributed, interregional connectivity during speaking was stronger in the left vs. right hemisphere, which may have underlined a more homogeneous overlap between the examined networks in the left hemisphere. Among these, the laryngeal motor cortex (LMC) established a core network that fully overlapped with all other speech-related networks, determining the extent of network interactions. Our data demonstrate complex interactions of large-scale brain networks controlling speech production and point to the critical role of the LMC, IPL, and cerebellum in the formation of speech production network. Copyright © 2015 the American Physiological Society.

  2. DRD2: Bridging the genome and ingestive behavior

    PubMed Central

    Sun, Xue; Luquet, Serge; Small, Dana M

    2017-01-01

    Recent work highlights the importance of genetic variants that influence brain structure and function in conferring risk for polygenic obesity. The neurotransmitter dopamine (DA) plays a pivotal role in energy balance by integrating metabolic signals with circuits supporting cognitive, perceptual and appetitive functions that guide feeding. It has also been established that diet and obesity alter DA signaling leading to compulsive-like feeding and neurocognitive impairments. This raises the possibility that genetic variants that influence DA signaling and adaptation confer risk for overeating and cognitive decline. We consider the role of two common gene variants, FTO and TaqIA rs1800497 in driving gene * environment interactions promoting obesity, metabolic dysfunction, and cognitive change via their influence on dopamine receptor subtype 2 signaling. PMID:28372879

  3. Task relevance modulates the behavioural and neural effects of sensory predictions

    PubMed Central

    Friston, Karl J.; Nobre, Anna C.

    2017-01-01

    The brain is thought to generate internal predictions to optimize behaviour. However, it is unclear whether predictions signalling is an automatic brain function or depends on task demands. Here, we manipulated the spatial/temporal predictability of visual targets, and the relevance of spatial/temporal information provided by auditory cues. We used magnetoencephalography (MEG) to measure participants’ brain activity during task performance. Task relevance modulated the influence of predictions on behaviour: spatial/temporal predictability improved spatial/temporal discrimination accuracy, but not vice versa. To explain these effects, we used behavioural responses to estimate subjective predictions under an ideal-observer model. Model-based time-series of predictions and prediction errors (PEs) were associated with dissociable neural responses: predictions correlated with cue-induced beta-band activity in auditory regions and alpha-band activity in visual regions, while stimulus-bound PEs correlated with gamma-band activity in posterior regions. Crucially, task relevance modulated these spectral correlates, suggesting that current goals influence PE and prediction signalling. PMID:29206225

  4. BAD and KATP channels regulate neuron excitability and epileptiform activity

    PubMed Central

    Fernández-Agüera, María Carmen; Nathwani, Nidhi; Lahmann, Carolina; Burnham, Veronica L

    2018-01-01

    Brain metabolism can profoundly influence neuronal excitability. Mice with genetic deletion or alteration of Bad (BCL-2 agonist of cell death) exhibit altered brain-cell fuel metabolism, accompanied by resistance to acutely induced epileptic seizures; this seizure protection is mediated by ATP-sensitive potassium (KATP) channels. Here we investigated the effect of BAD manipulation on KATP channel activity and excitability in acute brain slices. We found that BAD’s influence on neuronal KATP channels was cell-autonomous and directly affected dentate granule neuron (DGN) excitability. To investigate the role of neuronal KATP channels in the anticonvulsant effects of BAD, we imaged calcium during picrotoxin-induced epileptiform activity in entorhinal-hippocampal slices. BAD knockout reduced epileptiform activity, and this effect was lost upon knockout or pharmacological inhibition of KATP channels. Targeted BAD knockout in DGNs alone was sufficient for the antiseizure effect in slices, consistent with a ‘dentate gate’ function that is reinforced by increased KATP channel activity. PMID:29368690

  5. Simultaneous real-time monitoring of multiple cortical systems.

    PubMed

    Gupta, Disha; Jeremy Hill, N; Brunner, Peter; Gunduz, Aysegul; Ritaccio, Anthony L; Schalk, Gerwin

    2014-10-01

    Real-time monitoring of the brain is potentially valuable for performance monitoring, communication, training or rehabilitation. In natural situations, the brain performs a complex mix of various sensory, motor or cognitive functions. Thus, real-time brain monitoring would be most valuable if (a) it could decode information from multiple brain systems simultaneously, and (b) this decoding of each brain system were robust to variations in the activity of other (unrelated) brain systems. Previous studies showed that it is possible to decode some information from different brain systems in retrospect and/or in isolation. In our study, we set out to determine whether it is possible to simultaneously decode important information about a user from different brain systems in real time, and to evaluate the impact of concurrent activity in different brain systems on decoding performance. We study these questions using electrocorticographic signals recorded in humans. We first document procedures for generating stable decoding models given little training data, and then report their use for offline and for real-time decoding from 12 subjects (six for offline parameter optimization, six for online experimentation). The subjects engage in tasks that involve movement intention, movement execution and auditory functions, separately, and then simultaneously. Main Results: Our real-time results demonstrate that our system can identify intention and movement periods in single trials with an accuracy of 80.4% and 86.8%, respectively (where 50% would be expected by chance). Simultaneously, the decoding of the power envelope of an auditory stimulus resulted in an average correlation coefficient of 0.37 between the actual and decoded power envelopes. These decoders were trained separately and executed simultaneously in real time. This study yielded the first demonstration that it is possible to decode simultaneously the functional activity of multiple independent brain systems. Our comparison of univariate and multivariate decoding strategies, and our analysis of the influence of their decoding parameters, provides benchmarks and guidelines for future research on this topic.

  6. Simultaneous Real-Time Monitoring of Multiple Cortical Systems

    PubMed Central

    Gupta, Disha; Hill, N. Jeremy; Brunner, Peter; Gunduz, Aysegul; Ritaccio, Anthony L.; Schalk, Gerwin

    2014-01-01

    Objective Real-time monitoring of the brain is potentially valuable for performance monitoring, communication, training or rehabilitation. In natural situations, the brain performs a complex mix of various sensory, motor, or cognitive functions. Thus, real-time brain monitoring would be most valuable if (a) it could decode information from multiple brain systems simultaneously, and (b) this decoding of each brain system were robust to variations in the activity of other (unrelated) brain systems. Previous studies showed that it is possible to decode some information from different brain systems in retrospect and/or in isolation. In our study, we set out to determine whether it is possible to simultaneously decode important information about a user from different brain systems in real time, and to evaluate the impact of concurrent activity in different brain systems on decoding performance. Approach We study these questions using electrocorticographic (ECoG) signals recorded in humans. We first document procedures for generating stable decoding models given little training data, and then report their use for offline and for real-time decoding from 12 subjects (6 for offline parameter optimization, 6 for online experimentation). The subjects engage in tasks that involve movement intention, movement execution and auditory functions, separately, and then simultaneously. Main results Our real-time results demonstrate that our system can identify intention and movement periods in single trials with an accuracy of 80.4% and 86.8%, respectively (where 50% would be expected by chance). Simultaneously, the decoding of the power envelope of an auditory stimulus resulted in an average correlation coefficient of 0.37 between the actual and decoded power envelope. These decoders were trained separately and executed simultaneously in real time. Significance This study yielded the first demonstration that it is possible to decode simultaneously the functional activity of multiple independent brain systems. Our comparison of univariate and multivariate decoding strategies, and our analysis of the influence of their decoding parameters, provides benchmarks and guidelines for future research on this topic. PMID:25080161

  7. Audio-tactile integration and the influence of musical training.

    PubMed

    Kuchenbuch, Anja; Paraskevopoulos, Evangelos; Herholz, Sibylle C; Pantev, Christo

    2014-01-01

    Perception of our environment is a multisensory experience; information from different sensory systems like the auditory, visual and tactile is constantly integrated. Complex tasks that require high temporal and spatial precision of multisensory integration put strong demands on the underlying networks but it is largely unknown how task experience shapes multisensory processing. Long-term musical training is an excellent model for brain plasticity because it shapes the human brain at functional and structural levels, affecting a network of brain areas. In the present study we used magnetoencephalography (MEG) to investigate how audio-tactile perception is integrated in the human brain and if musicians show enhancement of the corresponding activation compared to non-musicians. Using a paradigm that allowed the investigation of combined and separate auditory and tactile processing, we found a multisensory incongruency response, generated in frontal, cingulate and cerebellar regions, an auditory mismatch response generated mainly in the auditory cortex and a tactile mismatch response generated in frontal and cerebellar regions. The influence of musical training was seen in the audio-tactile as well as in the auditory condition, indicating enhanced higher-order processing in musicians, while the sources of the tactile MMN were not influenced by long-term musical training. Consistent with the predictive coding model, more basic, bottom-up sensory processing was relatively stable and less affected by expertise, whereas areas for top-down models of multisensory expectancies were modulated by training.

  8. Network topology and functional connectivity disturbances precede the onset of Huntington's disease.

    PubMed

    Harrington, Deborah L; Rubinov, Mikail; Durgerian, Sally; Mourany, Lyla; Reece, Christine; Koenig, Katherine; Bullmore, Ed; Long, Jeffrey D; Paulsen, Jane S; Rao, Stephen M

    2015-08-01

    Cognitive, motor and psychiatric changes in prodromal Huntington's disease have nurtured the emergent need for early interventions. Preventive clinical trials for Huntington's disease, however, are limited by a shortage of suitable measures that could serve as surrogate outcomes. Measures of intrinsic functional connectivity from resting-state functional magnetic resonance imaging are of keen interest. Yet recent studies suggest circumscribed abnormalities in resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease, despite the spectrum of behavioural changes preceding a manifest diagnosis. The present study used two complementary analytical approaches to examine whole-brain resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease. Network topology was studied using graph theory and simple functional connectivity amongst brain regions was explored using the network-based statistic. Participants consisted of gene-negative controls (n = 16) and prodromal Huntington's disease individuals (n = 48) with various stages of disease progression to examine the influence of disease burden on intrinsic connectivity. Graph theory analyses showed that global network interconnectivity approximated a random network topology as proximity to diagnosis neared and this was associated with decreased connectivity amongst highly-connected rich-club network hubs, which integrate processing from diverse brain regions. However, functional segregation within the global network (average clustering) was preserved. Functional segregation was also largely maintained at the local level, except for the notable decrease in the diversity of anterior insula intermodular-interconnections (participation coefficient), irrespective of disease burden. In contrast, network-based statistic analyses revealed patterns of weakened frontostriatal connections and strengthened frontal-posterior connections that evolved as disease burden increased. These disturbances were often related to long-range connections involving peripheral nodes and interhemispheric connections. A strong association was found between weaker connectivity and decreased rich-club organization, indicating that whole-brain simple connectivity partially expressed disturbances in the communication of highly-connected hubs. However, network topology and network-based statistic connectivity metrics did not correlate with key markers of executive dysfunction (Stroop Test, Trail Making Test) in prodromal Huntington's disease, which instead were related to whole-brain connectivity disturbances in nodes (right inferior parietal, right thalamus, left anterior cingulate) that exhibited multiple aberrant connections and that mediate executive control. Altogether, our results show for the first time a largely disease burden-dependent functional reorganization of whole-brain networks in prodromal Huntington's disease. Both analytic approaches provided a unique window into brain reorganization that was not related to brain atrophy or motor symptoms. Longitudinal studies currently in progress will chart the course of functional changes to determine the most sensitive markers of disease progression. © 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.

  9. Brain substrates of unhealthy versus healthy food choices: influence of homeostatic status and body mass index.

    PubMed

    Harding, I H; Andrews, Z B; Mata, F; Orlandea, S; Martínez-Zalacaín, I; Soriano-Mas, C; Stice, E; Verdejo-Garcia, A

    2018-03-01

    Unhealthy dietary choices are a major contributor to harmful weight gain and obesity. This study interrogated the brain substrates of unhealthy versus healthy food choices in vivo, and evaluated the influence of hunger state and body mass index (BMI) on brain activation and connectivity. Thirty adults (BMI: 18-38 kg m -2 ) performed a food-choice task involving preference-based selection between beverage pairs consisting of high-calorie (unhealthy) or low-calorie (healthy) options, concurrent with functional magnetic resonance imaging (fMRI). Selected food stimuli were delivered to participants using an MRI-compatible gustometer. fMRI scans were performed both after 10-h fasting and when sated. Brain activation and hypothalamic functional connectivity were assessed when selecting between unhealthy-healthy beverage pairings, relative to unhealthy-unhealthy and healthy-healthy options. Results were considered significant at cluster-based family-wise error corrected P<0.05. Selecting between unhealthy and healthy foods elicited significant activation in the hypothalamus, the medial and dorsolateral prefrontal cortices, the anterior insula and the posterior cingulate. Hunger was associated with higher activation within the ventromedial and dorsolateral prefrontal cortices, as well as lower connectivity between the hypothalamus and both the ventromedial prefrontal cortex and dorsal striatum. Critically, people with higher BMI showed lower activation of the hypothalamus-regardless of hunger state-and higher activation of the ventromedial prefrontal cortex when hungry. People who are overweight and obese have weaker activation of brain regions involved in energy regulation and greater activation of reward valuation regions while making choices between unhealthy and healthy foods. These results provide evidence for a shift towards hedonic-based, and away from energy-based, food selection in obesity.

  10. Role of Monocarboxylate Transporters in Drug Delivery to the Brain

    PubMed Central

    Vijay, Nisha; Morris, Marilyn E.

    2014-01-01

    Monocarboxylate transporters (MCTs) are known to mediate the transport of short chain monocarboxylates such as lactate, pyruvate and butyrate. Currently, fourteen members of this transporter family have been identified by sequence homology, of which only the first four members (MCT1- MCT4) have been shown to mediate the proton-linked transport of monocarboxylates. Another transporter family involved in the transport of endogenous monocarboxylates is the sodium coupled MCTs (SMCTs). These act as a symporter and are dependent on a sodium gradient for their functional activity. MCT1 is the predominant transporter among the MCT isoforms and is present in almost all tissues including kidney, intestine, liver, heart, skeletal muscle and brain. The various isoforms differ in terms of their substrate specificity and tissue localization. Due to the expression of these transporters in the kidney, intestine, and brain, they may play an important role in influencing drug disposition. Apart from endogenous short chain monocarboxylates, they also mediate the transport of exogenous drugs such as salicylic acid, valproic acid, and simvastatin acid. The influence of MCTs on drug pharmacokinetics has been extensively studied for γ-hydroxybutyrate (GHB) including distribution of this drug of abuse into the brain and the results will be summarized in this review. The physiological role of these transporters in the brain and their specific cellular localization within the brain will also be discussed. This review will also focus on utilization of MCTs as potential targets for drug delivery into the brain including their role in the treatment of malignant brain tumors. PMID:23789956

  11. Normal variation in early parental sensitivity predicts child structural brain development.

    PubMed

    Kok, Rianne; Thijssen, Sandra; Bakermans-Kranenburg, Marian J; Jaddoe, Vincent W V; Verhulst, Frank C; White, Tonya; van IJzendoorn, Marinus H; Tiemeier, Henning

    2015-10-01

    Early caregiving can have an impact on brain structure and function in children. The influence of extreme caregiving experiences has been demonstrated, but studies on the influence of normal variation in parenting quality are scarce. Moreover, no studies to date have included the role of both maternal and paternal sensitivity in child brain maturation. This study examined the prospective relation between mothers' and fathers' sensitive caregiving in early childhood and brain structure later in childhood. Participants were enrolled in a population-based prenatal cohort. For 191 families, maternal and paternal sensitivity was repeatedly observed when the child was between 1 year and 4 years of age. Head circumference was assessed at 6 weeks, and brain structure was assessed using magnetic resonance imaging (MRI) measurements at 8 years of age. Higher levels of parental sensitivity in early childhood were associated with larger total brain volume (adjusted β = 0.15, p = .01) and gray matter volume (adjusted β = 0.16, p = .01) at 8 years, controlling for infant head size. Higher levels of maternal sensitivity in early childhood were associated with a larger gray matter volume (adjusted β = 0.13, p = .04) at 8 years, independent of infant head circumference. Associations with maternal versus paternal sensitivity were not significantly different. Normal variation in caregiving quality is related to markers of more optimal brain development in children. The results illustrate the important role of both mothers and fathers in child brain development. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Glutamatergic stimulation of the left dentate gyrus abolishes depressive-like behaviors in a rat learned helplessness paradigm.

    PubMed

    Seo, Jeho; Cho, Hojin; Kim, Gun Tae; Kim, Chul Hoon; Kim, Dong Goo

    2017-10-01

    Episodic experiences of stress have been identified as the leading cause of major depressive disorder (MDD). The occurrence of MDD is profoundly influenced by the individual's coping strategy, rather than the severity of the stress itself. Resting brain activity has been shown to alter in several mental disorders. However, the functional relationship between resting brain activity and coping strategies has not yet been studied. In the present study, we observed different patterns of resting brain activity in rats that had determined either positive (resilient to stress) or negative (vulnerable to stress) coping strategies, and examined whether modulation of the preset resting brain activity could influence the behavioral phenotype associated with negative coping strategy (i.e., depressive-like behaviors). We used a learned helplessness paradigm-a well-established model of MDD-to detect coping strategies. Differences in resting state brain activity between animals with positive and negative coping strategies were assessed using 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). Glutamatergic stimulation was used to modulate resting brain activity. After exposure to repeated uncontrollable stress, seven of 23 rats exhibited positive coping strategies, while eight of 23 rats exhibited negative coping strategies. Increased resting brain activity was observed only in the left ventral dentate gyrus of the positive coping rats using FDG-PET. Furthermore, glutamatergic stimulation of the left dentate gyrus abolished depressive-like behaviors in rats with negative coping strategies. Increased resting brain activity in the left ventral dentate gyrus helps animals to select positive coping strategies in response to future stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Impact of 36 h of total sleep deprivation on resting-state dynamic functional connectivity.

    PubMed

    Xu, Huaze; Shen, Hui; Wang, Lubin; Zhong, Qi; Lei, Yu; Yang, Liu; Zeng, Ling-Li; Zhou, Zongtan; Hu, Dewen; Yang, Zheng

    2018-06-01

    Resting-state functional magnetic resonance imaging (fMRI) studies using static functional connectivity (sFC) measures have shown that the brain function is severely disrupted after long-term sleep deprivation (SD). However, increasing evidence has suggested that resting-state functional connectivity (FC) is dynamic and exhibits spontaneous fluctuation on a smaller timescale. The process by which long-term SD can influence dynamic functional connectivity (dFC) remains unclear. In this study, 37 healthy subjects participated in the SD experiment, and they were scanned both during rested wakefulness (RW) and after 36 h of SD. A sliding-window based approach and a spectral clustering algorithm were used to evaluate the effects of SD on dFC based on the 26 qualified subjects' data. The outcomes showed that time-averaging FC across specific regions as well as temporal properties of the FC states, such as the dwell time and transition probability, was strongly influenced after SD in contrast to the RW condition. Based on the occurrences of FC states, we further identified some RW-dominant states characterized by anti-correlation between the default mode network (DMN) and other cortices, and some SD-dominant states marked by significantly decreased thalamocortical connectivity. In particular, the temporal features of these FC states were negatively correlated with the correlation coefficients between the DMN and dorsal attention network (dATN) and demonstrated high potential in classification of sleep state (with 10-fold cross-validation accuracy of 88.6% for dwell time and 88.1% for transition probability). Collectively, our results suggested that the temporal properties of the FC states greatly account for changes in the resting-state brain networks following SD, which provides new insights into the impact of SD on the resting-state functional organization in the human brain. Copyright © 2017. Published by Elsevier B.V.

  14. Chelation of neurotoxic zinc levels does not improve neurobehavioral outcome after traumatic brain injury

    PubMed Central

    Hellmich, Helen L.; Eidson, Kristine; Cowart, Jeremy; Crookshanks, Jeanna; Boone, Deborah K.; Shah, Syed; Uchida, Tatsuo; DeWitt, Douglas S.; Prough, Donald S.

    2008-01-01

    Increases of synaptically released zinc and intracellular accumulation of zinc in hippocampal neurons after traumatic or ischemic brain injury is neurotoxic and chelation of zinc has been shown to reduce neurodegeneration. Although our previous studies showed that zinc chelation in traumatically brain-injured rats correlated with an increase in whole-brain expression of several neuroprotective genes and reduced numbers of apoptotic neurons, the effect on functional outcome has not been determined, and the question of whether this treatment may actually be clinically relevant has not been answered. In the present study, we show that treatment of TBI rats with the zinc chelator calcium EDTA reduces the numbers of injured, Fluoro-Jade- positive neurons in the rat hippocampus 24 hours after injury but does not improve neurobehavioral outcome (spatial memory deficits) two weeks post-injury. Our data suggest that zinc chelation, despite providing short-term histological neuroprotection, fails to improve long-term functional outcome, perhaps because long-term disruptions in homeostatic levels of zinc adversely influence hippocampus-dependent spatial memory. PMID:18556117

  15. Persistent increase of D-aspartate in D-aspartate oxidase mutant mice induces a precocious hippocampal age-dependent synaptic plasticity and spatial memory decay.

    PubMed

    Errico, Francesco; Nisticò, Robert; Napolitano, Francesco; Oliva, Alessandra Bonito; Romano, Rosaria; Barbieri, Federica; Florio, Tullio; Russo, Claudio; Mercuri, Nicola B; Usiello, Alessandro

    2011-11-01

    The atypical amino acid d-aspartate (d-Asp) occurs at considerable amounts in the developing brain of mammals. However, during postnatal life, d-Asp levels diminish following the expression of d-aspartate oxidase (DDO) enzyme. The strict control of DDO over its substrate d-Asp is particularly evident in the hippocampus, a brain region crucially involved in memory, and highly vulnerable to age-related deterioration processes. Herein, we explored the influence of deregulated higher d-Asp brain content on hippocampus-related functions during aging of mice lacking DDO (Ddo(-/-)). Strikingly, we demonstrated that the enhancement of hippocampal synaptic plasticity and cognition in 4/5-month-old Ddo(-/-) mice is followed by an accelerated decay of basal glutamatergic transmission, NMDAR-dependent LTP and hippocampus-related reference memory at 13/14 months of age. Therefore, the precocious deterioration of hippocampal functions observed in mutants highlights for the first time a role for DDO enzyme in controlling the rate of brain aging process in mammals. Copyright © 2009 Elsevier Inc. All rights reserved.

  16. Diet and cognition: interplay between cell metabolism and neuronal plasticity.

    PubMed

    Gomez-Pinilla, Fernando; Tyagi, Ethika

    2013-11-01

    To discuss studies in humans and animals revealing the ability of foods to benefit the brain: new information with regards to mechanisms of action and the treatment of neurological and psychiatric disorders. Dietary factors exert their effects on the brain by affecting molecular events related to the management of energy metabolism and synaptic plasticity. Energy metabolism influences neuronal function, neuronal signaling, and synaptic plasticity, ultimately affecting mental health. Epigenetic regulation of neuronal plasticity appears as an important mechanism by which foods can prolong their effects on long-term neuronal plasticity. The prime focus of the discussion is to emphasize the role of cell metabolism as a mediator for the action of foods on the brain. Oxidative stress promotes damage to phospholipids present in the plasma membrane such as the omega-3 fatty acid docosahexenoic acid, disrupting neuronal signaling. Thus, dietary docosahexenoic acid seems crucial for supporting plasma membrane function, interneuronal signaling, and cognition. The dual action of brain-derived neurotrophic factor in neuronal metabolism and synaptic plasticity is crucial for activating signaling cascades under the action of diet and other environmental factors, using mechanisms of epigenetic regulation.

  17. Neuroanatomical and Cognitive Mediators of Age-Related Differences in Episodic Memory

    PubMed Central

    Head, Denise; Rodrigue, Karen M.; Kennedy, Kristen M.; Raz, Naftali

    2009-01-01

    Aging is associated with declines in episodic memory. In this study, the authors used a path analysis framework to explore the mediating role of differences in brain structure, executive functions, and processing speed in age-related differences in episodic memory. Measures of regional brain volume (prefrontal gray and white matter, caudate, hippocampus, visual cortex), executive functions (working memory, inhibitory control, task switching, temporal processing), processing speed, and episodic memory were obtained in a sample of young and older adults. As expected, age was linked to reduction in regional brain volumes and cognitive performance. Moreover, neural and cognitive factors completely mediated age differences in episodic memory. Whereas hippocampal shrinkage directly affected episodic memory, prefrontal volumetric reductions influenced episodic memory via limitations in working memory and inhibitory control. Age-related slowing predicted reduced efficiency in temporal processing, working memory, and inhibitory control. Lastly, poorer temporal processing directly affected episodic memory. No direct effects of age on episodic memory remained once these factors were taken into account. These analyses highlight the value of a multivariate approach with the understanding of complex relationships in cognitive and brain aging. PMID:18590361

  18. 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.

  19. The opportunities and challenges of large-scale molecular approaches to songbird neurobiology

    PubMed Central

    Mello, C.V.; Clayton, D.F.

    2014-01-01

    High-through put methods for analyzing genome structure and function are having a large impact in song-bird neurobiology. Methods include genome sequencing and annotation, comparative genomics, DNA microarrays and transcriptomics, and the development of a brain atlas of gene expression. Key emerging findings include the identification of complex transcriptional programs active during singing, the robust brain expression of non-coding RNAs, evidence of profound variations in gene expression across brain regions, and the identification of molecular specializations within song production and learning circuits. Current challenges include the statistical analysis of large datasets, effective genome curations, the efficient localization of gene expression changes to specific neuronal circuits and cells, and the dissection of behavioral and environmental factors that influence brain gene expression. The field requires efficient methods for comparisons with organisms like chicken, which offer important anatomical, functional and behavioral contrasts. As sequencing costs plummet, opportunities emerge for comparative approaches that may help reveal evolutionary transitions contributing to vocal learning, social behavior and other properties that make songbirds such compelling research subjects. PMID:25280907

  20. History of functional neurosurgery.

    PubMed

    Iskandar, B J; Nashold, B S

    1995-01-01

    Whereas in the early days of evil spirits, electric catfish, and phrenology, functional neurosurgery was based on crude observations and dogma, the progress made in neurophysiology at the turn of the century gave the field a strong scientific foundation. Subsequently, the advent of stereotaxis allowed access to deep brain regions and contributed an element of precision. Future directions include the development of frameless stereotaxy; the use of MRI-generated anatomic data, which would circumvent the serious problem of individual variations seen with standard brain atlases; the introduction of various chemicals into brain structures, in an attempt to influence neurochemically mediated disease processes; and finally, the use of the promising techniques of neural transplantation. On hearing of Penfield's intraoperative brain stimulations, Sherrington commented: "It must be great fun to have the physiological preparation speak to you." The idea of therapeutic neurophysiologic interventions is appealing, especially because many disorders show no obvious treatable pathologic cause (e.g., tumor, vascular malformation). As stereotactic technology becomes less cumbersome and more precise, more sophisticated in vivo neurophysiologic preparations become possible. In turn, as our understanding of nervous system physiology grows, our ability to understand pathophysiology and treat disease processes increases.

  1. Estradiol Membrane-Initiated Signaling in the Brain Mediates Reproduction.

    PubMed

    Micevych, Paul E; Mermelstein, Paul G; Sinchak, Kevin

    2017-11-01

    Over the past few years our understanding of estrogen signaling in the brain has expanded rapidly. Estrogens are synthesized in the periphery and in the brain, acting on multiple receptors to regulate gene transcription, neural function, and behavior. Various estrogen-sensitive signaling pathways often operate in concert within the same cell, increasing the complexity of the system. In females, estrogen concentrations fluctuate over the estrous/menstrual cycle, dynamically modulating estrogen receptor (ER) expression, activity, and trafficking. These dynamic changes influence multiple behaviors but are particularly important for reproduction. Using the female rodent model, we review our current understanding of estradiol signaling in the regulation of sexual receptivity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Physical Activity, Fitness, Cognitive Function, and Academic Achievement in Children: A Systematic Review

    PubMed Central

    Donnelly, Joseph E.; Hillman, Charles H.; Castelli, Darla; Etnier, Jennifer L.; Lee, Sarah; Tomporowski, Phillip; Lambourne, Kate; Szabo-Reed, Amanda N.

    2016-01-01

    Background The relation among physical activity (PA), fitness, cognitive function, and academic achievement in children is receiving considerable attention. The utility of PA to improve cognition and academic achievement is promising but uncertain; thus, this position stand will provide clarity from the available science. Objective To answer the following questions: (1) among children aged 5-13, do PA and physical fitness influence cognition, learning, brain structure, and brain function? (2) among children aged 5-13, do PA, physical education, and sports programs influence standardized achievement test performance and concentration/attention? Study Eligibility Criteria Primary source articles published in English in peer-reviewed journals. Articles that presented data on, PA, fitness or physical education (PE)/sport participation and cognition, learning, brain function/structure, academic achievement, or concentration/attention were included. Data Sources Two separate searches were performed to identify studies that focused on (1) cognition, learning, brain structure, and brain function; and (2) standardized achievement test performance and concentration/attention. PubMed, ERIC, PsychInfo, SportDiscus, Scopus, Web of Science, Academic Search Premier, and Embase were searched (January 1990- September 2014) for studies that met inclusion criteria. Sixty-four met inclusion criteria for the first search (cognition/learning/brain) and 73 studies met inclusion criteria for the second search (academic achievement/concentration). Study appraisal and synthesis methods Articles were grouped by study design as cross-sectional, longitudinal, acute, or intervention trials. Considerable heterogeneity existed for several important study parameters, therefore results were synthesized and presented by study design. Results A majority of the research supports the view that physical fitness, single bouts of PA, and PA interventions benefit children's cognitive functioning. Limited evidence was available concerning the effects of PA on learning, with only one cross-sectional study meeting the inclusion criteria. Evidence indicates that PA has a relation to areas of the brain that support complex cognitive processes during laboratory tasks. While favorable results have been obtained from cross-sectional and longitudinal studies related to academic achievement, the results obtained from controlled experiments evaluating the benefits of PA on academic performance are mixed and additional, well-designed studies are needed. Limitations Limitations in evidence meeting inclusion criteria for this review include a lack of randomized controlled trials, limited studies that are adequately powered, lack of information on participant characteristics, failure to blind for outcome measures, proximity of PA to measurement outcomes, and lack of accountability for known confounders. Therefore, many studies were ranked as high risk for bias due to multiple design limitations. Conclusions The present systematic review found evidence to suggest that there are positive associations among PA, fitness, cognition, and academic achievement. However, the findings are inconsistent and the effects of numerous elements of PA on cognition remain to be explored, such as type, amount, frequency, and timing. Many questions remain regarding how to best incorporate PA within schools, such as activity breaks versus active lessons in relation to improved academic achievement. Regardless, the literature suggests no indication that increases in PA negatively affect cognition or academic achievement and PA is important for growth and development and general health. Based on the evidence available, the authors concluded that PA has a positive influence on cognition as well as brain structure and function; however, more research is necessary to determine mechanisms and long-term impact as well as strategies to translate laboratory findings to the school environment. Therefore the Evidence Category rating is B. The literature suggests that PA and PE have a neutral effect on academic achievement. Thus, due to the limitations in the literature and the current information available, the Evidence Category rating for academic achievement is C. PMID:27182986

  3. Physical Activity, Fitness, Cognitive Function, and Academic Achievement in Children: A Systematic Review.

    PubMed

    Donnelly, Joseph E; Hillman, Charles H; Castelli, Darla; Etnier, Jennifer L; Lee, Sarah; Tomporowski, Phillip; Lambourne, Kate; Szabo-Reed, Amanda N

    2016-06-01

    The relationship among physical activity (PA), fitness, cognitive function, and academic achievement in children is receiving considerable attention. The utility of PA to improve cognition and academic achievement is promising but uncertain; thus, this position stand will provide clarity from the available science. The purpose of this study was to answer the following questions: 1) among children age 5-13 yr, do PA and physical fitness influence cognition, learning, brain structure, and brain function? 2) Among children age 5-13 yr, do PA, physical education (PE), and sports programs influence standardized achievement test performance and concentration/attention? This study used primary source articles published in English in peer-reviewed journals. Articles that presented data on, PA, fitness, or PE/sport participation and cognition, learning, brain function/structure, academic achievement, or concentration/attention were included. Two separate searches were performed to identify studies that focused on 1) cognition, learning, brain structure, and brain function and 2) standardized achievement test performance and concentration/attention. PubMed, ERIC, PsychInfo, SportDiscus, Scopus, Web of Science, Academic Search Premier, and Embase were searched (January 1990-September 2014) for studies that met inclusion criteria. Sixty-four studies met inclusion criteria for the first search (cognition/learning/brain), and 73 studies met inclusion criteria for the second search (academic achievement/concentration). Articles were grouped by study design as cross-sectional, longitudinal, acute, or intervention trials. Considerable heterogeneity existed for several important study parameters; therefore, results were synthesized and presented by study design. A majority of the research supports the view that physical fitness, single bouts of PA, and PA interventions benefit children's cognitive functioning. Limited evidence was available concerning the effects of PA on learning, with only one cross-sectional study meeting the inclusion criteria. Evidence indicates that PA has a relationship to areas of the brain that support complex cognitive processes during laboratory tasks. Although favorable results have been obtained from cross-sectional and longitudinal studies related to academic achievement, the results obtained from controlled experiments evaluating the benefits of PA on academic performance are mixed, and additional, well-designed studies are needed. Limitations in evidence meeting inclusion criteria for this review include lack of randomized controlled trials, limited studies that are adequately powered, lack of information on participant characteristics, failure to blind for outcome measures, proximity of PA to measurement outcomes, and lack of accountability for known confounders. Therefore, many studies were ranked as high risk for bias because of multiple design limitations. The present systematic review found evidence to suggest that there are positive associations among PA, fitness, cognition, and academic achievement. However, the findings are inconsistent, and the effects of numerous elements of PA on cognition remain to be explored, such as type, amount, frequency, and timing. Many questions remain regarding how to best incorporate PA within schools, such as activity breaks versus active lessons in relation to improved academic achievement. Regardless, the literature suggests no indication that increases in PA negatively affect cognition or academic achievement and PA is important for growth and development and general health. On the basis of the evidence available, the authors concluded that PA has a positive influence on cognition as well as brain structure and function; however, more research is necessary to determine mechanisms and long-term effect as well as strategies to translate laboratory findings to the school environment. Therefore, the evidence category rating is B. The literature suggests that PA and PE have a neutral effect on academic achievement. Thus, because of the limitations in the literature and the current information available, the evidence category rating for academic achievement is C.

  4. Sociochemosensory and Emotional Functions: Behavioral Evidence for Shared Mechanisms

    PubMed Central

    Zhou, Wen; Chen, Denise

    2009-01-01

    Olfaction and emotion are distinctively different systems. Nevertheless, there are reasons to suspect that they influence each other on the social level. Functionally, olfactory chemosensory communication is used by a wide range of animals to convey individual and group identity, as well as attraction or repulsion. Anatomically, the olfactory brain overlaps with the socioemotional brain, and is believed to have contributed to the evolution of the latter. Little is known about how the functional and anatomical links are manifested in behavior, however. Using human olfaction as a model, we demonstrate that chemosensory recognition of individuals—one of the most ubiquitous forms of social communication—is interconnected with both the cognitive and the visual processing of emotion. Our results provide the first behavioral evidence for mechanisms being shared by a sensory system and emotion. PMID:19686296

  5. Racial and ethnic disparities in functional, psychosocial, and neurobehavioral outcomes after brain injury.

    PubMed

    Arango-Lasprilla, Juan Carlos; Kreutzer, Jeffrey S

    2010-01-01

    Because of the growing minority population in the past 3 decades in the United States and the increasing numbers of individuals who sustain a traumatic brain injury (TBI), researchers and clinicians have started to pay more attention to the role of race and ethnicity in outcomes after TBI, with the goal of better serving this population. The aim of this article is to review the literature on the influence of race/ethnicity on functional, psychosocial, and neurobehavioral outcomes after TBI. Specifically, the following 8 areas of outcomes will be examined: (1) treatment outcomes, (2) neuropsychological outcomes, (3) employment/productivity, (4) functional outcomes, (5) community integration, (6) marital status, (7) quality of life/life satisfaction, and (8) emotional/neurobehavioral outcomes. To conclude this review, suggestions for improvements in professional competency, research, systems of care, and training are proposed.

  6. The consequences of fetal growth restriction on brain structure and neurodevelopmental outcome.

    PubMed

    Miller, Suzanne L; Huppi, Petra S; Mallard, Carina

    2016-02-15

    Fetal growth restriction (FGR) is a significant complication of pregnancy describing a fetus that does not grow to full potential due to pathological compromise. FGR affects 3-9% of pregnancies in high-income countries, and is a leading cause of perinatal mortality and morbidity. Placental insufficiency is the principal cause of FGR, resulting in chronic fetal hypoxia. This hypoxia induces a fetal adaptive response of cardiac output redistribution to favour vital organs, including the brain, and is in consequence called brain sparing. Despite this, it is now apparent that brain sparing does not ensure normal brain development in growth-restricted fetuses. In this review we have brought together available evidence from human and experimental animal studies to describe the complex changes in brain structure and function that occur as a consequence of FGR. In both humans and animals, neurodevelopmental outcomes are influenced by the timing of the onset of FGR, the severity of FGR, and gestational age at delivery. FGR is broadly associated with reduced total brain volume and altered cortical volume and structure, decreased total number of cells and myelination deficits. Brain connectivity is also impaired, evidenced by neuronal migration deficits, reduced dendritic processes, and less efficient networks with decreased long-range connections. Subsequent to these structural alterations, short- and long-term functional consequences have been described in school children who had FGR, most commonly including problems in motor skills, cognition, memory and neuropsychological dysfunctions. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  7. Influence of selected dietary components on the functioning of the human nervous system

    PubMed

    Wendołowicz, Agnieszka; Stefańska, Ewa; Ostrowska, Lucyna

    The diet is directly connected not only with the physical status but also with the functioning of the brain and the mental status. The potentially beneficial nutrients with a protective effect on the nervous system function include amino acids (tryptophan, phenylalanine, tyrosine, taurine), glucose and vitamins C, E, D and beta-carotene, B group vitamins (vitamin B12, vitamin B6, vitamin B4, vitamin B1) and minerals (selenium, zinc, magnesium, sodium, iron, copper, manganese, iodine). The presence of antioxidants in the diet protects against oxidative damage to nervous system cells. Biochemical data indicate that polyunsaturated fatty acids such as arachidonic acid (AA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) as structural components of the nervous system play a key role in its function. The nutrition of the entire body also influences the production of neurotransmitters in the brain. A diet without an appropriate supply of protein, mineral nutrients or vitamins may result in a failure to form appropriately balanced numbers of neurotransmitters, which, as a result, may lead to neurotransmission dysfunction. This is the reason why proper nutrition is based on vegetables, fruits, whole-grain cereal products supplemented with products providing full-value protein (dairy products, fish, lean meat) and high-quality fat products (vegetable oils, fish fats).

  8. GSK3 as a Sensor Determining Cell Fate in the Brain.

    PubMed

    Cole, Adam R

    2012-01-01

    Glycogen synthase kinase 3 (GSK3) is an unusual serine/threonine kinase that controls many neuronal functions, including neurite outgrowth, synapse formation, neurotransmission, and neurogenesis. It mediates these functions by phosphorylating a wide range of substrates involved in gene transcription, metabolism, apoptosis, cytoskeletal dynamics, signal transduction, lipid membrane dynamics, and trafficking, amongst others. This complicated list of diverse substrates generally follow a more simple pattern: substrates negatively regulated by GSK3-mediated phosphorylation favor a proliferative/survival state, while substrates positively regulated by GSK3 favor a more differentiated/functional state. Accordingly, GSK3 activity is higher in differentiated cells than undifferentiated cells and physiological (Wnt, growth factors) and pharmacological inhibitors of GSK3 promote the proliferative capacity of embryonic stem cells. In the brain, the level of GSK3 activity influences neural progenitor cell proliferation/differentiation in neuroplasticity and repair, as well as efficient neurotransmission in differentiated adult neurons. While defects in GSK3 activity are unlikely to be the primary cause of neurodegenerative diseases, therapeutic regulation of its activity to promote a proliferative/survival versus differentiated/mature functional environment in the brain could be a powerful strategy for treatment of neurodegenerative and other mental disorders.

  9. GSK3 as a Sensor Determining Cell Fate in the Brain

    PubMed Central

    Cole, Adam R.

    2012-01-01

    Glycogen synthase kinase 3 (GSK3) is an unusual serine/threonine kinase that controls many neuronal functions, including neurite outgrowth, synapse formation, neurotransmission, and neurogenesis. It mediates these functions by phosphorylating a wide range of substrates involved in gene transcription, metabolism, apoptosis, cytoskeletal dynamics, signal transduction, lipid membrane dynamics, and trafficking, amongst others. This complicated list of diverse substrates generally follow a more simple pattern: substrates negatively regulated by GSK3-mediated phosphorylation favor a proliferative/survival state, while substrates positively regulated by GSK3 favor a more differentiated/functional state. Accordingly, GSK3 activity is higher in differentiated cells than undifferentiated cells and physiological (Wnt, growth factors) and pharmacological inhibitors of GSK3 promote the proliferative capacity of embryonic stem cells. In the brain, the level of GSK3 activity influences neural progenitor cell proliferation/differentiation in neuroplasticity and repair, as well as efficient neurotransmission in differentiated adult neurons. While defects in GSK3 activity are unlikely to be the primary cause of neurodegenerative diseases, therapeutic regulation of its activity to promote a proliferative/survival versus differentiated/mature functional environment in the brain could be a powerful strategy for treatment of neurodegenerative and other mental disorders. PMID:22363258

  10. Infiltration of the basal ganglia by brain tumors is associated with the development of co-dominant language function on fMRI.

    PubMed

    Shaw, Katharina; Brennan, Nicole; Woo, Kaitlin; Zhang, Zhigang; Young, Robert; Peck, Kyung K; Holodny, Andrei

    2016-01-01

    Studies have shown that some patients with left-hemispheric brain tumors have an increased propensity for developing right-sided language support. However, the precise trigger for establishing co-dominant language function in brain tumor patients remains unknown. We analyzed the MR scans of patients with left-hemispheric tumors and either co-dominant (n=35) or left-hemisphere dominant (n=35) language function on fMRI to investigate anatomical factors influencing hemispheric language dominance. Of eleven neuroanatomical areas evaluated for tumor involvement, the basal ganglia was significantly correlated with co-dominant language function (p<0.001). Moreover, among patients whose tumors invaded the basal ganglia, those with language co-dominance performed significantly better on the Boston Naming Test, a clinical measure of aphasia, compared to their left-lateralized counterparts (56.5 versus 36.5, p=0.025). While further studies are needed to elucidate the role of the basal ganglia in establishing co-dominance, our results suggest that reactive co-dominance may afford a behavioral advantage to patients with left-hemispheric tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal.

    PubMed

    Riem, Madelon M E; van IJzendoorn, Marinus H; Tops, Mattie; Boksem, Maarten A S; Rombouts, Serge A R B; Bakermans-Kranenburg, Marian J

    2013-10-01

    The neuropeptide oxytocin has been implicated in a variety of social processes. However, recent studies indicate that oxytocin does not enhance prosocial behavior in all people in all circumstances. Here, we investigate effects of intranasal oxytocin administration on intrinsic functional brain connectivity with resting state functional magnetic resonance imaging. Participants were 42 women who received a nasal spray containing either 16 IU of oxytocin or a placebo and reported how often their mother used love withdrawal as a disciplinary strategy involving withholding love and affection after a failure or misbehavior. We found that oxytocin changes functional connectivity between the posterior cingulate cortex (PCC) and the brainstem. In the oxytocin group there was a positive connectivity between these regions, whereas the placebo group showed negative connectivity. In addition, oxytocin induced functional connectivity changes between the PCC, the cerebellum and the postcentral gyrus, but only for those participants who experienced low levels of maternal love withdrawal. We speculate that oxytocin enhances prosocial behavior by influencing complex brain networks involved in self-referential processing and affectionate touch, most prominently in individuals with supportive family backgrounds. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

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

    PubMed

    Batouli, Seyed Amir Hossein; Saba, Valiallah

    2017-08-14

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

  13. Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism.

    PubMed

    Dienel, Gerald A; Cruz, Nancy F

    2016-07-01

    Aerobic glycolysis occurs during brain activation and is characterized by preferential up-regulation of glucose utilization compared with oxygen consumption even though oxygen level and delivery are adequate. Aerobic glycolysis is a widespread phenomenon that underlies energetics of diverse brain activities, such as alerting, sensory processing, cognition, memory, and pathophysiological conditions, but specific cellular functions fulfilled by aerobic glycolysis are poorly understood. Evaluation of evidence derived from different disciplines reveals that aerobic glycolysis is a complex, regulated phenomenon that is prevented by propranolol, a non-specific β-adrenoceptor antagonist. The metabolic pathways that contribute to excess utilization of glucose compared with oxygen include glycolysis, the pentose phosphate shunt pathway, the malate-aspartate shuttle, and astrocytic glycogen turnover. Increased lactate production by unidentified cells, and lactate dispersal from activated cells and lactate release from the brain, both facilitated by astrocytes, are major factors underlying aerobic glycolysis in subjects with low blood lactate levels. Astrocyte-neuron lactate shuttling with local oxidation is minor. Blockade of aerobic glycolysis by propranolol implicates adrenergic regulatory processes including adrenal release of epinephrine, signaling to brain via the vagus nerve, and increased norepinephrine release from the locus coeruleus. Norepinephrine has a powerful influence on astrocytic metabolism and glycogen turnover that can stimulate carbohydrate utilization more than oxygen consumption, whereas β-receptor blockade 're-balances' the stoichiometry of oxygen-glucose or -carbohydrate metabolism by suppressing glucose and glycogen utilization more than oxygen consumption. This conceptual framework may be helpful for design of future studies to elucidate functional roles of preferential non-oxidative glucose utilization and glycogen turnover during brain activation. Aerobic glycolysis, the preferential up-regulation of glucose utilization (CMRglc ) compared with oxygen consumption (CMRO2 ) during brain activation, is blocked by propranolol. Epinephrine release from the adrenal gland stimulates vagus nerve signaling to the locus coeruleus, enhancing norepinephrine release in the brain, and regulation of astrocytic and neuronal metabolism to stimulate CMRglc more than CMRO2 . Propranolol suppresses CMRglc more than CMRO2 . © 2016 International Society for Neurochemistry.

  14. Kynurenine 3-Monooxygenase: An Influential Mediator of Neuropathology.

    PubMed

    Parrott, Jennifer M; O'Connor, Jason C

    2015-01-01

    Mounting evidence demonstrates that kynurenine metabolism may play an important pathogenic role in the development of multiple neurological and neuropsychiatric disorders. The kynurenine pathway consists of two functionally distinct branches that generate both neuroactive and oxidatively reactive metabolites. In the brain, the rate-limiting enzyme for one of these branches, kynurenine 3-monooxygenase (KMO), is predominantly expressed in microglia and has emerged as a pivotal point of metabolic regulation. KMO substrate and expression levels are upregulated by pro-inflammatory cytokines and altered by functional genetic mutations. Increased KMO metabolism results in the formation of metabolites that activate glutamate receptors and elevate oxidative stress, while recent evidence has revealed neurodevelopmental consequences of reduced KMO activity. Together, the evidence suggests that KMO is positioned at a critical metabolic junction to influence the development or trajectory of a myriad of neurological diseases. Understanding the mechanism(s) by which alterations in KMO activity are able to impair neuronal function, and viability will enhance our knowledge of related disease pathology and provide insight into novel therapeutic opportunities. This review will discuss the influence of KMO on brain kynurenine metabolism and the current understanding of molecular mechanisms by which altered KMO activity may contribute to neurodevelopment, neurodegenerative, and neuropsychiatric diseases.

  15. Kynurenine 3-Monooxygenase: An Influential Mediator of Neuropathology

    PubMed Central

    Parrott, Jennifer M.; O’Connor, Jason C.

    2015-01-01

    Mounting evidence demonstrates that kynurenine metabolism may play an important pathogenic role in the development of multiple neurological and neuropsychiatric disorders. The kynurenine pathway consists of two functionally distinct branches that generate both neuroactive and oxidatively reactive metabolites. In the brain, the rate-limiting enzyme for one of these branches, kynurenine 3-monooxygenase (KMO), is predominantly expressed in microglia and has emerged as a pivotal point of metabolic regulation. KMO substrate and expression levels are upregulated by pro-inflammatory cytokines and altered by functional genetic mutations. Increased KMO metabolism results in the formation of metabolites that activate glutamate receptors and elevate oxidative stress, while recent evidence has revealed neurodevelopmental consequences of reduced KMO activity. Together, the evidence suggests that KMO is positioned at a critical metabolic junction to influence the development or trajectory of a myriad of neurological diseases. Understanding the mechanism(s) by which alterations in KMO activity are able to impair neuronal function, and viability will enhance our knowledge of related disease pathology and provide insight into novel therapeutic opportunities. This review will discuss the influence of KMO on brain kynurenine metabolism and the current understanding of molecular mechanisms by which altered KMO activity may contribute to neurodevelopment, neurodegenerative, and neuropsychiatric diseases. PMID:26347662

  16. Robustness of Representative Signals Relative to Data Loss Using Atlas-Based Parcellations.

    PubMed

    Gajdoš, Martin; Výtvarová, Eva; Fousek, Jan; Lamoš, Martin; Mikl, Michal

    2018-04-24

    Parcellation-based approaches are an important part of functional magnetic resonance imaging data analysis. They are a necessary processing step for sorting data in structurally or functionally homogenous regions. Real functional magnetic resonance imaging datasets usually do not cover the atlas template completely; they are often spatially constrained due to the physical limitations of MR sequence settings, the inter-individual variability in brain shape, etc. When using a parcellation template, many regions are not completely covered by actual data. This paper addresses the issue of the area coverage required in real data in order to reliably estimate the representative signal and the influence of this kind of data loss on network analysis metrics. We demonstrate this issue on four datasets using four different widely used parcellation templates. We used two erosion approaches to simulate data loss on the whole-brain level and the ROI-specific level. Our results show that changes in ROI coverage have a systematic influence on network measures. Based on the results of our analysis, we recommend controlling the ROI coverage and retaining at least 60% of the area in order to ensure at least 80% of explained variance of the original signal.

  17. Influence of acute sleep loss on the neural correlates of alerting, orientating and executive attention components.

    PubMed

    Muto, Vincenzo; Shaffii-le Bourdiec, Anahita; Matarazzo, Luca; Foret, Ariane; Mascetti, Laura; Jaspar, Mathieu; Vandewalle, Gilles; Phillips, Christophe; Degueldre, Christian; Balteau, Evelyne; Luxen, André; Collette, Fabienne; Maquet, Pierre

    2012-12-01

    The Attention Network Test (ANT) is deemed to assess the alerting, orientating and executive components of human attention. Capitalizing on the opportunity to investigate three facets of attention in a single task, we used functional magnetic resonance imaging (fMRI) to assess the effect of sleep deprivation (SD) on brain responses associated with the three attentional components elicited by the ANT. Twelve healthy volunteers were scanned in two conditions 1 week apart, after a normal night of sleep (rested wakefulness, RW) or after one night of total sleep deprivation. Sleep deprivation was associated with a global increase in reaction times, which did not affect specifically any of the three attention effects. Brain responses associated with the alerting effect did not differ between RW and SD. Higher-order attention components (orientating and conflict effects) were associated with significantly larger thalamic responses during SD than during RW. These results suggest that SD influences different components of human attention non-selectively, through mechanisms that might either affect centrencephalic structures maintaining vigilance or ubiquitously perturb neuronal function. Compensatory responses can counter these effects transiently by recruiting thalamic responses, thereby supporting thalamocortical function. © 2012 European Sleep Research Society.

  18. Pain, dissociation and subliminal self-representations.

    PubMed

    Bob, Petr

    2008-03-01

    According to recent evidence, neurophysiological processes coupled to pain are closely related to the mechanisms of consciousness. This evidence is in accordance with findings that changes in states of consciousness during hypnosis or traumatic dissociation strongly affect conscious perception and experience of pain, and markedly influence brain functions. Past research indicates that painful experience may induce dissociated state and information about the experience may be stored or processed unconsciously. Reported findings suggest common neurophysiological mechanisms of pain and dissociation and point to a hypothesis of dissociation as a defense mechanism against psychological and physical pain that substantially influences functions of consciousness. The hypothesis is also supported by findings that information can be represented in the mind/brain without the subject's awareness. The findings of unconsciously present information suggest possible binding between conscious contents and self-functions that constitute self-representational dimensions of consciousness. The self-representation means that certain inner states of own body are interpreted as mental and somatic identity, while other bodily signals, currently not accessible to the dominant interpreter's access are dissociated and may be defined as subliminal self-representations. In conclusion, the neurophysiological aspects of consciousness and its integrative role in the therapy of painful traumatic memories are discussed.

  19. Tai Chi Chuan optimizes the functional organization of the intrinsic human brain architecture in older adults

    PubMed Central

    Wei, Gao-Xia; Dong, Hao-Ming; Yang, Zhi; Luo, Jing; Zuo, Xi-Nian

    2014-01-01

    Whether Tai Chi Chuan (TCC) can influence the intrinsic functional architecture of the human brain remains unclear. To examine TCC-associated changes in functional connectomes, resting-state functional magnetic resonance images were acquired from 40 older individuals including 22 experienced TCC practitioners (experts) and 18 demographically matched TCC-naïve healthy controls, and their local functional homogeneities across the cortical mantle were compared. Compared to the controls, the TCC experts had significantly greater and more experience-dependent functional homogeneity in the right post-central gyrus (PosCG) and less functional homogeneity in the left anterior cingulate cortex (ACC) and the right dorsal lateral prefrontal cortex. Increased functional homogeneity in the PosCG was correlated with TCC experience. Intriguingly, decreases in functional homogeneity (improved functional specialization) in the left ACC and increases in functional homogeneity (improved functional integration) in the right PosCG both predicted performance gains on attention network behavior tests. These findings provide evidence for the functional plasticity of the brain’s intrinsic architecture toward optimizing locally functional organization, with great implications for understanding the effects of TCC on cognition, behavior and health in aging population. PMID:24860494

  20. Phosphatidylserine in the Brain: Metabolism and Function

    PubMed Central

    Kim, Hee-Yong; Huang, Bill X.; Spector, Arthur A.

    2014-01-01

    Phosphatidylserine (PS) is the major anionic phospholipid class particularly enriched in the inner leaflet of the plasma membrane in neural tissues. PS is synthesized from phosphatidylcholine or phosphatidylethanolamine by exchanging the base head group with serine in reactions are catalyzed by phosphatidylserine synthase 1 and phosphatidylserine synthase 2 located in the endoplasmic reticulum. Activation of Akt, Raf-1 and protein kinase C signaling, which supports neuronal survival and differentiation, requires interaction of these proteins with PS localized in the cytoplasmic leaflet of the plasma membrane. Furthermore, neurotransmitter release by exocytosis and a number of synaptic receptors and proteins are modulated by PS present in the neuronal membranes. Brain is highly enriched with docosahexaenoic acid (DHA), and brain PS has a high DHA content. By promoting PS synthesis, DHA can uniquely expand the PS pool in neuronal membranes and thereby influence PS-dependent signaling and protein function. Ethanol decreases DHA-promoted PS synthesis and accumulation in neurons, which may contribute to the deleterious effects of ethanol intake. Improvement of some memory functions has been observed in cognitively impaired subjects as a result of PS supplementation, but the mechanism is unclear. PMID:24992464

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