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Sample records for adult brain function

  1. Adult neurogenesis and its role in neuropsychiatric disease, brain repair and normal brain function.

    PubMed

    Braun, S M G; Jessberger, S

    2014-02-01

    Neural stem/progenitor cells (NSPCs) in the mammalian brain retain the ability to generate new neurones throughout life in discrete brain regions, through a process called adult neurogenesis. Adult neurogenesis, a dramatic form of adult brain circuitry plasticity, has been implicated in physiological brain function and appears to be of pivotal importance for certain forms of learning and memory. In addition, failing or altered neurogenesis has been associated with a variety of brain diseases such as major depression, epilepsy and age-related cognitive decline. Here we review recent advances in our understanding of the basic biology underlying the neurogenic process in the adult brain, focusing on mechanisms that regulate quiescence, proliferation and differentiation of NSPCs. In addition, we discuss how neurogenesis influences normal brain function, and in particular its role in memory formation, as well as its contribution to neuropsychiatric diseases. Finally, we evaluate the potential of targeting endogenous NSPCs for brain repair.

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

    PubMed

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

    2011-12-05

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

  3. Roles for oestrogen receptor β in adult brain function.

    PubMed

    Handa, R J; Ogawa, S; Wang, J M; Herbison, A E

    2012-01-01

    Oestradiol exerts a profound influence upon multiple brain circuits. For the most part, these effects are mediated by oestrogen receptor (ER)α. We review here the roles of ERβ, the other ER isoform, in mediating rodent oestradiol-regulated anxiety, aggressive and sexual behaviours, the control of gonadotrophin secretion, and adult neurogenesis. Evidence exists for: (i) ERβ located in the paraventricular nucleus underpinning the suppressive influence of oestradiol on the stress axis and anxiety-like behaviour; (ii) ERβ expressed in gonadotrophin-releasing hormone neurones contributing to oestrogen negative-feedback control of gonadotrophin secretion; (iii) ERβ controlling the offset of lordosis behaviour; (iv) ERβ suppressing aggressive behaviour in males; (v) ERβ modulating responses to social stimuli; and (vi) ERβ in controlling adult neurogenesis. This review highlights two major themes; first, ERβ and ERα are usually tightly inter-related in the oestradiol-dependent control of a particular brain function. For example, even though oestradiol feedback to control reproduction occurs principally through ERα-dependent mechanisms, modulatory roles for ERβ also exist. Second, the roles of ERα and ERβ within a particular neural network may be synergistic or antagonistic. Examples of the latter include the role of ERα to enhance, and ERβ to suppress, anxiety-like and aggressive behaviours. Splice variants such as ERβ2, acting as dominant negative receptors, are of further particular interest because their expression levels may reflect preceeding oestradiol exposure of relevance to oestradiol replacement therapy. Together, this review highlights the predominant modulatory, but nonetheless important, roles of ERβ in mediating the many effects of oestradiol upon adult brain function.

  4. Hour-Long Nap May Boost Brain Function in Older Adults

    MedlinePlus

    ... fullstory_162923.html Hour-Long Nap May Boost Brain Function in Older Adults Linked to improved memory and ... during the day had any effects on their brain function. Nearly 60 percent of the people regularly napped ...

  5. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging

    PubMed Central

    Bell, Robert D.; Winkler, Ethan A.; Sagare, Abhay P.; Singh, Itender; LaRue, Barb; Deane, Rashid; Zlokovic, Berislav V.

    2010-01-01

    SUMMARY Pericytes play a key role in the development of cerebral microcirculation. The exact role of pericytes in the neurovascular unit in the adult brain and during brain aging remains, however, elusive. Using adult viable pericyte-deficient mice, we show that pericyte loss leads to brain vascular damage by two parallel pathways: (1) reduction in brain microcirculation causing diminished brain capillary perfusion, cerebral blood flow and cerebral blood flow responses to brain activation which ultimately mediates chronic perfusion stress and hypoxia, and (2) blood-brain barrier breakdown associated with brain accumulation of serum proteins and several vasculotoxic and/or neurotoxic macromolecules ultimately leading to secondary neuronal degenerative changes. We show that age-dependent vascular damage in pericyte-deficient mice precedes neuronal degenerative changes, learning and memory impairment and the neuroinflammatory response. Thus, pericytes control key neurovascular functions that are necessary for proper neuronal structure and function, and pericytes loss results in a progressive age-dependent vascular-mediated neurodegeneration. PMID:21040844

  6. Brain tumor - primary - adults

    MedlinePlus

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  7. Inflammation regulates functional integration of neurons born in adult brain.

    PubMed

    Jakubs, Katherine; Bonde, Sara; Iosif, Robert E; Ekdahl, Christine T; Kokaia, Zaal; Kokaia, Merab; Lindvall, Olle

    2008-11-19

    Inflammation influences several steps of adult neurogenesis, but whether it regulates the functional integration of the new neurons is unknown. Here, we explored, using confocal microscopy and whole-cell patch-clamp recordings, whether a chronic inflammatory environment affects the morphological and electrophysiological properties of new dentate gyrus granule cells, labeled with a retroviral vector encoding green fluorescent protein. Rats were exposed to intrahippocampal injection of lipopolysaccharide, which gave rise to long-lasting microglia activation. Inflammation caused no changes in intrinsic membrane properties, location, dendritic arborization, or spine density and morphology of the new cells. Excitatory synaptic drive increased to the same extent in new and mature cells in the inflammatory environment, suggesting increased network activity in hippocampal neural circuitries of lipopolysaccharide-treated animals. In contrast, inhibitory synaptic drive was more enhanced by inflammation in the new cells. Also, larger clusters of the postsynaptic GABA(A) receptor scaffolding protein gephyrin were found on dendrites of new cells born in the inflammatory environment. We demonstrate for the first time that inflammation influences the functional integration of adult-born hippocampal neurons. Our data indicate a high degree of synaptic plasticity of the new neurons in the inflammatory environment, which enables them to respond to the increase in excitatory input with a compensatory upregulation of activity and efficacy at their afferent inhibitory synapses.

  8. Delineating multiple functions of VEGF-A in the adult brain.

    PubMed

    Licht, Tamar; Keshet, Eli

    2013-05-01

    Vascular endothelial growth factor-A (abbreviated throughout this review as VEGF) is mostly known for its angiogenic activity, for its activity as a vascular permeability factor, and for its vascular survival activity [1]. There is a growing body of evidence, however, that VEGF fulfills additional less 'traditional' functions in multiple organs, both during development, as well as homeostatic functions in fully developed organs. This review focuses on the multiple roles of VEGF in the adult brain and is less concerned with the roles played by VEGF during brain development, functions described elsewhere in this review series. Most functions of VEGF that are essential for proper brain development are, in fact, dispensable in the adult brain as was clearly demonstrated using a conditional brain-specific VEGF loss-of-function (LOF) approach. Thus, in contrast to VEGF LOF in the developing brain, a process which is detrimental for the growth and survival of blood vessels and leads to massive neuronal apoptosis [2-4], continued signaling by VEGF in the mature brain is no longer required for maintaining already established cerebral vasculature and its inhibition does not cause appreciable vessel regression, hypoxia or apoptosis [4-7]. Yet, VEGF continues to be expressed in the adult brain in a constitutive manner. Moreover, VEGF is expressed in the adult brain in a region-specific manner and in distinctive spatial patterns incompatible with an angiogenic role (see below), strongly suggesting angiogenesis-independent and possibly also perfusion-independent functions. Here we review current knowledge on some of these 'non-traditional', often unexpected homeostatic VEGF functions, including those unrelated to its effects on the brain vasculature. These effects could be mediated directly (on non-vascular cells expressing cognate VEGF receptors) or indirectly (via the endothelium). Experimental approaches aimed at distinguishing between these possibilities for each particular

  9. Cardiovascular risks and brain function: a functional magnetic resonance imaging study of executive function in older adults.

    PubMed

    Chuang, Yi-Fang; Eldreth, Dana; Erickson, Kirk I; Varma, Vijay; Harris, Gregory; Fried, Linda P; Rebok, George W; Tanner, Elizabeth K; Carlson, Michelle C

    2014-06-01

    Cardiovascular (CV) risk factors, such as hypertension, diabetes, and hyperlipidemia are associated with cognitive impairment and risk of dementia in older adults. However, the mechanisms linking them are not clear. This study aims to investigate the association between aggregate CV risk, assessed by the Framingham general cardiovascular risk profile, and functional brain activation in a group of community-dwelling older adults. Sixty participants (mean age: 64.6 years) from the Brain Health Study, a nested study of the Baltimore Experience Corps Trial, underwent functional magnetic resonance imaging using the Flanker task. We found that participants with higher CV risk had greater task-related activation in the left inferior parietal region, and this increased activation was associated with poorer task performance. Our results provide insights into the neural systems underlying the relationship between CV risk and executive function. Increased activation of the inferior parietal region may offer a pathway through which CV risk increases risk for cognitive impairment.

  10. Brain function differences in language processing in children and adults with autism.

    PubMed

    Williams, Diane L; Cherkassky, Vladimir L; Mason, Robert A; Keller, Timothy A; Minshew, Nancy J; Just, Marcel Adam

    2013-08-01

    Comparison of brain function between children and adults with autism provides an understanding of the effects of the disorder and associated maturational differences on language processing. Functional imaging (functional magnetic resonance imaging) was used to examine brain activation and cortical synchronization during the processing of literal and ironic texts in 15 children with autism, 14 children with typical development, 13 adults with autism, and 12 adult controls. Both the children and adults with autism had lower functional connectivity (synchronization of brain activity among activated areas) than their age and ability comparison group in the left hemisphere language network during irony processing, and neither autism group had an increase in functional connectivity in response to increased task demands. Activation differences for the literal and irony conditions occurred in key language-processing regions (left middle temporal, left pars triangularis, left pars opercularis, left medial frontal, and right middle temporal). The children and adults with autism differed from each other in the use of some brain regions during the irony task, with the adults with autism having activation levels similar to those of the control groups. Overall, the children and adults with autism differed from the adult and child controls in (a) the degree of network coordination, (b) the distribution of the workload among member nodes, and (3) the dynamic recruitment of regions in response to text content. Moreover, the differences between the two autism age groups may be indicative of positive changes in the neural function related to language processing associated with maturation and/or educational experience.

  11. Combined Cognitive-Psychological-Physical Intervention Induces Reorganization of Intrinsic Functional Brain Architecture in Older Adults

    PubMed Central

    Zheng, Zhiwei; Zhu, Xinyi; Yin, Shufei; Wang, Baoxi; Niu, Yanan; Huang, Xin; Li, Rui; Li, Juan

    2015-01-01

    Mounting evidence suggests that enriched mental, physical, and socially stimulating activities are beneficial for counteracting age-related decreases in brain function and cognition in older adults. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate the functional plasticity of brain activity in response to a combined cognitive-psychological-physical intervention and investigated the contribution of the intervention-related brain changes to individual performance in healthy older adults. The intervention was composed of a 6-week program of combined activities including cognitive training, Tai Chi exercise, and group counseling. The results showed improved cognitive performance and reorganized regional homogeneity of spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signals in the superior and middle temporal gyri, and the posterior lobe of the cerebellum, in the participants who attended the intervention. Intriguingly, the intervention-induced changes in the coherence of local spontaneous activity correlated with the improvements in individual cognitive performance. Taken together with our previous findings of enhanced resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe regions following a combined intervention program in older adults, we conclude that the functional plasticity of the aging brain is a rather complex process, and an effective cognitive-psychological-physical intervention is helpful for maintaining a healthy brain and comprehensive cognition during old age. PMID:25810927

  12. Dietary resistant starch improves selected brain and behavioral functions in adult and aged rodents.

    PubMed

    Zhou, June; Keenan, Michael J; Fernandez-Kim, Sun Ok; Pistell, Paul J; Ingram, Donald K; Li, Bing; Raggio, Anne M; Shen, Li; Zhang, Hanjie; McCutcheon, Kathleen L; Tulley, Richard T; Blackman, Marc R; Keller, Jeffrey N; Martin, Roy J

    2013-11-01

    Resistant starch (RS) is a dietary fiber that exerts multiple beneficial effects. The current study explored the effects of dietary RS on selected brain and behavioral functions in adult and aged rodents. Because glucokinase (GK) expression in hypothalamic arcuate nucleus and area postrema of the brainstem is important for brain glucose sensing, GK mRNA was measured by brain nuclei microdissection and PCR. Adult RS-fed rats had a higher GK mRNA than controls in both brain nuclei, an indicator of improved brain glucose sensing. Next, we tested whether dietary RS improve selected behaviors in aged mice. RS-fed aged mice exhibited (i) an increased eating responses to fasting, a behavioral indicator of improvement in aged brain glucose sensing; (ii) a longer latency to fall from an accelerating rotarod, a behavioral indicator of improved motor coordination; and (iii) a higher serum active glucagon-like peptide-1 (GLP-1). Then, GLP-1 receptor null (GLP-1RKO) mice were used to test the role of GLP-1 in brain glucose sensing, and they exhibited impaired eating responses to fasting. We conclude that in rodents (i) dietary RS improves two important indicators of brain function: glucose sensing and motor coordination, and (ii) GLP-1 is important in the optimal feeding response to a fast.

  13. Executive control function, brain activation and white matter hyperintensities in older adults

    PubMed Central

    Venkatraman, Vijay K.; Aizenstein, Howard; Guralnik, Jack; Newman, Anne B.; Glynn, Nancy W.; Taylor, Christopher; Studenski, Stephanie; Launer, Lenore; Pahor, Marco; Williamson, Jeff; Rosano, Caterina

    2009-01-01

    Context Older adults responding to executive control function (ECF) tasks show greater brain activation on functional MRI (fMRI). It is not clear whether greater fMRI activation indicates a strategy to compensate for underlying brain structural abnormalities while maintaining higher performance. Objective To identify the patterns of fMRI activation in relationship with ECF performance and with brain structural abnormalities. Design Cross-sectional analysis. Main variables of interest: fMRI activation, accuracy while performing an ECF task (Digit Symbol Substitution Test), volume of white matter hyperintensities and of total brain atrophy. Setting Cohort of community-dwelling older adults. Participants Data were obtained on 25 older adults (20 women, 81 years mean age). Outcome Measure Accuracy (number of correct response / total number of responses) while performing the Digit Symbol Substitution Test. Results Greater accuracy was significantly associated with greater peak fMRI activation, from ECF regions, including left middle frontal gyrus and right posterior parietal cortex. Greater WMH was associated with lower activation within accuracy-related regions. The interaction of accuracy by white matter hyperintensities volume was significant within the left posterior parietal region. Specifically, the correlation of white matter hyperintensities volume with fMRI activation varied as a function of accuracy and it was positive for greater accuracy. Associations with brain atrophy were not significant. Conclusions Recruitment of additional areas and overall greater brain activation in older adults is associated with higher performance. Posterior parietal activation may be particularly important to maintain higher accuracy in the presence of underlying brain connectivity structural abnormalities. PMID:19922803

  14. Associations among executive function, cardiorespiratory fitness, and brain network properties in older adults

    PubMed Central

    Kawagoe, Toshikazu; Onoda, Keiichi; Yamaguchi, Shuhei

    2017-01-01

    Aging is associated with deterioration in a number of cognitive functions. Previous reports have demonstrated the beneficial effect of physical fitness on cognitive function, especially executive function (EF). The graph theoretical approach models the brain as a complex network represented graphically as nodes and edges. We analyzed several measures of EF, an index of physical fitness, and resting-state functional magnetic resonance imaging data from healthy older volunteers to elucidate the associations among EF, cardiorespiratory fitness, and brain network properties. The topological neural properties were significantly related to the level of EF and/or physical fitness. Global efficiency, which represents how well the whole brain is integrated, was positively related, whereas local efficiency, which represents how well the brain is functionally segregated, was negatively related, to the level of EF and fitness. The associations among EF, physical fitness and topological resting-state functional network property appear related to compensation and dedifferentiation in older age. A mediation analysis showed that high-fit older adults gain higher global efficiency of the brain at the expense of lower local efficiency. The results suggest that physical fitness may be beneficial in maintaining EF in healthy aging by enhancing the efficiency of the global brain network. PMID:28054664

  15. The effects of sleep deprivation on brain functioning in older adults.

    PubMed

    Almklov, Erin L; Drummond, Sean P A; Orff, Henry; Alhassoon, Omar M

    2015-01-01

    Few studies have examined the effects of total sleep deprivation (TSD) on cognitive performance and brain activation using functional MRI (fMRI) in older adults. The current study examines blood oxygen level-dependent (BOLD) activation in older adults and younger adults during the sustained attention (GO) and response inhibition (NOGO) portions of a GO-NOGO cognitive task following 36 hr of total sleep deprivation. No significant performance differences were observed between the groups on the behavioral outcome measures of total hits and false alarms. Neuroimaging results, however, revealed a significant interaction between age-group and sleep-deprivation status. Specifically, older adults showed greater BOLD activation as compared to younger adults after 36 hours total sleep deprivation in brain regions typically associated with attention and inhibitory processes. These results suggest in order for older adults to perform the GO-NOGO task effectively after sleep deprivation, they rely on compensatory recruitment of brain regions that aide in the maintenance of cognitive performance.

  16. 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

  17. The functional organisation of glia in the adult brain of Drosophila and other insects

    PubMed Central

    Edwards, Tara N.; Meinertzhagen, Ian A.

    2010-01-01

    This review annotates and categorises the glia of adult Drosophila and other model insects and describes the developmental origins of these in the Drosophila optic lobe. The functions of glia in the adult vary depending upon their sub-type and location in the brain. The task of annotating glia is essentially complete only for the glia of the fly's lamina, which comprise: two types of surface glia - the pseudocartridge and fenestrated glia; two types of cortex glia - the distal and proximal satellite glia; and two types of neuropile glia - the epithelial and marginal glia. We advocate that the term subretinal glia, as used to refer to both pseudocartridge and fenestrated glia, be abandoned. Other neuropiles contain similar glial subtypes, but other than the antennal lobes these have not been described in detail. Surface glia form the blood brain barrier, regulating the flow of substances into and out of the nervous system, both for the brain as a whole and the optic neuropiles in particular. Cortex glia provide a second level of barrier, wrapping axon fascicles and isolating neuronal cell bodies both from neighbouring brain regions and from their underlying neuropiles. Neuropile glia can be generated in the adult and a subtype, ensheathing glia, are responsible for cleaning up cellular debris during Wallerian degeneration. Both the neuropile ensheathing and astrocyte-like glia may be involved in clearing neurotransmitters from the extracellular space, thus modifying the levels of histamine, glutamate and possibly dopamine at the synapse to ultimately affect behaviour. PMID:20109517

  18. Brain volume and cognitive function in adult survivors of childhood acute lymphoblastic leukemia.

    PubMed

    Edelmann, Michelle N; Krull, Kevin R

    2013-10-01

    The survival rate for childhood acute lymphoblastic leukemia (ALL) is greater than 80%. However, many of these survivors develop long-term chronic health conditions, with a relatively common late effect being neurocognitive dysfunction. Although neurocognitive impairments have decreased in frequency and severity as treatment has evolved, there is a subset of survivors in the current treatment era that are especially vulnerable to the neurotoxic effects of ALL and its treatment. Additionally, little is known about long-term brain development as survivors mature into adulthood. A recent study by Zeller et al. compared neurocognitive function and brain volume in 130 adult survivors of childhood ALL to 130 healthy adults matched on age and sex. They identified the caudate as particularly sensitive to the neurotoxic effects of chemotherapy. We discuss the implications and limitations of this study, including how their findings support the concept of individual vulnerability to ALL and its treatment.

  19. Cognitive functioning in relation to brain amyloid-β in healthy adults with Down syndrome.

    PubMed

    Hartley, Sigan L; Handen, Benjamin L; Devenny, Darlynne A; Hardison, Regina; Mihaila, Iulia; Price, Julie C; Cohen, Annie D; Klunk, William E; Mailick, Marsha R; Johnson, Sterling C; Christian, Bradley T

    2014-09-01

    Nearly all adults with Down syndrome show neuropathology of Alzheimer's disease, including amyloid-β deposition, by their fifth decade of life. In the current study, we examined the association between brain amyloid-β deposition, assessed via in vivo assessments of neocortical Pittsburgh compound B, and scores on an extensive neuropsychological battery of measures of cognitive functioning in 63 adults (31 male, 32 female) with Down syndrome aged 30-53 years who did not exhibit symptoms of dementia. Twenty-two of the adults with Down syndrome were identified as having elevated neocortical Pittsburgh compound B retention levels. There was a significant positive correlation (r = 0.62, P < 0.0001) between age and neocortical Pittsburgh compound B retention. This robust association makes it difficult to discriminate normative age-related decline in cognitive functioning from any potential effects of amyloid-β deposition. When controlling for chronological age in addition to mental age, there were no significant differences between the adults with Down syndrome who had elevated neocortical Pittsburgh compound B retention levels and those who did not on any of the neuropsychological measures. Similarly, when examining Pittsburgh compound B as a continuous variable, after controlling for mental age and chronological age, only the Rivermead Picture Recognition score was significantly negatively associated with neocortical Pittsburgh compound B retention. Our findings indicate that many adults with Down syndrome can tolerate amyloid-β deposition without deleterious effects on cognitive functioning. However, we may have obscured true effects of amyloid-β deposition by controlling for chronological age in our analyses. Moreover, our sample included adults with Down syndrome who were most 'resistant' to the effects of amyloid-β deposition, as adults already exhibiting clinical symptoms of dementia symptoms were excluded from the study.

  20. Physical Activity and Brain Function in Older Adults at Increased Risk for Alzheimer’s Disease

    PubMed Central

    Smith, J. Carson; Nielson, Kristy A.; Woodard, John L.; Seidenberg, Michael; Rao, Stephen M.

    2013-01-01

    Leisure-time physical activity (PA) and exercise training are known to help maintain cognitive function in healthy older adults. However, relatively little is known about the effects of PA on cognitive function or brain function in those at increased risk for Alzheimer’s disease through the presence of the apolipoproteinE epsilon4 (APOE-ε4) allele, diagnosis of mild cognitive impairment (MCI), or the presence of metabolic disease. Here, we examine the question of whether PA and exercise interventions may differentially impact cognitive trajectory, clinical outcomes, and brain structure and function among individuals at the greatest risk for AD. The literature suggests that the protective effects of PA on risk for future dementia appear to be larger in those at increased genetic risk for AD. Exercise training is also effective at helping to promote stable cognitive function in MCI patients, and greater cardiorespiratory fitness is associated with greater brain volume in early-stage AD patients. In APOE-ε4 allele carriers compared to non-carriers, greater levels of PA may be more effective in reducing amyloid burden and are associated with greater activation of semantic memory-related neural circuits. A greater research emphasis should be placed on randomized clinical trials for exercise, with clinical, behavioral, and neuroimaging outcomes in people at increased risk for AD. PMID:24961307

  1. Long-chain omega-3 fatty acids improve brain function and structure in older adults.

    PubMed

    Witte, A Veronica; Kerti, Lucia; Hermannstädter, Henrike M; Fiebach, Jochen B; Schreiber, Stephan J; Schuchardt, Jan Philipp; Hahn, Andreas; Flöel, Agnes

    2014-11-01

    Higher intake of seafish or oil rich in long-chain omega-3 polyunsaturated fatty acids (LC-n3-FA) may be beneficial for the aging brain. We tested in a prospective interventional design whether high levels of supplementary LC-n3-FA would improve cognition, and addressed potential mechanisms underlying the effects. Sixty-five healthy subjects (50-75 years, 30 females) successfully completed 26 weeks of either fish oil (2.2 g/day LC-n3-FA) or placebo intake. Before and after the intervention period, cognitive performance, structural neuroimaging, vascular markers, and blood parameters were assayed. We found a significant increase in executive functions after LC-n3-FA compared with placebo (P = 0.023). In parallel, LC-n3-FA exerted beneficial effects on white matter microstructural integrity and gray matter volume in frontal, temporal, parietal, and limbic areas primarily of the left hemisphere, and on carotid intima media thickness and diastolic blood pressure. Improvements in executive functions correlated positively with changes in omega-3-index and peripheral brain-derived neurotrophic factor, and negatively with changes in peripheral fasting insulin. This double-blind randomized interventional study provides first-time evidence that LC-n3-FA exert positive effects on brain functions in healthy older adults, and elucidates underlying mechanisms. Our findings suggest novel strategies to maintain cognitive functions into old age.

  2. Functional Connectivity Abnormalities of Brain Regions with Structural Deficits in Young Adult Male Smokers

    PubMed Central

    Bu, Limei; Yu, Dahua; Su, Shaoping; Ma, Yao; von Deneen, Karen M.; Luo, Lin; Zhai, Jinquan; Liu, Bo; Cheng, Jiadong; Guan, Yanyan; Li, Yangding; Bi, Yanzhi; Xue, Ting; Lu, Xiaoqi; Yuan, Kai

    2016-01-01

    Smoking is one of the most prevalent dependence disorders. Previous studies have detected structural and functional deficits in smokers. However, few studies focused on the changes of resting state functional connectivity (RSFC) of the brain regions with structural deficits in young adult smokers. Twenty-six young adult smokers and 26 well-matched healthy non-smokers participated in our study. Voxel-based morphometry (VBM) and RSFC were employed to investigate the structural and functional changes in young adult smokers. Compared with healthy non-smokers, young smokers showed increased gray matter (GM) volume in the left putamen and decreased GM volume in the left anterior cingulate cortex (ACC). Moreover, GM volume in the left ACC has a negative correlation trend with pack-years and GM volume in the left putamen was positively correlated with pack-years. The left ACC and putamen with abnormal volumes were chosen as the regions of interest (ROIs) for the RSFC analysis. We found that smokers showed increased RSFC between the left ACC and right amygdala and between the left putamen and right anterior insula. We revealed structural and functional deficits within the frontostriatal circuits in young smokers, which may shed new insights into the neural mechanisms of smoking. PMID:27757078

  3. Purines regulate adult brain subventricular zone cell functions: contribution of reactive astrocytes.

    PubMed

    Boccazzi, Marta; Rolando, Chiara; Abbracchio, Maria P; Buffo, Annalisa; Ceruti, Stefania

    2014-03-01

    Brain injuries modulate activation of neural stem cells (NSCs) in the adult brain. In pathological conditions, the concentrations of extracellular nucleotides (eNTs) raise several folds, contribute to reactive gliosis, and possibly directly affect subventricular zone (SVZ) cell functioning. Among eNTs and derived metabolites, the P2Y1 receptor agonist ADP strongly promotes astrogliosis and might also influence SVZ progenitor activity. Here, we tested the ability of the stable P2Y1 agonist adenosine 5'-O-(2-thiodiphosphate) (ADPβS) to control adult NSC functions both in vitro and in vivo, with a focus on the possible effects exerted by reactive astrocytes. In the absence of growth factors, ADPβS promoted proliferation and differentiation of SVZ progenitors. Moreover, ADPβS-activated astrocytes markedly changed the pattern of released cytokines and chemokines, and strongly modulated neurosphere-forming capacity of SVZ progenitors. Notably, a significant enhancement in proliferation was observed when SVZ cells, initially grown in the supernatant of astrocytes exposed to ADPβS, were shifted to normal medium. In vivo, ADPβS administration in the lateral ventricle of adult mice by osmotic minipumps caused diffused reactive astrogliosis, and a strong response of SVZ progenitors. Indeed, proliferation of glial fibrillary acidic protein-positive NSCs increased and led to a significant expansion of SVZ transit-amplifying progenitors and neuroblasts. Lineage tracing experiments performed in the GLAST::CreERT2;Rosa-YFP transgenic mice further demonstrated that ADPβS promoted proliferation of glutamate/aspartate transporter-positive progenitors and sustained their progression toward the generation of rapidly dividing progenitors. Altogether, our results show that the purinergic system crucially affects SVZ progenitor activities both directly and through the involvement of reactive astrocytes.

  4. Intrinsic Functional Connectivity in the Adult Brain and Success in Second-Language Learning.

    PubMed

    Chai, Xiaoqian J; Berken, Jonathan A; Barbeau, Elise B; Soles, Jennika; Callahan, Megan; Chen, Jen-Kai; Klein, Denise

    2016-01-20

    There is considerable variability in an individual's ability to acquire a second language (L2) during adulthood. Using resting-state fMRI data acquired before training in English speakers who underwent a 12 week intensive French immersion training course, we investigated whether individual differences in intrinsic resting-state functional connectivity relate to a person's ability to acquire an L2. We focused on two key aspects of language processing--lexical retrieval in spontaneous speech and reading speed--and computed whole-brain functional connectivity from two regions of interest in the language network, namely the left anterior insula/frontal operculum (AI/FO) and the visual word form area (VWFA). Connectivity between the left AI/FO and left posterior superior temporal gyrus (STG) and between the left AI/FO and dorsal anterior cingulate cortex correlated positively with improvement in L2 lexical retrieval in spontaneous speech. Connectivity between the VWFA and left mid-STG correlated positively with improvement in L2 reading speed. These findings are consistent with the different language functions subserved by subcomponents of the language network and suggest that the human capacity to learn an L2 can be predicted by an individual's intrinsic functional connectivity within the language network. Significance statement: There is considerable variability in second-language learning abilities during adulthood. We investigated whether individual differences in intrinsic functional connectivity in the adult brain relate to success in second-language learning, using resting-state functional magnetic resonance imaging in English speakers who underwent a 12 week intensive French immersion training course. We found that pretraining functional connectivity within two different language subnetworks correlated strongly with learning outcome in two different language skills: lexical retrieval in spontaneous speech and reading speed. Our results suggest that the human

  5. Functional optoacoustic neuro-tomography of calcium fluxes in adult zebrafish brain in vivo.

    PubMed

    Deán-Ben, X Luís; Gottschalk, Sven; Sela, Gali; Shoham, Shy; Razansky, Daniel

    2017-03-01

    Genetically-encoded calcium indicators (GECIs) have revolutionized neuroimaging by enabling mapping of the activity of entire neuronal populations in vivo. Visualization of these powerful activity sensors has to date been limited to depth-restricted microscopic studies due to intense light scattering in the brain. We demonstrate, for the first time, in vivo real-time volumetric optoacoustic monitoring of calcium transients in adult transgenic zebrafish expressing the GCaMP5G calcium indicator. Fast changes in optoacoustic traces associated with GCaMP5G activity were detectable in the presence of other strongly absorbing endogenous chromophores, such as hemoglobin. The new functional optoacoustic neuroimaging method can visualize neural activity at penetration depths and spatio-temporal resolution scales not covered with the existing neuroimaging techniques.

  6. Reading in the brain of children and adults: A meta‐analysis of 40 functional magnetic resonance imaging studies

    PubMed Central

    Martin, Anna; Schurz, Matthias; Kronbichler, Martin

    2015-01-01

    Abstract We used quantitative, coordinate‐based meta‐analysis to objectively synthesize age‐related commonalities and differences in brain activation patterns reported in 40 functional magnetic resonance imaging (fMRI) studies of reading in children and adults. Twenty fMRI studies with adults (age means: 23–34 years) were matched to 20 studies with children (age means: 7–12 years). The separate meta‐analyses of these two sets showed a pattern of reading‐related brain activation common to children and adults in left ventral occipito‐temporal (OT), inferior frontal, and posterior parietal regions. The direct statistical comparison between the two meta‐analytic maps of children and adults revealed higher convergence in studies with children in left superior temporal and bilateral supplementary motor regions. In contrast, higher convergence in studies with adults was identified in bilateral posterior OT/cerebellar and left dorsal precentral regions. The results are discussed in relation to current neuroanatomical models of reading and tentative functional interpretations of reading‐related activation clusters in children and adults are provided. Hum Brain Mapp 36:1963–1981, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.. PMID:25628041

  7. Functional Integration of Adult-Born Hippocampal Neurons after Traumatic Brain Injury

    PubMed Central

    Villasana, Laura E.; Kim, Kristine N.

    2015-01-01

    Abstract Traumatic brain injury (TBI) increases hippocampal neurogenesis, which may contribute to cognitive recovery after injury. However, it is unknown whether TBI-induced adult-born neurons mature normally and functionally integrate into the hippocampal network. We assessed the generation, morphology, and synaptic integration of new hippocampal neurons after a controlled cortical impact (CCI) injury model of TBI. To label TBI-induced newborn neurons, we used 2-month-old POMC-EGFP mice, which transiently and specifically express EGFP in immature hippocampal neurons, and doublecortin-CreERT2 transgenic mice crossed with Rosa26-CAG-tdTomato reporter mice, to permanently pulse-label a cohort of adult-born hippocampal neurons. TBI increased the generation, outward migration, and dendritic complexity of neurons born during post-traumatic neurogenesis. Cells born after TBI had profound alterations in their dendritic structure, with increased dendritic branching proximal to the soma and widely splayed dendritic branches. These changes were apparent during early dendritic outgrowth and persisted as these cells matured. Whole-cell recordings from neurons generated during post-traumatic neurogenesis demonstrate that they are excitable and functionally integrate into the hippocampal circuit. However, despite their dramatic morphologic abnormalities, we found no differences in the rate of their electrophysiological maturation, or their overall degree of synaptic integration when compared to age-matched adult-born cells from sham mice. Our results suggest that cells born after TBI participate in information processing, and receive an apparently normal balance of excitatory and inhibitory inputs. However, TBI-induced changes in their anatomic localization and dendritic projection patterns could result in maladaptive network properties. PMID:26478908

  8. The effects of cognitive-behavioral therapy on intrinsic functional brain networks in adults with attention-deficit/hyperactivity disorder.

    PubMed

    Wang, Xiaoli; Cao, Qingjiu; Wang, Jinhui; Wu, Zhaomin; Wang, Peng; Sun, Li; Cai, Taisheng; Wang, Yufeng

    2016-01-01

    Cognitive-behavioral therapy (CBT) is an efficacious psychological treatment for adults with attention-deficit/hyperactivity disorder (ADHD), but the neural processes underlying the benefits of CBT are not well understood. This study aims to unravel psychosocial mechanisms for treatment ADHD by exploring the effects of CBT on functional brain networks. Ten adults with ADHD were enrolled and resting-state functional magnetic resonance imaging scans were acquired before and after a 12-session CBT. Twelve age- and gender-matched healthy controls were also scanned. We constructed whole-brain functional connectivity networks using graph-theory approaches and further computed the changes of regional functional connectivity strength (rFCS) between pre- and post-CBT in ADHD for measuring the effects of CBT. The results showed that rFCS was increased in the fronto-parietal network and cerebellum, the brain regions that were most often affected by medication, in adults with ADHD following CBT. Furthermore, the enhanced functional coupling between bilateral superior parietal gyrus was positively correlated with the improvement of ADHD symptoms following CBT. Together, these findings provide evidence that CBT can selectively modulate the intrinsic network connectivity in the fronto-parietal network and cerebellum and suggest that the CBT may share common brain mechanism with the pharmacology in adults with ADHD.

  9. Brain structures and functional connectivity associated with individual differences in Internet tendency in healthy young adults.

    PubMed

    Li, Weiwei; Li, Yadan; Yang, Wenjing; Zhang, Qinglin; Wei, Dongtao; Li, Wenfu; Hitchman, Glenn; Qiu, Jiang

    2015-04-01

    Internet addiction (IA) incurs significant social and financial costs in the form of physical side-effects, academic and occupational impairment, and serious relationship problems. The majority of previous studies on Internet addiction disorders (IAD) have focused on structural and functional abnormalities, while few studies have simultaneously investigated the structural and functional brain alterations underlying individual differences in IA tendencies measured by questionnaires in a healthy sample. Here we combined structural (regional gray matter volume, rGMV) and functional (resting-state functional connectivity, rsFC) information to explore the neural mechanisms underlying IAT in a large sample of 260 healthy young adults. The results showed that IAT scores were significantly and positively correlated with rGMV in the right dorsolateral prefrontal cortex (DLPFC, one key node of the cognitive control network, CCN), which might reflect reduced functioning of inhibitory control. More interestingly, decreased anticorrelations between the right DLPFC and the medial prefrontal cortex/rostral anterior cingulate cortex (mPFC/rACC, one key node of the default mode network, DMN) were associated with higher IAT scores, which might be associated with reduced efficiency of the CCN and DMN (e.g., diminished cognitive control and self-monitoring). Furthermore, the Stroop interference effect was positively associated with the volume of the DLPFC and with the IA scores, as well as with the connectivity between DLPFC and mPFC, which further indicated that rGMV variations in the DLPFC and decreased anticonnections between the DLPFC and mPFC may reflect addiction-related reduced inhibitory control and cognitive efficiency. These findings suggest the combination of structural and functional information can provide a valuable basis for further understanding of the mechanisms and pathogenesis of IA.

  10. Pharmacological reduction of adult hippocampal neurogenesis modifies functional brain circuits in mice exposed to a cocaine conditioned place preference paradigm.

    PubMed

    Castilla-Ortega, Estela; Blanco, Eduardo; Serrano, Antonia; Ladrón de Guevara-Miranda, David; Pedraz, María; Estivill-Torrús, Guillermo; Pavón, Francisco Javier; Rodríguez de Fonseca, Fernando; Santín, Luis J

    2016-05-01

    We investigated the role of adult hippocampal neurogenesis in cocaine-induced conditioned place preference (CPP) behaviour and the functional brain circuitry involved. Adult hippocampal neurogenesis was pharmacologically reduced with temozolomide (TMZ), and mice were tested for cocaine-induced CPP to study c-Fos expression in the hippocampus and in extrahippocampal addiction-related areas. Correlational and multivariate analysis revealed that, under normal conditions, the hippocampus showed widespread functional connectivity with other brain areas and strongly contributed to the functional brain module associated with CPP expression. However, the neurogenesis-reduced mice showed normal CPP acquisition but engaged an alternate brain circuit where the functional connectivity of the dentate gyrus was notably reduced and other areas (the medial prefrontal cortex, accumbens and paraventricular hypothalamic nucleus) were recruited instead of the hippocampus. A second experiment unveiled that mice acquiring the cocaine-induced CPP under neurogenesis-reduced conditions were delayed in extinguishing their drug-seeking behaviour. But if the inhibited neurons were generated after CPP acquisition, extinction was not affected but an enhanced long-term CPP retention was found, suggesting that some roles of the adult-born neurons may differ depending on whether they are generated before or after drug-contextual associations are established. Importantly, cocaine-induced reinstatement of CPP behaviour was increased in the TMZ mice, regardless of the time of neurogenesis inhibition. The results show that adult hippocampal neurogenesis sculpts the addiction-related functional brain circuits, and reduction of the adult-born hippocampal neurons increases cocaine seeking in the CPP model.

  11. Post-mortem brain pathology is related to declining respiratory function in community-dwelling older adults

    PubMed Central

    Buchman, Aron S.; Yu, Lei; Wilson, Robert S.; Dawe, Robert J.; VanderHorst, Veronique; Schneider, Julie A.; Bennett, David A.

    2015-01-01

    Damage to brain structures which constitute the distributed neural network that integrates respiratory muscle and pulmonary functions, can impair adequate ventilation and its volitional control. We tested the hypothesis that the level of brain pathology in older adults is associated with declining respiratory function measured during life. 1,409 older adults had annual testing with spirometry (SPI) and respiratory muscle strength (RMS) based on maximal inspiratory and maximal expiratory pressures (MEPs). Those who died underwent structured brain autopsy. On average, during 5 years of follow-up, SPI and RMS showed progressive decline which was moderately correlated (ρ = 0.57, p < 0.001). Among decedents (N = 447), indices of brain neuropathologies showed differential associations with declining SPI and RMS. Nigral neuronal loss was associated with the person-specific decline in SPI (Estimate, −0.016 unit/year, S.E. 0.006, p = 0.009) and reduction of the slope variance was equal to 4%. By contrast, Alzheimer’s disease (AD) pathology (Estimate, −0.030 unit/year, S.E. 0.009, p < 0.001) and macroscopic infarcts (−0.033 unit/year, S.E., 0.011, p = 0.003) were associated with the person-specific decline in RMS and reduction of the slope variance was equal to 7%. These results suggest that brain pathology is associated with the rate of declining respiratory function in older adults. PMID:26539108

  12. Functional Brain Network Abnormalities during Verbal Working Memory Performance in Adolescents and Young Adults with Dyslexia

    ERIC Educational Resources Information Center

    Wolf, Robert Christian; Sambataro, Fabio; Lohr, Christina; Steinbrink, Claudia; Martin, Claudia; Vasic, Nenad

    2010-01-01

    Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional…

  13. Unique and interactive effect of anxiety and depressive symptoms on cognitive and brain function in young and older adults

    PubMed Central

    Dotson, Vonetta M.; Szymkowicz, Sarah M.; Kirton, Joshua W.; McLaren, Molly E.; Green, Mackenzie L.; Rohani, Jessica Y.

    2014-01-01

    Objective Depression and anxiety and are associated with cognitive deficits and brain changes, especially in older adults. Despite the frequent co-occurrence of these conditions, cognitive neuroscience studies examining comorbid depression and anxiety are limited. The goal of the present study was to examine the unique and combined effect of depressive and anxiety symptoms on cognitive and brain functioning in young and older adults. Methods Seventy-one healthy, community-dwelling adults between the ages of 18 and 81 were administered a neuropsychological battery and completed the Center for Epidemiologic Studies Depression Scale (CES-D) and the trait form of the State-Trait Anxiety Inventory (STAI-T). A subset of 25 participants also underwent functional magnetic resonance imaging (fMRI) scanning while completing the n-back working memory task. Results Total depressive symptoms, depressed mood symptoms, and somatic symptoms were associated with deficits in speed, working memory and executive functions, especially in older adults. Symptoms of lack of well-being were not associated with any neuropsychological test. Anxiety was associated with better attention and working memory. Moreover, anxiety modified the relationship between depressive symptoms and executive functioning in older adults, as elevated depressive symptoms were associated with worse performance at low levels of anxiety, but not at higher anxiety levels. Similarly, analysis of fMRI data showed that total depressive symptoms and depressed mood symptoms were associated with decreased activity in the superior frontal gyrus at low anxiety levels, but not at high anxiety levels. Conclusion Results confirm previous reports that subthreshold depression and anxiety impact cognitive and brain functioning and suggest that the interaction of depression and anxiety results in distinct cognitive and brain changes. Findings highlight the importance of assessing and controlling for symptoms of depression and

  14. Effect of brain structure and function on reward anticipation in children and adults with attention deficit hyperactivity disorder combined subtype.

    PubMed

    Kappel, Viola; Lorenz, Robert C; Streifling, Martina; Renneberg, Babette; Lehmkuhl, Ulrike; Ströhle, Andreas; Salbach-Andrae, Harriet; Beck, Anne

    2015-07-01

    Attention deficit hyperactivity disorder (ADHD) is associated with decreased ventral-striatal responsiveness during reward anticipation. However, previous research mostly focused on adults with heterogeneous ADHD subtype and divers drug treatment status while studies in children with ADHD are sparse. Moreover, it remains unclear to what degree ADHD is characterized by a delay of normal brain structure or function maturation. We therefore attempt to determine whether results from structural and functional magnetic resonance imaging (fMRI) are associated with childhood and adult ADHD combined subtype (ADHD-CT). This study used fMRI to compare VS structure and function of 30 participants with ADHD-CT (16 adults, 14 children) and 30 controls (20 adults, 10 children), using a monetary incentive delay task. Joint analyses of structural and functional imaging data were conducted with Biological Parametric Mapping. Reward anticipation elicited decreased ventral-striatal responsiveness in adults but not in children with ADHD-CT. Children and adults with ADHD showed reduced ventral-striatal volume. Taking these gray matter differences into account, the results remained the same. These results suggest that decreased ventral-striatal responsiveness during reward anticipation is present in adults but not in children with ADHD-CT, irrespective of structural characteristics. The question arises whether ventral-striatal hypoactivity is an ADHD correlate that develops during the course of illness.

  15. Longitudinal alterations to brain function, structure, and cognitive performance in healthy older adults: A fMRI-DTI study.

    PubMed

    Hakun, Jonathan G; Zhu, Zude; Brown, Christopher A; Johnson, Nathan F; Gold, Brian T

    2015-05-01

    Cross-sectional research has shown that older adults tend to have different frontal cortex activation patterns, poorer brain structure, and lower task performance than younger adults. However, relationships between longitudinal changes in brain function, brain structure, and cognitive performance in older adults are less well understood. Here we present the results of a longitudinal, combined fMRI-DTI study in cognitive normal (CN) older adults. A two time-point study was conducted in which participants completed a task switching paradigm while fMRI data was collected and underwent the identical scanning protocol an average of 3.3 years later (SD=2 months). We observed longitudinal fMRI activation increases in bilateral regions of lateral frontal cortex at time point 2. These fMRI activation increases were associated with longitudinal declines in WM microstructure in a portion of the corpus callosum connecting the increasingly recruited frontal regions. In addition, the fMRI activation increase in the left VLPFC was associated with longitudinal increases in response latencies. Taken together, our results suggest that local frontal activation increases in CN older adults may in part reflect a response to reduced inter-hemispheric signaling mechanisms.

  16. Longitudinal Alterations to Brain Function, Structure, and Cognitive Performance in Healthy Older Adults: a fMRI-DTI study

    PubMed Central

    Hakun, Jonathan G.; Zhu, Zude; Brown, Christopher A.; Johnson, Nathan F.; Gold, Brian T.

    2015-01-01

    Cross-sectional research has shown that older adults tend to have different frontal cortex activation patterns, poorer brain structure, and lower task performance than younger adults. However, relationships between longitudinal changes in brain function, brain structure, and cognitive performance in older adults are less well understood. Here we present the results of a longitudinal, combined fMRI-DTI study in cognitive normal (CN) older adults. A two time-point study was conducted in which participants completed a task switching paradigm while fMRI data was collected and underwent the identical scanning protocol an average of 3.3 years later (SD = 2 months). We observed longitudinal fMRI activation increases in bilateral regions of lateral frontal cortex at time point 2. These fMRI activation increases were associated with longitudinal declines in WM microstructure in a portion of the corpus callosum connecting the increasingly recruited frontal regions. In addition, the fMRI activation increase in the left VLPFC was associated with longitudinal increases in response latencies. Taken together, our results suggest that local frontal activation increases in CN older adults may in part reflect a response to reduced inter-hemispheric signaling mechanisms. PMID:25862416

  17. Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function

    PubMed Central

    Garza-Lombó, Carla; Gonsebatt, María E.

    2016-01-01

    The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

  18. Intraindividual variability in physical and emotional functioning: comparison of adults with traumatic brain injuries and healthy adults.

    PubMed

    Burton, Catherine L; Hultsch, David F; Strauss, Esther; Hunter, Michael A

    2002-08-01

    Recent research has shown that individuals with certain neurological conditions demonstrate greater intraindividual variability on cognitive tasks compared to healthy controls. The present study investigated intraindividual variability in the domains of physical functioning and affect/stress in three groups: adults with mild head injuries, adults with moderate/severe head injuries, and healthy adults. Participants were assessed on 10 occasions and results indicated that (a) individuals with head injuries demonstrated greater variability in dominant finger dexterity and right grip strength than the healthy controls; (b) increased variability tended to be associated with poorer performance/report both within and across tasks; and (c) increased variability on one task was associated with increased variability on other tasks. The findings suggest that increased variability in physical function, as well as cognitive function, represents an indicator of neurological compromise.

  19. Functional brain asymmetry in adult novelty response: on fluidity of neonatal novelty exposure effects.

    PubMed

    Tang, Akaysha C; Reeb-Sutherland, Bethany; Yang, Zhen

    2011-08-01

    Novelty and surprises differentially modify the left and right sides of the brain. Here we show that repeated brief exposures to the novelty of a non-home environment during infancy and early adulthood lead to long-lasting changes in adulthood in the global bi-lateralization organization of the brain as indexed by a transiently detectable right-sided orientating bias upon the initial encounter with the novel environment. Most surprisingly, we show that in the same individuals, the short-term effect of the combined neonatal and adulthood novelty exposures on functional brain asymmetry measured at young adulthood (5 months of age) is distinctively different from the long-term effect measured at late adulthood (15 months of age). These results suggest that long-lasting, cumulative effects of early life experience on brain and behavior organization are not necessarily permanent, but continue to unfold, presumably via interactions with a multitude of unmonitored intervening life events.

  20. Bimanual Motor Coordination in Older Adults Is Associated with Increased Functional Brain Connectivity – A Graph-Theoretical Analysis

    PubMed Central

    Heitger, Marcus H.; Goble, Daniel J.; Dhollander, Thijs; Dupont, Patrick; Caeyenberghs, Karen; Leemans, Alexander; Sunaert, Stefan; Swinnen, Stephan P.

    2013-01-01

    In bimanual coordination, older and younger adults activate a common cerebral network but the elderly also have additional activation in a secondary network of brain areas to master task performance. It remains unclear whether the functional connectivity within these primary and secondary motor networks differs between the old and the young and whether task difficulty modulates connectivity. We applied graph-theoretical network analysis (GTNA) to task-driven fMRI data in 16 elderly and 16 young participants using a bimanual coordination task including in-phase and anti-phase flexion/extension wrist movements. Network nodes for the GTNA comprised task-relevant brain areas as defined by fMRI activation foci. The elderly matched the motor performance of the young but showed an increased functional connectivity in both networks across a wide range of connectivity metrics, i.e., higher mean connectivity degree, connection strength, network density and efficiency, together with shorter mean communication path length between the network nodes and also a lower betweenness centrality. More difficult movements showed an increased connectivity in both groups. The network connectivity of both groups had “small world” character. The present findings indicate (a) that bimanual coordination in the aging brain is associated with a higher functional connectivity even between areas also activated in young adults, independently from task difficulty, and (b) that adequate motor coordination in the context of task-driven bimanual control in older adults may not be solely due to additional neural recruitment but also to aging-related changes of functional relationships between brain regions. PMID:23637982

  1. Glial Cells and Their Function in the Adult Brain: A Journey through the History of Their Ablation

    PubMed Central

    Jäkel, Sarah; Dimou, Leda

    2017-01-01

    Glial cells, consisting of microglia, astrocytes, and oligodendrocyte lineage cells as their major components, constitute a large fraction of the mammalian brain. Originally considered as purely non-functional glue for neurons, decades of research have highlighted the importance as well as further functions of glial cells. Although many aspects of these cells are well characterized nowadays, the functions of the different glial populations in the brain under both physiological and pathological conditions remain, at least to a certain extent, unresolved. To tackle these important questions, a broad range of depletion approaches have been developed in which microglia, astrocytes, or oligodendrocyte lineage cells (i.e., NG2-glia and oligodendrocytes) are specifically ablated from the adult brain network with a subsequent analysis of the consequences. As the different glial populations are very heterogeneous, it is imperative to specifically ablate single cell populations instead of inducing cell death in all glial cells in general. Thanks to modern genetic manipulation methods, the approaches can now directly be targeted to the cell type of interest making the ablation more specific compared to general cell ablation approaches that have been used earlier on. In this review, we will give a detailed summary on different glial ablation studies, focusing on the adult mouse central nervous system and the functional readouts. We will also provide an outlook on how these approaches could be further exploited in the future. PMID:28243193

  2. Age of Acquisition Effects on the Functional Organization of Language in the Adult Brain

    ERIC Educational Resources Information Center

    Mayberry, Rachel I.; Chen, Jen-Kai; Witcher, Pamela; Klein, Denise

    2011-01-01

    Using functional magnetic resonance imaging (fMRI), we neuroimaged deaf adults as they performed two linguistic tasks with sentences in American Sign Language, grammatical judgment and phonemic-hand judgment. Participants' age-onset of sign language acquisition ranged from birth to 14 years; length of sign language experience was substantial and…

  3. Graphene Functionalized Scaffolds Reduce the Inflammatory Response and Supports Endogenous Neuroblast Migration when Implanted in the Adult Brain

    PubMed Central

    Zhou, Kun; Motamed, Sepideh; Thouas, George A.; Bernard, Claude C.; Li, Dan; Parkington, Helena C.; Coleman, Harold A.; Finkelstein, David I.; Forsythe, John S.

    2016-01-01

    Electroactive materials have been investigated as next-generation neuronal tissue engineering scaffolds to enhance neuronal regeneration and functional recovery after brain injury. Graphene, an emerging neuronal scaffold material with charge transfer properties, has shown promising results for neuronal cell survival and differentiation in vitro. In this in vivo work, electrospun microfiber scaffolds coated with self-assembled colloidal graphene, were implanted into the striatum or into the subventricular zone of adult rats. Microglia and astrocyte activation levels were suppressed with graphene functionalization. In addition, self-assembled graphene implants prevented glial scarring in the brain 7 weeks following implantation. Astrocyte guidance within the scaffold and redirection of neuroblasts from the subventricular zone along the implants was also demonstrated. These findings provide new functional evidence for the potential use of graphene scaffolds as a therapeutic platform to support central nervous system regeneration. PMID:26978268

  4. Exergame and Balance Training Modulate Prefrontal Brain Activity during Walking and Enhance Executive Function in Older Adults

    PubMed Central

    Eggenberger, Patrick; Wolf, Martin; Schumann, Martina; de Bruin, Eling D.

    2016-01-01

    Different types of exercise training have the potential to induce structural and functional brain plasticity in the elderly. Thereby, functional brain adaptations were observed during cognitive tasks in functional magnetic resonance imaging studies that correlated with improved cognitive performance. This study aimed to investigate if exercise training induces functional brain plasticity during challenging treadmill walking and elicits associated changes in cognitive executive functions. Forty-two elderly participants were recruited and randomly assigned to either interactive cognitive-motor video game dancing (DANCE) or balance and stretching training (BALANCE). The 8-week intervention included three sessions of 30 min per week and was completed by 33 participants (mean age 74.9 ± 6.9 years). Prefrontal cortex (PFC) activity during preferred and fast walking speed on a treadmill was assessed applying functional near infrared spectroscopy pre- and post-intervention. Additionally, executive functions comprising shifting, inhibition, and working memory were assessed. The results showed that both interventions significantly reduced left and right hemispheric PFC oxygenation during the acceleration of walking (p < 0.05 or trend, r = 0.25–0.36), while DANCE showed a larger reduction at the end of the 30-s walking task compared to BALANCE in the left PFC [F(1, 31) = 3.54, p = 0.035, r = 0.32]. These exercise training induced modulations in PFC oxygenation correlated with improved executive functions (p < 0.05 or trend, r = 0.31–0.50). The observed reductions in PFC activity may release cognitive resources to focus attention on other processes while walking, which could be relevant to improve mobility and falls prevention in the elderly. This study provides a deeper understanding of the associations between exercise training, brain function during walking, and cognition in older adults. PMID:27148041

  5. Exergame and Balance Training Modulate Prefrontal Brain Activity during Walking and Enhance Executive Function in Older Adults.

    PubMed

    Eggenberger, Patrick; Wolf, Martin; Schumann, Martina; de Bruin, Eling D

    2016-01-01

    Different types of exercise training have the potential to induce structural and functional brain plasticity in the elderly. Thereby, functional brain adaptations were observed during cognitive tasks in functional magnetic resonance imaging studies that correlated with improved cognitive performance. This study aimed to investigate if exercise training induces functional brain plasticity during challenging treadmill walking and elicits associated changes in cognitive executive functions. Forty-two elderly participants were recruited and randomly assigned to either interactive cognitive-motor video game dancing (DANCE) or balance and stretching training (BALANCE). The 8-week intervention included three sessions of 30 min per week and was completed by 33 participants (mean age 74.9 ± 6.9 years). Prefrontal cortex (PFC) activity during preferred and fast walking speed on a treadmill was assessed applying functional near infrared spectroscopy pre- and post-intervention. Additionally, executive functions comprising shifting, inhibition, and working memory were assessed. The results showed that both interventions significantly reduced left and right hemispheric PFC oxygenation during the acceleration of walking (p < 0.05 or trend, r = 0.25-0.36), while DANCE showed a larger reduction at the end of the 30-s walking task compared to BALANCE in the left PFC [F (1, 31) = 3.54, p = 0.035, r = 0.32]. These exercise training induced modulations in PFC oxygenation correlated with improved executive functions (p < 0.05 or trend, r = 0.31-0.50). The observed reductions in PFC activity may release cognitive resources to focus attention on other processes while walking, which could be relevant to improve mobility and falls prevention in the elderly. This study provides a deeper understanding of the associations between exercise training, brain function during walking, and cognition in older adults.

  6. Marijuana effects on changes in brain structure and cognitive function among HIV+ and HIV− adults

    PubMed Central

    Thames, April D.; Kuhn, Taylor P.; Williamson, Timothy J.; Jones, Jacob D.; Mahmood, Zanjbeel; Hammond, Andrea

    2017-01-01

    Background The current study examined the independent and interactive effects of HIV and marijuana (MJ) use on brain structure and cognitive function among a sample of HIV-positive (HIV +) and HIV-negative (HIV–) individuals. Methods Participants (HIV+, n = 48; HIV–, n = 29) individuals underwent cognitive testing, questionnaires about substance use, and brain MRI. The HIV+ group was clinically stable based upon current plasma CD4 count, 50% had undetectable viral load (i.e., < 20 copies/mL), and all were on a stable regimen of cART. Results For HIV+ and HIV− participants, higher levels of MJ use were associated with smaller volumes in the entorhinal cortex and fusiform gyrus. HIV status (but not MJ use) was associated with cingulate thickness, such that HIV+ participants evidenced smaller thickness of the cingulate, as compared to HIV-controls. Regarding neurocognitive functioning, there was a HIV*MJ interactive effect on global cognition, such that when the amount of MJ use was less than 1.43 g per week, the HIV− group displayed significantly better neurocognitive performance than the HIV+ group (t = 3.14, p = 0.002). However, when MJ use reached 1.43 g per week, there were no significant HIV group differences in global cognitive performance (t = 1.39, p = 0.168). Conclusions Our results show independent and interactive effects of HIV and MJ on brain structure and cognition. However, our results do not support that HIV+ MJ users are at greater risk for adverse brain or cognitive outcomes compared to HIV− MJ users. PMID:27889592

  7. Training-related changes in early visual processing of functionally illiterate adults: evidence from event-related brain potentials

    PubMed Central

    2013-01-01

    Background Event-related brain potentials (ERPs) were used to investigate training-related changes in fast visual word recognition of functionally illiterate adults. Analyses focused on the left-lateralized occipito-temporal N170, which represents the earliest processing of visual word forms. Event-related brain potentials were recorded from 20 functional illiterates receiving intensive literacy training for adults, 10 functional illiterates not participating in the training and 14 regular readers while they read words, pseudowords or viewed symbol strings. Subjects were required to press a button whenever a stimulus was immediately repeated. Results Attending intensive literacy training was associated with improvements in reading and writing skills and with an increase of the word-related N170 amplitude. For untrained functional illiterates and regular readers no changes in literacy skills or N170 amplitude were observed. Conclusions Results of the present study suggest that the word-related N170 can still be modulated in adulthood as a result of the improvements in literacy skills. PMID:24330622

  8. Cognitive function and brain structure after recurrent mild traumatic brain injuries in young-to-middle-aged adults

    PubMed Central

    List, Jonathan; Ott, Stefanie; Bukowski, Martin; Lindenberg, Robert; Flöel, Agnes

    2015-01-01

    Recurrent mild traumatic brain injuries (mTBIs) are regarded as an independent risk factor for developing dementia in later life. We here aimed to evaluate associations between recurrent mTBIs, cognition, and gray matter volume and microstructure as revealed by structural magnetic resonance imaging (MRI) in the chronic phase after mTBIs in young adulthood. We enrolled 20 young-to-middle-aged subjects, who reported two or more sports-related mTBIs, with the last mTBI > 6 months prior to study enrolment (mTBI group), and 21 age-, sex- and education matched controls with no history of mTBI (control group). All participants received comprehensive neuropsychological testing, and high resolution T1-weighted and diffusion tensor MRI in order to assess cortical thickness (CT) and microstructure, hippocampal volume, and ventricle size. Compared to the control group, subjects of the mTBI group presented with lower CT within the right temporal lobe and left insula using an a priori region of interest approach. Higher number of mTBIs was associated with lower CT in bilateral insula, right middle temporal gyrus and right entorhinal area. Our results suggest persistent detrimental effects of recurrent mTBIs on CT already in young-to-middle-aged adults. If additional structural deterioration occurs during aging, subtle neuropsychological decline may progress to clinically overt dementia earlier than in age-matched controls, a hypothesis to be assessed in future prospective trials. PMID:26052275

  9. Minimal functional brain differences between older adults with and without mild cognitive impairment during the stroop.

    PubMed

    Puente, Antonio Nicolas; Faraco, Carlos; Terry, Douglas P; Brown, Courtney; Miller, L Stephen

    2014-01-01

    This investigation compared the neural correlates of inhibition in normal older adults (OAs) and OAs with mild cognitive impairment (MCI). It was hypothesized the MCI group would require a greater amount of resources for inhibition, and therefore display greater functional activation in specific regions of interest (ROIs). Twenty-six OAs without and 17 with MCI completed the Stroop task during functional neuroimaging, and completed additional out-of-scanner neuropsychological measures. During inhibition, there were minimal functional Magnetic Resonance Imaging (fMRI) differences found between groups in a priori specified ROIs and with post-hoc multiple regression analyses. However, these minimal differences did not survive corrected thresholds. Robust differences were found with several tasks of a neuropsychological screening battery. The results of this study suggest only very minimal group differences in fMRI activation during inhibition which may not reliably identify MCI, and this condition may be best detected by traditional neuropsychological techniques.

  10. Distinct effects of childhood ADHD and cannabis use on brain functional architecture in young adults.

    PubMed

    Kelly, Clare; Castellanos, F Xavier; Tomaselli, Olivia; Lisdahl, Krista; Tamm, Leanne; Jernigan, Terry; Newman, Erik; Epstein, Jeffery N; Molina, Brooke S G; Greenhill, Laurence L; Potkin, Steven G; Hinshaw, Stephen; Swanson, James M

    2017-01-01

    One of the most salient long-term implications of a childhood diagnosis of ADHD is an increased risk for substance use, abuse, or dependence in adolescence and adulthood. The extent to which cannabis use affects ADHD-related alterations in brain functional organization is unknown, however. To address this research gap, we recruited a sample of 75 individuals aged 21-25 years with and without a childhood diagnosis of ADHD Combined Type, who were either frequent users or non-users of cannabis. These participants have been followed longitudinally since age 7-9.9 years as part of a large multi-site longitudinal study of ADHD, the Multimodal Treatment Study of Children with ADHD (MTA). We examined task-independent intrinsic functional connectivity (iFC) within 9 functional networks using a 2 × 2 design, which compared four groups of participants: (1) individuals with a childhood diagnosis of ADHD who currently use cannabis (n = 23); (2) individuals with ADHD who do not currently use cannabis (n = 22); (3) comparisons who currently use cannabis (n = 15); and (4) comparisons who do not currently use cannabis (n = 15). The main effects of childhood ADHD were primarily weakened iFC in networks supporting executive function and somatomotor control. Contrary to expectations, effects of cannabis use were distinct from those of diagnostic group and no interactions were observed. Exploratory brain-behavior analyses suggested that ADHD-related effects were primarily linked with poorer neurocognitive performance. Deficits in the integrity of functional networks supporting executive function and somatomotor control are consistent with the phenotypic and neurocognitive features of ADHD. Our data suggest that cannabis use does not exacerbate ADHD-related alterations, but this finding awaits replication in a larger sample. Longitudinal neuroimaging studies are urgently required to delineate the neurodevelopmental cascade that culminates in positive and negative outcomes

  11. Life stress in adolescence predicts early adult reward-related brain function and alcohol dependence.

    PubMed

    Casement, Melynda D; Shaw, Daniel S; Sitnick, Stephanie L; Musselman, Samuel C; Forbes, Erika E

    2015-03-01

    Stressful life events increase vulnerability to problematic alcohol use, and they may do this by disrupting reward-related neural circuitry. This is particularly relevant for adolescents because alcohol use rises sharply after mid-adolescence and alcohol abuse peaks at age 20. Adolescents also report more stressors compared with children, and neural reward circuitry may be especially vulnerable to stressors during adolescence because of prefrontal cortex remodeling. Using a large sample of male participants in a longitudinal functional magnetic resonance imaging study (N = 157), we evaluated whether cumulative stressful life events between the ages of 15 and 18 were associated with reward-related brain function and problematic alcohol use at age 20 years. Higher cumulative stressful life events during adolescence were associated with decreased response in the medial prefrontal cortex (mPFC) during monetary reward anticipation and following the receipt of monetary rewards. Stress-related decreases in mPFC response during reward anticipation and following rewarding outcomes were associated with the severity of alcohol dependence. Furthermore, mPFC response mediated the association between stressful life events and later symptoms of alcohol dependence. These data are consistent with neurobiological models of addiction that propose that stressors during adolescence increase risk for problematic alcohol use by disrupting reward circuit function.

  12. Brain imaging and brain function

    SciTech Connect

    Sokoloff, L.

    1985-01-01

    This book is a survey of the applications of imaging studies of regional cerebral blood flow and metabolism to the investigation of neurological and psychiatric disorders. Contributors review imaging techniques and strategies for measuring regional cerebral blood flow and metabolism, for mapping functional neural systems, and for imaging normal brain functions. They then examine the applications of brain imaging techniques to the study of such neurological and psychiatric disorders as: cerebral ischemia; convulsive disorders; cerebral tumors; Huntington's disease; Alzheimer's disease; depression and other mood disorders. A state-of-the-art report on magnetic resonance imaging of the brain and central nervous system rounds out the book's coverage.

  13. 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.

  14. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    SciTech Connect

    Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.; Tome, Wolfgang A.

    2012-07-15

    Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients

  15. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    SciTech Connect

    Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.; Tome, Wolfgang A.

    2013-02-01

    Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients

  16. Hippocampal Astrocyte Cultures from Adult and Aged Rats Reproduce Changes in Glial Functionality Observed in the Aging Brain.

    PubMed

    Bellaver, Bruna; Souza, Débora Guerini; Souza, Diogo Onofre; Quincozes-Santos, André

    2016-03-30

    Astrocytes are dynamic cells that maintain brain homeostasis, regulate neurotransmitter systems, and process synaptic information, energy metabolism, antioxidant defenses, and inflammatory response. Aging is a biological process that is closely associated with hippocampal astrocyte dysfunction. In this sense, we demonstrated that hippocampal astrocytes from adult and aged Wistar rats reproduce the glial functionality alterations observed in aging by evaluating several senescence, glutamatergic, oxidative and inflammatory parameters commonly associated with the aging process. Here, we show that the p21 senescence-associated gene and classical astrocyte markers, such as glial fibrillary acidic protein (GFAP), vimentin, and actin, changed their expressions in adult and aged astrocytes. Age-dependent changes were also observed in glutamate transporters (glutamate aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1)) and glutamine synthetase immunolabeling and activity. Additionally, according to in vivo aging, astrocytes from adult and aged rats showed an increase in oxidative/nitrosative stress with mitochondrial dysfunction, an increase in RNA oxidation, NADPH oxidase (NOX) activity, superoxide levels, and inducible nitric oxide synthase (iNOS) expression levels. Changes in antioxidant defenses were also observed. Hippocampal astrocytes also displayed age-dependent inflammatory response with augmentation of proinflammatory cytokine levels, such as TNF-α, IL-1β, IL-6, IL-18, and messenger RNA (mRNA) levels of cyclo-oxygenase 2 (COX-2). Furthermore, these cells secrete neurotrophic factors, including glia-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), S100 calcium-binding protein B (S100B) protein, and transforming growth factor-β (TGF-β), which changed in an age-dependent manner. Classical signaling pathways associated with aging, such as nuclear factor erythroid-derived 2-like 2 (Nrf2), nuclear factor kappa B (NFκ

  17. Neural repair in the adult brain

    PubMed Central

    Jessberger, Sebastian

    2016-01-01

    Acute or chronic injury to the adult brain often results in substantial loss of neural tissue and subsequent permanent functional impairment. Over the last two decades, a number of approaches have been developed to harness the regenerative potential of neural stem cells and the existing fate plasticity of neural cells in the nervous system to prevent tissue loss or to enhance structural and functional regeneration upon injury. Here, we review recent advances of stem cell-associated neural repair in the adult brain, discuss current challenges and limitations, and suggest potential directions to foster the translation of experimental stem cell therapies into the clinic. PMID:26918167

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

    PubMed

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

    2016-10-01

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

  19. Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.

    PubMed

    Hemmer, Kathrin; Zhang, Mingyue; van Wüllen, Thea; Sakalem, Marna; Tapia, Natalia; Baumuratov, Aidos; Kaltschmidt, Christian; Kaltschmidt, Barbara; Schöler, Hans R; Zhang, Weiqi; Schwamborn, Jens C

    2014-09-09

    Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  20. Theory and experiments on time-resolved reflectance from adult heads for functional tomographic imaging of brain activities

    NASA Astrophysics Data System (ADS)

    Tanifuji, T.; Suzuki, M.

    2014-02-01

    Finite difference time domain (FDTD) analysis has been formulated for predicting time-resolved reflectance from an adult head model with brain grooves containing a non-scattering layer. Mean delay (MD) dependences on source detector separation (d) and time-resolved reflectance calculated using the FDTD analysis were compared with in vivo experiments of human heads. It is shown that the theoretical and experimental MD dependences on d and the time-resolved reflectance are well predicted by FDTD analysis. These results have shown that tomographic imaging of brain activities is promising, which improves depth sensitivities by enhancing the contribution of late photons in time-resolved systems.

  1. Spatio-temporal regulations and functions of neuronal alternative RNA splicing in developing and adult brains.

    PubMed

    Iijima, Takatoshi; Hidaka, Chiharu; Iijima, Yoko

    2016-08-01

    Alternative pre-mRNA splicing is a fundamental mechanism that generates molecular diversity from a single gene. In the central nervous system (CNS), key neural developmental steps are thought to be controlled by alternative splicing decisions, including the molecular diversity underlying synaptic wiring, plasticity, and remodeling. Significant progress has been made in understanding the molecular mechanisms and functions of alternative pre-mRNA splicing in neurons through studies in invertebrate systems; however, recent studies have begun to uncover the potential role of neuronal alternative splicing in the mammalian CNS. This article provides an overview of recent findings regarding the regulation and function of neuronal alternative splicing. In particular, we focus on the spatio-temporal regulation of neurexin, a synaptic adhesion molecule, by neuronal cell type-specific factors and neuronal activity, which are thought to be especially important for characterizing neural development and function within the mammalian CNS. Notably, there is increasing evidence that implicates the dysregulation of neuronal splicing events in several neurological disorders. Therefore, understanding the detailed mechanisms of neuronal alternative splicing in the mammalian CNS may provide plausible treatment strategies for these diseases.

  2. Differences in Brain Structure and Function in Older Adults with Self-Reported Disabling and Non-Disabling Chronic Low Back Pain

    PubMed Central

    Buckalew, Neilly; Haut, Marc W.; Aizenstein, Howard; Morrow, Lisa; Perera, Subashan; Kuwabara, Hiroto; Weiner, Debra K.

    2010-01-01

    Objective The primary aim of this pilot study was to identify structural and functional brain differences in older adults with self-reported disabling chronic low back pain (CLBP) compared with those who reported non-disabling CLBP. Design Cross-sectional. Participants Sixteen cognitively intact older adults, eight with disabling CLBP and eight with non-disabling. Exclusions were psychiatric or neurological disorders, substance abuse, opioid use, or diabetes mellitus. Methods Participants underwent: structural and functional brain MRI; neuropsychological assessment using the Repeatable Battery for the Assessment of Neuropsychological Status, Trail Making Tests A and B; and physical performance assessment using the Short Physical Performance Battery. Results In the disabled group there was significantly lower white matter (WM) integrity (P < 0.05) of the splenium of the corpus callosum. This group also demonstrated activation of the right medial prefrontal cortex at rest whereas the non-disabled demonstrated activation of the left lateral prefrontal cortex. Combined groups analysis revealed a strong positive correlation (rs = 0.80, P < 0.0002) between WM integrity of the left centrum semiovale with gait-speed. Secondary analysis revealed a strong negative correlation between total months of CLBP and WM integrity of the SCC (rs = −0.59, P < 0.02). Conclusions Brain structure and function is different in older adults with disabling CLBP compared to those with non-disabling CLBP. Deficits in brain morphology combining groups are associated with pain duration and poor physical function. Our findings suggest brain structure and function may play a key role in chronic-pain-related-disability and may be important treatment targets. PMID:20609128

  3. Acupuncture stimulation induces neurogenesis in adult brain.

    PubMed

    Nam, Min-Ho; Ahn, Kwang Seok; Choi, Seung-Hoon

    2013-01-01

    The discovery of adult neurogenesis was a turning point in the field of neuroscience. Adult neurogenesis offers an enormous possibility to open a new therapeutic paradigm of neurodegenerative diseases and stroke. Recently, several studies suggested that acupuncture may enhance adult neurogenesis. Acupuncture has long been an important treatment for brain diseases in the East Asia. The scientific mechanisms of acupuncture treatment for the diseases, such as Alzheimer's disease, Parkinson's disease, and stroke, have not been clarified yet; however, the neurogenic effect of acupuncture can be a possible reason. Here, we have reviewed the studies on the effect of stimulation at various acupoints for neurogenesis, such as ST36 and GV20. The suggested mechanisms are also discussed including upregulation of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, basic fibroblast growth factor and neuropeptide Y, and activation of the function of primo vascular system.

  4. Split Brain Functioning.

    ERIC Educational Resources Information Center

    Cassel, Russell N.

    1978-01-01

    Summarizing recent research, this article defines the functions performed by the left and right sides of the human brain. Attention is given to the right side, or the nondominant side, of the brain and its potential in terms of perception of the environment, music, art, geometry, and the aesthetics. (JC)

  5. Left Brain/Right Brain Learning for Adult Education.

    ERIC Educational Resources Information Center

    Garvin, Barbara

    1986-01-01

    Contrasts and compares the theory and practice of adult education as it relates to the issue of right brain/left brain learning. The author stresses the need for a whole-brain approach to teaching and suggests that adult educators, given their philosophical directions, are the perfect potential users of this integrated system. (Editor/CT)

  6. 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…

  7. Brain and Spinal Cord Tumors in Adults

    MedlinePlus

    ... Search Search En Español Category Cancer A-Z Brain and Spinal Cord Tumors in Adults If you have a brain or spinal cord tumor or are close to ... cope. Here you can find out all about brain and spinal cord tumors in adults, including risk ...

  8. Altered functional brain connectivity in a non-clinical sample of young adults with attention-deficit/hyperactivity disorder.

    PubMed

    Cocchi, Luca; Bramati, Ivanei E; Zalesky, Andrew; Furukawa, Emi; Fontenelle, Leonardo F; Moll, Jorge; Tripp, Gail; Mattos, Paulo

    2012-12-05

    Attention-deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention and hyperactivity/impulsivity that often persist in adulthood. There is a growing consensus that ADHD is associated with abnormal function of diffuse brain networks, but such alterations remain poorly characterized. Using resting-state functional magnetic resonance imaging, we characterized multivariate (complex network measures), bivariate (network-based statistic), and univariate (regional homogeneity) properties of brain networks in a non-clinical, drug-naive sample of high-functioning young men and women with ADHD (nine males, seven females) and a group of matched healthy controls. Data from our sample allowed the isolation of intrinsic functional connectivity alterations specific to ADHD diagnosis and symptoms that are not related to developmental delays, general cognitive dysfunction, or history of medication use. Multivariate results suggested that frontal, temporal, and occipital cortices were abnormally connected locally as well as with the rest of the brain in individuals with ADHD. Results from the network-based statistic support and extend multivariate results by isolating two brain networks comprising regions between which inter-regional connectivity was significantly altered in the ADHD group; namely, a frontal amygdala-occipital network and a frontal temporal-occipital network. Brain behavior correlations further highlighted the key role of altered orbitofrontal-temporal and frontal-amygdala connectivity for symptoms of inattention and hyperactivity/impulsivity. All univariate properties were similar between groups. Taken together, results from this study show that the diagnosis and the two main symptom dimensions of ADHD are related to altered intrinsic connectivity in orbitofrontal-temporal-occipital and fronto-amygdala-occipital networks. Accordingly, our findings highlight the importance of extending the conceptualization of ADHD beyond segregated fronto

  9. Lutein and Brain Function

    PubMed Central

    Erdman, John W.; Smith, Joshua W.; Kuchan, Matthew J.; Mohn, Emily S.; Johnson, Elizabeth J.; Rubakhin, Stanislav S.; Wang, Lin; Sweedler, Jonathan V.; Neuringer, Martha

    2015-01-01

    Lutein is one of the most prevalent carotenoids in nature and in the human diet. Together with zeaxanthin, it is highly concentrated as macular pigment in the foveal retina of primates, attenuating blue light exposure, providing protection from photo-oxidation and enhancing visual performance. Recently, interest in lutein has expanded beyond the retina to its possible contributions to brain development and function. Only primates accumulate lutein within the brain, but little is known about its distribution or physiological role. Our team has begun to utilize the rhesus macaque (Macaca mulatta) model to study the uptake and bio-localization of lutein in the brain. Our overall goal has been to assess the association of lutein localization with brain function. In this review, we will first cover the evolution of the non-human primate model for lutein and brain studies, discuss prior association studies of lutein with retina and brain function, and review approaches that can be used to localize brain lutein. We also describe our approach to the biosynthesis of 13C-lutein, which will allow investigation of lutein flux, localization, metabolism and pharmacokinetics. Lastly, we describe potential future research opportunities. PMID:26566524

  10. Adult human brain cell culture for neuroscience research.

    PubMed

    Gibbons, Hannah M; Dragunow, Mike

    2010-06-01

    Studies of the brain have progressed enormously through the use of in vivo and in vitro non-human models. However, it is unlikely such studies alone will unravel the complexities of the human brain and so far no neuroprotective treatment developed in animals has worked in humans. In this review we discuss the use of adult human brain cell culture methods in brain research to unravel the biology of the normal and diseased human brain. The advantages of using adult human brain cells as tools to study human brain function from both historical and future perspectives are discussed. In particular, studies using dissociated cultures of adult human microglia, astrocytes, oligodendrocytes and neurons are described and the applications of these types of study are evaluated. Alternative sources of human brain cells such as adult neural stem cells, induced pluripotent stem cells and slice cultures of adult human brain tissue are also reviewed. These adult human brain cell culture methods could benefit basic research and more importantly, facilitate the translation of basic neuroscience research to the clinic for the treatment of brain disorders.

  11. Stem Cell-Mediated Regeneration of the Adult Brain

    PubMed Central

    Jessberger, Sebastian

    2016-01-01

    Acute or chronic injury of the adult mammalian brain is often associated with persistent functional deficits as its potential for regeneration and capacity to rebuild lost neural structures is limited. However, the discovery that neural stem cells (NSCs) persist throughout life in discrete regions of the brain, novel approaches to induce the formation of neuronal and glial cells, and recently developed strategies to generate tissue for exogenous cell replacement strategies opened novel perspectives how to regenerate the adult brain. Here, we will review recently developed approaches for brain repair and discuss future perspectives that may eventually allow for developing novel treatment strategies in acute and chronic brain injury. PMID:27781019

  12. Paracetamol (acetaminophen) administration during neonatal brain development affects cognitive function and alters its analgesic and anxiolytic response in adult male mice.

    PubMed

    Viberg, Henrik; Eriksson, Per; Gordh, Torsten; Fredriksson, Anders

    2014-03-01

    Paracetamol (acetaminophen) is one of the most commonly used drugs for the treatment of pain and fever in children, both at home and in the clinic, and is now also found in the environment. Paracetamol is known to act on the endocannabinoid system, involved in normal development of the brain. We examined if neonatal paracetamol exposure could affect the development of the brain, manifested as adult behavior and cognitive deficits, as well as changes in the response to paracetamol. Ten-day-old mice were administered a single dose of paracetamol (30 mg/kg body weight) or repeated doses of paracetamol (30 + 30 mg/kg body weight, 4h apart). Concentrations of paracetamol and brain-derived neurotrophic factor (BDNF) were measured in the neonatal brain, and behavioral testing was done when animals reached adulthood. This study shows that acute neonatal exposure to paracetamol (2 × 30 mg) results in altered locomotor activity on exposure to a novel home cage arena and a failure to acquire spatial learning in adulthood, without affecting thermal nociceptive responding or anxiety-related behavior. However, mice neonatally exposed to paracetamol (2 × 30 mg) fail to exhibit paracetamol-induced antinociceptive and anxiogenic-like behavior in adulthood. Behavioral alterations in adulthood may, in part, be due to paracetamol-induced changes in BDNF levels in key brain regions at a critical time during development. This indicates that exposure to and presence of paracetamol during a critical period of brain development can induce long-lasting effects on cognitive function and alter the adult response to paracetamol in mice.

  13. Primary brain tumours in adults.

    PubMed

    Ricard, Damien; Idbaih, Ahmed; Ducray, François; Lahutte, Marion; Hoang-Xuan, Khê; Delattre, Jean-Yves

    2012-05-26

    Important advances have been made in the understanding and management of adult gliomas and primary CNS lymphomas--the two most common primary brain tumours. Progress in imaging has led to a better analysis of the nature and grade of these tumours. Findings from large phase 3 studies have yielded some standard treatments for gliomas, and have confirmed the prognostic value of specific molecular alterations. High-throughput methods that enable genome-wide analysis of tumours have improved the knowledge of tumour biology, which should lead to a better classification of gliomas and pave the way for so-called targeted therapy trials. Primary CNS lymphomas are a group of rare non-Hodgkin lymphomas. High-dose methotrexate-based regimens increase survival, but the standards of care and the place of whole-brain radiotherapy remain unclear, and are likely to depend on the age of the patient. The focus now is on the development of new polychemotherapy regimens to reduce or defer whole-brain radiotherapy and its delayed complications.

  14. Functional effectiveness of the blood-brain barrier to small water-soluble molecules in developing and adult opossum (Monodelphis domestica).

    PubMed

    Ek, Carl Joakim; Dziegielewska, Katarzyna Magdalena; Stolp, Helen; Saunders, Norman Ruthven

    2006-05-01

    We have evaluated a small water-soluble molecule, biotin ethylenediamine (BED, 286 Da), as a permeability tracer across the blood-brain barrier. This molecule was found to have suitable characteristics in that it is stable in plasma, has low plasma protein binding, and appears to behave in a similar manner across brain barriers as established by permeability markers such as sucrose. BED, together with a 3000-Da biotin-dextran (BDA3000), was used to investigate the effectiveness of tight junctions in cortical vessels during development and adulthood of a marsupial opossum (Monodelphis domestica). Marsupial species are born at an early stage of brain development when cortical vessels are just beginning to appear. The tracers were administered systemically to opossums at various ages and localized in brains with light and electron microscopy. In adults, the tight junctions restricted the movement of both tracers. In neonates, as soon as vessels grow into the neocortex, their tight junctions are functionally restrictive, a finding supported by the presence of claudin-5 in endothelial cells. However, both tracers are also found within brain extracellular space soon after intraperitoneal administration. The main route of entry for the tracers into immature neocortex appears to be via the cerebrospinal fluid over the outer (subarachnoid) and inner (ventricular) surfaces of the brain. These experiments demonstrate that the previously described higher permeability of barriers to small molecules in the developing brain does not seem to be due to leakiness of cerebral endothelial tight junctions, but to a route of entry probably via the choroid plexuses and cerebrospinal fluid.

  15. Transgenerational disruption of functional 5-HT1AR-induced connectivity in the adult mouse brain by traumatic stress in early life.

    PubMed

    Razoux, F; Russig, H; Mueggler, T; Baltes, C; Dikaiou, K; Rudin, M; Mansuy, I M

    2017-04-01

    Traumatic stress in early life is a strong risk factor for psychiatric disorders that can affect individuals across several generations. Although the underlying mechanisms have been proposed to implicate serotonergic transmission in the brain, the neural circuits involved remain poorly delineated. Using pharmacological functional magnetic resonance imaging in mice, we demonstrate that traumatic stress in postnatal life alters 5-HT1A receptor-evoked local and global functions in both, the exposed animals and their progeny when adult. Disrupted functional connectivity is consistent across generations and match limbic circuits implicated in mood disorders, but also networks not previously linked to traumatic stress. These findings underscore the neurobiology and functional mapping of transgenerational effects of early life experiences.

  16. Processing demands upon cognitive, linguistic, and articulatory functions promote grey matter plasticity in the adult multilingual brain: Insights from simultaneous interpreters.

    PubMed

    Elmer, Stefan; Hänggi, Jürgen; Jäncke, Lutz

    2014-05-01

    Until now, considerable effort has been made to determine structural brain characteristics related to exceptional multilingual skills. However, at least one important question has not yet been satisfactorily addressed in the previous literature, namely whether and to which extent the processing demands upon cognitive, linguistic, and articulatory functions may promote grey matter plasticity in the adult multilingual brain. Based on the premise that simultaneous interpretation is a highly demanding linguistic task that places strong demands on executive and articulatory functions, here we compared grey matter volumes between professional simultaneous interpreters (SI) and multilingual control subjects. Thereby, we focused on a specific set of a-priori defined bilateral brain regions that have previously been shown to support neurocognitional aspects of language control and linguistic functions in the multilingual brain. These regions are the cingulate gyrus, caudate nucleus, frontal operculum (pars triangularis and opercularis), inferior parietal lobe (IPL) (supramarginal and angular gyrus), and the insula. As a main result, we found reduced grey matter volumes in professional SI, compared to multilingual controls, in the left middle-anterior cingulate gyrus, bilateral pars triangularis, left pars opercularis, bilateral middle part of the insula, and in the left supramarginal gyrus (SMG). Interestingly, grey matter volume in left pars triangularis, right pars opercularis, middle-anterior cingulate gyrus, and in the bilateral caudate nucleus was negatively correlated with the cumulative number of interpreting hours. Hence, we provide first evidence for an expertise-related grey matter architecture that may reflect a composite of brain characteristics that were still present before interpreting training and training-related changes.

  17. Anatomical and functional brain imaging in adult attention-deficit/hyperactivity disorder (ADHD)--a neurological view.

    PubMed

    Schneider, Marc; Retz, Wolfgang; Coogan, Andrew; Thome, Johannes; Rösler, Michael

    2006-09-01

    In this review, we discuss current structural and functional imaging data on ADHD in a neurological and neuroanatomical framework. At present, the literature on adult ADHD is somewhat sparse, and so results from imaging have to therefore be considered mainly from the childhood or adolescence perspective. Most work has considered the impairment of executive functions (motor execution, inhibition, working memory), and as such a number of attention networks and their anatomical correlates are discussed in this review (e.g. the cerebello-(thalamo-)-striato-cortical network seems to play a pivotal role in ADHD pathology from childhood to adulthood). The core findings in ADHD imaging are alterations in the architecture and function of prefrontal cortex and cerebellum. The dorsal part of anterior cingulated cortex (dACC) is an important region for decision making, and executive control is impaired in adult ADHD. Finally, dysfunction of basal ganglia is a consistent finding in childhood and adulthood ADHD, reflecting dysregulation of fronto-striatal circuitry. The cerebellum, and its role in affect and cognition, is also persistently implicated in the pathology of ADHD.

  18. Age-related variability in performance of a motor action selection task is related to differences in brain function and structure among older adults.

    PubMed

    Stewart, Jill Campbell; Tran, Xuan; Cramer, Steven C

    2014-02-01

    Task performance for behaviors that engage motor cognitive processes may be particularly sensitive to age-related changes. One well-studied model of cognitive motor function involves engagement of action selection (AS) processes. In young adults, task conditions that add AS demands result in increased preparation times and greater engagement of bilateral dorsal premotor (PMd) and parietal cortices. The current study investigated the behavioral and neural response to a change in motor cognitive demands in older adults through the addition of AS to a movement task. Sixteen older adults made a joystick movement under two conditions during functional magnetic resonance imaging. In the AS condition, participants moved right or left based on an abstract rule; in the execution only (EO) condition, participants moved in the same direction on every trial. Across participants, the AS condition, as compared to the EO condition, was associated with longer reaction time and increased activation of left inferior parietal lobule. Variability in behavioral response to the AS task between participants related to differences in brain function and structure. Overall, individuals with poorer AS task performance showed greater activation in left PMd and dorsolateral prefrontal cortex and decreased structural integrity of white matter tracts that connect sensorimotor, frontal, and parietal regions-key regions for AS task performance. Additionally, two distinct patterns of functional connectivity were found. Participants with a pattern of decreased primary motor-PMd connectivity in response to the AS condition, compared to those with a pattern of increased connectivity, were older and had poorer behavioral performance. These neural changes in response to increased motor cognitive demands may be a marker for age-related changes in the motor system and have an impact on the learning of novel, complex motor skills in older adults.

  19. Modulating brain oscillations to drive brain function.

    PubMed

    Thut, Gregor

    2014-12-01

    Do neuronal oscillations play a causal role in brain function? In a study in this issue of PLOS Biology, Helfrich and colleagues address this long-standing question by attempting to drive brain oscillations using transcranial electrical current stimulation. Remarkably, they were able to manipulate visual perception by forcing brain oscillations of the left and right visual hemispheres into synchrony using oscillatory currents over both hemispheres. Under this condition, human observers more often perceived an inherently ambiguous visual stimulus in one of its perceptual instantiations. These findings shed light on the mechanisms underlying neuronal computation. They show that it is the neuronal oscillations that drive the visual experience, not the experience driving the oscillations. And they indicate that synchronized oscillatory activity groups brain areas into functional networks. This points to new ways for controlled experimental and possibly also clinical interventions for the study and modulation of brain oscillations and associated functions.

  20. Modulating Brain Oscillations to Drive Brain Function

    PubMed Central

    Thut, Gregor

    2014-01-01

    Do neuronal oscillations play a causal role in brain function? In a study in this issue of PLOS Biology, Helfrich and colleagues address this long-standing question by attempting to drive brain oscillations using transcranial electrical current stimulation. Remarkably, they were able to manipulate visual perception by forcing brain oscillations of the left and right visual hemispheres into synchrony using oscillatory currents over both hemispheres. Under this condition, human observers more often perceived an inherently ambiguous visual stimulus in one of its perceptual instantiations. These findings shed light on the mechanisms underlying neuronal computation. They show that it is the neuronal oscillations that drive the visual experience, not the experience driving the oscillations. And they indicate that synchronized oscillatory activity groups brain areas into functional networks. This points to new ways for controlled experimental and possibly also clinical interventions for the study and modulation of brain oscillations and associated functions. PMID:25549340

  1. Effectiveness of executive functions training within a virtual supermarket for adults with traumatic brain injury: a pilot study.

    PubMed

    Jacoby, Michele; Averbuch, Sara; Sacher, Yaron; Katz, Noomi; Weiss, Patrice L; Kizony, Rachel

    2013-03-01

    Impairments of executive functions (EF) significantly affect the ability to lead an independent lifestyle. Virtual environments offer a way to rehabilitate EF due to their ecological validity. The purpose of this pilot study was to examine the effectiveness of a virtual reality (VR) supermarket (VMall) for treatment of EF in patients with Traumatic Brain Injury (TBI), compared to conventional occupational therapy (OT), in order to provide initial data regarding the effect sizes for calculation of sample size as well as to establish an intervention protocol for future Randomized Control Trials (RCTs). Twelve men and women, aged 19-55 years, who had TBI resulting in EF impairments participated in this study. Outcome measures were the Multiple Errands Test-Simplified Version (MET-SV) and the Executive Function Performance Test (EFPT). Cognitive treatment provided to both groups was based on the same principles; the participants in the experimental group received 10 45-min VR-based treatment sessions and the control group participants received 10 sessions of occupational therapy cognitive retraining without VR. Baseline performance prior to intervention showed no statistically significant differences between groups. Most participants improved their performance after therapy. Following a Bonferroni correction for multiple comparisons, no significant between or within group differences were found, Nevertheless, large effect sizes (0.51) for the percent (%) relative change of the MET-SV total score and EFPT total score after intervention were high in favor of the experimental group indicating a larger improvement in EF. Based on this pilot study, results show a trend towards an advantage to VR therapy compared to cognitive retraining OT without VR, as it leads to greater improvement in complex everyday activities.

  2. Brain stem auditory evoked responses in human infants and adults

    NASA Technical Reports Server (NTRS)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  3. Functional neurogenesis in the adult hippocampus

    NASA Astrophysics Data System (ADS)

    van Praag, Henriette; Schinder, Alejandro F.; Christie, Brian R.; Toni, Nicolas; Palmer, Theo D.; Gage, Fred H.

    2002-02-01

    There is extensive evidence indicating that new neurons are generated in the dentate gyrus of the adult mammalian hippocampus, a region of the brain that is important for learning and memory. However, it is not known whether these new neurons become functional, as the methods used to study adult neurogenesis are limited to fixed tissue. We use here a retroviral vector expressing green fluorescent protein that only labels dividing cells, and that can be visualized in live hippocampal slices. We report that newly generated cells in the adult mouse hippocampus have neuronal morphology and can display passive membrane properties, action potentials and functional synaptic inputs similar to those found in mature dentate granule cells. Our findings demonstrate that newly generated cells mature into functional neurons in the adult mammalian brain.

  4. Linked alterations in gray and white matter morphology in adults with high-functioning autism spectrum disorder: A multimodal brain imaging study

    PubMed Central

    Itahashi, Takashi; Yamada, Takashi; Nakamura, Motoaki; Watanabe, Hiromi; Yamagata, Bun; Jimbo, Daiki; Shioda, Seiji; Kuroda, Miho; Toriizuka, Kazuo; Kato, Nobumasa; Hashimoto, Ryuichiro

    2014-01-01

    Growing evidence suggests that a broad range of behavioral anomalies in people with autism spectrum disorder (ASD) can be linked with morphological and functional alterations in the brain. However, the neuroanatomical underpinnings of ASD have been investigated using either structural magnetic resonance imaging (MRI) or diffusion tensor imaging (DTI), and the relationships between abnormalities revealed by these two modalities remain unclear. This study applied a multimodal data-fusion method, known as linked independent component analysis (ICA), to a set of structural MRI and DTI data acquired from 46 adult males with ASD and 46 matched controls in order to elucidate associations between different aspects of atypical neuroanatomy of ASD. Linked ICA identified two composite components that showed significant between-group differences, one of which was significantly correlated with age. In the other component, participants with ASD showed decreased gray matter (GM) volumes in multiple regions, including the bilateral fusiform gyri, bilateral orbitofrontal cortices, and bilateral pre- and post-central gyri. These GM changes were linked with a pattern of decreased fractional anisotropy (FA) in several white matter tracts, such as the bilateral inferior longitudinal fasciculi, bilateral inferior fronto-occipital fasciculi, and bilateral corticospinal tracts. Furthermore, unimodal analysis for DTI data revealed significant reductions of FA along with increased mean diffusivity in those tracts for ASD, providing further evidence of disrupted anatomical connectivity. Taken together, our findings suggest that, in ASD, alterations in different aspects of brain morphology may co-occur in specific brain networks, providing a comprehensive view for understanding the neuroanatomy of this disorder. PMID:25610777

  5. Structure of brain functional networks.

    PubMed

    Kuchaiev, Oleksii; Wang, Po T; Nenadic, Zoran; Przulj, Natasa

    2009-01-01

    Brain is a complex network optimized both for segregated and distributed information processing. To perform cognitive tasks, different areas of the brain must "cooperate," thereby forming complex networks of interactions also known as brain functional networks. Previous studies have shown that these networks exhibit "small-world" characteristics. Small-world topology, however, is a general property of all brain functional networks and does not capture structural changes in these networks in response to different stimuli or cognitive tasks. Here we show how novel graph theoretic techniques can be utilized for precise analysis of brain functional networks. These techniques allow us to detect structural changes in brain functional networks in response to different stimuli or cognitive tasks. For certain types of cognitive tasks we have found that these networks exhibit geometric structure in addition to the small-world topology. The method has been applied to the electrocorticographic signals of six epileptic patients.

  6. The Effects of Face Expertise Training on the Behavioral Performance and Brain Activity of Adults with High Functioning Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Faja, Susan; Webb, Sara Jane; Jones, Emily; Merkle, Kristen; Kamara, Dana; Bavaro, Joshua; Aylward, Elizabeth; Dawson, Geraldine

    2012-01-01

    The effect of expertise training with faces was studied in adults with ASD who showed initial impairment in face recognition. Participants were randomly assigned to a computerized training program involving either faces or houses. Pre- and post-testing included standardized and experimental measures of behavior and event-related brain potentials…

  7. Brain Functioning Models for Learning.

    ERIC Educational Resources Information Center

    Tipps, Steve; And Others

    This paper describes three models of brain function, each of which contributes to an integrated understanding of human learning. The first model, the up-and-down model, emphasizes the interconnection between brain structures and functions, and argues that since physiological, emotional, and cognitive responses are inseparable, the learning context…

  8. Effects of environmental tobacco smoke on adult rat brain biochemistry.

    PubMed

    Fuller, Brian F; Gold, Mark S; Wang, Kevin K W; Ottens, Andrew K

    2010-05-01

    Environmental tobacco smoke (ETS) has been linked to deleterious health effects, particularly pulmonary and cardiac disease; yet, the general public considers ETS benign to brain function in adults. In contrast, epidemiological data have suggested that ETS impacts the brain and potentially modulates neurodegenerative disease. The present study begins to examine yet unknown biochemical effects of ETS on the adult mammalian brain. In the developed animal model, adult male rats were exposed to ETS 3 h a day for 3 weeks. Biochemical data showed altered glial fibrillary acid protein levels as a main treatment effect of ETS, suggestive of reactive astrogliosis. Yet, markers of oxidative and cell stress were unaffected by ETS exposure in the brain regions examined. Increased proteolytic degradation of alphaII-spectrin by caspase-3 and the dephosphorylation of serine(116) on PEA-15 indicated greater apoptotic cell death modulated by the extrinsic pathway in the brains of ETS-exposed animals. Further, beta-synuclein was upregulated by ETS, a neuroprotective protein previously reported to exhibit anti-apoptotic and anti-fibrillogenic properties. These findings demonstrate that ETS exposure alters the neuroproteome of the adult rat brain, and suggest modulation of inflammatory and cell death processes.

  9. Experience-dependent neural plasticity in the adult damaged brain

    PubMed Central

    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 extremity (hand and arm) impairments. A prolonged and widespread process of repair and reorganization of surviving neural circuits is instigated by injury to the adult brain. When experience impacts these same neural circuits, it interacts with degenerative and regenerative cascades to shape neural reorganization and functional outcome. This is evident in the cortical plasticity resulting from compensatory reliance on the “good” forelimb in rats with unilateral sensorimotor cortical infarcts. Behavioral interventions (e.g., rehabilitative training) can drive functionally beneficial neural reorganization in the injured hemisphere. However, experience can have both behaviorally beneficial and detrimental effects. The interactions between experience-dependent and injury-induced neural plasticity are complex, time-dependent, and varied with age and other factors. A better understanding of these interactions is needed to understand how to optimize brain remodeling and functional outcome. Learning outcomes Readers will be able to describe (a) experience effects that are maladaptive for behavioral outcome after brain damage, (b) manipulations of experience that drive functionally beneficial neural plasticity, and (c) reasons why rehabilitative training effects can be expected to vary with age, training duration and timing. PMID:21620413

  10. Two views of brain function.

    PubMed

    Raichle, Marcus E

    2010-04-01

    Traditionally studies of brain function have focused on task-evoked responses. By their very nature, such experiments tacitly encourage a reflexive view of brain function. Although such an approach has been remarkably productive, it ignores the alternative possibility that brain functions are mainly intrinsic, involving information processing for interpreting, responding to and predicting environmental demands. Here I argue that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources. Recognizing the importance of intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux.

  11. The Impact of Adult Vitamin D Deficiency on Behaviour and Brain Function in Male Sprague-Dawley Rats

    PubMed Central

    Turner, Karly M.; Eyles, Darryl W.; McGrath, John J.; Burne, Thomas H. J.

    2013-01-01

    Background Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD) deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats. Methods Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT) and the 5 choice continuous performance task (5C-CPT) and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS) task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum. Results AVD-deficient rats were deficient in vitamin D3 (<10 nM) and had normal calcium and phosphate levels after 8–10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI) than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA) responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum. Conclusions AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour. PMID:23951200

  12. Emerging concepts of brain function.

    PubMed

    Bach-Y-Rita, Paul

    2005-06-01

    For over 40 years, since I first obtained evidence for nonsynaptic diffusion neurotransmission (most scientists call it Volume Transmission), I have been convinced that we scientists were ignoring organizational dynamics other than the mechanistic synaptic organization of the brain. For many years it was an uneasy feeling, since I was aware there are so many avenues to explore in brain function. I have wondered how much we scientists have ignored, in our quest to understand how the brain really works, due to our efforts to "be scientific". In addition to the difficulty of understanding how the brain functions, how could we even begin to explore the human experience? In this paper I will first discuss some emerging concepts of brain function. I will then comment on the development of concepts that have been a part of my own research experience.

  13. [Physical activity and brain function].

    PubMed

    Kempermann, G

    2012-06-01

    Physical activity has direct and indirect effects on brain function in health and disease. Findings demonstrating that physical activity improves cognitive and non-cognitive functions and is preventive for several neuropsychiatric disorders have attracted particular interest. This short review focuses on sports and physical exercise in normal brain function and summarizes which mechanisms might underlie the observed effects, which methodological problems exist, which relationships exist to concepts of plasticity and neural reserves and what evolutionary relevance the initially surprising finding that physical exercise is good for the brain has.

  14. Atomoxetine Treatment Strengthens an Anti-Correlated Relationship between Functional Brain Networks in Medication-Naïve Adults with Attention-Deficit Hyperactivity Disorder: A Randomized Double-Blind Placebo-Controlled Clinical Trial

    PubMed Central

    Lin, Hsiang-Yuan

    2016-01-01

    Background: Although atomoxetine demonstrates efficacy in individuals with attention-deficit hyperactivity disorder, its treatment effects on brain resting-state functional connectivity remain unknown. Therefore, we aimed to investigate major brain functional networks in medication-naïve adults with attention-deficit hyperactivity disorder and the efficacy of atomoxetine treatment on resting-state functional connectivity. Methods: After collecting baseline resting-state functional MRI scans from 24 adults with attention-deficit hyperactivity disorder (aged 18–52 years) and 24 healthy controls (matched in demographic characteristics), the participants with attention-deficit hyperactivity disorder were randomly assigned to atomoxetine (n=12) and placebo (n=12) arms in an 8-week, double-blind, placebo-controlled trial. The primary outcome was functional connectivity assessed by a resting-state functional MRI. Seed-based functional connectivity was calculated and compared for the affective, attention, default, and cognitive control networks. Results: At baseline, we found atypical cross talk between the default, cognitive control, and dorsal attention networks and hypoconnectivity within the dorsal attention and default networks in adults with attention-deficit hyperactivity disorder. Our first-ever placebo-controlled clinical trial incorporating resting-state functional MRI showed that treatment with atomoxetine strengthened an anticorrelated relationship between the default and task-positive networks and modulated all major brain networks. The strengthened anticorrelations were associated with improving clinical symptoms in the atomoxetine-treated adults. Conclusions: Our results support the idea that atypical default mode network task-positive network interaction plays an important role in the pathophysiology of adult attention-deficit hyperactivity disorder. Strengthening this atypical relationship following atomoxetine treatment suggests an important pathway to

  15. Higher Brain Function.

    ERIC Educational Resources Information Center

    Chiaia, N.L.; Teyler, T.J.

    1983-01-01

    Focuses on how learning works. Discusses three major components related to processing information--sensory and perceptual systems, integration of information, and output of information--and developmental and environmental factors affecting brain information in each of these areas. Concludes with discussion of biological bases for cognitive and…

  16. Brain function, disease and dementia.

    PubMed

    Sandilyan, Malarvizhi Babu; Dening, Tom

    2015-05-27

    Dementia is a consequence of brain disease. This article, the second in this series on dementia, discusses normal brain function and how certain functions are localised to different areas of the brain. This is important in determining the symptoms of dementia, depending on which parts of the brain are most directly involved. The most common types of dementia - Alzheimer's disease, vascular dementia, dementia with Lewy bodies and frontotemporal dementia - affect the brain in different ways and cause different changes at the microscopic level. Dementia is affected by genetics, and recent advances in molecular techniques have improved our understanding of some of the mechanisms involved, which in turns suggests possibilities for new treatments in the future.

  17. Fetal brain 11β-hydroxysteroid dehydrogenase type 2 selectively determines programming of adult depressive-like behaviors and cognitive function, but not anxiety behaviors in male mice

    PubMed Central

    Wyrwoll, Caitlin; Keith, Marianne; Noble, June; Stevenson, Paula L.; Bombail, Vincent; Crombie, Sandra; Evans, Louise C.; Bailey, Matthew A.; Wood, Emma; Seckl, Jonathan R.; Holmes, Megan C.

    2015-01-01

    Summary Stress or elevated glucocorticoids during sensitive windows of fetal development increase the risk of neuropsychiatric disorders in adult rodents and humans, a phenomenon known as glucocorticoid programming. 11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2), which catalyses rapid inactivation of glucocorticoids in the placenta, controls access of maternal glucocorticoids to the fetal compartment, placing it in a key position to modulate glucocorticoid programming of behavior. However, the importance of the high expression of 11β-HSD2 within the midgestational fetal brain is unknown. To examine this, a brain-specific knockout of 11β-HSD2 (HSD2BKO) was generated and compared to wild-type littermates. HSD2BKO have markedly diminished fetal brain 11β-HSD2, but intact fetal body and placental 11β-HSD2 and normal fetal and placental growth. Despite normal fetal plasma corticosterone, HSD2BKO exhibit elevated fetal brain corticosterone levels at midgestation. As adults, HSD2BKO show depressive-like behavior and have cognitive impairments. However, unlike complete feto-placental deficiency, HSD2BKO show no anxiety-like behavioral deficits. The clear mechanistic separation of the programmed components of depression and cognition from anxiety implies distinct mechanisms of pathogenesis, affording potential opportunities for stratified interventions. PMID:26036451

  18. Adult Functional Competency: A Summary.

    ERIC Educational Resources Information Center

    Texas Univ., Austin. Div. of Extension.

    The Adult Performance Level (APL) project summary specifies the competencies which are functional to economic and educational success in society and describes devices developed for assessing those competencies. The APL theory of functional competency identifies adult needs in general knowledge areas (consumer economics, occupational knowledge,…

  19. Decreased segregation of brain systems across the healthy adult lifespan

    PubMed Central

    Chan, Micaela Y.; Park, Denise C.; Savalia, Neil K.; Petersen, Steven E.; Wig, Gagan S.

    2014-01-01

    Healthy aging has been associated with decreased specialization in brain function. This characterization has focused largely on describing age-accompanied differences in specialization at the level of neurons and brain areas. We expand this work to describe systems-level differences in specialization in a healthy adult lifespan sample (n = 210; 20–89 y). A graph-theoretic framework is used to guide analysis of functional MRI resting-state data and describe systems-level differences in connectivity of individual brain networks. Young adults’ brain systems exhibit a balance of within- and between-system correlations that is characteristic of segregated and specialized organization. Increasing age is accompanied by decreasing segregation of brain systems. Compared with systems involved in the processing of sensory input and motor output, systems mediating “associative” operations exhibit a distinct pattern of reductions in segregation across the adult lifespan. Of particular importance, the magnitude of association system segregation is predictive of long-term memory function, independent of an individual’s age. PMID:25368199

  20. Vitamin K and brain function.

    PubMed

    Ferland, Guylaine

    2013-11-01

    One of the fat-soluble vitamins, vitamin K was initially discovered for its role in blood coagulation. Although several vitamin K-dependent hemostatic proteins are particularly important for the brain, other vitamin K-dependent proteins (VKDPs), not associated with blood coagulation, also contribute to the brain function. In addition to the VKDPs, vitamin K participates in the nervous system through its involvement in sphingolipid metabolism, a class of lipids widely present in brain cell membranes. Classically known for their structural role, sphingolipids are biologically potent molecules involved in a wide range of cellular actions. Also, there is growing evidence that the K vitamer, menaquinone-4, has anti-inflammatory activity and offers protection against oxidative stress. Finally, although limited in numbers, reports point to a modulatory role of vitamin K in cognition. This short review presents an overview of the known role of vitamin K in brain function to date.

  1. Magnetic Resonance, Functional (fMRI) -- Brain

    MedlinePlus

    ... thought, speech, movement and sensation, which is called brain mapping. help assess the effects of stroke, trauma or degenerative disease (such as Alzheimer's) on brain function. monitor the growth and function of brain ...

  2. Subjective and objective cognitive function among older adults with a history of traumatic brain injury: A population-based cohort study

    PubMed Central

    Langa, Kenneth M.; Yaffe, Kristine

    2017-01-01

    Background Traumatic brain injury (TBI) is extremely common across the lifespan and is an established risk factor for dementia. The cognitive profile of the large and growing population of older adults with prior TBI who do not have a diagnosis of dementia, however, has not been well described. Our aim was to describe the cognitive profile associated with prior TBI exposure among community-dwelling older adults without dementia—an understudied but potentially vulnerable population. Methods and findings In this population-based cohort study, we studied 984 community-dwelling older adults (age 51 y and older and their spouses) without dementia who had been randomly selected from respondents to the 2014 wave of the Health and Retirement Study to participate in a comprehensive TBI survey and who either reported no prior TBI (n = 737) or prior symptomatic TBI resulting in treatment in a hospital (n = 247). Mean time since first TBI was 38 ± 19 y. Outcomes assessed included measures of global cognitive function, verbal episodic memory, semantic fluency, and calculation as well as a measure of subjective memory (“How would you rate your memory at the present time?”). We compared outcomes between the two TBI groups using regression models adjusting for demographics, medical comorbidities, and depression. Sensitivity analyses were performed stratified by TBI severity (no TBI, TBI without loss of consciousness [LOC], and TBI with LOC). Respondents with TBI were younger (mean age 64 ± 10 y versus 68 ± 11 y), were less likely to be female, and had higher prevalence of medical comorbidities and depression than respondents without TBI. Respondents with TBI did not perform significantly differently from respondents without TBI on any measure of objective cognitive function in either raw or adjusted models (fully adjusted: global cognitive function score 15.4 versus 15.2, p = 0.68; verbal episodic memory score 4.4 versus 4.3, p = 0.79; semantic fluency score 15.7 versus

  3. Functional Near-Infrared Spectroscopy Brain Imaging Investigation of Phonological Awareness and Passage Comprehension Abilities in Adult Recipients of Cochlear Implants

    ERIC Educational Resources Information Center

    Bisconti, Silvia; Shulkin, Masha; Hu, Xiaosu; Basura, Gregory J.; Kileny, Paul R.; Kovelman, Ioulia

    2016-01-01

    Purpose: The aim of this study was to examine how the brains of individuals with cochlear implants (CIs) respond to spoken language tasks that underlie successful language acquisition and processing. Method: During functional near-infrared spectroscopy imaging, CI recipients with hearing impairment (n = 10, mean age: 52.7 ± 17.3 years) and…

  4. DHA Effects in Brain Development and Function.

    PubMed

    Lauritzen, Lotte; Brambilla, Paolo; Mazzocchi, Alessandra; Harsløf, Laurine B S; Ciappolino, Valentina; Agostoni, Carlo

    2016-01-04

    Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Its accumulation in the fetal brain takes place mainly during the last trimester of pregnancy and continues at very high rates up to the end of the second year of life. Since the endogenous formation of DHA seems to be relatively low, DHA intake may contribute to optimal conditions for brain development. We performed a narrative review on research on the associations between DHA levels and brain development and function throughout the lifespan. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling. Most data from human studies concern the contribution of DHA to optimal visual acuity development. Accumulating data indicate that DHA may have effects on the brain in infancy, and recent studies indicate that the effect of DHA may depend on gender and genotype of genes involved in the endogenous synthesis of DHA. While DHA levels may affect early development, potential effects are also increasingly recognized during childhood and adult life, suggesting a role of DHA in cognitive decline and in relation to major psychiatric disorders.

  5. DHA Effects in Brain Development and Function

    PubMed Central

    Lauritzen, Lotte; Brambilla, Paolo; Mazzocchi, Alessandra; Harsløf, Laurine B. S.; Ciappolino, Valentina; Agostoni, Carlo

    2016-01-01

    Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Its accumulation in the fetal brain takes place mainly during the last trimester of pregnancy and continues at very high rates up to the end of the second year of life. Since the endogenous formation of DHA seems to be relatively low, DHA intake may contribute to optimal conditions for brain development. We performed a narrative review on research on the associations between DHA levels and brain development and function throughout the lifespan. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling. Most data from human studies concern the contribution of DHA to optimal visual acuity development. Accumulating data indicate that DHA may have effects on the brain in infancy, and recent studies indicate that the effect of DHA may depend on gender and genotype of genes involved in the endogenous synthesis of DHA. While DHA levels may affect early development, potential effects are also increasingly recognized during childhood and adult life, suggesting a role of DHA in cognitive decline and in relation to major psychiatric disorders. PMID:26742060

  6. Development of Large-Scale Functional Brain Networks in Children

    PubMed Central

    Supekar, Kaustubh; Musen, Mark; Menon, Vinod

    2009-01-01

    The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7–9 y) and 22 young-adults (ages 19–22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar “small-world” organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism. PMID:19621066

  7. Brain network activity in monolingual and bilingual older adults.

    PubMed

    Grady, Cheryl L; Luk, Gigi; Craik, Fergus I M; Bialystok, Ellen

    2015-01-01

    Bilingual older adults typically have better performance on tasks of executive control (EC) than do their monolingual peers, but differences in brain activity due to language experience are not well understood. Based on studies showing a relation between the dynamic range of brain network activity and performance on EC tasks, we hypothesized that life-long bilingual older adults would show increased functional connectivity relative to monolinguals in networks related to EC. We assessed intrinsic functional connectivity and modulation of activity in task vs. fixation periods in two brain networks that are active when EC is engaged, the frontoparietal control network (FPC) and the salience network (SLN). We also examined the default mode network (DMN), which influences behavior through reduced activity during tasks. We found stronger intrinsic functional connectivity in the FPC and DMN in bilinguals than in monolinguals. Although there were no group differences in the modulation of activity across tasks and fixation, bilinguals showed stronger correlations than monolinguals between intrinsic connectivity in the FPC and task-related increases of activity in prefrontal and parietal regions. This bilingual difference in network connectivity suggests that language experience begun in childhood and continued throughout adulthood influences brain networks in ways that may provide benefits in later life.

  8. Brain Network Activity in Monolingual and Bilingual Older Adults

    PubMed Central

    Grady, Cheryl L.; Luk, Gigi; Craik, Fergus I.M.; Bialystok, Ellen

    2016-01-01

    Bilingual older adults typically have better performance on tasks of executive control (EC) than do their monolingual peers, but differences in brain activity due to language experience are not well understood. Based on studies showing a relation between the dynamic range of brain network activity and performance on EC tasks, we hypothesized that life-long bilingual older adults would show increased functional connectivity relative to monolinguals in networks related to EC. We assessed intrinsic functional connectivity and modulation of activity in task vs. fixation periods in two brain networks that are active when EC is engaged, the frontoparietal control network (FPC) and the salience network (SLN). We also examined the default mode network (DMN), which influences behavior through reduced activity during tasks. We found stronger intrinsic functional connectivity in the FPC and DMN in bilinguals than in monolinguals. Although there were no group differences in the modulation of activity across tasks and fixation, bilinguals showed stronger correlations than monolinguals between intrinsic connectivity in the FPC and task-related increases of activity in prefrontal and parietal regions. This bilingual difference in network connectivity suggests that language experience begun in childhood and continued throughout adulthood influences brain networks in ways that may provide benefits in later life. PMID:25445783

  9. Epigenetic choreographers of neurogenesis in the adult mammalian brain

    PubMed Central

    Ma, Dengke K; Marchetto, Maria Carolina; Guo, Junjie U; Ming, Guo-li; Gage, Fred H; Song, Hongjun

    2012-01-01

    Epigenetic mechanisms regulate cell differentiation during embryonic development and also serve as important interfaces between genes and the environment in adulthood. Neurogenesis in adults, which generates functional neural cell types from adult neural stem cells, is dynamically regulated by both intrinsic state-specific cell differentiation cues and extrinsic neural niche signals. Epigenetic regulation by DNA and histone modifiers, non-coding RNAs and other self-sustained mechanisms can lead to relatively long-lasting biological effects and maintain functional neurogenesis throughout life in discrete regions of the mammalian brain. Here, we review recent evidence that epigenetic mechanisms carry out diverse roles in regulating specific aspects of adult neurogenesis and highlight the implications of such epigenetic regulation for neural plasticity and disorders. PMID:20975758

  10. Sialylation regulates brain structure and function

    PubMed Central

    Yoo, Seung-Wan; Motari, Mary G.; Susuki, Keiichiro; Prendergast, Jillian; Mountney, Andrea; Hurtado, Andres; Schnaar, Ronald L.

    2015-01-01

    Every cell expresses a molecularly diverse surface glycan coat (glycocalyx) comprising its interface with its cellular environment. In vertebrates, the terminal sugars of the glycocalyx are often sialic acids, 9-carbon backbone anionic sugars implicated in intermolecular and intercellular interactions. The vertebrate brain is particularly enriched in sialic acid-containing glycolipids termed gangliosides. Human congenital disorders of ganglioside biosynthesis result in paraplegia, epilepsy, and intellectual disability. To better understand sialoglycan functions in the nervous system, we studied brain anatomy, histology, biochemistry, and behavior in mice with engineered mutations in St3gal2 and St3gal3, sialyltransferase genes responsible for terminal sialylation of gangliosides and some glycoproteins. St3gal2/3 double-null mice displayed dysmyelination marked by a 40% reduction in major myelin proteins, 30% fewer myelinated axons, a 33% decrease in myelin thickness, and molecular disruptions at nodes of Ranvier. In part, these changes may be due to dysregulation of ganglioside-mediated oligodendroglial precursor cell proliferation. Neuronal markers were also reduced up to 40%, and hippocampal neurons had smaller dendritic arbors. Young adult St3gal2/3 double-null mice displayed impaired motor coordination, disturbed gait, and profound cognitive disability. Comparisons among sialyltransferase mutant mice provide insights into the functional roles of brain gangliosides and sialoglycoproteins consistent with related human congenital disorders.—Yoo, S.-W., Motari, M. G., Susuki, K., Prendergast, J., Mountney, A., Hurtado, A., Schnaar, R. L. Sialylation regulates brain structure and function. PMID:25846372

  11. Guidelines for Better Communication with Brain Impaired Adults

    MedlinePlus

    ... are here Home Guidelines for Better Communication with Brain Impaired Adults Printer-friendly version Communicating with a loved one with a brain disorder can indeed be challenging. Finding the right ...

  12. [Brain function and white matter].

    PubMed

    Wake, Hiroaki; Kato, Daisuke

    2015-04-01

    Accumulated evidence shows that neural information processing takes place in superficial layers of the brain called the gray matter. Synapses, which connect different neurons reside in the gray matter and are considered the major components of information processing and plasticity. On the other hand, myelinated axons lie beneath the gray matter. These bundles of cables connect neurons in the different brain regions to form functional neural circuits. Myelinated axons were of little of interest to neuroscientists and have long been ignored in the formation of functional neuronal circuits. Recent evidence shows that myelin formed by oligodendrocytes shows plastic changes depending on neuronal activity. In this issue, we discuss the plastic changes of myelin and its functional role in learning and training.

  13. Behavioral and magnetoencephalographic correlates of plasticity in the adult human brain

    PubMed Central

    Ramachandran, V. S.

    1993-01-01

    Recent behavioral and physiological evidence suggests that even brief sensory deprivation can lead to the rapid emergence of new and functionally effective neural connections in the adult human brain. Images Fig. 2 PMID:8248123

  14. Comprehensive cellular‐resolution atlas of the adult human brain

    PubMed Central

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

    2016-01-01

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

  15. 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

  16. 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.

  17. Investigation of genes important in neurodevelopment disorders in adult human brain.

    PubMed

    Maussion, Gilles; Diallo, Alpha B; Gigek, Carolina O; Chen, Elizabeth S; Crapper, Liam; Théroux, Jean-Francois; Chen, Gary G; Vasuta, Cristina; Ernst, Carl

    2015-10-01

    Several neurodevelopmental disorders (NDDs) are caused by mutations in genes expressed in fetal brain, but little is known about these same genes in adult human brain. Here, we test the hypothesis that genes associated with NDDs continue to have a role in adult human brain to explore the idea that NDD symptoms may be partially a result of their adult function rather than just their neurodevelopmental function. To demonstrate adult brain function, we performed expression analyses and ChIPseq in human neural stem cell(NSC) lines at different developmental stages and adult human brain, targeting two genes associated with NDDs, SATB2 and EHMT1, and the WNT signaling gene TCF7L2, which has not been associated with NDDs. Analysis of DNA interaction sites in neural stem cells reveals high (40-50 %) overlap between proliferating and differentiating cells for each gene in temporal space. Studies in adult brain demonstrate that consensus sites are similar to NSCs but occur at different genomic locations. We also performed expression analyses using BrainSpan data for NDD-associated genes SATB2, EHMT1, FMR1, MECP2, MBD5, CTNND2, RAI1, CHD8, GRIN2A, GRIN2B, TCF4, SCN2A, and DYRK1A and find high expression of these genes in adult brain, at least comparable to developing human brain, confirming that genes associated with NDDs likely have a role in adult tissue. Adult function of genes associated with NDDs might be important in clinical disease presentation and may be suitable targets for therapeutic intervention.

  18. Default brain functionality in blind people.

    PubMed

    Burton, H; Snyder, A Z; Raichle, M E

    2004-10-26

    We studied whether default functionality of the human brain, as revealed by task-independent decreases in activity occurring during goal-directed behaviors, is functionally reorganized by blindness. Three groups of otherwise normal adults were studied: early blind, adventitiously blind, and normally sighted. They were imaged by using functional MRI during performance of a word association task (verb generation to nouns) administered by using auditory stimuli in all groups and Braille reading in blind participants. In sighted people, this task normally produces robust task-independent decreases relative to a baseline of quiet wakefulness with eyes closed. Our functional MRI results indicate that task-independent decreases are qualitatively similar across all participant groups in medial and dorsal prefrontal, lateral parietal, anterior precuneus, and posterior cingulate cortices. Similarities in task-independent decreases are consistent with the hypothesis that functional reorganization resulting from the absence of a particular sensory modality does not qualitatively affect default functionality as revealed by task-independent decreases. More generally, these results support the notion that the brain largely operates intrinsically, with sensory information modulating rather than determining system operations.

  19. Graph analysis of functional brain networks for cognitive control of action in traumatic brain injury.

    PubMed

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

    2012-04-01

    Patients with traumatic brain injury show clear impairments in behavioural flexibility and inhibition that often persist beyond the time of injury, affecting independent living and psychosocial functioning. Functional magnetic resonance imaging studies have shown that patients with traumatic brain injury typically show increased and more broadly dispersed frontal and parietal activity during performance of cognitive control tasks. We constructed binary and weighted functional networks and calculated their topological properties using a graph theoretical approach. Twenty-three adults with traumatic brain injury and 26 age-matched controls were instructed to switch between coordination modes while making spatially and temporally coupled circular motions with joysticks during event-related functional magnetic resonance imaging. Results demonstrated that switching performance was significantly lower in patients with traumatic brain injury compared with control subjects. Furthermore, although brain networks of both groups exhibited economical small-world topology, altered functional connectivity was demonstrated in patients with traumatic brain injury. In particular, compared with controls, patients with traumatic brain injury showed increased connectivity degree and strength, and higher values of local efficiency, suggesting adaptive mechanisms in this group. Finally, the degree of increased connectivity was significantly correlated with poorer switching task performance and more severe brain injury. We conclude that analysing the functional brain network connectivity provides new insights into understanding cognitive control changes following brain injury.

  20. Acute moderate exercise enhances compensatory brain activation in older adults.

    PubMed

    Hyodo, Kazuki; Dan, Ippeita; Suwabe, Kazuya; Kyutoku, Yasushi; Yamada, Yuhki; Akahori, Mitsuya; Byun, Kyeongho; Kato, Morimasa; Soya, Hideaki

    2012-11-01

    A growing number of reports state that regular exercise enhances brain function in older adults. Recently a functional near-infrared spectroscopy (fNIRS) study revealed that an acute bout of moderate exercise enhanced activation of the left dorsolateral prefrontal cortex (L-DLPFC) associated with Stroop interference in young adults. Whether this acute effect is also applicable to older adults was examined. Sixteen older adults performed a color-word matching Stroop task before and after 10 minutes of exercise on a cycle ergometer at a moderate intensity. Cortical hemodynamics of the prefrontal area was monitored with a fNIRS during the Stroop task. We analyzed Stroop interference (incongruent-neutral) as Stroop performance. Though activation for Stroop interference was found in the bilateral prefrontal area before the acute bout of exercise, activation of the right frontopolar area (R-FPA) was enhanced after exercise. In the majority of participants, this coincided with improved performance reflected in Stroop interference results. Thus, an acute bout of moderate exercise improved Stroop performance in older adults, and this was associated with contralateral compensatory activation.

  1. 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.

  2. GABA regulates synaptic integration of newly generated neurons in the adult brain

    NASA Astrophysics Data System (ADS)

    Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

    2006-02-01

    Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

  3. Functional brain imaging across development.

    PubMed

    Rubia, Katya

    2013-12-01

    The developmental cognitive neuroscience literature has grown exponentially over the last decade. This paper reviews the functional magnetic resonance imaging (fMRI) literature on brain function development of typically late developing functions of cognitive and motivation control, timing and attention as well as of resting state neural networks. Evidence shows that between childhood and adulthood, concomitant with cognitive maturation, there is progressively increased functional activation in task-relevant lateral and medial frontal, striatal and parieto-temporal brain regions that mediate these higher level control functions. This is accompanied by progressively stronger functional inter-regional connectivity within task-relevant fronto-striatal and fronto-parieto-temporal networks. Negative age associations are observed in earlier developing posterior and limbic regions, suggesting a shift with age from the recruitment of "bottom-up" processing regions towards "top-down" fronto-cortical and fronto-subcortical connections, leading to a more mature, supervised cognition. The resting state fMRI literature further complements this evidence by showing progressively stronger deactivation with age in anti-correlated task-negative resting state networks, which is associated with better task performance. Furthermore, connectivity analyses during the resting state show that with development increasingly stronger long-range connections are being formed, for example, between fronto-parietal and fronto-cerebellar connections, in both task-positive networks and in task-negative default mode networks, together with progressively lesser short-range connections, suggesting progressive functional integration and segregation with age. Overall, evidence suggests that throughout development between childhood and adulthood, there is progressive refinement and integration of both task-positive fronto-cortical and fronto-subcortical activation and task-negative deactivation, leading to

  4. Isolation and Culture of Adult Zebrafish Brain-derived Neurospheres

    PubMed Central

    Lopez-Ramirez, Miguel A.; Calvo, Charles-Félix; Ristori, Emma; Thomas, Jean-Léon; Nicoli, Stefania

    2016-01-01

    The zebrafish is a highly relevant model organism for understanding the cellular and molecular mechanisms involved in neurogenesis and brain regeneration in vertebrates. However, an in-depth analysis of the molecular mechanisms underlying zebrafish adult neurogenesis has been limited due to the lack of a reliable protocol for isolating and culturing neural adult stem/progenitor cells. Here we provide a reproducible method to examine adult neurogenesis using a neurosphere assay derived from zebrafish whole brain or from the telencephalon, tectum and cerebellum regions of the adult zebrafish brain. The protocol involves, first the microdissection of zebrafish adult brain, then single cell dissociation and isolation of self-renewing multipotent neural stem/progenitor cells. The entire procedure takes eight days. Additionally, we describe how to manipulate gene expression in zebrafish neurospheres, which will be particularly useful to test the role of specific signaling pathways during adult neural stem/progenitor cell proliferation and differentiation in zebrafish. PMID:26967835

  5. Superbinding in Integrative Brain Function and Memory

    DTIC Science & Technology

    2007-11-02

    A:\\basar.doc 1 SUPERBINDING IN INTEGRATIVE BRAIN FUNCTION AND MEMORY E. Basar1,2, M. Özgören1,2, S. Karakas1,3 1TUBITAK Brain Dynamics...percepts and integrative brain function. Keywords- superbinding, oscillations, binding, coherence 1 Aim of the report The present report aims to...introduce the superbinding theory to describe the machineries of integrative brain function instead of single neuron doctrine. This concept is based on

  6. Low-Resolution Electromagnetic Tomography (LORETA) of changed Brain Function Provoked by Pro-Dopamine Regulator (KB220z) in one Adult ADHD case

    PubMed Central

    Steinberg, Bruce; Blum, Kenneth; McLaughlin, Thomas; Lubar, Joel; Febo, Marcelo; Braverman, Eric R.; Badgaiyan, Rajendra D

    2016-01-01

    Attention Deficit-Hyperactivity Disorder (ADHD) often continues into adulthood. Recent neuroimaging studies found lowered baseline dopamine tone in the brains of affected individuals that may place them at risk for Substance Use Disorder (SUD). This is an observational case study of the potential for novel management of Adult ADHD with a non-addictive glutaminergic-dopaminergic optimization complex KB200z. Low-resolution electromagnetic tomography (LORETA) was used to evaluate the effects of KB220z on a 72-year-old male with ADHD, at baseline and one hour following administration. The resultant z-scores, averaged across Eyes Closed, Eyes Open and Working Memory conditions, increased for each frequency band, in the anterior, dorsal and posterior cingulate regions, as well as the right dorsolateral prefrontal cortex during Working Memory, with KB220z. These scores are consistent with other human and animal neuroimaging studies that demonstrated increased connectivity volumes in reward circuitry and may offer a new approach to ADHD treatment. However, larger randomized trials to confirm these results are required. PMID:27610420

  7. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases

    PubMed Central

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and brain tumors. PMID:27375363

  8. Insulin action in brain regulates systemic metabolism and brain function.

    PubMed

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

    2014-07-01

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

  9. Preattentive sensory processing as indexed by the MMN and P3a brain responses is associated with cognitive and psychosocial functioning in healthy adults.

    PubMed

    Light, Gregory A; Swerdlow, Neal R; Braff, David L

    2007-10-01

    Understanding the basic neural processes that underlie complex higher order cognitive operations and psychosocial functioning is a fundamental goal of cognitive neuroscience. Event-related potentials allow investigators to probe the earliest stages of information processing. Mismatch negativity (MMN) and P3a are auditory event-related potential components that reflect automatic sensory discrimination. The aim of the present study was to determine if MMN and P3a are associated with higher order cognitive operations and psychosocial functioning in clinically normal healthy subjects. Twenty adults were assessed using standardized clinical, cognitive, and psychosocial functional instruments. All individuals were within the normal range on cognitive tests and functional ratings. Participants were also tested on a duration-deviant MMN/P3a paradigm (50-msec standard tones, p = .90; 100-msec deviant tones, p = .10; stimulus onset asynchrony [SOA] = 505 msec). Across fronto-central electrode regions, significant correlations were observed between psychosocial functioning and MMN (r = -.62, p < .01) and P3a (r = .63, p < .01) amplitudes. P3a amplitude was also highly associated with immediate and delayed recall of verbal information with robust correlations widely distributed across fronto-central recording areas (e.g., r = .72, p < .001). The latency of the P3a response was significantly associated with both working memory performance (r = -.53, p < .05) and functional ratings (r = -.48, p < .05). Neurophysiological measures of relatively automatic auditory sensory information processing are associated with higher order cognitive abilities and psychosocial functioning in normal subjects. Efficiency at elementary levels of information processing may underlie the successful encoding, retrieval, and discrimination of task-relevant information, which, in turn, facilitates the iterative and responsive processing necessary for adaptive cognitive and social functioning.

  10. Neuroimaging in adult penetrating brain injury: a guide for radiographers

    PubMed Central

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-01-01

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings. PMID:26229677

  11. Neuroimaging in adult penetrating brain injury: a guide for radiographers.

    PubMed

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-06-01

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings.

  12. Neuroimaging in adult penetrating brain injury: a guide for radiographers

    SciTech Connect

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-06-15

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings.

  13. Aging and functional brain networks

    SciTech Connect

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

    2011-07-11

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

  14. Functional Prions in the Brain.

    PubMed

    Rayman, Joseph B; Kandel, Eric R

    2017-01-03

    Prions are proteins that can adopt self-perpetuating conformations and are traditionally regarded as etiological agents of infectious neurodegenerative diseases in humans, such as Creutzfeldt-Jakob disease, kuru, and transmissible encephalopathies. More recently, a growing consensus has emerged that prion-like, self-templating mechanisms also underlie a variety of neurodegenerative disorders, including amyotrophic lateral sclerosis, Alzheimer's disease, and Huntington's disease. Perhaps most surprising, not all prion-like aggregates are associated with pathological changes. There are now several examples of prion-like proteins in mammals that serve positive biological functions in their aggregated state. In this review, we discuss functional prions in the nervous system, with particular emphasis on the cytoplasmic polyadenylation element-binding protein (CPEB) and the role of its prion-like aggregates in synaptic plasticity and memory. We also mention a more recent example of a functional prion-like protein in the brain, TIA-1, and its role during stress. These studies of functional prion-like proteins have provided a number of generalizable insights on how prion-based protein switches may operate to serve physiological functions in higher eukaryotes.

  15. Experimental induction of corpora amylacea in adult rat brain.

    PubMed

    Schipper, H M

    1998-10-01

    Corpora amylacea (CA) are glycoproteinaceous inclusions that accumulate in astroglia and other brain cells as a function of advancing age and, to an even greater extent, in several human neurodegenerative conditions. The mechanisms responsible for their biogenesis and their subcellular origin(s) remain unclear. We previously demonstrated that the sulfhydryl agent, cysteamine (CSH), promotes the accumulation of CA-like inclusions in cultured rat astroglia. In the present study, we show that subcutaneous administration of CSH to adult rats (150 mg/kg for 6 weeks followed by a 5-week drug-washout period) elicits the accumulation of CA in many cortical and subcortical brain regions. As in the aging human brain and in CSH-treated rat astrocyte cultures, the inclusions are periodic acid-Schiff -positive and are consistently immunostained with antibodies directed against mitochondrial epitopes and ubiquitin. Our findings support our contention that mitochondria are important structural precursors of CA, and that CSH accelerates aging-like processes in rat astroglia both in vitro and in the intact brain.

  16. Totally tubular: the mystery behind function and origin of the brain ventricular system.

    PubMed

    Lowery, Laura Anne; Sive, Hazel

    2009-04-01

    A unique feature of the vertebrate brain is the ventricular system, a series of connected cavities which are filled with cerebrospinal fluid (CSF) and surrounded by neuroepithelium. While CSF is critical for both adult brain function and embryonic brain development, neither development nor function of the brain ventricular system is fully understood. In this review, we discuss the mystery of why vertebrate brains have ventricles, and whence they originate. The brain ventricular system develops from the lumen of the neural tube, as the neuroepithelium undergoes morphogenesis. The molecular mechanisms underlying this ontogeny are described. We discuss possible functions of both adult and embryonic brain ventricles, as well as major brain defects that are associated with CSF and brain ventricular abnormalities. We conclude that vertebrates have taken advantage of their neural tube to form the essential brain ventricular system.

  17. Encoding of mechanical nociception differs in the adult and infant brain

    PubMed Central

    Fabrizi, Lorenzo; Verriotis, Madeleine; Williams, Gemma; Lee, Amy; Meek, Judith; Olhede, Sofia; Fitzgerald, Maria

    2016-01-01

    Newborn human infants display robust pain behaviour and specific cortical activity following noxious skin stimulation, but it is not known whether brain processing of nociceptive information differs in infants and adults. Imaging studies have emphasised the overlap between infant and adult brain connectome architecture, but electrophysiological analysis of infant brain nociceptive networks can provide further understanding of the functional postnatal development of pain perception. Here we hypothesise that the human infant brain encodes noxious information with different neuronal patterns compared to adults. To test this we compared EEG responses to the same time-locked noxious skin lance in infants aged 0–19 days (n = 18, clinically required) and adults aged 23–48 years (n = 21). Time-frequency analysis revealed that while some features of adult nociceptive network activity are present in infants at longer latencies, including beta-gamma oscillations, infants display a distinct, long latency, noxious evoked 18-fold energy increase in the fast delta band (2–4 Hz) that is absent in adults. The differences in activity between infants and adults have a widespread topographic distribution across the brain. These data support our hypothesis and indicate important postnatal changes in the encoding of mechanical pain in the human brain. PMID:27345331

  18. Life after Adolescent and Adult Moderate and Severe Traumatic Brain Injury: Self-Reported Executive, Emotional, and Behavioural Function 2–5 Years after Injury

    PubMed Central

    Finnanger, Torun Gangaune; Olsen, Alexander; Skandsen, Toril; Lydersen, Stian; Vik, Anne; Evensen, Kari Anne I.; Catroppa, Cathy; Håberg, Asta K.; Andersson, Stein; Indredavik, Marit S.

    2015-01-01

    Survivors of moderate-severe Traumatic Brain Injury (TBI) are at risk for long-term cognitive, emotional, and behavioural problems. This prospective cohort study investigated self-reported executive, emotional, and behavioural problems in the late chronic phase of moderate and severe TBI, if demographic characteristics (i.e., age, years of education), injury characteristics (Glasgow Coma Scale score, MRI findings such as traumatic axonal injury (TAI), or duration of posttraumatic amnesia), symptoms of depression, or neuropsychological variables in the first year after injury predicted long-term self-reported function. Self-reported executive, emotional, and behavioural functioning were assessed among individuals with moderate and severe TBI (N = 67, age range 15–65 years at time of injury) 2–5 years after TBI, compared to a healthy matched control group (N = 72). Results revealed significantly more attentional, emotional regulation, and psychological difficulties in the TBI group than controls. Demographic and early clinical variables were associated with poorer cognitive and emotional outcome. Fewer years of education and depressive symptoms predicted greater executive dysfunction. Younger age at injury predicted more aggressive and rule-breaking behaviour. TAI and depressive symptoms predicted Internalizing problems and greater executive dysfunction. In conclusion, age, education, TAI, and depression appear to elevate risk for poor long-term outcome, emphasising the need for long-term follow-up of patients presenting with risk factors. PMID:26549936

  19. Mechanisms of neuronal migration in the adult brain.

    PubMed

    Kaneko, Naoko; Sawada, Masato; Sawamoto, Kazunobu

    2017-03-02

    Adult neurogenesis was first observed nearly 60 years ago, and it has since grown into an important neurochemistry research field. Much recent research has focused on the treatment of brain diseases through neuronal regeneration with endogenously generated neurons. In the adult brain, immature neurons called neuroblasts are continuously generated in the ventricular-subventricular zone (V-SVZ). These neuroblasts migrate rapidly through the rostral migratory stream to the olfactory bulb, where they mature and are integrated into the neuronal circuitry. After brain insult, some of the neuroblasts in the V-SVZ migrate toward the lesion to repopulate the injured tissue. This notable migratory capacity of V-SVZ-derived neuroblasts is important for efficiently regenerating neurons in remote areas of the brain. As these neurons migrate for long distances through adult brain tissue, they are supported by various guidance cues and structures that act as scaffolds. Some of these mechanisms are unique to neuroblast migration in the adult brain, and are not involved in migration in the developing brain. Here, we review the latest findings on the mechanisms of neuroblast migration in the adult brain under physiological and pathological conditions, and discuss various issues that still need to be resolved. This article is protected by copyright. All rights reserved.

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

    PubMed

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

    2016-01-01

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

  1. Embryonic exposure to 10 μg L(-1) lead results in female-specific expression changes in genes associated with nervous system development and function and Alzheimer's disease in aged adult zebrafish brain.

    PubMed

    Lee, Jinyoung; Freeman, Jennifer L

    2016-06-01

    A developmental lead (Pb) exposure has been proposed as an environmental risk factor for adult neurodegenerative diseases including Alzheimer's disease (AD). Recent animal studies showed pathological characteristics of AD in adults with a developmental Pb exposure, but additional studies are needed to investigate this phenomenon. To further assess the relationship between an embryonic Pb exposure and latent neurological alterations, the brain of adult female and male zebrafish aged 12 months that were exposed to a control treatment or 10 μg L(-1) Pb only during embryogenesis (1-72 hours after fertilization) were analyzed on a zebrafish-specific microarray platform. Gene ontology and pathway analysis revealed similarities in the top disease and functional categories in both sexes, but females had 4.3 times more genes altered than males. In addition, alterations in genes associated with nervous system development and function were more pronounced with a set of 89 genes associated with AD including amyloid precursor protein (APP), apolipoprotein (APOE), and sortlin-related receptor precursor (SORL1) observed to be changed in adult females. Our observations suggest that an embryonic exposure to Pb at levels as low as 10 μg L(-1) disturb global gene expression patterns in a sex-specific manner that could lead to neurological alterations in later life. With these findings, future studies investigating the adverse neurological outcomes of these changes in gene expression will facilitate our understanding of the impact of an embryonic 10 μg L(-1) Pb exposure on neurological disease pathogenesis and the inclusion of additional concentrations will broaden our knowledge of dose-dependent changes.

  2. Human brain activity with functional NIR optical imager

    NASA Astrophysics Data System (ADS)

    Luo, Qingming

    2001-08-01

    In this paper we reviewed the applications of functional near infrared optical imager in human brain activity. Optical imaging results of brain activity, including memory for new association, emotional thinking, mental arithmetic, pattern recognition ' where's Waldo?, occipital cortex in visual stimulation, and motor cortex in finger tapping, are demonstrated. It is shown that the NIR optical method opens up new fields of study of the human population, in adults under conditions of simulated or real stress that may have important effects upon functional performance. It makes practical and affordable for large populations the complex technology of measuring brain function. It is portable and low cost. In cognitive tasks subjects could report orally. The temporal resolution could be millisecond or less in theory. NIR method will have good prospects in exploring human brain secret.

  3. Maturation of widely distributed brain function subserves cognitive development.

    PubMed

    Luna, B; Thulborn, K R; Munoz, D P; Merriam, E P; Garver, K E; Minshew, N J; Keshavan, M S; Genovese, C R; Eddy, W F; Sweeney, J A

    2001-05-01

    Cognitive and brain maturational changes continue throughout late childhood and adolescence. During this time, increasing cognitive control over behavior enhances the voluntary suppression of reflexive/impulsive response tendencies. Recently, with the advent of functional MRI, it has become possible to characterize changes in brain activity during cognitive development. In order to investigate the cognitive and brain maturation subserving the ability to voluntarily suppress context-inappropriate behavior, we tested 8-30 year olds in an oculomotor response-suppression task. Behavioral results indicated that adult-like ability to inhibit prepotent responses matured gradually through childhood and adolescence. Functional MRI results indicated that brain activation in frontal, parietal, striatal, and thalamic regions increased progressively from childhood to adulthood. Prefrontal cortex was more active in adolescents than in children or adults; adults demonstrated greater activation in the lateral cerebellum than younger subjects. These results suggest that efficient top-down modulation of reflexive acts may not be fully developed until adulthood and provide evidence that maturation of function across widely distributed brain regions lays the groundwork for enhanced voluntary control of behavior during cognitive development.

  4. Memory and Brain Volume in Adults Prenatally Exposed to Alcohol

    ERIC Educational Resources Information Center

    Coles, Claire D.; Goldstein, Felicia C.; Lynch, Mary Ellen; Chen, Xiangchuan; Kable, Julie A.; Johnson, Katrina C.; Hu, Xiaoping

    2011-01-01

    The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n = 26; Alcohol-related Neurodevelopmental Disorder, n = 36; and Dysmorphic, n = 30) were imaged using structural MRI with brain volume calculated for…

  5. The brain timewise: how timing shapes and supports brain function.

    PubMed

    Hari, Riitta; Parkkonen, Lauri

    2015-05-19

    We discuss the importance of timing in brain function: how temporal dynamics of the world has left its traces in the brain during evolution and how we can monitor the dynamics of the human brain with non-invasive measurements. Accurate timing is important for the interplay of neurons, neuronal circuitries, brain areas and human individuals. In the human brain, multiple temporal integration windows are hierarchically organized, with temporal scales ranging from microseconds to tens and hundreds of milliseconds for perceptual, motor and cognitive functions, and up to minutes, hours and even months for hormonal and mood changes. Accurate timing is impaired in several brain diseases. From the current repertoire of non-invasive brain imaging methods, only magnetoencephalography (MEG) and scalp electroencephalography (EEG) provide millisecond time-resolution; our focus in this paper is on MEG. Since the introduction of high-density whole-scalp MEG/EEG coverage in the 1990s, the instrumentation has not changed drastically; yet, novel data analyses are advancing the field rapidly by shifting the focus from the mere pinpointing of activity hotspots to seeking stimulus- or task-specific information and to characterizing functional networks. During the next decades, we can expect increased spatial resolution and accuracy of the time-resolved brain imaging and better understanding of brain function, especially its temporal constraints, with the development of novel instrumentation and finer-grained, physiologically inspired generative models of local and network activity. Merging both spatial and temporal information with increasing accuracy and carrying out recordings in naturalistic conditions, including social interaction, will bring much new information about human brain function.

  6. The brain timewise: how timing shapes and supports brain function

    PubMed Central

    Hari, Riitta; Parkkonen, Lauri

    2015-01-01

    We discuss the importance of timing in brain function: how temporal dynamics of the world has left its traces in the brain during evolution and how we can monitor the dynamics of the human brain with non-invasive measurements. Accurate timing is important for the interplay of neurons, neuronal circuitries, brain areas and human individuals. In the human brain, multiple temporal integration windows are hierarchically organized, with temporal scales ranging from microseconds to tens and hundreds of milliseconds for perceptual, motor and cognitive functions, and up to minutes, hours and even months for hormonal and mood changes. Accurate timing is impaired in several brain diseases. From the current repertoire of non-invasive brain imaging methods, only magnetoencephalography (MEG) and scalp electroencephalography (EEG) provide millisecond time-resolution; our focus in this paper is on MEG. Since the introduction of high-density whole-scalp MEG/EEG coverage in the 1990s, the instrumentation has not changed drastically; yet, novel data analyses are advancing the field rapidly by shifting the focus from the mere pinpointing of activity hotspots to seeking stimulus- or task-specific information and to characterizing functional networks. During the next decades, we can expect increased spatial resolution and accuracy of the time-resolved brain imaging and better understanding of brain function, especially its temporal constraints, with the development of novel instrumentation and finer-grained, physiologically inspired generative models of local and network activity. Merging both spatial and temporal information with increasing accuracy and carrying out recordings in naturalistic conditions, including social interaction, will bring much new information about human brain function. PMID:25823867

  7. Childhood Onset Schizophrenia: Cortical Brain Abnormalities as Young Adults

    ERIC Educational Resources Information Center

    Greenstein, Deanna; Lerch, Jason; Shaw, Philip; Clasen, Liv; Giedd, Jay; Gochman, Peter; Rapoport, Judith; Gogtay, Nitin

    2006-01-01

    Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset…

  8. Brain Blood Flow Related to Acoustic Laryngeal Reaction Time in Adult Developmental Stutterers.

    ERIC Educational Resources Information Center

    Watson, Ben C.; And Others

    1992-01-01

    This study sought to identify patterns of impaired acoustic laryngeal reaction time as a function of response complexity parallel to metabolic measures of brain function. Findings indicated that the disruption in speech motor control for 16 adult male developmental stutterers was systematically related to metabolic asymmetry in left superior and…

  9. Doublecortin expression in the normal and epileptic adult human brain.

    PubMed

    Liu, Y W J; Curtis, M A; Gibbons, H M; Mee, E W; Bergin, P S; Teoh, H H; Connor, B; Dragunow, M; Faull, R L M

    2008-12-01

    Mesial temporal lobe epilepsy (MTLE) is a neurological disorder associated with spontaneous recurrent complex partial seizures and hippocampal sclerosis. Although increased hippocampal neurogenesis has been reported in animal models of MTLE, increased neurogenesis has not been reported in the hippocampus of adult human MTLE cases. Here we showed that cells expressing doublecortin (Dcx), a microtubule-associated protein expressed in migrating neuroblasts, were present in the hippocampus and temporal cortex of the normal and MTLE adult human brain. In particular, increased numbers of Dcx-positive cells were observed in the epileptic compared with the normal temporal cortex. Importantly, 56% of Dcx-expressing cells in the epileptic temporal cortex coexpressed both the proliferative cell marker, proliferating cell nuclear antigen and early neuronal marker, TuJ1, suggesting that they may be newly generated neurons. A subpopulation of Dcx-positive cells in the epileptic temporal cortex also coexpressed the mature neuronal marker, NeuN, suggesting that epilepsy may promote the generation of new neurons in the temporal cortex. This study has identified, for the first time, a novel population of Dcx-positive cells in the adult human temporal cortex that can be upregulated by epilepsy and thus, raises the possibility that these cells may have functional significance in the pathophysiology of epilepsy.

  10. Functional data analysis in brain imaging studies.

    PubMed

    Tian, Tian Siva

    2010-01-01

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

  11. 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

  12. Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

    PubMed Central

    Kleinridders, André; Ferris, Heather A.; Cai, Weikang

    2014-01-01

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

  13. Bioengineered functional brain-like cortical tissue

    PubMed Central

    Tang-Schomer, Min D.; White, James D.; Tien, Lee W.; Schmitt, L. Ian; Valentin, Thomas M.; Graziano, Daniel J.; Hopkins, Amy M.; Omenetto, Fiorenzo G.; Haydon, Philip G.; Kaplan, David L.

    2014-01-01

    The brain remains one of the most important but least understood tissues in our body, in part because of its complexity as well as the limitations associated with in vivo studies. Although simpler tissues have yielded to the emerging tools for in vitro 3D tissue cultures, functional brain-like tissues have not. We report the construction of complex functional 3D brain-like cortical tissue, maintained for months in vitro, formed from primary cortical neurons in modular 3D compartmentalized architectures with electrophysiological function. We show that, on injury, this brain-like tissue responds in vitro with biochemical and electrophysiological outcomes that mimic observations in vivo. This modular 3D brain-like tissue is capable of real-time nondestructive assessments, offering previously unidentified directions for studies of brain homeostasis and injury. PMID:25114234

  14. The restless brain: how intrinsic activity organizes brain function.

    PubMed

    Raichle, Marcus E

    2015-05-19

    Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease.

  15. The restless brain: how intrinsic activity organizes brain function

    PubMed Central

    Raichle, Marcus E.

    2015-01-01

    Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease. PMID:25823869

  16. New Nerve Cells for the Adult Brain.

    ERIC Educational Resources Information Center

    Kempermann, Gerd; Gage, Fred H.

    1999-01-01

    Contrary to dogma, the human brain does produce new nerve cells in adulthood. The mature human brain spawns neurons routinely in the hippocampus, an area important to memory and learning. This research can make it possible to ease any number of disorders involving neurological damage and death. (CCM)

  17. Not(ch) just development: Notch signalling in the adult brain

    PubMed Central

    Ables, Jessica L.; Breunig, Joshua J.; Eisch, Amelia J.; Rakic, Pasko

    2011-01-01

    The Notch pathway is often regarded as a developmental pathway, but components of Notch signalling are expressed and active in the adult brain. With the advent of more sophisticated genetic manipulations, evidence has emerged that suggests both conserved and novel roles for Notch signalling in the adult brain. Not surprisingly, Notch is a key regulator of adult neural stem cells, but it is increasingly clear that Notch signalling also has roles in the regulation of migration, morphology, synaptic plasticity and survival of immature and mature neurons. Understanding the many functions of Notch signalling in the adult brain, and its dysfunction in neurodegenerative disease and malignancy, is crucial to the development of new therapeutics that are centred around this pathway. PMID:21505516

  18. Wnts in adult brain: from synaptic plasticity to cognitive deficiencies

    PubMed Central

    Oliva, Carolina A.; Vargas, Jessica Y.; Inestrosa, Nibaldo C.

    2013-01-01

    During development of the central nervous system the Wnt signaling pathway has been implicated in a wide spectrum of physiological processes, including neuronal connectivity and synapse formation. Wnt proteins and components of the Wnt pathway are expressed in the brain since early development to the adult life, however, little is known about its role in mature synapses. Here, we review evidences indicating that Wnt proteins participate in the remodeling of pre- and post-synaptic regions, thus modulating synaptic function. We include the most recent data in the literature showing that Wnts are constantly released in the brain to maintain the basal neural activity. Also, we review the evidences that involve components of the Wnt pathway in the development of neurological and mental disorders, including a special emphasis on in vivo studies that relate behavioral abnormalities to deficiencies in Wnt signaling. Finally, we include the evidences that support a neuroprotective role of Wnt proteins in Alzheimer’s disease. We postulate that deregulation in Wnt signaling might have a fundamental role in the origin of neurological diseases, by altering the synaptic function at stages where the phenotype is not yet established but when the cognitive decline starts. PMID:24348327

  19. Wnts in adult brain: from synaptic plasticity to cognitive deficiencies.

    PubMed

    Oliva, Carolina A; Vargas, Jessica Y; Inestrosa, Nibaldo C

    2013-12-03

    During development of the central nervous system the Wnt signaling pathway has been implicated in a wide spectrum of physiological processes, including neuronal connectivity and synapse formation. Wnt proteins and components of the Wnt pathway are expressed in the brain since early development to the adult life, however, little is known about its role in mature synapses. Here, we review evidences indicating that Wnt proteins participate in the remodeling of pre- and post-synaptic regions, thus modulating synaptic function. We include the most recent data in the literature showing that Wnts are constantly released in the brain to maintain the basal neural activity. Also, we review the evidences that involve components of the Wnt pathway in the development of neurological and mental disorders, including a special emphasis on in vivo studies that relate behavioral abnormalities to deficiencies in Wnt signaling. Finally, we include the evidences that support a neuroprotective role of Wnt proteins in Alzheimer's disease. We postulate that deregulation in Wnt signaling might have a fundamental role in the origin of neurological diseases, by altering the synaptic function at stages where the phenotype is not yet established but when the cognitive decline starts.

  20. Brain Function: Implications for Schooling.

    ERIC Educational Resources Information Center

    Edwards, Clifford H.

    1982-01-01

    The implications of cerebral dominance for curriculum and instruction are enormous. Cognitive style, sex differences, instructional materials preparation and selection, and testing are affected by right or left brain hemisphere dominance. (CJ)

  1. The gravitational field and brain function

    NASA Astrophysics Data System (ADS)

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

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

  2. Brain-specific ablation of Efr3a promotes adult hippocampal neurogenesis via the brain-derived neurotrophic factor pathway.

    PubMed

    Qian, Qi; Liu, Qiuji; Zhou, Dongming; Pan, Hongyu; Liu, Zhiwei; He, Fangping; Ji, Suying; Wang, Dongpi; Bao, Wangxiao; Liu, Xinyi; Liu, Zhaoling; Zhang, Heng; Zhang, Xiaoqin; Zhang, Ling; Wang, Mingkai; Xu, Ying; Huang, Fude; Luo, Benyan; Sun, Binggui

    2017-02-13

    Efr3 is a newly identified plasma membrane protein and plays an important role in the phosphoinositide metabolism on the plasma membrane. However, although it is highly expressed in the brain, the functional significance of Efr3 in the brain is not clear. In the present study, we generated Efr3a(f/f) mice and then crossed them with Nestin-Cre mice to delete Efr3a, one of the Efr3 isoforms, specifically in the brain. We found that brain-specific ablation of Efr3a promoted adult hippocampal neurogenesis by increasing survival and maturation of newborn neurons without affecting their dendritic tree morphology. Moreover, the brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) signaling pathway was significantly enhanced in the hippocampus of Efr3a-deficient mice, as reflected by increased expression of BDNF, TrkB, and the downstream molecules, including phospho-MAPK and phospho-Akt. Furthermore, the number of TUNEL(+) cells was decreased in the subgranular zone of dentate gyrus in Efr3a-deficient mice compared with that of control mice. Our data suggest that brain-specific deletion of Efr3a could promote adult hippocampal neurogenesis, presumably by upregulating the expression of BDNF and its receptor, TrkB, and therefore provide new insight into the roles of Efr3 in the brain.-Qian, Q., Liu, Q., Zhou, D., Pan, H., Liu, Z., He, F., Ji, S., Wang, D., Bao, W., Liu, X., Liu, Z., Zhang, H., Zhang, X., Zhang, L., Wang, M., Xu, Y., Huang, F., Luo, B., Sun B. Brain-specific ablation of Efr3a promotes adult hippocampal neurogenesis via the brain-derived neurotrophic factor pathway.

  3. A Reading Profile of Functionally Illiterate Adults.

    ERIC Educational Resources Information Center

    Roberts, Bette H.; Russell, Sheldon Noel

    In order to identify the reading behavior and instructional needs of functionally illiterate adults reading below fourth grade level, 50 adults were identified and diagnosed on the Durrell Analysis of Reading Difficulty test and the Slosson Intelligence Test for Children and Adults. In addition, a questionnaire was administered to Oklahoma City…

  4. [Modern methods of functional tomographic brain imaging for brain function reseaching in norm and pathology].

    PubMed

    Kireev, M V; Zakhs, D V; Korotkov, A D; Medvedev, S V

    2013-01-01

    For many years the modern methods of functional tomographic brain imaging (fMRI and PET) were actively used not only for the research of basic brain functions, but also in clinical practice. In present paper we described the basic characteristics of the signal registered with fMRI and PET, the principles of image reconstruction, as well as the methodological requirements, which are necessary to obtain reliable results. The advantages and limitations of modem tomographic methods of the brain functions investigation are discussed. The need of the complex approach use in brain study is emphasized and methods for the study of functional integration of the brain are suggested.

  5. BDNF Expression in Larval and Adult Zebrafish Brain: Distribution and Cell Identification

    PubMed Central

    Cacialli, Pietro; Gueguen, Marie-Madeleine; Coumailleau, Pascal; D’Angelo, Livia; Kah, Olivier; Lucini, Carla; Pellegrini, Elisabeth

    2016-01-01

    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has emerged as an active mediator in many essential functions in the central nervous system of mammals. BDNF plays significant roles in neurogenesis, neuronal maturation and/or synaptic plasticity and is involved in cognitive functions such as learning and memory. Despite the vast literature present in mammals, studies devoted to BDNF in the brain of other animal models are scarse. Zebrafish is a teleost fish widely known for developmental genetic studies and is emerging as model for translational neuroscience research. In addition, its brain shows many sites of adult neurogenesis allowing higher regenerative properties after traumatic injuries. To add further knowledge on neurotrophic factors in vertebrate brain models, we decided to determine the distribution of bdnf mRNAs in the larval and adult zebrafish brain and to characterize the phenotype of cells expressing bdnf mRNAs by means of double staining studies. Our results showed that bdnf mRNAs were widely expressed in the brain of 7 days old larvae and throughout the whole brain of mature female and male zebrafish. In adults, bdnf mRNAs were mainly observed in the dorsal telencephalon, preoptic area, dorsal thalamus, posterior tuberculum, hypothalamus, synencephalon, optic tectum and medulla oblongata. By combining immunohistochemistry with in situ hybridization, we showed that bdnf mRNAs were never expressed by radial glial cells or proliferating cells. By contrast, bdnf transcripts were expressed in cells with neuronal phenotype in all brain regions investigated. Our results provide the first demonstration that the brain of zebrafish expresses bdnf mRNAs in neurons and open new fields of research on the role of the BDNF factor in brain mechanisms in normal and brain repairs situations. PMID:27336917

  6. Neuropsychological assessment of executive functions following pediatric traumatic brain injury.

    PubMed

    Gaines, K Drorit; Soper, Henry V

    2016-09-27

    Assessment of executive functions in the adult is best captured at the stage where full maturation of brain development occurs. Assessment of executive functions of children, however, is considerably more complicated. First, assessment of executive functioning in children represents a snapshot of these developing functions at a particular time linked stage, which may have implications for further development. Second, neuropsychological measures available to assess executive functions in children are limited in number and scope and may not be sensitive to the gradual developmental changes. The present article provides an overview of the salient neurodevelopmental stages of executive functioning and discusses the utilization of recently developed neuropsychological measures to assess these stages. Comments on clinical implications of these findings regarding Traumatic Brain Injury will be provided.

  7. Using network science to evaluate exercise-associated brain changes in older adults.

    PubMed

    Burdette, Jonathan H; Laurienti, Paul J; Espeland, Mark A; Morgan, Ashley; Telesford, Qawi; Vechlekar, Crystal D; Hayasaka, Satoru; Jennings, Janine M; Katula, Jeffrey A; Kraft, Robert A; Rejeski, W Jack

    2010-01-01

    Literature has shown that exercise is beneficial for cognitive function in older adults and that aerobic fitness is associated with increased hippocampal tissue and blood volumes. The current study used novel network science methods to shed light on the neurophysiological implications of exercise-induced changes in the hippocampus of older adults. Participants represented a volunteer subgroup of older adults that were part of either the exercise training (ET) or healthy aging educational control (HAC) treatment arms from the Seniors Health and Activity Research Program Pilot (SHARP-P) trial. Following the 4-month interventions, MRI measures of resting brain blood flow and connectivity were performed. The ET group's hippocampal cerebral blood flow (CBF) exhibited statistically significant increases compared to the HAC group. Novel whole-brain network connectivity analyses showed greater connectivity in the hippocampi of the ET participants compared to HAC. Furthermore, the hippocampus was consistently shown to be within the same network neighborhood (module) as the anterior cingulate cortex only within the ET group. Thus, within the ET group, the hippocampus and anterior cingulate were highly interconnected and localized to the same network neighborhood. This project shows the power of network science to investigate potential mechanisms for exercise-induced benefits to the brain in older adults. We show a link between neurological network features and CBF, and it is possible that this alteration of functional brain networks may lead to the known improvement in cognitive function among older adults following exercise.

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

    PubMed

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

    2009-05-01

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

  9. Expansion of Multipotent Stem Cells from the Adult Human Brain

    PubMed Central

    Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

    2013-01-01

    The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

  10. Large-scale identification of coregulated enhancer networks in the adult human brain.

    PubMed

    Vermunt, Marit W; Reinink, Peter; Korving, Jeroen; de Bruijn, Ewart; Creyghton, Paul M; Basak, Onur; Geeven, Geert; Toonen, Pim W; Lansu, Nico; Meunier, Charles; van Heesch, Sebastiaan; Clevers, Hans; de Laat, Wouter; Cuppen, Edwin; Creyghton, Menno P

    2014-10-23

    Understanding the complexity of the human brain and its functional diversity remain a major challenge. Distinct anatomical regions are involved in an array of processes, including organismal homeostasis, cognitive functions, and susceptibility to neurological pathologies, many of which define our species. Distal enhancers have emerged as key regulatory elements that acquire histone modifications in a cell- and species-specific manner, thus enforcing specific gene expression programs. Here, we survey the epigenomic landscape of promoters and cis-regulatory elements in 136 regions of the adult human brain. We identify a total of 83,553 promoter-distal H3K27ac-enriched regions showing global characteristics of brain enhancers. We use coregulation of enhancer elements across many distinct regions of the brain to uncover functionally distinct networks at high resolution and link these networks to specific neuroglial functions. Furthermore, we use these data to understand the relevance of noncoding genomic variations previously linked to Parkinson's disease incidence.

  11. Brain, Mind and Language Functional Architectures

    PubMed Central

    Fingelkurts, Andrew A; Fingelkurts, Alexander A; Marchetti, Giorgio

    2010-01-01

    The interaction between brain and language has been investigated by a vast amount of research and different approaches, which however do not offer a comprehensive and unified theoretical framework to analyze how brain functioning performs the mental processes we use in producing language and in understanding speech. This Special Issue addresses the need to develop such a general theoretical framework, by fostering an interaction among the various scientific disciplines and methodologies, which centres on investigating the functional architecture of brain, mind and language, and is articulated along the following main dimensions of research: (a) Language as a regulatory contour of brain and mental processes; (b) Language as a unique human phenomenon; (c) Language as a governor of human behaviour and brain operations; (d) Language as an organizational factor of ontogenesis of mentation and behaviour. PMID:20922047

  12. Sex Differences in Functional Brain Asymmetry.

    DTIC Science & Technology

    1976-07-01

    to Wechsler’s norms [7], and their scores did not differ from either women with right-sided damage (t = 0.05, ns) or men with right-sided damage (t...brain injury. These findings suggest a greater degree of functional brain asym- metry in men than in women . A .c ....C . _t% :istr ivtiton ,tatrment...hemisphere specialization for spatial functions than did women . However, little is knovn about sex differences in the cerebral rep- resentation of verbal

  13. Humor, Rapport, and Uncomfortable Moments in Interactions with Adults with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Kovarsky, Dana; Schiemer, Christine; Murray, Allison

    2011-01-01

    We examined uncomfortable moments that damaged rapport during group interactions between college students in training to become speech-language pathologists and adults with traumatic brain injury. The students worked as staff in a community-based program affiliated with a university training program that functioned as a recreational gathering…

  14. Brain abscess caused by Citrobacter koseri infection in an adult.

    PubMed

    Liu, Heng-Wei; Chang, Chih-Ju; Hsieh, Cheng-Ta

    2015-04-01

    Citrobacter koseri is a gram-negative bacillus that causes mostly meningitis and brain abscesses in neonates and infants. However, brain abscess caused by Citrobacter koseri infection in an adult is extremely rare, and only 2 cases have been described. Here, we reported a 73-year-old male presenting with a 3-week headache. A history of diabetes mellitus was noted. The images revealed a brain abscess in the left frontal lobe and pus culture confirmed the growth of Citrobacter koseri. The clinical symptoms improved completely postoperatively.

  15. Inflammation is detrimental for neurogenesis in adult brain

    NASA Astrophysics Data System (ADS)

    Ekdahl, Christine T.; Claasen, Jan-Hendrik; Bonde, Sara; Kokaia, Zaal; Lindvall, Olle

    2003-11-01

    New hippocampal neurons are continuously generated in the adult brain. Here, we demonstrate that lipopolysaccharide-induced inflammation, which gives rise to microglia activation in the area where the new neurons are born, strongly impairs basal hippocampal neurogenesis in rats. The increased neurogenesis triggered by a brain insult is also attenuated if it is associated with microglia activation caused by tissue damage or lipopolysaccharide infusion. The impaired neurogenesis in inflammation is restored by systemic administration of minocycline, which inhibits microglia activation. Our data raise the possibility that suppression of hippocampal neurogenesis by activated microglia contributes to cognitive dysfunction in aging, dementia, epilepsy, and other conditions leading to brain inflammation.

  16. Functional connectivity hubs of the mouse brain.

    PubMed

    Liska, Adam; Galbusera, Alberto; Schwarz, Adam J; Gozzi, Alessandro

    2015-07-15

    Recent advances in functional connectivity methods have made it possible to identify brain hubs - a set of highly connected regions serving as integrators of distributed neuronal activity. The integrative role of hub nodes makes these areas points of high vulnerability to dysfunction in brain disorders, and abnormal hub connectivity profiles have been described for several neuropsychiatric disorders. The identification of analogous functional connectivity hubs in preclinical species like the mouse may provide critical insight into the elusive biological underpinnings of these connectional alterations. To spatially locate functional connectivity hubs in the mouse brain, here we applied a fully-weighted network analysis to map whole-brain intrinsic functional connectivity (i.e., the functional connectome) at a high-resolution voxel-scale. Analysis of a large resting-state functional magnetic resonance imaging (rsfMRI) dataset revealed the presence of six distinct functional modules related to known large-scale functional partitions of the brain, including a default-mode network (DMN). Consistent with human studies, highly-connected functional hubs were identified in several sub-regions of the DMN, including the anterior and posterior cingulate and prefrontal cortices, in the thalamus, and in small foci within well-known integrative cortical structures such as the insular and temporal association cortices. According to their integrative role, the identified hubs exhibited mutual preferential interconnections. These findings highlight the presence of evolutionarily-conserved, mutually-interconnected functional hubs in the mouse brain, and may guide future investigations of the biological foundations of aberrant rsfMRI hub connectivity associated with brain pathological states.

  17. Brain Activation during Semantic Processing in Autism Spectrum Disorders via Functional Magnetic Resonance Imaging

    ERIC Educational Resources Information Center

    Harris, Gordon J.; Chabris, Christopher F.; Clark, Jill; Urban, Trinity; Aharon, Itzhak; Steele, Shelley; McGrath, Lauren; Condouris, Karen; Tager-Flusberg, Helen

    2006-01-01

    Language and communication deficits are core features of autism spectrum disorders (ASD), even in high-functioning adults with ASD. This study investigated brain activation patterns using functional magnetic resonance imaging in right-handed adult males with ASD and a control group, matched on age, handedness, and verbal IQ. Semantic processing in…

  18. FACS purification of immunolabeled cell types from adult rat brain.

    PubMed

    Guez-Barber, Danielle; Fanous, Sanya; Harvey, Brandon K; Zhang, Yongqing; Lehrmann, Elin; Becker, Kevin G; Picciotto, Marina R; Hope, Bruce T

    2012-01-15

    Molecular analysis of brain tissue is greatly complicated by having many different classes of neurons and glia interspersed throughout the brain. Fluorescence-activated cell sorting (FACS) has been used to purify selected cell types from brain tissue. However, its use has been limited to brain tissue from embryos or transgenic mice with promoter-driven reporter genes. To overcome these limitations, we developed a FACS procedure for dissociating intact cell bodies from adult wild-type rat brains and sorting them using commercially available antibodies against intracellular and extracellular proteins. As an example, we isolated neurons using a NeuN antibody and confirmed their identity using microarray and real time PCR of mRNA from the sorted cells. Our FACS procedure allows rapid, high-throughput, quantitative assays of molecular alterations in identified cell types with widespread applications in neuroscience.

  19. Modular Brain Network Organization Predicts Response to Cognitive Training in Older Adults

    PubMed Central

    Gallen, Courtney L.; Baniqued, Pauline L.; Chapman, Sandra B.; Aslan, Sina; Keebler, Molly; Didehbani, Nyaz; D’Esposito, Mark

    2016-01-01

    Cognitive training interventions are a promising approach to mitigate cognitive deficits common in aging and, ultimately, to improve functioning in older adults. Baseline neural factors, such as properties of brain networks, may predict training outcomes and can be used to improve the effectiveness of interventions. Here, we investigated the relationship between baseline brain network modularity, a measure of the segregation of brain sub-networks, and training-related gains in cognition in older adults. We found that older adults with more segregated brain sub-networks (i.e., more modular networks) at baseline exhibited greater training improvements in the ability to synthesize complex information. Further, the relationship between modularity and training-related gains was more pronounced in sub-networks mediating “associative” functions compared with those involved in sensory-motor processing. These results suggest that assessments of brain networks can be used as a biomarker to guide the implementation of cognitive interventions and improve outcomes across individuals. More broadly, these findings also suggest that properties of brain networks may capture individual differences in learning and neuroplasticity. Trail Registration: ClinicalTrials.gov, NCT#00977418 PMID:28006029

  20. Structure and function of complex brain networks.

    PubMed

    Sporns, Olaf

    2013-09-01

    An increasing number of theoretical and empirical studies approach the function of the human brain from a network perspective. The analysis of brain networks is made feasible by the development of new imaging acquisition methods as well as new tools from graph theory and dynamical systems. This review surveys some of these methodological advances and summarizes recent findings on the architecture of structural and functional brain networks. Studies of the structural connectome reveal several modules or network communities that are interlinked by hub regions mediating communication processes between modules. Recent network analyses have shown that network hubs form a densely linked collective called a "rich club," centrally positioned for attracting and dispersing signal traffic. In parallel, recordings of resting and task-evoked neural activity have revealed distinct resting-state networks that contribute to functions in distinct cognitive domains. Network methods are increasingly applied in a clinical context, and their promise for elucidating neural substrates of brain and mental disorders is discussed.

  1. Functional Imaging of Working Memory and Peripheral Endothelial Function in Middle-Aged Adults

    ERIC Educational Resources Information Center

    Gonzales, Mitzi M.; Tarumi, Takashi; Tanaka, Hirofumi; Sugawara, Jun; Swann-Sternberg, Tali; Goudarzi, Katayoon; Haley, Andreana P.

    2010-01-01

    The current study examined the relationship between a prognostic indicator of vascular health, flow-mediated dilation (FMD), and working memory-related brain activation in healthy middle-aged adults. Forty-two participants underwent functional magnetic resonance imaging while completing a 2-Back working memory task. Brachial artery…

  2. Bilateral Brain Regions Associated with Naming in Older Adults

    ERIC Educational Resources Information Center

    Obler, Loraine K.; Rykhlevskaia, Elena; Schnyer, David; Clark-Cotton, Manuella R.; Spiro, Avron, III; Hyun, JungMoon; Kim, Dae-Shik; Goral, Mira; Albert, Martin L.

    2010-01-01

    To determine structural brain correlates of naming abilities in older adults, we tested 24 individuals aged 56-79 on two confrontation-naming tests (the Boston Naming Test (BNT) and the Action Naming Test (ANT)), then collected from these individuals structural Magnetic-Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) data. Overall,…

  3. Functional brain regeneration in the acoel worm Symsagittifera roscoffensis

    PubMed Central

    Sprecher, Simon G.; Bernardo-Garcia, F. Javier; van Giesen, Lena; Hartenstein, Volker; Reichert, Heinrich; Neves, Ricardo; Bailly, Xavier; Martinez, Pedro; Brauchle, Michael

    2015-01-01

    ABSTRACT The ability of some animals to regrow their head and brain after decapitation provides a striking example of the regenerative capacity within the animal kingdom. The acoel worm Symsagittifera roscoffensis can regrow its head, brain and sensory head organs within only a few weeks after decapitation. How rapidly and to what degree it also reacquires its functionality to control behavior however remains unknown. We provide here a neuroanatomical map of the brain neuropils of the adult S. roscoffensis and show that after decapitation a normal neuroanatomical organization of the brain is restored in the majority of animals. By testing different behaviors we further show that functionality of both sensory perception and the underlying brain architecture are restored within weeks after decapitation. Interestingly not all behaviors are restored at the same speed and to the same extent. While we find that phototaxis recovered rapidly, geotaxis is not restored within 7 weeks. Our findings show that regeneration of the head, sensory organs and brain result in the restoration of directed navigation behavior, suggesting a tight coordination in the regeneration of certain sensory organs with that of their underlying neural circuits. Thus, at least in S. roscoffensis, the regenerative capacity of different sensory modalities follows distinct paths. PMID:26581588

  4. Functional Connectivity Hubs and Networks in the Awake Marmoset Brain

    PubMed Central

    Belcher, Annabelle M.; Yen, Cecil Chern-Chyi; Notardonato, Lucia; Ross, Thomas J.; Volkow, Nora D.; Yang, Yihong; Stein, Elliot A.; Silva, Afonso C.; Tomasi, Dardo

    2016-01-01

    In combination with advances in analytical methods, resting-state fMRI is allowing unprecedented access to a better understanding of the network organization of the brain. Increasing evidence suggests that this architecture may incorporate highly functionally connected nodes, or “hubs”, and we have recently proposed local functional connectivity density (lFCD) mapping to identify highly-connected nodes in the human brain. Here, we imaged awake nonhuman primates to test whether, like the human brain, the marmoset brain contains FC hubs. Ten adult common marmosets (Callithrix jacchus) were acclimated to mild, comfortable restraint using individualized helmets. Following restraint training, resting BOLD data were acquired during eight consecutive 10 min scans for each subject. lFCD revealed prominent cortical and subcortical hubs of connectivity across the marmoset brain; specifically, in primary and secondary visual cortices (V1/V2), higher-order visual association areas (A19M/V6[DM]), posterior parietal and posterior cingulate areas (PGM and A23b/A31), thalamus, dorsal and ventral striatal areas (caudate, putamen, lateral septal nucleus, and anterior cingulate cortex (A24a). lFCD hubs were highly connected to widespread areas of the brain, and further revealed significant network-network interactions. These data provide a baseline platform for future investigations in a nonhuman primate model of the brain’s network topology. PMID:26973476

  5. Thyroid, brain and mood modulation in affective disorder: insights from molecular research and functional brain imaging.

    PubMed

    Bauer, M; London, E D; Silverman, D H; Rasgon, N; Kirchheiner, J; Whybrow, P C

    2003-11-01

    The efficacy resulting from adjunctive use of supraphysiological doses of levothyroxine has emerged as a promising approach to therapy and prophylaxis for refractory mood disorders. Most patients with mood disorders who receive treatment with supraphysiological doses of levothyroxine have normal peripheral thyroid hormone levels, and also respond differently to the hormone and tolerate it better than healthy individuals and patients with primary thyroid diseases. Progress in molecular and functional brain imaging techniques has provided a new understanding of these phenomena, illuminating the relationship between thyroid function, mood modulation and behavior. Thyroid hormones are widely distributed in the brain and have a multitude of effects on the central nervous system. Notably many of the limbic system structures where thyroid hormone receptors are prevalent have been implicated in the pathogenesis of mood disorders. The influence of the thyroid system on neurotransmitters (particularly serotonin and norepinephrine), which putatively play a major role in the regulation of mood and behavior, may contribute to the mechanisms of mood modulation. Recent functional brain imaging studies using positron emission tomography (PET) with [ (18)F]-fluorodeoxyglucose demonstrated that thyroid hormone treatment with levothyroxine affects regional brain metabolism in patients with hypothyroidism and bipolar disorder. Theses studies confirm that thyroid hormones are active in modulating metabolic function in the mature adult brain, and provide intriging neuroanatomic clues that may guide future research.

  6. Thyroid hormone receptors in brain development and function.

    PubMed

    Bernal, Juan

    2007-03-01

    Thyroid hormones are important during development of the mammalian brain, acting on migration and differentiation of neural cells, synaptogenesis, and myelination. The actions of thyroid hormones are mediated through nuclear thyroid hormone receptors (TRs) and regulation of gene expression. The purpose of this article is to review the role of TRs in brain maturation. In developing humans maternal and fetal thyroid glands provide thyroid hormones to the fetal brain, but the timing of receptor ontogeny agrees with clinical data on the importance of the maternal thyroid gland before midgestation. Several TR isoforms, which are encoded by the THRA and THRB genes, are expressed in the brain, with the most common being TRalpha1. Deletion of TRalpha1 in rodents is not, however, equivalent to hormone deprivation and, paradoxically, even prevents the effects of hypothyroidism. Unliganded receptor activity is, therefore, probably an important factor in causing the harmful effects of hypothyroidism. Accordingly, expression of a mutant receptor with impaired triiodothyronine (T(3)) binding and dominant negative activity affected cerebellar development and motor performance. TRs are also involved in adult brain function. TRalpha1 deletion, or expression of a dominant negative mutant receptor, induces consistent behavioral changes in adult mice, leading to severe anxiety and morphological changes in the hippocampus.

  7. aBEAT: A Toolbox for Consistent Analysis of Longitudinal Adult Brain MRI

    PubMed Central

    Dai, Yakang; Wang, Yaping; Wang, Li; Wu, Guorong; Shi, Feng; Shen, Dinggang

    2013-01-01

    Longitudinal brain image analysis is critical for revealing subtle but complex structural and functional changes of brain during aging or in neurodevelopmental disease. However, even with the rapid increase of clinical research and trials, a software toolbox dedicated for longitudinal image analysis is still lacking publicly. To cater for this increasing need, we have developed a dedicated 4D Adult Brain Extraction and Analysis Toolbox (aBEAT) to provide robust and accurate analysis of the longitudinal adult brain MR images. Specially, a group of image processing tools were integrated into aBEAT, including 4D brain extraction, 4D tissue segmentation, and 4D brain labeling. First, a 4D deformable-surface-based brain extraction algorithm, which can deform serial brain surfaces simultaneously under temporal smoothness constraint, was developed for consistent brain extraction. Second, a level-sets-based 4D tissue segmentation algorithm that incorporates local intensity distribution, spatial cortical-thickness constraint, and temporal cortical-thickness consistency was also included in aBEAT for consistent brain tissue segmentation. Third, a longitudinal groupwise image registration framework was further integrated into aBEAT for consistent ROI labeling by simultaneously warping a pre-labeled brain atlas to the longitudinal brain images. The performance of aBEAT has been extensively evaluated on a large number of longitudinal MR T1 images which include normal and dementia subjects, achieving very promising results. A Linux-based standalone package of aBEAT is now freely available at http://www.nitrc.org/projects/abeat. PMID:23577105

  8. Pedophilic brain potential responses to adult erotic stimuli.

    PubMed

    Knott, Verner; Impey, Danielle; Fisher, Derek; Delpero, Emily; Fedoroff, Paul

    2016-02-01

    Cognitive mechanisms associated with the relative lack of sexual interest in adults by pedophiles are poorly understood and may benefit from investigations examining how the brain processes adult erotic stimuli. The current study used event-related brain potentials (ERP) to investigate the time course of the explicit processing of erotic, emotional, and neutral pictures in 22 pedophilic patients and 22 healthy controls. Consistent with previous studies, early latency anterior ERP components were highly selective for erotic pictures. Although the ERPs elicited by emotional stimuli were similar in patients and controls, an early frontal positive (P2) component starting as early as 185 ms was significantly attenuated and slow to onset in pedophilia, and correlated with a clinical measure of cognitive distortions. Failure of rapid attentional capture by erotic stimuli suggests a relative reduction in early processing in pedophilic patients which may be associated with relatively diminished sexual interest in adults.

  9. [Brain mechanisms of male sexual function].

    PubMed

    Wang, Ying; Dou, Xin; Li, Jun-Fa; Luo, Yan-Lin

    2011-08-01

    In this paper, we reviewed the brain imaging studies of male sexual function in recent years from three aspects: the brain mechanism of normal sexual function, the brain mechanism of sexual dysfunction, and the mechanism of drug therapy for sexual dysfunction. Studies show that the development stages of male sexual activities, such as the excitement phase, plateau phase and orgasm phase, are controlled by different neural networks. The mesodiencephalic transition zone may play an important role in the start up of male ejaculation. There are significant differences between sexual dysfunction males and normal males in activation patterns of the brain in sexual arousal. The medial orbitofrontal cortex and inferior frontal gyrus in the abnormal activation pattern are correlated with sexual dysfunction males in sexual arousal. Serum testosterone and morphine are commonly used drugs for male sexual dysfunction, whose mechanisms are to alter the activating levels of the medial orbitofrontal cortex, insula, claustrum and inferior temporal gyrus.

  10. Metabolism and functions of copper in brain.

    PubMed

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

    2014-05-01

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

  11. Toward discovery science of human brain function.

    PubMed

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

    2010-03-09

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

  12. The Brain Prize 2014: complex human functions.

    PubMed

    Grigaityte, Kristina; Iacoboni, Marco

    2014-11-01

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

  13. Prospects for Optogenetic Augmentation of Brain Function

    PubMed Central

    Jarvis, Sarah; Schultz, Simon R.

    2015-01-01

    The ability to optically control neural activity opens up possibilities for the restoration of normal function following neurological disorders. The temporal precision, spatial resolution, and neuronal specificity that optogenetics offers is unequalled by other available methods, so will it be suitable for not only restoring but also extending brain function? As the first demonstrations of optically “implanted” novel memories emerge, we examine the suitability of optogenetics as a technique for extending neural function. While optogenetics is an effective tool for altering neural activity, the largest impediment for optogenetics in neural augmentation is our systems level understanding of brain function. Furthermore, a number of clinical limitations currently remain as substantial hurdles for the applications proposed. While neurotechnologies for treating brain disorders and interfacing with prosthetics have advanced rapidly in the past few years, partially addressing some of these critical problems, optogenetics is not yet suitable for use in humans. Instead we conclude that for the immediate future, optogenetics is the neurological equivalent of the 3D printer: its flexibility providing an ideal tool for testing and prototyping solutions for treating brain disorders and augmenting brain function. PMID:26635547

  14. Imaging visual function of the human brain

    SciTech Connect

    Marg, E.

    1988-10-01

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

  15. Relationships between gene expression and brain wiring in the adult rodent brain.

    PubMed

    French, Leon; Pavlidis, Paul

    2011-01-06

    We studied the global relationship between gene expression and neuroanatomical connectivity in the adult rodent brain. We utilized a large data set of the rat brain "connectome" from the Brain Architecture Management System (942 brain regions and over 5000 connections) and used statistical approaches to relate the data to the gene expression signatures of 17,530 genes in 142 anatomical regions from the Allen Brain Atlas. Our analysis shows that adult gene expression signatures have a statistically significant relationship to connectivity. In particular, brain regions that have similar expression profiles tend to have similar connectivity profiles, and this effect is not entirely attributable to spatial correlations. In addition, brain regions which are connected have more similar expression patterns. Using a simple optimization approach, we identified a set of genes most correlated with neuroanatomical connectivity, and find that this set is enriched for genes involved in neuronal development and axon guidance. A number of the genes have been implicated in neurodevelopmental disorders such as autistic spectrum disorder. Our results have the potential to shed light on the role of gene expression patterns in influencing neuronal activity and connectivity, with potential applications to our understanding of brain disorders. Supplementary data are available at http://www.chibi.ubc.ca/ABAMS.

  16. Network Structure among Brain Systems in Adult ADHD is Uniquely Modified by Stimulant Administration.

    PubMed

    Cary, Robert P; Ray, Siddharth; Grayson, David S; Painter, Julia; Carpenter, Samuel; Maron, Leeza; Sporns, Olaf; Stevens, Alexander A; Nigg, Joel T; Fair, Damien A

    2016-07-14

    Current research in connectomics highlights that self-organized functional networks or "communities" of cortical areas can be detected in the adult brain. This perspective may provide clues to mechanisms of treatment response in psychiatric conditions. Here we examine functional brain community topology based on resting-state fMRI in adult Attention-Deficit/Hyperactivity Disorder (ADHD; n = 22) and controls (n = 31). We sought to evaluate ADHD patterns in adulthood and their modification by short term stimulants administration. Participants with ADHD were scanned one or two weeks apart, once with medication and once without; comparison participants were scanned at one time-point. Functional connectivity was estimated from these scans and community detection applied to determine cortical network topology. Measures of change in connectivity profile were calculated via a graph measure, termed the Node Dissociation Index (NDI). Compared to controls, several cortical networks had atypical connectivity in adults with ADHD when withholding stimulants, as measured by NDI. In most networks stimulants significantly reduced, but did not eliminate, differences in the distribution of connections between key brain systems relative to the control sample. These findings provide an enriched model of connectivity in ADHD and demonstrate how stimulants may exert functional effects by altering connectivity profiles in the brain.

  17. Functional brain network efficiency predicts intelligence.

    PubMed

    Langer, Nicolas; Pedroni, Andreas; Gianotti, Lorena R R; Hänggi, Jürgen; Knoch, Daria; Jäncke, Lutz

    2012-06-01

    The neuronal causes of individual differences in mental abilities such as intelligence are complex and profoundly important. Understanding these abilities has the potential to facilitate their enhancement. The purpose of this study was to identify the functional brain network characteristics and their relation to psychometric intelligence. In particular, we examined whether the functional network exhibits efficient small-world network attributes (high clustering and short path length) and whether these small-world network parameters are associated with intellectual performance. High-density resting state electroencephalography (EEG) was recorded in 74 healthy subjects to analyze graph-theoretical functional network characteristics at an intracortical level. Ravens advanced progressive matrices were used to assess intelligence. We found that the clustering coefficient and path length of the functional network are strongly related to intelligence. Thus, the more intelligent the subjects are the more the functional brain network resembles a small-world network. We further identified the parietal cortex as a main hub of this resting state network as indicated by increased degree centrality that is associated with higher intelligence. Taken together, this is the first study that substantiates the neural efficiency hypothesis as well as the Parieto-Frontal Integration Theory (P-FIT) of intelligence in the context of functional brain network characteristics. These theories are currently the most established intelligence theories in neuroscience. Our findings revealed robust evidence of an efficiently organized resting state functional brain network for highly productive cognitions.

  18. Life Satisfaction in Adult Survivors of Childhood Brain Tumors

    PubMed Central

    Crom, Deborah B.; Li, Zhenghong; Brinkman, Tara M.; Hudson, Melissa M.; Armstrong, Gregory T.; Neglia, Joseph; Ness, Kirsten K.

    2014-01-01

    Adult survivors of childhood brain tumors experience multiple, significant, life-long deficits as a consequence of their malignancy and therapy. Current survivorship literature documents the substantial impact such impairments have on survivors’ physical health and quality of life. Psychosocial reports detail educational, cognitive, and emotional limitations characterizing survivors as especially fragile, often incompetent, and unreliable in evaluating their circumstances. Anecdotal data suggests some survivors report life experiences similar to those of healthy controls. The aim of our investigation was to determine whether life satisfaction in adult survivors of childhood brain tumors differs from that of healthy controls and to identify potential predictors of life satisfaction in survivors. This cross-sectional study compared 78 brain tumor survivors with population–based matched controls. Chi-square tests, t-tests, and linear regression models were used to investigate patterns of life satisfaction and identify potential correlates. Results indicated life satisfaction of adult survivors of childhood brain tumors was similar to that of healthy controls. Survivors’ general health expectations emerged as the primary correlate of life satisfaction. Understanding life satisfaction as an important variable will optimize the design of strategies to enhance participation in follow-up care, reduce suffering, and optimize quality of life in this vulnerable population. PMID:25027187

  19. Life satisfaction in adult survivors of childhood brain tumors.

    PubMed

    Crom, Deborah B; Li, Zhenghong; Brinkman, Tara M; Hudson, Melissa M; Armstrong, Gregory T; Neglia, Joseph; Ness, Kirsten K

    2014-01-01

    Adult survivors of childhood brain tumors experience multiple, significant, lifelong deficits as a consequence of their malignancy and therapy. Current survivorship literature documents the substantial impact such impairments have on survivors' physical health and quality of life. Psychosocial reports detail educational, cognitive, and emotional limitations characterizing survivors as especially fragile, often incompetent, and unreliable in evaluating their circumstances. Anecdotal data suggest some survivors report life experiences similar to those of healthy controls. The aim of our investigation was to determine whether life satisfaction in adult survivors of childhood brain tumors differs from that of healthy controls and to identify potential predictors of life satisfaction in survivors. This cross-sectional study compared 78 brain tumor survivors with population-based matched controls. Chi-square tests, t tests, and linear regression models were used to investigate patterns of life satisfaction and identify potential correlates. Results indicated that life satisfaction of adult survivors of childhood brain tumors was similar to that of healthy controls. Survivors' general health expectations emerged as the primary correlate of life satisfaction. Understanding life satisfaction as an important variable will optimize the design of strategies to enhance participation in follow-up care, reduce suffering, and optimize quality of life in this vulnerable population.

  20. Advantages in functional imaging of the brain

    PubMed Central

    Mier, Walter; Mier, Daniela

    2015-01-01

    As neuronal pathologies cause only minor morphological alterations, molecular imaging techniques are a prerequisite for the study of diseases of the brain. The development of molecular probes that specifically bind biochemical markers and the advances of instrumentation have revolutionized the possibilities to gain insight into the human brain organization and beyond this—visualize structure-function and brain-behavior relationships. The review describes the development and current applications of functional brain imaging techniques with a focus on applications in psychiatry. A historical overview of the development of functional imaging is followed by the portrayal of the principles and applications of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), two key molecular imaging techniques that have revolutionized the ability to image molecular processes in the brain. We conclude that the juxtaposition of PET and fMRI in hybrid PET/MRI scanners enhances the significance of both modalities for research in neurology and psychiatry and might pave the way for a new area of personalized medicine. PMID:26042013

  1. The Social Environment and Neurogenesis in the Adult Mammalian Brain

    PubMed Central

    Lieberwirth, Claudia; Wang, Zuoxin

    2012-01-01

    Adult neurogenesis – the formation of new neurons in adulthood – has been shown to be modulated by a variety of endogenous (e.g., trophic factors, neurotransmitters, and hormones) as well as exogenous (e.g., physical activity and environmental complexity) factors. Research on exogenous regulators of adult neurogenesis has focused primarily on the non-social environment. More recently, however, evidence has emerged suggesting that the social environment can also affect adult neurogenesis. The present review details the effects of adult–adult (e.g., mating and chemosensory interactions) and adult–offspring (e.g., gestation, parenthood, and exposure to offspring) interactions on adult neurogenesis. In addition, the effects of a stressful social environment (e.g., lack of social support and dominant–subordinate interactions) on adult neurogenesis are reviewed. The underlying hormonal mechanisms and potential functional significance of adult-generated neurons in mediating social behaviors are also discussed. PMID:22586385

  2. Prenatal ethanol exposure increases brain cholesterol content in adult rats.

    PubMed

    Barceló-Coblijn, Gwendolyn; Wold, Loren E; Ren, Jun; Murphy, Eric J

    2013-11-01

    Fetal alcohol syndrome is the most severe expression of the fetal alcohol spectrum disorders (FASD). Although alterations in fetal and neonate brain fatty acid composition and cholesterol content are known to occur in animal models of FASD, the persistence of these alterations into adulthood is unknown. To address this question, we determined the effect of prenatal ethanol exposure on individual phospholipid class fatty acid composition, individual phospholipid class mass, and cholesterol mass in brains from 25-week-old rats that were exposed to ethanol during gestation beginning at gestational day 2. While total phospholipid mass was unaffected, phosphatidylinositol and cardiolipin mass was decreased 14 and 43 %, respectively. Exposure to prenatal ethanol modestly altered brain phospholipid fatty acid composition, and the most consistent change was a significant 1.1-fold increase in total polyunsaturated fatty acids (PUFA), in the n-3/n-6 ratio, and in the 22:6n-3 content in ethanolamine glycerophospholipids and in phosphatidylserine. In contrast, prenatal ethanol consumption significantly increased brain cholesterol mass 1.4-fold and the phospholipid to cholesterol ratio was significantly increased 1.3-fold. These results indicate that brain cholesterol mass was significantly increased in adult rats exposed prenatally to ethanol, but changes in phospholipid mass and phospholipid fatty acid composition were extremely limited. Importantly, suppression of postnatal ethanol consumption was not sufficient to reverse the large increase in cholesterol observed in the adult rats.

  3. Individual Differences in General Intelligence Correlate with Brain Function during Nonreasoning Tasks.

    ERIC Educational Resources Information Center

    Haier, Richard J.; White, Nathan S.; Alkire, Michael T.

    2003-01-01

    Administered Raven's Advanced Progressive Matrices to 22 adults and measured cerebral glucose activity as subjects viewed videos on 2 occasions. Data provide evidence that individual differences in intelligence correlate with brain function even when the brain is engaged in non-reasoning tasks. (SLD)

  4. Organization of Cognitive Functions in the Brain.

    ERIC Educational Resources Information Center

    Smith, Aaron

    Neuropsychological research on the effects of hemispherectomy-the excision of one of the cerebral hemispheres-in children and adults adds to knowledge about the division of labor between the left cerebral hemisphere, which specializes in language and verbal cognitive functions, and the right hemisphere, which specializes in nonlanguage functions.…

  5. The adverse effects of reduced cerebral perfusion on cognition and brain structure in older adults with cardiovascular disease

    PubMed Central

    Alosco, Michael L; Gunstad, John; Jerskey, Beth A; Xu, Xiaomeng; Clark, Uraina S; Hassenstab, Jason; Cote, Denise M; Walsh, Edward G; Labbe, Donald R; Hoge, Richard; Cohen, Ronald A; Sweet, Lawrence H

    2013-01-01

    Background It is well established that aging and vascular processes interact to disrupt cerebral hemodynamics in older adults. However, the independent effects of cerebral perfusion on neurocognitive function among older adults remain poorly understood. We examined the associations among cerebral perfusion, cognitive function, and brain structure in older adults with varying degrees of vascular disease using perfusion magnetic resonance imaging (MRI) arterial spin labeling (ASL). Materials and methods 52 older adults underwent neuroimaging and were administered the Mini Mental State Examination (MMSE), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and measures of attention/executive function. ASL and T1-weighted MRI were used to quantify total brain perfusion, total brain volume (TBV), and cortical thickness. Results Regression analyses showed reduced total brain perfusion was associated with poorer performance on the MMSE, RBANS total index, immediate and delayed memory composites, and Trail Making Test B. Reduced frontal lobe perfusion was associated with worse executive and memory function. A similar pattern emerged between temporal lobe perfusion and immediate memory. Regression analyses revealed that decreased total brain perfusion was associated with smaller TBV and mean cortical thickness. Regional effects of reduced total cerebral perfusion were found on temporal and parietal lobe volumes and frontal and temporal cortical thickness. Discussion Reduced cerebral perfusion is independently associated with poorer cognition, smaller TBV, and reduced cortical thickness in older adults. Conclusion Prospective studies are needed to clarify patterns of cognitive decline and brain atrophy associated with cerebral hypoperfusion. PMID:24363966

  6. Clinical review: Brain-body temperature differences in adults with severe traumatic brain injury.

    PubMed

    Childs, Charmaine; Lunn, Kueh Wern

    2013-04-22

    Surrogate or 'proxy' measures of brain temperature are used in the routine management of patients with brain damage. The prevailing view is that the brain is 'hotter' than the body. The polarity and magnitude of temperature differences between brain and body, however, remains unclear after severe traumatic brain injury (TBI). The focus of this systematic review is on the adult patient admitted to intensive/neurocritical care with a diagnosis of severe TBI (Glasgow Coma Scale score of less than 8). The review considered studies that measured brain temperature and core body temperature. Articles published in English from the years 1980 to 2012 were searched in databases, CINAHL, PubMed, Scopus, Web of Science, Science Direct, Ovid SP, Mednar and ProQuest Dissertations & Theses Database. For the review, publications of randomised controlled trials, non-randomised controlled trials, before and after studies, cohort studies, case-control studies and descriptive studies were considered for inclusion. Of 2,391 records identified via the search strategies, 37 were retrieved for detailed examination (including two via hand searching). Fifteen were reviewed and assessed for methodological quality. Eleven studies were included in the systematic review providing 15 brain-core body temperature comparisons. The direction of mean brain-body temperature differences was positive (brain higher than body temperature) and negative (brain lower than body temperature). Hypothermia is associated with large brain-body temperature differences. Brain temperature cannot be predicted reliably from core body temperature. Concurrent monitoring of brain and body temperature is recommended in patients where risk of temperature-related neuronal damage is a cause for clinical concern and when deliberate induction of below-normal body temperature is instituted.

  7. Electrophysiological Recording in the Brain of Intact Adult Zebrafish

    PubMed Central

    Johnston, Lindsey; Ball, Rebecca E.; Acuff, Seth; Gaudet, John; Sornborger, Andrew; Lauderdale, James D.

    2013-01-01

    Previously, electrophysiological studies in adult zebrafish have been limited to slice preparations or to eye cup preparations and electrorentinogram recordings. This paper describes how an adult zebrafish can be immobilized, intubated, and used for in vivo electrophysiological experiments, allowing recording of neural activity. Immobilization of the adult requires a mechanism to deliver dissolved oxygen to the gills in lieu of buccal and opercular movement. With our technique, animals are immobilized and perfused with habitat water to fulfill this requirement. A craniotomy is performed under tricaine methanesulfonate (MS-222; tricaine) anesthesia to provide access to the brain. The primary electrode is then positioned within the craniotomy window to record extracellular brain activity. Through the use of a multitube perfusion system, a variety of pharmacological compounds can be administered to the adult fish and any alterations in the neural activity can be observed. The methodology not only allows for observations to be made regarding changes in neurological activity, but it also allows for comparisons to be made between larval and adult zebrafish. This gives researchers the ability to identify the alterations in neurological activity due to the introduction of various compounds at different life stages. PMID:24300281

  8. Removing brakes on adult brain plasticity: from molecular to behavioral interventions

    PubMed Central

    Bavelier, D.; Levi, D.M.; Li, R.W.; Dan, Y.; Hensch, T.K.

    2010-01-01

    Adult brain plasticity, although possible, remains more restricted in scope than during development. Here, we address conditions under which circuit rewiring may be facilitated in the mature brain. At a cellular and molecular level, adult plasticity is actively limited. Some of these “brakes” are structural, such as peri-neuronal nets or myelin, which inhibit neurite outgrowth. Others are functional, acting directly upon excitatory-inhibitory balance within local circuits. Plasticity in adulthood can be induced either by lifting these brakes through invasive interventions or by exploiting endogenous permissive factors, such as neuromodulators. Using the amblyopic visual system as a model, we discuss genetic, pharmacological, and environmental removal of brakes to enable recovery of vision in adult rodents. Although these mechanisms remain largely uncharted in the human, we consider how they may provide a biological foundation for the remarkable increase in plasticity after action video game play by amblyopic subjects. PMID:21068299

  9. A meal preparation treatment protocol for adults with brain injury.

    PubMed

    Neistadt, M E

    1994-05-01

    Adults with acquired brain injury often demonstrate dysfunction in meal preparation due to deficits in component cognitive-perceptual skills. Although occupational therapy for these clients routinely includes meal preparation training, there are no protocols in the occupational therapy literature to help structure that activity to address clients' cognitive-perceptual deficits. This paper describes a meal preparation treatment protocol based on cognitive-perceptual information processing theory that has been pilot tested in a treatment outcome study with adult men with traumatic or anoxic acquired brain injury. In that study, the group of 23 subjects treated with this meal preparation protocol showed significant improvement in their meal preparation skill, as measured by the Rabideau Kitchen Evaluation-Revised (RKE-R), a test of meal preparation skill, and in their cognitive-perceptual skill, as measured by the WAIS-R Block Design Test. The treatment protocol includes descriptions of the structure, grading, and cuing methods for light meal preparation activities.

  10. Abstracting meaning from complex information (gist reasoning) in adult traumatic brain injury.

    PubMed

    Vas, Asha Kuppachi; Spence, Jeffrey; Chapman, Sandra Bond

    2015-01-01

    Gist reasoning (abstracting meaning from complex information) was compared between adults with moderate-to-severe traumatic brain injury (TBI, n = 30) at least one year post injury and healthy adults (n = 40). The study also examined the contribution of executive functions (working memory, inhibition, and switching) and memory (immediate recall and memory for facts) to gist reasoning. The correspondence between gist reasoning and daily function was also examined in the TBI group. Results indicated that the TBI group performed significantly lower than the control group on gist reasoning, even after adjusting for executive functions and memory. Executive function composite was positively associated with gist reasoning (p < .001). Additionally, performance on gist reasoning significantly predicted daily function in the TBI group beyond the predictive ability of executive function alone (p = .011). Synthesizing and abstracting meaning(s) from information (i.e., gist reasoning) could provide an informative index into higher order cognition and daily functionality.

  11. Brain Functional and Structural Predictors of Language Performance.

    PubMed

    Skeide, Michael A; Brauer, Jens; Friederici, Angela D

    2016-05-01

    The relation between brain function and behavior on the one hand and the relation between structural changes and behavior on the other as well as the link between the 2 aspects are core issues in cognitive neuroscience. It is an open question, however, whether brain function or brain structure is the better predictor for age-specific cognitive performance. Here, in a comprehensive set of analyses, we investigated the direct relation between hemodynamic activity in 2 pairs of frontal and temporal cortical areas, 2 long-distance white matter fiber tracts connecting each pair and sentence comprehension performance of 4 age groups, including 3 groups of children between 3 and 10 years as well as young adults. We show that the increasing accuracy of processing complex sentences throughout development is correlated with the blood-oxygen-level-dependent activation of 2 core language processing regions in Broca's area and the posterior portion of the superior temporal gyrus. Moreover, both accuracy and speed of processing are correlated with the maturational status of the arcuate fasciculus, that is, the dorsal white matter fiber bundle connecting these 2 regions. The present data provide compelling evidence for the view that brain function and white matter structure together best predict developing cognitive performance.

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

    SciTech Connect

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

    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, 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.

  13. Brain-expressed imprinted genes and adult behaviour: the example of Nesp and Grb10.

    PubMed

    Dent, Claire L; Isles, Anthony R

    2014-02-01

    Imprinted genes are defined by their parent-of-origin-specific monoallelic expression. Although the epigenetic mechanisms regulating imprinted gene expression have been widely studied, their functional importance is still unclear. Imprinted genes are associated with a number of physiologies, including placental function and foetal growth, energy homeostasis, and brain and behaviour. This review focuses on genomic imprinting in the brain and on two imprinted genes in particular, Nesp and paternal Grb10, which, when manipulated in animals, have been shown to influence adult behaviour. These two genes are of particular interest as they are expressed in discrete and overlapping neural regions, recognised as key "imprinting hot spots" in the brain. Furthermore, these two genes do not appear to influence placental function and/or maternal provisioning of offspring. Consequently, by understanding their behavioural function we may begin to shed light on the evolutionary significance of imprinted genes in the adult brain, independent of the recognised role in maternal care. In addition, we discuss the potential future directions of research investigating the function of these two genes and the behavioural role of imprinted genes more generally.

  14. Neural Underpinnings of Working Memory in Adult Survivors of Childhood Brain Tumors.

    PubMed

    King, Tricia Z; Na, Sabrina; Mao, Hui

    2015-08-01

    Adult survivors of childhood brain tumors are at risk for cognitive performance deficits that require the core cognitive skill of working memory. Our goal was to examine the neural mechanisms underlying working memory performance in survivors. We studied the working memory of adult survivors of pediatric posterior fossa brain tumors using a letter n-back paradigm with varying cognitive workload (0-, 1-, 2-, and 3-back) and functional magnetic resonance imaging as well as neuropsychological measures. Survivors of childhood brain tumors evidenced lower working memory performance than demographically matched healthy controls. Whole-brain analyses revealed significantly greater blood-oxygen level dependent (BOLD) activation in the left superior / middle frontal gyri and left parietal lobe during working memory (2-back versus 0-back contrast) in survivors. Left frontal BOLD response negatively correlated with 2- and 3-back working memory performance, Auditory Consonant Trigrams (ACT), and Digit Span Backwards. In contrast, parietal lobe BOLD response negatively correlated with 0-back (vigilance task) and ACT. The results revealed that adult survivors of childhood posterior fossa brain tumors recruited additional cognitive control resources in the prefrontal lobe during increased working memory demands. This increased prefrontal activation is associated with lower working memory performance and is consistent with the allocation of latent resources theory.

  15. Classroom Seating and Functional Brain Asymmetry

    ERIC Educational Resources Information Center

    Gur, Raquel E.; And Others

    1975-01-01

    This study examined the relationship between functional brain assymetry, as measured by the characteristic direction of eye movements in response to face-to-face questioning, and sitting on the left or right side of a classroom. Results are congruent with other findings comparing right and left movers. (Author/BJG)

  16. Integrating Retinoic Acid Signaling with Brain Function

    ERIC Educational Resources Information Center

    Luo, Tuanlian; Wagner, Elisabeth; Drager, Ursula C.

    2009-01-01

    The vitamin A derivative retinoic acid (RA) regulates the transcription of about a 6th of the human genome. Compelling evidence indicates a role of RA in cognitive activities, but its integration with the molecular mechanisms of higher brain functions is not known. Here we describe the properties of RA signaling in the mouse, which point to…

  17. Ketone-body utilization by homogenates of adult rat brain

    SciTech Connect

    Lopes-Cardozo, M.; Klein, W.

    1982-06-01

    The regulation of ketone-body metabolism and the quantitative importance of ketone bodies as lipid precursors in adult rat brain has been studied in vitro. Utilization of ketone bodies and of pyruvate by homogenates of adult rat brain was measured and the distribution of /sup 14/C from (3-/sup 14/C)ketone bodies among the metabolic products was analysed. The rate of ketone-body utilization was maximal in the presence of added Krebs-cycle intermediates and uncouplers of oxidative phosphorylation. The consumption of acetoacetate was faster than that of D-3-hydroxybutyrate, whereas, pyruvate produced twice as much acetyl-CoA as acetoacetate under optimal conditions. Millimolar concentrations of ATP in the presence of uncoupler lowered the consumption of ketone bodies but not of pyruvate. Indirect evidence is presented suggesting that ATP interferes specifically with the mitochondrial uptake of ketone bodies. Interconversion of ketone bodies and the accumulation of acid-soluble intermediates (mainly citrate and glutamate) accounted for the major part of ketone-body utilization, whereas only a small part was oxidized to CO/sub 2/. Ketone bodies were not incorporated into lipids or protein. We conclude that adult rat-brain homogenates use ketone bodies exclusively for oxidative purposes.

  18. Health Problems Precede Traumatic Brain Injury in Older Adults

    PubMed Central

    Dams-O’Connor, Kristen; Gibbons, Laura E; Landau, Alexandra; Larson, Eric B; Crane, Paul K.

    2016-01-01

    Objectives To evaluate whether indices of pre-injury health and functioning were associated with risk for incident traumatic brain injury (TBI) with loss of consciousness (LOC), and evaluated health-related factors associated with mortality among those with an incident TBI. Design Prospective community cohort study. Setting Group Health, Seattle Washington. Participants 3,363 individuals aged 65 and older with no self-reported prior TBI with LOC were enrolled and followed every 2 years for an average of 7.5 years (range 0–18 years). Measurements We used Weibull survival models to evaluate baseline and time-varying predictors of incident TBI with LOC, including measures of depression, activities of daily living, cerebrovascular disease, and disease comorbidity. Results In an adjusted multivariate model, baseline depression symptoms as measured by CES-D score (hazard ratio (HR) and 95% confidence interval (CI) for 4 points = 1.34 (1.13, 1.58); p<0.05) and baseline impairment in activities of daily living (ADL; HR (95% CI) = 2.37 (1.24, 4.53); p<0.01) were associated with incident TBI. In a model that included time-dependent covariates, cerebrovascular disease at the previous visit (HR (95% CI) = 2.28 (1.37, 3.78); p<0.01), CES-D score the previous visit (HR for 4 points (95% CI) = 1.23 (1.02, 1.49); p<0.05) and baseline impairment in ADL (HR (95% CI) 2.14 (1.11, 4.13); p<0.05) predicted incident TBI. Of factors considered, cerebrovascular disease and ADL impairment were associated with earlier mortality among those with an incident TBI with LOC. Conclusion Indices of health, mood, and functional status predict incident TBI with LOC in older adults. These findings may have implications for injury prevention and post-injury clinical management. PMID:26925541

  19. Time Spent Caregiving and Help Received by Spouses and Adult Children of Brain-Impaired Adults.

    ERIC Educational Resources Information Center

    Enright, Robert B., Jr.

    1991-01-01

    Surveyed 233 family caregivers for brain-impaired adults. Spousal caregivers (both husbands and wives) devoted much time to caregiving. Most caregivers received little assistance from other family members and friends, but husbands received more than others. Employed spouses received more paid help than unemployed spouses; employment did not affect…

  20. [Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain].

    PubMed

    Respondek, Michalina; Buszman, Ewa

    2015-12-31

    Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC), which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells.

  1. Social Functioning in Adults with Learning Disabilities.

    ERIC Educational Resources Information Center

    Vogel, Susan A.; Forness, Steven R.

    1992-01-01

    Reviews literature on possible causes of social functioning deficits in adults with learning disabilities including language disorders, information processing deficits, and behavioral and/or attention problems. Discusses co-occurrence of social functioning deficits with nonverbal learning disability, and effects of educational isolation,…

  2. Structure and function of complex brain networks

    PubMed Central

    Sporns, Olaf

    2013-01-01

    An increasing number of theoretical and empirical studies approach the function of the human brain from a network perspective. The analysis of brain networks is made feasible by the development of new imaging acquisition methods as well as new tools from graph theory and dynamical systems. This review surveys some of these methodological advances and summarizes recent findings on the architecture of structural and functional brain networks. Studies of the structural connectome reveal several modules or network communities that are interlinked by hub regions mediating communication processes between modules. Recent network analyses have shown that network hubs form a densely linked collective called a “rich club,” centrally positioned for attracting and dispersing signal traffic. In parallel, recordings of resting and task-evoked neural activity have revealed distinct resting-state networks that contribute to functions in distinct cognitive domains. Network methods are increasingly applied in a clinical context, and their promise for elucidating neural substrates of brain and mental disorders is discussed. PMID:24174898

  3. Electromagnetic inverse applications for functional brain imaging

    SciTech Connect

    Wood, C.C.

    1997-10-01

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). This project addresses an important mathematical and computational problem in functional brain imaging, namely the electromagnetic {open_quotes}inverse problem.{close_quotes} Electromagnetic brain imaging techniques, magnetoencephalography (MEG) and electroencephalography (EEG), are based on measurements of electrical potentials and magnetic fields at hundreds of locations outside the human head. The inverse problem is the estimation of the locations, magnitudes, and time-sources of electrical currents in the brain from surface measurements. This project extends recent progress on the inverse problem by combining the use of anatomical constraints derived from magnetic resonance imaging (MRI) with Bayesian and other novel algorithmic approaches. The results suggest that we can achieve significant improvements in the accuracy and robustness of inverse solutions by these two approaches.

  4. Homological scaffolds of brain functional networks

    PubMed Central

    Petri, G.; Expert, P.; Turkheimer, F.; Carhart-Harris, R.; Nutt, D.; Hellyer, P. J.; Vaccarino, F.

    2014-01-01

    Networks, as efficient representations of complex systems, have appealed to scientists for a long time and now permeate many areas of science, including neuroimaging (Bullmore and Sporns 2009 Nat. Rev. Neurosci. 10, 186–198. (doi:10.1038/nrn2618)). Traditionally, the structure of complex networks has been studied through their statistical properties and metrics concerned with node and link properties, e.g. degree-distribution, node centrality and modularity. Here, we study the characteristics of functional brain networks at the mesoscopic level from a novel perspective that highlights the role of inhomogeneities in the fabric of functional connections. This can be done by focusing on the features of a set of topological objects—homological cycles—associated with the weighted functional network. We leverage the detected topological information to define the homological scaffolds, a new set of objects designed to represent compactly the homological features of the correlation network and simultaneously make their homological properties amenable to networks theoretical methods. As a proof of principle, we apply these tools to compare resting-state functional brain activity in 15 healthy volunteers after intravenous infusion of placebo and psilocybin—the main psychoactive component of magic mushrooms. The results show that the homological structure of the brain's functional patterns undergoes a dramatic change post-psilocybin, characterized by the appearance of many transient structures of low stability and of a small number of persistent ones that are not observed in the case of placebo. PMID:25401177

  5. Electroencephalographic imaging of higher brain function

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  6. Structural and functional brain imaging in schizophrenia.

    PubMed Central

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

    1991-01-01

    We present an evaluation of the contribution of structural and functional brain imaging to our understanding of schizophrenia. Methodological influences on the validity of the data generated by these new technologies include problems with measurement and clinical and anatomic heterogeneity. These considerations greatly affect the interpretation of the data generated by these technologies. Work in these fields to date, however, has produced strong evidence which suggests that schizophrenia is a disease which involves abnormalities in the structure and function of many brain areas. Structural brain imaging studies of schizophrenia using computed tomography (CT) and magnetic resonance imaging (MRI) are reviewed and their contribution to current theories of the pathogenesis of schizophrenia are discussed. Positron emission tomography (PET) studies of brain metabolic activity and dopamine receptor binding in schizophrenia are summarized and the critical questions raised by these studies are outlined. Future studies in these fields have the potential to yield critical insights into the pathophysiology of schizophrenia; new directions for studies of schizophrenia using these technologies are identified. PMID:1911736

  7. Robust Transient Dynamics and Brain Functions

    PubMed Central

    Rabinovich, Mikhail I.; Varona, Pablo

    2011-01-01

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

  8. Adult Age Differences in Functional Connectivity during Executive Control

    PubMed Central

    Madden, David J.; Costello, Matthew C.; Dennis, Nancy A.; Davis, Simon W.; Shepler, Anne M.; Spaniol, Julia; Bucur, Barbara; Cabeza, Roberto

    2010-01-01

    Task switching requires executive control processes that undergo age-related decline. Previous neuroimaging studies have identified age-related differences in brain activation associated with global switching effects (dual-task blocks vs. single-task blocks), but age-related differences in activation during local switching effects (switch trials vs. repeat trials, within blocks) have not been investigated. This experiment used functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI), to examine adult age differences in task switching across adjacent trials (i.e., local task switching). During fMRI scanning, participants performed a cued, word categorization task. From interspersed cue-only trials, switch-related processing associated with the cue was estimated separately from the target. Activation associated with task switching, within a distributed frontoparietal network, differed for cue- and target-related processing. The magnitude of event-related activation for task switching was similar for younger adults (n = 20; 18-27 years) and older adults (n = 20; 60-85 years), although activation sustained throughout the on-tasks periods exhibited some age-related decline. Critically, the functional connectivity of switch-related regions, during cue processing, was higher for younger adults than for older adults, whereas functional connectivity during target processing was comparable across the age groups. Further, individual differences in cue-related functional connectivity shared a substantial portion of the age-related variability in the efficiency of target categorization response (drift rate). This age-related difference in functional connectivity, however, was independent of white matter integrity within task-relevant regions. These findings highlight the functional connectivity of frontoparietal activation as a potential source of age-related decline in executive control. PMID:20434565

  9. Dynamic geometry, brain function modeling, and consciousness.

    PubMed

    Roy, Sisir; Llinás, Rodolfo

    2008-01-01

    Pellionisz and Llinás proposed, years ago, a geometric interpretation towards understanding brain function. This interpretation assumes that the relation between the brain and the external world is determined by the ability of the central nervous system (CNS) to construct an internal model of the external world using an interactive geometrical relationship between sensory and motor expression. This approach opened new vistas not only in brain research but also in understanding the foundations of geometry itself. The approach named tensor network theory is sufficiently rich to allow specific computational modeling and addressed the issue of prediction, based on Taylor series expansion properties of the system, at the neuronal level, as a basic property of brain function. It was actually proposed that the evolutionary realm is the backbone for the development of an internal functional space that, while being purely representational, can interact successfully with the totally different world of the so-called "external reality". Now if the internal space or functional space is endowed with stochastic metric tensor properties, then there will be a dynamic correspondence between events in the external world and their specification in the internal space. We shall call this dynamic geometry since the minimal time resolution of the brain (10-15 ms), associated with 40 Hz oscillations of neurons and their network dynamics, is considered to be responsible for recognizing external events and generating the concept of simultaneity. The stochastic metric tensor in dynamic geometry can be written as five-dimensional space-time where the fifth dimension is a probability space as well as a metric space. This extra dimension is considered an imbedded degree of freedom. It is worth noticing that the above-mentioned 40 Hz oscillation is present both in awake and dream states where the central difference is the inability of phase resetting in the latter. This framework of dynamic

  10. Atypical Brain Activation during Simple & Complex Levels of Processing in Adult ADHD: An fMRI Study

    ERIC Educational Resources Information Center

    Hale, T. Sigi; Bookheimer, Susan; McGough, James J.; Phillips, Joseph M.; McCracken, James T.

    2007-01-01

    Objective: Executive dysfunction in ADHD is well supported. However, recent studies suggest that more fundamental impairments may be contributing. We assessed brain function in adults with ADHD during simple and complex forms of processing. Method: We used functional magnetic resonance imaging with forward and backward digit spans to investigate…

  11. Functional brain imaging in respiratory medicine.

    PubMed

    Pattinson, Kyle

    2015-06-01

    Discordance of clinical symptoms with markers of disease severity remains a conundrum in a variety of respiratory conditions. The breathlessness of chronic lung disease correlates poorly with spirometry, yet is a better predictor of mortality. In chronic cough, symptoms are often evident without clear physical cause. In asthma, the terms 'over perceivers' and 'under perceivers' are common parlance. In all these examples, aberrant brain mechanisms may explain the mismatch between symptoms and pathology. Functional MRI is a non-invasive method of measuring brain function. It has recently become significantly advanced enough to be useful in clinical research and to address these potential mechanisms. This article explains how FMRI works, current understanding from FMRI in breathlessness, cough and asthma and suggests possibilities for future research.

  12. Localization and regulation of PML bodies in the adult mouse brain.

    PubMed

    Hall, Małgorzata H; Magalska, Adriana; Malinowska, Monika; Ruszczycki, Błażej; Czaban, Iwona; Patel, Satyam; Ambrożek-Latecka, Magdalena; Zołocińska, Ewa; Broszkiewicz, Hanna; Parobczak, Kamil; Nair, Rajeevkumar R; Rylski, Marcin; Pawlak, Robert; Bramham, Clive R; Wilczyński, Grzegorz M

    2016-06-01

    PML is a tumor suppressor protein involved in the pathogenesis of promyelocytic leukemia. In non-neuronal cells, PML is a principal component of characteristic nuclear bodies. In the brain, PML has been implicated in the control of embryonic neurogenesis, and in certain physiological and pathological phenomena in the adult brain. Yet, the cellular and subcellular localization of the PML protein in the brain, including its presence in the nuclear bodies, has not been investigated comprehensively. Because the formation of PML bodies appears to be a key aspect in the function of the PML protein, we investigated the presence of these structures and their anatomical distribution, throughout the adult mouse brain. We found that PML is broadly expressed across the gray matter, with the highest levels in the cerebral and cerebellar cortices. In the cerebral cortex PML is present exclusively in neurons, in which it forms well-defined nuclear inclusions containing SUMO-1, SUMO 2/3, but not Daxx. At the ultrastructural level, the appearance of neuronal PML bodies differs from the classic one, i.e., the solitary structure with more or less distinctive capsule. Rather, neuronal PML bodies have the form of small PML protein aggregates located in the close vicinity of chromatin threads. The number, size, and signal intensity of neuronal PML bodies are dynamically influenced by immobilization stress and seizures. Our study indicates that PML bodies are broadly involved in activity-dependent nuclear phenomena in adult neurons.

  13. Brain cannabinoid receptor 2: expression, function and modulation.

    PubMed

    Chen, De-Jie; Gao, Ming; Gao, Fen-Fei; Su, Quan-Xi; Wu, Jie

    2017-03-01

    Cannabis sativa (marijuana) is a fibrous flowering plant that produces an abundant variety of molecules, some with psychoactive effects. At least 4% of the world's adult population uses cannabis annually, making it one of the most frequently used illicit drugs in the world. The psychoactive effects of cannabis are mediated primarily through cannabinoid receptor (CBR) subtypes. The prevailing view is that CB1Rs are mainly expressed in the central neurons, whereas CB2Rs are predominantly expressed in peripheral immune cells. However, this traditional view has been challenged by emerging strong evidence that shows CB2Rs are moderately expressed and function in specific brain areas. New evidence has demonstrated that brain CB2Rs modulate animal drug-seeking behaviors, suggesting that these receptors may exist in brain regions that regulate drug addiction. Recently, we further confirmed that functional CB2Rs are expressed in mouse ventral tegmental area (VTA) dopamine (DA) neurons and that the activation of VTA CB2Rs reduces neuronal excitability and cocaine-seeking behavior. In addition, CB2R-mediated modulation of hippocampal CA3 neuronal excitability and network synchronization has been reported. Here, we briefly summarize recent lines of evidence showing how CB2Rs modulate function and pathophysiology in the CNS.

  14. Brain cannabinoid receptor 2: expression, function and modulation

    PubMed Central

    Chen, De-jie; Gao, Ming; Gao, Fen-fei; Su, Quan-xi; Wu, Jie

    2017-01-01

    Cannabis sativa (marijuana) is a fibrous flowering plant that produces an abundant variety of molecules, some with psychoactive effects. At least 4% of the world's adult population uses cannabis annually, making it one of the most frequently used illicit drugs in the world. The psychoactive effects of cannabis are mediated primarily through cannabinoid receptor (CBR) subtypes. The prevailing view is that CB1Rs are mainly expressed in the central neurons, whereas CB2Rs are predominantly expressed in peripheral immune cells. However, this traditional view has been challenged by emerging strong evidence that shows CB2Rs are moderately expressed and function in specific brain areas. New evidence has demonstrated that brain CB2Rs modulate animal drug-seeking behaviors, suggesting that these receptors may exist in brain regions that regulate drug addiction. Recently, we further confirmed that functional CB2Rs are expressed in mouse ventral tegmental area (VTA) dopamine (DA) neurons and that the activation of VTA CB2Rs reduces neuronal excitability and cocaine-seeking behavior. In addition, CB2R-mediated modulation of hippocampal CA3 neuronal excitability and network synchronization has been reported. Here, we briefly summarize recent lines of evidence showing how CB2Rs modulate function and pathophysiology in the CNS. PMID:28065934

  15. Brain activation during visual working memory correlates with behavioral mobility performance in older adults.

    PubMed

    Kawagoe, Toshikazu; Suzuki, Maki; Nishiguchi, Shu; Abe, Nobuhito; Otsuka, Yuki; Nakai, Ryusuke; Yamada, Minoru; Yoshikawa, Sakiko; Sekiyama, Kaoru

    2015-01-01

    Functional mobility and cognitive function often decline with age. We previously found that functional mobility as measured by the Timed Up and Go Test (TUG) was associated with cognitive performance for visually-encoded (i.e., for location and face) working memory (WM) in older adults. This suggests a common neural basis between TUG and visual WM. To elucidate this relationship further, the present study aimed to examine the neural basis for the WM-mobility association. In accordance with the well-known neural compensation model in aging, we hypothesized that "attentional" brain activation for easy WM would increase in participants with lower mobility. The data from 32 healthy older adults were analyzed, including brain activation during easy WM tasks via functional Magnetic Resonance Imaging (fMRI) and mobility performance via both TUG and a simple walking test. WM performance was significantly correlated with TUG but not with simple walking. Some prefrontal brain activations during WM were negatively correlated with TUG performance, while positive correlations were found in subcortical structures including the thalamus, putamen and cerebellum. Moreover, activation of the subcortical regions was significantly correlated with WM performance, with less activation for lower WM performers. These results indicate that older adults with lower mobility used more cortical (frontal) and fewer subcortical resources for easy WM tasks. To date, the frontal compensation has been proposed separately in the motor and cognitive domains, which have been assumed to compensate for dysfunction of the other brain areas; however, such dysfunction was less clear in previous studies. The present study observed such dysfunction as degraded activation associated with lower performance, which was found in the subcortical regions. We conclude that a common dysfunction-compensation activation pattern is likely the neural basis for the association between visual WM and functional mobility.

  16. Brain activation during visual working memory correlates with behavioral mobility performance in older adults

    PubMed Central

    Kawagoe, Toshikazu; Suzuki, Maki; Nishiguchi, Shu; Abe, Nobuhito; Otsuka, Yuki; Nakai, Ryusuke; Yamada, Minoru; Yoshikawa, Sakiko; Sekiyama, Kaoru

    2015-01-01

    Functional mobility and cognitive function often decline with age. We previously found that functional mobility as measured by the Timed Up and Go Test (TUG) was associated with cognitive performance for visually-encoded (i.e., for location and face) working memory (WM) in older adults. This suggests a common neural basis between TUG and visual WM. To elucidate this relationship further, the present study aimed to examine the neural basis for the WM-mobility association. In accordance with the well-known neural compensation model in aging, we hypothesized that “attentional” brain activation for easy WM would increase in participants with lower mobility. The data from 32 healthy older adults were analyzed, including brain activation during easy WM tasks via functional Magnetic Resonance Imaging (fMRI) and mobility performance via both TUG and a simple walking test. WM performance was significantly correlated with TUG but not with simple walking. Some prefrontal brain activations during WM were negatively correlated with TUG performance, while positive correlations were found in subcortical structures including the thalamus, putamen and cerebellum. Moreover, activation of the subcortical regions was significantly correlated with WM performance, with less activation for lower WM performers. These results indicate that older adults with lower mobility used more cortical (frontal) and fewer subcortical resources for easy WM tasks. To date, the frontal compensation has been proposed separately in the motor and cognitive domains, which have been assumed to compensate for dysfunction of the other brain areas; however, such dysfunction was less clear in previous studies. The present study observed such dysfunction as degraded activation associated with lower performance, which was found in the subcortical regions. We conclude that a common dysfunction—compensation activation pattern is likely the neural basis for the association between visual WM and functional

  17. Violent Video Games Alter Brain Function in Young Men

    MedlinePlus

    ... News from the RSNA Annual Meeting Violent Video Games Alter Brain Function in Young Men At A ... MRI, researchers have found that playing violent video games for one week causes changes in brain function. ...

  18. Physical Activity Is Linked to Greater Moment-To-Moment Variability in Spontaneous Brain Activity in Older Adults

    PubMed Central

    Burzynska, Agnieszka Z.; Wong, Chelsea N.; Voss, Michelle W.; Cooke, Gillian E.; Gothe, Neha P.; Fanning, Jason; McAuley, Edward; Kramer, Arthur F.

    2015-01-01

    Higher cardiorespiratory fitness (CRF) and physical activity (PA) in old age are associated with greater brain structural and functional integrity, and higher cognitive functioning. However, it is not known how different aspects of lifestyle such as sedentariness, light PA (LI-PA), or moderate-to-vigorous physical activity (MV-PA) relate to neural activity in aging. In addition, it is not known whether the effects of PA on brain function differ or overlap with those of CRF. Here, we objectively measured CRF as oxygen consumption during a maximal exercise test and measured PA with an accelerometer worn for 7 days in 100 healthy but low active older adults (aged 60–80 years). We modeled the relationships between CRF, PA, and brain functional integrity using multivariate partial least squares analysis. As an index of functional brain integrity we used spontaneous moment-to-moment variability in the blood oxygenation level-dependent signal (SDBOLD), known to be associated with better cognitive functioning in aging. We found that older adults who engaged more in LI-PA and MV-PA had greater SDBOLD in brain regions that play a role in integrating segregated functional domains in the brain and benefit from greater CRF or PA, such as precuneus, hippocampus, medial and lateral prefrontal, and temporal cortices. Our results suggest that engaging in higher intensity PA may have protective effects on neural processing in aging. Finally, we demonstrated that older adults with greater overall WM microstructure were those showing more LI-PA and MV-PA and greater SDBOLD. We conclude that SDBOLD is a promising correlate of functional brain health in aging. Future analyses will evaluate whether SDBOLD is modifiable with interventions aimed to increase PA and CRF in older adults. PMID:26244873

  19. Brain plasticity and functional losses in the aged: scientific bases for a novel intervention.

    PubMed

    Mahncke, Henry W; Bronstone, Amy; Merzenich, Michael M

    2006-01-01

    Aging is associated with progressive losses in function across multiple systems, including sensation, cognition, memory, motor control, and affect. The traditional view has been that functional decline in aging is unavoidable because it is a direct consequence of brain machinery wearing down over time. In recent years, an alternative perspective has emerged, which elaborates on this traditional view of age-related functional decline. This new viewpoint--based upon decades of research in neuroscience, experimental psychology, and other related fields--argues that as people age, brain plasticity processes with negative consequences begin to dominate brain functioning. Four core factors--reduced schedules of brain activity, noisy processing, weakened neuromodulatory control, and negative learning--interact to create a self-reinforcing downward spiral of degraded brain function in older adults. This downward spiral might begin from reduced brain activity due to behavioral change, from a loss in brain function driven by aging brain machinery, or more likely from both. In aggregate, these interrelated factors promote plastic changes in the brain that result in age-related functional decline. This new viewpoint on the root causes of functional decline immediately suggests a remedial approach. Studies of adult brain plasticity have shown that substantial improvement in function and/or recovery from losses in sensation, cognition, memory, motor control, and affect should be possible, using appropriately designed behavioral training paradigms. Driving brain plasticity with positive outcomes requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis, in a behavioral context designed to re-engage and strengthen the neuromodulatory systems that control learning in adults, with the goal of increasing the fidelity, reliability, and power of cortical representations. Such a training program would serve a substantial unmet need in

  20. Nuclear receptors of the honey bee: annotation and expression in the adult brain.

    PubMed

    Velarde, Rodrigo A; Robinson, Gene E; Fahrbach, Susan E

    2006-10-01

    The Drosophila genome encodes 18 canonical nuclear receptors. All of the Drosophila nuclear receptors are here shown to be present in the genome of the honey bee (Apis mellifera). Given that the time since divergence of the Drosophila and Apis lineages is measured in hundreds of millions of years, the identification of matched orthologous nuclear receptors in the two genomes reveals the fundamental set of nuclear receptors required to 'make' an endopterygote insect. The single novelty is the presence in the A. mellifera genome of a third insect gene similar to vertebrate photoreceptor-specific nuclear receptor (PNR). Phylogenetic analysis indicates that this novel gene, which we have named AmPNR-like, is a new member of the NR2 subfamily not found in the Drosophila or human genomes. This gene is expressed in the developing compound eye of the honey bee. Like their vertebrate counterparts, arthropod nuclear receptors play key roles in embryonic and postembryonic development. Studies in Drosophila have focused primarily on the role of these transcription factors in embryogenesis and metamorphosis. Examination of an expressed sequence tag library developed from the adult bee brain and analysis of transcript expression in brain using in situ hybridization and quantitative RT-PCR revealed that several members of the nuclear receptor family (AmSVP, AmUSP, AmERR, AmHr46, AmFtz-F1, and AmHnf-4) are expressed in the brain of the adult bee. Further analysis of the expression of AmUSP and AmSVP in the mushroom bodies, the major insect brain centre for learning and memory, revealed changes in transcript abundance and, in the case of AmUSP, changes in transcript localization, during the development of foraging behaviour in the adult. Study of the honey bee therefore provides a model for understanding nuclear receptor function in the adult brain.

  1. Eating disorder psychopathology, brain structure, neuropsychological correlates and risk mechanisms in very preterm young adults.

    PubMed

    Micali, Nadia; Kothari, Radha; Nam, Kie Woo; Gioroukou, Elena; Walshe, Muriel; Allin, Matthew; Rifkin, Larry; Murray, Robin M; Nosarti, Chiara

    2015-03-01

    This study investigates the prevalence of eating disorder (ED) psychopathology, neuropsychological function, structural brain correlates and risk mechanisms in a prospective cohort of very preterm (VPT) young adults. We assessed ED psychopathology and neuropsychological correlates in 143 cohort individuals born at <33 weeks of gestation. Structural brain correlates and risk factors at birth, in childhood and adolescence, were investigated using prospectively collected data throughout childhood/adolescence. VPT-born individuals had high levels of ED psychopathology at age 21 years. Executive function did not correlate with ED symptomatology. VPT adults presenting with ED psychopathology had smaller grey matter volume at age 14/15 years in the left posterior cerebellum and smaller white matter volume in the fusiform gyrus bilaterally, compared with VPT adults with no ED psychopathology. Caesarean delivery predicted engaging in compensatory behaviours, and severe eating difficulty at age 14 years predicted ED symptomatology in young adulthood. VPT individuals are at risk for ED symptomatology, with evidence of associated structural alterations in posterior brain regions. Further prospective studies are needed to clarify the pathways that lead from perinatal/obstetric complications to ED and relevant neurobiological mechanisms. © 2015 The Authors. European Eating Disorders Review published by John Wiley &Sons, Ltd.

  2. Tangential migration of neuronal precursors of glutamatergic neurons in the adult mammalian brain

    PubMed Central

    Sun, Gerald J.; Zhou, Yi; Stadel, Ryan P.; Moss, Jonathan; Yong, Jing Hui A.; Ito, Shiori; Kawasaki, Nicholas K.; Phan, Alexander T.; Oh, Justin H.; Modak, Nikhil; Reed, Randall R.; Toni, Nicolas; Song, Hongjun; Ming, Guo-li

    2015-01-01

    In a classic model of mammalian brain formation, precursors of principal glutamatergic neurons migrate radially along radial glia fibers whereas GABAergic interneuron precursors migrate tangentially. These migration modes have significant implications for brain function. Here we used clonal lineage tracing of active radial glia-like neural stem cells in the adult mouse dentate gyrus and made the surprising discovery that proliferating neuronal precursors of glutamatergic granule neurons exhibit significant tangential migration along blood vessels, followed by limited radial migration. Genetic birthdating and morphological and molecular analyses pinpointed the neuroblast stage as the main developmental window when tangential migration occurs. We also developed a partial “whole-mount” dentate gyrus preparation and observed a dense plexus of capillaries, with which only neuroblasts, among the entire population of progenitors, are directly associated. Together, these results provide insight into neuronal migration in the adult mammalian nervous system. PMID:26170290

  3. Arginine vasotocin neuronal development and its projection in the adult brain of the medaka.

    PubMed

    Kagawa, Nao; Honda, Akira; Zenno, Akiko; Omoto, Ryosuke; Imanaka, Saya; Takehana, Yusuke; Naruse, Kiyoshi

    2016-02-02

    The neurohypophysial peptide arginine vasotocin (AVT) and its mammalian ortholog arginine vasopressin function in a wide range of physiological and behavioral events. Here, we generated a new line of transgenic medaka (Oryzias latipes), which allowed us to monitor AVT neurons by enhanced green fluorescent protein (EGFP) and demonstrate AVT neuronal development in the embryo and the projection of AVT neurons in the adult brain of avt-egfp transgenic medaka. The onset of AVT expression manifested at 2 days postfertilization (dpf) as a pair of signals in the telencephalon of the brain. The telencephalic AVT neurons migrated and converged on the preoptic area (POA) by 4dpf. At the same stage, another onset of AVT expression manifested in the central optic tectum (OT), and they migrated to the ventral part of the hypothalamus (VH) by 6dpf. In the adult brain, the AVT somata with EGFP signals existed in the gigantocellular POA (gPOA), magnocellular POA (mPOA), and parvocellular POA (pPOA) and in the VH. Whereas the major projection of AVT fibers was found from the pPOA and VH to the posterior pituitary, it was also found that AVT neurons in the three POAs send their fibers into wide regions of the brain such as the telencephalon, mesencephalon and diencephalon. This study suggests that the avt-egfp transgenic medaka is a useful model to explore AVT neuronal development and function.

  4. 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.

  5. Circadian clocks, brain function, and development.

    PubMed

    Frank, Ellen; Sidor, Michelle M; Gamble, Karen L; Cirelli, Chiara; Sharkey, Katherine M; Hoyle, Nathaniel; Tikotzky, Liat; Talbot, Lisa S; McCarthy, Michael J; Hasler, Brant P

    2013-12-01

    Circadian clocks are temporal interfaces that organize biological systems and behavior to dynamic external environments. Components of the molecular clock are expressed throughout the brain and are centrally poised to play an important role in brain function. This paper focuses on key issues concerning the relationship among circadian clocks, brain function, and development, and discusses three topic areas: (1) sleep and its relationship to the circadian system; (2) systems development and psychopathology (spanning the prenatal period through late life); and (3) circadian factors and their application to neuropsychiatric disorders. We also explore circadian genetics and psychopathology and the selective pressures on the evolution of clocks. Last, a lively debate is presented on whether circadian factors are central to mood disorders. Emerging from research on circadian rhythms is a model of the interaction among genes, sleep, and the environment that converges on the circadian clock to influence susceptibility to developing psychopathology. This model may lend insight into effective treatments for mood disorders and inform development of new interventions.

  6. Differential Distribution of Major Brain Gangliosides in the Adult Mouse Central Nervous System

    PubMed Central

    Vajn, Katarina; Viljetić, Barbara; Degmečić, Ivan Večeslav; Schnaar, Ronald L.; Heffer, Marija

    2013-01-01

    Gangliosides - sialic acid-bearing glycolipids - are major cell surface determinants on neurons and axons. The same four closely related structures, GM1, GD1a, GD1b and GT1b, comprise the majority of total brain gangliosides in mammals and birds. Gangliosides regulate the activities of proteins in the membranes in which they reside, and also act as cell-cell recognition receptors. Understanding the functions of major brain gangliosides requires knowledge of their tissue distribution, which has been accomplished in the past using biochemical and immunohistochemical methods. Armed with new knowledge about the stability and accessibility of gangliosides in tissues and new IgG-class specific monoclonal antibodies, we investigated the detailed tissue distribution of gangliosides in the adult mouse brain. Gangliosides GD1b and GT1b are widely expressed in gray and white matter. In contrast, GM1 is predominately found in white matter and GD1a is specifically expressed in certain brain nuclei/tracts. These findings are considered in relationship to the hypothesis that gangliosides GD1a and GT1b act as receptors for an important axon-myelin recognition protein, myelin-associated glycoprotein (MAG). Mediating axon-myelin interactions is but one potential function of the major brain gangliosides, and more detailed knowledge of their distribution may help direct future functional studies. PMID:24098718

  7. Distinct Brain and Behavioral Benefits from Cognitive vs. Physical Training: A Randomized Trial in Aging Adults.

    PubMed

    Chapman, Sandra B; Aslan, Sina; Spence, Jeffrey S; Keebler, Molly W; DeFina, Laura F; Didehbani, Nyaz; Perez, Alison M; Lu, Hanzhang; D'Esposito, Mark

    2016-01-01

    Insidious declines in normal aging are well-established. Emerging evidence suggests that non-pharmacological interventions, specifically cognitive and physical training, may counter diminishing age-related cognitive and brain functions. This randomized trial compared effects of two training protocols: cognitive training (CT) vs. physical training (PT) on cognition and brain function in adults 56-75 years. Sedentary participants (N = 36) were randomized to either CT or PT group for 3 h/week over 12 weeks. They were assessed at baseline-, mid-, and post-training using neurocognitive, MRI, and physiological measures. The CT group improved on executive function whereas PT group's memory was enhanced. Uniquely deploying cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) MRI, the CT cohort showed increased CBF within the prefrontal and middle/posterior cingulate cortex (PCC) without change to CVR compared to PT group. Improvements in complex abstraction were positively associated with increased resting CBF in dorsal anterior cingulate cortex (dACC). Exercisers with higher CBF in hippocampi bilaterally showed better immediate memory. The preliminary evidence indicates that increased cognitive and physical activity improves brain health in distinct ways. Reasoning training enhanced frontal networks shown to be integral to top-down cognitive control and brain resilience. Evidence of increased resting CBF without changes to CVR implicates increased neural health rather than improved vascular response. Exercise did not improve cerebrovascular response, although CBF increased in hippocampi of those with memory gains. Distinct benefits incentivize testing effectiveness of combined protocols to strengthen brain health.

  8. Distinct Brain and Behavioral Benefits from Cognitive vs. Physical Training: A Randomized Trial in Aging Adults

    PubMed Central

    Chapman, Sandra B.; Aslan, Sina; Spence, Jeffrey S.; Keebler, Molly W.; DeFina, Laura F.; Didehbani, Nyaz; Perez, Alison M.; Lu, Hanzhang; D'Esposito, Mark

    2016-01-01

    Insidious declines in normal aging are well-established. Emerging evidence suggests that non-pharmacological interventions, specifically cognitive and physical training, may counter diminishing age-related cognitive and brain functions. This randomized trial compared effects of two training protocols: cognitive training (CT) vs. physical training (PT) on cognition and brain function in adults 56–75 years. Sedentary participants (N = 36) were randomized to either CT or PT group for 3 h/week over 12 weeks. They were assessed at baseline-, mid-, and post-training using neurocognitive, MRI, and physiological measures. The CT group improved on executive function whereas PT group's memory was enhanced. Uniquely deploying cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) MRI, the CT cohort showed increased CBF within the prefrontal and middle/posterior cingulate cortex (PCC) without change to CVR compared to PT group. Improvements in complex abstraction were positively associated with increased resting CBF in dorsal anterior cingulate cortex (dACC). Exercisers with higher CBF in hippocampi bilaterally showed better immediate memory. The preliminary evidence indicates that increased cognitive and physical activity improves brain health in distinct ways. Reasoning training enhanced frontal networks shown to be integral to top-down cognitive control and brain resilience. Evidence of increased resting CBF without changes to CVR implicates increased neural health rather than improved vascular response. Exercise did not improve cerebrovascular response, although CBF increased in hippocampi of those with memory gains. Distinct benefits incentivize testing effectiveness of combined protocols to strengthen brain health. PMID:27462210

  9. Chemogenetic tools to interrogate brain functions.

    PubMed

    Sternson, Scott M; Roth, Bryan L

    2014-01-01

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

  10. Central artery stiffness, baroreflex sensitivity, and brain white matter neuronal fiber integrity in older adults.

    PubMed

    Tarumi, Takashi; de Jong, Daan L K; Zhu, David C; Tseng, Benjamin Y; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B; Kerwin, Diana R; Lu, Hanzhang; Munro Cullum, C; Zhang, Rong

    2015-04-15

    Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65 ± 6 years) with normal cognitive function or mild cognitive impairment (MCI) were tested. The neuronal fiber integrity of brain WM was assessed from diffusion metrics acquired by diffusion tensor imaging. BRS was measured in response to acute changes in blood pressure induced by bolus injections of vasoactive drugs. Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). The WM diffusion metrics including fractional anisotropy (FA) and radial (RD) and axial (AD) diffusivities, BRS, and cfPWV were not different between the control and MCI groups. Thus, the data from both groups were combined for subsequent analyses. Across WM, fiber tracts with decreased FA and increased RD were associated with lower BRS and higher cfPWV, with many of the areas presenting spatial overlap. In particular, the BRS assessed during hypotension was strongly correlated with FA and RD when compared with hypertension. Executive function performance was associated with FA and RD in the areas that correlated with cfPWV and BRS. These findings suggest that baroreflex-mediated control of systemic arterial perfusion, especially during hypotension, may play a crucial role in maintaining neuronal fiber integrity of brain WM in older adults.

  11. Adolescent and young adult survivors of childhood brain tumors: Life after treatment in their own words

    PubMed Central

    Hobbie, Wendy L.; Ogle, Sue; Reilly, Maureen; Barakat, Lamia; Lucas, Matthew S.; Ginsberg, Jill P.; Fisher, Michael J.; Volpe, Ellen M.; Deatrick, Janet A.

    2015-01-01

    Background To date there are few studies that examine the perspectives of older survivors of childhood brain tumors who are living with their families in terms of their sense of self and their role in their families. Objective To describe how adolescent and young adult survivors (AYA) of childhood brain tumors describe their HRQOL, that is their physical, emotional, and social functioning. Methods This qualitative descriptive study included a purposive sample of 41 AYA survivors of a childhood brain tumor who live with their families. Home interviews were conducted using a semi-structured interview guide. Directed content analytic techniques were used to analyze data using HRQOL as a framework. Results This group of brain tumor survivors described their everyday lives in terms of their physical health, neurocognitive functioning, emotional health, social functioning, and self-care abilities. Overall, survivors struggle for normalcy in the face of changed functioning due to their cancer and the (late) effects of their treatment. Conclusions Neurocognitive issues seemed most compelling in the narratives. The importance of families went beyond the resources, structure, and support for functioning. Their families provided the recognition that they were important beings and their existence mattered to someone. Implications for Practice The value and complexity of care coordination was highlighted by the multifaceted needs of the survivors. Advocacy for appropriate and timely educational, vocational, and social support is critical as part of comprehensive cancer survivorship care. PMID:25950583

  12. Transgenerational epigenetic effects on brain functions.

    PubMed

    Bohacek, Johannes; Gapp, Katharina; Saab, Bechara J; Mansuy, Isabelle M

    2013-02-15

    Psychiatric diseases are multifaceted disorders with complex etiology, recognized to have strong heritable components. Despite intense research efforts, genetic loci that substantially account for disease heritability have not yet been identified. Over the last several years, epigenetic processes have emerged as important factors for many brain diseases, and the discovery of epigenetic processes in germ cells has raised the possibility that they may contribute to disease heritability and disease risk. This review examines epigenetic mechanisms in complex diseases and summarizes the most illustrative examples of transgenerational epigenetic inheritance in mammals and their relevance for brain function. Environmental factors that can affect molecular processes and behavior in exposed individuals and their offspring, and their potential epigenetic underpinnings, are described. Possible routes and mechanisms of transgenerational transmission are proposed, and the major questions and challenges raised by this emerging field of research are considered.

  13. The function of BDNF in the adult auditory system.

    PubMed

    Singer, Wibke; Panford-Walsh, Rama; Knipper, Marlies

    2014-01-01

    The inner ear of vertebrates is specialized to perceive sound, gravity and movements. Each of the specialized sensory organs within the cochlea (sound) and vestibular system (gravity, head movements) transmits information to specific areas of the brain. During development, brain-derived neurotrophic factor (BDNF) orchestrates the survival and outgrowth of afferent fibers connecting the vestibular organ and those regions in the cochlea that map information for low frequency sound to central auditory nuclei and higher-auditory centers. The role of BDNF in the mature inner ear is less understood. This is mainly due to the fact that constitutive BDNF mutant mice are postnatally lethal. Only in the last few years has the improved technology of performing conditional cell specific deletion of BDNF in vivo allowed the study of the function of BDNF in the mature developed organ. This review provides an overview of the current knowledge of the expression pattern and function of BDNF in the peripheral and central auditory system from just prior to the first auditory experience onwards. A special focus will be put on the differential mechanisms in which BDNF drives refinement of auditory circuitries during the onset of sensory experience and in the adult brain. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'.

  14. Evaluation of an automatic brain segmentation method developed for neonates on adult MR brain images

    NASA Astrophysics Data System (ADS)

    Moeskops, Pim; Viergever, Max A.; Benders, Manon J. N. L.; Išgum, Ivana

    2015-03-01

    Automatic brain tissue segmentation is of clinical relevance in images acquired at all ages. The literature presents a clear distinction between methods developed for MR images of infants, and methods developed for images of adults. The aim of this work is to evaluate a method developed for neonatal images in the segmentation of adult images. The evaluated method employs supervised voxel classification in subsequent stages, exploiting spatial and intensity information. Evaluation was performed using images available within the MRBrainS13 challenge. The obtained average Dice coefficients were 85.77% for grey matter, 88.66% for white matter, 81.08% for cerebrospinal fluid, 95.65% for cerebrum, and 96.92% for intracranial cavity, currently resulting in the best overall ranking. The possibility of applying the same method to neonatal as well as adult images can be of great value in cross-sectional studies that include a wide age range.

  15. Regional Brain Responses Are Biased Toward Infant Facial Expressions Compared to Adult Facial Expressions in Nulliparous Women

    PubMed Central

    Zhang, Dajun; Wei, Dongtao; Qiao, Lei; Wang, Xiangpeng; Che, Xianwei

    2016-01-01

    Recent neuroimaging studies suggest that neutral infant faces compared to neutral adult faces elicit greater activity in brain areas associated with face processing, attention, empathic response, reward, and movement. However, whether infant facial expressions evoke larger brain responses than adult facial expressions remains unclear. Here, we performed event-related functional magnetic resonance imaging in nulliparous women while they were presented with images of matched unfamiliar infant and adult facial expressions (happy, neutral, and uncomfortable/sad) in a pseudo-randomized order. We found that the bilateral fusiform and right lingual gyrus were overall more activated during the presentation of infant facial expressions compared to adult facial expressions. Uncomfortable infant faces compared to sad adult faces evoked greater activation in the bilateral fusiform gyrus, precentral gyrus, postcentral gyrus, posterior cingulate cortex-thalamus, and precuneus. Neutral infant faces activated larger brain responses in the left fusiform gyrus compared to neutral adult faces. Happy infant faces compared to happy adult faces elicited larger responses in areas of the brain associated with emotion and reward processing using a more liberal threshold of p < 0.005 uncorrected. Furthermore, the level of the test subjects’ Interest-In-Infants was positively associated with the intensity of right fusiform gyrus response to infant faces and uncomfortable infant faces compared to sad adult faces. In addition, the Perspective Taking subscale score on the Interpersonal Reactivity Index-Chinese was significantly correlated with precuneus activity during uncomfortable infant faces compared to sad adult faces. Our findings suggest that regional brain areas may bias cognitive and emotional responses to infant facial expressions compared to adult facial expressions among nulliparous women, and this bias may be modulated by individual differences in Interest-In-Infants and

  16. Abundant Production of Brain-Derived Neurotrophic Factor by Adult Visceral Epithelia

    PubMed Central

    Lommatzsch, Marek; Braun, Armin; Mannsfeldt, Anne; Botchkarev, Vladimir A.; Botchkareva, Natalia V.; Paus, Ralf; Fischer, Axel; Lewin, Gary R.; Renz, Harald

    1999-01-01

    Brain-derived neurotrophic factor (BDNF) plays a crucial role for the survival of visceral sensory neurons during development. However, the physiological sources and the function of BDNF in the adult viscera are poorly described. We have investigated the cellular sources and the potential role of BDNF in adult murine viscera. We found markedly different amounts of BDNF protein in different organs. Surprisingly, BDNF levels in the urinary bladder, lung, and colon were higher than those found in the brain or skin. In situ hybridization experiments revealed that BDNF mRNA was made by visceral epithelial cells, several types of smooth muscle, and neurons of the myenteric plexus. Epithelia that expressed BDNF lacked both the high- and low-affinity receptors for BDNF, trkB and p75NTR. In contrast, both receptors were present on neurons of the peripheral nervous system. Studies with BDNF−/−mice demonstrated that epithelial and smooth muscle cells developed normally in the absence of BDNF. These data provide evidence that visceral epithelia are a major source, but not a target, of BDNF in the adult viscera. The abundance of BDNF protein in certain internal organs suggests that this neurotrophin may regulate the function of adult visceral sensory and motor neurons. PMID:10514401

  17. Brain activation during interference resolution in young and older adults: an fMRI study.

    PubMed

    Zhu, David C; Zacks, Rose T; Slade, Jill M

    2010-04-01

    A rapid event-related fMRI arrow flanker task was used to study aging-associated decline in executive functions related to interference resolution. Older adults had more difficulty responding to Incongruent cues during the flanker task compared to the young adults; the response time difference between the Incongruent and Congruent conditions in the older group was over 50% longer compared to the young adults. In the frontal regions, differential activation ("Incongruent-Congruent" conditions) was observed in the inferior and middle frontal gyri in within-group analyses for both groups. However, the cluster was smaller in the older group and the centroid location was shifted by 19.7 mm. The left superior and medial frontal gyri also appeared to be specifically recruited by older adults during interference resolution, partially driven by errors. The frontal right lateralization found in the young adults was maintained in the older adults during successful trials. Interestingly, bilateral activation was observed when error trials were combined with successful trials highlighting the influence of brain activation associated with errors during cognitive processing. In conclusion, aging appears to result in modified functional regions that may contribute to reduced interference resolution. In addition, error processing should be considered and accounted for when studying age-related cognitive changes as errors may confound the interpretation of task specific age-related activation differences.

  18. Enhanced task related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation.

    PubMed

    Bowtell, Joanna L; Aboo-Bakkar, Zainie; Conway, Myra; Adlam, Anna-Lynne R; Fulford, Jonathan

    2017-03-01

    Blueberries are rich in flavonoids, which possess antioxidant and anti-inflammatory properties. High flavonoid intakes attenuate age-related cognitive decline, but data from human intervention studies are sparse. We investigated whether 12 weeks of blueberry concentrate supplementation improved brain perfusion, task-related activation and cognitive function in healthy older adults. Participants were randomised to consume either 30 ml blueberry concentrate providing 387 mg anthocyanidins (5 female, 7 male; age 67.5±3.0 y; BMI, 25.9±3.3 kg.m-2) or isoenergetic placebo (8 female, 6 male; age 69.0 ±3.3 y; BMI, 27.1±.4.0 kg.m-2). Pre- and post-supplementation, participants undertook a battery of cognitive function tests and a numerical Stroop test within a 1.5T MRI scanner while functional magnetic resonance images (fMRI) were continuously acquired. Quantitative resting brain perfusion was determined using an arterial spin labelling (ASL) technique, and blood biomarkers of inflammation and oxidative stress were measured. Significant increases in brain activity were observed in response to blueberry supplementation relative to the placebo group within Brodmann areas 4/6/10/21/40/44/45, precuneus, anterior cingulate, and insula/thalamus (p<0.001), as well as significant improvements in grey matter perfusion in the parietal (5.0±1.8 vs -2.9±2.4 %, p=0.013) and occipital (8.0±2.6 vs -0.7±3.2 %, p=0.031) lobes. There was also evidence suggesting improvement in working memory (two back test) after blueberry versus placebo supplementation (p=0.05). Supplementation with an anthocyanin rich blueberry concentrate improved brain perfusion and activation in brain areas associated with cognitive function in healthy older adults.

  19. Immunohistochemical and ultrastructural changes in the brain in probable adult glycogenosis type IV: adult polyglucosan body disease.

    PubMed

    Wierzba-Bobrowicz, Teresa; Lewandowska, Eliza; Stepień, Tomasz; Modzelewska, Joanna

    2008-01-01

    Glycogenosis type IV is caused by a deficiency of glycogen branching enzyme (alpha-1,4 glucan 6-transglucosylase). Adult polyglucosan body disease (APBD) may represent a neuropathological hallmark of the adult form of this storage disease of the central nervous system. We analysed a case of a 45-year-old unconscious woman who died three days after admission to the hospital. Neuropathological examination revealed massive accumulation of polyglucosan bodies (PBs) in the cortex and white matter of the whole brain. PBs were located in the processes of neurons, astrocytes and microglial cells. The storage material in the cytoplasm of neurons and glial cells was visible as fine granules. Ultrastructurally, PBs consisted of non-membrane-bound deposits of branched and densely packed filaments, measuring about 7-10 nm in diameter, typical of polyglucosan bodies. APBD patients develop upper and lower neuron disease and dementia, probably secondary to the disruption of neuron and astrocyte functions.

  20. Doublecortin in Oligodendrocyte Precursor Cells in the Adult Mouse Brain

    PubMed Central

    Boulanger, Jenna J.; Messier, Claude

    2017-01-01

    Key Points Oligodendrocyte precursor cells express doublecortin, a microtubule-associated protein.Oligodendrocyte precursor cells express doublecortin, but at a lower level of expression than in neuronal precursor.Doublecortin is not associated with a potential immature neuronal phenotype in Oligodendrocyte precursor cells. Oligodendrocyte precursor cells (OPC) are glial cells that differentiate into myelinating oligodendrocytes during embryogenesis and early stages of post-natal life. OPCs continue to divide throughout adulthood and some eventually differentiate into oligodendrocytes in response to demyelinating lesions. There is growing evidence that OPCs are also involved in activity-driven de novo myelination of previously unmyelinated axons and myelin remodeling in adulthood. Considering these roles in the adult brain, OPCs are likely mobile cells that can migrate on some distances before they differentiate into myelinating oligodendrocytes. A number of studies have noted that OPCs express doublecortin (DCX), a microtubule-associated protein expressed in neural precursor cells and in migrating immature neurons. Here we describe the distribution of DCX in OPCs. We found that almost all OPCs express DCX, but the level of expression appears to be much lower than what is found in neural precursor. We found that DCX is downregulated when OPCs start expressing mature oligodendrocyte markers and is absent in myelinating oligodendrocytes. DCX does not appear to signal an immature neuronal phenotype in OPCs in the adult mouse brain. Rather, it could be involved either in cell migration, or as a marker of an immature oligodendroglial cell phenotype.

  1. Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain.

    PubMed

    Feliciano, David M; Bordey, Angélique; Bonfanti, Luca

    2015-09-18

    Two decades after the discovery that neural stem cells (NSCs) populate some regions of the mammalian central nervous system (CNS), deep knowledge has been accumulated on their capacity to generate new neurons in the adult brain. This constitutive adult neurogenesis occurs throughout life primarily within remnants of the embryonic germinal layers known as "neurogenic sites." Nevertheless, some processes of neurogliogenesis also occur in the CNS parenchyma commonly considered as "nonneurogenic." This "noncanonical" cell genesis has been the object of many claims, some of which turned out to be not true. Indeed, it is often an "incomplete" process as to its final outcome, heterogeneous by several measures, including regional location, progenitor identity, and fate of the progeny. These aspects also strictly depend on the animal species, suggesting that persistent neurogenic processes have uniquely adapted to the brain anatomy of different mammals. Whereas some examples of noncanonical neurogenesis are strictly parenchymal, others also show stem cell niche-like features and a strong link with the ventricular cavities. This work will review results obtained in a research field that expanded from classic neurogenesis studies involving a variety of areas of the CNS outside of the subventricular zone (SVZ) and subgranular zone (SGZ). It will be highlighted how knowledge concerning noncanonical neurogenic areas is still incomplete owing to its regional and species-specific heterogeneity, and to objective difficulties still hampering its full identification and characterization.

  2. Ribosomal protein L11 is related to brain maturation during the adult phase in Apis cerana cerana (Hymenoptera, Apidae).

    PubMed

    Meng, Fei; Lu, Wenjing; Yu, Feifei; Kang, Mingjiang; Guo, Xingqi; Xu, Baohua

    2012-05-01

    Ribosomal proteins (RPs) play pivotal roles in developmental regulation. The loss or mutation of ribosomal protein L11 (RPL11) induces various developmental defects. However, few RPs have been functionally characterized in Apis cerana cerana. In this study, we isolated a single copy gene, AccRPL11, and characterized its connection to brain maturation. AccRPL11 expression was highly concentrated in the adult brain and was significantly induced by abiotic stresses such as pesticides and heavy metals. Immunofluorescence assays demonstrated that AccRPL11 was localized to the medulla, lobula and surrounding tissues of esophagus in the brain. The post-transcriptional knockdown of AccRPL11 gene expression resulted in a severe decrease in adult brain than in other tissues. The expression levels of other brain development-related genes, p38, ERK2, CacyBP and CREB, were also reduced. Immunofluorescence signal attenuation was also observed in AccRPL11-rich regions of the brain in dsAccRPL11-injected honeybees. Taken together, these results suggest that AccRPL11 may be functional in brain maturation in honeybee adults.

  3. Ribosomal protein L11 is related to brain maturation during the adult phase in Apis cerana cerana (Hymenoptera, Apidae)

    NASA Astrophysics Data System (ADS)

    Meng, Fei; Lu, Wenjing; Yu, Feifei; Kang, Mingjiang; Guo, Xingqi; Xu, Baohua

    2012-05-01

    Ribosomal proteins (RPs) play pivotal roles in developmental regulation. The loss or mutation of ribosomal protein L11 ( RPL11) induces various developmental defects. However, few RPs have been functionally characterized in Apis cerana cerana. In this study, we isolated a single copy gene, AccRPL11, and characterized its connection to brain maturation. AccRPL11 expression was highly concentrated in the adult brain and was significantly induced by abiotic stresses such as pesticides and heavy metals. Immunofluorescence assays demonstrated that AccRPL11 was localized to the medulla, lobula and surrounding tissues of esophagus in the brain. The post-transcriptional knockdown of AccRPL11 gene expression resulted in a severe decrease in adult brain than in other tissues. The expression levels of other brain development-related genes, p38, ERK2, CacyBP and CREB, were also reduced. Immunofluorescence signal attenuation was also observed in AccRPL11-rich regions of the brain in ds AccRPL11-injected honeybees. Taken together, these results suggest that AccRPL11 may be functional in brain maturation in honeybee adults.

  4. Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging.

    PubMed

    Voss, Michelle W; Weng, Timothy B; Burzynska, Agnieszka Z; Wong, Chelsea N; Cooke, Gillian E; Clark, Rachel; Fanning, Jason; Awick, Elizabeth; Gothe, Neha P; Olson, Erin A; McAuley, Edward; Kramer, Arthur F

    2016-05-01

    Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the default mode network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks.

  5. The brain and the braincase: a spatial analysis on the midsagittal profile in adult humans.

    PubMed

    Bruner, Emiliano; Amano, Hideki; de la Cuétara, José Manuel; Ogihara, Naomichi

    2015-09-01

    The spatial relationships between brain and braincase represent a major topic in surgery and evolutionary neuroanatomy. In paleoneurology, neurocranial landmarks are often used as references for brain areas. In this study, we analyze the variation and covariation of midsagittal brain and skull coordinates in a sample of adult modern humans in order to demonstrate spatial associations between hard and soft tissues. The correlation between parietal lobe size and parietal bone size is very low, and there is a marked individual variation. The distances between lobes and bones are partially influenced by the dimensions of the parietal lobes. The main pattern of morphological variability among individuals, associated with the size of the precuneus, apparently does not influence the position of the neurocranial sutures. Therefore, variations in precuneal size modify the distance between the paracentral lobule and bregma, and between the parietal lobe and lambda. Hence, the relative position of the cranial and cerebral landmarks can change as a function of the parietal dimensions. The slight correlation and covariation among these elements suggests a limited degree of spatial integration between soft and hard tissues. Therefore, although the brain influences the cranial size and shape during morphogenesis, the specific position of the cerebral components is sensitive to multiple effects and local factors, without a strict correspondence with the bone landmarks. This absence of correspondent change between brain and skull boundaries suggests caution when making inferences about the brain areas from the position of the cranial sutures. The fact that spatial relationships between cranial and brain areas may vary according to brain proportions must be considered in paleoneurology, when brain anatomy is inferred from cranial evidence.

  6. Neuroanatomical distribution of galectin-3 in the adult rat brain.

    PubMed

    Yoo, Hong-Il; Kim, Eu-Gene; Lee, Eun-Jin; Hong, Sung-Young; Yoon, Chi-Sun; Hong, Min-Ju; Park, Sang-Jin; Woo, Ran-Sook; Baik, Tai-Kyoung; Song, Dae-Yong

    2017-04-01

    Galectin-3 is a member of the lectin subfamily that enables the specific binding of β-galactosides. It is expressed in a broad spectrum of species and organs, and is known to have various functions related to cell adhesion, signal transduction, and proinflammatory responses. Although, expression of galectin-3 in some activated neuroglia under neuroinflammation has been well documented in the central nervous system, little is known about the neuronal expression and distribution of galectin-3 in normal brain. To describe the cellular and neuroanatomical expression map of galectin-3, we performed galectin-3 immunohistochemistry on the entire normal rat brain and subsequently analyzed the neuronal distribution. Galectin-3 expression was observed not only in some neuroglia but also in neurons. Neuronal expression of galectin-3 was observed in many functional parts of the cerebral cortex and various other subcortical nuclei in the hypothalamus and brainstem. Neuroanatomical analysis revealed that robust galectin-3 immuno-signals were present in many hypothalamic nuclei related to a variety of physiological functions responsible for mediating anxiety responses, energy balance, and neuroendocrine regulation. In addition, the regions highly connected with these hypothalamic nuclei also showed intense galectin-3 expression. Moreover, multiple key regions involved in regulating autonomic functions exhibited high levels of galectin-3 expression. In contrast, the subcortical nuclei responsible for the control of voluntary motor functions and limbic system exhibited no galectin-3 immunoreactivity. These observations suggest that galectin-3 expression in the rat brain seems to be regulated by developmental cascades, and that functionally and neuroanatomically related brain nuclei constitutively express galectin-3 in adulthood.

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

    ERIC Educational Resources Information Center

    Omarzu, Julia

    2004-01-01

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

  8. Structure and function of large-scale brain systems.

    PubMed

    Koziol, Leonard F; Barker, Lauren A; Joyce, Arthur W; Hrin, Skip

    2014-01-01

    This article introduces the functional neuroanatomy of large-scale brain systems. Both the structure and functions of these brain networks are presented. All human behavior is the result of interactions within and between these brain systems. This system of brain function completely changes our understanding of how cognition and behavior are organized within the brain, replacing the traditional lesion model. Understanding behavior within the context of brain network interactions has profound implications for modifying abstract constructs such as attention, learning, and memory. These constructs also must be understood within the framework of a paradigm shift, which emphasizes ongoing interactions within a dynamically changing environment.

  9. Traumatic Brain Injury Severity Affects Neurogenesis in Adult Mouse Hippocampus.

    PubMed

    Wang, Xiaoting; Gao, Xiang; Michalski, Stephanie; Zhao, Shu; Chen, Jinhui

    2016-04-15

    Traumatic brain injury (TBI) has been proven to enhance neural stem cell (NSC) proliferation in the hippocampal dentate gyrus. However, various groups have reported contradictory results on whether TBI increases neurogenesis, partially due to a wide range in the severities of injuries seen with different TBI models. To address whether the severity of TBI affects neurogenesis in the injured brain, we assessed neurogenesis in mouse brains receiving different severities of controlled cortical impact (CCI) with the same injury device. The mice were subjected to mild, moderate, or severe TBI by a CCI device. The effects of TBI severity on neurogenesis were evaluated at three stages: NSC proliferation, immature neurons, and newly-generated mature neurons. The results showed that mild TBI did not affect neurogenesis at any of the three stages. Moderate TBI promoted NSC proliferation without increasing neurogenesis. Severe TBI increased neurogenesis at all three stages. Our data suggest that the severity of injury affects adult neurogenesis in the hippocampus, and thus it may partially explain the inconsistent results of different groups regarding neurogenesis following TBI. Further understanding the mechanism of TBI-induced neurogenesis may provide a potential approach for using endogenous NSCs to protect against neuronal loss after trauma.

  10. Fast Optical Imaging of Human Brain Function

    PubMed Central

    Gratton, Gabriele; Fabiani, Monica

    2010-01-01

    Great advancements in brain imaging during the last few decades have opened a large number of new possibilities for neuroscientists. The most dominant methodologies (electrophysiological and magnetic resonance-based methods) emphasize temporal and spatial information, respectively. However, theorizing about brain function has recently emphasized the importance of rapid (within 100 ms or so) interactions between different elements of complex neuronal networks. Fast optical imaging, and in particular the event-related optical signal (EROS, a technology that has emerged over the last 15 years) may provide descriptions of localized (to sub-cm level) brain activity with a temporal resolution of less than 100 ms. The main limitations of EROS are its limited penetration, which allows us to image cortical structures not deeper than 3 cm from the surface of the head, and its low signal-to-noise ratio. Advantages include the fact that EROS is compatible with most other imaging methods, including electrophysiological, magnetic resonance, and trans-cranial magnetic stimulation techniques, with which can be recorded concurrently. In this paper we present a summary of the research that has been conducted so far on fast optical imaging, including evidence for the possibility of recording neuronal signals with this method, the properties of the signals, and various examples of applications to the study of human cognitive neuroscience. Extant issues, controversies, and possible future developments are also discussed. PMID:20631845

  11. Electrophysiological Properties of Subventricular Zone Cells in Adult Mouse Brain

    PubMed Central

    Lai, Bin; Mao, Xiao Ou; Xie, Lin; Chang, Su-Youne; Xiong, Zhi-Gang; Jin, Kunlin; Greenberg, David A.

    2010-01-01

    The subventricular zone (SVZ) is a principal site of adult neurogenesis and appears to participate in the brain’s response to injury. Thus, measures that enhance SVZ neurogenesis may have a role in treatment of neurological disease. To better characterize SVZ cells and identify potential targets for therapeutic intervention, we studied electrophysiological properties of SVZ cells in adult mouse brain slices using patch-clamp techniques. Electrophysiology was correlated with immunohistochemical phenotype by injecting cells with lucifer yellow and by studying transgenic mice carrying green fluorescent protein under control of the doublecortin (DCX) or glial fibrillary acidic protein (GFAP) promoter. We identified five types of cells in the adult mouse SVZ: type 1 cells, with 4-aminopyridine (4-AP)/tetraethylammonium (TEA)-sensitive and CdCl2-sensitive inward currents; type 2 cells, with Ca2+-sensitive K+ and both 4-AP/TEA-sensitive and -insensitive currents; type 3 cells, with 4-AP/TEA-sensitive and -insensitive and small Na+ currents; type 4 cells, with slowly activating, large linear outward current and sustained outward current without fast-inactivating component; and type 5 cells, with a large outward rectifying current with a fast inactivating component. Type 2 and 3 cells expressed DCX, types 4 and 5 cells expressed GFAP, and type 1 cells expressed neither. We propose that SVZ neurogenesis involves a progression of electrophysiological cell phenotypes from types 4 and 5 cells (astrocytes) to type 1 cells (neuronal progenitors) to types 2 and 3 cells (nascent neurons), and that drugs acting on. ion channels expressed during neurogenesis might promote therapeutic neurogenesis in the injured brain. PMID:20434436

  12. Acquisition of Visual Perception in Blind Adults Using the BrainPort Artificial Vision Device

    PubMed Central

    Pintar, Christine; Arnoldussen, Aimee; Fisher, Christopher

    2015-01-01

    OBJECTIVE. We sought to determine whether intensive low vision rehabilitation would confer any functional improvement in a sample of blind adults using the BrainPort artificial vision device. METHOD. Eighteen adults ages 28–69 yr (n = 10 men and n = 8 women) who had light perception only or worse vision bilaterally spent up to 6 hr per day for 1 wk undergoing structured rehabilitation interventions. The functional outcomes of object identification and word recognition were tested at baseline and after rehabilitation training. RESULTS. At baseline, participants were unable to complete the two functional assessments. After participation in the 1-wk training protocol, participants were able to use the BrainPort device to complete the two tasks with moderate success. CONCLUSION. Without training, participants were not able to perform above chance level using the BrainPort device. As artificial vision technologies become available, occupational therapy practitioners can play a key role in clients’ success or failure in using these devices. PMID:25553750

  13. Language of the aging brain: Event-related potential studies of comprehension in older adults

    PubMed Central

    Wlotko, Edward W.; Lee, Chia-Lin; Federmeier, Kara D.

    2010-01-01

    Normal aging brings increased richness in knowledge and experience as well as declines in cognitive abilities. Event-related brain potential (ERP) studies of language comprehension corroborate findings showing that the structure and organization of semantic knowledge remains relatively stable with age. Highlighting the advantages of the temporal and functional specificity of ERPs, this survey focuses on age-related changes in higher-level processes required for the successful comprehension of meaning representations built from multiple words. Older adults rely on different neural pathways and cognitive processes during normal, everyday comprehension, including a shift away from the predictive use of sentential context, differential recruitment of neural resources, and reduced engagement of controlled processing. Within age groups, however, there are important individual differences that, for example, differentiate a subset of older adults whose processing patterns more closely resemble that of young adults, providing a window into cognitive skills and abilities that may mediate or moderate age-related declines. PMID:20823949

  14. Functional literacy of Young Guyanese Adults

    NASA Astrophysics Data System (ADS)

    Jennings, Zellyne

    2000-05-01

    Functional literacy is interpreted as the ability of the individual to apply skills in reading, writing, calculation and basic problem-solving in those activities in which literacy is required for effective functioning in his/her own group and community. The paper describes the rationale, development and administration of the test used for measuring levels (high, moderate, low) of achievement in functional literacy in three domains (document, prose and quantitative). An assumption of the study was that a high level of functional literacy was required for the individual to function effectively in his/her own group and community. The context of the study is Guyana the most underdeveloped and impoverished country in the English-speaking Caribbean. The subjects are out of school youth in Guyana aged 14-25. Amongst the main findings are: only approximately 11% of the young people show a high level of functional literacy; females tend to have a higher level of functional literacy than males: and most of those at the low level never went beyond primary and low status secondary schools and usually end up unemployed or in semi- or unskilled jobs. Attention is drawn to the difficulty of attracting funding for literacy programmes from international aid agencies, given the inflated adult literacy rate which is reported for Guyana in international statistics. While they credit Guyana with an adult literacy rate of 97.5%, the study suggests that a more realistic figure is in the 70s. The importance of adult and continuing education is underscored in view of the need to help those who are out of school to meet the ever-changing demands of society for improved skills in literacy and numeracy.

  15. Canonical Genetic Signatures of the Adult Human Brain

    PubMed Central

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

    2015-01-01

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

  16. Functional communication screening in individuals with traumatic brain injury.

    PubMed

    Drummond, Sakina S; Boss, Michelle R

    2004-01-01

    The feasibility of a novel instrument, the Functional Communication Scale (FCS), was determined for individuals with moderate-to-mild cognitive-communication deficits secondary to traumatic brain injury (TBI). A group design including 30 adults with confirmed diagnosis and communication problems was utilized. Conversational samples with each participant were videotaped and rated for 13 FCS items. Three raters with diverse clinical experiences rated the elicited samples. Results identified significant and positive relationships between the cognitive-communication severities and the total FCS scores. Significant inter- and intra-rater reliability scores were found for the three raters. The FCS also determined significant differences between individuals with and without concurrent aphasia or dysarthria. No obvious differences were found between males and females nor between individuals with the primary diagnosis of TBI vs other neurological aetiologies. These findings have implications for assessing the adequacy of functional communication of individuals who are candidates for community re-entry.

  17. Hippocampal Brain Volume Is Associated with Faster Facial Emotion Identification in Older Adults: Preliminary Results

    PubMed Central

    Szymkowicz, Sarah M.; Persson, Jonas; Lin, Tian; Fischer, Håkan; Ebner, Natalie C.

    2016-01-01

    Quick correct identification of facial emotions is highly relevant for successful social interactions. Research suggests that older, compared to young, adults experience increased difficulty with face and emotion processing skills. While functional neuroimaging studies suggest age differences in neural processing of faces and emotions, evidence about age-associated structural brain changes and their involvement in face and emotion processing is scarce. Using structural magnetic resonance imaging (MRI), this study investigated the extent to which volumes of frontal and temporal brain structures were related to reaction time in accurate identification of facial emotions in 30 young and 30 older adults. Volumetric segmentation was performed using FreeSurfer and gray matter volumes from frontal and temporal regions were extracted. Analysis of covariances (ANCOVAs) models with response time (RT) as the dependent variable and age group and regional volume, and their interaction, as independent variables were conducted, controlling for total intracranial volume (ICV). Results indicated that, in older adults, larger hippocampal volumes were associated with faster correct facial emotion identification. These preliminary observations suggest that greater volume in brain regions associated with face and emotion processing contributes to improved facial emotion identification performance in aging. PMID:27610082

  18. Acute effects of aerobic exercise on cognitive function in older adults.

    PubMed

    Kamijo, Keita; Hayashi, Yoichi; Sakai, Tomoaki; Yahiro, Tatsuhisa; Tanaka, Kiyoji; Nishihira, Yoshiaki

    2009-05-01

    The present study investigated the effects of acute aerobic exercise on cognitive brain functions of older adults. Twenty-four males (12 older and 12 younger adults) performed a modified flanker task during a baseline session (no exercise) and after light and moderate cycling exercise in counterbalanced order on different days while measures of task performance and the P3 component of an event-related brain potential were collected. The results indicated that, for both age groups, reaction time following moderate exercise was shorter relative to the other sessions, and P3 latencies following both light and moderate exercise were shorter compared with the baseline session. In contrast, P3 amplitude increased only following moderate exercise in younger adults. These findings suggest that light and moderate exercises improve cognitive function across the adult lifespan, although the mechanisms underlying the effects of observed acute aerobic exercise on cognitive function may be age dependent.

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

    PubMed

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

    2016-04-01

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

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

    PubMed Central

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

    2016-01-01

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

  1. Largely typical patterns of resting-state functional connectivity in high-functioning adults with autism.

    PubMed

    Tyszka, J Michael; Kennedy, Daniel P; Paul, Lynn K; Adolphs, Ralph

    2014-07-01

    A leading hypothesis for the neural basis of autism postulates globally abnormal brain connectivity, yet the majority of studies report effects that are either very weak, inconsistent across studies, or explain results incompletely. Here we apply multiple analytical approaches to resting-state BOLD-fMRI data at the whole-brain level. Neurotypical and high-functioning adults with autism displayed very similar patterns and strengths of resting-state connectivity. We found only limited evidence in autism for abnormal resting-state connectivity at the regional level and no evidence for altered connectivity at the whole-brain level. Regional abnormalities in functional connectivity in autism spectrum disorder were primarily in the frontal and temporal cortices. Within these regions, functional connectivity with other brain regions was almost exclusively lower in the autism group. Further examination showed that even small amounts of head motion during scanning have large effects on functional connectivity measures and must be controlled carefully. Consequently, we suggest caution in the interpretation of apparent positive findings until all possible confounding effects can be ruled out. Additionally, we do not rule out the possibility that abnormal connectivity in autism is evident at the microstructural synaptic level, which may not be reflected sensitively in hemodynamic changes measured with BOLD-fMRI.

  2. Neurobiological markers of exercise-related brain plasticity in older adults.

    PubMed

    Voss, Michelle W; Erickson, Kirk I; Prakash, Ruchika Shaurya; Chaddock, Laura; Kim, Jennifer S; Alves, Heloisa; Szabo, Amanda; Phillips, Siobhan M; Wójcicki, Thomas R; Mailey, Emily L; Olson, Erin A; Gothe, Neha; Vieira-Potter, Victoria J; Martin, Stephen A; Pence, Brandt D; Cook, Marc D; Woods, Jeffrey A; McAuley, Edward; Kramer, Arthur F

    2013-02-01

    The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, and (b) the extent to which pre-intervention growth factor levels were associated with training-related changes in functional connectivity. In 65 participants (mean age=66.4), we found that although there were no group-level changes in growth factors as a function of the intervention, increased temporal lobe connectivity between the bilateral parahippocampus and the bilateral middle temporal gyrus was associated with increased BDNF, IGF-1, and VEGF for an aerobic walking group but not for a non-aerobic control group, and greater pre-intervention VEGF was associated with greater training-related increases in this functional connection. Results are consistent with animal models of exercise and the brain, but are the first to show in humans that exercise-induced increases in temporal lobe functional connectivity are associated with changes in growth factors and may be augmented by greater baseline VEGF.

  3. New Perspectives on Genomic Imprinting, an Essential and Multifaceted Mode of Epigenetic Control in the Developing and Adult Brain

    PubMed Central

    Perez, Julio D.; Rubinstein, Nimrod D.; Dulac, Catherine

    2016-01-01

    Mammalian evolution entailed multiple innovations in gene regulation, including the emergence of genomic imprinting, an epigenetic regulation leading to the preferential expression of a gene from its maternal or paternal allele. Genomic imprinting is highly prevalent in the brain, yet, until recently, its central roles in neural processes have not been fully appreciated. Here, we provide a comprehensive survey of adult and developmental brain functions influenced by imprinted genes, from neural development and wiring to synaptic function and plasticity, energy balance, social behaviors, emotions, and cognition. We further review the widespread identification of parental biases alongside monoallelic expression in brain tissues, discuss their potential roles in dosage regulation of key neural pathways, and suggest possible mechanisms underlying the dynamic regulation of imprinting in the brain. This review should help provide a better understanding of the significance of genomic imprinting in the normal and pathological brain of mammals including humans. PMID:27145912

  4. Functional brain networks involved in reality monitoring.

    PubMed

    Metzak, Paul D; Lavigne, Katie M; Woodward, Todd S

    2015-08-01

    Source monitoring refers to the recollection of variables that specify the context and conditions in which a memory episode was encoded. This process involves using the qualitative and quantitative features of a memory trace to distinguish its source. One specific class of source monitoring is reality monitoring, which involves distinguishing internally generated from externally generated information, that is, memories of imagined events from real events. The purpose of the present study was to identify functional brain networks that underlie reality monitoring, using an alternative type of source monitoring as a control condition. On the basis of previous studies on self-referential thinking, it was expected that a medial prefrontal cortex (mPFC) based network would be more active during reality monitoring than the control condition, due to the requirement to focus on a comparison of internal (self) and external (other) source information. Two functional brain networks emerged from this analysis, one reflecting increasing task-related activity, and one reflecting decreasing task-related activity. The second network was mPFC based, and was characterized by task-related deactivations in areas resembling the default-mode network; namely, the mPFC, middle temporal gyri, lateral parietal regions, and the precuneus, and these deactivations were diminished during reality monitoring relative to source monitoring, resulting in higher activity during reality monitoring. This result supports previous research suggesting that self-referential thinking involves the mPFC, but extends this to a network-level interpretation of reality monitoring.

  5. Phosphatidylserine in the brain: metabolism and function.

    PubMed

    Kim, Hee-Yong; Huang, Bill X; Spector, Arthur A

    2014-10-01

    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, and this reaction is 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.

  6. Early Brain Stimulation May Help Stroke Survivors Recover Language Function

    MedlinePlus

    ... Making News on Heart.org Learn More Early brain stimulation may help stroke survivors recover language function ... org and strokeassociation.org Related Images Infographic - Thiel-Brain Stimulation copyright American Heart Association Download (311.8 ...

  7. Methylene blue modulates functional connectivity in the human brain.

    PubMed

    Rodriguez, Pavel; Singh, Amar P; Malloy, Kristen E; Zhou, Wei; Barrett, Douglas W; Franklin, Crystal G; Altmeyer, Wilson B; Gutierrez, Juan E; Li, Jinqi; Heyl, Betty L; Lancaster, Jack L; Gonzalez-Lima, F; Duong, Timothy Q

    2016-03-10

    Methylene blue USP (MB) is a FDA-grandfathered drug used in clinics to treat methemoglobinemia, carbon monoxide poisoning and cyanide poisoning that has been shown to increase fMRI evoked blood oxygenation level dependent (BOLD) response in rodents. Low dose MB also has memory enhancing effect in rodents and humans. However, the neural correlates of the effects of MB in the human brain are unknown. We tested the hypothesis that a single low oral dose of MB modulates the functional connectivity of neural networks in healthy adults. Task-based and task-free fMRI were performed before and one hour after MB or placebo administration utilizing a randomized, double-blinded, placebo-controlled design. MB administration was associated with a reduction in cerebral blood flow in a task-related network during a visuomotor task, and with stronger resting-state functional connectivity in multiple regions linking perception and memory functions. These findings demonstrate for the first time that low-dose MB can modulate task-related and resting-state neural networks in the human brain. These neuroimaging findings support further investigations in healthy and disease populations.

  8. Dietary boron, brain function, and cognitive performance.

    PubMed Central

    Penland, J G

    1994-01-01

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

  9. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

    PubMed

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P < 0.001), anterior vermis (40%, P < 0.001) and fusiform gyrus (20%, P < 0.001) compared with controls or siblings, and lower metabolism in hippocampus (12%, P = 0.05) compared with controls, and showed significant intersubject variability (decreases in vermis ranged from 18% to 60%). Participants with ataxia-telangiectasia also had higher metabolism in globus pallidus (16%, P = 0.05), which correlated negatively with motor performance. Asymptomatic relatives had lower metabolism in anterior vermis (12%; P = 0.01) and hippocampus (19%; P = 0.002) than controls. Our results indicate that, in addition to the expected decrease in cerebellar metabolism, participants with ataxia-telangiectasia had widespread changes in metabolic

  10. Brain self-protection: the role of endogenous neural progenitor cells in adult brain after cerebral cortical ischemia.

    PubMed

    Li, Bin; Piao, Chun-Shu; Liu, Xiao-Yun; Guo, Wen-Ping; Xue, Yue-Qiang; Duan, Wei-Ming; Gonzalez-Toledo, Maria E; Zhao, Li-Ru

    2010-04-23

    Convincing evidence has shown that brain ischemia causes the proliferation of neural stem cells/neural progenitor cells (NSCs/NPCs) in both the subventricular zone (SVZ) and the subgranular zone (SGZ) of adult brain. The role of brain ischemia-induced NSC/NPC proliferation, however, has remained unclear. Here we have determined whether brain ischemia-induced amplification of the NSCs/NPCs in adult brain is required for brain self-protection. The approach of intracerebroventricular (ICV) infusion of cytosine arabinoside (Ara-C), an inhibitor for cell proliferation, for the first 7days after brain ischemia was used to block ischemia-induced NSC/NPC proliferation. We observed that ICV infusion of Ara-C caused a complete blockade of NSC/NPC proliferation in the SVZ and a dramatic reduction of NSC/NPC proliferation in the SGZ. Additionally, as a result of the inhibition of ischemia-induced NSC/NPC pool amplification, the number of neurons in the hippocampal CA1 and CA3 was significantly reduced, the infarction size was significantly enlarged, and neurological deficits were significantly worsened after focal brain ischemia. We also found that an NSC/NPC-conditioned medium showed neuroprotective effects in vitro and that adult NSC/NPC-released brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) are required for NSC/NPC-conditioned medium-induced neuroprotection. These data suggest that NSC/NPC-generated trophic factors are neuroprotective and that brain ischemia-triggered NSC/NPC proliferation is crucial for brain protection. This study provides insights into the contribution of endogenous NSCs/NPCs to brain self-protection in adult brain after ischemia injury.

  11. Order and disorder in the brain function.

    PubMed

    Quadens, Olga

    2003-01-01

    The interest in studying the brain electrical activity as a function of the development of intelligence has been spurred by the need to understand how the brain responds to environmental information. The description of sleep in mentally retarded children reveals deviant patterns of the EEG-spindles and of the eye movement activity (REM sleep) when compared to normal children. The patterns may be considered as a valuable index of mental function. According to experimental evidence, the distribution of the eye movements of sleep appears either as random or ordered. The latter are altered in the mentally handicapped in whom the appearance out of chaos, of the order which is needed for intelligence and memory to function, is altered. The sleep signs are redundant as from birth. Their pattern is also related to the psychomotor development of the infant. If their distribution remains random, or appears in long uninterrupted sequences of waves as in epilepsy, intelligence does not develop. A similar strategy appears to function in the foetus when nature organizes the structures that will lead to the development of intelligence. The eye movement patterns of sleep change in the pregnant women as a function of term and resemble those of premature babies of a similar gestational age. They also change as a function of the menstrual cycle and more generally as a function of age. The hypothesis that attention is the diurnal equivalent of REM sleep is discussed. Attempts at modelling the eye movement patterns of REM sleep as a function of near zero gravity environments have been made. 1) By means of a Montecarlo simulation using the semi Markov model during the Spacelab 1 flight. 2) With the method of the single and multiple g-phase transition analysis of the strange attractor dimension (d) during parabolic flights. The implication of the latter for the neural processes involved in learning is that the central nervous system can preserve intact, from input to output, over a

  12. Mismatch negativity, social cognition, and functional outcomes in patients after traumatic brain injury

    PubMed Central

    Sun, Hui-yan; Li, Qiang; Chen, Xi-ping; Tao, Lu-yang

    2015-01-01

    Mismatch negativity is generated automatically, and is an early monitoring indicator of neuronal integrity impairment and functional abnormality in patients with brain injury, leading to decline of cognitive function. Antipsychotic medication cannot affect mismatch negativity. The present study aimed to explore the relationships of mismatch negativity with neurocognition, daily life and social functional outcomes in patients after brain injury. Twelve patients with traumatic brain injury and 12 healthy controls were recruited in this study. We examined neurocognition with the Wechsler Adult Intelligence Scale-Revised China, and daily and social functional outcomes with the Activity of Daily Living Scale and Social Disability Screening Schedule, respectively. Mismatch negativity was analyzed from electroencephalogram recording. The results showed that mismatch negativity amplitudes decreased in patients with traumatic brain injury compared with healthy controls. Mismatch negativity amplitude was negatively correlated with measurements of neurocognition and positively correlated with functional outcomes in patients after traumatic brain injury. Further, the most significant positive correlations were found between mismatch negativity in the fronto-central region and measures of functional outcomes. The most significant positive correlations were also found between mismatch negativity at the FCz electrode and daily living function. Mismatch negativity amplitudes were extremely positively associated with Social Disability Screening Schedule scores at the Fz electrode in brain injury patients. These experimental findings suggest that mismatch negativity might efficiently reflect functional outcomes in patients after traumatic brain injury. PMID:26170824

  13. CILIA FORMATION IN THE ADULT CAT BRAIN AFTER PARGYLINE TREATMENT

    PubMed Central

    Milhaud, Monique; Pappas, George D.

    1968-01-01

    The brains of four adult cats treated with pargyline (a nonhydrazide monoaminoxidase inhibitor) were examined at both the light and electron microscopic levels. Formation of typical mature cilia with the 9 + 2 pattern was observed in neural cells in the following areas: habenula nuclei, interpeduncular nuclei, hippocampus, mammillary bodies, thalamus, and caudate nucleus. The most marked ciliation occurs in the habenula nuclei. In general, glial cells greatly predominate in the formation of cilia. It is not clear whether ciliation in the central nervous system is the direct result of pargyline or if it occurs indirectly as a result of inhibition of monoaminoxidase. These findings are compared with the serotonin effect on ciliation in the embryogenesis of lower forms. It is suggested that pharmacological stimulation of centriolar reproduction without subsequent mitosis may lead to ciliary formation. PMID:11905194

  14. A model for genomic imprinting in the social brain: adults.

    PubMed

    Ubeda, Francisco; Gardner, Andy

    2011-02-01

    Genomic imprinting refers to genes that are silenced when inherited via sperm or via egg. The silencing of genes conditional upon their parental origin requires an evolutionary explanation. The most widely accepted theory for the evolution of genomic imprinting-the kinship theory-argues that conflict between maternally inherited and paternally inherited genes over phenotypes with asymmetric effects on matrilineal and patrilineal kin results in self-imposed silencing of one of the copies. This theory has been applied to imprinting of genes expressed in the placenta, and infant brain determining the allocation of parental resources being the source of conflict parental promiscuity. However, there is growing evidence that imprinted genes are expressed in the postinfant brain where parental promiscuity per se is no longer a source of conflict. Here, we advance the kinship theory by developing an evolutionary model of genomic imprinting in adults, driven by intragenomic conflict over allocation to parental versus communal care. We consider the role of sex differences in dispersal and variance in reproductive success as sources of conflict. We predict that, in hominids and birds, parental care will be expressed by maternally inherited genes. In nonhominid mammals, we predict more diversity, with some mammals showing the same pattern and other showing the reverse. We use the model to interpret experimental data on imprinted genes in the house mouse: specifically, paternally expressed Peg1 and Peg3 genes, underlying maternal care, and maternally expressed Gnas and paternally expressed Gnasxl genes, underlying communal care. We also use the model to relate ancestral demography to contemporary imprinting disorders of adults, in humans and other taxa.

  15. Brain microvascular function during cardiopulmonary bypass

    SciTech Connect

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

    1987-11-01

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

  16. Low level methylmercury exposure affects neuropsychological function in adults

    PubMed Central

    Yokoo, Edna M; Valente, Joaquim G; Grattan, Lynn; Schmidt, Sérgio Luís; Platt, Illeane; Silbergeld, Ellen K

    2003-01-01

    Background The neurotoxic effects of methylmercury (MeHg) have been demonstrated in both human and animal studies. Both adult and fetal brains are susceptible to the effects of MeHg toxicity. However, the specific effects of adult exposures have been less well-documented than those of children with prenatal exposures. This is largely because few studies of MeHg exposures in adults have used sensitive neurological endpoints. The present study reports on the results of neuropsychological testing and hair mercury concentrations in adults (>17 yrs) living in fishing communities of Baixada Cuiabana (Mato Grosso) in the Pantanal region of Brazil. Methods A cross-sectional study was conducted in six villages on the Cuiaba River. Participants included 129 men and women older than 17 years of age. They were randomly selected in proportion to the age range and number of inhabitants in each village. Questionnaire information was collected on demographic variables, including education, occupation, and residence history. Mercury exposure was determined by analysis of hair using flameless atomic absorption spectrophotometry. The neurocognitive screening battery included tests from the Wechsler Memory Scale and the Wechsler Adult Intelligence Scale, Concentrated Attention Test of the Toulouse-Pierron Factorial Battery, the Manual Ability Subtests of the Tests of Mechanical Ability, and the Profile of Mood States. Results Mercury exposures in this population were associated with fish consumption. The hair mercury concentration in the 129 subjects ranged from 0.56 to 13.6 μg/g; the mean concentration was 4.2 ± 2.4 micrograms/g and the median was 3.7 μg/g. Hair mercury levels were associated with detectable alterations in performance on tests of fine motor speed and dexterity, and concentration. Some aspects of verbal learning and memory were also disrupted by mercury exposure. The magnitude of the effects increased with hair mercury concentration, consistent with a dose

  17. Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells.

    PubMed

    Cox, Charles S; Hetz, Robert A; Liao, George P; Aertker, Benjamin M; Ewing-Cobbs, Linda; Juranek, Jenifer; Savitz, Sean I; Jackson, Margaret L; Romanowska-Pawliczek, Anna M; Triolo, Fabio; Dash, Pramod K; Pedroza, Claudia; Lee, Dean A; Worth, Laura; Aisiku, Imoigele P; Choi, Huimahn A; Holcomb, John B; Kitagawa, Ryan S

    2017-04-01

    Preclinical studies using bone marrow derived cells to treat traumatic brain injury have demonstrated efficacy in terms of blood-brain barrier preservation, neurogenesis, and functional outcomes. Phase 1 clinical trials using bone marrow mononuclear cells infused intravenously in children with severe traumatic brain injury demonstrated safety and potentially a central nervous system structural preservation treatment effect. This study sought to confirm the safety, logistic feasibility, and potential treatment effect size of structural preservation/inflammatory biomarker mitigation in adults to guide Phase 2 clinical trial design. Adults with severe traumatic brain injury (Glasgow Coma Scale 5-8) and without signs of irreversible brain injury were evaluated for entry into the trial. A dose escalation format was performed in 25 patients: 5 controls, followed 5 patients in each dosing cohort (6, 9, 12 ×10(6) cells/kg body weight), then 5 more controls. Bone marrow harvest, cell processing to isolate the mononuclear fraction, and re-infusion occurred within 48 hours after injury. Patients were monitored for harvest-related hemodynamic changes, infusional toxicity, and adverse events. Outcome measures included magnetic resonance imaging-based measurements of supratentorial and corpus callosal volumes as well as diffusion tensor imaging-based measurements of fractional anisotropy and mean diffusivity of the corpus callosum and the corticospinal tract at the level of the brainstem at 1 month and 6 months postinjury. Functional and neurocognitive outcomes were measured and correlated with imaging data. Inflammatory cytokine arrays were measured in the plasma pretreatment, posttreatment, and at 1 and 6 month follow-up. There were no serious adverse events. There was a mild pulmonary toxicity of the highest dose that was not clinically significant. Despite the treatment group having greater injury severity, there was structural preservation of critical regions of interest

  18. Resting state fMRI entropy probes complexity of brain activity in adults with ADHD.

    PubMed

    Sokunbi, Moses O; Fung, Wilson; Sawlani, Vijay; Choppin, Sabine; Linden, David E J; Thome, Johannes

    2013-12-30

    In patients with attention deficit hyperactivity disorder (ADHD), quantitative neuroimaging techniques have revealed abnormalities in various brain regions, including the frontal cortex, striatum, cerebellum, and occipital cortex. Nonlinear signal processing techniques such as sample entropy have been used to probe the regularity of brain magnetoencephalography signals in patients with ADHD. In the present study, we extend this technique to analyse the complex output patterns of the 4 dimensional resting state functional magnetic resonance imaging signals in adult patients with ADHD. After adjusting for the effect of age, we found whole brain entropy differences (P=0.002) between groups and negative correlation (r=-0.45) between symptom scores and mean whole brain entropy values, indicating lower complexity in patients. In the regional analysis, patients showed reduced entropy in frontal and occipital regions bilaterally and a significant negative correlation between the symptom scores and the entropy maps at a family-wise error corrected cluster level of P<0.05 (P=0.001, initial threshold). Our findings support the hypothesis of abnormal frontal-striatal-cerebellar circuits in ADHD and the suggestion that sample entropy is a useful tool in revealing abnormalities in the brain dynamics of patients with psychiatric disorders.

  19. Brain surface conformal parameterization with algebraic functions.

    PubMed

    Wang, Yalin; Gu, Xianfeng; Chan, Tony F; Thompson, Paul M; Yau, Shing-Tung

    2006-01-01

    In medical imaging, parameterized 3D surface models are of great interest for anatomical modeling and visualization, statistical comparisons of anatomy, and surface-based registration and signal processing. Here we introduce a parameterization method based on algebraic functions. By solving the Yamabe equation with the Ricci flow method, we can conformally map a brain surface to a multi-hole disk. The resulting parameterizations do not have any singularities and are intrinsic and stable. To illustrate the technique, we computed parameterizations of several types of anatomical surfaces in MRI scans of the brain, including the hippocampi and the cerebral cortices with various landmark curves labeled. For the cerebral cortical surfaces, we show the parameterization results are consistent with selected landmark curves and can be matched to each other using constrained harmonic maps. Unlike previous planar conformal parameterization methods, our algorithm does not introduce any singularity points. It also offers a method to explicitly match landmark curves between anatomical surfaces such as the cortex, and to compute conformal invariants for statistical comparisons of anatomy.

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

    NASA Astrophysics Data System (ADS)

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

    1999-05-01

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

  1. Functional specializations for music processing in the human newborn brain.

    PubMed

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

    2010-03-09

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

  2. APOE Polymorphism Affects Brain Default Mode Network in Healthy Young Adults

    PubMed Central

    Su, Yun Yan; Liang, Xue; Schoepf, U. Joseph; Varga-Szemes, Akos; West, Henry C.; Qi, Rongfeng; Kong, Xiang; Chen, Hui Juan; Lu, Guang Ming; Zhang, Long Jiang

    2015-01-01

    Abstract To investigate the effect of apolipoprotein E (APOE) gene polymorphism on the resting-state brain function, structure, and blood flow in healthy adults younger than 35 years, using multimodality magnetic resonance (MR) imaging. Seventy-six healthy adults (34 men, 23.7 ± 2.8 y; 31 APOE ε4/ε3 carriers, 31 ε3/ε3 carriers, and 14 ε2/ε3 carriers) were included. For resting-state functional MRI data, default mode network (DMN) and amplitude of low-frequency fluctuation maps were extracted and analyzed. Voxel-based morphometry, diffusion tensor imaging from structural imaging, and cerebral blood flow based on arterial spin labeling MR imaging were also analyzed. Correlation analysis was performed between the above mentioned brain parameters and neuropsychological tests. There were no differences in neuropsychological performances, amplitude of low-frequency fluctuation, gray/white matter volumes, fractional anisotropy, mean diffusivity, or whole brain cerebral blood flow among the 3 groups. As for DMN, the ε4/ε3 group showed increased functional connectivities (FCs) in the left medial prefrontal cortex and bilateral posterior cingulate cortices/precuneus compared with the ε3/ε3 group, and increased FCs in the left medial prefrontal cortex and right temporal lobe compared with the ε2/ε3 group (P < 0.05, Alphasim corrected). No differences of DMN FCs were found between the ε2/ε3 and ε3/ε3 groups. FCs in the right temporal lobe positively correlated with the performances of vocabulary learning, delayed recall, and graph recall in all participants (P < 0.05). APOE ε4 carriers exhibited significantly increased DMN FCs when compared with ε3 and ε2 carriers. The ε4 affects DMN FCs before brain structure and blood flow in cognitively intact young patients, suggesting DMN FC may serve as a potential biomarker for the detection of early manifestations of genetic effect. PMID:26717353

  3. Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides.

    PubMed

    Kizil, Caghan; Iltzsche, Anne; Thomas, Alvin Kuriakose; Bhattarai, Prabesh; Zhang, Yixin; Brand, Michael

    2015-01-01

    Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs) that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI), RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs) and identified two- polyR and Trans - that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael's addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues.

  4. Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides

    PubMed Central

    Thomas, Alvin Kuriakose; Bhattarai, Prabesh; Zhang, Yixin; Brand, Michael

    2015-01-01

    Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs) that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI), RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs) and identified two– polyR and Trans – that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael’s addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues. PMID:25894337

  5. Mapping Functional Connectivity in Patients with Brain Lesions

    PubMed Central

    Guggisberg, Adrian G.; Honma, Susanne M.; Findlay, Anne M.; Dalal, Sarang S.; Kirsch, Heidi E.; Berger, Mitchel S.; Nagarajan, Srikantan S.

    2013-01-01

    OBJECTIVE Although electrophysiological measures of functional connectivity between brain areas are widely used, the spatial distribution of functional interactions as well as the disturbance introduced by focal brain lesions remains poorly understood. Based on the rationale that damaged brain tissue can be expected to be disconnected from the physiological interactions among healthy areas, this study aimed to map the functionality of brain areas according to their connectivity with other areas. METHODS Magnetoencephalographic (MEG) recordings of spontaneous cortical activity during resting state were obtained from 15 consecutive patients with focal brain lesions and from 14 healthy controls. Neural activity at each volume element (voxel) in the brain was estimated using an adaptive spatial filtering technique. For each brain voxel, the mean imaginary coherence of all its connections with other brain voxels was then caluculated as an index of functional connectivity, and the results compared across brain regions and between subjects. RESULTS The magnitude of the mean imaginary coherence of all voxels and subjects was greatest in the alpha frequency range corresponding to the human cortical idling rhythm. In healthy subjects, functionally critical brain areas such as the somatosensory and language cortices had the highest alpha coherence. When compared to healthy controls, all lesion patients had diffuse or scattered brain areas with decreased coherence. Patients with lesion-induced neurological deficits displayed decreased connectivity estimates in the corresponding brain area compared to intact contralateral regions. In tumor patients without preoperative neurological deficits, brain areas showing decreased coherence could be surgically resected without the occurrence of post-surgical deficits. CONCLUSION Resting state coherence measured with MEG is capable of mapping the functional connectivity of the brain, and can therefore offer valuable information for use in

  6. 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.

  7. Progressive Gender Differences of Structural Brain Networks in Healthy Adults: A Longitudinal, Diffusion Tensor Imaging Study

    PubMed Central

    Sun, Yu; Lee, Renick; Chen, Yu; Collinson, Simon; Thakor, Nitish; Bezerianos, Anastasios; Sim, Kang

    2015-01-01

    Sexual dimorphism in the brain maturation during childhood and adolescence has been repeatedly documented, which may underlie the differences in behaviors and cognitive performance. However, our understanding of how gender modulates the development of structural connectome in healthy adults is still not entirely clear. Here we utilized graph theoretical analysis of longitudinal diffusion tensor imaging data over a five-year period to investigate the progressive gender differences of brain network topology. The brain networks of both genders showed prominent economical “small-world” architecture (high local clustering and short paths between nodes). Additional analysis revealed a more economical “small-world” architecture in females as well as a greater global efficiency in males regardless of scan time point. At the regional level, both increased and decreased efficiency were found across the cerebral cortex for both males and females, indicating a compensation mechanism of cortical network reorganization over time. Furthermore, we found that weighted clustering coefficient exhibited significant gender-time interactions, implying different development trends between males and females. Moreover, several specific brain regions (e.g., insula, superior temporal gyrus, cuneus, putamen, and parahippocampal gyrus) exhibited different development trajectories between males and females. Our findings further prove the presence of sexual dimorphism in brain structures that may underlie gender differences in behavioral and cognitive functioning. The sex-specific progress trajectories in brain connectome revealed in this work provide an important foundation to delineate the gender related pathophysiological mechanisms in various neuropsychiatric disorders, which may potentially guide the development of sex-specific treatments for these devastating brain disorders. PMID:25742013

  8. Functional involvement of cerebral cortex in adult sleepwalking.

    PubMed

    Oliviero, A; Della Marca, G; Tonali, P A; Pilato, F; Saturno, E; Dileone, M; Rubino, M; Di Lazzaro, V

    2007-08-01

    The pathophysiology of adult sleepwalking is still poorly understood. However, it is widely accepted that sleepwalking is a disorder of arousal. Arousal circuits widely project to the cortex, including motor cortex. We hypothesized that functional abnormality of these circuits could lead to changes in cortical excitability in sleepwalkers, even during wakefulness. We used transcranial magnetic stimulation (TMS) to examine the excitability of the human motor cortex during wakefulness in a group of adult sleepwalkers. When compared with the healthy control group, short interval intracortical inhibition (SICI), cortical silent period (CSP) duration, and short latency afferent inhibition (SAI) were reduced in adult sleepwalkers during wakefulness. Mean CSP duration was shorter in patients than in controls (80.9 +/- 41 ms vs. 139.4 +/- 37 ms; p = 0.0040). Mean SICI was significantly reduced in patients than in controls (73.5 +/- 38.4% vs. 36.7 +/- 13.1%; p = 0.0061). Mean SAI was also significantly reduced in patients than in controls (65.8 +/- 14.2% vs. 42.8 +/- 16.9%; p = 0.0053). This neurophysiological study suggests that there are alterations in sleepwalkers consistent with an impaired efficiency of inhibitory circuits during wakefulness. This inhibitory impairment could represent the neurophysiological correlate of brain "abnormalities" of sleepwalkers like "immaturity" of some neural circuits, synapses, or receptors.

  9. Mapping distributed brain function and networks with diffuse optical tomography

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

  10. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    PubMed

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc.

  11. Brain activation changes during locomotion in middle-aged to older adults with multiple sclerosis.

    PubMed

    Hernandez, Manuel E; Holtzer, Roee; Chaparro, Gioella; Jean, Kharine; Balto, Julia M; Sandroff, Brian M; Izzetoglu, Meltem; Motl, Robert W

    2016-11-15

    Mobility and cognitive impairments are common in persons with multiple sclerosis (MS), and are expected to worsen with increasing age. However, no studies, to date, in part due to limitations of conventional neuroimaging methods, have examined changes in brain activation patterns during active locomotion in older patients with MS. This study used functional Near Infrared Spectroscopy (fNIRS) to evaluate real-time neural activation differences in the pre-frontal cortex (PFC) between middle-aged to older adults with MS and healthy controls during single (Normal Walk; NW) and dual-task (Walking While Talking; WWT) locomotion tasks. Eight middle-aged to older adults with MS and eight healthy controls underwent fNIRS recording while performing the NW and WWT tasks with an fNIRS cap consisting of 16 optodes positioned over the forehead. The MS group had greater elevations in PFC oxygenation levels during WWT compared to NW than healthy controls. There was no walking performance difference between groups during locomotion. These findings suggest that middle-aged to older individuals with MS might be able to achieve similar levels of performance through the use of increased brain activation. This study is the first to investigate brain activation changes during the performance of simple and divided-attention locomotion tasks in MS using fNIRS.

  12. Dopamine from the brain promotes spinal motor neuron generation during development and adult regeneration.

    PubMed

    Reimer, Michell M; Norris, Anneliese; Ohnmacht, Jochen; Patani, Rickie; Zhong, Zhen; Dias, Tatyana B; Kuscha, Veronika; Scott, Angela L; Chen, Yu-Chia; Rozov, Stanislav; Frazer, Sarah L; Wyatt, Cameron; Higashijima, Shin-ichi; Patton, E Elizabeth; Panula, Pertti; Chandran, Siddharthan; Becker, Thomas; Becker, Catherina G

    2013-06-10

    Coordinated development of brain stem and spinal target neurons is pivotal for the emergence of a precisely functioning locomotor system. Signals that match the development of these far-apart regions of the central nervous system may be redeployed during spinal cord regeneration. Here we show that descending dopaminergic projections from the brain promote motor neuron generation at the expense of V2 interneurons in the developing zebrafish spinal cord by activating the D4a receptor, which acts on the hedgehog pathway. Inhibiting this essential signal during early neurogenesis leads to a long-lasting reduction of motor neuron numbers and impaired motor responses of free-swimming larvae. Importantly, during successful spinal cord regeneration in adult zebrafish, endogenous dopamine promotes generation of spinal motor neurons, and dopamine agonists augment this process. Hence, we describe a supraspinal control mechanism for the development and regeneration of specific spinal cell types that uses dopamine as a signal.

  13. Micromanipulation of gene expression in the adult zebrafish brain using cerebroventricular microinjection of morpholino oligonucleotides.

    PubMed

    Kizil, Caghan; Iltzsche, Anne; Kaslin, Jan; Brand, Michael

    2013-05-23

    Manipulation of gene expression in tissues is required to perform functional studies. In this paper, we demonstrate the cerebroventricular microinjection (CVMI) technique as a means to modulate gene expression in the adult zebrafish brain. By using CVMI, substances can be administered into the cerebroventricular fluid and be thoroughly distributed along the rostrocaudal axis of the brain. We particularly focus on the use of antisense morpholino oligonucleotides, which are potent tools for knocking down gene expression in vivo. In our method, when applied, morpholino molecules are taken up by the cells lining the ventricular surface. These cells include the radial glial cells, which act as neurogenic progenitors. Therefore, knocking down gene expression in the radial glial cells is of utmost importance to analyze the widespread neurogenesis response in zebrafish, and also would provide insight into how vertebrates could sustain adult neurogenesis response. Such an understanding would also help the efforts for clinical applications in human neurodegenerative disorders and central nervous system regeneration. Thus, we present the cerebroventricular microinjection method as a quick and efficient way to alter gene expression and neurogenesis response in the adult zebrafish forebrain. We also provide troubleshooting tips and other useful information on how to carry out the CVMI procedure.

  14. Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine.

    PubMed

    Jedynak, Paulina; Kos, Tomasz; Sandi, Carmen; Kaczmarek, Leszek; Filipkowski, Robert K

    2014-09-01

    The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression.

  15. The Union of Shortest Path Trees of Functional Brain Networks.

    PubMed

    Meier, Jil; Tewarie, Prejaas; Van Mieghem, Piet

    2015-11-01

    Communication between brain regions is still insufficiently understood. Applying concepts from network science has shown to be successful in gaining insight in the functioning of the brain. Recent work has implicated that especially shortest paths in the structural brain network seem to play a major role in the communication within the brain. So far, for the functional brain network, only the average length of the shortest paths has been analyzed. In this article, we propose to construct the union of shortest path trees (USPT) as a new topology for the functional brain network. The minimum spanning tree, which has been successful in a lot of recent studies to comprise important features of the functional brain network, is always included in the USPT. After interpreting the link weights of the functional brain network as communication probabilities, the USPT of this network can be uniquely defined. Using data from magnetoencephalography, we applied the USPT as a method to find differences in the network topology of multiple sclerosis patients and healthy controls. The new concept of the USPT of the functional brain network also allows interesting interpretations and may represent the highways of the brain.

  16. Topographic Brain Mapping: A Window on Brain Function?

    ERIC Educational Resources Information Center

    Karniski, Walt M.

    1989-01-01

    The article reviews the method of topographic mapping of the brain's electrical activity. Multiple electroencephalogram (EEG) electrodes and computerized analysis of the EEG signal are used to generate maps of frequency and voltage (evoked potential). This relatively new technique holds promise in the evaluation of children with behavioral and…

  17. Functional magnetic resonance imaging of internet addiction in young adults

    PubMed Central

    Sepede, Gianna; Tavino, Margherita; Santacroce, Rita; Fiori, Federica; Salerno, Rosa Maria; Di Giannantonio, Massimo

    2016-01-01

    AIM: To report the results of functional magnetic resonance imaging (fMRI) studies pertaining internet addiction disorder (IAD) in young adults. METHODS: We conducted a systematic review on PubMed, focusing our attention on fMRI studies involving adult IAD patients, free from any comorbid psychiatric condition. The following search words were used, both alone and in combination: fMRI, internet addiction, internet dependence, functional neuroimaging. The search was conducted on April 20th, 2015 and yielded 58 records. Inclusion criteria were the following: Articles written in English, patients’ age ≥ 18 years, patients affected by IAD, studies providing fMRI results during resting state or cognitive/emotional paradigms. Structural MRI studies, functional imaging techniques other than fMRI, studies involving adolescents, patients with comorbid psychiatric, neurological or medical conditions were excluded. By reading titles and abstracts, we excluded 30 records. By reading the full texts of the 28 remaining articles, we identified 18 papers meeting our inclusion criteria and therefore included in the qualitative synthesis. RESULTS: We found 18 studies fulfilling our inclusion criteria, 17 of them conducted in Asia, and including a total number of 666 tested subjects. The included studies reported data acquired during resting state or different paradigms, such as cue-reactivity, guessing or cognitive control tasks. The enrolled patients were usually males (95.4%) and very young (21-25 years). The most represented IAD subtype, reported in more than 85% of patients, was the internet gaming disorder, or videogame addiction. In the resting state studies, the more relevant abnormalities were localized in the superior temporal gyrus, limbic, medial frontal and parietal regions. When analyzing the task related fmri studies, we found that less than half of the papers reported behavioral differences between patients and normal controls, but all of them found significant

  18. Neuronal Organization of Deep Brain Opsin Photoreceptors in Adult Teleosts

    PubMed Central

    Hang, Chong Yee; Kitahashi, Takashi; Parhar, Ishwar S.

    2016-01-01

    Biological impacts of light beyond vision, i.e., non-visual functions of light, signify the need to better understand light detection (or photoreception) systems in vertebrates. Photopigments, which comprise light-absorbing chromophores bound to a variety of G-protein coupled receptor opsins, are responsible for visual and non-visual photoreception. Non-visual opsin photopigments in the retina of mammals and extra-retinal tissues of non-mammals play an important role in non-image-forming functions of light, e.g., biological rhythms and seasonal reproduction. This review highlights the role of opsin photoreceptors in the deep brain, which could involve conserved neurochemical systems that control different time- and light-dependent physiologies in in non-mammalian vertebrates including teleost fish. PMID:27199680

  19. Intersubject variability of and genetic effects on the brain's functional connectivity during infancy.

    PubMed

    Gao, Wei; Elton, Amanda; Zhu, Hongtu; Alcauter, Sarael; Smith, J Keith; Gilmore, John H; Lin, Weili

    2014-08-20

    Infancy is a period featuring a high level of intersubject variability but the brain basis for such variability and the potential genetic/environmental contributions remain largely unexplored. The assessment of the brain's functional connectivity during infancy by the resting state functional magnetic resonance imaging (rsfMRI) technique (Biswal et al., 1995) provides a unique means to probe the brain basis of intersubject variability during infancy. In this study, an unusually large typically developing human infant sample including 58 singletons, 132 dizygotic twins, and 98 monozygotic twins with rsfMRI scans during the first 2 years of life was recruited to delineate the spatial and temporal developmental patterns of both the intersubject variability of and genetic effects on the brain's functional connectivity. Through systematic voxelwise functional connectivity analyses, our results revealed that the intersubject variability at birth features lower variability in primary functional areas but higher values in association areas. Although the relative pattern remains largely consistent, the magnitude of intersubject variability undergoes an interesting U-shaped growth during the first 2 years of life. Overall, the intersubject variability patterns during infancy show both adult-like and infant-specific characteristics (Mueller et al., 2013). On the other hand, age-dependent genetic effects were observed showing significant but bidirectional relationships with intersubject variability. The temporal and spatial patterns of the intersubject variability of and genetic contributions to the brain's functional connectivity documented in this study shed light on the largely uncharted functional development of the brain during infancy.

  20. Non-Exercise Estimated Cardiorespiratory Fitness: Associations with Brain Structure, Cognition, and Memory Complaints in Older Adults

    PubMed Central

    McAuley, Edward; Szabo, Amanda N.; Mailey, Emily L.; Erickson, Kirk I.; Voss, Michelle; White, Siobhan M.; Wójcicki, Thomas R.; Gothe, Neha; Olson, Erin A.; Mullen, Sean P.; Kramer, Arthur F.

    2011-01-01

    There is increasing evidence that cardiorespiratory fitness (CRF) is associated with brain structure and function, and improvements in CRF through exercise training have been associated with neural and cognitive functioning in older adults. The objectives of this study were to validate the use of a non-exercise estimate of CRF, and to examine its association with cognitive function, brain structure and subjective memory complaints. Low active, older adults (N = 86; M age= 65.14) completed a physician-supervised maximal exercise test, a 1-mile timed walk, several measures of cognitive function, and a 3 Tesla structural MRI. Fitness was also calculated from an equation derived by (Jurca et al., 2005) based on age, sex, body mass index, resting heart rate, and self-reported physical activity level. Analyses indicated that all three measures of CRF were significantly correlated with one another. In addition, measures of cognitive function, hippocampus volume, and memory complaints were significantly correlated with each measure of fitness. These findings have implications for using a low-risk, low-cost, non-exercise estimate of CRF in determining fitness associations with brain structure and cognitive function in older adults. As such, this measure may have utility for larger population based studies. Further validation is required, as is determination of whether such relationships hold over the course of exercise interventions. PMID:21808657

  1. Infrared Imaging System for Studying Brain Function

    NASA Technical Reports Server (NTRS)

    Mintz, Frederick; Mintz, Frederick; Gunapala, Sarath

    2007-01-01

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

  2. Adult attachment predicts maternal brain and oxytocin response to infant cues

    PubMed Central

    Strathearn, Lane; Fonagy, Peter; Amico, Janet; Montague, P. Read

    2010-01-01

    Infant cues, such as smiling or crying facial expressions, are powerful motivators of human maternal behavior, activating dopamine-associated brain reward circuits. Oxytocin, a neurohormone of attachment, promotes maternal care in animals, although its role in human maternal behavior is unclear. We examined 30 first-time new mothers to test whether differences in attachment, based on the Adult Attachment Interview, were related to brain reward and peripheral oxytocin response to infant cues. On viewing their own infant’s smiling and crying faces during functional MRI scanning, mothers with secure attachment showed greater activation of brain reward regions, including the ventral striatum, and the oxytocin-associated hypothalamus/pituitary region. Peripheral oxytocin response to infant contact at 7 months was also significantly higher in secure mothers, and was positively correlated with brain activation in both regions. Insecure/dismissing mothers showed greater insular activation in response to their own infant’s sad faces. These results suggest that individual differences in maternal attachment may be linked with development of the dopaminergic and oxytocinergic neuroendocrine systems. PMID:19710635

  3. Brain serotonin and pituitary-adrenal functions

    NASA Technical Reports Server (NTRS)

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

    1973-01-01

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

  4. Youthful Brains in Older Adults: Preserved Neuroanatomy in the Default Mode and Salience Networks Contributes to Youthful Memory in Superaging

    PubMed Central

    Sun, Felicia W.; Stepanovic, Michael R.; Andreano, Joseph

    2016-01-01

    Decline in cognitive skills, especially in memory, is often viewed as part of “normal” aging. Yet some individuals “age better” than others. Building on prior research showing that cortical thickness in one brain region, the anterior midcingulate cortex, is preserved in older adults with memory performance abilities equal to or better than those of people 20–30 years younger (i.e., “superagers”), we examined the structural integrity of two large-scale intrinsic brain networks in superaging: the default mode network, typically engaged during memory encoding and retrieval tasks, and the salience network, typically engaged during attention, motivation, and executive function tasks. We predicted that superagers would have preserved cortical thickness in critical nodes in these networks. We defined superagers (60–80 years old) based on their performance compared to young adults (18–32 years old) on the California Verbal Learning Test Long Delay Free Recall test. We found regions within the networks of interest where the cerebral cortex of superagers was thicker than that of typical older adults, and where superagers were anatomically indistinguishable from young adults; hippocampal volume was also preserved in superagers. Within the full group of older adults, thickness of a number of regions, including the anterior temporal cortex, rostral medial prefrontal cortex, and anterior midcingulate cortex, correlated with memory performance, as did the volume of the hippocampus. These results indicate older adults with youthful memory abilities have youthful brain regions in key paralimbic and limbic nodes of the default mode and salience networks that support attentional, executive, and mnemonic processes subserving memory function. SIGNIFICANCE STATEMENT Memory performance typically declines with age, as does cortical structural integrity, yet some older adults maintain youthful memory. We tested the hypothesis that superagers (older individuals with

  5. Gut microbial communities modulating brain development and function.

    PubMed

    Al-Asmakh, Maha; Anuar, Farhana; Zadjali, Fahad; Rafter, Joseph; Pettersson, Sven

    2012-01-01

    Mammalian brain development is initiated in utero and internal and external environmental signals can affect this process all the way until adulthood. Recent observations suggest that one such external cue is the indigenous microbiota which has been shown to affect developmental programming of the brain. This may have consequences for brain maturation and function that impact on cognitive functions later in life. This review discusses these recent findings from a developmental perspective.

  6. Effective factors on linguistic disorder during acute phase following traumatic brain injury in adults.

    PubMed

    Chabok, Shahrokh Yousefzadeh; Kapourchali, Sara Ramezani; Leili, Ehsan Kazemnezhad; Saberi, Alia; Mohtasham-Amiri, Zahra

    2012-06-01

    Traumatic brain injury (TBI) has been known to be the leading cause of breakdown and long-term disability in people under 45 years of age. This study highlights the effective factors on post-traumatic (PT) linguistic disorder and relations between linguistic and cognitive function after trauma in adults with acute TBI. A cross-sectional design was employed to study 60 post-TBI hospitalized adults aged 18-65 years. Post-traumatic (PT) linguistic disorder and cognitive deficit after TBI were respectively diagnosed using the Persian Aphasia Test (PAT) and Persian version of Mini-Mental State Examination (MMSE) at discharge. Primary post-resuscitation consciousness level was determined using the Glasgow Coma Scale (GCS). Paracilinical data was obtained by CT scan technique. Multiple logistic regression analysis illustrated that brain injury severity was the first powerful significant predictor of PT linguistic disorder after TBI and frontotemporal lesion was the second. It was also revealed that cognitive function score was significantly correlated with score of each language skill except repetition. Subsequences of TBI are more commonly language dysfunctions that demand cognitive flexibility. Moderate, severe and fronto-temporal lesion can increase the risk of processing deficit in linguistic macrostructure production and comprehension. The dissociation risk of cortical and subcortical pathways related to cognitive-linguistic processing due to intracranial lesions can augment possibility of lexical-semantic processing deficit in acute phase which probably contributes to later cognitive-communication disorder.

  7. Insulin in the brain: sources, localization and functions.

    PubMed

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

    2013-02-01

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

  8. Brain training in older adults: evidence of transfer to memory span performance and pseudo-Matthew effects.

    PubMed

    McDougall, Siné; House, Becky

    2012-01-01

    In this study the effects of 'brain training' using the Nintendo DS Brain Training program were examined in two groups of older adults; the cognitive performance of an experimental group (n = 21) who were asked to use the Nintendo DS regularly over a 6-week period was compared with the control group (n = 20). Groups were matched on age (mean age = 74 years), education, computer experience, daily activities (time spent reading or watching television), and initial scores of Wechsler Adult Intelligence Scale. Analyses revealed that improvements were primarily in the Digit Span Test, specifically Digits Backwards. Although the Brain Training package appeared to have some efficacy, other factors such as perceived quality of life and perceived cognitive functioning were at least equally important in determining training outcomes. The implications of these findings for cognitive training are discussed.

  9. Estimating functional brain networks by incorporating a modularity prior

    PubMed Central

    Qiao, Lishan; Zhang, Han; Kim, Minjeong; Teng, Shenghua; Zhang, Limei; Shen, Dinggang

    2017-01-01

    Functional brain network analysis has become one principled way of revealing informative organization architectures in healthy brains, and providing sensitive biomarkers for diagnosis of neurological disorders. Prior to any post hoc analysis, however, a natural issue is how to construct “ideal” brain networks given, for example, a set of functional magnetic resonance imaging (fMRI) time series associated with different brain regions. Although many methods have been developed, it is currently still an open field to estimate biologically meaningful and statistically robust brain networks due to our limited understanding of the human brain as well as complex noises in the observed data. Motivated by the fact that the brain is organized with modular structures, in this paper, we propose a novel functional brain network modeling scheme by encoding a modularity prior under a matrix-regularized network learning framework, and further formulate it as a sparse low-rank graph learning problem, which can be solved by an efficient optimization algorithm. Then, we apply the learned brain networks to identify patients with mild cognitive impairment (MCI) from normal controls. We achieved 89.01% classification accuracy even with a simple feature selection and classification pipeline, which significantly outperforms the conventional brain network construction methods. Moreover, we further explore brain network features that contributed to MCI identification, and discovered potential biomarkers for personalized diagnosis. PMID:27485752

  10. New aspects in fenestrated capillary and tissue dynamics in the sensory circumventricular organs of adult brains.

    PubMed

    Miyata, Seiji

    2015-01-01

    The blood-brain barrier (BBB) generally consists of endothelial tight junction barriers that prevent the free entry of blood-derived substances, thereby maintaining the extracellular environment of the brain. However, the circumventricular organs (CVOs), which are located along the midlines of the brain ventricles, lack these endothelial barriers and have fenestrated capillaries; therefore, they have a number of essential functions, including the transduction of information between the blood circulation and brain. Previous studies have demonstrated the extensive contribution of the CVOs to body fluid and thermal homeostasis, energy balance, the chemoreception of blood-derived substances, and neuroinflammation. In this review, recent advances have been discussed in fenestrated capillary characterization and dynamic tissue reconstruction accompanied by angiogenesis and neurogliogenesis in the sensory CVOs of adult brains. The sensory CVOs, including the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), and area postrema (AP), have size-selective and heterogeneous vascular permeabilities. Astrocyte-/tanycyte-like neural stem cells (NSCs) sense blood- and cerebrospinal fluid-derived information through the transient receptor potential vanilloid 1, a mechanical/osmotic receptor, Toll-like receptor 4, a lipopolysaccharide receptor, and Nax, a Na-sensing Na channel. They also express tight junction proteins and densely and tightly surround mature neurons to protect them from blood-derived neurotoxic substances, indicating that the NSCs of the CVOs perform BBB functions while maintaining the capacity to differentiate into new neurons and glial cells. In addition to neurogliogenesis, the density of fenestrated capillaries is regulated by angiogenesis, which is accompanied by the active proliferation and sprouting of endothelial cells. Vascular endothelial growth factor (VEGF) signaling may be involved in angiogenesis and neurogliogenesis, both of

  11. Wearable sensor network to study laterality of brain functions.

    PubMed

    Postolache, Gabriela B; Girao, Pedro S; Postolache, Octavian A

    2015-08-01

    In the last decade researches on laterality of brain functions have been reinvigorated. New models of lateralization of brain functions were proposed and new methods for understanding mechanisms of asymmetry between right and left brain functions were described. We design a system to study laterality of motor and autonomic nervous system based on wearable sensors network. A mobile application was developed for analysis of upper and lower limbs movements, cardiac and respiratory function. The functionalities and experience gained with deployment of the system are described.

  12. Expression of cyclin E in postmitotic neurons during development and in the adult mouse brain.

    PubMed

    Ikeda, Yayoi; Matsunaga, Yuko; Takiguchi, Masahito; Ikeda, Masa-Aki

    2011-01-01

    Cyclin E, a member of the G1 cyclins, is essential for the G1/S transition of the cell cycle in cultured cells, but its roles in vivo are not fully defined. The present study characterized the spatiotemporal expression profile of cyclin E in two representative brain regions in the mouse, the cerebral and cerebellar cortices. Western blotting showed that the levels of cyclin E increased towards adulthood. In situ hybridization and immunohistochemistry showed the distributions of cyclin E mRNA and protein were comparable in the cerebral cortex and the cerebellum. Immunohistochemistry for the proliferating cell marker, proliferating cell nuclear antigen (PCNA) revealed that cyclin E was expressed by both proliferating and non-proliferating cells in the cerebral cortex at embryonic day 12.5 (E12.5) and in the cerebellum at postnatal day 1 (P1). Subcellular localization in neurons was examined using immunofluorescence and western blotting. Cyclin E expression was nuclear in proliferating neuronal precursor cells but cytoplasmic in postmitotic neurons during embryonic development. Nuclear cyclin E expression in neurons remained faint in newborns, increased during postnatal development and was markedly decreased in adults. In various adult brain regions, cyclin E staining was more intense in the cytoplasm than in the nucleus in most neurons. These data suggest a role for cyclin E in the development and function of the mammalian central nervous system and that its subcellular localization in neurons is important. Our report presents the first detailed analysis of cyclin E expression in postmitotic neurons during development and in the adult mouse brain.

  13. Violent Video Games Alter Brain Function in Young Men

    MedlinePlus

    ... RSS feed News from the RSNA Annual Meeting Violent Video Games Alter Brain Function in Young Men ... Using functional MRI, researchers have found that playing violent video games for one week causes changes in ...

  14. Functional MRI and diffusion tensor imaging of brain reorganization after experimental stroke.

    PubMed

    Dijkhuizen, Rick M; van der Marel, Kajo; Otte, Willem M; Hoff, Erik I; van der Zijden, Jet P; van der Toorn, Annette; van Meer, Maurits P A

    2012-03-01

    The potential of the adult brain to reorganize after ischemic injury is critical for functional recovery and provides a significant target for therapeutic strategies to promote brain repair. Despite the accumulating evidence of brain plasticity, the interaction and significance of morphological and physiological modifications in post-stroke brain tissue remain mostly unclear. Neuroimaging techniques such as functional MRI (fMRI) and diffusion tensor imaging (DTI) enable in vivo assessment of the spatial and temporal pattern of functional and structural changes inside and outside ischemic lesion areas. This can contribute to the elucidation of critical aspects in post-stroke brain remodeling. Task/stimulus-related fMRI, resting-state fMRI, or pharmacological MRI enables direct or indirect measurement of neuronal activation, functional connectivity, or neurotransmitter system responses, respectively. DTI allows estimation of the structural integrity and connectivity of white matter tracts. Together, these MRI methods provide an unprecedented means to (a) measure longitudinal changes in tissue structure and function close by and remote from ischemic lesion areas, (b) evaluate the organizational profile of neural networks after stroke, and (c) identify degenerative and restorative processes that affect post-stroke functional outcome. Besides, the availability of MRI in clinical institutions as well as research laboratories provides an optimal basis for translational research on stroke recovery. This review gives an overview of the current status and perspectives of fMRI and DTI applications to study brain reorganization in experimental stroke models.

  15. Persistent Postconcussive Symptoms Are Accompanied by Decreased Functional Brain Oxygenation.

    PubMed

    Helmich, Ingo; Saluja, Rajeet S; Lausberg, Hedda; Kempe, Mathias; Furley, Philip; Berger, Alisa; Chen, Jen-Kai; Ptito, Alain

    2015-01-01

    Diagnostic methods are considered a major concern in the determination of mild traumatic brain injury. The authors examined brain oxygenation patterns in subjects with severe and minor persistent postconcussive difficulties and a healthy control group during working memory tasks in prefrontal brain regions using functional near-infrared spectroscopy. The results demonstrated decreased working memory performances among concussed subjects with severe postconcussive symptoms that were accompanied by decreased brain oxygenation patterns. An association appears to exist between decreased brain oxygenation, poor performance of working memory tasks, and increased symptom severity scores in subjects suffering from persistent postconcussive symptoms.

  16. Brain activation during dual-task processing is associated with cardiorespiratory fitness and performance in older adults

    PubMed Central

    Wong, Chelsea N.; Chaddock-Heyman, Laura; Voss, Michelle W.; Burzynska, Agnieszka Z.; Basak, Chandramallika; Erickson, Kirk I.; Prakash, Ruchika S.; Szabo-Reed, Amanda N.; Phillips, Siobhan M.; Wojcicki, Thomas; Mailey, Emily L.; McAuley, Edward; Kramer, Arthur F.

    2015-01-01

    Higher cardiorespiratory fitness is associated with better cognitive performance and enhanced brain activation. Yet, the extent to which cardiorespiratory fitness-related brain activation is associated with better cognitive performance is not well understood. In this cross-sectional study, we examined whether the association between cardiorespiratory fitness and executive function was mediated by greater prefrontal cortex activation in healthy older adults. Brain activation was measured during dual-task performance with functional magnetic resonance imaging in a sample of 128 healthy older adults (59–80 years). Higher cardiorespiratory fitness was associated with greater activation during dual-task processing in several brain areas including the anterior cingulate and supplementary motor cortex (ACC/SMA), thalamus and basal ganglia, right motor/somatosensory cortex and middle frontal gyrus, and left somatosensory cortex, controlling for age, sex, education, and gray matter volume. Of these regions, greater ACC/SMA activation mediated the association between cardiorespiratory fitness and dual-task performance. We provide novel evidence that cardiorespiratory fitness may support cognitive performance by facilitating brain activation in a core region critical for executive function. PMID:26321949

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  18. Functional Imaging of Working Memory and Peripheral Endothelial Function in Middle-Aged Adults

    PubMed Central

    Gonzales, Mitzi M.; Tarumi, Takashi; Tanaka, Hirofumi; Sugawara, Jun; Swann-Sternberg, Tali; Goudarzi, Katyoon; Haley, Andreana P.

    2010-01-01

    The current study examined the relationship between a prognostic indicator of vascular health, flow-mediated dilation (FMD), and working memory-related brain activation in healthy middle-aged adults. Forty-two participants underwent functional magnetic resonance imaging while completing a 2-Back working memory task. Brachial artery endothelial-dependent flow-mediated dilation (FMD) was assessed using B-mode ultrasound. The relationship between FMD and task-related brain activation in a priori regions of interest was modeled using hierarchical linear regression. Brachial FMD, was significantly related to reduced working memory-related activation in the right superior parietal lobule (β=0.338, p=0.027), independent of age, sex, systolic blood pressure, and full scale IQ (F(5,36)=2.66, p=0.038). These data provide preliminary support for the association between a preclinical marker of endothelial dysfunction and cerebral hemodynamic alterations in healthy middle-aged adults. Considering the modifiable nature of endothelial function, additional investigations on the prognostic significance of FMD on future cognitive impairment are warranted. PMID:20493622

  19. [Brain functional MRI: physiological, technical, and methodological bases, and clinical applications].

    PubMed

    Hertz-Pannier, L; Lehéricy, S; Cordoliani, Y; Le Bihan, D; Marsault, C; Brunelle, F

    2000-06-01

    Brain functional MRI (fMRI) provides an indirect mapping of cerebral activity, based on the detection of the local blood flow and oxygenation changes following neuronal activity (BOLD contrast, Blood Oxygenation Level Dependent). fMRI allows us to study non invasively the normal and pathological aspects of cortical functional organization. Each fMRI study compares two different states of activity. Echo-Planar Imaging (EPI) is the technic of choice that makes it possible to study the whole brain at a rapid pace. Activation maps are calculated from a statistical analysis of the local signal changes. Functional MRI is now becoming an essential tool in the neurofunctional work-up of many neurosurgery patients, as well as the reference method to image normal or pathologic functional brain organization in adults and children.

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

    PubMed

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

    2013-10-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Mandonnet, Emmanuel; Duffau, Hugues

    2014-01-01

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

  3. The modular and integrative functional architecture of the human brain

    PubMed Central

    Bertolero, Maxwell A.; Yeo, B. T. Thomas; D’Esposito, Mark

    2015-01-01

    Network-based analyses of brain imaging data consistently reveal distinct modules and connector nodes with diverse global connectivity across the modules. How discrete the functions of modules are, how dependent the computational load of each module is to the other modules’ processing, and what the precise role of connector nodes is for between-module communication remains underspecified. Here, we use a network model of the brain derived from resting-state functional MRI (rs-fMRI) data and investigate the modular functional architecture of the human brain by analyzing activity at different types of nodes in the network across 9,208 experiments of 77 cognitive tasks in the BrainMap database. Using an author–topic model of cognitive functions, we find a strong spatial correspondence between the cognitive functions and the network’s modules, suggesting that each module performs a discrete cognitive function. Crucially, activity at local nodes within the modules does not increase in tasks that require more cognitive functions, demonstrating the autonomy of modules’ functions. However, connector nodes do exhibit increased activity when more cognitive functions are engaged in a task. Moreover, connector nodes are located where brain activity is associated with many different cognitive functions. Connector nodes potentially play a role in between-module communication that maintains the modular function of the brain. Together, these findings provide a network account of the brain’s modular yet integrated implementation of cognitive functions. PMID:26598686

  4. Manifold learning on brain functional networks in aging.

    PubMed

    Qiu, Anqi; Lee, Annie; Tan, Mingzhen; Chung, Moo K

    2015-02-01

    We propose a new analysis framework to utilize the full information of brain functional networks for computing the mean of a set of brain functional networks and embedding brain functional networks into a low-dimensional space in which traditional regression and classification analyses can be easily employed. For this, we first represent the brain functional network by a symmetric positive matrix computed using sparse inverse covariance estimation. We then impose a Log-Euclidean Riemannian manifold structure on brain functional networks whose norm gives a convenient and practical way to define a mean. Finally, based on the fact that the computation of linear operations can be done in the tangent space of this Riemannian manifold, we adopt Locally Linear Embedding (LLE) to the Log-Euclidean Riemannian manifold space in order to embed the brain functional networks into a low-dimensional space. We show that the integration of the Log-Euclidean manifold with LLE provides more efficient and succinct representation of the functional network and facilitates regression analysis, such as ridge regression, on the brain functional network to more accurately predict age when compared to that of the Euclidean space of functional networks with LLE. Interestingly, using the Log-Euclidean analysis framework, we demonstrate the integration and segregation of cortical-subcortical networks as well as among the salience, executive, and emotional networks across lifespan.

  5. Sleep and synaptic plasticity in the developing and adult brain.

    PubMed

    Frank, Marcos G

    2015-01-01

    Sleep is hypothesized to play an integral role in brain plasticity. This has traditionally been investigated using behavioral assays. In the last 10-15 years, studies combining sleep measurements with in vitro and in vivo models of synaptic plasticity have provided exciting new insights into how sleep alters synaptic strength. In addition, new theories have been proposed that integrate older ideas about sleep function and recent discoveries in the field of synaptic plasticity. There remain, however, important challenges and unanswered questions. For example, sleep does not appear to have a single effect on synaptic strength. An unbiased review of the literature indicates that the effects of sleep vary widely depending on ontogenetic stage, the type of waking experience (or stimulation protocols) that precede sleep and the type of neuronal synapse under examination. In this review, I discuss these key findings in the context of current theories that posit different roles for sleep in synaptic plasticity.

  6. The chemokine receptor cxcr5 regulates the regenerative neurogenesis response in the adult zebrafish brain

    PubMed Central

    2012-01-01

    Background Unlike mammals, zebrafish exhibits extensive neural regeneration after injury in adult stages of its lifetime due to the neurogenic activity of the radial glial cells. However, the genes involved in the regenerative neurogenesis response of the zebrafish brain are largely unknown. Thus, understanding the underlying principles of this regeneration capacity of the zebrafish brain is an interesting research realm that may offer vast clinical ramifications. Results In this paper, we characterized the expression pattern of cxcr5 and analyzed the function of this gene during adult neurogenesis and regeneration of the zebrafish telencephalon. We found that cxcr5 was upregulated transiently in the RGCs and neurons, and the expression in the immune cells such as leukocytes was negligible during both adult neurogenesis and regeneration. We observed that the transgenic misexpression of cxcr5 in the ventricular cells using dominant negative and full-length variants of the gene resulted in altered proliferation and neurogenesis response of the RGCs. When we knocked down cxcr5 using antisense morpholinos and cerebroventricular microinjection, we observed outcomes similar to the overexpression of the dominant negative cxcr5 variant. Conclusions Thus, based on our results, we propose that cxcr5 imposes a proliferative permissiveness to the radial glial cells and is required for differentiation of the RGCs to neurons, highlighting novel roles of cxcr5 in the nervous system of vertebrates. We therefore suggest that cxcr5 is an important cue for ventricular cell proliferation and regenerative neurogenesis in the adult zebrafish telencephalon. Further studies on the role of cxcr5 in mediating neuronal replenishment have the potential to produce clinical ramifications in efforts for regenerative therapeutic applications for human neurological disorders or acute injuries. PMID:22824261

  7. Abnormal Brain Connectivity Patterns in Adults with ADHD: A Coherence Study

    PubMed Central

    Sato, João Ricardo; Hoexter, Marcelo Queiroz; Castellanos, Xavier Francisco; Rohde, Luis A.

    2012-01-01

    Studies based on functional magnetic resonance imaging (fMRI) during the resting state have shown decreased functional connectivity between the dorsal anterior cingulate cortex (dACC) and regions of the Default Mode Network (DMN) in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD) relative to subjects with typical development (TD). Most studies used Pearson correlation coefficients among the BOLD signals from different brain regions to quantify functional connectivity. Since the Pearson correlation analysis only provides a limited description of functional connectivity, we investigated functional connectivity between the dACC and the posterior cingulate cortex (PCC) in three groups (adult patients with ADHD, n = 21; TD age-matched subjects, n = 21; young TD subjects, n = 21) using a more comprehensive analytical approach – unsupervised machine learning using a one-class support vector machine (OC-SVM) that quantifies an abnormality index for each individual. The median abnormality index for patients with ADHD was greater than for TD age-matched subjects (p = 0.014); the ADHD and young TD indices did not differ significantly (p = 0.480); the median abnormality index of young TD was greater than that of TD age-matched subjects (p = 0.016). Low frequencies below 0.05 Hz and around 0.20 Hz were the most relevant for discriminating between ADHD patients and TD age-matched controls and between the older and younger TD subjects. In addition, we validated our approach using the fMRI data of children publicly released by the ADHD-200 Competition, obtaining similar results. Our findings suggest that the abnormal coherence patterns observed in patients with ADHD in this study resemble the patterns observed in young typically developing subjects, which reinforces the hypothesis that ADHD is associated with brain maturation deficits. PMID:23049834

  8. Centrality of Social Interaction in Human Brain Function.

    PubMed

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

    2015-10-07

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

  9. The association of brain structure with gait velocity in older adults: a quantitative volumetric analysis of brain MRI

    PubMed Central

    Katz, Mindy J.; Lipton, Michael L.; Lipton, Richard B.; Verghese, Joe

    2015-01-01

    Introduction While cortical processes play an important role in controlling locomotion, the underlying structural brain changes associated with slowing of gait in aging are not yet fully established. Our study aimed to examine the relationship between cortical gray matter volume (GM), white matter volume (WM), ventricular volume (VV), hippocampal and hippocampal subfield volumes, and gait velocity in older adults free of dementia. Methods Gait and cognitive performance was tested in 112 community-residing adults, age 70 years and over, participating in the Einstein Aging Study. Gait velocity (cm/s) was obtained using an instrumented walkway. Volumetric MRI measures were estimated using a FreeSurfer software. We examined the cross-sectional relationship of GM, WM, VV, and hippocampal total and subfield volumes and gait velocity using linear regression models. In complementary models, the effect of memory performance on the relationship between gait velocity and regional volumes was evaluated. Results Slower gait velocity was associated with smaller cortical GM and total hippocampal volumes. There was no association between gait velocity and WM or VV. Among hippocampal subfields, only smaller presubiculum volume was significantly associated with decrease in gait velocity. Addition of the memory performance to the models attenuated the association between gait velocity and all volumetric measures. Conclusions Our findings indicate that total GM and hippocampal volumes as well as specific hippocampal subfield volumes are inversely associated with locomotor function. These associations are probably affected by cognitive status of study population. PMID:25921321

  10. Adolescent social defeat alters markers of adult dopaminergic function.

    PubMed

    Novick, Andrew M; Forster, Gina L; Tejani-Butt, Shanaz M; Watt, Michael J

    2011-08-10

    Stressful experiences during adolescence can alter the trajectory of neural development and contribute to psychiatric disorders in adulthood. We previously demonstrated that adolescent male rats exposed to repeated social defeat stress show changes in mesocorticolimbic dopamine content both at baseline and in response to amphetamine when tested in adulthood. In the present study we examined whether markers of adult dopamine function are also compromised by adolescent experience of social defeat. Given that the dopamine transporter as well as dopamine D1 receptors act as regulators of psychostimulant action, are stress sensitive and undergo changes during adolescence, quantitative autoradiography was used to measure [(3)H]-GBR12935 binding to the dopamine transporter and [(3)H]-SCH23390 binding to dopamine D1 receptors, respectively. Our results indicate that social defeat during adolescence led to higher dopamine transporter binding in the infralimbic region of the medial prefrontal cortex and higher dopamine D1 receptor binding in the caudate putamen, while other brain regions analyzed were comparable to controls. Thus it appears that social defeat during adolescence causes specific changes to the adult dopamine system, which may contribute to behavioral alterations and increased drug seeking.

  11. Adolescent social defeat alters markers of adult dopaminergic function

    PubMed Central

    Novick, Andrew M.; Forster, Gina L.; Tejani-Butt, Shanaz M.; Watt, Michael J.

    2011-01-01

    Stressful experiences during adolescence can alter the trajectory of neural development and contribute to psychiatric disorders in adulthood. We previously demonstrated that adolescent male rats exposed to repeated social defeat stress show changes in mesocorticolimbic dopamine content both at baseline and in response to amphetamine when tested in adulthood. In the present study we examined whether markers of adult dopamine function are also compromised by adolescent experience of social defeat. Given that the dopamine transporter as well as dopamine D1 receptors act as regulators of psychostimulant action, are stress sensitive and undergo changes during adolescence, quantitative autoradiography was used to measure [3H]-GBR12935 binding to the dopamine transporter and [3H]-SCH23390 binding to dopamine D1 receptors, respectively. Our results indicate that social defeat during adolescence led to higher dopamine transporter binding in the infralimbic region of the medial prefrontal cortex and higher dopamine D1 receptor binding in the caudate putamen, while other brain regions analyzed were comparable to controls. Thus it appears that social defeat during adolescence causes specific changes to the adult DA system, which may contribute to behavioral alterations and increased drug seeking. PMID:21741457

  12. Adult axolotls can regenerate original neuronal diversity in response to brain injury

    PubMed Central

    Amamoto, Ryoji; Huerta, Violeta Gisselle Lopez; Takahashi, Emi; Dai, Guangping; Grant, Aaron K; Fu, Zhanyan; Arlotta, Paola

    2016-01-01

    The axolotl can regenerate multiple organs, including the brain. It remains, however, unclear whether neuronal diversity, intricate tissue architecture, and axonal connectivity can be regenerated; yet, this is critical for recovery of function and a central aim of cell replacement strategies in the mammalian central nervous system. Here, we demonstrate that, upon mechanical injury to the adult pallium, axolotls can regenerate several of the populations of neurons present before injury. Notably, regenerated neurons acquire functional electrophysiological traits and respond appropriately to afferent inputs. Despite the ability to regenerate specific, molecularly-defined neuronal subtypes, we also uncovered previously unappreciated limitations by showing that newborn neurons organize within altered tissue architecture and fail to re-establish the long-distance axonal tracts and circuit physiology present before injury. The data provide a direct demonstration that diverse, electrophysiologically functional neurons can be regenerated in axolotls, but challenge prior assumptions of functional brain repair in regenerative species. DOI: http://dx.doi.org/10.7554/eLife.13998.001 PMID:27156560

  13. Gut Microbiota and Brain Function: An Evolving Field in Neuroscience.

    PubMed

    Foster, Jane A; Lyte, Mark; Meyer, Emeran; Cryan, John F

    2016-05-01

    There is a growing appreciation of the importance of gut microbiota to health and disease. This has been driven by advances in sequencing technology and recent findings demonstrating the important role of microbiota in common health disorders such as obesity. Moreover, the potential role of gut microbiota in influencing brain function, behavior, and mental health has attracted the attention of neuroscientists and psychiatrists. At the 29(th) International College of Neuropsychopharmacology (CINP) World Congress held in Vancouver, Canada, in June 2014, a group of experts presented the symposium, "Gut microbiota and brain function: Relevance to psychiatric disorders" to review the latest findings in how gut microbiota may play a role in brain function, behavior, and disease. The symposium covered a broad range of topics, including gut microbiota and neuroendocrine function, the influence of gut microbiota on behavior, probiotics as regulators of brain and behavior, and imaging the gut-brain axis in humans. This report provides an overview of these presentations.

  14. Brain function with complex decision making using electroencephalography.

    PubMed

    Davis, C Ervin; Hauf, Jessica D; Wu, D Qiang; Everhart, D Erik

    2011-02-01

    A computer-administered assessment for decision making relevant to daily-living decisions, using the technique of complex decision making (CDM), has been previously developed and tested in our laboratory. The present study sought to identify unique patterns of brain activity in the alpha band associated with CDM. We recorded electroencephalogram (EEG) from 30 scalp sites, during a series of baseline, eyes open fixation tasks, and CDM tasks, in different contexts, in a group of 9 male and 7 female young healthy adults, aged 18 to 34. The decision making contexts, designed to simulate real-world, daily-living decisions, were about taking a bus, choosing a friend, job, medication, and participating in research. Electroencephalograms (EEGs) were divided into the frequency bands, alpha, beta, delta, theta, and gamma, though the primary focus of this paper is the alpha band. Analysis of mean EEG power spectra across the alpha bands - alpha1 (8-10 Hz), alpha2 (10-12 Hz), and alpha 3 (12-14 Hz) - showed significant decreases from baseline to the CDM task. In addition, we observed significant increases in delta, theta, beta, and gamma. There were also significant bivariate correlations between EEG spectra, mostly in low and mid alpha bands, behavioral performance on the CDM task, and scores on standardized measures of executive functioning, including the Trail-making Test and the Wisconsin Card Sorting Task. These results demonstrate how brain activity in complex decision making is distributed across alpha frequency bands and electrode regions and this activity relates to executive functioning.

  15. Functional Impacts of Adult Literacy Programme on Rural Women

    ERIC Educational Resources Information Center

    Mbah, Blessing Akaraka

    2015-01-01

    This study assessed the functional impacts of adult literacy programme among rural women participants in Ishielu Local Government Area (LGA) of Ebonyi State, Nigeria. Descriptive survey design was used for the study. The population of the study was made up of 115 adult instructors and 2,408 adult learners giving a total of 2,623. The sample…

  16. Monte Carlo simulation of light propagation in the adult brain

    NASA Astrophysics Data System (ADS)

    Mudra, Regina M.; Nadler, Andreas; Keller, Emanuella; Niederer, Peter

    2004-06-01

    When near infrared spectroscopy (NIRS) is applied noninvasively to the adult head for brain monitoring, extra-cerebral bone and surface tissue exert a substantial influence on the cerebral signal. Most attempts to subtract extra-cerebral contamination involve spatially resolved spectroscopy (SRS). However, inter-individual variability of anatomy restrict the reliability of SRS. We simulated the light propagation with Monte Carlo techniques on the basis of anatomical structures determined from 3D-magnetic resonance imaging (MRI) exhibiting a voxel resolution of 0.8 x 0.8 x 0.8 mm3 for three different pairs of T1/T2 values each. The MRI data were used to define the material light absorption and dispersion coefficient for each voxel. The resulting spatial matrix was applied in the Monte Carlo Simulation to determine the light propagation in the cerebral cortex and overlaying structures. The accuracy of the Monte Carlo Simulation was furthermore increased by using a constant optical path length for the photons which was less than the median optical path length of the different materials. Based on our simulations we found a differential pathlength factor (DPF) of 6.15 which is close to with the value of 5.9 found in the literature for a distance of 4.5cm between the external sensors. Furthermore, we weighted the spatial probability distribution of the photons within the different tissues with the probabilities of the relative blood volume within the tissue. The results show that 50% of the NIRS signal is determined by the grey matter of the cerebral cortex which allows us to conclude that NIRS can produce meaningful cerebral blood flow measurements providing that the necessary corrections for extracerebral contamination are included.

  17. Beyond localized and distributed accounts of brain functions. Comment on “Understanding brain networks and brain organization” by Pessoa

    NASA Astrophysics Data System (ADS)

    Cauda, Franco; Costa, Tommaso; Tamietto, Marco

    2014-09-01

    Recent evidence in cognitive neuroscience lends support to the idea that network models of brain architecture provide a privileged access to the understanding of the relation between brain organization and cognitive processes [1]. The core perspective holds that cognitive processes depend on the interactions among distributed neuronal populations and brain structures, and that the impact of a given region on behavior largely depends on its pattern of anatomical and functional connectivity [2,3].

  18. Nerve growth factor in the adult brain of a teleostean model for aging research: Nothobranchius furzeri.

    PubMed

    D'Angelo, L; Castaldo, L; Cellerino, A; de Girolamo, P; Lucini, C

    2014-07-01

    Nerve growth factor (NGF) acts on central nervous system neurons, regulating naturally occurring cell death, synaptic connectivity, fiber guidance and dendritic morphology. The dynamically regulated production of NGF beginning in development, extends throughout adult life and aging, exerting numerous roles through a surprising variety of neurons and glial cells. This study analyzes the localization of NGF in the brain of the teleost fish Nothobranchius furzeri, an emerging model for aging research due to its short lifespan. Immunochemical and immunohistochemical experiments were performed by employing an antibody mapping at the N-terminus of the mature chain human origin NGF. Western blot analysis revealed an intense and well defined band of 20 kDa, which corresponds to proNGF of N. furzeri. Immunohistochemistry revealed NGF immunoreactivity (IR) diffused throughout all regions of telencephalon, diencephalon, mesencephalon and rhomboencephalon. It was detected in neurons and in glial cells, the latter mostly lining the mesencephalic and rhomboencephalic ventricles. Particularly in neurons, NGF IR was localized in perikarya and, to a less extent, in fibers. The widespread distribution of proNGF suggests that it might modulate numerous physiological functions in the adult brain of N. furzeri. The present survey constitutes a baseline study to enhance the understanding of the mechanisms underlying the role of NGF during aging processes.

  19. Elephant brain. Part I: gross morphology, functions, comparative anatomy, and evolution.

    PubMed

    Shoshani, Jeheskel; Kupsky, William J; Marchant, Gary H

    2006-06-30

    We report morphological data on brains of four African, Loxodonta africana, and three Asian elephants, Elephas maximus, and compare findings to literature. Brains exhibit a gyral pattern more complex and with more numerous gyri than in primates, humans included, and in carnivores, but less complex than in cetaceans. Cerebral frontal, parietal, temporal, limbic, and insular lobes are well developed, whereas the occipital lobe is relatively small. The insula is not as opercularized as in man. The temporal lobe is disproportionately large and expands laterally. Humans and elephants have three parallel temporal gyri: superior, middle, and inferior. Hippocampal sizes in elephants and humans are comparable, but proportionally smaller in elephant. A possible carotid rete was observed at the base of the brain. Brain size appears to be related to body size, ecology, sociality, and longevity. Elephant adult brain averages 4783 g, the largest among living and extinct terrestrial mammals; elephant neonate brain averages 50% of its adult brain weight (25% in humans). Cerebellar weight averages 18.6% of brain (1.8 times larger than in humans). During evolution, encephalization quotient has increased by 10-fold (0.2 for extinct Moeritherium, approximately 2.0 for extant elephants). We present 20 figures of the elephant brain, 16 of which contain new material. Similarities between human and elephant brains could be due to convergent evolution; both display mosaic characters and are highly derived mammals. Humans and elephants use and make tools and show a range of complex learning skills and behaviors. In elephants, the large amount of cerebral cortex, especially in the temporal lobe, and the well-developed olfactory system, structures associated with complex learning and behavioral functions in humans, may provide the substrate for such complex skills and behavior.

  20. Predicting Cognitive Function from Clinical Measures of Physical Function and Health Status in Older Adults

    PubMed Central

    Bolandzadeh, Niousha; Kording, Konrad; Salowitz, Nicole; Davis, Jennifer C.; Hsu, Liang; Chan, Alison; Sharma, Devika; Blohm, Gunnar; Liu-Ambrose, Teresa

    2015-01-01

    Introduction Current research suggests that the neuropathology of dementia—including brain changes leading to memory impairment and cognitive decline—is evident years before the onset of this disease. Older adults with cognitive decline have reduced functional independence and quality of life, and are at greater risk for developing dementia. Therefore, identifying biomarkers that can be easily assessed within the clinical setting and predict cognitive decline is important. Early recognition of cognitive decline could promote timely implementation of preventive strategies. Methods We included 89 community-dwelling adults aged 70 years and older in our study, and collected 32 measures of physical function, health status and cognitive function at baseline. We utilized an L1–L2 regularized regression model (elastic net) to identify which of the 32 baseline measures were strongly predictive of cognitive function after one year. We built three linear regression models: 1) based on baseline cognitive function, 2) based on variables consistently selected in every cross-validation loop, and 3) a full model based on all the 32 variables. Each of these models was carefully tested with nested cross-validation. Results Our model with the six variables consistently selected in every cross-validation loop had a mean squared prediction error of 7.47. This number was smaller than that of the full model (115.33) and the model with baseline cognitive function (7.98). Our model explained 47% of the variance in cognitive function after one year. Discussion We built a parsimonious model based on a selected set of six physical function and health status measures strongly predictive of cognitive function after one year. In addition to reducing the complexity of the model without changing the model significantly, our model with the top variables improved the mean prediction error and R-squared. These six physical function and health status measures can be easily implemented in a

  1. Effect of Smoking on Cognitive Functioning in Young Saudi Adults

    PubMed Central

    Bashir, Shahid; Alghamdi, Faisal; Alhussien, Ahmed; Alohali, Meshal; Alatawi, Abdullah; Almusned, Tariq; Habib, Syed Shahid

    2017-01-01

    Background Smoking is the predominant form of tobacco consumption and is growing worldwide, particularly in the younger generation in the Middle-East. We aimed to determine the effects of tobacco smoking on cognitive functions among young Saudi adults. Material/Methods We recruited a group of cigarette smokers (N=22) and a group of controls (non-smokers) (N=30) from apparently healthy male volunteers aged 18–29 years. Cognitive function was assessed by using the Cambridge Neuropsychological Automated Battery (CANTAB). The cognitive functions outcome variables were the response time (attention-switching task [AST]), and the percentage of correct response (pattern recognition memory [PRM] task). Clinical, demographic, blood markers (brain-derived neurotrophic factor (BDNF) and apolipoprotein E) were assessed between groups. Results The 2 groups were matched for age and educational status. In comparison to the control group, smokers showed significant cognitive impairments in AST-Latency (p=0.001), AST-Congruent (p=0.001), and AST-Incongruent condition (p=0.001). There was not significant difference in BDNF APOE serum level between the 2 groups. Conclusions These results indicate that attention and alertness were significantly impaired in smokers compared to non-smokers. PMID:28223681

  2. The chemorepulsive axon guidance protein semaphorin3A is a constituent of perineuronal nets in the adult rodent brain.

    PubMed

    Vo, Tam; Carulli, Daniela; Ehlert, Erich M E; Kwok, Jessica C F; Dick, Gunnar; Mecollari, Vasil; Moloney, Elizabeth B; Neufeld, Gera; de Winter, Fred; Fawcett, James W; Verhaagen, Joost

    2013-09-01

    In the adult rodent brain, subsets of neurons are surrounded by densely organised extracellular matrix called perineuronal nets (PNNs). PNNs consist of hyaluronan, tenascin-R, chondroitin sulphate proteoglycans (CSPGs), and the link proteins Crtl1 and Bral2. PNNs restrict plasticity at the end of critical periods and can be visualised with Wisteria floribunda agglutinin (WFA). Using a number of antibodies raised against the different regions of semaphorin3A (Sema3A) we demonstrate that this secreted chemorepulsive axon guidance protein is localised to WFA-positive PNNs around inhibitory interneurons in the cortex and several other PNN-bearing neurons throughout the brain and co-localises with aggrecan, versican, phosphacan and tenascin-R. Chondroitinase ABC (ChABC) was injected in the cortex to degrade glycosaminoglycans (GAGs) from the CSPGs, abolishing WFA staining of PNNs around the injection site. Sema3A-positive nets were no longer observed in the area devoid of WFA staining. In mice lacking the link protein Crtl1 in the CNS only vestigial PNNs are present, and in these mice there were no Sema3A-positive PNN structures. A biochemical analysis shows that Sema3A protein binds with high-affinity to CS-GAGs and aggrecan and versican extracted from PNNs in the adult rat brain, and a significant proportion of Sema3A is retrieved in brain extracts that are enriched in PNN-associated GAGs. The Sema3A receptor components PlexinA1 and A4 are selectively expressed by inhibitory interneurons in the cortex that are surrounded by Sema3A positive PNNs. We conclude that the chemorepulsive axon guidance molecule Sema3A is present in PNNs of the adult rodent brain, bound to the GAGs of the CSPGs. These observations suggest a novel concept namely that chemorepulsive axon guidance molecules like Sema3A may be important functional attributes of PNNs in the adult brain.

  3. Treatment Efficacy: Cognitive-Communicative Disorders Resulting from Traumatic Brain Injury in Adults.

    ERIC Educational Resources Information Center

    Coelho, Carl A.; And Others

    1996-01-01

    This article discusses adults with brain injuries and resulting cognitive communicative disorders. The incidence of brain injuries, the effects of cognitive-communication disorders, the role of the speech-language pathologist, the benefits of treatment, and the effects of different treatments are discussed. Charts are included that summarize…

  4. Connectivity and functional profiling of abnormal brain structures in pedophilia.

    PubMed

    Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-06-01

    Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia.

  5. Hierarchical organization of brain functional networks during visual tasks.

    PubMed

    Zhuo, Zhao; Cai, Shi-Min; Fu, Zhong-Qian; Zhang, Jie

    2011-09-01

    The functional network of the brain is known to demonstrate modular structure over different hierarchical scales. In this paper, we systematically investigated the hierarchical modular organizations of the brain functional networks that are derived from the extent of phase synchronization among high-resolution EEG time series during a visual task. In particular, we compare the modular structure of the functional network from EEG channels with that of the anatomical parcellation of the brain cortex. Our results show that the modular architectures of brain functional networks correspond well to those from the anatomical structures over different levels of hierarchy. Most importantly, we find that the consistency between the modular structures of the functional network and the anatomical network becomes more pronounced in terms of vision, sensory, vision-temporal, motor cortices during the visual task, which implies that the strong modularity in these areas forms the functional basis for the visual task. The structure-function relationship further reveals that the phase synchronization of EEG time series in the same anatomical group is much stronger than that of EEG time series from different anatomical groups during the task and that the hierarchical organization of functional brain network may be a consequence of functional segmentation of the brain cortex.

  6. Hierarchical organization of brain functional networks during visual tasks

    NASA Astrophysics Data System (ADS)

    Zhuo, Zhao; Cai, Shi-Min; Fu, Zhong-Qian; Zhang, Jie

    2011-09-01

    The functional network of the brain is known to demonstrate modular structure over different hierarchical scales. In this paper, we systematically investigated the hierarchical modular organizations of the brain functional networks that are derived from the extent of phase synchronization among high-resolution EEG time series during a visual task. In particular, we compare the modular structure of the functional network from EEG channels with that of the anatomical parcellation of the brain cortex. Our results show that the modular architectures of brain functional networks correspond well to those from the anatomical structures over different levels of hierarchy. Most importantly, we find that the consistency between the modular structures of the functional network and the anatomical network becomes more pronounced in terms of vision, sensory, vision-temporal, motor cortices during the visual task, which implies that the strong modularity in these areas forms the functional basis for the visual task. The structure-function relationship further reveals that the phase synchronization of EEG time series in the same anatomical group is much stronger than that of EEG time series from different anatomical groups during the task and that the hierarchical organization of functional brain network may be a consequence of functional segmentation of the brain cortex.

  7. Let thy left brain know what thy right brain doeth: Inter-hemispheric compensation of functional deficits after brain damage.

    PubMed

    Bartolomeo, Paolo; Thiebaut de Schotten, Michel

    2016-12-01

    Recent evidence revealed the importance of inter-hemispheric communication for the compensation of functional deficits after brain damage. This review summarises the biological consequences observed using histology as well as the longitudinal findings measured with magnetic resonance imaging methods in brain damaged animals and patients. In particular, we discuss the impact of post-stroke brain hyperactivity on functional recovery in relation to time. The reviewed evidence also suggests that the proportion of the preserved functional network both in the lesioned and in the intact hemispheres, rather than the simple lesion location, determines the extent of functional recovery. Hence, future research exploring longitudinal changes in patients with brain damage may unveil potential biomarkers underlying functional recovery.

  8. Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods

    PubMed Central

    Barth, Claudia; Villringer, Arno; Sacher, Julia

    2015-01-01

    Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal experiments and human studies reporting interactions between sex hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how sex hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in sex hormones influence functional connectivity, neurotransmission and brain structure in vivo. PMID:25750611

  9. Can we observe epigenetic effects on human brain function?

    PubMed

    Nikolova, Yuliya S; Hariri, Ahmad R

    2015-07-01

    Imaging genetics has identified many contributions of DNA sequence variation to individual differences in brain function, behavior, and risk for psychopathology. Recent studies have extended this work beyond the genome by mapping epigenetic differences, specifically gene methylation in peripherally assessed DNA, onto variability in behaviorally and clinically relevant brain function. These data have generated understandable enthusiasm for the potential of such research to illuminate biological mechanisms of risk. We use our research on the effects of genetic and epigenetic variation in the human serotonin transporter on brain function to generate a guardedly optimistic opinion that the available data encourage continued research in this direction, and suggest strategies to promote faster progress.

  10. Relationship Functioning Among Adult Children of Alcoholics*

    PubMed Central

    Kearns-Bodkin, Jill N.; Leonard, Kenneth E.

    2008-01-01

    Objective: The purpose of the current research was to examine the impact of both maternal and paternal alcoholism on the relationship functioning of husbands and wives over the early years of marriage. Method: Couples (N = 634) were assessed at the time of marriage, and again at their first, second, and fourth anniversaries. Husbands and wives completed separate, self-administered questionnaires at home. Results: Results of separate repeated measures analyses of covariance revealed that, for both husbands and wives, the appraisal of their marital relationship was associated with alcoholism in the opposite gender parent. That is, for husbands, alcoholism in the mother was associated with lower marital satisfaction across the 4 years of marriage. For wives, alcoholism in the father was related to lower marital intimacy. Husbands' physical aggression was influenced by mother's and father's alcoholism; high levels of physical aggression were present among men with alcoholic mothers and nonalcoholic fathers. Interestingly, wives' experience of husband's aggression was also highest among women with alcoholic mothers and nonalcoholic fathers. Wives also reported engaging in high levels of physical aggression when they had an alcoholic mother and a nonalcoholic father, but this effect was restricted to the early part of the marriage. Finally, parental alcoholism was associated with both husbands' and wives' attachment representations. Conclusions: The present findings suggest that children raised in alcoholic families may carry the problematic effects of their early family environment into their adult romantic relationships. PMID:18925353

  11. Future Concerns of Adult Siblings of Persons with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Degeneffe, Charles Edmund; Olney, Marjorie F.

    2008-01-01

    This study examined future concerns conveyed by adult siblings who provided regular caregiving support to their brothers and sisters with traumatic brain injury (TBI). The authors surveyed a national sample of 280 adult siblings of persons with TBI. Using a constant comparative approach to text analysis, the authors analyzed responses to the…

  12. Correlates of Depression in Adult Siblings of Persons with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Degeneffe, Charles Edmund; Lynch, Ruth Torkelson

    2006-01-01

    Using Pearlin's stress process model, this study examined correlates of depression in 170 adult siblings of persons with traumatic brain injury (TBI). Approximately 39% of adult sibling participants evinced "Center for Epidemiologic Studies-Depression" (CES-D; Radloff, 1977) scores indicating clinically significant depressive symptoms. Background…

  13. Development of a Conceptual Model to Predict Physical Activity Participation in Adults with Brain Injuries

    ERIC Educational Resources Information Center

    Driver, Simon

    2008-01-01

    The purpose was to examine psychosocial factors that influence the physical activity behaviors of adults with brain injuries. Two differing models, based on Harter's model of self-worth, were proposed to examine the relationship between perceived competence, social support, physical self-worth, affect, and motivation. Adults numbering 384 with…

  14. Strategies to promote differentiation of newborn neurons into mature functional cells in Alzheimer brain.

    PubMed

    Schaeffer, Evelin L; Novaes, Barbara A; da Silva, Emanuelle R; Skaf, Heni D; Mendes-Neto, Alvaro G

    2009-10-01

    Adult neurogenesis occurs in the subgranular zone (SGZ) and subventricular zone (SVZ). New SGZ neurons migrate into the granule cell layer of the dentate gyrus (DG). New SVZ neurons seem to enter the association neocortex and entorhinal cortex besides the olfactory bulb. Alzheimer disease (AD) is characterized by neuron loss in the hippocampus (DG and CA1 field), entorhinal cortex, and association neocortex, which underlies the learning and memory deficits. We hypothesized that, if the AD brain can support neurogenesis, strategies to stimulate the neurogenesis process could have therapeutic value in AD. We reviewed the literature on: (a) the functional significance of adult-born neurons; (b) the occurrence of endogenous neurogenesis in AD; and (c) strategies to stimulate the adult neurogenesis process. We found that: (a) new neurons in the adult DG contribute to memory function; (b) new neurons are generated in the SGZ and SVZ of AD brains, but they fail to differentiate into mature neurons in the target regions; and (c) numerous strategies (Lithium, Glatiramer Acetate, nerve growth factor, environmental enrichment) can enhance adult neurogenesis and promote maturation of newly generated neurons. Such strategies might help to compensate for the loss of neurons and improve the memory function in AD.

  15. Similar brain activation during false belief tasks in a large sample of adults with and without autism.

    PubMed

    Dufour, Nicholas; Redcay, Elizabeth; Young, Liane; Mavros, Penelope L; Moran, Joseph M; Triantafyllou, Christina; Gabrieli, John D E; Saxe, Rebecca

    2013-01-01

    Reading about another person's beliefs engages 'Theory of Mind' processes and elicits highly reliable brain activation across individuals and experimental paradigms. Using functional magnetic resonance imaging, we examined activation during a story task designed to elicit Theory of Mind processing in a very large sample of neurotypical (N = 462) individuals, and a group of high-functioning individuals with autism spectrum disorders (N = 31), using both region-of-interest and whole-brain analyses. This large sample allowed us to investigate group differences in brain activation to Theory of Mind tasks with unusually high sensitivity. There were no differences between neurotypical participants and those diagnosed with autism spectrum disorder. These results imply that the social cognitive impairments typical of autism spectrum disorder can occur without measurable changes in the size, location or response magnitude of activity during explicit Theory of Mind tasks administered to adults.

  16. Dynamic reconfiguration of structural and functional connectivity across core neurocognitive brain networks with development.

    PubMed

    Uddin, Lucina Q; Supekar, Kaustubh S; Ryali, Srikanth; Menon, Vinod

    2011-12-14

    Brain structural and functional development, throughout childhood and into adulthood, underlies the maturation of increasingly sophisticated cognitive abilities. High-level attentional and cognitive control processes rely on the integrity of, and dynamic interactions between, core neurocognitive networks. The right fronto-insular cortex (rFIC) is a critical component of a salience network (SN) that mediates interactions between large-scale brain networks involved in externally oriented attention [central executive network (CEN)] and internally oriented cognition [default mode network (DMN)]. How these systems reconfigure and mature with development is a critical question for cognitive neuroscience, with implications for neurodevelopmental pathologies affecting brain connectivity. Using functional and effective connectivity measures applied to fMRI data, we examine interactions within and between the SN, CEN, and DMN. We find that functional coupling between key network nodes is stronger in adults than in children, as are causal links emanating from the rFIC. Specifically, the causal influence of the rFIC on nodes of the SN and CEN was significantly greater in adults compared with children. Notably, these results were entirely replicated on an independent dataset of matched children and adults. Developmental changes in functional and effective connectivity were related to structural connectivity along these links. Diffusion tensor imaging tractography revealed increased structural integrity in adults compared with children along both within- and between-network pathways associated with the rFIC. These results suggest that structural and functional maturation of rFIC pathways is a critical component of the process by which human brain networks mature during development to support complex, flexible cognitive processes in adulthood.

  17. Optogenetic probing of functional brain circuitry.

    PubMed

    Mancuso, James J; Kim, Jinsook; Lee, Soojung; Tsuda, Sachiko; Chow, Nicholas B H; Augustine, George J

    2011-01-01

    Recently developed optogenetic technologies offer the promise of high-speed mapping of brain circuitry. Genetically targeted light-gated channels and pumps, such as channelrhodopsins and halorhodopsin, allow optical control of neuronal activity with high spatial and temporal resolution. Optogenetic probes of neuronal activity, such as Clomeleon and Mermaid, allow light to be used to monitor the activity of a genetically defined population of neurons. Combining these two complementary sets of optogenetic probes will make it possible to perform all-optical circuit mapping. Owing to the improved efficiency and higher speed of data acquisition, this hybrid approach should enable high-throughput mapping of brain circuitry.

  18. Neuroprotective pathways: lifestyle activity, brain pathology, and cognition in cognitively normal older adults.

    PubMed

    Wirth, Miranka; Haase, Claudia M; Villeneuve, Sylvia; Vogel, Jacob; Jagust, William J

    2014-08-01

    This study used path analysis to examine effects of cognitive activity and physical activity on cognitive functioning in older adults, through pathways involving beta-amyloid (Aβ) burden, cerebrovascular lesions, and neural injury within the brain regions affected in Alzheimer's disease (AD). Ninety-two cognitively normal older adults (75.2 ± 5.6 years) reported lifetime cognitive activity and current physical activity using validated questionnaires. For each participant, we evaluated cortical Aβ burden (using [(11)C] labeled Pittsburgh-Compound-B positron emission tomography), cerebrovascular lesions (using magnetic resonance imaging-defined white matter lesion [WML]), and neural integrity within AD regions (using a multimodal neuroimaging biomarker). Path models (adjusted for age, gender, and education) indicated that higher lifetime cognitive activity and higher current physical activity was associated with fewer WMLs. Lower WML volumes were in turn related to higher neural integrity and higher global cognitive functioning. As shown previously, higher lifetime cognitive activity was associated with lower [(11)C] labeled Pittsburgh-Compound-B retention, which itself moderated the impact of neural integrity on cognitive functioning. Lifestyle activity may thus promote cognitive health in aging by protecting against cerebrovascular pathology and Aβ pathology thought to be relevant to AD development.

  19. Neuroprotective Pathways: Lifestyle activity, brain pathology and cognition in cognitively normal older adults

    PubMed Central

    Wirth, Miranka; Haase, Claudia M.; Villeneuve, Sylvia; Vogel, Jacob; Jagust, William J.

    2014-01-01

    This study used path analysis to examine effects of cognitive activity and physical activity on cognitive functioning in older adults, through pathways involving beta-amyloid (Aβ) burden, cerebrovascular lesions, and neural injury within brain regions affected in Alzheimer’s disease (AD). Ninety-two cognitively normal older adults (75.2±5.6 years) reported lifetime cognitive activity and current physical activity using validated questionnaires. For each participant, we evaluated cortical Aβ burden (using PIB-PET), cerebrovascular lesions (using MRI-defined white matter lesion (WML)), and neural integrity within AD regions (using a multimodal biomarker). Path models (adjusted for age, gender, and education) indicated that higher lifetime cognitive activity and higher current physical activity was associated with fewer WMLs. Lower WML volumes were in turn related to higher neural integrity and higher global cognitive functioning. As shown previously, higher lifetime cognitive activity was associated with lower PIB retention, which itself moderated the impact of neural integrity on cognitive functioning. Lifestyle activity may thus promote cognitive health in aging by protecting against cerebrovascular pathology and Aβ pathology thought to be relevant to AD development. PMID:24656834

  20. Mapping functional brain development: Building a social brain through interactive specialization.

    PubMed

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

    2009-01-01

    The authors review a viewpoint on human functional brain development, interactive specialization (IS), and its application to the emerging network of cortical regions referred to as the social brain. They advance the IS view in 2 new ways. First, they extend IS into a domain to which it has not previously been applied--the emergence of social cognition and mentalizing computations in the brain. Second, they extend the implications of the IS view from the emergence of specialized functions within a cortical region to a focus on how different cortical regions with complementary functions become orchestrated into networks during human postnatal development.

  1. Complex Networks - A Key to Understanding Brain Function

    SciTech Connect

    Olaf Sporns

    2008-01-23

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

  2. Complex Networks - A Key to Understanding Brain Function

    SciTech Connect

    Sporns, Olaf

    2008-01-23

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

  3. Complex Networks - A Key to Understanding Brain Function

    ScienceCinema

    Olaf Sporns

    2016-07-12

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

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  5. Neural Substrate Expansion for the Restoration of Brain Function

    PubMed Central

    Chen, H. Isaac; Jgamadze, Dennis; Serruya, Mijail D.; Cullen, D. Kacy; Wolf, John A.; Smith, Douglas H.

    2016-01-01

    Restoring neurological and cognitive function in individuals who have suffered brain damage is one of the principal objectives of modern translational neuroscience. Electrical stimulation approaches, such as deep-brain stimulation, have achieved the most clinical success, but they ultimately may be limited by the computational capacity of the residual cerebral circuitry. An alternative strategy is brain substrate expansion, in which the computational capacity of the brain is augmented through the addition of new processing units and the reconstitution of network connectivity. This latter approach has been explored to some degree using both biological and electronic means but thus far has not demonstrated the ability to reestablish the function of large-scale neuronal networks. In this review, we contend that fulfilling the potential of brain substrate expansion will require a significant shift from current methods that emphasize direct manipulations of the brain (e.g., injections of cellular suspensions and the implantation of multi-electrode arrays) to the generation of more sophisticated neural tissues and neural-electric hybrids in vitro that are subsequently transplanted into the brain. Drawing from neural tissue engineering, stem cell biology, and neural interface technologies, this strategy makes greater use of the manifold techniques available in the laboratory to create biocompatible constructs that recapitulate brain architecture and thus are more easily recognized and utilized by brain networks. PMID:26834579

  6. Generating Text from Functional Brain Images

    PubMed Central

    Pereira, Francisco; Detre, Greg; Botvinick, Matthew

    2011-01-01

    Recent work has shown that it is possible to take brain images acquired during viewing of a scene and reconstruct an approximation of the scene from those images. Here we show that it is also possible to generate text about the mental content reflected in brain images. We began with images collected as participants read names of concrete items (e.g., “Apartment’’) while also seeing line drawings of the item named. We built a model of the mental semantic representation of concrete concepts from text data and learned to map aspects of such representation to patterns of activation in the corresponding brain image. In order to validate this mapping, without accessing information about the items viewed for left-out individual brain images, we were able to generate from each one a collection of semantically pertinent words (e.g., “door,” “window” for “Apartment’’). Furthermore, we show that the ability to generate such words allows us to perform a classification task and thus validate our method quantitatively. PMID:21927602

  7. Brain Hemispheric Functions and the Native American.

    ERIC Educational Resources Information Center

    Ross, Allen Chuck

    1982-01-01

    Uses brain research conducted by Dr. Roger Sperry to show that traditional Native Americans are more dominant in right hemisphere thinking, setting them apart from a modern left hemisphere-oriented society (especially emphasized in schools). Describes some characteristics of Native American thinking that illustrate a right hemisphere orientation…

  8. Hyper-connectivity of functional networks for brain disease diagnosis

    PubMed Central

    Jie, Biao; Wee, Chong-Yaw

    2017-01-01

    Exploring structural and functional interactions among various brain regions enables better understanding of pathological underpinnings of neurological disorders. Brain connectivity network, as a simplified representation of those structural and functional interactions, has been widely used for diagnosis and classification of neurodegenerative diseases, especially for Alzheimer’s disease (AD) and its early stage - mild cognitive impairment (MCI). However, the conventional functional connectivity network is usually constructed based on the pairwise correlation among different brain regions and thus ignores their higher-order relationships. Such loss of high-order information could be important for disease diagnosis, since neurologically a brain region predominantly interacts with more than one other brain regions. Accordingly, in this paper, we propose a novel framework for estimating the hyper-connectivity network of brain functions and then use this hyper-network for brain disease diagnosis. Here, the functional connectivity hyper-network denotes a network where each of its edges representing the interactions among multiple brain regions (i.e., an edge can connect with more than two brain regions), which can be naturally represented by a hyper-graph. Specifically, we first construct connectivity hyper-networks from the resting-state fMRI (R-fMRI) time series by using sparse representation. Then, we extract three sets of brain-region specific features from the connectivity hyper-networks, and further exploit a manifold regularized multi-task feature selection method to jointly select the most discriminative features. Finally, we use multi-kernel support vector machine (SVM) for classification. The experimental results on both MCI dataset and attention deficit hyperactivity disorder (ADHD) dataset demonstrate that, compared with the conventional connectivity network-based methods, the proposed method can not only improve the classification performance, but also

  9. Effects of methylphenidate on resting-state brain activity in normal adults: an fMRI study.

    PubMed

    Zhu, Yihong; Gao, Bin; Hua, Jianming; Liu, Weibo; Deng, Yichao; Zhang, Lijie; Jiang, Biao; Zang, Yufeng

    2013-02-01

    Methylphenidate (MPH) is one of the most commonly used stimulants for the treatment of attention deficit hyperactivity disorder (ADHD). Although several studies have evaluated the effects of MPH on human brain activation during specific cognitive tasks using functional magnetic resonance imaging (fMRI), few studies have focused on spontaneous brain activity. In the current study, we investigated the effect of MPH on the intra-regional synchronization of spontaneous brain activity during the resting state in 18 normal adult males. A handedness questionnaire and the Wechsler Adult Intelligence Scale were applied before medication, and a resting-state fMRI scan was obtained 1 h after medication (20 mg MPH or placebo, order counterbalanced between participants). We demonstrated that: (1) there were no significant differences in the performance of behavioral tasks between the MPH and placebo groups; (2) the left middle and superior temporal gyri had stronger MPHrelated regional homogeneity (ReHo); and (3) the left lingual gyrus had weaker MPH-related ReHo. Our findings showed that the ReHo in some brain areas changes with MPH compared to placebo in normal adults, even though there are no behavioral differences. This method can be applied to patients with mental illness who may be treated with MPH, and be used to compare the difference between patients taking MPH and normal participants, to help reveal the mechanism of how MPH works.

  10. Effects of Unpredictable Variable Prenatal Stress (UVPS) on Bdnf DNA Methylation and Telomere Length in the Adult Rat Brain

    NASA Technical Reports Server (NTRS)

    Blaze, Jennifer; Asok, A.; Moyer, E. L.; Roth, T. L.; Ronca, A. E.

    2015-01-01

    In utero exposure to stress can shape neurobiological and behavioral outcomes in offspring, producing vulnerability to psychopathology later in life. Animal models of prenatal stress likewise have demonstrated long-­-term alterations in brain function and behavioral deficits in offspring. For example, using a rodent model of unpredictable variable prenatal stress (UVPS), in which dams are exposed to unpredictable, variable stress across pregnancy, we have found increased body weight and anxiety-­-like behavior in adult male, but not female, offspring. DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could be responsible for the long-­-term effects of UVPS. Here, we measured methylation of brain-­-derived neurotrophic factor (bdnf), a gene important in development and plasticity, and telomere length in the brains of adult offspring from the UVPS model. Results indicate that prenatally stressed adult males have greater methylation in the medial prefrontal cortex (mPFC) compared to non-­-stressed controls, while females have greater methylation in the ventral hippocampus compared to controls. Further, prenatally stressed males had shorter telomeres than controls in the mPFC. These findings demonstrate the ability of UVPS to produce epigenetic alterations and changes in telomere length across behaviorally-­-relevant brain regions, which may have linkages to the phenotypic outcomes.

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

    PubMed Central

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

    2008-01-01

    Functional brain networks detected in task-free (“resting-state”) functional magnetic resonance imaging (fMRI) have a small-world architecture that reflects a robust functional organization of the brain. Here, we examined whether this functional organization is disrupted in Alzheimer's disease (AD). Task-free fMRI data from 21 AD subjects and 18 age-matched controls were obtained. Wavelet analysis was applied to the fMRI data to compute frequency-dependent correlation matrices. Correlation matrices were thresholded to create 90-node undirected-graphs of functional brain networks. Small-world metrics (characteristic path length and clustering coefficient) were computed using graph analytical methods. In the low frequency interval 0.01 to 0.05 Hz, functional brain networks in controls showed small-world organization of brain activity, characterized by a high clustering coefficient and a low characteristic path length. In contrast, functional brain networks in AD showed loss of small-world properties, characterized by a significantly lower clustering coefficient (p<0.01), indicative of disrupted local connectivity. Clustering coefficients for the left and right hippocampus were significantly lower (p<0.01) in the AD group compared to the control group. Furthermore, the clustering coefficient distinguished AD participants from the controls with a sensitivity of 72% and specificity of 78%. Our study provides new evidence that there is disrupted organization of functional brain networks in AD. Small-world metrics can characterize the functional organization of the brain in AD, and our findings further suggest that these network measures may be useful as an imaging-based biomarker to distinguish AD from healthy aging. PMID:18584043

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

    PubMed Central

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

    2013-01-01

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

  13. Systemic vascular function is associated with muscular power in adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-associated loss of muscular strength and muscular power are critical determinants of loss of physical function and progression to disability in older adults. In this study, we examined the association of systemic vascular function and measures of muscle strength and power in older adults. Measu...

  14. Functional Outcomes in the Treatment of Adults with ADHD

    ERIC Educational Resources Information Center

    Adler, Lenard A.; Spencer, Thomas J.; Levine, Louise R.; Ramsey, Janet L.; Tamura, Roy; Kelsey, Douglas; Ball, Susan G.; Allen, Albert J.; Biederman, Joseph

    2008-01-01

    Objective: ADHD is associated with significant functional impairment in adults. The present study examined functional outcomes following 6-month double-blind treatment with either atomoxetine or placebo. Method: Patients were 410 adults (58.5% male) with "DSM-IV"--defined ADHD. They were randomly assigned to receive either atomoxetine 40 mg/day to…

  15. Functional Impairment and Occupational Outcome in Adults with ADHD

    ERIC Educational Resources Information Center

    Gjervan, Bjorn; Torgersen, Terje; Nordahl, Hans M.; Rasmussen, Kirsten

    2012-01-01

    Objective: ADHD is associated with poor functional outcomes. The objectives were to investigate the prevalence of functional impairment and occupational status in a clinically referred sample of adults with ADHD and explore factors predicting occupational outcome. Method: A sample of 149 adults with a confirmed diagnosis of ADHD participated in…

  16. Efficient regeneration by activation of neurogenesis in homeostatically quiescent regions of the adult vertebrate brain.

    PubMed

    Berg, Daniel A; Kirkham, Matthew; Beljajeva, Anna; Knapp, Dunja; Habermann, Bianca; Ryge, Jesper; Tanaka, Elly M; Simon, András

    2010-12-01

    In contrast to mammals, salamanders and teleost fishes can efficiently repair the adult brain. It has been hypothesised that constitutively active neurogenic niches are a prerequisite for extensive neuronal regeneration capacity. Here, we show that the highly regenerative salamander, the red spotted newt, displays an unexpectedly similar distribution of active germinal niches with mammals under normal physiological conditions. Proliferation zones in the adult newt brain are restricted to the forebrain, whereas all other regions are essentially quiescent. However, ablation of midbrain dopamine neurons in newts induced ependymoglia cells in the normally quiescent midbrain to proliferate and to undertake full dopamine neuron regeneration. Using oligonucleotide microarrays, we have catalogued a set of differentially expressed genes in these activated ependymoglia cells. This strategy identified hedgehog signalling as a key component of adult dopamine neuron regeneration. These data show that brain regeneration can occur by activation of neurogenesis in quiescent brain regions.

  17. Age-Related Differences in the Brain Areas outside the Classical Language Areas among Adults Using Category Decision Task

    ERIC Educational Resources Information Center

    Cho, Yong Won; Song, Hui-Jin; Lee, Jae Jun; Lee, Joo Hwa; Lee, Hui Joong; Yi, Sang Doe; Chang, Hyuk Won; Berl, Madison M.; Gaillard, William D.; Chang, Yongmin

    2012-01-01

    Older adults perform much like younger adults on language. This similar level of performance, however, may come about through different underlying brain processes. In the present study, we evaluated age-related differences in the brain areas outside the typical language areas among adults using a category decision task. Our results showed that…

  18. [The advantages and limitations of brain function analyses by PET].

    PubMed

    Kato, M; Taniwaki, T; Kuwabara, Y

    2000-12-01

    PET has been proved to be a powerful tool for exploring the brain function. We discussed the advantages and limitations of PET for analyzing the brain function on the basis of our clinical and experimental experiences of functional imaging. A multimodality PET study measuring cerebral energy metabolism (CMRO2 and CMRglc), cerebral blood flow (CBF), oxygen extraction fraction (OEF) and neurotransmitter function (presynaptic and postsynaptic) opens up a closer insight into a precise pathophysiology of the brain dysfunction: In cerebral infarction, it reveals a state of "misery perfusion" in the acute stage, "luxury perfusion" in the intermediate stage, and proportionately decreased CBF and CMRO2 in the chronic stage. Neurotransmitter function may identify specifically a neuronal subgroup of dysfunction. Owing to the low temporal resolution of PET, a neuronal activity may propagate transsynaptically to remote areas during the period of scanning, resulting in an obscured primary site of the neuronal activity. Uncoupling between neuronal activities and cerebral energy metabolism/CBF may occur under a certain state of brain pathology, particularly after an acute destructive lesion, according to our experimental studies. Neurotransmitter function may reveal the effect of drugs on the brain function, and may be useful for developing a new method of drug therapy for brain diseases in the future.

  19. Control of adult neurogenesis by programmed cell death in the mammalian brain.

    PubMed

    Ryu, Jae Ryun; Hong, Caroline Jeeyeon; Kim, Joo Yeon; Kim, Eun-Kyoung; Sun, Woong; Yu, Seong-Woon

    2016-04-21

    The presence of neural stem cells (NSCs) and the production of new neurons in the adult brain have received great attention from scientists and the public because of implications to brain plasticity and their potential use for treating currently incurable brain diseases. Adult neurogenesis is controlled at multiple levels, including proliferation, differentiation, migration, and programmed cell death (PCD). Among these, PCD is the last and most prominent process for regulating the final number of mature neurons integrated into neural circuits. PCD can be classified into apoptosis, necrosis, and autophagic cell death and emerging evidence suggests that all three may be important modes of cell death in neural stem/progenitor cells. However, the molecular mechanisms that regulate PCD and thereby impact the intricate balance between self-renewal, proliferation, and differentiation during adult neurogenesis are not well understood. In this comprehensive review, we focus on the extent, mechanism, and biological significance of PCD for the control of adult neurogenesis in the mammalian brain. The role of intrinsic and extrinsic factors in the regulation of PCD at the molecular and systems levels is also discussed. Adult neurogenesis is a dynamic process, and the signals for differentiation, proliferation, and death of neural progenitor/stem cells are closely interrelated. A better understanding of how adult neurogenesis is influenced by PCD will help lead to important insights relevant to brain health and diseases.

  20. Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility.

    PubMed

    Coleman, Leon Garland; Liu, Wen; Oguz, Ipek; Styner, Martin; Crews, Fulton T

    2014-01-01

    Adolescents binge drink more than any other age group, increasing risk of disrupting the development of the frontal cortex. We hypothesized that adolescent binge drinking would lead to persistent alterations in adulthood. In this study, we modeled adolescent weekend underage binge-drinking, using adolescent mice (post-natal days [P] 28-37). The adolescent intermittent binge ethanol (AIE) treatment includes 6 binge intragastric doses of ethanol in an intermittent pattern across adolescence. Assessments were conducted in adulthood following extended abstinence to determine if there were persistent changes in adults. Reversal learning, open field and other behavioral assessments as well as brain structure using magnetic imaging and immunohistochemistry were determined. We found that AIE did not impact adult Barnes Maze learning. However, AIE did cause reversal learning deficits in adults. AIE also caused structural changes in the adult brain. AIE was associated with adulthood volume enlargements in specific brain regions without changes in total brain volume. Enlarged regions included the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in adults after AIE is consistent with previous imaging studies in human adolescents. AIE treatment was associated with significant increases in the expression of several extracellular matrix (ECM) proteins in the adult OFC including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP (5%). These findings are consistent with AIE causing persistent changes in brain structure that could contribute to a lack of behavioral flexibility.

  1. Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility

    PubMed Central

    Coleman, Leon Garland; Liu, Wen; Oguz, Ipek; Styner, Martin; Crews, Fulton T.

    2014-01-01

    Adolescents binge drink more than any other age group, increasing risk of disrupting the development of the frontal cortex. We hypothesized that adolescent binge drinking would lead to persistent alterations in adulthood. In this study, we modeled adolescent weekend underage binge-drinking, using adolescent mice (post-natal days [P] 28–37). The adolescent intermittent binge ethanol (AIE) treatment includes 6 binge intragastric doses of ethanol in an intermittent pattern across adolescence. Assessments were conducted in adulthood following extended abstinence to determine if there were persistent changes in adults. Reversal learning, open field and other behavioral assessments as well as brain structure using magnetic imaging and immunohistochemistry were determined. We found AIE did not impact adult Barnes Maze learning. However, AIE did cause reversal learning deficits in adults. AIE also caused structural changes in the adult brain. AIE was associated with adulthood volume enlargements in specific brain regions without changes in total brain volume. Enlarged regions included the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in adults after AIE is consistent with previous imaging studies in human adolescents. AIE treatment was associated with significant increases in the expression of several extracellular matrix (ECM) proteins in the adult OFC including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP (5%). These findings are consistent with AIE causing persistent changes in brain structure that could contribute to a lack of behavioral flexibility. PMID:24275185

  2. Breakdown of the brain's functional network modularity with awareness.

    PubMed

    Godwin, Douglass; Barry, Robert L; Marois, René

    2015-03-24

    Neurobiological theories of awareness propose divergent accounts of the spatial extent of brain changes that support conscious perception. Whereas focal theories posit mostly local regional changes, global theories propose that awareness emerges from the propagation of neural signals across a broad extent of sensory and association cortex. Here we tested the scalar extent of brain changes associated with awareness using graph theoretical analysis applied to functional connectivity data acquired at ultra-high field while subjects performed a simple masked target detection task. We found that awareness of a visual target is associated with a degradation of the modularity of the brain's functional networks brought about by an increase in intermodular functional connectivity. These results provide compelling evidence that awareness is associated with truly global changes in the brain's functional connectivity.

  3. Functional brain imaging in schizophrenia: selected results and methods.

    PubMed

    Brown, Gregory G; Thompson, Wesley K

    2010-01-01

    Functional brain imaging studies of patients with schizophrenia may be grouped into those that assume that the signs and symptoms of schizophrenia are due to disordered circuitry within a critical brain region and studies that assume that the signs and symptoms are due to disordered connections among brain regions. Studies have investigated the disordered functional brain anatomy of both the positive and negative symptoms of schizophrenia. Studies of spontaneous hallucinations find that although hallucinations are associated with abnormal brain activity in primary and secondary sensory areas, disordered brain activation associated with hallucinations is not limited to sensory systems. Disordered activation in non-sensory regions appear to contribute to the emotional strength and valence of hallucinations, to be a factor underlying an inability to distinguish ongoing mental processing from memories, and to reflect the brain's attempt to modulate the intensity of hallucinations and resolve conflicts with other processing demands. Brain activation studies support the view that auditory/verbal hallucinations are associated with an impaired ability of internal speech plans to modulate neural activation in sensory language areas. In early studies, negative symptoms of schizophrenia were hypothesized to be associated with impaired function in frontal brain areas. In support of this hypothesis meta-analytical studies have found that resting blood flow or metabolism in frontal cortex is reduced in schizophrenia, though the magnitude of the effect is only small to moderate. Brain activation studies of working memory (WM) functioning are typically associated with large effect sizes in the frontal cortex, whereas studies of functions other than WM generally reveal smaller effects. Findings from some functional connectivity studies have supported the hypothesis that schizophrenia patients experience impaired functional connections between frontal and temporal cortex, although

  4. PDYN, a gene implicated in brain/mental disorders, is targeted by REST in the adult human brain.

    PubMed

    Henriksson, Richard; Bäckman, Cristina M; Harvey, Brandon K; Kadyrova, Helena; Bazov, Igor; Shippenberg, Toni S; Bakalkin, Georgy

    2014-11-01

    The dynorphin κ-opioid receptor system is implicated in mental health and brain/mental disorders. However, despite accumulating evidence that PDYN and/or dynorphin peptide expression is altered in the brain of individuals with brain/mental disorders, little is known about transcriptional control of PDYN in humans. In the present study, we show that PDYN is targeted by the transcription factor REST in human neuroblastoma SH-SY5Y cells and that that interfering with REST activity increases PDYN expression in these cells. We also show that REST binding to PDYN is reduced in the adult human brain compared to SH-SY5Y cells, which coincides with higher PDYN expression. This may be related to MIR-9 mediated down-regulation of REST as suggested by a strong inverse correlation between REST and MIR-9 expression. Our results suggest that REST represses PDYN expression in SH-SY5Y cells and the adult human brain and may have implications for mental health and brain/mental disorders.

  5. Important Roles of Ring Finger Protein 112 in Embryonic Vascular Development and Brain Functions.

    PubMed

    Tsou, Jen-Hui; Yang, Ying-Chen; Pao, Ping-Chieh; Lin, Hui-Ching; Huang, Nai-Kuei; Lin, Shih-Ting; Hsu, Kuei-Sen; Yeh, Che-Ming; Lee, Kuen-Haur; Kuo, Chu-Jen; Yang, De-Ming; Lin, Jiann-Her; Chang, Wen-Chang; Lee, Yi-Chao

    2017-04-01

    Rnf112 is a member of the RING finger protein family. The expression of Rnf112 is abundant in the brain and is regulated during brain development. Our previous study has revealed that Rnf112 can promote neuronal differentiation by inhibiting the progression of the cell cycle in cell models. In this study, we further revealed the important functions of Rnf112 in embryo development and in adult brain. Our data showed that most of the Rnf112 (-/-) embryos exhibited blood vascular defects and died in utero. Upon further investigation, we found that the survival rate of homozygous Rnf112 knockout mice in 129/sv and C57BL/6 mixed genetic background was increased. The survived newborns of Rnf112 (-/-) mice manifested growth retardation as indicated by smaller size and a reduced weight. Although the overall organization of the brain did not appear to be severely affected in Rnf112 (-/-) mice, using in vivo 3D MRI imaging, we found that when compared to wild-type littermates, brains of Rnf112 (-/-) mice were smaller. In addition, Rnf112 (-/-) mice displayed impairment of brain functions including motor balance, and spatial learning and memory. Our results provide important aspects for the study of Rnf112 gene functions.

  6. Functional brain network modularity predicts response to cognitive training after brain injury

    PubMed Central

    Chen, Anthony J.-W.; Novakovic-Agopian, Tatjana; Gratton, Caterina; Nomura, Emi M.; D'Esposito, Mark

    2015-01-01

    Objective: We tested the value of measuring modularity, a graph theory metric indexing the relative extent of integration and segregation of distributed functional brain networks, for predicting individual differences in response to cognitive training in patients with brain injury. Methods: Patients with acquired brain injury (n = 11) participated in 5 weeks of cognitive training and a comparison condition (brief education) in a crossover intervention study design. We quantified the measure of functional brain network organization, modularity, from functional connectivity networks during a state of tonic attention regulation measured during fMRI scanning before the intervention conditions. We examined the relationship of baseline modularity with pre- to posttraining changes in neuropsychological measures of attention and executive control. Results: The modularity of brain network organization at baseline predicted improvement in attention and executive function after cognitive training, but not after the comparison intervention. Individuals with higher baseline modularity exhibited greater improvements with cognitive training, suggesting that a more modular baseline network state may contribute to greater adaptation in response to cognitive training. Conclusions: Brain network properties such as modularity provide valuable information for understanding mechanisms that influence rehabilitation of cognitive function after brain injury, and may contribute to the discovery of clinically relevant biomarkers that could guide rehabilitation efforts. PMID:25788557

  7. Telemedicine for evaluation of brain function by a metacomputer.

    PubMed

    Mizuno-Matsumoto, Y; Date, S; Tabuchi, Y; Tamura, S; Sato, Y; Zoroofi, R A; Shimojo, S; Kadobayashi, Y; Tatsumi, H; Nogawa, H; Shinosaki, K; Takeda, M; Inouye, T; Miyahara, H

    2000-06-01

    A method of evaluating brain function using the metacomputer concept of the Globus system combined with a message-passing interface is described. The proposed method has the ability to exploit various geographically distributed resources and parallel computing linked to a high-technology medical instrumentation system, magnetoencephalography, to analyze the functional state of the brain. It is envisaged that the method will lead to the realization of an efficient telemedicine system for health care.

  8. [Functions of microglia in the healthy brain: focus on neuroplasticity].

    PubMed

    Tishkina, A O; Stepanichev, M Iu; Aniol, V A; Guliaeva, N V

    2014-01-01

    Microglia is in the center of modern research because it is involved in neuroinflammation processes, which is considered as an important part of pathogenesis of many brain pathologies. On the contrary, normal physiological functions of microglia are less studied. Here we review modern data on functioning of microglia in the healthy brain. We consider involvement of microglia in angiogenesis, neurogenesis, synaptogenesis, long-term potentiation, and the mechanisms of microglia-neuron interaction. We further consider modern concept on active interaction of microglia with neurons in developing and healthy mature brain and the essential role of microglia in neuroplasticity mechanisms at various levels.

  9. TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation.

    PubMed

    Ji, Rui; Tian, Shifu; Lu, Helen J; Lu, Qingjun; Zheng, Yan; Wang, Xiaomin; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

    2013-12-15

    TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3(-/-)Axl(-/-)Mertk(-/-) triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1β, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains. Conditioned medium from TKO microglia cultures inhibits neuron stem cell proliferation and neuronal differentiation. IL-6 knockout in Axl(-/-)Mertk(-/-) double-knockout mice overcomes the inflammatory inhibition of neurogenesis, suggesting that IL-6 is a major downstream neurotoxic mediator under homeostatic regulation by TAM receptors in microglia. Additionally, autonomous trophic function of the TAM receptors on the proliferating neuronal progenitors may also promote progenitor differentiation into immature neurons.

  10. Language control in bilingual adults with and without history of mild traumatic brain injury.

    PubMed

    Ratiu, Ileana; Azuma, Tamiko

    2017-03-01

    Adults with a history of traumatic brain injury often show deficits in executive functioning (EF), including the ability to inhibit, switch, and attend to tasks. These abilities are critical for language processing in bilinguals. This study examined the effect of mild traumatic brain injury (mTBI) on EF and language processing in bilinguals using behavioral and eye-tracking measures. Twenty-two bilinguals with a history of mTBI and twenty healthy control bilinguals were administered executive function and language processing tasks. Bilinguals with a history of mTBI showed deficits in specific EFs and had higher rates of language processing errors than healthy control bilinguals. Additionally, individuals with a history of mTBI have different patterns of eye movements during reading than healthy control bilinguals. These data suggest that language processing deficits are related to underlying EF abilities. The findings provide important information regarding specific EF and language control deficits in bilinguals with a history mTBI.

  11. Perivascular instruction of cell genesis and fate in the adult brain.

    PubMed

    Goldman, Steven A; Chen, Zhuoxun

    2011-10-26

    The perivascular niche for neurogenesis was first reported as the co-association of newly generated neurons and their progenitors with both dividing and mitotically quiescent endothelial cells in restricted regions of the brain in adult birds and mammals alike. This review attempts to summarize our present understanding of the interaction of blood vessels with neural stem and progenitor cells, addressing both glial and neuronal progenitor cell interactions in the perivascular niche. We review the molecular interactions that are most critical to the endothelial control of stem and progenitor cell mobilization and differentiation. The focus throughout will be on defining those perivascular ligand-receptor interactions shared among these systems, as well as those that clearly differ as a function of cell type and setting, by which specificity may be achieved in the development of targeted therapeutics.

  12. In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9

    PubMed Central

    Swiech, Lukasz; Heidenreich, Matthias; Banerjee, Abhishek; Habib, Naomi; Li, Yinqing; Trombetta, John; Sur, Mriganka; Zhang, Feng

    2015-01-01

    Probing gene function in the mammalian brain can be greatly assisted with methods to manipulate the genome of neurons in vivo. The clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated endonuclease (Cas)9 from Streptococcus pyogenes (SpCas9)1 can be used to edit single or multiple genes in replicating eukaryotic cells, resulting in frame-shifting insertion/deletion (indel) mutations and subsequent protein depletion. Here, we delivered SpCas9 and guide RNAs using adeno-associated viral (AAV) vectors to target single (Mecp2) as well as multiple genes (Dnmt1, Dnmt3a and Dnmt3b) in the adult mouse brain in vivo. We characterized the effects of genome modifications in postmitotic neurons using biochemical, genetic, electrophysiological and behavioral readouts. Our results demonstrate that AAV-mediated SpCas9 genome editing can enable reverse genetic studies of gene function in the brain. PMID:25326897

  13. Voluntary Running Prevents Progressive Memory Decline and Increases Adult Hippocampal Neurogenesis and Growth Factor Expression After Whole-Brain Irradiation

    PubMed Central

    Wong-Goodrich, Sarah J.E.; Pfau, Madeline L.; Flores, Catherine T.; Fraser, Jennifer A.; Williams, Christina L.; Jones, Lee W.

    2010-01-01

    Whole-brain irradiation (WBI) therapy produces progressive learning and memory deficits in patients with primary or secondary brain tumors. Exercise enhances memory and adult hippocampal neurogenesis in the intact brain, so we hypothesized that exercise may be an effective treatment to alleviate consequences of WBI. Previous studies using animal models to address this issue have yielded mixed results and have not examined potential molecular mechanisms. We investigated the short- and long-term effects of WBI on spatial learning and memory retention, and determined whether voluntary running after WBI aids recovery of brain and cognitive function. Forty adult female C57Bl/6 mice given a single dose of 5 Gy or sham WBI were trained 2.5 weeks and up to four months after WBI in a Barnes maze. Half of the mice received daily voluntary wheel access starting one month after sham- or WBI. Daily running following WBI prevented the marked decline in spatial memory retention observed months after irradiation. Bromodeoxyuridine (BrdU) immunolabeling and ELISA indicated that this behavioral rescue was accompanied by a partial restoration of newborn BrdU+/NeuN+ neurons in the dentate gyrus and increased hippocampal expression of brain-derived vascular endothelial growth factor and insulin-like growth factor, and occurred despite irradiation-induced elevations in hippocampal pro-inflammatory cytokines. WBI in adult mice produced a progressive memory decline consistent with what has been reported in cancer patients receiving WBI therapy. Our findings show that running can abrogate this memory decline and aid recovery of adult hippocampal plasticity, thus highlighting exercise as a potential therapeutic intervention. PMID:20884629

  14. Sustained deep-tissue pain alters functional brain connectivity.

    PubMed

    Kim, Jieun; Loggia, Marco L; Edwards, Robert R; Wasan, Ajay D; Gollub, Randy L; Napadow, Vitaly

    2013-08-01

    Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure cuff affords an excellent opportunity to evaluate functional connectivity change to more clinically relevant sustained deep-tissue pain. Connectivity in specific networks known to be modulated by evoked pain (sensorimotor, salience, dorsal attention, frontoparietal control, and default mode networks: SMN, SLN, DAN, FCN, and DMN) was evaluated with functional-connectivity magnetic resonance imaging, both at rest and during a sustained (6-minute) pain state in healthy adults. We found that pain was stable, with no significant changes of subjects' pain ratings over the stimulation period. Sustained pain reduced connectivity between the SMN and the contralateral leg primary sensorimotor (S1/M1) representation. Such SMN-S1/M1 connectivity decreases were also accompanied by and correlated with increased SLN-S1/M1 connectivity, suggesting recruitment of activated S1/M1 from SMN to SLN. Sustained pain also increased DAN connectivity to pain processing regions such as mid-cingulate cortex, posterior insula, and putamen. Moreover, greater connectivity during pain between contralateral S1/M1 and posterior insula, thalamus, putamen, and amygdala was associated with lower cuff pressures needed to reach the targeted pain sensation. These results demonstrate that sustained pain disrupts resting S1/M1 connectivity by shifting it to a network known to process stimulus salience. Furthermore, increased connectivity between S1/M1 and both sensory and affective processing areas may be an important contribution to interindividual differences in pain sensitivity.

  15. MeCP2 is critical for maintaining mature neuronal networks and global brain anatomy during late stages of postnatal brain development and in the mature adult brain.

    PubMed

    Nguyen, Minh Vu Chuong; Du, Fang; Felice, Christy A; Shan, Xiwei; Nigam, Aparna; Mandel, Gail; Robinson, John K; Ballas, Nurit

    2012-07-18

    Mutations in the X-linked gene, methyl-CpG binding protein 2 (Mecp2), underlie a wide range of neuropsychiatric disorders, most commonly, Rett Syndrome (RTT), a severe autism spectrum disorder that affects approximately one in 10,000 female live births. Because mutations in the Mecp2 gene occur in the germ cells with onset of neurological symptoms occurring in early childhood, the role of MeCP2 has been ascribed to brain maturation at a specific developmental window. Here, we show similar kinetics of onset and progression of RTT-like symptoms in mice, including lethality, if MeCP2 is removed postnatally during the developmental stage that coincides with RTT onset, or adult stage. For the first time, we show that brains that lose MeCP2 at these two different stages are actively shrinking, resulting in higher than normal neuronal cell density. Furthermore, we show that mature dendritic arbors of pyramidal neurons are severely retracted and dendritic spine density is dramatically reduced. In addition, hippocampal astrocytes have significantly less complex ramified processes. These changes accompany a striking reduction in the levels of several synaptic proteins, including CaMKII α/β, AMPA, and NMDA receptors, and the synaptic vesicle proteins Vglut and Synapsin, which represent critical modifiers of synaptic function and dendritic arbor structure. Importantly, the mRNA levels of these synaptic proteins remains unchanged, suggesting that MeCP2 likely regulates these synaptic proteins post-transcriptionally, directly or indirectly. Our data suggest a crucial role for MeCP2 in post-transcriptional regulation of critical synaptic proteins involved in maintaining mature neuronal networks during late stages of postnatal brain development.

  16. Ontogenetic development of cannabinoid receptor expression and signal transduction functionality in the human brain.

    PubMed

    Mato, Susana; Del Olmo, Elena; Pazos, Angel

    2003-05-01

    Previous evidence suggests that the endogenous cannabinoid system emerges relatively early during brain development in the rat. However, the pre- and postnatal pattern of appearance of CB1 cannabinoid receptors in humans has not been analysed in detail. Furthermore, there is a complete lack of information about the functional ability of these proteins to activate signal transduction mechanisms during human development. In the present study we have explored CB1 receptor expression throughout the different areas of the developing human brain by [3H]CP55 940 autoradiography. We have also assessed CB1 functional coupling to G proteins during brain development by agonist-stimulated [35S]GTPgammaS autoradiography in the same cases. Our results indicate a significant density of cannabinoid receptors at 19 weeks' gestation in the same areas that contain these receptors in the adult human brain. Autoradiographic levels of CB1 receptors in these structures seem to increase progressively from early prenatal stages to adulthood. Interestingly, high densities of cannabinoid receptors have also been detected during prenatal development in fibre-enriched areas that are practically devoid of them in the adult brain. In parallel with these data, we have found that brain cannabinoid receptors are functionally coupled to signal transduction mechanisms from early prenatal stages. This early pattern of expression of functionally active cannabinoid receptors, along with the transient and atypical localization of these proteins in white matter areas during the prenatal stages, suggest an specific role of the endocannabinoid system in the events related to human neural development.

  17. Sex, stress and the brain: interactive actions of hormones on the developing and adult brain.

    PubMed

    McEwen, B S

    2014-12-01

    The brain is a target of steroid hormone actions that affect brain architecture, molecular and neurochemical processes, behavior and neuroprotection via both genomic and non-genomic actions. Estrogens have such effects throughout the brain and this article provides an historical and current view of how this new view has come about and how it has affected the study of sex differences, as well as other areas of neuroscience, including the effects of stress on the brain.

  18. Clonal development and organization of the adult Drosophila central brain

    PubMed Central

    Yu, Hung-Hsiang; Awasaki, Takeshi; Schroeder, Mark David; Long, Fuhui; Yang, Jacob S.; He, Yisheng; Ding, Peng; Kao, Jui-Chun; Wu, Gloria Yueh-Yi; Peng, Hanchuan; Myers, Gene; Lee, Tzumin

    2013-01-01

    Summary Background The insect brain can be divided into neuropils that are formed by neurites of both local and remote origin. The complexity of the interconnections obscures how these neuropils are established and interconnected through development. The Drosophila central brain develops from a fixed number of neuroblasts (NBs) that deposit neurons in regional clusters. Results By determining individual NB clones and pursuing their projections into specific neuropils we unravel the regional development of the brain neural network. Exhaustive clonal analysis revealed 95 stereotyped neuronal lineages with characteristic cell body locations and neurite trajectories. Most clones show complex projection patterns, but despite the complexity, neighboring clones often co-innervate the same local neuropil(s) and further target a restricted set of distant neuropils. Conclusions These observations argue for regional clonal development of both neuropils and neuropil connectivity throughout the Drosophila central brain. PMID:23541733

  19. Special surgical considerations for functional brain mapping.

    PubMed

    Kekhia, Hussein; Rigolo, Laura; Norton, Isaiah; Golby, Alexandra J

    2011-04-01

    The development of functional mapping techniques gives neurosurgeons many options for preoperative planning. Integrating functional and anatomic data can inform patient selection and surgical planning and makes functional mapping more accessible than when only invasive studies were available. However, the applications of functional mapping to neurosurgical patients are still evolving. Functional imaging remains complex and requires an understanding of the underlying physiologic and imaging characteristics. Neurosurgeons must be accustomed to interpreting highly processed data. Successful implementation of functional image-guided procedures requires efficient interactions between neurosurgeon, neurologist, radiologist, neuropsychologist, and others, but promises to enhance the care of patients.

  20. EEG-based research on brain functional networks in cognition.

    PubMed

    Wang, Niannian; Zhang, Li; Liu, Guozhong

    2015-01-01

    Recently, exploring the cognitive functions of the brain by establishing a network model to understand the working mechanism of the brain has become a popular research topic in the field of neuroscience. In this study, electroencephalography (EEG) was used to collect data from subjects given four different mathematical cognitive tasks: recite numbers clockwise and counter-clockwise, and letters clockwise and counter-clockwise to build a complex brain function network (BFN). By studying the connectivity features and parameters of those brain functional networks, it was found that the average clustering coefficient is much larger than its corresponding random network and the average shortest path length is similar to the corresponding random networks, which clearly shows the characteristics of the small-world network. The brain regions stimulated during the experiment are consistent with traditional cognitive science regarding learning, memory, comprehension, and other rational judgment results. The new method of complex networking involves studying the mathematical cognitive process of reciting, providing an effective research foundation for exploring the relationship between brain cognition and human learning skills and memory. This could help detect memory deficits early in young and mentally handicapped children, and help scientists understand the causes of cognitive brain disorders.

  1. Changes in the modulation of brain activity during context encoding vs. context retrieval across the adult lifespan.

    PubMed

    Ankudowich, E; Pasvanis, S; Rajah, M N

    2016-06-14

    Age-related deficits in context memory may arise from neural changes underlying both encoding and retrieval of context information. Although age-related functional changes in the brain regions supporting context memory begin at midlife, little is known about the functional changes with age that support context memory encoding and retrieval across the adult lifespan. We investigated how age-related functional changes support context memory across the adult lifespan by assessing linear changes with age during successful context encoding and retrieval. Using functional magnetic resonance imaging (fMRI), we compared young, middle-aged and older adults during both encoding and retrieval of spatial and temporal details of faces. Multivariate behavioral partial least squares (B-PLS) analysis of fMRI data identified a pattern of whole-brain activity that correlated with a linear age term and a pattern of whole-brain activity that was associated with an age-by-memory phase (encoding vs. retrieval) interaction. Further investigation of this latter effect identified three main findings: 1) reduced phase-related modulation in bilateral fusiform gyrus, left superior/anterior frontal gyrus and right inferior frontal gyrus that started at midlife and continued to older age, 2) reduced phase-related modulation in bilateral inferior parietal lobule that occurred only in older age, and 3) changes in phase-related modulation in older but not younger adults in left middle frontal gyrus and bilateral parahippocampal gyrus that was indicative of age-related over-recruitment. We conclude that age-related reductions in context memory arise in midlife and are related to changes in perceptual recollection and changes in fronto-parietal retrieval monitoring.

  2. Neurological Gait Abnormalities Moderate the Functional Brain Signature of the Posture First Hypothesis

    PubMed Central

    Verghese, Joe; Allali, Gilles; Izzetoglu, Meltem; Wang, Cuiling; Mahoney, Jeannette R.

    2015-01-01

    The posture first hypothesis suggests that under dual-task walking conditions older adults prioritize gait over cognitive task performance. Functional neural confirmation of this hypothesis, however, is lacking. Herein, we determined the functional neural correlates of the posture first hypothesis and hypothesized that the presence of neurological gait abnormalities (NGA) would moderate associations between brain activations, gait and cognitive performance. Using functional near-infrared spectroscopy we assessed changes in oxygenated hemoglobin levels in the pre-frontal cortex (PFC) during normal walk and walk while talk (WWT) conditions in a large cohort of non-demented older adults (n = 236; age = 75.5 ± 6.49 years; female = 51.7 %). NGA were defined as central (due to brain diseases) or peripheral (neuropathic gait) following a standardized neurological examination protocol. Double dissociations between brain activations and behavior emerged as a function of NGA. Higher oxygenation levels during WWT were related to better cognitive performance (estimate = 0.145; p < 0.001) but slower gait velocity (estimate = −6.336, p <0.05) among normals. In contrast, higher oxygenation levels during WWT among individuals with peripheral NGA were associated with worse cognitive performance (estimate = −0.355; p <0.001) but faster gait velocity (estimate = 14.855; p <0.05). Increased activation in the PFC during locomotion may have a compensatory function that is designed to support gait among individuals with peripheral NGA. PMID:26613725

  3. Effects of Methylphenidate on Memory Functions of Adults with ADHD.

    PubMed

    Fuermaier, Anselm B M; Tucha, Lara; Koerts, Janneke; Weisbrod, Matthias; Lange, Klaus W; Aschenbrenner, Steffen; Tucha, Oliver

    2016-04-18

    Neuropsychological research on adults with attention deficit hyperactivity disorder (ADHD) revealed considerable impairments in memory functions related to executive control. However, only limited evidence exists supporting the effects of pharmacological treatment using methylphenidate (MPH) on memory functions. The aim of the present study was, therefore, to explore the impact of MPH on various memory functions of adults with ADHD. Thirty-one adults with ADHD treated with MPH, 36 adults with ADHD not-treated with MPH, and 36 healthy individuals were assessed on several aspects of memory, including short-term memory, working memory, retrospective memory, prospective memory, and source memory. Multivariate statistical analyses were applied to compare memory functions between groups. Nonmedicated adults with ADHD showed considerable impairments in memory functions related to executive control. Adults with ADHD treated with MPH showed improved memory functions when compared to nonmedicated patients, but were still impaired when compared to healthy controls. The present study emphasized the severity of memory impairments of adults with ADHD. A pharmacological treatment with MPH appeared to improve memory, but does not normalize functioning. Additional treatment intervention (e.g., cognitive-behavioral therapy) is therefore necessary.

  4. Brain structural deficits and working memory fMRI dysfunction in young adults who were diagnosed with ADHD in adolescence.

    PubMed

    Roman-Urrestarazu, Andres; Lindholm, Päivi; Moilanen, Irma; Kiviniemi, Vesa; Miettunen, Jouko; Jääskeläinen, Erika; Mäki, Pirjo; Hurtig, Tuula; Ebeling, Hanna; Barnett, Jennifer H; Nikkinen, Juha; Suckling, John; Jones, Peter B; Veijola, Juha; Murray, Graham K

    2016-05-01

    When adolescents with ADHD enter adulthood, some no longer meet disorder diagnostic criteria but it is unknown if biological and cognitive abnorma lities persist. We tested the hypothesis that people diagnosed with ADHD during adolescence present residual brain abnormalities both in brain structure and in working memory brain function. 83 young adults (aged 20-24 years) from the Northern Finland 1986 Birth Cohort were classified as diagnosed with ADHD in adolescence (adolescence ADHD, n = 49) or a control group (n = 34). Only one patient had received medication for ADHD. T1-weighted brain scans were acquired and processed in a voxel-based analysis using permutation-based statistics. A sub-sample of both groups (ADHD, n = 21; controls n = 23) also performed a Sternberg working memory task whilst acquiring fMRI data. Areas of structural difference were used as a region of interest to evaluate the implications that structural abnormalities found in the ADHD group might have on working memory function. There was lower grey matter volume bilaterally in adolescence ADHD participants in the caudate (p < 0.05 FWE corrected across the whole brain) at age 20-24. Working memory was poorer in adolescence ADHD participants, with associated failure to show normal load-dependent caudate activation. Young adults diagnosed with ADHD in adolescence have structural and functional deficits in the caudate associated with abnormal working memory function. These findings are not secondary to stimulant treatment, and emphasise the importance of taking a wider perspective on ADHD outcomes than simply whether or not a particular patient meets diagnostic criteria at any given point in time.

  5. Event-related brain potentials - Comparison between children and adults

    NASA Technical Reports Server (NTRS)

    Courchesne, E.

    1977-01-01

    The reported investigation shows that nontarget stimuli which are infrequently presented and deviate from the background elicit Nc and Pc waves in children. The same stimuli elicit P3 waves in adults. The scalp distribution of P3 waves in adults appears to vary with the ease of stimulus recognition or the degree of stimulus novelty. However, the Nc and Pc distributions in children do not seem to vary with these factors. The differences between children and adults in event-related potentials suggest corresponding differences in the mode of processing employed by each when rare, deviant stimuli are encountered

  6. Morphological brain network assessed using graph theory and network filtration in deaf adults.

    PubMed

    Kim, Eunkyung; Kang, Hyejin; Lee, Hyekyoung; Lee, Hyo-Jeong; Suh, Myung-Whan; Song, Jae-Jin; Oh, Seung-Ha; Lee, Dong Soo

    2014-09-01

    Prolonged deprivation of auditory input can change brain networks in pre- and postlingual deaf adults by brain-wide reorganization. To investigate morphological changes in these brains voxel-based morphometry, voxel-wise correlation with the primary auditory cortex, and whole brain network analyses using morphological covariance were performed in eight prelingual deaf, eleven postlingual deaf, and eleven hearing adults. Network characteristics based on graph theory and network filtration based on persistent homology were examined. Gray matter density in the primary auditor cortex was preserved in prelingual deafness, while it tended to decrease in postlingual deafness. Unlike postlingual, prelingual deafness showed increased bilateral temporal connectivity of the primary auditory cortex compared to the hearing adults. Of the graph theory-based characteristics, clustering coefficient, betweenness centrality, and nodal efficiency all increased in prelingual deafness, while all the parameters of postlingual deafness were similar to the hearing adults. Patterns of connected components changing during network filtration were different between prelingual deafness and hearing adults according to the barcode, dendrogram, and single linkage matrix representations, while these were the same in postlingual deafness. Nodes in fronto-limbic and left temporal components were closely coupled, and nodes in the temporo-parietal component were loosely coupled, in prelingual deafness. Patterns of connected components changing in postlingual deafness were the same as hearing adults. We propose that the preserved density of auditory cortex associated with increased connectivity in prelingual deafness, and closer coupling between certain brain areas, represent distinctive reorganization of auditory and related cortices compared with hearing or postlingual deaf adults. The differential network reorganization in the prelingual deaf adults could be related to the absence of auditory speech

  7. 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.

  8. Isolation and culture of adult human microglia within mixed glial cultures for functional experimentation and high-content analysis.

    PubMed

    Smith, Amy M; Gibbons, Hannah M; Lill, Claire; Faull, Richard L M; Dragunow, Mike

    2013-01-01

    Microglia are thought to be involved in diseases of the adult human brain as well as normal aging processes. While neonatal and rodent microglia are often used in studies investigating microglial function, there are important differences between rodent microglia and their adult human counterparts. Human brain tissue provides a unique and valuable tool for microglial cell and molecular biology. Routine protocols can now enable use of this culture method in many laboratories. Detailed protocols and advice for culture of human brain microglia are provided here. We demonstrate the protocol for culturing human adult microglia within a mixed glial culture and use a phagocytosis assay as an example of the functional studies possible with these cells as well as a high-content analysis method of quantification.

  9. Expression of fragile X mental retardation protein in neurons and glia of the developing and adult mouse brain.

    PubMed

    Gholizadeh, Shervin; Halder, Sebok Kumar; Hampson, David R

    2015-01-30

    Fragile X syndrome is the most common inherited form of mental retardation and autism. It is caused by a reduction or elimination of the expression of fragile X mental retardation protein (FMRP). Because fragile X syndrome is a neurodevelopmental disorder, it is important to fully document the cell type expression in the developing CNS to provide a better understanding of the molecular function of FMRP, and the pathogenesis of the syndrome. We investigated FMRP expression in the brain using double-labeling immunocytochemistry and cell type markers for neurons (NeuN), astrocytes (S100β), microglia (Iba-1), and oligodendrocyte precursor cells (NG2). The hippocampus, striatum, cingulate cortex, retrosplenial cortex, corpus callosum and cerebellum were assessed in wild-type C57/BL6 mice at postnatal days 0, 10, 20, and adult. Our results demonstrate that FMRP is ubiquitously expressed in neurons at all times and brain regions studied, except for corpus callosum where FMRP was predominantly present in astrocytes at all ages. FMRP expression in Iba-1 and NG2-positive cells was detected at postnatal day 0 and 10 and gradually decreased to very low or undetectable levels in postnatal day 20 and adult mice. Our results reveal that in addition to continuous and extensive expression in neurons in the immature and mature brain, FMRP is also present in astrocytes, oligodendrocyte precursor cells, and microglia during the early and mid-postnatal developmental stages of brain maturation. Prominent expression of FMRP in glia during these crucial stages of brain development suggests an important contribution to normal brain function, and in its absence, to the fragile X phenotype.

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

    PubMed

    Li, Guangye; Zhang, Dingguo

    2016-01-01

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

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

    PubMed Central

    2016-01-01

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

  12. Proteomic and transcriptomic study of brain microvessels in neonatal and adult mice

    PubMed Central

    Porte, Baptiste; Chatelain, Clémence; Hardouin, Julie; Derambure, Céline; Zerdoumi, Yasmine; Hauchecorne, Michèle; Dupré, Nicolas; Bekri, Soumeya; Gonzalez, Bruno; Marret, Stéphane; Cosette, Pascal

    2017-01-01

    Infants born before 29 weeks gestation incur a major risk of preterm encephalopathy and subependymal/intracerebral/intraventricular haemorrhage. In mice, an ontogenic window of haemorrhage risk was recorded up to 5 days after birth in serpine1 knock-out animals. Using proteome and transcriptome approaches in mouse forebrain microvessels, we previously described the remodelling of extracellular matrix and integrins likely strengthening the vascular wall between postnatal day 5 (P5) and P10. Haemorrhage is the ultimate outcome of vessel damage (i.e., during ischaemia), although discreet vessel insults may be involved in the aetiology of preterm encephalopathy. In this study, we examined proteins identified by mass spectrometry and segregating in gene ontology pathways in forebrain microvessels in P5, P10, and adult wild type mice. In parallel, comparative transcript levels were obtained using RNA hybridization microarrays and enriched biological pathways were extracted from genes exhibiting at least a two-fold change in expression. Five major biological functions were observed in those genes detected both as proteins and mRNA expression undergoing at least a two-fold change in expression in one or more age comparisons: energy metabolism, protein metabolism, antioxidant function, ion exchanges, and transport. Adult microvessels exhibited the highest protein and mRNA expression levels for a majority of genes. Energy metabolism–enriched gene ontology pathways pointed to the preferential occurrence of glycolysis in P5 microvessels cells versus P10 and adult preparations enriched in aerobic oxidative enzymes. Age-dependent levels of RNA coding transport proteins at the plasma membrane and mitochondria strengthened our findings based on protein data. The data suggest that immature microvessels have fewer energy supply alternatives to glycolysis than mature structures. In the context of high energy demand, this constraint might account for vascular damage and maintenance

  13. Adaptive Modulation of Adult Brain Gray and White Matter to High Altitude: Structural MRI Studies

    PubMed Central

    Zhang, Jiaxing; Zhang, Haiyan; Li, Jinqiang; Chen, Ji; Han, Qiaoqing; Lin, Jianzhong; Yang, Tianhe; Fan, Ming

    2013-01-01

    The aim of this study was to investigate brain structural alterations in adult immigrants who adapted to high altitude (HA). Voxel-based morphometry analysis of gray matter (GM) volumes, surface-based analysis of cortical thickness, and Tract-Based Spatial Statistics analysis of white matter fractional anisotropy (FA) based on MRI images were conducted on 16 adults (20–22 years) who immigrated to the Qinghai-Tibet Plateau (2300–4400 m) for 2 years. They had no chronic mountain sickness. Control group consisted of 16 matched sea level subjects. A battery of neuropsychological tests was also conducted. HA immigrants showed significantly decreased GM volumes in the right postcentral gyrus and right superior frontal gyrus, and increased GM volumes in the right middle frontal gyrus, right parahippocampal gyrus, right inferior and middle temporal gyri, bilateral inferior ventral pons, and right cerebellum crus1. While there was some divergence in the left hemisphere, surface-based patterns of GM changes in the right hemisphere resembled those seen for VBM analysis. FA changes were observed in multiple WM tracts. HA immigrants showed significant impairment in pulmonary function, increase in reaction time, and deficit in mental rotation. Parahippocampal and middle frontal GM volumes correlated with vital capacity. Superior frontal GM volume correlated with mental rotation and postcentral GM correlated with reaction time. Paracentral lobule and frontal FA correlated with mental rotation reaction time. There might be structural modifications occurred in the adult immigrants during adaptation to HA. The changes in GM may be related to impaired respiratory function and psychological deficits. PMID:23874692

  14. Characterizing dynamic local functional connectivity in the human brain

    PubMed Central

    Deng, Lifu; Sun, Junfeng; Cheng, Lin; Tong, Shanbao

    2016-01-01

    Functional connectivity (FC), obtained from functional magnetic resonance imaging (fMRI), brings insights into the functional organization of the brain. Recently, rich and complex behaviour of brain has been revealed by the dynamic fluctuation of FC, which had previously been regarded as confounding ‘noise’. While the dynamics of long-distance, inter-regional FC has been extensively studied, the dynamics of local FC within a few millimetres in space remains largely unexplored. In this study, the local FC was depicted by regional homogeneity (ReHo), and the dynamics of local FC was obtained using sliding windows method. We observed a robust positive correlation between ReHo and its temporal variability, which was shown to be an intrinsic feature of the brain rather than a pure stochastic effect. Furthermore, fluctuation of ReHo was associated with global functional organization: (i) brain regions with higher centrality of inter-regional FC tended to possess higher ReHo variability; (ii) coherence of ReHo fluctuation was higher within brain’s functional modules. Finally, we observed alteration of ReHo variability during a motor task compared with resting-state. Our findings associated the temporal fluctuation of ReHo with brain function, opening up the possibility of dynamic local FC study in the future. PMID:27231194

  15. Functional neuroimaging of traumatic brain injury: advances and clinical utility

    PubMed Central

    Irimia, Andrei; Van Horn, John Darrell

    2015-01-01

    Functional deficits due to traumatic brain injury (TBI) can have significant and enduring consequences upon patients’ life quality and expectancy. Although functional neuroimaging is essential for understanding TBI pathophysiology, an insufficient amount of effort has been dedicated to the task of translating functional neuroimaging findings into information with clinical utility. The purpose of this review is to summarize the use of functional neuroimaging techniques – especially functional magnetic resonance imaging, diffusion tensor imaging, positron emission tomography, magnetic resonance spectroscopy, and electroencephalography – for advancing current knowledge of TBI-related brain dysfunction and for improving the rehabilitation of TBI patients. We focus on seven core areas of functional deficits, namely consciousness, motor function, attention, memory, higher cognition, personality, and affect, and, for each of these, we summarize recent findings from neuroimaging studies which have provided substantial insight into brain function changes due to TBI. Recommendations are also provided to aid in setting the direction of future neuroimaging research and for understanding brain function changes after TBI. PMID:26396520

  16. A novel method for fast imaging of brain function, non-invasively, with light

    NASA Astrophysics Data System (ADS)

    Chance, Britton; Anday, Endla; Nioka, Shoko; Zhou, Shuoming; Hong, Long; Worden, Katherine; Li, C.; Murray, T.; Ovetsky, Y.; Pidikiti, D.; Thomas, R.

    1998-05-01

    Imaging of the human body by any non-invasive technique has been an appropriate goal of physics and medicine, and great success has been obtained with both Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) in brain imaging. Non-imaging responses to functional activation using near infrared spectroscopy of brain (fNIR) obtained in 1993 (Chance, et al. [1]) and in 1994 (Tamura, et al. [2]) are now complemented with images of pre-frontal and parietal stimulation in adults and pre-term neonates in this communication (see also [3]). Prior studies used continuous [4], pulsed [3] or modulated [5] light. The amplitude and phase cancellation of optical patterns as demonstrated for single source detector pairs affords remarkable sensitivity of small object detection in model systems [6]. The methods have now been elaborated with multiple source detector combinations (nine sources, four detectors). Using simple back projection algorithms it is now possible to image sensorimotor and cognitive activation of adult and pre- and full-term neonate human brain function in times < 30 sec and with two dimensional resolutions of < 1 cm in two dimensional displays. The method can be used in evaluation of adult and neonatal cerebral dysfunction in a simple, portable and affordable method that does not require immobilization, as contrasted to MRI and PET.

  17. Self-portraits of the brain: cognitive science, data visualization, and communicating brain structure and function.

    PubMed

    Goldstone, Robert L; Pestilli, Franco; Börner, Katy

    2015-08-01

    With several large-scale human brain projects currently underway and a range of neuroimaging techniques growing in availability to researchers, the amount and diversity of data relevant for understanding the human brain is increasing rapidly. A complete understanding of the brain must incorporate information about 3D neural location, activity, timing, and task. Data mining, high-performance computing, and visualization can serve as tools that augment human intellect; however, the resulting visualizations must take into account human abilities and limitations to be effective tools for exploration and communication. In this feature review, we discuss key challenges and opportunities that arise when leveraging the sophisticated perceptual and conceptual processing of the human brain to help researchers understand brain structure, function, and behavior.

  18. [Functional imaging of deep brain stimulation in idiopathic Parkinson's disease].

    PubMed

    Hilker, R

    2010-10-01

    Functional brain imaging allows the effects of deep brain stimulation (DBS) on the living human brain to be investigated. In patients with advanced Parkinson's disease (PD), positron emission tomography (PET) studies were undertaken at rest as well as under motor, cognitive or behavioral activation. DBS leads to a reduction of abnormal PD-related network activity in the motor system, which partly correlates with the improvement of motor symptoms. The local increase of energy consumption within the direct target area suggests a predominant excitatory influence of the stimulation current on neuronal tissue. Remote effects of DBS of the subthalamic nucleus (STN) on frontal association cortices indicate an interference of stimulation energy with associative and limbic basal ganglia loops. Taken together, functional brain imaging provides very valuable data for advancement of the DBS technique in PD therapy.

  19. Effect of glycolysis inhibition on mitochondrial function in rat brain.

    PubMed

    Cano-Ramírez, D; Torres-Vargas, C E; Guerrero-Castillo, S; Uribe-Carvajal, S; Hernández-Pando, R; Pedraza-Chaverri, J; Orozco-Ibarra, M

    2012-05-01

    Inhibition of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase enhances the neural vulnerability to excitotoxicity both in vivo and in vitro through an unknown mechanism possibly related to mitochondrial failure. However, as the effect of glycolysis inhibition on mitochondrial function in brain has not been studied, the aim of the present work was to evaluate the effect of glycolysis inhibition induced by iodoacetate on mitochondrial function and oxidative stress in brain. Mitochondria were isolated from brain cortex, striatum and cerebellum of rats treated systemically with iodoacetate (25 mg/kg/day for 3 days). Oxygen consumption, ATP synthesis, transmembrane potential, reactive oxygen species production, lipoperoxidation, glutathione levels, and aconitase activity were assessed. Oxygen consumption and aconitase activity decreased in the brain cortex and striatum, showing that glycolysis inhibition did not trigger severe mitochondrial impairment, but a slight mitochondrial malfunction and oxidative stress were present.

  20. Resiliency of EEG-Based Brain Functional Networks.

    PubMed

    Jalili, Mahdi

    2015-01-01

    Applying tools available in network science and graph theory to study brain networks has opened a new era in understanding brain mechanisms. Brain functional networks extracted from EEG time series have been frequently studied in health and diseases. In this manuscript, we studied failure resiliency of EEG-based brain functional networks. The network structures were extracted by analysing EEG time series obtained from 30 healthy subjects in resting state eyes-closed conditions. As the network structure was extracted, we measured a number of metrics related to their resiliency. In general, the brain networks showed worse resilient behaviour as compared to corresponding random networks with the same degree sequences. Brain networks had higher vulnerability than the random ones (P < 0.05), indicating that their global efficiency (i.e., communicability between the regions) is more affected by removing the important nodes. Furthermore, the breakdown happened as a result of cascaded failures in brain networks was severer (i.e., less nodes survived) as compared to randomized versions (P < 0.05). These results suggest that real EEG-based networks have not been evolved to possess optimal resiliency against failures.

  1. Resiliency of EEG-Based Brain Functional Networks

    PubMed Central

    Jalili, Mahdi

    2015-01-01

    Applying tools available in network science and graph theory to study brain networks has opened a new era in understanding brain mechanisms. Brain functional networks extracted from EEG time series have been frequently studied in health and diseases. In this manuscript, we studied failure resiliency of EEG-based brain functional networks. The network structures were extracted by analysing EEG time series obtained from 30 healthy subjects in resting state eyes-closed conditions. As the network structure was extracted, we measured a number of metrics related to their resiliency. In general, the brain networks showed worse resilient behaviour as compared to corresponding random networks with the same degree sequences. Brain networks had higher vulnerability than the random ones (P < 0.05), indicating that their global efficiency (i.e., communicability between the regions) is more affected by removing the important nodes. Furthermore, the breakdown happened as a result of cascaded failures in brain networks was severer (i.e., less nodes survived) as compared to randomized versions (P < 0.05). These results suggest that real EEG-based networks have not been evolved to possess optimal resiliency against failures. PMID:26295341

  2. Prenatal immune activation leads to multiple changes in basal neurotransmitter levels in the adult brain: implications for brain disorders of neurodevelopmental origin such as schizophrenia.

    PubMed

    Winter, Christine; Djodari-Irani, Anais; Sohr, Reinhard; Morgenstern, Rudolf; Feldon, Joram; Juckel, Georg; Meyer, Urs

    2009-05-01

    Maternal infection during pregnancy enhances the offspring's risk for severe neuropsychiatric disorders in later life, including schizophrenia. Recent attempts to model this association in animals provided further experimental evidence for a causal relationship between in-utero immune challenge and the postnatal emergence of a wide spectrum of behavioural, pharmacological and neuroanatomical dysfunctions implicated in schizophrenia. However, it still remains unknown whether the prenatal infection-induced changes in brain and behavioural functions may be associated with multiple changes at the neurochemical level. Here, we tested this hypothesis in a recently established mouse model of viral-like infection. Pregnant dams on gestation day 9 were exposed to viral mimetic polyriboinosinic-polyribocytidilic acid (PolyI:C, 5 mg/kg i.v.) or vehicle treatment, and basal neurotransmitter levels were then compared in the adult brains of animals born to PolyI:C- or vehicle-treated mothers by high-performance liquid chromatography on post-mortem tissue. We found that prenatal immune activation significantly increased the levels of dopamine and its major metabolites in the lateral globus pallidus and prefrontal cortex, whilst at the same time it decreased serotonin and its metabolite in the hippocampus, nucleus accumbens and lateral globus pallidus. In addition, a specific reduction of the inhibitory amino acid taurine in the hippocampus was noted in prenatally PolyI:C-exposed offspring relative to controls, whereas central glutamate and gamma-aminobutyric acid (GABA) content was largely unaffected by prenatal immune activation. Our results thus confirm that maternal immunological stimulation during early/middle pregnancy is sufficient to induce long-term changes in multiple neurotransmitter levels in the brains of adult offspring. This further supports the possibility that infection-mediated interference with early fetal brain development may predispose the developing organism

  3. Joint brain connectivity estimation from diffusion and functional MRI data

    NASA Astrophysics Data System (ADS)

    Chu, Shu-Hsien; Lenglet, Christophe; Parhi, Keshab K.

    2015-03-01

    Estimating brain wiring patterns is critical to better understand the brain organization and function. Anatomical brain connectivity models axonal pathways, while the functional brain connectivity characterizes the statistical dependencies and correlation between the activities of various brain regions. The synchronization of brain activity can be inferred through the variation of blood-oxygen-level dependent (BOLD) signal from functional MRI (fMRI) and the neural connections can be estimated using tractography from diffusion MRI (dMRI). Functional connections between brain regions are supported by anatomical connections, and the synchronization of brain activities arises through sharing of information in the form of electro-chemical signals on axon pathways. Jointly modeling fMRI and dMRI data may improve the accuracy in constructing anatomical connectivity as well as functional connectivity. Such an approach may lead to novel multimodal biomarkers potentially able to better capture functional and anatomical connectivity variations. We present a novel brain network model which jointly models the dMRI and fMRI data to improve the anatomical connectivity estimation and extract the anatomical subnetworks associated with specific functional modes by constraining the anatomical connections as structural supports to the functional connections. The key idea is similar to a multi-commodity flow optimization problem that minimizes the cost or maximizes the efficiency for flow configuration and simultaneously fulfills the supply-demand constraint for each commodity. In the proposed network, the nodes represent the grey matter (GM) regions providing brain functionality, and the links represent white matter (WM) fiber bundles connecting those regions and delivering information. The commodities can be thought of as the information corresponding to brain activity patterns as obtained for instance by independent component analysis (ICA) of fMRI data. The concept of information

  4. Executive Function Impairments in High IQ Adults with ADHD

    ERIC Educational Resources Information Center

    Brown, Thomas E.; Reichel, Philipp C.; Quinlan, Donald M.

    2009-01-01

    Objectives: To demonstrate that high IQ adults diagnosed with ADHD suffer from executive function (EF) impairments that: a) can be identified with a combination of standardized measures and self-report data; and b) occur more commonly in this group than in the general population. Method: 157 ADHD adults with IQ greater than or equal to 120 were…

  5. Rural Youth and Adults' Knowledge of Governmental Functions.

    ERIC Educational Resources Information Center

    Edington, Everett D.; And Others

    In l976 Dane County, Wisconsin was the site of a survey to determine the knowledge of rural youth and adults as to how their government functioned. The area was chosen because its residents were thought to be more politically active than individuals in other parts of the state. Personal or telephone interviews were conducted with 112 adults and…

  6. Cognitive Functioning and Work Success in Adults with Dyslexia

    ERIC Educational Resources Information Center

    Leather, Carol; Hogh, Henriette; Seiss, Ellen; Everatt, John

    2011-01-01

    Dyslexic adults completed questionnaires designed to investigate relationships between cognitive functioning, especially executive aspects, and work success. The study was designed to determine whether quantitative support could be provided for the model of adult dyslexic success derived from the work of Gerber and his colleagues (Gerber,…

  7. Structural and Functional MRI Differences in Master Sommeliers: A Pilot Study on Expertise in the Brain

    PubMed Central

    Banks, Sarah J.; Sreenivasan, Karthik R.; Weintraub, David M.; Baldock, Deanna; Noback, Michael; Pierce, Meghan E.; Frasnelli, Johannes; James, Jay; Beall, Erik; Zhuang, Xiaowei; Cordes, Dietmar; Leger, Gabriel C.

    2016-01-01

    Our experiences, even as adults, shape our brains. Regional differences have been found in experts, with the regions associated with their particular skill-set. Functional differences have also been noted in brain activation patterns in some experts. This study uses multimodal techniques to assess structural and functional patterns that differ between experts and non-experts. Sommeliers are experts in wine and thus in olfaction. We assessed differences in Master Sommeliers’ brains, compared with controls, in structure and also in functional response to olfactory and visual judgment tasks. MRI data were analyzed using voxel-based morphometry as well as automated parcellation to assess structural properties, and group differences between tasks were calculated. Results indicate enhanced volume in the right insula and entorhinal cortex, with the cortical thickness of the entorhinal correlating with experience. There were regional activation differences in a large area involving the right olfactory and memory regions, with heightened activation specifically for sommeliers during an olfactory task. Our results indicate that sommeliers’ brains show specialization in the expected regions of the olfactory and memory networks, and also in regions important in integration of internal sensory stimuli and external cues. Overall, these differences suggest that specialized expertise and training might result in enhancements in the brain well into adulthood. This is particularly important given the regions involved, which are the first to be impacted by many neurodegenerative diseases. PMID:27597821

  8. Whole-brain grey matter density predicts balance stability irrespective of age and protects older adults from falling.

    PubMed

    Boisgontier, Matthieu P; Cheval, Boris; van Ruitenbeek, Peter; Levin, Oron; Renaud, Olivier; Chanal, Julien; Swinnen, Stephan P

    2016-03-01

    Functional and structural imaging studies have demonstrated the involvement of the brain in balance control. Nevertheless, how decisive grey matter density and white matter microstructural organisation are in predicting balance stability, and especially when linked to the effects of ageing, remains unclear. Standing balance was tested on a platform moving at different frequencies and amplitudes in 30 young and 30 older adults, with eyes open and with eyes closed. Centre of pressure variance was used as an indicator of balance instability. The mean density of grey matter and mean white matter microstructural organisation were measured using voxel-based morphometry and diffusion tensor imaging, respectively. Mixed-effects models were built to analyse the extent to which age, grey matter density, and white matter microstructural organisation predicted balance instability. Results showed that both grey matter density and age independently predicted balance instability. These predictions were reinforced when the level of difficulty of the conditions increased. Furthermore, grey matter predicted balance instability beyond age and at least as consistently as age across conditions. In other words, for balance stability, the level of whole-brain grey matter density is at least as decisive as being young or old. Finally, brain grey matter appeared to be protective against falls in older adults as age increased the probability of losing balance in older adults with low, but not moderate or high grey matter density. No such results were observed for white matter microstructural organisation, thereby reinforcing the specificity of our grey matter findings.

  9. Long-term supratentorial brain structure and cognitive function following cerebellar tumour resections in childhood.

    PubMed

    Moberget, T; Andersson, S; Lundar, T; Due-Tønnessen, B J; Heldal, A; Endestad, T; Westlye, L T

    2015-03-01

    The cerebellum is connected to extensive regions of the cerebrum, and cognitive deficits following cerebellar lesions may thus be related to disrupted cerebello-cerebral connectivity. Moreover, early cerebellar lesions could affect distal brain development, effectively inducing long-term changes in brain structure and cognitive function. Here, we characterize supratentorial brain structure and cognitive function in 20 adult patients treated for cerebellar tumours in childhood (mean age at surgery: 7.1 years) and 26 matched controls. Relative to controls, patients showed reduced cognitive function and increased grey matter density in bilateral cingulum, left orbitofrontal cortex and the left hippocampus. Within the patient group, increased grey matter density in these regions was associated with decreased performance on tests of processing speed and executive function. Further, diffusion tensor imaging revealed widespread alterations in white matter microstructure in patients. While current ventricle volume (an index of previous hydrocephalus severity it patients) was associated with grey matter density and white matter microstructure in patients, this could only partially account for the observed group differences in brain structure and cognitive function. In conclusion, our results show distal effects of cerebellar lesions on cerebral integrity and wiring, likely caused by a combination of neurodegenerative processes and perturbed neurodevelopment.

  10. Cranial irradiation induces bone marrow-derived microglia in adult mouse brain tissue.

    PubMed

    Okonogi, Noriyuki; Nakamura, Kazuhiro; Suzuki, Yoshiyuki; Suto, Nana; Suzue, Kazutomo; Kaminuma, Takuya; Nakano, Takashi; Hirai, Hirokazu

    2014-07-01

    Postnatal hematopoietic progenitor cells do not contribute to microglial homeostasis in adult mice under normal conditions. However, previous studies using whole-body irradiation and bone marrow (BM) transplantation models have shown that adult BM cells migrate into the brain tissue and differentiate into microglia (BM-derived microglia; BMDM). Here, we investigated whether cranial irradiation alone was sufficient to induce the generation of BMDM in the adult mouse brain. Transgenic mice that express green fluorescent protein (GFP) under the control of a murine stem cell virus (MSCV) promoter (MSCV-GFP mice) were used. MSCV-GFP mice express GFP in BM cells but not in the resident microglia in the brain. Therefore, these mice allowed us to detect BM-derived cells in the brain without BM reconstitution. MSCV-GFP mice, aged 8-12 weeks, received 13.0 Gy irradiation only to the cranium, and BM-derived cells in the brain were quantified at 3 and 8 weeks after irradiation. No BM-derived cells were detected in control non-irradiated MSCV-GFP mouse brains, but numerous GFP-labeled BM-derived cells were present in the brain stem, basal ganglia and cerebral cortex of the irradiated MSCV-GFP mice. These BM-derived cells were positive for Iba1, a marker for microglia, indicating that GFP-positive BM-derived cells were microglial in nature. The population of BMDM was significantly greater at 8 weeks post-irradiation than at 3 weeks post-irradiation in all brain regions examined. Our results clearly show that cranial irradiation alone is sufficient to induce the generation of BMDM in the adult mouse.

  11. 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.

  12. Receptor protein tyrosine phosphatase σ binds to neurons in the adult mouse brain

    PubMed Central

    Yi, Jae-Hyuk; Katagiri, Yasuhiro; Yu, Panpan; Lourie, Jacob; Bangayan, Nathanael J.; Symes, Aviva J.; Geller, Herbert M.

    2014-01-01

    The role of type IIA receptor protein tyrosine phosphatases (RPTPs), which includes LAR, RPTPσ and RPTPδ, in the nervous system is becoming increasingly recognized. Evidence supports a significant role for these RPTPs during the development of the nervous system as well as after injury, and mutations in RPTPs are associated with human disease. However, a major open question is the nature of the ligands that interact with type IIA RPTPs in the adult brain. Candidates include several different proteins as well as the glycosaminoglycan chains of proteoglycans. In order to investigate this problem, we used a receptor affinity probe assay with RPTPσ-AP fusion proteins on sections of adult mouse brain and to cultured neurons. Our results demonstrate that the major binding sites for RPTPσ in adult mouse brain are on neurons and are not proteoglycan GAG chains, as RPTPσ binding overlaps with the neuronal marker NeuN and was not significantly altered by treatments which eliminate chondroitin sulfate, heparan sulfate, or both. We also demonstrate no overlap of binding of RPTPσ with perineuronal nets, and a unique modulation of RPTPσ binding to brain by divalent cations. Our data therefore point to neuronal proteins, rather than CSPGs, as being the ligands for RPTPσ in the adult, uninjured brain. PMID:24530640

  13. Vascular function and brain-derived neurotrophic factor: The functional capacity factor.

    PubMed

    Alomari, Mahmoud A; Khabour, Omar F; Maikano, Abubakar; Alawneh, Khaldoon

    2015-12-01

    Brain-derived neurotrophic factor (BDNF) is essential for neurocognitive function. This study aims at establishing a plausible link between level of serum BDNF, functional capacity (FC), and vascular function in 181 young (age 25.5±9.1 years old), apparently healthy adults. Fasting blood samples were drawn from participants' antecubital veins into plain glass tubes while they were in a sitting position to evaluate serum BDNF using enzyme-linked immunosorbent assay (ELISA). Mercury-in-silastic strain-gauge plethysmography was used to determine arterial function indices, blood flow and vascular resistance at rest and following 5 minutes of arterial ischemia. The 6-minute walk distance (6MWD) test was used to determine FC, according to the American Thoracic Society Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories guidelines. It was conducted in an enclosed corridor on a flat surface with a circular track 33 meters long. The walking course was demarcated with bright colored cones. The 6MWD correlated with BDNF (r=0.3, p=0.000), as well as with forearm blood inflow (r=0.5, p=0.000) and vascular resistance (r = -0.4, p=0.000). Subsequent comparison showed that BDNF and blood inflow were greater (p<0.05) while vascular resistance was less (p<0.05) in participants who achieved a longer 6MWD. Similarly, BDNF correlated with forearm blood inflow (r=0.4, p=0.000) and vascular resistance (r = -0.4, p=0.000). Subsequent comparison showed improved vascular function (p<0.05) in the participants with greater BDNF. In conclusion, these findings might suggest that improved vascular function in individuals with greater FC is mediated, at least partially, by an enhanced serum BDNF level.

  14. Civic Engagement for Older Adults With Functional Limitations: Piloting an Intervention for Adult Day Health Participants

    ERIC Educational Resources Information Center

    Dabelko-Schoeny, Holly; Anderson, Keith A.; Spinks, Katie

    2010-01-01

    Purpose: Past research has demonstrated the importance of civic engagement for older adults, yet previous studies have not focused specifically on the potential benefits of civic engagement for older adults with functional limitations. This pilot study explored the feasibility and effectiveness of an intervention designed to promote civic…

  15. Functional approach using intraoperative brain mapping and neurophysiological monitoring for the surgical treatment of brain metastases in the central region.

    PubMed

    Sanmillan, Jose L; Fernández-Coello, Alejandro; Fernández-Conejero, Isabel; Plans, Gerard; Gabarrós, Andreu

    2017-03-01

    OBJECTIVE Brain metastases are the most frequent intracranial malignant tumor in adults. Surgical intervention for metastases in eloquent areas remains controversial and challenging. Even when metastases are not infiltrating intra-parenchymal tumors, eloquent areas can be affected. Therefore, this study aimed to describe the role of a functional guided approach for the resection of brain metastases in the central region. METHODS Thirty-three patients (19 men and 14 women) with perirolandic metastases who were treated at the authors' institution were reviewed. All participants underwent resection using a functional guided approach, which consisted of using intraoperative brain mapping and/or neurophysiological monitoring to aid in the resection, depending on the functionality of the brain parenchyma surrounding each metastasis. Motor and sensory functions were monitored in all patients, and supplementary motor and language area functions were assessed in 5 and 4 patients, respectively. Clinical data were analyzed at presentation, discharge, and the 6-month follow-up. RESULTS The most frequent presenting symptom was seizure, followed by paresis. Gross-total removal of the metastasis was achieved in 31 patients (93.9%). There were 6 deaths during the follow-up period. After the removal of the metastasis, 6 patients (18.2%) presented with transient neurological worsening, of whom 4 had worsening of motor function impairment and 2 had acquired new sensory disturbances. Total recovery was achieved before the 3rd month of follow-up in all cases. Excluding those patients who died due to the progression of systemic illness, 88.9% of patients had a Karnofsky Performance Scale score greater than 80% at the 6-month follow-up. The mean survival time was 24.4 months after surgery. CONCLUSIONS The implementation of intraoperative electrical brain stimulation techniques in the resection of central region metastases may improve surgical planning and resection and may spare eloquent

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

    PubMed Central

    Mandonnet, Emmanuel; Duffau, Hugues

    2014-01-01

    Historically, cerebral processing has been conceptualized as a framework based on statically localized functions. However, a growing amount of evidence supports a hodotopical (delocalized) and flexible organization. A number of studies have reported absence of a permanent neurological deficit after massive surgical resections of eloquent brain tissue. These results highlight the tremendous plastic potential of the brain. Understanding anatomo-functional correlates underlying this cerebral reorganization is a prerequisite to restore brain functions through brain-computer interfaces (BCIs) in patients with cerebral diseases, or even to potentiate brain functions in healthy individuals. Here, we review current knowledge of neural networks that could be utilized in the BCIs that enable movements and language. To this end, intraoperative electrical stimulation in awake patients provides valuable information on the cerebral functional maps, their connectomics and plasticity. Overall, these studies indicate that the complex cerebral circuitry that underpins interactions between action, cognition and behavior should be throughly investigated before progress in BCI approaches can be achieved. PMID:24834030

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

    SciTech Connect

    Minoshima, S.; Koeppe, R.A.; Frey, A.; Ishihara, M.; Kuhl, D.E.

    1994-06-01

    In the routine analysis of functional brain images obtained by PET, subjective visual interpretation is often used for anatomic localization. To enhance the accuracy and consistency of the anatomic interpretation, a PET stereotactic atlas and localization approach was designed for functional brain images. The PET atlas was constructed from a high-resolution [{sup 18}F]fluorodeoxyglucose (FDG) image set of a normal volunteer (a 41-yr-ld woman). The image set was reoriented stereotactically, according to the intercommissural (anterior and posterior commissures) line and transformed to the standard stereotactic atlas coordinates. Cerebral structures were annotated on the transaxial planes using a proportional grid system and surface-rendered images. The stereotactic localization technique was applied to image sets from patients with Alzheimer`s disease, and areas of functional alteration were localized visually by referring to the PET atlas. Major brain structures were identified on both transaxial planes and surface-rendered images. In the stereotactic system, anatomic correspondence between the PET atlas and stereotactically reoriented individual image sets of patients with Alzheimer`s disease facil